SMJ

E-ISSN 2228-8082

Volume 74, Number 11, November 2022

ORIGINAL ARTICLE REVIEW ARTICLE

MONTHLY

Indexed by

Siriraj Medical Journal

The world-leading biomedical science of Thailand

THAILAND SECTION 1954

https://he02.tci-thaijo.org/index.php/sirirajmedj/index

E-mail: sijournal92@gmail.com

By Chanagun Tounkhrua, et al.

Siriraj Medical Journal SMJ

Volume 74, Number 11, November 2022

ORIGINAL ARTICLE

721 Three-dimensional Kinematic Analysis and Muscle Activation of the Upper Extremity in Ruesi Dutton Exercises

Thanaphak Chaowpeerapong, et al.

731 Factors Influencing Willingness to Pay for Teledermatology among Patients with Psoriasis

Thanachat Rutnumnoi, et al.

739 Long-term Oncologic Outcomes After Curative Surgery in Stage I–III Thai Colorectal Cancer Patients

Aitsariya Mongkhonsupphawan, et al.

747 Medial Closing-Wedge Distal Femoral Varus Osteotomy via Lateral Approach: The Modified Technique for Treating Valgus Osteoarthritic Knee as case series Chaturong Pornrattanamaneewong, et al.

754 Tissue Elimination of Large Vascular Corrosion Casting for Anatomy Education

Chanagun Tounkhrua, et al.

760 Psychometric Properties of Scales for Assessing Experiential Avoidance

Thanayot Sumalrot, et al.

769 Surgical Outcomes of Bariatric Surgery in Siriraj Hospital for the First 100 Morbidly Obese Patients Treated

Nicha Srisuworanan, et al.

778 The Comparison between Frozen Elephant Trunk Technique and Conventional Total Arch Replacement, a Single-center Study

Amarit Phothikun, et al.

787 Occupational Post-exposure Prophylaxis after Blood and Body Fluids Exposure among Healthcare Workers in Siriraj Hospital

Narasak Changraksa, et al.

792 Untargeted Metabolomics Analysis using LC-MS-QTOF for Metabolite Profile Comparison between Patients with Myofascial Pain of Upper Trapezius Muscle versus Controls

Manmas Vannabhum, et al.

804 The Intention to Use Telemedicine by Surgical Patients in Response to COVID-19

Arunotai Siriussawakul, et al.

Review Article

819 The Prevalence of Cleft Lip and Palate and Their Effect on Growth and Development: A Narrative Review

Nattharin Wongsirichat, et al.

SMJ

SIRIRAJ MEDICAL JOURNAL

www.smj.si.mahidol.ac.th

First Editor: Ouay Ketusinh Emeritus Editors: Somchai Bovornkitti, Adulya Viriyavejakul, Sommai Toongsuwan, Nanta Maranetra, Niphon Poungvarin, Prasit Watanapa, Vithya Vathanophas, Pipop Jirapinyo, Sanya Sukpanichnant, Somboon Kunathikom

Executive Editor: Prasit Watanapa Editorial Director: Manee Rattanachaiyanont

Managing Editor: Gulapar Srisawasdi, Chenchit Chayachinda

Editor-in-Chief: Thawatchai Akaraviputh

Associate Editor: Varut Lohsiriwat, Prapat Wanitpongpan Online Editor: Puttinun Patpituck

International Editorial Board

Philip Board (Australian National University, Australia) Richard J. Deckelbaum (Columbia University, USA) Yozo Miyake (Aichi Medical University, Japan)

Yik Ying Teo (National University of Singapore, Singapore) Harland Winter (Massachusetts General Hospital, USA)

Philip A. Brunell (State University of New York At Buffalo, USA) Noritaka Isogai (Kinki University, Japan)

Yuji Murata (Aizenbashi Hospital, Japan)

Keiichi Akita (Tokyo Medical and Dental University Hospital, Japan) Shuji Shimizu (Kyushu University Hospital, Japan)

David S. Sheps (University of Florida, USA)

Robin CN Williamson (Royal Postgraduate Medical School, UK) Tai-Soon Yong (Yonsei University, Korea)

Anusak Yiengpruksawan (The Valley Robotic Institute, USA) Stanlay James Rogers (University of California, San Francisco, USA) Kyoichi Takaori (Kyoto University Hospital, Japan)

Tomohisa Uchida (Oita University, Japan)

Yoshiki Hirooka (Nagoya University Hospital, Japan)

Hidemi Goto (Nagoya University Graduate School of Medicine, Japan) Kazuo Hara (Aichi Cancer Center Hospital, Japan)

Shomei Ryozawa (Saitama Medical University, Japan) Christopher Khor (Singapore General Hospital, Singapore) Yasushi Sano (Director of Gastrointestinal Center, Japan) Mitsuhiro Kida (Kitasato University & Hospital, Japan) Seigo Kitano (Oita University, Japan)

Ichizo Nishino (National Institute of Neuroscience NCNP, Japan)

Masakazu Yamamoto (Tokyo Women’s Medical University, Japan) Dong-Wan Seo (University of Ulsan College of Medicine, Korea) George S. Baillie (University of Glasgow, UK)

G. Allen Finley (Delhousie University, Canada)

Sara Schwanke Khilji (Oregon Health & Science University, USA) Matthew S. Dunne (Institute of Food, Nutrition, and Health, Switzerland) Marianne Hokland (University of Aarhus, Denmark)

Marcela Hermoso Ramello (University of Chile, Chile) Ciro Isidoro (University of Novara, Italy)

Moses Rodriguez (Mayo Clinic, USA)

Robert W. Mann (University of Hawaii, USA)

Wikrom Karnsakul (Johns Hopkins Children’s Center, USA)

Frans Laurens Moll (University Medical Center Ultrecht, Netherlands) James P. Dolan (Oregon Health & Science University, USA)

John Hunter (Oregon Health & Science University, USA) Nima Rezaei (Tehran University of Medical Sciences, Iran) Dennis J. Janisse (Subsidiary of DJO Global, USA)

Folker Meyer (Argonne National Laboratory, USA)

David Wayne Ussery (University of Arkansas for Medical Sciences, USA) Intawat Nookaew (University of Arkansas for Medical Sciences, USA)

Victor Manuel Charoenrook de la Fuente (Centro de Oftalmologia Barraquer, Spain)

Karl Thomas Moritz

(Swedish University of Agricultural Sciences, Sweden)

Nam H. CHO (University School of Medicine and Hospital, Korea)

Watchara Kasinrerk (Chiang Mai University, Thailand)

Editorial Board

Pornchai O-Charoenrat (Siriraj Hospital, Mahidol University, Thailand)

Rungroj Krittayaphong (Siriraj Hospital, Mahidol University, Thailand) Wiroon Laupattrakasem (Khon Kaen University, Thailand)

Anuwat Pongkunakorn (Lampang Hospital, Thailand) Nopporn Sittisombut (Chiang Mai University, Thailand)

Vasant Sumethkul (Ramathibodi Hospital, Mahidol University, Thailand) Yuen Tanniradorm (Chulalongkorn University, Thailand)

Saranatra Waikakul (Siriraj Hospital, Mahidol University, Thailand) Pa-thai Yenchitsomanus (Siriraj Hospital, Mahidol University, Thailand) Surapol Issaragrisil (Siriraj Hospital, Mahidol University,Thailand) Jaturat Kanpittaya (Khon Kaen University, Thailand)

Suneerat Kongsayreepong (Siriraj Hospital, Mahidol University, Thailand)

Statistician: Saowalak Hunnangkul (Mahidol University, Thailand)

Nopphol Pausawasdi (Siriraj Hospital, Mahidol University, Thailand)

Supakorn Rojananin (Siriraj Hospital, Mahidol University, Thailand) Jarupim Soongswang (Siriraj Hospital, Mahidol University, Thailand) Suttipong Wacharasindhu (Chulalongkorn University, Thailand) Prapon Wilairat (Mahidol University, Thailand)

Pornprom Muangman (Siriraj Hospital, Mahidol University, Thailand)

Ampaiwan Chuansumrit

(Ramathibodi Hospital, Mahidol University, Thailand)

Sayomporn Sirinavin

(Ramathibodi Hospital, Mahidol University, Thailand)

Vitoon Chinswangwatanakul

(Siriraj Hospital, Mahidol University, Thailand)

Medical Illustrator: Chananya Hokierti (Nopparat Rajathanee Hospital, Thailand)

Online Assistant: Surang Promsorn, Wilailuck Amornmontien, Hatairat Ruangsuwan Editorial Office Secretary: Amornrat Sangkaew

SIRIRAJ MEDICAL JOURNAL is published bimonthly, 6 issues a year (Jan-Feb, Mar-Apr, May-Jun, Jul-Aug, Sep-Oct and Nov-Dec) and distributed by the end of the last month of that issue.

SIRIRAJ MEDICAL JOURNAL is listed as a journal following the Uniform Requirements for Manuscripts Submitted to Biomedical Journals (URM) by the International Committee of Medical Journal Editors (ICMJE) since 9 July 2010 [http://www.icmje.org/journals.html].

Three-dimensional Kinematic Analysis and Muscle Activation of the Upper Extremity in Ruesi Dutton Exercises

Thanaphak Chaowpeerapong, B.ATM.*, Ketmanee Jongjiamdee, B.ATM.*, Pichitpol Kerdsomnuek, M.Sc.**, Suksalin Booranasubkajorn, Ph.D.*, Bavornrat Vanadurongwan, M.D.**, Weerawat Limroongreungrat, Ph.D.***, Pravit Akarasereenont, Ph.D.*, Apichat Asavamongkolkul, M.D.**

*Center of Applied Thai Traditional Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, **Department of Orthopedic

Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, ***College of Sports Science and Technology, Mahidol University, Bangkok, Thailand.

ABSTRACT

Objective: To investigate 3-D upper extremity joint angles and muscle activities in selected Ruesi-Dutton exercises. Material and Methods: Twenty-six healthy participants (mean age of 25.65, mean height of 165.08 cm, and mean weight of 56.69 Kg) volunteered to take part in this study. 3-D motion analysis consisted of eight cameras synchronized with a wireless electromyography (EMG) system to collect kinematic data and muscle activity. Participants performed five postures, including the Kae Lom Kho Mue posture, Kae Puat Thong Kae Kho Thao posture, Kae Kiat posture, Kae Puat Thong Sabak Chom posture, and Kae Lom Puat Sisa. The upper extremity joint angles and range of motion (ROM) and EMG were analyzed.

Results: Most postures were in the normal range of motion. The percentage of MVIC was more than 1% and the Trapezius muscle is the most active in all postures.

Conclusion: The data in this research is useful to help select the correct posture and exercise for a specific condition.

Keywords: Ruesi-Dutton; Hermit Doing Body Contortion; biomechanics; upper extremity (Siriraj Med J 2022; 74: 721-730)

INTRODUCTION

Ruesi-Dutton or Hermit Doing Body Contortion (HDBC) is an exercise that has been used for over 200 years in health care.1 Its origin is still unclear, but it was believed to have been developed by hermits who practiced it in India.2 “Ruesi-Dutton” is composed of two words; Ruesi, which means hermit or monk from the Buddhist era and refers to people who renounced their home, practiced Buddhist teachings, and sought peace, and “Dutton”, which means an exercise.3 Therefore,

Ruesi Dutton means movement or the many postures the Ruesi used to practice Buddhist teachings and relieve pain. HDBC exercises (also known as postures) are commonly performed by moving a part of the body in a sequence or performed simultaneously for a determined posture and held for five to 10 seconds, similar to an active static exercise. Then, the body is slowly returned to the start position. Each posture is repeated three to five times.4 HDBC consists of 80 postures, including the standing posture, sitting posture, and supine posture.1

Corresponding author: Apichat Asavamongkolkul E-mail: apichat.asa@mahidol.ac.th

Received 20 May 2022 Revised 23 June 2022 Accepted 21 July 2022 ORCID ID:http://orcid.org/0000-0002-7868-7426 http://dx.doi.org/10.33192/Smj.2022.85

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

There are many benefits of HDBC exercises such as pain reduction, decreased blood pressure, increased angle of joints, increased muscle strength, and improved quality of life.5-7

Although HDBC is widely practiced, it is still unclear how to do this exercise correctly. This problem is the result of insufficient evidence on how to perform this exercise. For example, statues in Wat Phra Chetuphon Wimonmangkalaram or paintings only display the end posture of a contortion. Moreover, a poem in Thai scripture only describes the hermit’s history, the benefits of postures, and the preliminary steps leading to variations in HDBC. In addition, research studies relating to HDBC are associated with the effectiveness of the postures. Currently, no study has comprehensively investigated movement patterns and muscle activity in HDBS. Understanding these movement patterns and how the muscles perform provides essential information to study the characteristics of the exercise. Therefore, this study aims to investigate the 3-dimensional kinematics and muscle activities of HDBC postures related to the upper extremities.

MATERIALS AND METHODS

Study design

This cross-sectional study was conducted at the Faculty of Medicine Siriraj Hospital, Bangkok, Thailand. The protocol of this study was approved by the Siriraj Institutional Review Board [Si 365/2016 (EC3)] and registered in the Thai Clinical Trials Registry (TCTR20211014004). The experimental protocol, risks, and benefits of the study were clearly explained to participants. All participants

then signed and gave their informed consent before data collection.

Subjects and Sample Size calculation

Healthy volunteers aged between 18-32 were recruited for this study. The inclusion criteria was a waist circumference of less than or equal to 90 cm (36 inches) in males and 80 cm (32 inches) in females. Participants were excluded if they were pregnant, had neurological diseases, had musculoskeletal diseases, or had a history of allergic reactions to alcohol and adhesive tape.

The sample size was calculated for primary objectives. A study on degrees of movement of the neck8 was determined as follows; two-tailed test, confidence interval of 95%, standard deviation of s 11.1, and an acceptable error of

5.4. Twenty-six participants were required for this study. We enrolled participants compatible with our eligibility criteria using a convenience sampling method. A total of 26 subjects consisting of 13 males and 13 females, with a mean age of 25.65 ± 2.77, mean weight of 56.69 ± 10.54 kg, a mean height of 165.08 ± 8.50 cm, mean BMI of

20.65 ± 2.49 kg/m2 (which is considered normal), mean length of right arm being 55.12 ± 4.68 cm., and a mean length of the left arm 55.12 ± 4.68 cm were enrolled.

Ruesi Dutton exercises

The selected five postures were as follows; Kae Lom Kho Mue posture (P1), Kae Puat Thong Kae Kho Thao posture (P2), Kae Kiat posture (P3), Kae Puat Thong Sabak Chom posture (P4), and Kae Lom Puat Sisa posture (P5). The procedures for the postures were chosen from Kaiborihan Baep Ruesi Dutton Volume 1.4

Fig 1. Five postures of Ruesi-Dutton; Kae Lom Kho Mue Posture (P1) consists of left (P1-Lt) directions, Kae Puat Thong Kae Kho Thao Posture (P2) has 1 direction, Kae Kiat Posture (P3) consists of 3 directions as follows, left (P3-Lt), right (P3-Rt), and upward (P3-Up). Kae Puat Thong Sabak Chom Posture (P4) has 1 direction, and Kae Lom Puat Sisa Posture (P5) consists of 4 directions as follows, left knees left side(P5-LKLS), left knee right side (LKRS), right knee right side (RKRS), and right knee left side (RKLS).

Study Flow

Participants who passed the criteria were trained to perform the five postures using video media and were closely advised by Applied Thai Traditional practitioners while training for a total of 120 minutes. After that, participants were assessed on each posture by three expert Applied Thai Traditional practitioners with at least 10-years of experience. Following this, various areas of the participants’ skin was prepared by cleaning it with alcohol and shaving skin hair to reduce interference noise when attaching an EMG to the surface. The surface Electromyography (Trigno Wireless system, Delsys Inc, Boston, MA USA) was set at a sampling rate of 1,000 Hz and placed on the Deltoid Medius muscle, the Upper Trapezius muscle, the Middle Trapezius muscle, the Lower Trapezius muscle, the Biceps muscle, and the Triceps muscle as indicated per the SENIAM protocol.9 Maximum Voluntary Isometric Contraction (MVIC) data was collected by stimulating static muscle strength.10 Participants were warmed up by being told to do stretching exercises for five minutes, and then begin the determined position and to slowly start increasing their force to maximum and hold it for five seconds and promptly relax. They were then asked to repeat these three times, with a pause period of 30 seconds in between tests.

Then, reflective markers were attached on the skin of participants according to the Plug-in gait protocol.11 The markers were attached at the following positions: left and right front head, left and right back head, 7th cervical vertebrae, 10th thoracic vertebrae, clavicle, sternum, and right back, right and left shoulder, right and left upper arm, right and left elbow, right and left forearms, medial and lateral right and left wrists, right and left fingers, right and left ASIS and PSIS. Five postures were collected for three trials with a three-minute rest between each posture. The sequence of the postures was determined for 26 batches by a randomized sampling method and given to participants in sequence according to the order of enrollment. Kinematic data was collected using eight

infrared cameras (Raptor-E, Motion Analysis Corporation, Santa, CA, USA) at the sampling rate of 100 Hz.

Data processing

Data was converted from analog to digital by Cortex software, Motion Analysis Corporation, Santa, CA, USA. Kinematic data was smoothed by Butterworth low-pass filtered at a cutoff frequency of 1 Hz, and EMG data was smoothed by Butterworth high-pass filtered at a cutoff frequency of 50 Hz and Butterworth lowpass filtered at a cutoff frequency of 500 Hz. The RMS values were normalized using the averaged MVIC amplitudes of each respective muscle. Visual 3D version 2020.08.3.

Data analysis

Descriptive statistics, mean, and standard deviations were performed using the PAWS statistics program (SPSS 18.0). Demographic data, joint kinematics, and muscle function were presented and reported.

RESULTS

Upper extremity joint movement in Ruesi Dutton

For cervical spine movement (Table 1), P4 was most active, followed by P3 in the left and right direction, and P2, P5. As for P1, there was very little movement on this axis. In the Y-axis (Table 2), there was lateral bending; and P3 in the right and left directions had the most movement. In the Z-axis (Table 3), P1 of the right and left rotation had the most movement, followed by the Kae Kiat posture in right and left direction, while the rest had little movement in this axis (not more than 10 degrees).

For thoracic spine movement (Table 1), the movement of P1, P3, P4, P5 was trunk flexion, and P5 had the most movement, followed by P3 in the left and right direction, P1, and P4, and P2 with movement in the form of trunk extension. In the Y-axis (Table 2), trunk movement was in the form of lateral bending and P5 had the most movement, followed by P1 and other postures without

Fig 2. Flow chart of the study

TABLE 1. Sagittal plane joint angles.

Joint angle [Degrees (Mean±SD)]

Phase

Neck

Trunk

Shoulders

Rt. Lt.

Elbows

Rt. Lt.

Wrist

Rt.

Lt.

P1 (Left) 5.40 -14.04 41.55 10.29 112.89 129.97 -21.62 -42.83

P1 (Right)

2.96

-13.61

3.24

46.5

131.95 109.18

-28.32

-32.66

± 9.10

± 10.87

±11.01 ±9.20

±7.71

± 8.53

±47.31

±25.82

± 8.67 ± 11.19 ± 10.45 ± 11.43 ± 9.49 ± 7.07 ± 25.68 ±38.93

P2 29.03 22.65 140.09 143.10 43.88 43.72 -15.85 -17.92

P3 (Left)

35.35

-29.13

98.57

104.89

21.52

19.51

14.68

12.84

±13.26

±15.94

±8.71

±8.82

±9.43

±9.37

±32.39

±32.01

±16.46 ±28.62 ±56.37 ±41.01 ±7.31 ±8.77 ±9.01 ±10.21

P3 (Right) 33.50 -28.95 101.08 99.19 19.47 21.99 22.59 3.05

P3 (Upward)

14.40

±12.81

-6.58

±12.47

147.44 151.12

±15.78 ±8.57

26.85

±8.34

26.21

±8.43

6.13

±39.43

-8.79

±29.26

±13.61 ±15.26 ±9.66 ±8.31 ±9.50 ±8.25 ±38.34 ±26.90

P4 47.93 -11.76 -53.26 -41.16 88.65 87.06 -60.1 -70.9

P5 (LKLS)

15.22

-37.27

148.20 144.35

118.50 118.21

-57.45

-56.02

±7.88

±16.96

±22.51 ±7.75

±4.62

±4.62

±10.20

±16.00

±14.86 ±13.89 ± 50.00 ± 51.99 ± 8.89 ± 8.44 ± 19.80 ± 12.94

P5 (LKRS) 16.68 -37.43 139.43 144.72 121.65 116.52 -62.17 -51.04

P5 (RKLS)

16.68

-37.51

146.39 148.66

119.38 119.58

-55.58

-49.84

±11.61

±14.63

±9.37

±10.87

±5.15

±4.14

±10.61

±36.85

±10.12 ±17.16 ±63.26 ±8.29 ±5.09 ±4.87 ±13.75 ±12.78

P5 (RKRS) 15.68 -38.08 142.25 147.95 121.81 117.67 -57.89 -52.46

±11.45 ±15.02 ±16.77 ±9.58 ±5.16 ±4.86 ±11.11 ±16.08

Cervical and thoracic spine: X axis in (+) extension, (-) flexion, Right shoulder joint: X axis (+) forward flexion, (-) extension. Left shoulder joint: X axis (+) forward flexion, (-) extension, Right elbow joint: X axis (+) flexion, (-) extension, Left elbow joint; X axis (+) flexion, (-) extension, Right wrist: X axis (+) palmar flexion, (-) wrist dorsiflexion. Left wrist joint, X axis (+) palmar flexion, (-) wrist dorsiflexion. Kae Lom Kho Mue Posture (P1), Kae Puat Thong Kae Kho Thao Posture (P2), Kae Kiat Posture (P3), Kae Puat Thong Sabak Chom Posture (P4), and Kae Lom Puat Sisa Posture (P5)

TABLE 2. Frontal plane joint angles.

Joint angle [Degrees (Mean±SD)]

Phase

Neck

Trunk

Shoulders

Rt. Lt.

Elbows

Rt. Lt.

Wrist

Rt.

Lt.

P1 (Left) 1.59 10.97 -0.34 30.70 13.09 -14.12 -47.89 58.82

P1 (Right)

-3.23

-8.50

-31.84

-6.01

11.23

-22.95

-63.47

45.99

±7.96

±5.73

±10.57 ±10.25

±6.39

± 8.88

±16.53

±12.81

±6.3 ± 5.22 ± 11.05 ± 10.7 ± 8.85 ± 5.88 ±18.44 ±12.69

P2 -1.36 1.28 -13.43 13.70 -6.90 4.05 -12.50 12.41

P3 (Left)

7.47

-4.23

9.81

22.27

-7.44

5.16

-51.06

57.25

±8.94

±7.17

±8.86

±11.90

±5.79

±6.29

±14.36

±15.29

±3.37 ±1.70 ±3.71 ±5.23 ±7.19 ±6.23 ±8.77 ±8.00

P3 (Right) -8.35 2.60 -23.86 -11.15 -8.81 2.78 -56.90 47.74

P3 (Upward)

-0.42

±4.05

0.32

±2.11

-14.72

±4.59

13.98

±5.70

-6.91

±5.96

4.31

±6.79

-55.76

±16.97

56.95

±14.00

±10.99 ±6.88 ±14.49 ±10.60 ±5.64 ±6.95 ±15.68 ±16.89

P4 -0.94 -0.83 -70.68 73.67 -5.02 6.7 -37.68 33.6

P5 (LKLS)

-1.21

-17.99

-45.00

41.83

6.58

-10.20

-15.10

16.58

±5.97

±9.56

±5.92

±6.59

±7.96

±6.42

±17.68

±12.44

± 3.65 ± 6.10 ± 9.26 ± 8.82 ± 7.68 ± 6.82 ± 22.00 ± 17.77

P5 (LKRS) 1.57 -17.51 -48.56 38.63 6.45 -9.63 -16.27 16.39

P5 (RKLS)

-0.51

17.74

-44.19

43.22

5.95±

-9.54±

-16.21

17.42

±4.07

±10.51

±5.07

±4.95

7.93

6.83

±16.90

±14.51

±4.41 ±10.08 ±5.65 ±5.35 ±7.89 ±6.83 ±17.55 ±11.93

P5 (RKRS) 2.27 19.00 -47.11 39.87 6.29 -9.21 -17.01 14.37

±4.66 ±10.23 ±5.54 ±4.83 ±7.83 ±6.76 ±16.75 ±11.34

Cervical and thoracic spine: Y axis (+) right tilt (-) left tilt, Right shoulder joint: Y axis (+) adduction and (-) abduction. Left shoulder joint: Y axis (+) abduction, (-) adduction. Right elbow joint: Y axis (+) medial tilt, (-) lateral tilt. Left elbow joint; Y axis (+) lateral tilt, (-) medial tilt. Right wrist: Y axis (+) ulnar deviation, (-) radial deviation. Left wrist joint, Y axis (+) radial deviation, (-) ulnar deviation. Kae Lom Kho Mue Posture (P1), Kae Puat Thong Kae Kho Thao Posture (P2), Kae Kiat Posture (P3), Kae Puat Thong Sabak Chom Posture (P4), and Kae Lom Puat Sisa Posture (P5)

TABLE 3. Transverse plane joint angles.

Joint angle [Degrees (Mean±SD)]

Phase

Neck

Trunk

Shoulders

Elbows

Wrist

Rt.

Lt.

Rt.

Lt.

Rt.

Lt.

P1 (Left) 58.99 34.76 71.79 -11.48 70.32 -70.22 35.01 -30.76

P1 (Right)

-62.72

-31.81

5.86

-65.79

67.21

-71.19

37.86

-24.63

± 13.81

±6.59

±22.19 ±14.02

±20.93 ±15.97

±50.17

±19.34

± 12.61 ± 34.76 ± 11.86 ± 19.97 ± 20.05 ± 15.43 ±33.41 ±35.47

P2 -0.40 -5.98 58.21 -54.72 62.72 -62.32 -4.97 5.88

P3 (Left)

10.37

26.16

72.92

-75.27

98.19

-110.60 90.33

-80.50

±9.79

±14.06

±17.52 ±16.22

±19.19 ±24.74

±35.34

±38.78

±5.08 ±35.14 ±18.59 ±13.45 ±16.25 ±14.62 ±15.97 ±12.67

P3 (Right) -12.73 -22.18 80.12 -65.56 95.33 -112.95 87.22 -68.76

P3 (Upward)

-0.71

±4.89

1.45

±2.97

82.08 -76.54

±18.43 ±14.93

96.69 -109.22 82.41

±18.15 ±18.90 ±39.00

-65.75

±28.79

±12.65 ±18.72 ±16.68 ±17.09 ±22.66 ±24.46 ±44.93 ±32.84

P4 -1.61 1.8 -102.49 87.19 71.33 -70.56 11.14 -1.04

P5 (LKLS)

-3.44

-4.59

70.58

-58.35

51.02

-49.43

-1.30

0.29

±7.73

±5.08

±15.68 ±12.28

±19.13 ±16.12

±10.50

±9.60

± 5.43 ± 2.68 ± 79.49 ± 78.29 ± 19.13 ± 15.85 ± 21.70 ± 11.10

P5 (LKRS) -6.53 -4.05 70.38 -57.42 50.57 -50.81 1.88 0.44

P5 (RKLS)

2.68

7.50

63.23

-61.68

50.65

-49.68

-1.98

-0.96

±5.77

±4.36

±11.10 ±13.10

±19.56 ±16.09

±9.77

±10.69

±7.58 ±4.45 ±14.88 ±11.43 ±19.44 ±14.92 ±9.95 ±11.22

P5 (RKRS) -0.54 8.17 61.70 -60.62 49.56 -50.06 -5.64 -1.71

±6.03 ±4.75 ±12.11 ±11.21 ±19.50 ±15.63 ±33.32 ±9.63

Cervical and thoracic spine: Z axis (+), (-) right rotation. Right shoulder joint: Z axis (+) internal rotation, (-) external rotation. Left shoulder joint: Z axis (+) external rotation, (-) internal rotation. Right elbow joint: Z axis (+) internal rotation of arm, (-) external rotation of arm. Left elbow joint; Z axis (+) external rotation of arm, (-) internal rotation of arm. Right wrist: Z axis (+) pronation, (-) supination. Left wrist joint: Z axis (+) supination, (-) pronation. Kae Lom Kho Mue Posture (P1), Kae Puat Thong Kae Kho Thao Posture (P2), Kae Kiat Posture (P3), Kae Puat Thong Sabak Chom Posture (P4), and Kae Lom Puat Sisa Posture (P5)

lateral bending. In the Z-axis (Table 3), the movement was in the form of trunk rotation and P1 and P3 in the right and left directions were very similar to those of the cervical spine.

The movement of the shoulder joint in the X-axis (Table 1) was in form of shoulder flexion in which P2, P5, and P3 in the upward direction had more than 140

- 180 degrees of movement whereas there were less than 100 degrees in other positions, and in P4 in the form of shoulder extension. In the Y-axis (Table 2), P4 and P5 saw the most extension of the arms whereas other postures had less than 40 degrees of extended arms. In the Z-axis (Table 3), most postures had an internal rotation of no more than 90 degrees, except for P4 which had an external rotation of greater than 100 degrees, which is higher than the degree of normal movement.

Elbow joint movement in the X-axis (Table 1) was elbow flexion, with the most flexion being P1, followed by P5, and other postures with no more than 90 degrees of flexion. In the Y-axis (Table 2), the medial till and lateral till, with very little movement, were no more than 15 degrees. In the Z-axis (Table 3), the medial rotation of the arm, with P3 had the most movement, whereas other postures did not move more than 70 degrees.

The movement of the wrist joints (Table 1) was in form of wrist extension, with P4 having the most movement, followed by P1, while other postures had movement of less than 50 degrees. In the Y-axis (Table 2), every posture was in form of radial deviation, and was most commonly found in P1, P3, P4 in which the degree was greater than normal, while other postures had movements less than 20 degrees. In the Z-axis (Table 3), P1, P3, P4 movement was in form of pronation wrist movement in which P3 had more than 80 degrees of movement while P2 and P5 were supinations, and not more than 20 degrees.

Muscle activation of upper extremities in Ruesi Dutton

P5 had the highest Biceps activity in the range of

12.54 - 14.40% MVIC, while other postures were in the range of 1.86 - 6.67% MVIC (Table 4). In the Triceps muscle, P3 had most muscle activity in the range of

19.53 – 32.67 %MVIC while other postures were in the range of 5.05-11.55% MVIC. In the Deltoids muscle, almost all postures had muscle activity in the range of

27.40 - 111.28% MVIC except for P1 which was in the range 3.94 - 10.82% MVIC. In the Lower Trapezius, P3 in the left and right directions, P5, P4, and P1 had muscle activity in the range of 78.73-121.33% MVIC while P4 and P3 in the upwards direction had muscle activities in the range of 30.01 - 48.87% MVIC. In the Middle

Trapezius muscle, P4 had the greatest muscle activity in the range of 63.50 - 65.19% MVIC, followed by P1 had muscle activity in the range of 41.19 - 49.04% MVIC while other postures had muscle activity in the range of

4.56 - 32.88% MVIC. For the Upper Trapezius, P5 had the greatest muscle activity in the range of 74.93 - 83.25% MVIC, and P2 and P4 had similar muscle activity in the range of 55.26 - 59.45% MVIC, while P3 had muscle activity in the range of 32.71 - 47.13% MVIC and P1 had muscle activity in the range of 12.79 - 14.53% MVIC.

DISCUSSION

The primary objective of this study was to investigate upper extremity joint angles and muscle activity while performing select HDBC postures. To the authors’ knowledge, this is the first study to fully describe 3D kinematic motion and muscle activation in HDBC. The movement of each joint had a range of motion within that joint’s normal range12-14 and in daily activity,15-17 but there was more radial deviation and extension in the wrists. In addition, caution was taken in people who had injuries or disease around the wrist. However, these exercises may be more suitable for carpal tunnel syndrome, as they are similar to tendon gliding exercises18 and require care in the movement of the neck and shoulders in the elderly and those who are overweight. This is because in such cases, the degree of motion is reduced14,19 and the external rotation angle of the shoulder is greater than the degree of normal movement so caution is necessary while performing these postures. Moreover, HDBC is recommended for patients with frozen shoulders due to the shoulder movement being greater than the range of motion of the disease.20 Therefore, further studies may be needed.

From the study of muscle function, it was found that the relationship between the posture name and its benefits could not be clearly explained because it was a study of the superficial muscle function in the upper extremities only, and it did not look at the muscles related to the name of the posture. In P1, the Lower and Middle Trapezius muscles are used more than any other bundle which can reduce wrist pain from myofascial pain syndrome which has a trigger point at the shoulder and upper back.21 However, EMG devices should be attached to pronator teres muscle, flexor, and extensor muscle group of the forearms and brachioradialis muscle because these muscles are directly related to wrist function. The lower and upper Trapezius have the most function in P2 but the benefits do not relate to the name of posture because the protocol for placing devices is not focused on proving the relationship. Therefore, EMG devices

TABLE 4. Muscle activity in Ruesi Dutton of upper extremities follows as; biceps, triceps, deltoid, upper trapezius, middle trapezius, and lower trapezius.

Kae Lom Kho Mue Posture (P1), Kae Puat Thong Kae Kho Thao Posture (P2), Kae Kiat Posture (P3), Kae Puat Thong Sabak Chom Posture (P4), and Kae Lom Puat Sisa Posture (P5)

should be attached to the abdominal muscle and lower legs. P3 can reduce tiredness and laziness4 according to the results and all the muscles had a function in the study. In P4, the three compartments of the Trapezius muscle have the most function which corresponds to the name of posture and benefits.4 Moreover, there is also research on the use of this posture to treat and prevent myofascial pain syndrome at the scapular and shoulder.5 In a further study, there must be an EMG device attached to the abdomen muscle. In P5, the muscles on the neck, shoulder, and upper back have functions that can help reduce tension-type headaches or myofascial pain syndrome21-23 but there should be a further study to prove the efficiency and mechanisms.

In addition, the muscle function was close to 15 yoga postures.24 The movement patterns of HDBC and asana yoga were found to have similar movement characteristics: to move the body in one position and hold still in the position for a period of time.4,25 Therefore, the function of the muscles is working similarly. Moreover, in the Triceps muscle, 1/3 of a bench press exercise had a value greater than D1 flexion and scapular exercise.26-27

CONCLUSION

This study explains the pattern of joints movement and muscle activity of the Ruesi Dutton exercise which can be used as a guide in choosing appropriate postures for different conditions to ensure maximum efficacy and safety for practitioners and trainers. In addition, this data supports evidence of Thai Traditional medicine.

ACKNOWLEDGEMENTS

The authors would like to thank the Routine to Research unit (R2R), the Center of Applied Thai Traditional Medicine, and the Department of Orthopedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University for supporting this study.

REFERENCES

1. The Fine Arts Department. Samut Phap Khlong Ruesi Datton. Bangkok: Amarin Printing and Publishing, 2551.

2. Somdet Phraborom Wong Thoe Kromphraya Damrong Ra Chanu Phap. “Ruesi Datton”. Nithan Borankhadi, 10th ed. Bangkok: Khasem Ban Na Kit, 2503.

3. The Office of Royal Society. Photchananukrom Chabap Ratchabandittayasathan B.E. 2554 Chaloemphrakiat PhraBatSomdetPhrachaoyuhua Nueang Nai Okat Phraratchaphithi Maha Mongkhon Chaloemphrachonphansa anniversary 7th. Bangkok: Sirivatana Interprint, 2556.

4. Ayurved Thamrong school, Center of Applied Thai Traditional Medicine, Faculty of Siriraj Medicine Hospital, Mahidol university. Kaiborihan Baep Ruesi Datton. Vol 1. Bangkok: Suppha Wanit Publishing, 2554.

5. Butdapan P, Narajeenarone K, Apichartvorakit A, Kade S, Jansomsarit S, Jamjuntra P, et al. The Effect of the Posture of the “Hermit Doing Body Contortion” on Relief of Shoulder and Scapular Pain Caused by Chronic Myofascial Pain Syndrome: A Randomized, Parallel Group, Controlled Trial. Siriraj Med

   J. 2016;68:350-7.

6. Tanasugarn L, Natearpha P, Kongsakon R, Chaosaowapa M, Choatwongwachira W, Seanglaw D, et al. Physical effects and cognitive function after exercising “Rue-si-dad-ton” (Exercise using the posture of the hermit doing body contortion): A randomized controlled pilot trial. J Med Assoc Thai. 2015;98(3): 306-13.

7. Ngowsiri K, Tanmahasamut P, Sukonthasab S. Rusie Dutton traditional Thai exercise promotes health related physical fitness and quality of life in menopausal women. Complement Ther Clin Pract. 2014;20(3):164-71.

8. Inokuchi H, Tojima M, Mano H, Ishikawa Y, Ogata N, Haga N. Neck range of motion measurements using a new three- dimensional motion analysis system: validity and repeatability. Eur Spine J. 2015: 2807-15.

9. SENIAM Project [Internet]. Netherland: Roessingh Research and Development; 2006 [cited 2019 Mar 9]. Available from: http://seniam.org/

10. Konrad P. The ABC of EMG-A practical introduction to Kinesiological Electromyography. U.S.A. Noraxon Inc., 2006.

11. Vicon Motion Systems Limited. Plug-in Gait Reference Guide [Internet]. 2017 [cited 2021 Dec 29]. Available from: https:// docs.vicon.com/

12. Boone DC, Azen SP. Normal range of motion of joints in male subjects. JBJS. 1979;61(5):756-9.

13. Youdas JW, Garrett TR, Suman VJ, Bogard CL, Hallman HO, Carey JR. Normal range of motion of the cervical spine: an initial goniometric study. Phys Ther. 1992;72(11):770-80.

14. Barnes CJ, Van Steyn SJ, Fischer RA. The effects of age, sex, and shoulder dominance on range of motion of the shoulder. J Shoulder Elbow Surg. 2001;10(3):242-6.

15. Rundquist PJ, Obrecht C, Woodruff L. Three-dimensional shoulder kinematics to complete activities of daily living. Am J Phys Med Rehabil. 2009;88(8):623-9.

16. Namdari S, Yagnik G, Ebaugh DD, Nagda S, Ramsey ML, Williams Jr GR, et al. Defining functional shoulder range of motion for activities of daily living. J Shoulder Elbow Surg. 2012;21(9): 1177-83.

17. Ryu J, Cooney III WP, Askew LJ, An KN, Chao EY. Functional ranges of motion of the wrist joint. J Hand Surg. 1991;16(3): 409-19.

18. Akalin E, El Ö, Peker Ö, Senocak Ö, Tamci S, Gülbahar S, et al. Treatment of carpal tunnel syndrome with nerve and tendon gliding exercises. Am J Phys Med Rehabil. 2002;81(2): 108-13.

19. Castro WH, Sautmann A, Schilgen M, Sautmann M. Noninvasive three-dimensional analysis of cervical spine motion in normal subjects in relation to age and sex: an experimental examination. Spine. 2000;25(4):443-9.

20. Rundquist PJ, Anderson DD, Guanche CA, Ludewig PM. Shoulder kinematics in subjects with frozen shoulder. Arch Phys Med Rehabil. 2003;84(10):1473-9.

21. Headaches disorder [Internet]. Switzerland: World Health Organization; 2016 [cited 2022 Jan 14]. Available from: https:// www.who.int/news-room/fact-sheets/detail/headache-disorders.

    
    

22. Prateepavanich P. Myofascial pain syndrome ca. In: Prateepavanich P, Chaudakshetrin P, editors. Myofascial pain syndrome: a common problem in clinical practice. 1st ed. Bangkok: Amarin Printing and Publishing; 2542.p.273-320.

23. Prateepavanich P. Subscapularis Muscle. In: Prateepavanich P, Chaudakshetrin P, editors. Myofascial pain syndrome: a common problem in clinical practice. 1st ed. Bangkok: Amarin Printing and Publishing; 2542.p.388-91.

24. Chopp-Hurley JN, Prophet C, Thistle B, Pollice J, Maly MR. Scapular muscle activity during static yoga postures. J Orthop Sports Phys Ther. 2018;48(6):504-9.

25. Govindaraj R, Karmani S, Varambally S, Gangadhar BN. Yoga and physical exercise–a review and comparison. Int Rev Psychiatry 2016;28(3):242-53.

26. Lauver JD, Cayot TE, Scheuermann BW. Influence of bench angle on upper extremity muscular activation during bench press exercise. Eur J Sport Sci. 2016;16(3):309-16.

27. Scott R, Yang HS, James CR, Sawyer SF, Sizer Jr PS. Volitional preemptive abdominal contraction and upper extremity muscle latencies during D1 flexion and scaption shoulder exercises. J Athl Train. 2018;53(12):1181-9.

Factors Influencing Willingness to Pay for Teledermatology among Patients with Psoriasis

Thanachat Rutnumnoi, M.D., Chayada Chaiyabutr, M.D., Narumol Silpa-archa, M.D., Chanisada Wongpraparut, M.D., Leena Chularojanamontri, M.D.

Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

ABSTRACT

Objective: To determine the proportion of patients with psoriasis prepared to pay for TD. Attitudes and factors influencing their willingness to pay (WTP) were evaluated.

Materials and Methods: This cross-sectional study was conducted from July 2020 to October 2021. Adult patients with psoriasis completed a 2-page self-administered questionnaire.

Results: Of 200 patients, 133 (66.5%) were unfamiliar with TD. However, 144 (72%) were prepared to pay for TD if it were introduced. The majority of patients answered that 300 Bath was the maximum price that they were willing to pay for TD service. Compared with traditional in-person visits, the significant positive influencing factors on WTP were TD’s quicker delivery of treatment, lower costs, and non-inferiority to usual care. Multivariate analysis showed that the independent factors for WTP were higher educational levels, elimination of out-of-pocket, in-hospital visit expenses, owning a business, TD options suited to psoriasis, and no adverse effects on the patient-doctor relationship. Conclusion: Knowing patients’ attitudes toward TD and the factors influencing their WTP is essential for developing efficient services. Data from this study can be used to develop successful TD services for patients with psoriasis.

Keywords: Psoriasis; Teledermatology; Telemedicine; Willingness to pay (Siriraj Med J 2022; 74: 731-738)

The abstract of this article was presented at the 46th DST Annual Meeting 2022.

INTRODUCTION

Psoriasis is a chronic, immune-related, inflammatory skin disease with various clinical features. It is found most frequently in 30- to 40-year-olds, and its incidence in children and adults has grown over the last 3 decades.1,2 The prevalence of psoriasis among adults has been reported to range from 0.51% to 11.43% of the world’s population.3 In addition to the physical burden of the disease, psoriasis can create a socioeconomic burden due to its direct and indirect costs. Traditional face-to-face patient care has several indirect financial and non-financial costs, such as lost income, time missed from school or work, and travel costs. Teledermatology (TD) alone can never be

better than face-to-face, in-office dermatology. However, it can decrease the number of face-to-face visits that are needed, increase access to dermatological care (the ability to obtain care), and improve the accessibility of dermatological care (the ease of obtaining care).4

During the COVID-19 pandemic, many countries adopted TD to provide treatment services for acne and chronic autoimmune inflammatory skin diseases.5 The TD systems can be classified into 3 distinct formats: “store-and-forward,” “real-time,” and “hybrid.” Store-and- forward involves the submission of digital photographs and related information. These are evaluated later to determine a diagnosis and an appropriate management

Corresponding author: Leena Chularojanamontri E-mail: leenajim@gmail.com

Received 3 August 2022 Revised 19 August 2022 Accepted 22 August 2022 ORCID ID:http://orcid.org/0000-0001-6625-6445 http://dx.doi.org/10.33192/Smj.2022.86

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

strategy. The store-and-forward format contrasts with real-time TD (for example, the use of video conferencing and online meeting rooms), in which the consultation and diagnosis take place synchronously. The third format, hybrid TD, combines the store-and-forward and real-time formats. All 3 formats can be used for direct care, clinical counseling, triage, and follow-up treatment.6,7 However, TD involves costs for items such as its administration and imaging support services. These extra costs are typically charged to patients by private hospitals and, for service outside standard consultation hours, by public hospitals. Private or public health insurance does not cover these additional expenses in several countries.

Due to technological advancements, TD can be as efficient as face-to-face visits.8,9 Additionally, TD is less time-consuming for patients.10-12 Different factors are associated with the willingness to use TD versus the willingness to pay (WPT) for TD. Werner et al studied the willingness to use telemedicine for routine care and specialized care. Their findings indicated that the participants were more willing to use telemedicine for routine care than specialized care. The patients’ willingness to use telemedicine was also negatively influenced by their concerns about using new technology, attitudes toward telemedicine, and fear that the patient-physician relationship might be undermined.13 However, the factors influencing patients’ willingness to use telemedicine and their attitudes toward telemedicine may not be the same as the factors and attitudes relating to WTP for telemedicine. Moreover, only a few studies have used a WTP approach to compare the preferences for TD versus traditional in-hospital visits of patients with psoriasis. This study investigated the attitudes of patients with psoriasis toward TD and the factors influencing

their WTP for TD.

MATERIALS AND METHODS

This cross-sectional study was conducted at the Department of Dermatology outpatient clinic, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand, from July 2020 through October 2021. Before this research began, its protocol was approved by the Siriraj Institutional Review Board (Si 490/2020). The eligibility criteria were adult patients with psoriasis who were 18 years or older. Patients were excluded if they could not read or understand the study questionnaire or had mental or psychological diseases. All participating patients provided written informed consent.

Patients individually completed a 2-page, self- administered questionnaire. It was designed to identify attitudes toward TD technology and factors influencing

WTP for TD. Patients needing assistance with any aspect of the questionnaire could ask for the help of an investigator. Details of the following were collected: demographic data (age, sex, education, occupation, income, and comorbid diseases), information related to face-to-face visits to the hospital (waiting time to see a doctor, out-of-pocket expenses, type of medical insurance, and frequency of visits), attitudes toward TD, and WTP for TD. We determined the patient’s WTP out-of-pocket by using the payment card model of contingent valuation methods. The patients indicated the maximum value they were WTP for a range of amounts depending on the actual out-patient dermatological care services.

The frequencies of face-to-face visits to Siriraj Hospital to receive psoriasis treatment were classified as “very often” (≥ 1 time/month), “often” (1 time/3 months–< 1 time/month), and “not often” (< 1 time/3 months). The severity of psoriasis was classified according to the nature of the treatment provided and the Self- Administered Simplified Psoriasis Index score. Patients with “moderate to severe psoriasis” were defined as those receiving at least 1 type of systemic treatment for their psoriasis. Patients with “mild psoriasis” were considered those given topical treatments only. Patients with a Self-Administered Simplified Psoriasis Index severity score of < 10 and ≥ 20 were defined as having mild and severe psoriasis, respectively.14 In the case of patients who indicated a WTP for TD, they were asked to select 1 of 4 possible out-of-pocket costs that they would be willing to pay for the TD service: 200 Baht ($6, €5.40); 300 Baht ($9, €8.10); 400 Baht ($12, €10.80); and 500

Baht ($15, €13.50). Biding format was not used in this study. Thus, higher or lower price than that of patient’s answer did not offer.

To improve our understanding of the factors influencing WTP for TD services, we also divided patients into 2 groups. “Group A” comprised patients interviewed during the first wave of the COVID-19 epidemic in Thailand (July 2020–December 15, 2020). “Group B” consisted of patients interviewed during the second wave of the COVID-19 pandemic (December 16, 2020–October 2021). These groupings were made because TD began to be increasingly used after the first wave as part of measures to reduce the spread of COVID-19 infections in Thailand. We postulated that more patients in the second wave would have had experience with or known about TD than in the first wave.

Statistical analysis

Statistical analyses were conducted using PASW Statistics for Windows, version 18.0 (SPSS Inc., Chicago, IL,

USA). Continuous data are presented as the mean ± standard deviation (SD) and median (interquartile range), whereas categorical data are presented as frequencies and percentages. As appropriate, group comparisons were made using the Mann–Whitney U test, the two-tailed test, the Chi2 test, or Fisher’s exact test. Statistical significance was defined as P values less than 0.05. The factors associated with WTP for TD were analyzed using multiple logistic regression. This analysis included only those variables with a P value of less than 0.2 in a univariate analysis.

RESULTS

The 200 enrolled patients had a mean age of

45.38 ± 13.22 years. There were 115 women (57.50%) and 85 men (42.50%), and most of the patients lived in urban areas (69%). The majority (73.5%) also had postsecondary education (at universities, colleges, trade schools, or vocational schools; Table 1).

Although most of the patients were full- or part- time workers, 127 (63.5%) stated that they did not need to take time off from work to visit the hospital. The most common comorbid diseases were hypertension, dyslipidemia, diabetes mellitus, and psoriatic arthritis, in decreasing order of frequency. Most patients (80.5%) had had psoriasis for more than 5 years. Based on their treatments, 152 (76%) had moderate to severe psoriasis. Most patients often visited the hospital, and the waiting time to see a dermatologist was at least 30 minutes. Public and private insurance were used to cover the medical expenses of 63% and 7.5% of the patients, respectively. The additional out-of-pocket expenses associated with the in-person hospital visits (such as travel costs and the hospital’s administrative charge) were more than 200 Baht ($6, €5.40) for most patients.

One hundred thirty-three patients (66.5%) were unfamiliar with TD. However, 144 patients (72%) indicated that they were willing to pay for the service if it were introduced. Most patients believed TD would provide several benefits for psoriasis treatment in terms of a more efficient and quicker service, reduced costs (by eliminating the out-of-pocket expenses for in-person hospital visits), and no adverse effects on the doctor-patient relationship (Table 2). The proportion of patients with these positive attitudes was significantly higher among patients who indicated a WTP than patients who did not. It should be noted that the proportion of patients who knew about TD was higher among the WTP group than the non-WPT group.

Furthermore, the WTP group of patients had substantially fewer concerns about TD in general than the non-WPT group (P = 0.010). However, there were no

significant differences in the specific points of concern of the 2 groups: the use of new forms of technology, the quality of internet connections, and online privacy and safety. The patients in the WTP group had significantly higher levels of education and greater out-of-pocket expenses for their in-person hospital visits than those in the non-WTP group. Regarding the out-of-pocket costs that patients were still prepared to pay for the TD service, 43.1%, 34%, 5.6%, and 17.4% selected 200 Baht, 300 Baht, 400 Baht, and 500 Baht, respectively (data not shown).

Univariate analysis revealed that the significant factors associated with WTP were higher educational levels, reduction of in-hospital visit expenses, TD options suited to psoriasis treatment, ability to undertake routine appointments, reduction in treatment duration, cheaper than a face-to-face visit, absence of adverse effects on the doctor-patient relationship, and concerns about the use of TD for psoriasis treatment (Table 3). Using multivariate analysis, the independent factors associated with WTP were higher educational levels, elimination of out-of-pocket, in-hospital visit expenses, owning a business, TD options suited to psoriasis treatment, and no adverse effects on the doctor-patient relationship.

In a comparison between WTP for TD among patients during the first and second waves of the COVID-19 pandemic in Thailand, a significantly higher proportion of patients during the second wave knew about TD than during the first wave (49.1% vs 27.9%; P = 0.005). All patients in the second wave (100%) believed that TD could be used for psoriasis treatment and routine appointments. The corresponding values for the patients in the first wave were significantly lower (89.1% for psoriasis treatment [P = 0.007] and 91.8% for routine appointments [P = 0.039]; data not shown).

DISCUSSION

Even before the COVID-19 pandemic era, the use of TD had been growing dramatically for 2 decades. This development resulted from steady advances in technology that enabled patients to easily access medical care even if they lived in usually difficult-to-reach public health locations. The effectiveness of TD was found to be comparable to that of face-to-face visits by a randomized controlled trial in 2019 (N = 592) and a systemic review in 2020 (4 randomized controlled trials, 2 prospective cohorts, and 1 case series; N = 596).15 Even when using TD for psoriasis treatment, there were significant improvements in psychological impairment (evaluated by psychological functioning and the Dermatology Life Quality Index) and disease severity (assessed by the Psoriasis Area and

TABLE 1. Demographic data and related information of 200 patients with psoriasis visiting hospital from July 2020 through October 2021.

Variables Values

Sex, n (%)

Females 115 (57.5)

Age (years), mean ± SD 45.38 ± 13.22

Current address, n (%)

Urban area 138 (69)

Education level, n (%)

Less than or equal to secondary school Postsecondary

53 (26.5)

147 (73.5)

Rural area 62 (31)

Occupations, n (%)

Full-time worker 115 (57.5)

Part-time worker 76 (38)

Income (Baht/month), n (%)

≤ 5,000

5,001–10,000

10,001–20,000

20,001–50,000

> 50,000

36 (18)

19 (9.5)

48 (24)

71 (35.5)

26 (13)

Business owner 9 (4.50)

Underlying diseases, n (%) 121 (60.5)

Hypertension 56 (28)

Dyslipidemia 38 (19)

Diabetes mellitus 32 (16)

Duration of psoriasis (years), n (%)

< 5

5–10

> 10

39 (19.5)

53 (26.50)

108 (54)

Psoriatic arthritis 31 (15.50)

Severity scores as assessed by the Self-Administered Simplified Psoriasis Index, n (%)

Mild (< 10) 135 (67.5)

Moderate (10 –< 20) 52 (26)

Current treatment, n (%)

Only topical treatment Systemic treatment

48 (24)

152 (76)

Severe (≥ 20) 13 (6.5)

Frequency of hospital visits due to psoriasis, n (%)

Very often (≥ 1 times/month) 15 (7.50)

Often (1 time/3 months–< 1 time/month) 148 (74)

Waiting time to see a doctor, n (%)

< 15 minutes

15–30 minutes

31–< 60 minutes

1–2 hours

> 2 hours

6 (3)

58 (29)

57 (28.5)

50 (25)

29 (14.5)

Not often (< 1 time/3 months) 37 (18.50)

Medical insurance, n (%)

Public insurance 126 (63)

Private insurance 15 (7.5)

Extra expense for hospital visit (Baht), n (%)

≤ 200 Baht (≤ $6, €5.40)

> 200 Baht (> $6, €5.40)

56 (28)

144 (72)

Self-insured 59 (29.5)

Abbreviation: SD; standard deviation

TABLE 2. Comparison of attitudes of patients with psoriasis who were willing and not willing to pay for teledermatology.

*Indicates statistical significance

Severity Index, Physician Global Assessment, and body surface area). Furthermore, TD improved the patient- physician relationship as it was easier for patients to see a doctor.15

Attitudes toward TD differ between subgroups of populations and patients, depending on factors such as a country’s economic development, socioeconomic status, and culture. A survey in the United States of the attitudes of 100 dermatology patients toward synchronous TD during the COVID‐19 era reported that 88.9% were satisfied, and 81.8% had not experienced any technical difficulties. However, despite the immense satisfaction with synchronous TD, 68.7% of the patients preferred a face-to-face consultation for their next visit.16 Another study of 168 dermatology patients from the United States reported that most of the patients liked TD due to the more efficient use of their time (81.1%), transportation not being required (74.2%), and the ability to maintain social distancing (73.6%). The 2 most common criticisms

given by the minority of patients who did not like TD were lack of physical touch (26.8%) and a perception that they received inadequate assessments (15.7%). Regarding whether TD could adequately substitute for in-person visits, 55% agreed that it could, 25% disagreed, while the remaining 20% neither agreed nor disagreed.17

Most patients in the studies conducted in Thailand and the United States perceived TD to be more efficient and less time-consuming than traditional in-person visits. On the other hand, the patients surveyed in both countries expressed concerns about a possible deterioration of the doctor-patient relationship and the lack of physical touch. Given that Thailand and the United States are very different in terms of ethnicity, culture, and social and economic development, the commonalities between the findings suggest that those positive and negative attitudes may be widespread.

We searched the PubMed and Embase databases using the keywords “willingness to pay,” “telemedicine,”

TABLE 3. Multiple logistic regression analysis of factors associated with willingness to pay for teledermatology for the treatment of psoriasis.

Quicker than face-to-face visits

Teledermatology can reduce 6.961 (1.309–37.004) 0.023* 0.543 (0.028–10.356) 0.685

Cheaper than face-to-face visits Teledermatology has the potential to

reduce the cost of treatment

13.596 (2.836–65.172) 0.001*

7.624 (0.819–70.991)

0.074

the length of treatment

Concerned about teledermatology use

for psoriasis

0.435 (0.228–0.827)

0.011*

0.499 (0.220–1.136)

0.098

Teledermatology will impair the doctor-patient 0.252 (0.130–0.490) < 0.001* 0.314 (0.129–0.762) 0.011* relationship

*Indicates statistical significance

“teledermatology,” and “skin diseases.” Table 4 summarizes the findings of published studies evaluating factors that influence WTP for TD to treat skin diseases (psoriasis, melanoma, acne, and skin cancer).18-22 Qureshi et al reported that 95% of patients with psoriasis and melanoma were willing to pay out of pocket for TD if it provided quicker access to care, compared to only 58% if the access times for TD and traditional in-person visits were the same. The patients also reported that they were willing to pay

a median of $25 out of pocket for TD consultations.18 Seeing specialists (dermatologists) to detect melanoma and skin cancer was a critical factor in favor of TD.19 For patients with acne, the critical factors supporting the use of TD were a less expensive service, fewer hours away from work or school, a reduction in lost income, and lower travel costs. Mori et al studied WTP for electronic follow-up visits among acne patients on isotretinoin therapy in the United States. Sixty-four patients (61%)

TABLE 4. Factors associated with willingness to pay for teledermatology of patients with skin diseases.

N/A, not available

were willing to pay out of pocket for an e-visit, for a median cost of $25.21 Most of the participants (64.8%) reported having no concerns about the safety of e-visits. Our study added further information for patients with psoriasis. Specifically, it identified that the independent factors associated with WTP for TD services were higher educational levels, elimination of out-of-pocket, in-hospital

visit expenses, owning a business, TD options suited to psoriasis treatment, and no adverse effects on the doctor- patient relationship. The payment card method used in this study had some limitations, including a range bias, in which participants tended to choose the lower half of the stated price, and the range of provided amounts had the potential to affect the maximum cost of TD.

CONCLUSION

In conclusion, although TD cannot replace face- to-face visits for psoriasis treatment, its use is likely to continue to increase markedly. Understanding the attitudes of patients and the factors associated with WTP is essential for developing successful TD services and broadening their appeal to patients with psoriasis.

ACKNOWLEDGMENTS

We thank Mrs. O. Supapueng for her assistance with the statistical analyses. The authors are also indebted to Mr. David Park for the English-language editing of this paper.

Funding sources

No funding was received for conducting this study.

Conflicts of interest

The authors have no relevant financial or non- financial interests to disclose.

Abbreviations

CI: confidence interval N/A: not available

OR: odds ratio

SD: standard deviation TD: teledermatology WTP: willingness to pay

REFERENCES

1. Pezzolo E, Naldi L. Epidemiology of major chronic inflammatory immune-related skin diseases in 2019. Expert Rev Clin Immunol. 2020;16(2):155-66.

2. Icen M, Crowson CS, McEvoy MT, Dann FJ, Gabriel SE, Kremes HM. Trends in incidence of adult-onset psoriasis over three decades: a population-based study. J Am Acad Dermatol. 2009; 60(3):394-401.

3. Michalek I, Loring B, John S. A systematic review of worldwide epidemiology of psoriasis. J Eur Acad Dermatol Venereol. 2017; 31(2):205-12.

4. Landow SM, Mateus A, Korgavkar K, Nightingale D, Weinstock MA. Teledermatology: key factors associated with reducing face-to-face dermatology visits. J Am Acad Dermatol. 2014;71(3): 570-6.

5. Elsner P. Teledermatology in the times of COVID‐19–a systematic review. J Dtsch Dermatol Ges. 2020;18(8):841-5.

6. Coates SJ, Kvedar J, Granstein RD. Teledermatology: from historical perspective to emerging techniques of the modern era: part I: history, rationale, and current practice. J Am Acad Dermatol. 2015;72(4):563-74.

7. Pasquali P, Sonthalia S, Moreno-Ramirez D, Sharma P, Agrawa M, Gupta S, et al. Teledermatology and its current perspective. Indian Dermatol Online J. 2020;11(1):12-20.

8. Uscher-Pines L, Malsberger R, Burgette L, Mulcahy A, Mehrotra

   A. Effect of teledermatology on access to dermatology care

   among Medicaid enrollees. JAMA Dermatol. 2016;152(8): 905-12.

9. Chambers CJ, Parsi KK, Schupp C, Armstrong AW. Patient- centered online management of psoriasis: a randomized controlled equivalency trial. J Am Acad Dermatol. 2012;66(6):948-53.

10. Wang RH, Barbieri JS, Nguyen HP, Stavert R, Forman HP, Bolognia JL, et al. Clinical effectiveness and cost-effectiveness of teledermatology: Where are we now, and what are the barriers to adoption? J Am Acad Dermatol. 2020;83(1):299- 307.

11. Zakaria A, Maurer T, Su G, Amerson E. Impact of teledermatology on the accessibility and efficiency of dermatology care in an urban safety-net hospital: A pre-post analysis. J Am Acad Dermatol. 2019;81(6):1446-52.

12. Warshaw EM, Hillman YJ, Greer NL, Hagel EM, MacDonald R, Rutks IR, et al. Teledermatology for diagnosis and management of skin conditions: a systematic review. J Am Acad Dermatol. 2011;64(4):759-72.

13. Werner P, Karnieli E. A model of the willingness to use telemedicine for routine and specialized care. J Telemed Telecare. 2003;9(5):264-72.

14. Chularojanamontri L, Wongpraparut C, Winayanuwattikun W, Griffiths CE, Chalmers RJ, et al. A reevaluation of the Simplified Psoriasis Index (SPI) using the Thai language version: a study examining the validity, reliability, and interpretability of SPI when used in translation. Journal of Psoriasis and Psoriatic Arthritis. 2020;5:32-9. Available from: https://doi.org/10.1177/ 2475530319892196

15. Dahy A, El‐Qushayri AE, Mahmoud AR, Al-kelany TA, Salman S. Telemedicine approach for psoriasis management, time for application? A systematic review of published studies. Dermatol Ther. 2020;33(6):e13908.

16. Pearlman RL, Le PB, Brodell RT, Nahar VK. Evaluation of patient attitudes towards the technical experience of synchronous teledermatology in the era of COVID-19. Arch Dermatol Res. 2021;313(9):769-72.

17. Yeroushalmi S, Millan SH, Nelson K, Sparks A, Friedman AJ. Patient Perceptions and Satisfaction With Teledermatology During the COVID-19 Pandemic: A Survey-Based Study. J Drugs Dermatol. 2021;20(2):178-83.

18. Qureshi AA, Brandling-Bennett HA, Wittenberg E, Chen SC, Sober AJ, Kvedar JC. Willingness-to-pay stated preferences for telemedicine versus in-person visits in patients with a history of psoriasis or melanoma. Telemed J E Health. 2006;12(6):639- 43.

19. Spinks J, Janda M, Soyer HP, Whitty JA. Consumer preferences for teledermoscopy screening to detect melanoma early. J Telemed Telecare. 2016;22(1):39-46.

20. Pathipati AS, Ko JM. Implementation and evaluation of Stanford Health Care direct-care teledermatology program. SAGE Open Med. 2016;4:2050312116659089.

21. Mori WS, Houston N, Moreau JF, Prevost N, Gehris RP, Ferris LK, et al. Personal burden of isotretinoin therapy and willingness to pay for electronic follow-up visits. JAMA Dermatol. 2016; 152(3):338-40.

22. Snoswell CL, Whitty JA, Caffery LJ, Loescher LJ, Gillespie N, Janda M. Direct-to-consumer mobile teledermoscopy for skin cancer screening: Preliminary results demonstrating willingness- to-pay in Australia. J Telemed Telecare. 2018;24(10):683-9.

Long-term Oncologic Outcomes After Curative Surgery in Stage I–III Thai Colorectal Cancer Patients

Aitsariya Mongkhonsupphawan, M.D., Nutchaphol Sethalao, M.D., Woramin Riansuwan, M.D.

Colorectal Surgery Unit, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

ABSTRACT

Objective: The survival rate for colorectal cancer varies and there are limited reports regarding the long-term outcomes after curative treatment in Thai patients. This study aimed to determine the long-term oncologic results in non-metastatic Thai colorectal cancer patients after curative surgery.

Materials and Methods: We performed a retrospective review of a prospectively collected colorectal cancer registry. Short-term and long-term outcomes were analyzed.

Results: 626 patients were included in the study, 51.9% colon cancer and 48.1% rectal cancer patients. The mean age was 63.6 ± 12.7 years. The median follow-up time was 5.4 years [IQR: 2.1–7.4]. The 5-year local recurrence was 6.4%; 3.3% in colon cancer and 9.9% in rectal cancer. The 5-year overall survival (5-yr OS) in the colon cancer patients was 76.3%; 94.6% in stage I, 80.8% in stage II, and 65.3% in stage III. The 5-yr OS in the rectal cancer patients was 65.1%; 84.7% in stage I, 75% in stage II, and 51% in stage III. The 5-year disease-free survival (5-yr DFS) in the colon cancer patients was 76.5%; 91.4% in stage I, 81.3% in stage II, and 66.4% in stage III. The 5-yr DFS in the rectal cancer patients was 63.8%; 81.5% in stage I, 75.1% in stage II, and 50.1% in stage III.

Conclusion: The long-term oncologic outcomes after curative treatments in this study were acceptable. The prognosis of treatment depends on the disease stage. Comparing stage by stage, colon cancer has a better prognosis than rectal cancer.

Keywords: Colorectal cancer; long-term outcomes; overall survival; disease-free survival; Asian; Thai (Siriraj Med J 2022; 74: 739-746)

INTRODUCTION

Colorectal cancer is one of the most common public health problems. According to the International Agency for Research on Cancer and the World Health Organization, colorectal cancer is the third-most common cancer in men and the second-most common in women worldwide.1 When diagnosing the disease, most patients would like to know their stage of disease and prognosis. The survival rate of colorectal cancer can vary based on a variety of factors, particularly the stage of the disease. The mortality rate from colorectal cancer has declined from the past

because surgeons can now diagnose it earlier and as the treatments have improved. Most of the data regarding long-term survival are reported from Western countries. While there are some publications regarding treatment in colorectal cancer reported from Asian countries, data on the long-term outcomes after curative treatment in stage I–III colorectal cancer, particularly in Thailand, are limited. We, therefore, conducted this study to determine the long-term oncologic results in stage I–III colorectal cancer patients after curative surgery.

Corresponding author: Aitsariya Mongkhonsupphawan E-mail: Aitsariya.mon@mahidol.ac.th

Received 2 July 2022 Revised 8 August 2022 Accepted 17 August 2022 ORCID ID:http://orcid.org/0000-0003-1273-918X http://dx.doi.org/10.33192/Smj.2022.87

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

MATERIALS AND METHODS

After approval by the Siriraj Institute Review Board (Si 581/2015), we performed a retrospective review of the prospectively collected colorectal cancer registry in the Colorectal Surgery Unit, Department of Surgery, Faculty of Medicine Siriraj Hospital. We retrieved data including stage I–III colorectal cancer patients who underwent curative surgery between 2007 and 2011. Patients’ information was abstracted from the registry, such as patients’ demographic data (age, gender, co- morbidities), preoperative carcinoembryonic antigen (CEA), location of the tumor, type of surgery, short-term outcomes (postoperative complications and mortality), pathological staging, date of the last visit, current survival, and recurrence. The 5-year local recurrence rate (5-yr LR), 5-year overall survival (5-yr OS), and 5-year disease- free survival (5-yr DFS) were analyzed.

The exclusion criteria were 1) patients who had synchronous or a history of other primary cancers or who had developed other primary cancers during the study period, 2) histology other than adenocarcinoma, 3) stage IV disease, 4) patients who did not receive curative-intent surgery, 5) hereditary colorectal cancer syndrome, such as Lynch syndrome and familial adenomatous polyposis (FAP), and 6) either synchronous or metachronous colorectal adenocarcinoma.

Statistical analysis

We exported the retrieved data to SPSS version 23 statistical software for performing all the statistical analysis. We examined the baseline characteristics of the enrolled patients using descriptive statistics. We report the categorical data by number and percentage, while continuous data, such as age, preoperative CEA level, and follow-up time, were reported by the mean and standard deviation or median and interquartile range depending on the skewness of the data. We estimated the distribution of overall survival and disease-free survival through Kaplan–Meier survival analysis.

RESULTS

Study population

We retrieve the data related to 1,010 colorectal cancer patients who underwent surgery in our unit during the study period, but then excluded 384 patients according to our exclusion criteria. Therefore, the data of 626 stage I-III colorectal adenocarcinoma patients were analyzed comprising 325 colon cancer patients and 301 rectal cancer patients. The median follow-up time was

5.4 years [IQR: 2.1-7.4].

Patient characteristics

The mean age ± standard deviation of the patients was

63.6 ±12.7 years old. There were 335 (53.5%) male and 291 (46.5%) female patients. The most common co-morbidity was hypertension (33.9%) followed by diabetes mellitus (17.3%), cardiovascular disease (12.6%), dyslipidemia

(10.4%), neurovascular disease (8%), respiratory disease (6.5%), and renal disease (3.4%), respectively. The median preoperative CEA was 4.4 ng/mL [IQR; 2.5-12.1]. Forty- one patients (6.5%) presented with acute obstruction. Of these, 15 patients were treated with colonic stent; 10 patients with Hartmann’s procedure; 12 patients with one- stage colonic resection and anastomosis; and 4 patients with subtotal colectomy and ileorectal anastomosis. Nine percent of the rectal cancer patients received preoperative neoadjuvant concurrent chemoradiation.

Tumor locations and operations

Regarding colon cancer, 99 patients (30.5%) had right-sided colon cancer, including 27 cecum, 26 ascending colons, 21 hepatic flexure, and 25 transverse colons. Meanwhile, 226 patients (69.5%) had left-sided tumors, including 10 splenic flexure colons, 43 descending colons, 123 sigmoid colons, and 50 rectosigmoid colons. For the rectal cancers, 74 lesions were located above the peritoneal reflection, 62 at the peritoneal reflection, and 165 below the peritoneal reflection. Considering the surgery technique, most patients in this study (94.7%) were operated with open surgery. Only 5.3% of patients were operated with minimally invasive surgical techniques, including both laparoscopic-assisted and hand-assisted surgery. The most common type of operation in colon cancer was sigmoidectomy or anterior resection (59.7%). Overall, 212 (70.4%) of the rectal cancer patients could have had a sphincter preserving operation. Of these, 33 patients (15.6%) had a protective diverting stoma. Meanwhile, 89 patients (29.6%) underwent abdominoperineal resection.

Pathology and staging

This cohort consisted of 56 (8.9%) well differentiated carcinomas, 536 (85.6%) moderately differentiated

carcinomas, 24 (3.8%) poorly differentiated carcinomas, 4

(0.6%) signet ring cell carcinomas, and 3 (0.5%) mucinous carcinomas. Regarding pT staging, the tumors were 27 (4.3%) T1, 133 (21.2%) T2, 399 (63.7%) T3, 42 (6.7%)

T4a, and 25 (4%) T4b. More than one-quarter of patients (27.8%) had lymphovascular invasion and 20.6% of patients had a perineural invasion. The median number of total harvested lymph nodes was 19 [IQR: 14-27]. The positive all resection margin rate in the specimens was

9.3%; comprising 8.1% positive circumferential margin (CRM) and 1.3% positive distal resection margin. As per our anticipation, there were more positive CRM cases in rectal cancer than in colon cancer (10.6% versus 5.8%), as well as more positive distal resection margin cases in rectal cancer than in colon cancer (1.9% versus 0.6%). Most patients had pathological stage II and III diseases, both for colon and rectal cancer (Fig 1).

Short-term outcomes

The overall complication rate in this study was 20.8%; 7.2% medical-related complications, and 17.1% surgical- related complications. Respiratory complication was the most common medical-related complication (3.2%) followed by 2.2% urinary tract infection, 1.6% cardiac complication, and 0.5% thromboembolism complications. Meanwhile, superficial surgical site infection was the most common surgical-related complication (10.1%), followed by 7.8% stoma complication, 2.7% urinary retention, 1.9% intraabdominal collection, 0.8% wound dehiscence, and 0.5% deep surgical site infection. The overall anastomotic leakage rate was 3%; 1.7% in colon cancer operations and 5.2% in rectal cancer operations. One percent of patients had to be re-admitted within 30 days after surgery. Approximately, 12.8% of patients required postoperative ICU stay and the postoperative mortality rate was 1%.

Long-term outcomes

The 5-yr OS of all the patients in this cohort (stage I–III, including both colon and rectal cancer) was 70.9%;

89.1% in stage I, 78.6% in stage II, and 57.9% in stage III; while the 5-yr DFS of all the patients in this cohort was 70.4%; 85.9% in stage I, 79% in stage II, and 57.8% in stage III. Comparing stage by stage, rectal cancer had a poorer prognosis than colon cancer, as demonstrated by the 5-yr OS and 5-yr DFS (Table 1, Fig 2, and Fig 3). Compared to the colon cancer patients, the rectal cancer patients had a higher 5-year local recurrence rate: 3.1% in colon cancer and 8.3% in rectal cancer, respectively. The overall distant recurrence rate of both the colon and rectal cancer patients in this study was approximately 24%; 20% in colon cancer patients and 28.6% in rectal cancer patients. The liver was the most common distant recurrence site in colon cancer, while the lung was the most common distant recurrence site in rectal cancer (Table 2).

Factors related to distant recurrences

On multivariate analysis, the independent predictors of distant recurrence in rectal cancer patients were preoperative CEA > 5 ng/mL, (HR=1.701; 95% CI, 1.069-2.706; P = 0.025), N2 stage (HR=2.837; 95% CI, 1.779-4.524; P <

1. , presence of tumor deposit (HR=3.567; 95% CI, 1.539-8.271; P = 0.003), positive circumferential margin (HR=2.117; 95% CI, 1.226-3.657; P= 0.007), and tumor

   located below peritoneal reflection (HR=2.279; 95% CI, 1.239-4.192; P=0.008). Howerever, preoperative CEA > 5 ng/mL, (HR=2.363; 95% CI, 1.399-3.989; P = 0.001)

   and pathological N2 staging (HR = 4.254 ; 95% CI, 2.228- 8.123; p < 0.001) were related to distant recurrence in colon cancer patients.

   
   

   Fig 1. Pathological staging of the study cohort.

   
   

   
   

   TABLE 1. Kaplan–Meier estimated 5-year overall survival and 5-year disease-free survival in stage I–III colon and rectal cancer patients.

   
   

   Stage Colon and rectal cancer Colon cancer Rectal cancer
   	5-yr OS	5-yr DFS	5-yr OS	5-yr DFS	5-yr OS	5-yr DFS
   Stages I–III	70.9%	70.4%	76.3%	76.5%	65.1%	63.8%
   Stage I	89.1%	85.9%	94.6%	91.4%	84.7%	81.5%
   Stage II	78.6%	79.0%	80.8%	81.3%	75.0%	75.1%
   Stage IIA	81.6%	78.6%	83.2%	80.6%	79.1%	75.7%
   Stage IIB	66.7%	84.4%	70.0%	88.9%	60.0%	80.0%
   Stage IIC	50.0%	80.0%	62.5%	83.3%	25.0%	75.0%
   Stage III	57.9%	57.8%	65.3%	66.4%	51.0%	50.1%
   Stage IIIA	72.7%	79.8%	81.3%	86.7%	50.0%	55.6%
   Stage IIIB	65.1%	63.1%	71.7%	71.4%	58.3%	55.1%
   Stage IIIC	36.3%	37.7%	34.5%	33.4%	37.3%	39.6%

   Abbreviations: 5-yr OS = 5-year overall survival; 5-yr DFS = 5-year disease free survival.

   
   

   Fig 2. Five-year overall survival in stage I-III colon and rectal cancer patients.

   
   

   
   

   
   

   Fig 3. Five-year disease-free survival in stage I-III colon and rectal cancer patients

   
   

   TABLE 2. Sites of distant recurrence in stage I–III colon and rectal cancer patients.

   
   

   Colon cancer Rectal cancer (n = 325) (n = 301)

   DISCUSSION

   Local	10 (3.1%)	25 (8.3%)
   Distant	65 (20%)	86 (28.6%)
   Liver	39 (12%)	32 (10.6%)
   Lung	24 (7.4%)	47 (15.6%)
   Peritoneal	8 (2.5%)	12 (3.9%)
   Bone	8 (2.5%)	16 (5.3%)
   Brain	4 (1.2%)	3 (1%)
   Supraclavicular lymph node	3 (0.9%)	0 (0%)
   Para-aortic lymph node	6 (1.8%)	3 (1%)

   In our study, the age incidence of colorectal cancer was between the fifth and seventh decades of life. The incidence was higher in males than females. These patient characteristics were comparable to the previous studies reported in Western countries.2-7 Regarding the locations of the tumors, approximately half of the patients were diagnosed with rectal cancer, which was a relatively high proportion. For the colon cancers, most were in the left- sided colon and located distal to the splenic flexure. We also noticed that most tumors were locally advanced stage. The incidence of acute obstruction was 6.5%, which was similar to previous reports. The postulated reasons to explain these results were: 1) most rectal cancer patients who needed multimodalities treatment were referred to our hospital, which is a tertiary university hospital, and

   2) most patients presented with symptoms and signs of colorectal cancer rather than asymptomatic ones. This might reflect the low participation rate in colorectal

   
   

   cancer screening programs and poor patient education on colorectal cancer in our country.

   Concerning the treatment modalities, surgery was the primary treatment for both colon and rectal cancer. Most patients were operated with the open technique, because the long-term oncologic outcomes of minimally invasive surgery in colon cancer were just reported as an acceptable treatment and comparable to the open surgical technique during the study period. Meanwhile, minimally invasive surgery for rectal cancer was still debatable during that time. The abdominoperineal resection rate in rectal cancer in this study was 29.5%, which is acceptable for a standard colorectal cancer surgery center.8-12 In colon cancer, postoperative adjuvant chemotherapy was given if the stage of disease was pathological stage III or high-risk pathological stage II, i.e., obstruction, perforation, poorly differentiated histology, positive lymphovascular or perineural invasion, and if the total lymph nodes harvested was less than 12 nodes. Postoperative adjuvant concurrent chemoradiation was given in most pathological stage II and stage III rectal cancer patients, while less than 10 % of rectal cancer patients in this study received preoperative neoadjuvant concurrent chemoradiation. This could be explained by the long waiting list for radiation therapy in our hospital. However, the setting up of a multidisciplinary team in our hospital among surgeons, radiation oncologists, and medical oncologists in colorectal cancer management has now resolved this problem. Previous reports have emphasized the significance of a multidisciplinary team in colorectal cancer.13-15

   The patients in this cohort seemed to have multiple co-morbidities and a high rate of ICU admission because our hospital is a tertiary referral university hospital as previously mentioned. Nonetheless, the mortality rate and readmission rate were acceptable and quite low, as were other short-term outcomes, including medical-related complications, wound complications, and other surgical- related complications. Although approximately 15% of the rectal cancer patients who underwent low anterior resection had protective diversion of the stoma proximal to the anastomosis selectively performed, the anastomotic leakage rate was acceptable, as was the anastomotic leakage rate in colon cancer surgery. These promising short-term outcomes might result from the experience and colorectal surgery sub-specialty of the surgeons who mostly performed the operations in this study. Previous publications have underscored the association between the surgeon factor and the outcomes of colorectal cancer surgery.16-21

   Focusing on the long-term oncologic outcomes,

   the pathological stage of the disease has a major impact on the 5-year survival rate. Appropriate multimodalities curative treatment in non-metastasis cases results in a good prognosis. With a median follow-up time of 5.4 years in this study, the 5-yr OS and 5-yr DFS in stage I–III both in colon and rectal cancer were 70.9% and 70.4%, respectively, which were comparable to a previous report from Thailand by Techawathanawanna et al. They reported the 5-year OS in stage I–III colorectal cancers was 83% overall and the 5-yr DFS was 72% overall. The 5-year DFS in the specific stages I–III was 90%, 85%, and 58%; while the 5-year OS in the specific stages I–III was 93%, 93%, and 73%.22 Meanwhile, a study from another Asian country, namely one in China by Yuan et al., reported 3-year and 5-year overall survival rates of 74% and 68% respectively.23 When looking into the long-term oncologic outcomes stage by stage, either in colon or rectal cancer, the results from our study were comparable to the results reported from Western countries; for instance, the report by O’Connell et al. in 2004. They reported 5-year cancer-specific survival rates in 119,363 colon cancer patients in sub-stages as 93.2% for stage I, 84.7% for stage II A, 72.2% for stage II B, 83.4% for stage III A, 64.1% for stage III B, and 44.3% for stage III C.24

   Comparing stage by stage, rectal cancer had a worse prognosis than colon cancer. Local recurrence of colon and rectal cancer in our study was also acceptable and comparable to in other recent publications. Authors from the Cleveland Clinic Foundation described 5-year overall local recurrence rates in colon cancer as 5.1%; 2.2%, 5.3%, and 7.7 for stages I, II, and III respectively.25 As reported in other studies, distant recurrence in our study was still high, particularly in locally advanced stages.26 These reflect the current clinical practice that stage III patients receive chemotherapy, whereas stage II patients do not. To improve long-term survival and decrease distant recurrence, we should reconsider the paradigm of management in locally advanced colorectal cancer. These strategies might include: 1) postoperative adjuvant chemotherapy in high-risk patients beyond current indications directed by tissue marker, 2) preoperative neoadjuvant chemotherapy as demonstrated by preliminary studies of the FOxTROT trial in locally advanced colon cancer27, and 3) total neoadjuvant therapy in locally advanced rectal cancer, either with induction or consolidation chemotherapy, as demonstrated by the PROSPECT trial (induction chemotherapy before a long course of concurrent chemoradiation), the Time testing trial (consolidation therapy after a long course of concurrent chemoradiation)28,29, and the RAPIDO

   
   

   trial (short-course radiation followed by consolidation chemotherapy).30

   From our multivariate analysis, we could identify the colorectal cancer patients with high risk of distant recurrence who might have benefit if the new paradigm of preoperative treatment is given. Therefore, preoperative neoadjuvant chemotherapy should be considered particularly in colon cancer patients with high preoperative CEA or clinically multiple enlarged lymph nodes (more than 3 lymph nodes). Meanwhile, rectal cancer patients with high preoperative CEA level, N2 stage, presence of tumor deposit, threaten circumferential margin, and tumor located below the peritoneal reflection might have benefit from receiving preoperative total neoadjuvant therapy.

   Our study had some limitations to note. First, it was a retrospective study design. Another was that some patients’ data were missing because they were referred to receive postoperative adjuvant therapy and surveillance at their primary care hospital. This suggests we require a national colorectal cancer registry database to answer more complicated questions and should set up a guideline for the management of Thai colorectal cancer patients.

   
   

   CONCLUSION

   The long-term oncologic outcomes after the curative treatments in this study were acceptable and comparable to previous publications. The prognosis of treatment depends on the disease stage. Comparing stage by stage, colon cancer has a better prognosis than rectal cancer. The new paradigm such as preoperative neoadjuvant chemotherapy in colon cancer patients or total neoadjuvant therapy in rectal cancer patients should be considered in patients with high risk of distant recurrence.

   
   

   ACKNOWLEDGMENTS

   We would like to acknowledge Dr.Orawan Supapueng, a biostatistician in the Division of Clinical Epidemiology, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand for her assistance with the statistical analysis.

   
   

   Conflict of interest: All the authors declare they have no conflicts of interest for this study.

   
   

   REFERENCES

   1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5): E359-86.

   2. Brenner H, Hoffmeister M, Arndt V, Haug U. Gender differences in colorectal cancer: implications for age at initiation of screening. Br J Cancer. 2007;96(5):828-31.

   3. Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70(3):145-64.

   4. Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol. 2019;14(2):89-103.

   5. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683-91.

   6. Abancens M, Bustos V, Harvey H, McBryan J, Harvey BJ. Sexual Dimorphism in Colon Cancer. Front Oncol. 2020;10:607909.

   7. Gao RN, Neutel CI, Wai E. Gender differences in colorectal cancer incidence, mortality, hospitalizations and surgical procedures in Canada. J Public Health (Oxf). 2008;30(2):194- 201.

   8. Tilney HS, Heriot AG, Purkayastha S, Antoniou A, Aylin P, Darzi AW, et al. Anationalperspective onthedeclineofabdominoperineal resection for rectal cancer. Ann Surg. 2008;247(1):77-84.

   9. Keller DS, Reif de Paula T, Kiran RP. Ready for the National Accreditation Programs for Rectal Cancer? Auditing rectal cancer outcomes in the United States. Colorectal Dis. 2019;21(10):1213-5.

   10. Roxburgh CSD, Strombom P, Lynn P, Cercek A, Gonen M, Smith JJ, et al. Changes in the multidisciplinary management of rectal cancer from 2009 to 2015 and associated improvements in short-term outcomes. Colorectal Dis. 2019;21(10):1140-50.

   11. Warschkow R, Ebinger SM, Brunner W, Schmied BM, Marti L. Survival after Abdominoperineal and Sphincter-Preserving Resection in Nonmetastatic Rectal Cancer: A Population- Based Time-Trend and Propensity Score-Matched SEER Analysis. Gastroenterol Res Pract. 2017;2017:6058907.

   12. Marwan K, Staples MP, Thursfield V, Bell SW. The rate of abdominoperineal resections for rectal cancer in the state of Victoria, Australia: a population-based study. Dis Colon Rectum. 2010;53(12):1645-51.

   13. Obias VJ, Reynolds HL Jr. Multidisciplinary teams in the management of rectal cancer. Clin Colon Rectal Surg. 2007; 20(3):143-7.

   14. Peng D, Cheng YX, Cheng Y. Improved Overall Survival of Colorectal Cancer under Multidisciplinary Team: A Meta- Analysis. Biomed Res Int. 2021;2021:5541613.

   15. Fehervari M, Hamrang-Yousefi S, Fadel MG, Mills SC, Warren OJ, Tekkis PP, et al. A systematic review of colorectal multidisciplinary team meetings: an international comparison. BJS Open. 2021; 5(3):zrab044.

   16. Bhoday J, Martling A, Straßburg J, Brown G. Session 1: The surgeon as a prognostic factor in colon and rectal cancer? Colorectal Dis. 2018;20 Suppl 1:36-38.

   17. Hermanek P, Mansmann U, Staimmer DS, Riedl S, Hermanek P. The German experience: the surgeon as a prognostic factor in colon and rectal cancer surgery. Surg Oncol Clin N Am. 2000; 9(1):33-49, vi.

   18. Porter GA, Soskolne CL, Yakimets WW, Newman SC. Surgeon- related factors and outcome in rectal cancer. Ann Surg. 1998; 227(2):157-67.

   19. van Gijn W, Gooiker GA, Wouters MW, Post PN, Tollenaar RA, van de Velde CJ. Volume and outcome in colorectal cancer surgery. Eur J Surg Oncol. 2010;36 Suppl 1:S55-63.

   20. van Groningen JT, Marang-van de Mheen PJ, Henneman D, Beets GL, Wouters MWJM. Surgeon perceived most important factors to achieve the best hospital performance on colorectal

       
       

       cancer surgery: a Dutch modified Delphi method. BMJ Open. 2019;9(9):e025304.

   21. Renzulli P, Lowy A, Maibach R, Egeli RA, Metzger U, Laffer UT. The influence of the surgeon’s and the hospital’s caseload on survival and local recurrence after colorectal cancer surgery. Surgery. 2006;139(3):296-304.

   22. Techawathanawanna S, Nimmannit A, Akewanlop C. Clinical characteristics and disease outcome of UICC stages I-III colorectal cancer patients at Siriraj Hospital. J Med Assoc Thai. 2012;95 Suppl 2:S189-98.

   23. Yuan Y, Li MD, Hu HG, Dong CX, Chen JQ, Li XF, et al. Prognostic and survival analysis of 837 Chinese colorectal cancer patients. World J Gastroenterol. 2013; 19(17):2650-9.

   24. O’Connell JB, Maggard MA, Ko CY. Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J Natl Cancer Inst. 2004; 96(19):1420-5.

   25. Liang J, Fazio V, Lavery I, Remzi F, Hull T, Strong S, et al. Primacy of surgery for colorectal cancer. Br J Surg. 2015;102(7): 847-52.

   26. Sargent DJ, Wieand HS, Haller DG, Gray R, Benedetti JK, Buyse M, et al. Disease-free survival versus overall survival as a primary end point for adjuvant colon cancer studies: individual

       patient data from 20,898 patients on 18 randomized trials. J Clin Oncol. 2005;23(34):8664-70.

   27. Foxtrot Collaborative Group. Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomized controlled trial. Lancet Oncol. 2012;13(11):1152-60.

   28. Schrag D, Weiser MR, Goodman KA, Gonen M, Hollywood E, Cercek A, et al. Neoadjuvant chemotherapy without the routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial. J Clin Oncol. 2014;32(6):513-8.

   29. Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, et al. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015;16(8):957-66.

   30. Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(1): 29-42.

Medial Closing-Wedge Distal Femoral Varus Osteotomy via Lateral Approach: The Modified Technique for Treating Valgus Osteoarthritic Knee as case series

Chaturong Pornrattanamaneewong, M.D., Pakpoom Ruangsomboon, M.D., Rapeepat Narkbunnam, M.D., Keerati Chareancholvanich, M.D.

Department of Orthopaedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

ABSTRACT

Objective: The medial closing-wedge distal femoral varus osteotomy (MCW-DFVO) was an excellent operation for painful valgus lateral unicompartmental osteoarthritic (OA) knee, especially in the young patient. Originally, it requires a medial approach that has more precarious. On top of that, releasing of the iliotibial band that is the deforming force needs added incision. Therefore, this study aims to describe the modified surgical technique of MCW-DFVO that uses a lateral approach and lateral plating to treat the valgus OA knee. Additionally, we also reveal the outcomes of our technique as the case series.

Materials and Methods: Ten patients (12 knees) who underwent MCW-DFVO via a lateral approach were retrospectively reviewed. The inclusion criteria were age 18-60 years, isolated lateral compartmental OA knee (Kellgren-Lawrence grade 3-4), no significant patellofemoral pain, and range of motion (ROM) > 90 degrees. We excluded the inflammatory joint disease, unstable knee (femorotibial joint subluxation > 1 cm), and prior surgical procedure. Demographic data, pre- and postoperative ROM, radiographic outcomes, complications, and survivorship were recorded.

Results: The mean age, body mass index, and preoperative ROM were 55.3 ± 4.0 years, 25.4 ± 3.7 kg/m2 and 113.3

± 11.5 degrees, respectively. The preoperative mechanical femorotibial angle was 162.3 ± 4.8 degrees, and the final post-operative alignment was 182.3 ± 2.6 degrees. Overall mean operative time of this technique was 92.5 ± 26.7 minutes. During the mean follow-up period of 8.3 ± 3.1 years, all osteotomy were united and the final postoperative ROM was decreased to 108.8 ± 11.7 degrees. One knee required plate removal due to hardware irritation, and another knee required subsequent total knee arthroplasty at 1 and 8.5 years after MCW-DFVO, respectively. The survivorship of this technique was 91.7% at the mean survival time of 13.8 years (95% confidence interval, 11.9 – 15.7 years). Conclusion: This study proposed the modified surgical technique of MCW-DFVO via a lateral approach. This technique provided the excellent correction angle, union rate and survivorship.

Keywords: Distal femoral varus osteotomy; medial closing wedge; survivorship; osteoarthritis; knee (Siriraj Med J 2022; 74: 747-753)

Corresponding author: Keerati Chareancholvanich E-mail: keesi93@gmail.com

Received 30 May 2022 Revised 10 July 2022 Accepted 14 September 2022 ORCID ID:http://orcid.org/0000-0003-2837-9182 http://dx.doi.org/10.33192/Smj.2022.88

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

INTRODUCTION

The distal femoral varus osteotomy (DFVO) was the ideal surgical treatment for fail conservative, painful valgus lateral unicompartmental osteoarthritic (OA) knee because it shifts the load from damage lateral compartment to the healthy medial compartment. In the case of valgus deformity, Matsuda et al.1 found that the lateral femoral condyle was hypoplasia and was severely distorted compared to normal and varus OA knee. Previous investigators found that it provides better outcomes compared to the proximal tibial varus osteotomy.2,3 Generally, DFVO is recommended for patients who have age < 60 years, isolated lateral compartmental OA knee, no significant patellofemoral pain, high demand activities, and a good range of motion (ROM).4 The contraindications include inflammatory joint disease and unstable knee (femorotibial joint subluxation > 1 cm).5

The surgical techniques of this procedure can be divided into three types; medial closing-wedge (MCW- DFVO), lateral opening-wedge (LOW-DFVO), and dome DFVO (D-DFVO). MCW-DFVO is a common and widely used technique proposed by McDermott et al.6 This technique offers a stable osteotomy site, needless to use the bone graft and good results.5,6 However, MCW- DFVO has several limitations. Originally, it requires a medial approach that has more precarious. On top of that, releasing of the iliotibial band (ITB) that is the critical deforming force needs added incision.7 Moreover, medial plating has not achieved a biomechanical benefit because it was applied at the adductor moment side, which cannot provide a tension band function.5

Therefore, this study aims to describe the modified surgical technique of MCW-DFVO that uses a lateral approach and lateral plating to treat the valgus OA knee. Additionally, we also reveal the outcomes of our technique as the case series.

MATERIALS AND METHODS

Our institutional review board approved this study (Si 226/2014).Ten patients (12 knees) who underwent MCW-DFVO via a lateral approach were retrospectively reviewed. The inclusion criteria were age 18-60 years, isolated lateral compartmental OA knee (Kellgren- Lawrence grade 3-4), no significant patellofemoral pain, and ROM > 90 degrees. We excluded the inflammatory joint disease, unstable knee (femorotibial joint subluxation

> 1 cm), and prior surgical procedure. Demographic data, pre- and post-operative ROM, radiographic outcomes, complications, and survivorship were recorded. All procedures were performed in accordance with relevant guidelines.

Preoperative planning

The mechanical femorotibial angle (FTA) was measured to define the severity of valgus deformity based on bilateral full length standing alignment film. The preoperative mechanical axis was drawn from the center of the femoral head to the talus’s center. It indicated where the weight passed through the knee. According to the method of Dugdale et al.8, the final weight-bearing line was placed at a position 48-50% across the tibial plateau width from medial to lateral. The acceptable final alignment was 0-3 degree varus (180-183 degrees) of FTA.9 The angle between the line from the center of the femoral head to the point of 48% across the tibial plateau width and the line from the center of talus to the point of 48% coordinate was measured and named radiographic correction angle. Then, the angle between the distal femoral joint line and the proximal tibial joint line was measured and called the condylar angle. This angle could be corrected by releasing ITB intraoperatively. Thus, the intended correction angle (ICA) was finally calculated from the radiographic correction angle minus the condylar angle.

The lateral and axial radiographs of the knee were also assessed for sagittal plane deformity and patellofemoral joint conditions. The Rosenberg view10, a 45 degrees posteroanterior flexion weight-bearing radiograph at of knee, was additionally used to diagnosis the early OA in the posterior compartment of the knee.

Surgical technique

This surgical technique was established and performed by the senior author (KC). The patient was placed in a supine position on the radiolucent table. This procedure could be performed with or without using the sterile thigh tourniquet. A curvilinear incision was started from Gerdy’s tubercle and then along the lateral side of the femoral shaft. The incisional length was approximately 8-10 cm. ITB was identified and released from Gerdy’s tubercle (Figs 1A and 1B). Vastus lateralis muscle was detached from the intermuscular septum and retracted anteromedially to visualize the distal femur.

Under fluoroscopic exam, the Kirsch wires (K-wire) were inserted to guide the osteotomy cut. The first K-wire was inserted at the metaphysodiaphyseal junction of the lateral side of the distal femur that was proximal to the trochlear groove. Its direction was aimed parallel to the distal femoral joint line. The second K-wire was then inserted with an entry point just distal to the first K-wire. Using an intraoperative goniometer assisted, the direction of the second K-wire was planned to make the angle with the first K-wire equal to ICA. The final direction

was confirmed by measuring ICA from a fluoroscopic image (Figs 2A and 2B).

The Homann’s retractor was placed close to the medial cortex and retracted anteromedially to visualize the anterior cortex and protect the vascular structures. Another Homann’s retractor was placed close to the posterior cortex and retracted posteriorly to identify the distal femur’s posterior cortex. Then, the osteotomy was performed along the first guided wire using an oscillating saw. The plane of the saw blade was set perpendicular to the lateral femoral shaft axis. The anterior, posterior, and lateral cortices were completely cut. The medial cortex’s 5 mm thickness remained to reduce the risk of vascular injury and preserve the stability of the distal femur for the second osteotomy cut. The second osteotomy cut was done along the second K-wire with the remaining 5 mm thickness of the medial cortex.

In the correction of sagittal plane deformity, the angle setting between two osteotomy planes was crucial. Flexion contracture of the knee could be improved by cutting the second osteotomy with the posterior slope while genu recurvatum could be improved by cutting with anterior slope. After that, the two osteotomies were completely cut using the osteotome, and the cut bone wedge was removed. Without the lateral hinge, the distal

femoral fragment could be freely moved and adjusted the position to reduce the geometric deformity of the distal femur-the final alignment in the desired FTA of 0-3 degree varus (Figs 3A, 3B and 3C). After satisfying, two divergent temporary K-wires fixation was done from the anterolateral part of the distal fragment to the posteromedial part of the proximal fragment. The entry points of these wires had not hindered the plate placement (Fig 4A).

For the fixation technique, the 5-hole titanium distal femoral locking compression plate (DF-LCP, Synthes, Solothurn, Switzerland) was selected and bend into the contour of the distal femur. After creating the tunnel, DF-LCP was placed along the center of the lateral side of the distal femur (Fig 4B). The most distal screw hole was placed just above the intercondylar notch. At least 4 locking screws were inserted into the distal fragments, while at least 3 locking screws were inserted into the proximal fragment via the stab skin incisions. The final alignment, plate, and screw positions were rechecked (Fig 4C). At the end of the operation, a vacuum drain was placed along with the plate. The fascia sheath was then repaired. Subcutaneous tissue and skin were sutured. The non-compressive dressing was applied.

a

c

d

b

A

c

d

c

d

B

In the postoperative rehabilitation, isometric

A

ITB

B

Fig 1A. The patient was placed in a supine position on the radiolucent table. A curvilinear incision was started from Gerdy’s tubercle and then along the lateral side of the femoral shaft.

Fig 1B. The incisional length was approximately 8-10 cm. ITB was identified and released from Gerdy’s tubercle

Fig 2A. The Homann’s retractor (a) was placed close to the medial cortex. Another Homann’s retractor (b) was placed close to the posterior cortex and retracted posteriorly to identify the distal femur's posterior cortex

Fig 2B. The fluoroscopic exam shjow the first K-wire (c) was inserted at the metaphysodiaphyseal junction of the lateral side of the distal femur that was proximal to the trochlear groove. The second K-wire

(d) was then inserted with an entry point just distal to the first K-wire.

A

B

C

Fig 3. The osteotomy (A) was performed along the guided wire using an oscillating saw. After that, the two osteotomies were completely cut using the osteotome (B), and the cut bone wedge was removed. Without the lateral hinge, the distal femoral fragment could be freely moved and adjusted the position to reduce the geometric deformity of the distal femur (C).

A Fig 4. After satisfying, two divergent

temporary K-wires fixation was done from the anterolateral part of the distal fragment to the posteromedial part of the proximal fragment (A). After creating the tunnel, DF-LCP was placed along the center of the lateral side of the distal femur (B). The final alignment, plate, and screw positions were rechecked (C).

C

B

quadriceps exercise and ankle pumping were started as soon as possible to prevent venous thromboembolism. The ROM exercise and walking with toe-touch weight- bearing was allowed in the first operative day. The drain was left in place for 48 hours. Partial weight-bearing was permitted beginning 2 weeks after surgery, and full weight-bearing was permitted after the radiographic union was observed.

Declarations

Ethical approval and consent to participate: This study included human participants. It had been approved by Siriraj Institutional (Si 226/2014 ID 221/2014 (EC2)). Informed consent was obtained from all individual participants included in the study. This study was approved by Siriraj Institutional Review Board (SIRB) and retrospectively registered at Thaiclinicaltrial. gov (TCTR202010427002).

RESULTS

The patients’ data were shown in Table 1. The mean age, body mass index, and preoperative ROM were 55.3

± 4.0 years, 25.4 ± 3.7 kg/m2 and 113.3 ± 11.5 degrees, respectively. The preoperative valgus deformity was 162.3

± 4.8 degrees, and the final postoperative alignment was

182.3 ± 2.6 degrees. Overall mean operative time of this technique was 92.5 ± 26.7 minutes. During the mean

follow-up period of 8.3 ± 3.1 years, all osteotomy were united and the final postoperative ROM was decreased to 108.8 ± 11.7 degrees. One knee required plate removal due to hardware irritation, and another knee required subsequent total knee arthroplasty (TKA) at 1 and 8.5 years after MCW-DFVO, respectively. The survivorship of this technique was 91.7% at the mean survival time of

13.8 years (95% confidence interval, 11.9 – 15.7 years). The Kaplan-Meier curve was demonstrated in Fig 5.

Fig 5. The Kaplan-Meier curve of the medial closing-wedge (MCW- DFVO) in the study.

TABLE 1. Data of the patients.

Abbreviations: BMI; body mass index, FTA; femorotibial angle, TKA; total knee arthroplasty

DISCUSSION

Our senior author (KC) proposed the modified surgical technique of MCW-DFVO via a lateral approach for treating isolated lateral compartmental OA knee. It contributed to good outcomes and survivorship. Our technique had the combined advantages of MCW-DFVO and lateral approach, including stable osteotomy site, unnecessary to use the bone graft, ability to release ITB for reducing the deforming and biomechanical-benefit lateral plating. Nevertheless, this technique still had technically demanded. Furthermore, complete osteotomy cut in our technique led to the loss of lateral hinge that affected in decreased stability. But the ability to adjust distal femoral fragment for reducing the geometric deformity was superseded.

Because a small number of patients were suitable for DFVO, most of the previous studies9,12-22 were case series. In MCW-DFVO, the survivorships of 64-87% were reported at 10 years follow-up.12-14 While, the survivorships of 79-100% were reported in LOW-DFVO during the follow-up period of 5-8 years.18,20-22 The summary of the DFVO outcomes from previous literature review was

demonstrated in Table 2. When included all techniques of DFVO, a systematic review of Saithna et al.23 reported that the overall survivorship of DFVO was 64-84% at 10 years. For the long-term outcomes of DFVO, Kosashvili et al.16 reported that 48.5% of patients required subsequent TKA. While 30.3% and 21.2% of patients had good and poor functional outcomes, respectively. The mean follow-up time in their series was 15.1 years. Compare to our study, the modified technique provides excellent results. The survivorship of our technique was 91.7% at the mean survival time of 13.8 years (95% confidence interval, 11.9-15.7 years).

For the complications, a previous systematic review23 reveals that the most common complications of overall DFVO were hardware irritation that required subsequent removal of the plate. The loss of correction angle was the problem after MCW-DFVO due to inadequate fixation or poor bone quality.13,24 While LOW-DFVO had a higher incidence of delayed union or non-union of the osteotomy site that might be needed bone graft,9,19 our surgical technique could address these problems. However, hardware irritation still existed in our series.

TABLE 2. Previous studies and outcomes of distal femoral varus osteotomy (DFVO).

There were several limitations to this study. First, the number of patients was minimal. However, we would like to demonstrate the modified surgical technique in this series. In the future, we tried to collect more number of patients and reported the outcomes. Second, because this study was retrospective design, bias and confounder were difficult to control. Furthermore, we had no data about the functional outcome or activity level of the patients after surgery.

CONCLUSION

This study proposed the modified surgical technique of MCW-DFVO via a lateral approach. This technique provided the satisfactory outcomes including correction angle union rate and excellent survivorship. However, further study with a larger sample size was required.

ACKNOWLEDGMENTS

The authors acknowledge the assistance given by Nichakorn Khomawut with data collection. We also acknowledge Suthipol Udompunthurak, MSc. (Applied Statistics), for his assistance with the statistical analyses.

Disclosure

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Funding

There is no funding source.

REFERENCES

1. Matsuda S, Miura H, Nagamine R, Mawatari T, Tokunaga M, Nabeyama R, et al. Anatomical analysis of the femoral condyle in normal and osteoarthritic knees. J Orthop Res Off Publ Orthop Res Soc. 2004;22(1):104-9.

2. Shoji H, Insall J. High tibial osteotomy for osteoarthritis of the knee with valgus deformity. J Bone Joint Surg Am. 1973;55(5):963- 73.

3. Coventry MB. Proximal tibial varus osteotomy for osteoarthritis of the lateral compartment of the knee. J Bone Joint Surg Am. 1987;69(1):32-8.

4. Tírico LEP, Demange MK, Bonadio MB, Helito CP, Gobbi RG, Pécora JR. Medial Closing-Wedge Distal Femoral Osteotomy: Fixation With Proximal Tibial Locking Plate. Arthrosc Tech. 2015;4(6):e687-95.

5. Puddu G, Cipolla M, Cerullo G, Franco V, Giannì E. Which osteotomy for a valgus knee? Int Orthop. 2010;34(2):239-47.

6. McDermott AG, Finklestein JA, Farine I, Boynton EL, MacIntosh DL, Gross A. Distal femoral varus osteotomy for valgus deformity of the knee. J Bone Joint Surg Am. 1988;70(1):110-6.

7. Favorito PJ, Mihalko WM, Krackow KA. Total knee arthroplasty in the valgus knee. J Am Acad Orthop Surg. 2002;10(1):16-24.

8. Dugdale TW, Noyes FR, Styer D. Preoperative planning for

   high tibial osteotomy. The effect of lateral tibiofemoral separation and tibiofemoral length. Clin Orthop. 1992;(274):248-64.

9. Stähelin T, Hardegger F, Ward JC. Supracondylar osteotomy of the femur with use of compression. Osteosynthesis with a malleable implant. J Bone Joint Surg Am. 2000;82(5):712-22.

10. Rosenberg TD, Paulos LE, Parker RD, Coward DB, Scott SM. The forty-five-degree posteroanterior flexion weight-bearing radiograph of the knee. J Bone Joint Surg Am. 1988;70(10):1479- 83.

11. Krettek C, Miclau T, Grün O, Schandelmaier P, Tscherne H. Intraoperative control of axes, rotation and length in femoral and tibial fractures. Technical note. Injury. 1998;29 Suppl 3: C29-39.

12. Finkelstein JA, Gross AE, Davis A. Varus osteotomy of the distal part of the femur. A survivorship analysis. J Bone Joint Surg Am. 1996;78(9):1348-52.

13. Wang J-W, Hsu C-C. Distal femoral varus osteotomy for osteoarthritis of the knee. J Bone Joint Surg Am. 2005;87(1):127- 33.

14. Backstein D, Morag G, Hanna S, Safir O, Gross A. Long-term follow-up of distal femoral varus osteotomy of the knee. J Arthroplasty. 2007;22(4 Suppl 1):2-6.

15. Omidi-Kashani F, Hasankhani IG, Mazlumi M, Ebrahimzadeh MH. Varus distal femoral osteotomy in young adults with valgus knee. J Orthop Surg. 2009;4:15.

16. Kosashvili Y, Safir O, Gross A, Morag G, Lakstein D, Backstein

    D. Distal femoral varus osteotomy for lateral osteoarthritis of the knee: a minimum ten-year follow-up. Int Orthop. 2010;34(2): 249-54.

17. Das DH, Sijbesma T, Hoekstra H, W. van Leeuwen. Distal femoral opening-wedge osteotomy for lateral compartment osteoarthritis of the knee. Open Access Surg. 2008;1:25-9.

18. Zarrouk A, Bouzidi R, Karray B, Kammoun S, Mourali S, Kooli M. Distal femoral varus osteotomy outcome: Is associated femoropatellar osteoarthritis consequential? Orthop Traumatol Surg Res OTSR. 2010;96(6):632-6.

19. Jacobi M, Wahl P, Bouaicha S, Jakob RP, Gautier E. Distal femoral varus osteotomy: problems associated with the lateral open-wedge technique. Arch Orthop Trauma Surg. 2011;131(6): 725-8.

20. Thein R, Bronak S, Thein R, Haviv B. Distal femoral osteotomy for valgus arthritic knees. J Orthop Sci Off J Jpn Orthop Assoc. 2012;17(6):745-9.

21. Dewilde TR, Dauw J, Vandenneucker H, Bellemans J. Opening wedge distal femoral varus osteotomy using the Puddu plate and calcium phosphate bone cement. Knee Surg Sports Traumatol Arthrosc Off J ESSKA. 2013;21(1):249-54.

22. Saithna A, Kundra R, Getgood A, Spalding T. Opening wedge distal femoral varus osteotomy for lateral compartment osteoarthritis in the valgus knee. The Knee. 2014;21(1):172-5.

23. Saithna A, Kundra R, Modi CS, Getgood A, Spalding T. Distal femoral varus osteotomy for lateral compartment osteoarthritis in the valgus knee. A systematic review of the literature. Open Orthop J. 2012;6:313-9.

24. Edgerton BC, Mariani EM, Morrey BF. Distal femoral varus osteotomy for painful genu valgum. A five-to-11-year follow- up study. Clin Orthop. 1993;(288):263-9.

Tissue Elimination of Large Vascular Corrosion Casting for Anatomy Education

Chanagun Tounkhrua, M.D., Adisorn Ratanayotha, M.D., Rosarin Ratanalekha, M.D., Natipong Chatthai, B.Sc., Parkpoom Piyaman, M.D.

Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

ABSTRACT

Objective: Vascular corrosion casting is crucial tool for three-dimensional study. Focusing on the casting for gross anatomy, large fatty tissue reacts with corrosive agents resulting in extensive saponification. Our study aimed to prevent saponification by a) finding the optimal corrosion temperature and concentration of corrosive agent and

b) comparing the flow of the agent with conventional “non-flow” setting.

Materials and Methods: Phase I: pig fatty tissues, weighing 10 g each, were immersed in still (non-flowing) solution containing 0.5%, 1%, and 5% sodium hydroxide. Different temperatures were set to find the minimum soap-free temperature for each concentration. Phases II, III: 6 pig hearts were injected via the coronary arteries with polymethyl methacrylate. Three hearts were immersed in non-flowing 0.5%, 1%, and 5% NaOH solution, while another three were placed in a flowing solution. The flow was set in a vertical upward fashion in a specialized chamber while the outflow residue was collected from the system. The temperature was set at the minimum soap-free temperature. The durations of the corrosion were compared.

Results: The minimum soap-free temperatures for the 0.5%, 1%, and 5% concentrations were 55°C, 54°C, and 47°C, respectively. The corrosion times for the non-flowing 0.5%, 1%, and 5% concentrations were 216 h, 114 h, and 24 h, respectively. Flowing of the solution reduced the corrosion time by 25%-39% compared with the non-flowing.

Conclusion: The most efficient condition for soap-free coronary corrosion casting is 5% NaOH solution at a minimal temperature of 47°C.

Keywords: Coronary artery; Angiography; Saponification; Alkaline liquefaction; Sus scrofa domesticus (Siriraj Med J 2022; 74: 754-759)

INTRODUCTION

Cadaveric dissection is still the basis of anatomical education for medical students. Students’ greatest challenge is understanding the complexity of the vascular system, which is hard to accomplish in a relatively limited time. To tackle this challenge, virtual 3D anatomy has been introduced to aid learning, but the lack of tactile feedback can leave kinesthetic learners behind.1 On the other hand, the tangible model has shown better teaching outcomes than virtual dissection in the cardiovascular class.2 This

model can replicate or be derived from a real specimen (e.g., plastination or vascular corrosion casting).

Vascular corrosion casting has been utilized in vascular research for centuries.3 However, since the 1960s, the research trend has shifted from the gross to the microscopic level in line with the rise of scanning electron microscopy (SEM). The casting technique has been developed accordingly to focus on the microscopic vessels of tiny specimens.4-6 On the other hand, macroscopic cast production has been somewhat sidelined, with some

Corresponding author: Parkpoom Piyaman E-mail: ppiyaman@gmail.com

Received 7 July 2022 Revised 15 August 2022 Accepted 20 August 2022 ORCID ID:http://orcid.org/0000-0003-4261-6762 http://dx.doi.org/10.33192/Smj.2022.89

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

technical difficulties remaining unresolved. Vascular corrosion casting consists of two steps: casting medium injection and the corrosion process. First, the medium is selected from certain polymers that have water-like fluidity in the monomeric form and rigidity in the polymeric form. Hence the medium is injected in the monomeric form and allowed to polymerize in the lumen of the blood vessel. The most popular medium is polymethyl methacrylate (pMMA). However, this polymer losses its strength at high temperature.7 Therefore, unnecessary heat to the cast should be avoided during the whole process.

Corrosion, the second step, eliminates the surrounding tissue, typically by alkaline solution (e.g., NaOH and KOH).4-6,8,9 Alkalis, once dissociated in water, produce hydroxide ions that react with proteins in a process called solubilization10, which is also known as alkaline liquefaction11 and alkaline hydrolysis.12 Meanwhile, hydroxide ions also saponify the fat, producing an undesirable by-product as a solid soap residue.4-6,8,9 A constant heat at 40–60°C is applied to the solution for two purposes: (a) to increase the soap solubility in water and (b) to accelerate protein solubilization. Despite the heat input, this process could take up to 7–8 days5 and some residue (e.g., soap) is usually still nestled in the cast (Fig 1), requiring additional washing by running water.5,6,8,9 To reduce the corrosion time and cut the washing process, the circulating laminar outflow chamber (CLOC) system was developed.13 The CLOC system (Fig 2) consists of three parts connected in one circuit:

(1) the heater, (2) the pump, and (3) the chambers. The former two generate a circulating flow of hot corrosive

solution to wash the tissue and fat away. The latter part, the chambers, are composed of a specimen chamber and outflow chamber. The solution flows to the specimen chamber, then to the outflow chamber, and returns to the heat and pump unit. The wash-out residue is contained in the outflow chamber and prevented from re-circulation. A recent study13 demonstrated the feasibility of the system for the mass production of casts. However, two questions remain: (a) what is the optimal temperature for the corrosion process? and (b) How much time efficiency does the CLOC system have for corrosion process compared to conventional corrosion process? This study approached the first question by attempting to find the “minimum soap-free temperature”, defined as the lowest temperature of the corrosive solution where solid soap is not formed during the corrosion process. This temperature, on the other hand, would minimize the heat damage on pMMA cast, hence presumably an optimal temperature for the corrosion process. The second question was tackled by comparing the duration of the corrosion process (corrosion time) between the conventional, non-flowing solution and flowing solution in CLOC system.

MATERIALS AND METHODS

Pig hearts and fatty tissues were purchased from a butcher shop in Bangkok Noi District, Bangkok. The pigs were slaughtered for commercial purposes at a registered slaughterhouse in Nakhon Pathom. The study is appoved by Siriraj Laboratory Animal Research and Care Center, Faculty of Medicine Siriraj Hospital, Mahidol University (Si 008/2022). Pig fat was cut from the subcutis into

Fig 1. Photograph of a vascular corrosion cast that was processed via a corrosion step at too low a temperature. White solid soap residue is formed and can be seen attached to the cast.

Fig 2. Diagram of the circulating laminar outflow chamber (CLOC) system. The system is composed of the pump (1), the heater (2) and the chamber (3) connected in a circuit (4, 5, 6). The arrows indicate the cyclic flow of the corrosive solution.

identical pieces weighing 10 g. On the other hand, the pig hearts were cannulated via the right and left coronary arteries. Then, 12 ml of polymethyl methacrylate (pMMA) (Ruthinium® group, Italy) was injected via the cannulae, 5 ml into right coronary artery and 7 ml into left coronary artery. The rate of injection was approximately 1 ml per second. The quality of the specimens, the technique, and the materials were all standardized. The specimens were allocated into three phases of experiments, as follow:

Phase I aimed to find the minimum soap-free temperatures; presumptive optimal temperature for corrosion process, at three concentrations of NaOH solution: 0.5%, 1.0%, and 5.0% (Fig 3). The volume of the solution was 3,000 ml, which, by calculation, contained an excessive amount of NaOH to complete the saponification reaction.14 Each trial involved immersing three pieces of fat in three separate containers filled with the same NaOH concentration. The first trial started at an initial temperature of 45°C. The initial temperature was derived from the study on solubility of the tallow soap in aqueous solution.15 After 24 h, the presence of solid soap was checked. If positive, the next trial would be repeated at a 1°C higher temperature and the presence of solid soap was checked for again. The cycle continued until the solid soap was completely absent and then the minimum soap-free temperature was declared.

Phase II aimed to measure the corrosion time (time efficiency) of the conventional corrosion process at the minimum soap-free temperature (Fig 4). The injected hearts were allocated to three concentrations of NaOH solution: 0.5% 1.0%, and 5.0%, one heart per one concentration. The temperature was set at the minimum soap-free temperature of each concentration.

The corrosion process was checked regularly until tissue was eliminated completely from the cast.

Phase III aimed to compare the corrosion time (time efficiency) of the CLOC system with the conventional process (Fig 4). The CLOC system was assembled from three units: the chambers, the pump, and the heater (Fig 2).13 The specimen chamber was fitted to contain one heart and was surrounded by an outflow chamber. The CLOC was connected to the pump and heater by a plastic tube in a circuit. The injected hearts were processed as described in phase II, but the corrosive solution was pumped at a flow rate of 600 ml/min. The temperature was set at the minimum soap-free temperature of each NaOH concentration.

RESULTS

In phase I, the minimum soap-free temperatures for the 0.5%, 1%, and 5% NaOH concentrations were

55 °C, 54 °C, and 47 °C, respectively (Table 1).

In phase II, the minimum soap-free temperatures successfully produced residue-free corrosion casts (Fig 5). In each case, heat-induced deformity was undetectable, and the anatomy of the vessel was preserved. The corrosion times of the non-flowing 0.5%, 1%, and 5% concentrations

were 216, 114, and 24 h, respectively (Table 1).

In phase III, the circulating laminar outflow chamber (CLOC) system also produced residue-free and anatomically correct casts. The CLOC reduced the corrosion time for the 0.5%, 1%, and 5% concentrations to 132, 76, and 18 h, respectively (Table 1). Compared to the non-flowing group, the reductions were 39%, 33%, and 25% for the 0.5%, 1%, and 5% concentrations, respectively.

Fig 3. Flow chart depicting the phase I study aiming to find the minimum soap-free temperature at three concentrations of NaOH solution; 0.5%, 1%, and 5%.

Fig 4. Flow chart depicting the phase II and phase III studies. Phase II aimed to measure the corrosion time of non-flowing NaOH solution at 0.5%, 1%, and 5% concentrations. The corrosion temperatures were set at the minimum soap-free temperatures. Whereas the phase III study aimed to measure the corrosion time in a flowing corrosive solution in the CLOC system.

TABLE 1. Minimum soap-free temperature at three concentrations of NaOH solution (phase I). Corrosion time in a non-flowing NaOH solution (phase II) and flowing NaOH solution in the CLOC system (phase III) at the minimum soap-free temperature.

Concentration of NaOH solution (%w/v)

0.5 1.0 5.0

Phase I

Minimum soap-free temperature (ºC)

Phase II

Corrosion time in still solution (hours)

Phase III

Corrosion time in flowing solution (hours)

Phase II vs III

Reduction of the corrosion time

55 54 47

216 114 24

132 76 18

39% 33% 25%

DISCUSSION

The solubility of soap in water depends on the composition of fatty acid in the soap16, the temperature of the water16, and the co-existing electrolytes.17 To explore these issues, we introduced a new term: the “minimum soap-free temperature”, despite existing

terms being available, such as the clearing temperature17 and solubility curve.15 Our rationale was based on the instrumental limitations and practicality. First, we could not measure the concentration of all the phases that were collectively dissolved in the soap solution; micelles, hydrated crystals, and monomers.18 Second, we needed

Fig 5. Photographs of a vascular corrosion cast produced at the minimum soap-free temperature. Three colors of pMMA were injected into three branches of coronary artery: red represents the left anterior descending artery (LAD); yellow represents the left circumflex artery (LCX); and blue represents the right coronary artery (RCA). The cast shows no heat deformity. No soap residue remained on the cast. Aorta (Ao), left coronary artery (LCA), left anterior descending artery (LAD), diagonal branch of left anterior descending artery (Di), left marginal branch of left circumflex artery (LM), sinoatrial nodal branch (SN), right marginal branch of right coronary artery (RM) and posterior descending artery (PAD)

a more specific term to describe the absence of soap residue in the corrosion casting. There was no solubility curve for lard (pig fat) soap available to be compared with our data. Fortunately, the composition of fatty acid in lard, tard (cow fat)18, and humans19 is similar; namely about one-half oleic acid and one-quarter palmitic acid. Therefore, the solubility curve of tallow soap should be analogous to lard and human fat soap. Our minimum

soap-free temperatures corresponded to the solubility curve of tallow soap.15 This implies the validity of the experiment and applicability of the corrosion casting for human specimens.

Focusing on the saponification reaction, the results of phase I seemed counterintuitive in suggesting that a higher NaOH concentration required a lower minimum soap-free temperature. One might think that the more NaOH is added, the more sodium soap is produced, and thus a higher temperature is required to dissolve the soap. Nevertheless, all the NaOH concentrations in phase I, i.e., 0.5%, 1%, and 5%, contained a copious amount of NaOH that would overwhelm fat in the saponification reaction. The amount of sodium soap was therefore equal in every NaOH concentration. Next, the question is why an equal amount of soap produced at different NaOH concentrations dissolved differently. The quantities of the electrolytes Na+ and OH- were not actually measured, but the quantity and pH were certainly increased in the 0.5%, 1.0%, to 5% groups. Surprisingly, we could find no study in the literature describing the effect of the basicity of water on the solubility of sodium soap. On the other hand, we found one study17 that demonstrated clearly that the more Na+ is added to a solution, the lower the soap solubility is, and the higher temperature is required to completely dissolve it. If the latter concept is applied here, the highest concentration group, i.e., 5% NaOH, would be supposed to show the highest minimum soap- free temperature. However, the actual result contradicted this assumption. In practice, the data could be explained better by the protein solubilization reactions.

According to previous studies11,12, 5% NaOH would show the highest rate of protein solubilization. By this assumption, the reaction might be so rapid that the structural proteins (e.g., collagen fiber) holding the adipocyte together would be dissolved before saponification could take place in situ. Therefore, the subsequent sodium soap would be produced from the free, colloidal phase of fatty tissue. In contrast to the lowest concentration group, i.e., 0.5% NaOH, the slowest solubilization might allow saponification to take place in situ while the structural proteins are still intact. Thus, the higher minimum soap- free temperature would be required to break the saponified tissue and dissolve it.

The success in phases II and III confirmed the validity of our minimum soap-free temperature. From these findings, we could set an appropriate temperature for the corrosion process for each NaOH concentration. Moreover, we could cut the corrosion time and subsequent washing process through the double actions of corrosion and washing in the CLOC system.

CONCLUSION

The most efficient corrosion process to produce a coronary vascular corrosion cast was 5% NaOH via the CLOC system at 47°C, which involved the shortest corrosion time at 18 h.

ACKNOWLEDGEMENTS

The authors are grateful to Phattarapong Predapramote of Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University for assistance with angiography.

Financial disclosure: None of the authors has a financial interest in any of the products or devices mentioned in this manuscript.

Abbreviations:

pMMA, polymethyl methacrylate NaOH, sodium hydroxide

KOH, potassium hydroxide

CLOC, Circulating laminar outflow chamber LAD, left anterior descending artery

LCX, left circumflex artery RCA, right coronary artery

REFERENCES

1. Johnson M. Evaluation of Learning Style for First Year Medical Students. International Journal Scholarship of Teaching & Learning. 2009;3(1). Available from: https://doi.org/10.20429/ ijsotl.2009.030120

2. Lombardi SA, Hicks RE, Thompson KV, Marbach-Ad G. Are all hands-on activities equally effective? Effect of using plastic models, organ dissections, and virtual dissections on student learning and perceptions. Adv Physiol Educ. 2014;38(1):80-86.

3. Grabherr S, Cadas H, Riederer BM, Charlier P, Djonov V. Postmortem Angiography: A Historical Review. In: Grabherr S, Grimm JM, Heinemann A, editors. Atlas of Postmortem Angiography. Cham: Springer International Publishing; 2016. p.53-70.

4. Verli FD, Rossi-Schneider TR, Schneider FL, Yurgel LS, de Souza MAL. Vascular Corrosion Casting Technique Steps. Scanning. 2007;29(3):128-32.

5. Prozorowska E, Jackowiak H. The vascular corrosion casting (VCC) and scanning electron microscopy study on changes of vascular networks arrangement in the organs undergoing

   cyclic volume changes. Microscopy: advances in scientific research education 6th ed Badajoz, Spain: Formatex Research Center. 2014.p.112-18.

6. Walocha J, Litwin JA, Miodoński AJ. Corrosion casting technique. In: Schatten H, editor. Scanning Electron Microscopy for the Life Sciences. Cambridge: Cambridge University Press; 2012. p.16-32.

7. Abdel-Wahab AA, Ataya S, Silberschmidt VV. Temperature- dependent mechanical behaviour of PMMA: Experimental analysis and modelling. Polymer Testing. 2017;58:86-95.

8. Shanthini S, Suma HY. An innovative method in venous coronary cast technique. Anat Cell Biol. 2019;52(2):191-5.

9. Kupczyńska M, Barszcz K, Olbrych K, Polguj M, Wysiadecki G, Topol M, et al. Coronary arteries of the European bison (Bison bonasus). Acta Veterinaria Scandinavica. 2015;57:1-7.

10. Gupta PK. Chapter 23 - Toxic effects of caustics (corrosives). In: Gupta PK, editor. Fundamentals of Toxicology: Academic Press; 2016.p.267-75.

11. Zheng JL, Zhu MQ, Wu HT. Alkaline hydrothermal liquefaction of swine carcasses to bio-oil. Waste Manag. 2015;43:230-8.

12. Wang T, Wu J-H, Yi Y, Qi J-C. Optimization of Process Conditions for Infected Animal Tissues by Alkaline Hydrolysis Technology. Procedia Environmental Sciences. 2016;31:366-74.

13. Ratanalekha R. Development of Vascular Corrosion Casting for Education in Gross Anatomy. In: Laohaprasitthiphorn D, editor. Outstanding Innovation, Quality Fair, 2018, Faculty of Medicine Siriraj Hospital, Mahidol University. Bangkok, Thailand: Division of Quality Development, Faculty of Medicine Siriraj Hospital, Mahidol University; 2018.p.136-40.

14. Spitz L. Glossary. In: Spitz L, editor. Soap Manufacturing Technology. United Kingdom: Elsevier Inc; 2016.p.267-80.

15. McBain JW, Sierichs WC. The solubility of sodium and potassium soaps and the phase diagrams of aqueous potassium soaps. Journal of the American Oil Chemists Society. 1948;25(6):221-5. Available from: https://doi.org/10.1007/BF02645899

16. Hall N. Implications of Soap Structure for Formulation and User Properties. In: Spitz L, editor. Soap Manufacturing Technology. United Kingdom: Elsevier Inc; 2016.p.1-33.

17. Lin B, McCormick AV, Davis HT, Strey R. Solubility of sodium soaps in aqueous salt solutions. J Colloid Interface Sci. 2005; 291(2):543-9.

18. Hill M, Moaddel T. 2 - Soap Structure and Phase Behavior. In: Spitz L, editor. Soap Manufacturing Technology (Second Edition): AOCS Press; 2016.p.35-54.

19. Kingsbury KJ, Paul S, Crossley A, Morgan DM. The fatty acid composition of human depot fat. Biochem J. 1961;78(3):541- 50.

Psychometric Properties of Scales for Assessing Experiential Avoidance

Thanayot Sumalrot, Ph.D.*, Naphol Phannajit, M.Sc.**, Sucheera Phattharayuttawat, Ph.D.*

*Department of Psychiatry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, **Saint Andrews International School Bangkok, Thailand.

ABSTRACT

Objective: To study and compare the psychometric properties, reliability, and validity of the Acceptance and Action Questionnaire (AAQ-II) and the Multidimensional Experiential Avoidance Questionnaire (MEAQ), which were translated into Thai.

Materials and Methods: This study used the AAQ-II and MEAQ, which were back translated into Thai. The Depression Anxiety Stress Scale 21 (DASS-21) and Satisfaction with Life Scale (SWLS) were used in conjunction to collect data from 35 graduate students (females 77.1%) and 462 people from the general population of Bangkok (females 74.2%).

Result: Item Objective Congruence (IOC) of AAQ-II and MEAQ was 0.79 and 0.87, respectively. Both had high correlation coefficients with DASS-21 and SWLS, indicating criteria-related validity. Moreover, Confirmatory Factor Analysis (CFA) was also carried out. The correlation coefficient to the original was high (0.96 for AAQ-II and MEAQ, and subscales ranging from 0.83-0.94). They also had high internal consistency, with Cronbach’s alpha being 0.89 in AAQ-II and 0.92 in MEAQ, with high construct reliability (0.88 and 0.79-0.86).

Conclusion: The translated versions of AAQ-II and MEAQ have good psychometric properties. When comparing AAQ-II with MEAQ, it was noted that the correlation between AAQ and other scales was higher than MEAQ, which only had a moderate correlation. AAQ-II also tends to have a high association with distress variables. However, it is still possible to assess experiential avoidance. Thus, the use of each questionnaire will be depended on certain objectives.

Keywords: Acceptance and Action Questionnaire – II (AAQ-II); Multidimensional Experiential Avoidance Questionnaire (MEAQ); Psychometric Properties (Siriraj Med J 2022; 74: 760-768)

INTRODUCTION

Nowadays, it is suggested that psychological problems emerge from a desire to avoid, suppress, or control an undesirable situation rather than mere thought and emotion. This desire increases the intensity of, psychological disorders and symptoms. Experiential avoidance, introduced by Steven C. Hayes, is a response by individuals to avoid undesirable events and involves attempts to evade, alter, or control experiences despite it being a part of their values or goals.1-4 Hayes3 defined

the causes of experiential avoidance as: 1) Bidirectional nature of human language which links undesirable events and certain uses of language, possibly leading to people re-experiencing certain events and thus a desire to avoid it; 2) Inappropriate generalization of human language, which makes an individual use an ineffective coping mechanism prepared beforehand to avoid certain events;

3) Social encouragement and modeling which promotes individuals to imitate the use of experiential avoidance; and 4) Cultural support for emotions and cognitions

Corresponding author: Thanayot Sumalrot E-mail: thanayot.sum@mahidol.edu

Received 8 September 2022 Revised 23 September 2022 Accepted 25 September 2022 ORCID ID:http://orcid.org/0000-0001-7506-4429 http://dx.doi.org/10.33192/Smj.2022.90

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

in which an individual is shaped by the socio-cultural environment and perceives certain emotions and thoughts as improper and thus chooses to avoid them. All these causes lead to an inflexible coping mechanism and inability to separate one’s sense of self and behavior which can have a negative impact such as the use of alcohol, drugs, or a relapse5-7 and psychological distress.4,8,9 It also prevents opportunities to experience valuable events. In summary, experiential avoidance is caused by human language proficiency and human nature which leads to a certain state of psychopathology.

As a response to experiential avoidance, Acceptance and Commitment Therapy (ACT) was developed under the rationale of Relational Frame Theory (RFT)10, which focuses on language proficiency as the root cause of a person’s psychological inflexibility. In ACT, the main purpose is to promote psychological flexibility and enable individuals to interact effectively in the present moment. This therapy features several questionnaires to assess the level of experiential avoidance. The most accepted and widely used questionnaire is known as the Acceptance and Action Questionnaire (AAQ). However, due to problems associated with its psychometric properties, a new version was developed, known as the Acceptance and Action Questionnaire – II (AAQ – II) to assess experiential avoidance and psychological inflexibility.11 Concurrently, the Multidimensional Experiential Avoidance Questionnaire (MEAQ) was developed to cover elements of experiential avoidance in broader terms. However, there is still disagreement over the differences of MEAQ and AAQ – II, and on the latter’s focus, which assesses the construct and is associated with neuroticism and negative affectivity rather than experiential avoidance.12 Experiential avoidance can be found in any population,

so it is important to not only be aware, but be careful in its application. Until now, there are some studies related to Experiential Avoidance such as Thai version of the Philadelphia Mindfulness Scale (PHLMS)13 but there has not been a study exploring experiential avoidance in the Thai population, including the psychometric property of AAQ and MEAQ due to a lack of translated questionnaires. Hence, this research translated the AAQ –II and MEAQ into Thai to study and compare their psychometric properties. This study used a sample of Bangkok residents in early adulthood (aged 18-40) as they are most likely to experience stress from inappropriate use of experiential avoidance. Thus, studying experiential avoidance as well as translating the questionnaires would lead to a better understanding in the context of the Thai population and help further develop relevant research and therapies in Thailand.

MATERIALS AND METHODS

Sample

Sample group 1 or the bilingual group consisted of 35 participants proficient in both Thai and English from Faculty of Medicine Siriraj Hospital, (77.1% females) aged between 22 and 29 s (M = 24.71, SD = 1.61), and with an English proficiency score (MU GRAD TEST) between 60 and 88 (M = 68.94, SD = 7.21). Sample group 2 was calculated using the W.G. Cochran formula, with a confidence interval of 95% and acceptable deviation of 5%. The sample had 462 participants (74.2% females), aged 18 to 40 years (M = 24.65, SD = 5.65). All of them resided in Bangkok.

Instruments

Acceptance and Action Questionnaire – II (AAQ-II)11

The AAQ-II is a 7-item, 7-point Likert-type scale (7 = always, 1 = never true). It measures experiential avoidance and psychological inflexibility. The original version by Bond, Hayes11 showed good psychometric properties (mean alpha of 0.84, 3 and 12 month test-retest reliability of 0.81 and 0.79) and one-factor structure.

Multidimensional Experiential Avoidance Questionnaire (MEAQ)12

The MEAQ is a 62-item, 6-point Likert-type scale (6 = strongly agree, 1 = strongly disagree) which measures multidimensional experiential avoidance (behavioral avoidance, distress aversion, procrastination, distraction/ suppression, repression/denial, and distress endurance). The original version by Gamez, Chmielewski12 showed good psychometric properties (mean alpha of 0.85).

Depression Anxiety Stress Scale 21 (DASS-21)14

The DASS-21 is a 21-item, 4-point Likert-type scale. It contains three subscales (depression, anxiety, and stress). The Thai version by Oei, Sawang14 showed good psychometric properties (alpha value of depression was 0.86, anxiety was 0.81, and stress 0.70) Medium to strong positive correlations were expected between the AAQ-II and DASS-21 subscales.

Satisfaction with Life Scale (SWLS)15

The SWLS is a 5-item, 4-point Likert-type scale. It measures global cognitive judgment of satisfaction with one's life. The original version showed good psychometric properties (coefficient alpha was 0.87, test-retest reliability was 0.82).

Design

The study procedure was approved by the Institutional

Review Board of the Faculty of Medicine Siriraj Hospital. (Si. 666/2018) Following a suggestion by Nantaga Sawasdipanich and Sujitra Tiansawad16, the researcher chose to first translate the questionnaires into Thai and then consult with a professional translation consultant. Then, the researcher chose to back translate as suggested by the language expert. Next, the language expert and a psychology expert compared the original questionnaire to the backward translated version for revisions. Afterwards, the content was examined by three psychology experts and an Item-Objective Congruence (IOC) was obtained for every item in the questionnaire. An IOC of more than

0.5 was considered as valid.17 The researcher improved the language as suggested by the expert to make the questionnaire more complete. As a result, two sets of questionnaires, or the Acceptance and Action Questionnaire–II: Thai version (AAQ-II), and Multidimensional Experiential Avoidance Questionnaire: Thai version (MEAQ) were delivered.

In sample group 1, the administration of the questionnaire was collective and conducted with a consent form distributed with a brief about the aim of the study, followed by an assignment to respond to AAQ-II, MEAQ, AAQ-II Thai version, MEAQ Thai version.

In sample group 2, the administration of the questionnaire was collective and conducted online with detailed information and consent provided and explained, followed by a task to respond to the AAQ-II Thai version, MEAQ Thai version, DASS-21, SWLS.

Data analysis

The first task was to use the score to examine content validity using Item-Objective Congruence (IOC). All statistical analyses were conducted using PASW Statistics (v. 18.0; SPSS Inc., Chicago, IL, USA).

Data from sample group 1 was examined using parallel form reliability analysis. Data from sample group 2 was examined using the corrected item-total correlation (CITC), reliability: internal consistency, validity: criterion-related validity, and construct validity. Validity and, construct validity

RESULTS

The response rate or questionnaires returned from graduate students was 35 or 100% of all samples. Meanwhile, the response rate or ordinary people who answered and returned the questionnaires was 462, which also accounted for 100% of samples. The sample size had a ratio of 25.8% males and 74.2% females. The sample age range was between 18 and 40 years (M = 24.56, SD = 5.65).

Reliability

Table 1 shows the mean and standard deviation of both AAQ-II and MEAQ in the Thai version and original questionnaire, which were noted to be similar. Moreover, the results indicate high parallel form reliability of the Thai AAQ-II and MEAQ questionnaires, so they can be used in Thai context as well.

Table 2 shows the Cronbach’s alpha coefficient for the total AAQ-II, and MEAQ scores, behavioural avoidance, distress aversion, procrastination, distraction and suppression, repression and denial, and distress endurance. Moreover, most items in both questionnaires had a CITC above 0.218, except some items in MEAQ which will be explained in detail in the discussion section. This indicates that those with a high score in these items also have a high total score and vice versa. These finding indicate high internal consistency of both questionnaires, and the degree of interrelationship among items on the scale along with their consistency and ability to measure the same thing.

Validity

The results of IOC from three psychology experts verified content validity, which means the IOC of the Thai version of the AAQ-II and MEAQ were 0.79 and 0.87, respectively. The finding indicates content validity of both questionnaires was acceptable and capable of assessing the objectives of the questionnaires.

Table 3 shows the correlation between the Thai version of AAQ-II, MEAQ and DASS-21 and SWLS. According to the results, AAQ-II’s score correlates with depression, anxiety, stress, and satisfaction with life score. Moreover, the correlation coefficient between MEAQ, together with its sub-scale, and DASS-21 (depression, anxiety and stress) and SWLS significantly correlated with depression, anxiety, stress, and satisfaction with life score. Besides distraction and suppression, which only correlated with stress and distress endurance correlated with depression, anxiety, and satisfaction with life score,

but not the stress scale.

Confirmatory Factor Analysis (CFA) was conducted to examine the construct validity of 462 samples. In Table 4, the results of confirmatory factor analysis found that the hypothesized measurement model of the Thai version of AAQ-II and MEAQ did not fit well with the empirical data. For the models to relate, the researcher modified them by deleting each item which had a factor load below 0.4 and/or high measurement error. The result was that the modified AAQ-II (6 items), and MEAQ (39 items) obtained construct validity with admissible fit indices.

TABLE 1. Parallel form reliability of AAQ-II and MEAQ (both English and Thai versions). Data was analyzed from sample group 1 (n = 35).

Abbreviations: AAQ-II; Acceptance and Action Questionnaire – II, MEAQ; Multidimensional Experiential Avoidance Questionnaire, BA; Behavioral Avoidance, DA; Distress Aversion, P; Procrastination, DS; Distraction & Suppression, RD; Repression & Denial, DE, Distress Endurance, * p < .05, ** p < .01.

TABLE 2. Reliability and Corrected Item-Total Correlation of the AAQ-II and MEAQ translated into Thai. Data was analyzed from sample group 2 (n = 462).

Abbreviations: AAQ-II; Acceptance and Action Questionnaire – II, MEAQ; Multidimensional Experiential Avoidance Questionnaire, BA; Behavioral Avoidance, DA; Distress Aversion, P; Procrastination, DS; Distraction & Suppression, RD; Repression & Denial, DE; Distress Endurance, SWLS; Satisfaction with life Scale, * p < .05, ** p < .01.

Table 5 shows both questionnaires before model modification. Each item on the AAQ-II Thai Version had a standardized factor load between 0.65-0.82. After modification, the factor load rose from 0.70 to 0.79. For items in each domain of the Thai version of MEAQ, the standardized factor load before model modification

ranged between 0.20-0.77. After modification, each domain’s factor loads increased.

When considering the squared multiple correlation (R2) of items or reliability of indicators for the Thai version of AAQ-II, the score ranged between 0.42-0.67. When the model was modified, the score was still similar. For the

TABLE 3. Criterion-Related Validity of the AAQ-II and MEAQ. Data was analyzed from sample group 2 (n = 462).

Abbreviations: AAQ-II; Acceptance and Action Questionnaire – II, MEAQ; Multidimensional Experiential Avoidance Questionnaire, BA; Behavioral Avoidance, DA; Distress Aversion, P; Procrastination, DS; Distraction & Suppression, RD; Repression & Denial, DE; Distress Endurance, D; Depress from Depression Anxiety Stress Scale 21, A; Anxiety from Depression Anxiety Stress Scale 21, S; Stress from Depression Anxiety Stress Scale 21, SWLS; Satisfaction with life Scale, * p < .05, ** p < .01.

TABLE 4. Fit indices from of Confirmatory Factor Analysis of the Thai version of the Acceptance and Action Questionnaire - II and Thai version of the Multidimensional Experiential Avoidance Questionnaire.

Abbreviations: χ2; Chi-square, df; degree of freedom, RMSEA; Root Mean Square Error of Approximation, CFI; Comparative Fit Index, SRMR; Standardized Root Mean Square Residual, NNFI; Non-Normed Fit Index

Thai version of the MEAQ, the R2 ranged between 0.06-

0.57 before modification. Afterwards, the R2 increased as follows: 1) behavioral avoidance (0.23-0.73); 2) distress

aversion (0.25-0.48); 3) procrastination (0.33-0.53); 4)

distraction and suppression (0.27-0.55); 5) repression

and denial (0.27-0.59); and 6) distress endurance (0.28-

0.57).

The construct reliability (CR) of the Thai version of AAQ-II before modification was 0.892. After modification, it was similar or 0.883. For the Thai version of MEAQ, the CR before modification was between 0.797-0.853, and was similar after or in the range of 0.792-0.862. Each domain was scored as follows: 1) behavioral avoidance (0.818);

2) distress aversion (0.802); 3) procrastination (0.810);

Factor loading

R2

CR

Original Modified Original Modified Original Modified

AVE

Original Modified

TABLE 5. Factor loading, Squared multiple correlation, Construct Reliability, Average Variance Extracted of the Thai version of the Acceptance and Action Questionnaire - II and Thai version of the Multidimensional Experiential Avoidance Questionnaire.

Abbreviations: R2; Squared multiple correlation, CR; Construct Reliability, AVE; Average Variance Extracted, AAQ-II; Acceptance and Action Questionnaire – II, MEAQ; Multidimensional Experiential Avoidance Questionnaire, BA; Behavioral Avoidance, DA; Distress Aversion, P; Procrastination, DS; Distraction & Suppression, RD; Repression & Denial, DE; Distress Endurance, * p < .05, ** p < .01

1. distraction and suppression (0.827); 5) repression

   and denial (0.862); and 6) distress endurance (0.792). Meanwhile, the average variance extracted (AVE) of the Thai version of AAQ-II before modification was 0.543. After modification, it increased to 0.557. For the Thai version of MEAQ, AVE ranged between 0.287-0.370 before modification. Afterwards, it increased to 0.393-

   0.456 and the results of each domain are as follows:

   1) behavioral avoidance (0.393); 2) distress aversion

   (0.406); 3) procrastination (0.416); 4) distraction and

   suppression (0.409); 5) repression and denial (0.456);

   and 6) distress endurance (0.393).

   DISCUSSION

   The reliability of backward translated questionnaires was equivalent to the original versions as both had statistically significant high correlation coefficients. This indicates that scores measured by the original and the backward translated version are related and consistent. In addition, by using Internal Consistency Reliability analysis, the researcher noted high internal consistency in which the alpha value of AAQ-II was 0.89 and 0.92 for MEAQ. These values are similar to the original version, in which alpha of AAQ-II and MEAQ were 0.84 and 0.85, respectively. The alpha values of other translated of other translated questionnaires or the Spanish version19 were 0.75, and

   0.93, respectively. When compared to total CITC scores, it was found that most items had a score of greater than 0.218, except item 23 – ‘I’m in touch with my emotions’. MEAQ, which is a reversed item, had a score of 0.169. This may have been caused by a misunderstanding among participants when responding to questionnaires which had a mix of both negative and positive items. However, the reliability of translated questionnaires is consistent and equivalent to the original.

   Moreover, carrying out confirmatory factor analysis after modifying the model, the squared multiple correlation (R2), which signifies reliability of indicators or items in the AAQ-II, ranged between 0.49-0.62. Meanwhile, each item in the Thai version of MEAQ obtained R2 in the following range: 1) behavioral avoidance (0.23- 0.73); 2) distress aversion (0.25-0.48); 3) procrastination

   (0.33-0.53); 4) distraction and suppression (0.27-0.55);

2. repression and denial (0.27-0.59); and 6) distress endurance (0.28-0.57). After considering construct reliability (CR) to measure latent variables, it was found that after modification, the Thai version of AAQ-II was 0.883 and between 0.792-0.862 for MEAQ. The domain in each was as follows: 1) behavioral avoidance (0.818);

2) distress aversion (0.802); 3) procrastination (0.810); 4) distraction and suppression = (0.827); 5) repression and denial = (0.862); and 6) distress endurance = (0.792). For

average variance extracted (AVE) after modification, the score for the Thai version of AAQ-II: Thai Version was

.557 and of between 0.393-0.456 for MEAQ. In each, the domain was as follows: 1) behavioral avoidance (0.393);

2) distress aversion = (0.406); 3) procrastination (0.416);

4) distraction and suppression (0.409); 5) repression

and denial (0.456); and 6) distress endurance (0.393). Ultimately, the criteria suggests that both CR and AVE were above 0.5.20 All domains of the Thai MEAQ had AVE below 0.5, but since Fornell and Larcker stated that if AVE is less than 0.5, but the construct reliability is higher than 0.6, we can accept convergent validity of the construct as still adequate.21 Hence, this indicated that both the Thai version of AAQ-II and MEAQ had a good level of reliability in terms of questionnaire and in respect to each domain, including the reliability of in measuring latent variables of each construct.

Regardingvalidity, itwasfoundthatbothquestionnaires had good content validity. Each item complied with factors under consideration of the expert. In examining the relationship of scores measured using AAQ-II and MEAQ, and from DASS-21 and SWLS, statistical significance of both questionnaires’ ability to measure depression, anxiety, stress, and life satisfaction scores was observed. Still, while considering each element of the MEAQ, the researcher found that subscale distraction and suppression were not related to depression, anxiety, and life satisfaction but distress. While there is no relationship between the Distress Endurance Subscale and stress, there is a negative relationship with depression and anxiety and a positive relationship with life satisfaction. This correlates with the original study.12 Ultimately, this indicates that if an individual intentionally uses distraction and suppression to ignore certain events, it may make that individual stressed, but it does not affect depression, anxiety, or satisfaction of life. An individual with distress endurance means he/she encounters distress, but solves the problem without fear. This might result in a decrease in the individual’s depression and anxiety and increases life satisfaction.

A confirmatory factor analysis examining the factors found that the hypothesized measurement model of the Thai AAQ-II and MEAQ did not fit well with empirical data. For the models to relate more, the researcher modified them based on the modification index, factor loading value, squared multiple correlations (R2), and measurement error. Other factors considered were based on theory and an item’s suitability.22 The result was that the modified Thai AAQ-II and MEAQ obtained construct validity with admissible fit indices that decreased the Thai AAQ-II to six items, with a factor load between 0.70-0.79. For

the Thai version of MEAQ, although there were still six component aspects, the number of items decreased to 39 with factor loading ranging from 0.5-0.89, including:

1. behavioral avoidance (0.53-0.73); 2) distress aversion

   (0.50-0.69); 3) procrastination (0.58-0.73); 4) distraction and suppression (0.52-0.74); 5) repression and denial (0.52-0.77); and 6) distress endurance (0.53-0.76). All had a statistical significance of .05. The result from confirmatory factor analyses of these research sample groups validated both questionnaires’ ability to ‘EA’. The Thai version of the AAQ-II had good constructs to measure. Also, it was a one-factor model as its first item was eliminated due to excessive difficulty of comprehension. However, the second and third items were allowed as their deviations correlated with one another. Thus, when using the Thai version of AAQ-II, one must be cautious and consider the first item. Meanwhile, the Thai version of the MEAQ had admissible levels of construct to measure before modification. Still, after modification and elimination of some items, which had factor load below 0.422 and/ or low R2, there was relatively high measurement error (the eliminated items were 1, 2, 4, 6, 7, 8, 13, 16, 18, 19,

   21, 23, 24, 26, 30, 31, 34, 39, 46, 48, 53, 54, 62). This made

   the model more consistent with empirical data and thus confirmed that the Thai version of MEAQ was a six- factor model which correlated with the study by Gamez, Chmielewski12 and Rochefort, Baldwin.23 However, by eliminating 23 items, when using the MEAQ, one must be careful and modify the quality of these items for the Thai version.

   In summary, the validity of both questionnaires is appropriate in terms of f content, criteria, and construct validity.

   When comparing AAQ-II and MEAQ, the researcher found that the correlation between AAQ and other scales was higher compared to MEAQ, which only has a moderate correlation. This could imply that AAQ-II is associated with distress variables such as neuroticism and negative effects than experiential avoidance.12,24 Consequently, AAQ-II is more related to scales linked to distress than MEAQ. However, this was also the limitation of this study. Thus, future research should further examine valid criteria between the Thai version of AAQ-II and MEAQ and other scales relating to avoidance. Moreover, confirmatory factor analysis to confirm structure of both hypothesized measurement models found that it was necessary to modify the model by eliminating some items so that the models are more consistent with empirical data and have the items that can explain or assess the remaining EA. Thus, the use of these two questionnaires depends on measuring objectives. For example, if one

   
   

   wants to measure psychological distress, the Thai version of the AAQ-II might be more suitable. However, if one wants to measure issues involving behavioral avoidance, the Thai version of MEAQ might be better. However, the psychometric properties of these questionnaires were assessed and analyzed from a specific sample as the study population is between 18 and 40 years old and is female more than male, so the results may have gender deference, and it is not generalizable to the rest of the age, gender, and the wider context.

   
   

   CONCLUSION

   This study found that the Thai versions of the AAQ- II and MEAQ have an acceptable level of psychometric properties in terms of validity and reliability since they are applicable to the Thai population aged between 18-40. Still, according to the results, there may be some items that require special attention and caution.

   When comparing the Thai versions of AAQ-II and MEAQ, we can see that both questionnaires have a similar level of validity and reliability considered admissible. However, upon further investigation, the correlation between the Thai version of the AAQ-II and other scales is higher compared to MEAQ which only has a moderate correlation. This is in agreement with other reviews stating that AAQ-II tends to be associated with distress variables such as depression, anxiety, and stress. However, it is still able to assess experiential avoidance.12,24 Hence, the use of each questionnaire will be depended on certain objectives. If one wants to measure psychological well- being or assess psychological distress such as anxiety, depression or emotional distress, the Thai version of the AAQ-II may be more suitable than its MEAQ counterpart, which concentrates on measuring behavior relating to avoidance. Still, further studies regarding the ability of both questionnaires to measure avoidance compared to other tests is required.

   
   

   ACKNOWLEDGMENTS

   This research was supported by Siriraj Graduate Scholarship. We would like to thank the Faculty of Medicine Siriraj Hospital, Mahidol University, in providing scholarships to support this research. We would like to express our appreciation to Dr. Wakiza Gamez who helped translate the MEAQ into Thai and Dr. Steven

   C. Hayes who gave permission to translate the AAQ-II into Thai.

   
   

   Conflicts of interest: Ethical approval for this study was been granted by the Institutional Review Board of the Faculty of Medicine Siriraj Hospital at Mahidol

   University. Sections of these findings were presented at Siriraj Graduate Forum, Bangkok, Thailand, 2019. We have no conflicts of interest to disclose.

   
   

   REFERENCES

   1. Hayes SC, Strosahl KD, Wilson KG. Acceptance and commitment therapy: An experiential approach to behavior change. New York: Guilford Press; 1999.

   2. Hayes SC, Wilson KG. Acceptance and commitment therapy: Altering the verbal support for experiential avoidance. Behav Anal. 1994;17(2):289-303.

   3. Hayes SC, Wilson KG, Gifford EV, Follette VM, Strosahl K. Experimental avoidance and behavioral disorders: a functional dimensional approach to diagnosis and treatment. J Consult Clin Psychol. 1996;64(6):1152-68.

   4. Kashdan TB, Barrios V, Forsyth JP, Steger MF. Experiential avoidance as a generalized psychological vulnerability: comparisons with coping and emotion regulation strategies. Behav Res Ther. 2006;44(9):1301-20.

   5. Stewart SH, Zvolensky MJ, Eifert GH. The relations of anxiety sensitivity, experiential avoidance, and alexithymic coping to young adults' motivations for drinking. Behav Modif. 2002;26(2): 274-96.

   6. Westrup D. Experiential avoidance and alcohol dependence relapse (Doctoral Dissertation, West Virginia University, 1999). Dissertation Abstracts International. 1999;62:568.

   7. Shorey RC, Gawrysiak MJ, Elmquist J, Brem M, Anderson S, Stuart GL. Experiential avoidance, distress tolerance, and substance use cravings among adults in residential treatment for substance use disorders. J Addict Dis. 2017;36(3):151-7.

   8. Kashdan TB, Morina N, Priebe S. Post-traumatic stress disorder, social anxiety disorder, and depression in survivors of the Kosovo War: experiential avoidance as a contributor to distress and quality of life. J Anxiety Disord. 2009;23(2):185-96.

   9. Spendelow JS, Joubert HE. Does Experiential Avoidance Mediate the Relationship Between Gender Role Conflict and Psychological Distress? Am J Mens Health. 2017:1557988317748123.

   10. Hayes SC, Barnes-Holmes D, Roche B. Relational frame theory: a post-Skinnerian account of human language and cognition. Adv Child Dev Behav. 2001;28:101-38.

   11. Bond FW, Hayes SC, Baer RA, Carpenter KM, Guenole N, Orcutt HK, et al. Preliminary psychometric properties of the Acceptance and Action Questionnaire-II: a revised measure of psychological inflexibility and experiential avoidance. Behav Ther. 2011;42(4): 676-88.

   12. Gamez W, Chmielewski M, Kotov R, Ruggero C, Watson D. Development of a measure of experiential avoidance: the Multidimensional Experiential Avoidance Questionnaire. Psychol Assess. 2011;23(3):692-713.

   13. Silpakit O, Silpakit C. The Psychometric Property of the Short Thai Version of the Philadelphia Mindfulness Scale. Siriraj Med J. 2018;70(4):310-26.

   14. Oei TP, Sawang S, Goh YW, Mukhtar F. Using the Depression Anxiety Stress Scale 21 (DASS-21) across cultures. Int J Psychol. 2013;48(6):1018-29.

   15. Diener E, Emmons RA, Larsen RJ, Griffin S. The Satisfaction with Life Scale. J Pers Assess. 1985;49(1):71-5.

   16. Sawasdipanich N, Tiansawad S. Instrument Translation for Cross-Cultural Research: Technique and Issues to be Considered.

       
       

       Thai Journal of Nursing Counsil. 2011;26(1):19-28.

   17. Choochom O. Construction and Development of Measuring Instruments in Behavioral Science. Srinarkharinwirot University. Behavioral Science Research Institute; 2002.

   18. Streiner DL, Norman GR, Cairney J. Health Measurement Scales: A practical guide to their development and use: Oxford University Press; 2014.

   19. Ruiz FJ, Langer Herrera AI, Luciano C, Cangas AJ, Beltran I. Measuring experiential avoidance and psychological inflexibility: The Spanish version of the Acceptance and Action Questionnaire

       - II. Psicothema. 2013;25(1):123-9.

   20. Joseph F. Hair, William C. Black, Babin BJ. Multivariate Data Analysis: A Global Perspective. 7th ed. Upper Saddle River:

       Pearson Education; 2010.

   21. Fornell C, Larcker DF. Evaluating structural equation models with unobservable variables and measurement error. Journal of Marketing Research. 1981;18(1):39-50.

   22. Stevens JP. Applied multivariate statistics for the social sciences, 5th ed. New York, NY, US: Routledge/Taylor & Francis Group; 2009. xii, 651-xii, p.

   23. Rochefort C, Baldwin AS, Chmielewski M. Experiential Avoidance: An Examination of the Construct Validity of the AAQ-II and MEAQ. Behav Ther. 2018;49(3):435-49.

   24. Wolgast M. What Does the Acceptance and Action Questionnaire (AAQ-II) Really Measure? Behav Ther. 2014;45(6):831-9.

Surgical Outcomes of Bariatric Surgery in Siriraj Hospital for the First 100 Morbidly Obese Patients Treated

Nicha Srisuworanan, M.D.*, Vitoon Chinswangwatanakul, M.D.*, Asada Methasate, M.D.*, Thawatchai Akaraviputh, M.D.*, Jirawat Swangsri, M.D.*, Atthaphorn Trakarnsanga, M.D.*, Chainarong Phalanusitthepha, M.D.*, Thammawat Parakonthun, M.D.*, Tharathorn Suwatthanarak, M.D.*, Thikhamporn Tawantanakorn, M.D.*, Thanyadej Nimmanwudipong, M.D.*, Handy Wing, M.D.**, Voraboot Taweerutchana, M.D.*

*Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

**Digestive Surgery Division, EMC Hospital Alam Sutera Tangerang, Indonesia.

ABSTRACT

Objective: Bariatric surgery is considered the most effective treatment for morbid obesity, and is increasingly performed in Thailand and globally. We aimed to establish the outcomes of bariatric surgery performed at Siriraj Hospital, Bangkok.

Materials and Methods: This was a retrospective study of patients who underwent bariatric surgery between January 2012 and June 2016.

Results: The records of the first 100 patients who underwent bariatric surgery were reviewed, comprising 58 patients who underwent laparoscopic sleeve gastrectomy (LSG) and 42 patients who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB). The median patient age, preoperative body weight, and BMI were 36 years old, 129 kg, and 46.3 kg/m2. All the procedures were performed by a laparoscopic approach. The median operative times for LSG and LRYGB were 156 [85-435] and 265 [180-435] minutes. The median hospital stay was 3 days [3-14]. The major complication rate was 4%. There was no mortality in the 30-day postoperative period. The mean %excess weight loss (%EWL) of LSG was 56.8 ± 19.8%, 59.9 ± 21.7%, and 55.1 ± 21.3%, at 1, 2, and 3 years after surgery. The

mean %EWL of LRYGB was 67 ± 18.3%, 66.2 ± 21.4%, and 63.6 ± 19.9%, at 1, 2, and 3 years after surgery. In the patients with type-II diabetes mellitus, 67% had complete diabetic remission at 1 year. The median FBS dropped from 127 to 99 mg/dL (p < 0.001) and HbA1c from 6.6% to 5.5% (p < 0.001). The remission rates of hypertension and dyslipidemia were 58% and 73%.

Conclusion: The bariatric procedures are safe with a low complication rate. The procedures also provide good outcomes in postoperative weight loss and comorbidity resolution.

Keywords: Bariatric surgery; laparoscopic sleeve gastrectomy; laparoscopic Roux-en-Y gastric bypass; outcomes (Siriraj Med J 2022; 74: 769-777)

INTRODUCTION

Obesity increases the risk of many serious health problems, including diabetes mellitus (DM), hypertension, and dyslipidemia. It is also a major cause of death, particularly attributable to cardiovascular disease, stroke, and cancers.

The prevalence of obesity has been increasing worldwide in recent decades, linked to the trends of excessive food intake and lack of physical activity. The most common treatment strategies are behavioral changes through healthy diet and exercise. In addition to the principle of

Corresponding author: Nicha Srisuworanan E-mail: nicha.srw@gmail.com

Received 15 August 2022 Revised 23 September 2022 Accepted 27 September 2022 ORCID ID:http://orcid.org/0000-0003-3079-9848 http://dx.doi.org/10.33192/Smj.2022.91

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

behavioral changes, the three main treatment option for morbid obesity consist of lifestyle modification, medical therapy, and bariatric surgery.

Bariatric surgery has been proven to be the most effective treatment in weight loss and comorbidity resolution in the long term. Many studies have shown that bariatric surgery enables better weight reduction, comorbidity resolution, and quality of life compared to non-surgical methods. The current standard approach for bariatric surgery is the laparoscopic approach. This offers the benefits of faster recovery, a lower complication rate, and shorter hospital stay compared with open approaches.

In Thailand, the annual prevalence of obesity has been increasing dramatically over the past few decades. By 2009, the prevalence of obesity class II (BMI >30 kg/ m2) in Thai adults had reached 7% in men and 12% in women1, prompting the promotion of many lifestyle modification strategies, as well as the introduction of more effective treatments in Thailand, including bariatric surgery.

Since then, bariatric procedures have been increasingly performed; however, while outcome assessment is also important it has been less reported. Consequently, in this study we aimed to establish the surgical outcomes of the initial experience of bariatric surgery in Siriraj Hospital, regarding the efficacy of weight loss, comorbidity resolution, and complications.

MATERIALS AND METHODS

This study was approved by the Siriraj Institutional Review Board. (Si 813/2016) The first 100 patients who underwent bariatric surgery as treatment for morbid obesity between January 2012 and June 2016 in Siriraj Hospital were enrolled in the study.

The criteria for bariatric surgery in Siriraj Hospital, and according to the Asia-Pacific Bariatric Surgery society consensus 2005, are obese patients who: (1) have a BMI

> 37 kg/m2; (2) have a BMI > 32 kg/m2 with diabetes or

two significant obesity-related comorbidities; (3) have been unable to lose weight through dietary or medical treatment; and (4) are 18–65 years old.2 Also, all the patients must be absent of any endocrine disorder causing massive obesity, psychologic instability, and alcohol or drug abuse. Revisional bariatric procedures were also excluded from this study.

The main procedures for bariatric surgery performed in Siriraj Hospital are laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). After preoperative counseling, the patients choose the surgical procedure by themselves, providing there are no contraindications.

The patients’ demographic data and clinical characteristics, including age, gender, preoperative body weight, preoperative body mass index (BMI), obesity- related comorbidities, preoperative laboratory studies, operative time, intraoperative blood loss, length of hospital stay, overall complications, and 30-day morbidity and mortality were reviewed. Concomitant cholecystectomy was performed if preoperative abdominal ultrasound showed any gallstones, regardless of the patient’s symptoms.

For the patient’s comorbidities, we recorded both preoperative and postoperative HbA1c, fasting blood glucose (FBG), blood pressure, serum cholesterol, triglycerides, LDL, HDL, and medications.

The outcomes of the surgery were studied in two aspects: (1) postoperative weight loss and (2) comorbidity resolution. Postoperative weight loss was reported as percent total weight loss (%TWL), and percent excess weight loss (%EWL), calculated as shown in Fig 1.

There are various definitions of successful weight loss after bariatric surgery. In our center, we use the definition of >20% TWL or >50%EWL in the first year after bariatric surgery. These are the most widely used definitions based on the evidence of comorbidities and cardiovascular risk improvement.3

The outcome of comorbidity resolution was reported according to the American Society of Metabolic and

Fig 1. Calculation of postoperative weight loss

Bariatric Surgery (ASMBS) reporting standards 2015. For type-2 diabetes mellitus (DM), complete remission was stated if HbA1c < 6% and FBG < 100 mg/dL, and partial remission was considered when HbA1c = 6.0–6.5% and FBG = 100–125 mg/dL for at least 1 year with the absence of anti-diabetic medication. Disease improvement was considered when HbA1c and FBS were significantly reduced but did not meet the criteria for remission or were decreased but with anti-diabetic medication required. Hypertension remission was documented if BP < 120/80 mmHg without medication. Dyslipidemia remission was considered when LDL < 100 mg/dL, total cholesterol < 200 mg/dL, and triglycerides < 150 mg/dL.

Postoperative complications were reported as early (<30 days) and late (>30 days postoperative) complications. Major complications, according to the ASMBS outcome reporting standards 2015, were defined as any complications that prolonged the hospital stay beyond 7 days, receiving anticoagulant therapy, reintervention, or reoperation.3 Before surgery, all patients must be evaluated by a multidisciplinary team, including a bariatric surgeon, nutritionist, cardiologist, pulmonologist, psychiatrist, and physical therapist. An education session covering the principles of a healthy diet and physical activity is provided for patients during the preoperative visits. Preoperative checklist, according to AACE/TOS/ASMBS Clinical Practice Guidelines 2013, was evaluated including cardiopulmonary evaluation with sleep apnea screening if indicates.4 For the patients with severe obstructive sleep apnea (OSA), Optimizing CPAP treatment must be achieved at least 4 weeks prior to surgery. A very low calorie diet (600–800 kcal/day) is suggested to all patients 2 weeks before surgery for preoperative weight loss if there is no contraindication. We recommend 5–10 kg preoperative weight loss in every patient before surgery.

Surgical techniques Laparoscopic sleeve gastrectomy

In laparoscopic sleeve gastrectomy (LSG), the patient is placed in a supine position. A 36-French orogastric tube is inserted, and 5000 units of unfractionated heparin are injected subcutaneously to prevent deep vein thrombosis. A Veress needle is inserted into the abdomen at Palmer’s point for insufflation. A 12 mm camera port is placed 20 cm below the xiphoid and 4 cm to the left of the midline, using an Optiview trocar and a 10 mm zero- degree laparoscope. Then, the camera is exchanged for a 30-degree laparoscope. The patient position is changed to a reverse Trendelenburg position. Nathanson’s liver retractor is applied to the left lobe of the liver via a small incision at the epigastrium. Two 5 mm ports are placed

at the left anterior axillary line and right midclavicular line about 15 cm below the xyphoid process. Then, a 15 mm port is placed 20 cm inferior to the xiphoid and 2 cm to the right of the midline.

The omentum of the greater curvature of the stomach is divided using a Ligasure advanced bipolar device (Medtronic) from 4 cm proximal to the pylorus up to the angle of His. The blood supplies along the greater curvature, including the short gastric arteries, are ligated completely. Using the orogastric tube as a calibrator, a hook cautery is used to mark the resection line of the stomach. The Medtronic Autostapler (iDrive) is introduced via the 15 mm port. Then, the stomach is transected over the orogastric tube calibrator using 60 mm black cartridges at the antrum and purple cartridges at the body. The posterior wall of the gastric tube is fixed to the posterior side with interrupted 3-0 Prolene stitches in order to prevent the gastric tube from twisting. Leak tests with methylene blue dye and drain placement are performed in selected cases. Hemostasis is checked, and then the resected stomach is removed via an endobag. The 12 and 15 mm port sites are closed using 1-0 Vicryl on a suture passer, Then, the skin is closed in the standard fashion.

Laparoscopic Roux-en-Y gastric bypass

In Laparoscopic Roux-en-Y gastric bypass (LRYGB), the patient position and preoperative preparation are similar to in LSG as mentioned above. A 12 mm camera port is placed 22 cm below the xiphoid and 2 cm to the left of midline. Nathanson’s liver retractor is applied to the left lobe of the liver. A 5 mm port is placed at the left anterior axillary line as an assistant port. Three 12 mm ports are placed on the right midclavicular line, 2 cm to the right of midline and left midclavicular line. The transverse mesocolon is retracted caudally to expose the ligament of Treitz. The jejunum is measured to 100 cm distal to the DJ junction. Then, the jejunum is transected, including its mesentery, using a 60 mm autostapler (iDrive) tan cartridge to create a 100 cm biliopancreatic limb (BP limb). Another 100 cm of the jejunum is measured. Then, by using a 45 mm tan cartridge, a stapled side-to-side jejunojejunostomy is made between the biliopancreatic limb and jejunum to create a 100 cm Roux limb. The enterotomy site is closed using a running 3-0 Vicryl and the mesenteric defect is

closed to its base with a running 3-0 Prolene.

Then, the greater omentum is split in a left paramedian plane to 1 cm away from the transverse colon using a harmonic scalpel. The lesser omentum of the stomach is entered at the level of 6 cm from the EG junction to

create the gastric pouch. Then, a 3-cm horizontal firing is made across the stomach using a 45 mm autostapler purple cartridge. Sequential vertical firings by EndoGIA 60 mm purple cartridges are used to carry on the staple line upward to a point just lateral to the angle of His. This ensures the complete gastrogastric division. The blunt tip of an oral anvil of a 25 mm transoral circular stapler (EEA OrVil, Medtronic) is inserted into the distal part of the gastric pouch.

The 12 mm port at the left midclavicular line is replaced with the handle of the transoral circular stapler (EEA XL). The staple line at the end of the Roux limb is divided and the tip of the stapler handle is inserted. The Roux limb with the circular stapler is brought upward to the gastric pouch, and then the circular gastrojejunostomy anastomosis is created. The blind end including the enterotomy of the Roux limb is cut off using a 45 mm autostapler tan cartridge. A leak test is performed by instilling 50 mL of dilute methylene blue (2 mL per 100 mL of NSS) into the orogastric tube.

The Petersen’s defect is closed by suturing the mesentery of the Roux limb to the mesentery of the transverse mesocolon using a running 3-0 Prolene. A 10-French JP drain is placed near the gastrojejunostomy through the LUQ port site. The 12 and 15 mm port sites are closed using a 1-0 Vicryl on a suture passer and the skin is closed in the standard fashion.

Postoperative care

A dietary program is initiated with a clear liquid diet on postoperative day 1, and then advanced to a full liquid diet (high-protein supplement) on postoperative day 3. IV-PCA (intravenous patient-controlled analgesia) with an opioid is given to patients for postoperative pain control. A sequential compression device is used as routine for DVT prophylaxis. Then after early ambulation is initiated on postoperative day 1, the compression device can be removed.

After discharge, the patients return to the bariatric clinic for a follow-up visit at 2 weeks after surgery and will be advised on a diet comprising 3 small meals with micronutrient supplementation. A proton pump inhibitor is given to the patients for use for 3 months after surgery for marginal ulcer prevention; especially in patients who underwent LRYGB. Ursodeoxycholic acid is given to the patients for 6 months for gall stone prevention.

Follow-up appointments for clinical and nutritional assessment are scheduled at 3 months, 6 months, 9 months, 12 months, and then annually. Routine postoperative esophagogastroduodenoscopy (EGD) is performed in every patient at 1 year after surgery.

Statistical analysis

Categorical data were reported using the number and percentage. Continuous data were expressed as the mean with the standard deviation and median value with a range of the minimum and maximum. The mean and median preoperative and postoperative parameters were compared using the paired sample t-test and Wilcoxon signed rank test, respectively. IBM SPSS Statistics version

26.0 (SPSS, Chicago, Illinois, USA) for Mac was used for all the statistical analyses. A p-value of less than 0.05 was considered as statistically significant.

RESULTS

Among the first 100 bariatric surgery patients in Siriraj Hospital, 69% were female and 31% male. The median age was 36 years old [16-64]. The median preoperative body weight and BMI were 129 kg [88-270] and 46.3 kg/m2 [34.0-83.3], respectively. For pre-existing comorbidity, 45% of patients had been diagnosed with type 2 diabetes mellitus (DM), 65% with hypertension, 38% with dyslipidemia, 4% with coronary artery disease, 35% with obstructive sleep apnea (OSA), and 10% with osteoarthritis of the knee. The patients’ demographic data are summarized in Table 1.

There were 58 cases of laparoscopic sleeve gastrectomy (LSG) and 42 cases of laparoscopic Roux-en-Y gastric bypass (LRYGB). All the operations had been performed by laparoscopic approach successfully without conversion to the open approach. The median operative time for LSG

(N = 100)

TABLE 1. Patients’ demographic data.

Sex (F:M) 69:31

Age, year 36 [16–64]

Preoperative body weight, kg 129 [88–270]

Preoperative BMI, kg/m2 46.3 [34.0–83.3]

Pre-existing comorbidity

DM (type 2) 45 (45%)

Diet control (2/45)

Oral hypoglycemic drug (37/45) Insulin therapy (6/45)

was 156 minutes [85-435] and 265 minutes [180-435] for LRYGB. The concomitant procedures generally took longer operative time than normal bariatric procedures. The longest operation of LSG (435 minutes) was firstly attempted for LRYGB but was failed due to severe adhesion from previous abdominal surgery and then was converted to LSG. The mean estimated blood loss was 20 ml and 25 ml for LSG and LRYGB, respectively. The median postoperative length of hospital stay was 3 days [3-14], as shown in Table 2.

TABLE 2. Operative and postoperative data of the bariatric surgery patients.

Operative data (N = 100)

Operative time (min)

LSG 156 [85–435]

LRYGB 265 [180–435]

Estimated blood loss (ml) LSG

LRYGB

20 [5–300]

25 [5–400]

Conversion to open approach 0

Postoperative complication (case) Early (≤ 30 day)

Length of hospital stay (days) 3 [3–14]

Abbreviation: IPOM; Intraperitoneal onlay mesh repair; laparoscopic hernia repair for ventral hernia

Weight loss outcome

The follow-up rates at 1 year, 2 years, and 3 years after surgery were 76%, 57%, and 55%, respectively. The mean %TWL and mean %EWL at 3 months, 6 months, 9 months, 1 year, 2 years, and 3 years are shown in Table 3,

Table 4 and Fig 2.

The mean %TWL of the patients who underwent LSG at 1 year, 2 years, and 3 years were 30.2 ± 10.4%,

30.9 ± 11.2%, and 28.4 ± 11.3%, respectively. The mean

%EWL of the LSG patients at 1 year, 2 years, and 3 years were 56.8 ± 19.8%, 59.9 ± 21.7%, and 55.1 ± 21.3%,

respectively. As for the patients who underwent LRYGB, the mean %TWL at 1 year, 2 years, and 3 years were 33.4

± 7.5%, 33.2 ± 9.6%, and 31.9 ± 8.6%, respectively. The mean %EWL of the LRYGB patients at 1 year, 2 years, and 3 years were 67 ± 18.3%, 66.2 ± 21.4%, and 63.6 ±

19.9%, respectively.

Comorbidity outcomes

For the 45 patients with pre-existing type-II diabetes, 33 patients reached the follow-up time at 1 year, comprising 9 LSG cases and 24 LRYGB cases. All 6 of the patients who had received insulin therapy had underwent LRYGB. At 1 year after surgery, the median fasting blood glucose (FBG) dropped from 127 to 99 mg/dL (p < 0.001) and HbA1c also dropped from 6.6% to 5.5% (p < 0.001) with statistical significance. Of these 33 patients, 67% of the patients (22/33) had complete diabetic remission, while 6% of the patients (2/33) had partial remission, and 21% of the patients (7/33) showed disease improvement. Five of the six patients (5/6) who received insulin therapy prior to surgery could be successfully weaned off insulin

and 4 of them achieved complete diabetic remission.

Among the 65 patients with hypertension, 38 reached the follow-up time at 1 year. The remission rate of hypertension was 58% (22/38). There were significant differences between preoperative and postoperative blood pressure. The mean systolic BP dropped from 138 ± 18 mmHg to 129 ± 13 mmHg (p = 0.004) and diastolic BP from 81 ± 15 mmHg to 77 ± 10 mmHg (p = 002).

As for the 38 patients with dyslipidemia, 22 reached the follow-up time at 1 year. The remission rate of dyslipidemia was 73% (16/22). The median serum LDL was 101 mg/ dl [65-165], and the median serum triglyceride was 80 mg/dl [38-168] at 1 year after surgery, as also shown in Table 5.

Overall complications

The overall 30-day postoperative complication rate was 9%, and the rate of major complications was 4% (Table 2). There were 2 cases of venous thromboembolic

TABLE 3. Weight loss outcome of laparoscopic sleeve gastrectomy (LSG).

TABLE 4. Weight loss outcome of laparoscopic Roux-en-Y gastric bypass (LRYGB).

Fig 2. Weight loss outcome after bariatric surgery.

TABLE 5. Preoperative and 1-year postoperative parameters of patients in the comorbidity group.

event (comprising 1 case of pulmonary embolism and 1 case of deep vein thrombosis), where anticoagulant therapy was given to the patients. One patient who underwent LRYGB developed a small intra-abdominal collection at postoperative day 7 without anastomotic leakage, as confirmed by a contrast study. The patient was successfully treated with intravenous antibiotics. There was 1 case of reoperation, in which a patient who had underwent LRYGB developed an intestinal obstruction on postoperative day 7 due to jejunojejunostomy stenosis. Laparoscopic adhesiolysis with jejunojejunostomy revision was performed at that time. There was no mortality in the 30-day postoperative period.

Regarding late complications, among the 42 patients who underwent LRYGB, 2 patients (4.8%) developed dumping syndrome in which the symptom could be improved by dietary modification. Seven patients (16.7%) had marginal ulcer detected in surveillance endoscopy at 1 year after surgery. Proton pump inhibitor (PPI) therapy was given to those patients without endoscopic intervention or surgery required.

Among the 58 patients who underwent LSG, 21 patients (36.2%) developed gastroesophageal reflux, including 1 patient (1.7%) with severe reflux esophagitis (LA classification grade C) and 1 patient (1.7%) with Barrett’s esophagus. Nine patients (15.5%) with gastroesophageal reflux complication had a concomitant sliding hiatal hernia detected by EGD at 1 year after surgery.

Moreover, 7 of the patients (12.1%) later received conversion surgery from sleeve gastrectomy to Roux-en-Y gastric bypass due to an indication of severe gastroesophageal reflux symptom (3 cases), inadequate weight loss or weight regain (3 cases), and sleeve tube stricture (1 case). The median time to conversion surgery was 3 years (ranging from 3–5 years) after the primary surgery.

DISCUSSION

Obesity has become a global health concern as its prevalence has been rising in many countries. The impact of obesity is not only an individual health problem but also the economic burden of the treatment cost for obesity- related illnesses. The goal of treatment is to reduce the risk of developing complications related to obesity and to improve the quality of life of the patients.

In morbidly obese patients, bariatric surgery is considered to be the most effective treatment to achieve long-term outcomes both in weight loss and comorbidity resolution. Several studies have shown that bariatric surgery has significantly better outcomes for weight loss, comorbidity resolution, and quality of life compared with non-surgical methods both in the short term and

long term.5-7 A recent meta-analysis demonstrated the durable outcomes of bariatric surgery with a 10-year follow-up. The mean %EWL of sleeve gastrectomy was 58.3% in 2 studies, while Roux-en-Y gastric bypass was 56.7% in 18 studies.8

In this study, we demonstrated the short-term outcomes of bariatric surgery performed in Siriraj Hospital. Our center has demonstrated good weight loss outcomes with mean %EWL for LSG and LRYGB as 56.8% and 67% at 1 year after surgery, and maintenance of a mean

%EWL of >50% at the follow-up time of 3 years after surgery. Other studies have reported the 1-year %EWL of LSG at between 56%–72.6%9-11, and LRYGB at 62.6%- 80.4%.12-14 These indicate that the results of our center are comparable with the outcomes of the other studies. Preoperative comorbidity, including type-2 DM, hypertension, and dyslipidemia, were found to be improved after surgery at our center. As for type 2 DM, our center has reported excellent outcomes, with a complete remission rate of 67% at 1 year after surgery. This result is comparable to other studies, in which the complete diabetic remission rate after bariatric surgery has been reported to be between 50.6%-67.9%.15,16 Several studies have shown that bariatric surgery has a significant better outcome for glycemic control compared with non-surgical methods, both in the short term and long

term.6,7

Regarding the operation safety, the complication rate of our center was considerably low. The major complication rate was reported at 4% without mortality. Ibrahim et al. reported the serious complication rate from 165 bariatric excellence centers in the United States ranged from 0.6%-4.9% in high-volume centers and 0.6%–10.3% in medium-volume centers.17 Anastomotic leakage, which is the most serious complication of bariatric surgery, was not detected in our study.

Gastroesophageal reflux disease (GERD) is the most common complication after sleeve gastrectomy. The incidence was reported at 36.2% in our study. In our literature review, the incident of de novo GERD was reported at 40%–60%18-20, based on clinical symptoms and endoscopic findings. Even so, the relationship between GERD and sleeve gastrectomy has long been controversial. Many studies have shown that the anatomical changes of LSG may worsen the existing GERD or cause GERD in some patients without pre-existing symptoms.21 Meanwhile, some studies have also shown that LSG can improve GERD after surgery.9,22 Some studies mentioned that the surgical technique and the shape of the gastric tube play important roles in preventing GERD after sleeve gastrectomy. Daes et al. proposed standardized

techniques and identified the technical errors that can lead to the development of GERD, including a narrowing at the junction of the vertical and horizontal part of the sleeve.22 Therefore, in our center, we routinely use a 36-French bougie as the calibrator and keep the area at the incisura angularis >2 cm to make sure that the angle between the vertical and horizontal parts of the sleeve is not too narrow. Moreover, we believe that another mechanism associated with GERD is the disruption of the phrenoesophageal ligament around the esophagogastric junction (EGJ). So we only dissect the gastric fundus to the level of the left diaphragmatic crus and avoid circumferential dissection around the EGJ.

Another predisposing factor related to GERD after sleeve gastrectomy is a pre-existing hiatal hernia.22,23 Many experts have suggested that a hiatal hernia should be repaired at the same time as sleeve gastrectomy.24 In our center, we found that 15.5% of the patients who underwent LSG had a hiatal hernia at the endoscopy performed 1-year after surgery. The reason for this might be because the lesions were too small and may have been missed during the surgery, or the sleeve tube itself may have later migrated upward into the chest. Therefore, we think that careful identification of a hiatal hernia, both preoperatively and during surgery, and adding concomitant hiatal hernia repair would help reduce the incidence of GERD after sleeve gastrectomy in the future.

One specific complication that can occur after RYGB is a marginal ulcer. The rate of marginal ulcers varies from 7%-34%.25-27 In our center, we found 16.7% of the RYGB patients had marginal ulcers at the routine postoperative endoscopy. Most of the patients were asymptomatic, so no early endoscopy had been performed before 1 year after surgery.

A marginal ulcer is believed to be associated with many local factors, such as inflammation, ischemia, and high acid production. A larger size of gastric pouch contains more parietal cells, causing more acidity and a greater risk of ulceration. Azagury et al. demonstrated that the gastric pouch length of the patients with marginal ulcers was significantly larger compared with a non- marginal ulcer group (5.6 ± 2 vs 4.9 ± 1.7, OR 1.2, p = 0.02).28 Edholm et al. also showed that a smaller gastric pouch can reduce the risk of marginal ulcers.29 So, in our center, we measure the gastric pouch length at 5–6 cm, so that the gastric pouch would not be >6 cm and

<4 cm in length. We believe that a gastric pouch length of less than 4 cm might increase the tension around the gastrojejunostomy anastomosis, which could lead to acute ischemia and become a risk of leakage or the

formation of a marginal ulcer afterward.

Moreover, there are multiple risk factors related to marginal ulcers, including smoking27,28,30, chronic non- steroidal anti-inflammatory drugs (NSAIDs) use27,30, Helicobacter pylori infection30, untreated obstructive sleep apnea30, and immunosuppression.27 Therefore, to reduce the risk of marginal ulcer formation, we aim to ensure that all the risk modifications must be achieved before a Roux-en-Y gastric bypass procedure is performed.

This study has demonstrated safety and feasibility of bariatric procedures in Siriraj Hospital performed between 2012 and 2016 by the standard laparoscopic approach. With the good results of surgical outcomes and low complication rate in this study, we established the standard protocol of preoperative and postoperative care for bariatric procedures in our center, including the robotic bariatric procedures which was later performed in 2017.31,32 In addition, The long-term results should be considered in a further study.

Limitations of this study

There are some limitations in this study to note. Our follow-up rate appeared to be less than in other studies, which might be due to the ineffectiveness of the follow-up system at the time of our initial experience. Moreover, this study was conducted in the early period of our experience. Therefore, the operative time was perhaps longer compared with other centers. However, despite the longer operative time, the complication rate of our center was also considerably low. Lastly, this was a retrospective study based on a chart review, which may means of some missing data.

CONCLUSION

Bariatric surgery, both laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass, can provide good outcomes in weight loss and comorbidity resolution. In Siriraj Hospital, the overall and major complication rates are low and comparable to other bariatric excellence centers.

Disclosure statement: No competing financial interests exist.

REFERENCES

1. Aekplakorn W, Inthawong R, Kessomboon P, Sangthong R, Chariyalertsak S, Putwatana P, et al. Prevalence and trends of obesity and association with socioeconomic status in Thai adults: National Health Examination Surveys, 1991-2009. J Obes. 2014;2014:410259.

2. Lee WJ, Wang W. Bariatric surgery: Asia-Pacific perspective. Obes Surg. 2005;15:751-57.

3. Brethauer SA, Kim J, el Chaar M, Papasavas P, Eisenberg D,

   
   

   Rogers A, et al. Standardized outcomes reporting in metabolic and bariatric surgery. Surg Obes Relat Dis. 2015;11(3):489-506.

4. Mechanick JI, Youdim A, Jones DB, Garvey WT, Hurley DL, McMahon MM, et al. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient--2013 update: cosponsored by American Association of Clinical Endocrinologists, the Obesity Society, and American Society for Metabolic & Bariatric Surgery. Surg Obes Relat Dis. 2013;9(2):159-91.

5. Gloy VL, Briel M, Bhatt DL, Kashyap SR, Schauer PR, Mingrone G, et al. Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised controlled trials. BMJ. 2013;347:f5934.

6. Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Aminian A, Brethauer SA, et al. Bariatric Surgery versus Intensive Medical Therapy for Diabetes - 5-Year Outcomes. N Engl J Med. 2017; 376(7):641-51.

7. Syn NL, Cummings DE, Wang LZ, Lin DJ, Zhao JJ, Loh M, et al. Association of metabolic-bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta- analysis of matched cohort and prospective controlled studies with 174 772 participants. Lancet. 2021;397(10287):1830-41.

8. O'Brien PE, Hindle A, Brennan L, Skinner S, Burton P, Smith A, et al. Long-Term Outcomes After Bariatric Surgery: a Systematic Review and Meta-analysis of Weight Loss at 10 or More Years for All Bariatric Procedures and a Single-Centre Review of 20-Year Outcomes After Adjustable Gastric Banding. Obes Surg. 2019;29(1):3-14.

9. Rawlins L, Rawlins MP, Brown CC, Schumacher DL. Sleeve gastrectomy: 5-year outcomes of a single institution. Surg Obes Relat Dis. 2013;9(1):21–5.

10. Jaruvongvanich V, Wongjarupong N, Vantanasiri K, Samakkarnthai P, Ungprasert P. Midterm Outcome of Laparoscopic Sleeve Gastrectomy in Asians: a Systematic Review and Meta- analysis. Obes Surg. 2020;30(4):1459-67.

11. Fischer L, Hildebrandt C, Bruckner T, Kenngott H, Linke GR, Gehrig T, et al. Excessive weight loss after sleeve gastrectomy: a systematic review. Obes Surg. 2012;22(5):721-31.

12. Corcelles R, Boules M, Froylich D, Hag A, Daigle CR, Aminian A, et al. Total weight loss as the outcome measure of choice after Roux-en-Y gastric bypass. Obes Surg. 2016;26(8):1794-8.

13. Garb J, Welch G, Zagarins S, Kuhn J, Romanelli J. Bariatric surgery for the treatment of morbid obesity: a meta-analysis of weight loss outcomes for laparoscopic adjustable gastric banding and laparoscopic gastric bypass. Obes Surg. 2009;19(10): 1447-55.

14. Ignat M, Vix M, Imad I, D’Urso A, Perretta S, Marescaux J, et al. Randomized trial of Roux-en-Y gastric bypass versus sleeve gastrectomy in achieving excess weight loss. Br J Surg. 2017; 104(3):248-56.

15. Lemus R, Karni D, Hong D, Gmora S, Breau R, Anvari M. The impact of bariatric surgery on insulin-treated type 2 diabetes patients. Surg Endosc. 2018;32:990-1001.

16. Peterli R, Wölnerhanssen BK, Peters T, Vetter D, Kroll D, Borbely Y, et al. Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss in Patients With Morbid Obesity: The SM-BOSS Randomized Clinical Trial. JAMA. 2018;319(3):255-65.

17. Ibrahim AM, Ghaferi AA, Thumma JR, Dimick JB. Variation in Outcomes at Bariatric Surgery Centers of Excellence. JAMA Surg. 2017;152(7):629-36.

18. King K, Sudan R, Bardaro S, Soriano I, Petrick AT, Daly SC, et al. Assessment and management of gastroesophageal reflux disease following bariatric surgery. Surg Obes Relat Dis. 2021; 17(11):1919-25.

19. Soricelli E, Casella G, Baglio G, Maselli R, Ernesti I, Genco A. Lack of correlation between gastroesophageal reflux disease symptoms and esophageal lesion after sleeve gastrectomy. Surg Obes Relat Dis. 2018;14(6):751-6.

20. Oor JE, Roks DJ, Ünlü Ç, Hazebroek EJ. Laparoscopic sleeve gastrectomy and gastroesophageal reflux disease: a systematic review and meta-analysis. Am J Surg. 2016;211(1):250-67.

21. Raj PP, Bhattacharya S, Misra S, Kumar SS, Khan MJ, Gunasekaran SC, et al. Gastroesophageal reflux-related physiologic changes after sleeve gastrectomy and Roux-en-Y gastric bypass: a prospective comparative study. Surg Obes Relat Dis. 2019;15(8): 1261-9.

22. Daes J, Jimenez ME, Said N. Improvement of Gastroesophageal Reflux Symptoms After Standardized Laparoscopic Sleeve Gastrectomy. Obes Surg. 2014;24:536-540.

23. Altieri MS, Pryor AD. Gastroesophageal reflux disease after bariatric procedures. Surg Clin North Am. 2015;95(3):579-591.

24. Rosenthal RJ, International Sleeve Gastrectomy Expert Panel, Diaz AA, Arvidsson D, Baker RS, Basso N, et al. International Sleeve Gastrectomy Expert Panel Consensus Statement: best practice guidelines based on experience of >12,000 cases. Surg Obes Relat Dis. 2012;8(1):8-19.

25. Moon RC, Teixeira AF, Goldbach M, Jawad MA. Management and treatment outcomes of marginal ulcers after Roux-en-Y gastric bypass at a single high volume bariatric center. Surg Obes Relat Dis. 2014;10(2):229-234.

26. El-Hayek K, Timratana P, Shimizu H, Chand B. Marginal ulcer after Roux-en-Y gastric bypass: what have we really learned? Surg Endosc. 2012;26(10):2789-96.

27. Di Palma A, Liu B, Maeda A, Anvari M, Jackson T, Okrainec A. Marginal ulceration following Roux-en-Y gastric bypass: risk factors for ulcer development, recurrence and need for revisional surgery. Surg Endosc. 2021;35(5):2347-53.

28. Azagury DE, Abu Dayyeh BK, Greenwalt IT, Thompson CC. Marginal ulceration after Roux-en-Y gastric bypass surgery: characteristics, risk factors, treatment, and outcomes. Endoscopy. 2011;43(11):950-4.

29. Edholm D, Ottosson J, Sundbom M. Importance of pouch size in laparoscopic Roux-en-Y gastric bypass: a cohort study of 14,168 patients. Surg Endosc. 2016;30:2011-5.

30. Rodrigo DC, Jill S, Daniel M, Kimberly C, Maher EC. Which Factors Correlate with Marginal Ulcer After Surgery for Obesity? Obes Surg. 2020;30(12):4821-7.

31. Taweerutchana V, Suwatthanarak T, Srisuworanan N, Rich NC. The First Robotic Bariatric Surgery Performed in Thailand – Surgical Techniques and Review of the Literature. Siriraj Med J. 2020;72:181-7.

32. Taweerutchana V, Nimmanwudipong T, Chinswangwatanakul V, Methasate A, Akaraviputh T, Swangsri J, et al. Outcome of Robotic Approach for Bariatric Surgery: Our Initial Experience in Siriraj Hospital. J Med Assoc Thai. 2020;103:93.

The Comparison between Frozen Elephant Trunk Technique and Conventional Total Arch Replacement, a Single-center Study

Amarit Phothikun, M.D.*,**,***, Dit Yoongtong, M.D.*, Weerachai Nawarawong, M.D.*,***, Surin Woragidpoonpol, M.D.*,***

*Cardiovascular and Thoracic Surgery Unit, Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, **Clinical Epidemiology and Clinical Statistic Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, ***Clinical Surgical Research Center, Chiang Mai University, Chiang Mai, Thailand.

ABSTRACT

Objective: The advantage of the frozen elephant trunk technique (FET) is treating the aortic pathology extending from the aortic arch to the descending aorta in a one-stage operation. This study aimed to determine the early and long-term outcomes of total arch replacement with the frozen elephant trunk technique compared to conventional total arch replacement (cTAR).

Materials and Methods: This study was a single-center, retrospective cohort study. Patients who underwent aortic arch replacement between January 2009 and December 2020 were enrolled and divided into two groups. 32 patients underwent the FET and 47 patients underwent cTAR. Outcomes and survival analysis were compared.

Results: The 5-year survival for FET and cTAR were 87.27% and 82.55% and the aortic-related mortality was not significantly different (HR 0.97, 95%CI 0.22-0.43). Aortic re-intervention was significantly lower in the FET group accounting for 3.57%, while there was 39.1% in the cTAR group. FET significantly reduced aortic re-intervention compared with cTAR (HR 0.09, 95%CI 0.01-0.81). There were no differences in the incidence of stroke between the two groups. However, FET patients had significantly increased risks of paraplegia by 21% when compared to cTAR (Risk difference +0.21, 95%CI 0.02-0.40).

Conclusions: The FET technique had comparable early outcomes in terms of mortality, renal function, postoperative bleeding, and recurrent laryngeal nerve injury. Even though FET had a significant risk of postoperative paraplegia, FET reduced the aortic re-intervention rate without increasing aortic-related death.

Keywords: Aortic arch; Frozen elephant trunk technique; Conventional total arch replacement (Siriraj Med J 2022; 74: 778-786)

INTRODUCTION

One advantage of aortic arch replacement with frozen elephant trunk technique (FET) over conventional total arch replacement (cTAR) is that it allows treatment of the aortic pathology extending from the aortic arch to the descending aorta in a single operation.1,2 In some cTAR operations, the aortic pathology lies in the descending

aorta or there is residual disease present after the initial operation. Thus, requiring a possible second aortic intervention to manage the remaining aortic disease.3-6 Another advantage is that the distal anastomosis between the native aortic tissue and prosthetic graft can be achieved more proximally than in cTAR regardless of the location of the distal diseased aorta. In FET, the

Corresponding author: Amarit Phothikun E-mail: Armadillos176@gmail.com

Received 29 August 2022 Revised 19 September 2022 Accepted 27 September 2022 ORCID ID:http://orcid.org/0000-0002-0015-411X http://dx.doi.org/10.33192/Smj.2022.92

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

anastomosis can be completed within Ishimaru’s aortic zone 0 to zone 3.7,8 Therefore, this technique doesn’t require dissection of the para-aortic tissue toward the distal part of each zone of the aortic arch, resulting in a decrease in the circulatory arrest time and a decrease in the incidence of recurrent laryngeal nerve injury.9,10 Despite many advantages of using FET, the incidence

of spinal cord ischemia (SCI) or post-operative paraplegia should be considered. The incidence of SCI is significantly more frequent in a patient with longer stent coverage, prolonged circulatory arrest time, and postoperative hemodynamic instability.9

Therefore, this study aimed to determine the early and long-term outcomes of aortic arch replacement with FET compared with cTAR. Upon the hypothesis that FET is non-inferior to a conventional technique, the outcomes were also determined in aspects of aortic- related mortality and aortic re-intervention.

MATERIALS AND METHODS

Patients

A retrospective cohort study was conducted at Maharaj Hospital, Faculty of Medicine, Chiang Mai University, Thailand, and was approved by the Research Ethics Committee no.4 of Faculty of Medicine, Chiang Mai University. (SUR-2021-08696, Research ID: 8696) Patients 18 years old or older who underwent aortic arch replacement between January 2009 and December 2020 were enrolled in this study. The operation included both emergency and elective surgery. The etiology of aortic disease included acute and chronic aortic dissection, dissection variants, and aneurysms. There were no differences in operative techniques in all patients even at different emergency levels or with different aortic etiology. The other aortic arch operation (hemiarch replacement, partial arch replacement) was excluded from the study. Also, patients who underwent total arch replacement via thoracotomy were excluded from the study.

The 79 cases of aortic arch replacement included in this study were divided into two groups: patients who underwent aortic arch replacement with the FET technique, FET group (n=32, 43.2%); and patients who underwent total arch replacement using a conventional technique, cTAR group (n=47, 56.8%).

Operative technique and procedure

Conventional total arch replacement

The operation was performed via median sternotomy. Cardiopulmonary bypass was set up with arterial inflow via central, peripheral, or both-site cannulation.

Venous drainage was obtained from a two-stage venous cannula that was inserted via the right atrial appendage. Cardiopulmonary bypass was run via a roller pump with the non-pulsatile flow. Myocardial protection was performed by selective, antegrade, and retrograde perfusion with cold Bretschneider’s solution (Custodiol® Essential Pharmaceuticals, LLC). Deep hypothermia (20-24°C) concurrent with selective antegrade cerebral perfusion was used as a neuroprotective strategy during circulatory arrest with near-infrared spectroscopy (NIRS) monitoring.

All specific details of the surgical technique are defined as a total arch replacement. The distal anastomosis was performed with complete transection of the proximal descending aorta (Ishimaru’s zone 3).7 Then the distal part of the commercial or self-made quadrifurcated graft was anastomosed to the descending aorta with a 3-0 polypropylene running suture. This was followed by anastomosis of the left subclavian artery, left common carotid artery, and a brachiocephalic branch with 5-0 polypropylene. In addition, a proximal anastomosis was connected to the residual good pathological ascending aorta with 3-0 polypropylene running sutures.

Frozen elephant trunk technique

The initial approach and cardio-pulmonary bypass technique were similar to cTAR. The stent graft devices used for FET included the commercial hybrid stent graft (E-vita open plus (Jotec® Inc., Germany), Thoraflex™ hybrid (Vascutek Terumo, Scotland, UK)) or non- commercial stent graft. In non-commercial devices, the stent graft (Relay® plus NBS (Vascutek Terumo, Scotland, UK), Valiant™ Captivia (Medtronic, Minnesota, USA), Zenith TX2® or Zenith Alpha™ (Cook® medical, Indiana, USA) was deployed either in an antegrade or retrograde fashion. The distal anastomosis was from Ishimaru’s aortic arch zone 0 to zone 3 and running continuous sutures with 3-0 polypropylene between the prosthetic graft and native aortic tissue with a stent graft inside. The aortic arch branches were debranched and reimplanted proximally to the distal anastomosis arch zones or sequence anastomosed to quadrifurcated grafts, similar to conventional total arch replacement.

Concomitant procedures

Concomitant procedures included aortic valve replacement in 14 patients, aortic root surgery in 16 patients, and coronary artery bypass grafting in 12 patients.

Spinal drainage and post-operative management

Spinal fluid drainage was selectively used in patients

that underwent FET and needed long stent coverage in the descending aorta beyond the T9 vertebra level or when the total stent graft length was longer than 200 mm. Cerebrospinal fluid (CSF) drainage was initiated when the CSF pressure was more than 10 mmHg. The spinal fluid drainage catheter was removed postoperatively on day 3 after confirmation of no existing neurological deficit. Target postoperative mean arterial pressure was 80 to 100 mmHg. If the patient developed paraplegia and spinal cord ischemia was diagnosed, spinal fluid drainage was initiated in patients without prior placement and the target means arterial pressure was raised above 100 mmHg. Intravenous corticosteroids and mannitol were used as adjunct treatments for spinal cord ischemia.

Follow-up

In the follow-up periods, hypertension and dyslipidemia were controlled by medical treatment. The first-line drug was beta-blockers and statins. Patients were also advised to quit smoking. Computed tomography angiography (CTA) of the aorta was the first choice for both techniques.

Definition

Mortality was defined as aortic-related death after the operation. Aortic re-intervention was defined as any re-operation for aortic surgery (including endovascular or/and open aortic surgery) after the first operation. Stroke was defined if there was any brain lesion identified in the brain CT corresponding to the symptoms. Paraplegia was defined as a new impairment in the neurologic function of the lower extremities which occurred after the operation. Acute kidney injury was defined if the postoperative creatinine level increased > 0.5 mg/dL compared to the pre-operative level or a new post- operative renal replacement therapy. The recurrent laryngeal nerve injury was defined as a post-operative vocal cord paralysis resulting in hoarseness, aspiration, and voice change.

Statistical analysis

Statistical analyses were performed using STATA software, version 16.1. The sample size was calculated by test-comparing two independent means based on studies in which the outcomes were similar to this study.9

Continuous data were analyzed by T-test analysis for normal distribution and Ranksum test for non-normal distribution. Categorical data were analyzed by Fisher’s exact test. A propensity score for adjustment was calculated using the following parameters: age, sex, hypertension, current smoker, aortic etiology, emergency surgery, CSF drainage, and lowest body temp. The differences in

propensity score between the two groups were shown in Table 1.

Aortic-related death and freedom from aortic re- intervention were calculated using the Kaplan–Meier method. Differences in these rates between both groups were analyzed using the log-rank test. Independent survival and aortic re-operation predictors were identified using multivariable Cox regression analysis and adjusted with propensity scores. Binary risk regression analysis was used to identify the post-op adverse outcome between the two study groups. Logistic regression analysis was used to identify the independent risk factors.

In all statistical tests, differences between the groups were considered significant at p<0.05.

RESULTS

Patient demographics

In Table 1, the comparison revealed the patients in the FET group were older than the cTAR group. However, the overall underlying diseases in both groups were comparable. Most of the aortic pathologies in cTAR were acute and chronic aortic dissection. In the FET group, aortic aneurysms represented most of the aortic pathologies. In concomitant procedures, an aortic root procedure was performed more frequently in the cTAR group.

The operative data showed no differences between the two groups’ total operation time, cardiopulmonary bypass time, aortic cross-clamp time, and lower body circulatory arrest time. The mean total length of the stent graft in FET was 179.4±38.9 millimeters.

Aortic-related mortality

The mortality was lower in the FET group accounting for 4 cases (12.5%), while there were 9 cases (19.2%) in the cTAR group. The 5-year survival for FET and cTAR was 87.27% and 82.55%. The Kaplan-Meier curves and hazard ratio (HR) showed no significant difference between the two groups (Fig 1).

Aortic re-intervention

Aortic re-intervention was lower in the FET group accounting for 3.57%, while there was 39.1% in the cTAR group. 5-year re-intervention free for FET and cTAR were 93.75% and 55.61%. The median re-intervention time for cTAR was 5.42 years. The Kaplan-Meier curves and HR showed that FET had significantly reduced aortic re-intervention when compared to cTAR (Fig 2).

In the cTAR group, 9 patients underwent thoracic endovascular aortic repair (TEVAR) for re-intervention due to an aneurysmal change of the distal aorta and the

TABLE 1. Baseline characteristics and operative data.

Abbreviations: FET, Frozen elephant trunk technique; cTAR, Conventional total arch replacement; CAD, Coronary artery disease; CVA, Cerebrovascular accident; LVEF, left ventricular ejection fraction; eGFR, estimated glomerular filtration rate; IMH, Intra-mural hematoma; PAU, Penetrating aortic ulcer; CABG, Coronary artery bypass grafting; CPB, Cardio-pulmonary bypass; CSF, Cerebrospinal fluid.

*A propensity score was calculated by age, sex, hypertension, current smoker, aortic etiology, emergency surgery, CSF drainage, and lowest body temp.

Statistically significant at p<0.05

FET, Frozen elephant trunk technique; cTAR, Conventional total arch replacement

P < 0.05: statistically significant different.

Fig 1. Kaplan-Meier for freedom from aortic- related death.

FET, Frozen elephant trunk technique; cTAR, Conventional total arch replacement

P < 0.05: statistically significant different.

Fig 2. Kaplan-Meier for freedom from aortic re-intervention.

remaining patients underwent open surgery. One patient in the FET group underwent re-intervention upon which TEVAR was performed due to type IB endoleak.

Postoperative outcomes

Postoperative outcomes are summarized in Table 2. The incidence of stroke was similar in both groups, but paraplegia was significantly higher in the FET group. FET patients had a significantly increased risk of paraplegia by 21% when compared to cTAR (Risk difference +0.21, p=0.029) (Table 3). Of all 5 paraplegic patients in the FET group, 3 cases were undergoing pre-operative spinal drainage. And 2 cases were undergoing spinal drainage after the patients had post-operative paraplegic symptoms. Only 1 patient was fully recovering from paraplegia

within 1 year after intensive re-habitation, and other patients demonstrated varying degrees of neurological improvement. The prognostic risk factors for postoperative paraplegia in the FET technique were explored and listed in Table 4. Furthermore, the incidence rate of recurrent laryngeal nerve (RLN) injury was comparable between the two groups.

DISCUSSION

Open surgical repair has remained the gold standard for treating aortic arch pathology since 1975, following the publication of the case series by Griepp and colleagues.11,12 The classic elephant trunk (ET) basic principle provides a length of tubing into the descending aorta to facilitate further distal aortic procedures. ET also facilitates and

TABLE 2. Post-operative outcomes.

Abbreviations: FET, Frozen elephant trunk technique; cTAR, Conventional total arch replacement; AKI, Acute kidney injury. Statistically significant at p<0.05

TABLE 3. Binomial (Risk) regression adjusted with propensity score for the adverse outcome of Frozen elephant trunk technique versus total arch replacement.

Abbreviations: RD; Risk difference, RR; Risk ratio, Re-op, Re-operation; AKI, Acute kidney injury; RRT, Renal replacement therapy; RLN, Recurrent laryngeal nerve.

Statistically significant at p<0.05

TABLE 4. Prognostic risk factor of paraplegia in frozen elephant trunk technique by logistic regression.

Abbreviations: OR; Odd ratio, LVEF; left ventricular ejection fraction, pre-op; Pre-operative.

*Multivariable was calculated in an exploratory model based on the risk factor of paraplegia including age, sex, type of emergency, aortic disease etiology, pre-operative spinal drainage, operative time, aortic clamp time, and length of the stent.

Statistically significant at p < 0.05

shortens clamping time during the second opening of the thoracoabdominal aortic surgery.2,3 The FET technique was developed from ET by using a stent graft to replace the tubing graft in descending aorta.13 In acute type A aortic dissection, FET is recommended for treating the entry tear in the distal arch or the proximal part of the descending aorta.4 In acute and chronic type B aortic dissection when the endovascular repair is in the presence of an inadequate proximal landing zone, FET is the preferred procedure.3,4

In this study, the results showed that operative- related mortality was comparable between the FET and cTAR. Similar to Hirano, et al.9 studied FET and cTAR and found that there was no difference in operative mortality between the two techniques (FET 5.3%, cTAR 2.6%, p=0.500). A meta-analysis by Preventza et al.14 focused on the mortality rate in FET procedures in which overall mortality was 8.8%. Kremer, et al.15 found that FET operative mortality was 13.2%, which was close to

this study’s aortic-related mortality result.

The FET was developed to decrease the incidence of re-operation, but FET still had occurrences of aortic reintervention. Ius F, et al.16 found that at 1-, 5- and 10- year freedom from distal aortic re-operation were 81 ± 4, 67 ± 5, and 43 ± 13%, respectively for the FET procedure. Nonetheless, in this study, the aortic re-intervention rate was significantly lower in the FET group compared to the cTAR group. The difference in the pathology of aortic disease is also the factor in the difference in re- intervention. The patients who had aortic dissection had a high incidence of aortic reintervention.4,13 Ius F, et al.16 also found that chronic aortic dissection was identified as an independent risk factor for distal aortic operation (odds ratio (OR) = 3.8; 95% CI 1.5-9.3; p = 0.004). In this study, the cTAR might had a higher re-intervention rate because it had a higher incidence of aortic dissection.

Additionally, there was no significant difference in the incidence of stroke, acute kidney injury, and

re-operation due to postoperative bleeding. The meta- analysis by Preventza and colleagues14 reported a 7.6% stroke rate, similar to another meta-analysis, which found no difference between FET and ET in the stroke (6.5% vs. 9.7%).

Even though there was no statistically significant difference, the result showed the incidence of RLN injury was low in the FET group (FET 0%, cTAR 6.5%). The most frequent distal aortic anastomosis site in this study was Ishimaru’s zone 3 in cTAR and Ishimaru’s zone 1 in FET. The difference in anastomosis site location may be the reason why the incidence of RLN injury was higher in the cTAR group. Similar to the previous study results by Hirano et al showed that recurrent nerve injury was low in the FET group (9.2%) compared with the cTAR group (25.6%).9

With an average stent length of 179.4 millimeters for FET in this study, FET patients had a significantly increased risk of paraplegia by 21% when compared to those who underwent cTAR. A meta-analysis study by Preventza, et al14 showed that the overall rate of spinal cord ischemia was 7.6% with 95% CI 2.9% to 12.3%. They found that when the spinal cord coverage beyond T8 or stent length was more than 150 millimeters, patients had a higher incidence of spinal cord ischemia when compared to those with a stent length of 100 millimeters (11.6% vs 2.5%). Furthermore, Hirano et al9 also found that chronic dissection or spinal drainage had high OR for paraplegia.

Several limitations in this study warrant mentioning. First, this study was a retrospective cohort study and there was heterogeneity in patient characteristics such as aorta pathology differences. However, statistical methods were used to correct this confounding factor and unequal baselines were adjusted to be properly statistically compared. In addition, the most frequent sites of distal aortic anastomosis in the FET group were in Ishimaru’s zone 3. However, over the last two years, as the FET operative strategy evolved, a more simplified distal aortic anastomosis was performed at zone 2 or more proximally. Therefore, the outcomes of the FET group may differ from the initiation of the study to the present time.

CONCLUSION

The FET technique had comparable early outcomes in terms of mortality, renal function, postoperative bleeding, and recurrent laryngeal nerve injury. However, the incidence of postoperative paraplegia increased. The FET technique had favorable outcomes that reduced the aortic re-intervention rate without increasing aortic-

related death. Therefore, treatment methods and strategies should be carefully selected according to the patient’s risk factors.

ACKNOWLEDGEMENTS

We thank the staff of Chiang Mai university English language team (CELT) for language editing assistance.

Funding: This research did not receive any specific grant from funding agencies or the commercial sector.

Conflict of interest: All authors have no conflicts of interest to declare.

REFERENCES

1. Cekmecelioglu D, Coselli JS. Aortic arch repair with frozen elephant trunk versus conventional elephant trunk. Ann Cardiothorac Surg. 2020;9(3):223-5.

2. Czerny M, Schmidli J, Adler S, van den Berg JC, Bertoglio L, Carrel T, et al. Current options and recommendations for the treatment of thoracic aortic pathologies involving the aortic arch: an expert consensus document of the European Association for Cardio-Thoracic surgery (EACTS) and the European Society for Vascular Surgery (ESVS). Eur J Cardiothorac Surg. 2019; 55(1):133-62.

3. Di Bartolomeo R, Murana G, Di Marco L, Pantaleo A, Alfonsi J, Leone A, et al. Frozen versus conventional elephant trunk technique: application in clinical practice. Eur J Cardiothorac Surg. 2017;51(Suppl 1):i20-i8.

4. Uchida N, Shibamura H, Katayama A, Shimada N, Sutoh M, Ishihara H. Operative strategy for acute type a aortic dissection: ascending aortic or hemiarch versus total arch replacement with frozen elephant trunk. Ann Thorac Surg. 2009;87(3):773-7.

5. Nienaber CA, Kische S, Rousseau H, Eggebrecht H, Rehders TC, Kundt G, et al. Endovascular repair of type B aortic dissection: long-term results of the randomized investigation of stent grafts in aortic dissection trial. Circ Cardiovasc Interv. 2013;6(4): 407-16.

6. Poon SS, Theologou T, Harrington D, Kuduvalli M, Oo A, Field M. Hemiarch versus total aortic arch replacement in acute type A dissection: asystematicreviewandmeta-analysis. Ann Cardiothorac Surg. 2016;5(3):156-73.

7. Erbel R, Aboyans V, Boileau C, Bossone E, Bartolomeo RD, Eggebrecht H, et al. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). Eur Heart J. 2014;35(41):2873-926.

8. Tian DH, Ha H, Joshi Y, Yan TD. Long-term outcomes of the frozen elephant trunk procedure: a systematic review. Ann Cardiothorac Surg. 2020;9(3):144-51.

9. Hirano K, Tokui T, Nakamura B, Inoue R, Inagaki M, Hirano R, et al. Impact of the Frozen Elephant Trunk Technique on Total Aortic Arch Replacement. Ann Vasc Surg. 2020;65:206-16.

10. Shrestha M, Martens A, Kaufeld T, Beckmann E, Bertele S, Krueger H, et al. Single-centre experience with the frozen elephant

    
    

    trunk technique in 251 patients over 15 years. Eur J Cardiothorac Surg. 2017;52(5):858-66.

11. Griepp RB, Stinson EB, Hollingsworth JF, Buehler D. Prosthetic replacement of the aortic arch. J Thorac Cardiovasc Surg. 1975; 70(6):1051-63.

12. Al Kindi AH, Al Kimyani N, Alameddine T, Al Abri Q, Balan B, Al Sabti H. “Open” approach to aortic arch aneurysm repair. J Saudi Heart Assoc. 2014;26(3):152-61.

13. Rylski B, Beyersdorf F, Desai ND, Euringer W, Siepe M, Kari FA, et al. Distal aortic reintervention after surgery for acute DeBakey type I or II aortic dissection: open versus endovascular repair. Eur J Cardiothorac Surg. 2015;48(2):258-63.

14. Preventza O, Liao JL, Olive JK, Simpson K, Critsinelis AC, Price MD, et al. Neurologic complications after the frozen elephant trunk procedure: A meta-analysis of more than 3000 patients. J Thorac Cardiovasc Surg. 2020;160(1):20-33.e4.

15. Kremer J, Preisner F, Dib B, Tochtermann U, Ruhparwar A, Karck M, et al. Aortic arch replacement with frozen elephant trunk technique - a single-center study. J Cardiothorac Surg. 2019; 14(1):147.

16. Ius F, Fleissner F, Pichlmaier M, Karck M, Martens A, Haverich A, et al. Total aortic arch replacement with the frozen elephant trunk technique: 10-year follow-up single-centre experience. Eur J Cardiothorac Surg. 2013;44(5):949-57.

Occupational Post-exposure Prophylaxis after Blood and Body Fluids Exposure among Healthcare Workers in Siriraj Hospital

Narasak Changraksa, M.D.*, Ladda Pannapoch, B.N.S.**, Phatharajit Phatharodom, M.D., M.P.H.**, Peerawong Werarak, M.D.**, Winai Ratanasuwan, M.D., M.P.H.**, Oranich Navanukroh, M.D., MCR.**

*Department of Internal Medicine, **Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

ABSTRACT

Objective: The present study aimed to describe the characteristics of occupational exposure to bloodborne pathogens and occupational post-exposure prophylaxis (oPEP) in Siriraj Hospital.

Materials and Methods: A descriptive, retrospective cohort study was performed of healthcare workers (HCWs) who had experienced occupational injury in Siriraj Hospital in 2015. Data were extracted from the hospital database. Results: In total, 389 injury episodes were described; of which 293 (75.3%) involved female staff, and 112 (28.8%) involved nurses. The highest number of accidents (112, 28.8%) occurred in the operation room. Needlestick injury (210, 54%) was the most common injury.

Overall, 94 (24.1%) HCWs received oPEP; 67 (71.2%) events carried a risk of HIV acquisition, and in 27 (28.7%) cases, the patients decided to take oPEP. Common oPEP regimens were TDF/XTC/LPV/r (33, 35.1%) and TDF/ XTC/RPV (32, 34%). Nearly half of the HCWs who received an LPV/r-based oPEP regimen had gastrointestinal intolerance and switched to second-line regimens. Among those who received oPEP, 52 (77.6%) returned at 1 month and 26 (38.8%) returned at 3 months after exposure for a serology test. There was no seroconversion in this cohort. Conclusion: Occupational exposure to bloodborne pathogens is a common and increasing risk of infection among HCWs. oPEP with effective antiretroviral drugs within 72 hours after exposure is the main strategy for HIV prevention. The selection of an oPEP regimen with less toxic pills should be considered for efficacy, safety, and adherence. Interventions such as a tracking system or message reminders should be implemented to improve the follow-up rate among HCWs.

Keywords: Healthcare worker; Occupational post-exposure prophylaxis; antiretroviral drugs; HIV prevention (Siriraj Med J 2022; 74: 787-791)

INTRODUCTION

Healthcare workers (HCWs) are at risk of blood or body fluids exposure through sharp and needlestick injuries or mucocutaneous exposure during patient care or waste disposal. Many pathogens can be transmitted via blood or body fluids. The most important bloodborne pathogens in healthcare settings are human immunodeficiency

virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Exposure to blood or body fluids poses a risk of infection of these pathogens and psychological concerns after injury among HCWs.1,2 In Thailand, the annual incidence of occupational blood and body fluid exposure was estimated to be 10.0–51.5 events per 100 HCWs during the period 1991–1997.3-5

Corresponding author: Oranich Navanukroh E-mail: oranich.nav@mahidol.ac.th

Received 13 August 2022 Revised 28 September 2022 Accepted 3 October 2022 ORCID ID:http://orcid.org/0000-0002-7798-367X http://dx.doi.org/10.33192/Smj.2022.93

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

The uptake of antiretroviral drugs for occupational post-exposure prophylaxis (oPEP) not later than 72 hours after exposure has been shown to decrease the risk of HIV seroconversion since the early 2000s.6,7 Since early 2000s, Centers for Disease Control (CDC) and the World Health Organization(WHO) published oPEP guidelines for healthcare settings, and these guidelines have been updated regularly based on the availability of recommended antiretroviral regimens for oPEP and follow- up schedules.8,9 oPEP courses with highly effective, less toxic, combination pills and once daily dosing regimens are currently recommended worldwide to reduce risk of HIV acquisition after exposure to blood or body fluids.

Siriraj Hospital is a 2,300-bed university hospital in Bangkok, Thailand, that has more than 13,000 clinical staff and students. Despite training and implementing strategies to prevent HCWs from being exposed to bloodborne pathogens, occupational exposure to bloodborne pathogens are frequently reported among all levels of clinical staff and workers. This study aimed to describe the characteristics of the occupational exposure to blood or body fluids and post-exposure management in Siriraj Hospital.

MATERIALS AND METHODS

Data collection

A retrospective study was conducted among HCWs who experienced occupational exposure to blood and body fluids in Siriraj Hospital between January 1 and December 31, 2015. We excluded accidents that occurred outside Siriraj Hospital. The informed consent process was waived due to this being a retrospective study.

Data were abstracted from medical records and the occupational health registry. De-identified data, including age, sex, type of HCW; hospital unit; work shift; injury details; serologic status of HIV, HBV, and HCV of the exposed persons and sources; antiretroviral regimens for oPEP; adverse effects; and follow-up visit were recorded. High risk exposure is defined as a sharp, needlestick, non-intact skin or mucosal exposure to blood or body fluid of an HIV seropositive or suspected HIV source. oPEP is eligible when an accident is defined as carrying a high risk of HIV acquisition, the injured person presents no later than 72 hours and has negative HIV serostatus at baseline.

Statistical analysis

Descriptive statistics were presented as a number and percentage for categorical variables and as the mean with standard deviation for continuous variables. All the statistical analyses were performed using the SPSS Statistics program, version 18.0.

IRB / IEC Certification: The study was conducted under the Siriraj Institutional Review Board’s (SIRB) approval (Si 363/2016).

RESULTS

A total of 389 episodes were reported over a 1-year period. The incidence of occupational injury was 7.5 episodes per week. The majority of the exposed HCWs were female (293, 75.3%). Nurses (112, 28.8%) were the most frequently exposed, followed by residents and fellows (101, 26%). The highest incidence occurred in the operation room (112, 28.8%). Needlestick injury (210, 54%) and exposure to blood (328, 84.3%) were the most common type of injury and exposed substance, respectively. The characteristics of the occupational exposures are shown in Table 1.

HCW serologic status

All the HCWs were seronegative for HIV at baseline. Nine (2.3%) HCWs were seropositive for HBsAg. A total of 342 (87.9%) HCWs were considered immune to HBV (anti-HBs ≥ 10 mIU/mL). One HCW had HCV infection.

Source serologic status

The sources known to be positive for HIV, HBV, and HCV numbered 39 (10%), 27 (6.9%), and 12 (3.1%), respectively. Sources with unknown HIV, HBV, and HCV status were 40 (10.3%), 59 (15.2%), and 57 (14.7%),

respectively.

Post-exposure management

Of the 389 episodes reported during the study period, 94 (24.2%) HCWs initiated oPEP; 24 (25.5%) discontinued oPEP earlier because of confirmation of an HIV-negative source, 3 (3.2%) were lost to follow-up before the completion of oPEP.

Of the 67 HCWs who received a 28-day course; 18 (25.7%) switched to second-line oPEP due to drug toxicities or exposure to drug-resistant HIV (15 gastrointestinal adverse effects; 1 hepatitis; 1 drug allergy; 1 exposed to an HIV-resistant source). Table 2 shows the oPEP regimens prescribed in this cohort. Fifty-two (77.6%) HCWs attended follow-up at 1 month and 26 (38.8%) attended follow-up at 3 months after exposure. There was no seroconversion in this study.

DISCUSSION

Exposure to blood or body fluids is a common injury among healthcare workers and increases the risk of HIV, HBV, and HCV acquisition. Appropriate wound care, prompt risk identification, and the administration

TABLE 1. Demographic characteristics of 389 episodes of occupational exposure to bloodborne pathogens.

TABLE 2. Initial prescribed oPEP regimens and switching oPEP regimens.

Antiretroviral regimens for oPEP Number (%)

First oPEP regimens

Abbreviations: TDF, tenofovir disoproxil fumarate; XTC, lamivudine or emtricitabine; LPV/r, lopinavir/ritonavir; RPV, rilpivirine; FTC, emtricitabine; RAL, raltegravir; ATV/r, atazanavir/ritonavir; AZT, zidovudine; DRV/r, darunavir/ritonavir; 3TC, lamivudine

of post-exposure prophylaxis with an effective oPEP regimen in a timely manner are important measures to mitigate the risk of acquiring an infection.

The present study demonstrated a similar incidence of occupational exposure to blood or body fluids compared with other reported studies in Thailand.3-5,10 Nurses and in-training physicians are at an increased risk of exposure due to their more frequent involvement in direct patient care and performing medical procedures. Medical students were the third most common personnel type at risk of exposure, possibly duetothempracticingmedicalprocedures while still having less experience. Needlestick injuries were more common than mucocutaneous exposure, which was similar to reported in other studies.3,4,10-13 Several studies reported needle stick injuries occurred commonly among medical students during perineorrhaphy and reported time pressure and lack of skills as perceived causes.14,15

Recommended antiretroviral drugs for oPEP have changed over time in order to improve the efficacy to drug-resistant HIV, toxicities, and adherence. In early 2000s, overall adverse effects were reported between 64-76%.16-18 The common prescribed drugs at that time were AZT, ritonavir-boosted nelfinavir or indinavir or lopinavir, which are not used as first-line drugs for HIV treatment and prevention due to their toxicities and pill burden. The overall adverse effects led to oPEP discontinuation in approximately 34% of cases in a study in Thailand19, confirming that oPEP regimen selection with less toxic pills should be considered to improve tolerability and adherence. Currently, integrase inhibitor- based, rilpivirine-based, and DRV/r-based in combination with with tenofovir disoproxil fumarate or tenofovir alafenamide (TXF)/lamivudine or emtricitabine (XTC) are recommended for oPEP.20,21 These regimens are potent, less adverse effects, less drug-drug interactions, and convenient compared to previous regimens and hence adherence improves.

Our study reported a poor follow-up rate (38.8%) at 3 months after exposure among those who were eligible for 28-day oPEP. Compared to another study from Thailand, the follow-up rates were higher than in our study, 89% at 6 weeks and 77% at 3 months, respectively.10 However, we did not explore the reasons for the loss to follow-up. We did not have a tracking system or send reminders via a text message or phone call to HCWs. Thus, strategies to improve adherence, such as a tracking system or reminders, should be implemented as part of an occupational injury care system.

We also found that some HCWs in this study did not have immunity to HBV. In our hospital, pre-placement evaluation of HBV vaccine status and a quantitative anti-HBs antibody test are required for clinical staff. Nevertheless, some HCWs are employed as general workers but they have to work with medical instruments during disposal or waste management, which pose a risk of blood or body fluid exposure. The local pre-placement evaluation policy for HBV vaccine and immune status to HBV should be customized with details of the job description, not only the position.

This study has several limitations to note. First, some data that might affect the incidence, such as work experience and personal protective equipment use, were not recorded. Second, the incidence was probably underreported because we did not collect data from the central occurrence report system. Those who were exposed to a known negative source may not have visited the occupational clinic for a proper risk evaluation.

In conclusion, occupational exposure to blood and

body fluids is common and poses a risk of acquiring bloodborne pathogens among HCWs. Antiretroviral regimens with highly effective, less toxicity, combination pills that are applied in a timely manner can mitigate the risk of HIV infection and improve adherence to oPEP. Despite training and policy implementation on safety procedures to prevent injury, occupational exposure to bloodborne pathogens occurs frequently. A regular training program for common medical procedures and safety practices should be implemented for all HCWs that may be exposed to blood or body fluids. In addition, interventions such as a tracking system or message reminders should be further studied and implemented to improve the follow-up rate among HCWs.

Conflict of interest: The authors declares no conflict of interest.

REFERENCES

1. Zhang MX, Yu Y. A study of the psychological impact of sharps injuries on health care workers in China. Am J Infect Control. 2013;41(2):186-7.

2. Lee JM, Botteman MF, Xanthakos N, Nicklasson L. Needlestick injuries in the United States. Epidemiologic, economic, and quality of life issues. AAOHN J. 2005;53(3):117-33.

3. Danchaivijitr S, Kachintorn K, Sangkard K. Needlesticks and cuts with sharp objects in Siriraj Hospital 1992. J Med Assoc Thai. 1995;78 Suppl 2:S108-11.

4. Pungpapong S, Phanuphak P, Pungpapong K, Ruxrungtham

   K. The risk of occupational HIV exposure among Thai healthcare workers. Southeast Asian J Trop Med Public Health. 1999;30(3): 496-503.

5. Hiransuthikul N, Tanthitippong A, Jiamjarasrangsi W. Occupational exposures among nurses and housekeeping personnel in King Chulalongkorn Memorial Hospital. J Med Assoc Thai. 2006;89 Suppl 3:S140-9.

6. Wnuk AM. Occupational exposure to HIV infection in health care workers. Med Sci Monit. 2003;9(5):CR197-200.

7. Cardo DM, Culver DH, Ciesielski CA, Srivastava PU, Marcus R, Abiteboul D, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. N Engl J Med. 1997;337(21):1485-90.

8. Center for Disease Control. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR Recomm Rep. 2001;50(RR-11):1-52.

9. Occupational and non-occupational post-exposure prophylaxis for HIV infection (HIV-PEP): Joint ILO/WHO Technical

   Meeting for the Development of Policy and Guidelines: summary report2005. Available from: https://www.ilo.org/wcmsp5/groups/ public/---ed_protect/---protrav/--ilo_aids/documents/publication/ wcms_116563.pdf.

10. Chaiwarith R, Ngamsrikam T, Fupinwong S, Sirisanthana T. Occupational exposure to blood and body fluids among healthcare workers in a teaching hospital: an experience from northern Thailand. Jpn J Infect Dis. 2013;66(2):121-5.

11. Kiertiburanakul S, Wannaying B, Tonsuttakul S, Kehachindawat P, Apivanich S, Somsakul S, et al. Use of HIV Postexposure Prophylaxis in healthcare workers after occupational exposure: a Thai university hospital setting. J Med Assoc Thai. 2006;89(7): 974-8.

12. Wilburn SQ, Eijkemans G. Preventing needlestick injuries among healthcare workers: a WHO-ICN collaboration. Int J Occup Environ Health. 2004;10(4):451-6.

13. Frijstein G, Hortensius J, Zaaijer HL. Needlestick injuries and infectious patients in a major academic medical centre from 2003 to 2010. Neth J Med. 2011;69(10):465-8.

14. Liyanage IK, Caldera T, Rwma R, Liyange CK, De Silva P, Karunathilake IM. Sharps injuries among medical students in the Faculty of Medicine, Colombo, Sri Lanka. Int J Occup Med Environ Health. 2012;25(3):275-80.

15. Panichyawat N LT. The incidence of needlestick injuries during perineorrhaphy and attitudes toward occurrence reports among medical students. Siriraj Medical Journal. 2016;68:209-17.

16. Tetteh RA, Nartey ET, Lartey M, Mantel-Teeuwisse AK, Leufkens HG, Nortey PA, et al. Adverse events and adherence to HIV post-exposure prophylaxis: a cohort study at the Korle-Bu Teaching Hospital in Accra, Ghana. BMC Public Health. 2015;15:573.

17. Lee LM, Henderson DK. Tolerability of postexposure antiretroviral prophylaxis for occupational exposures to HIV. Drug Saf. 2001; 24(8):587-97.

18. Wang SA, Panlilio AL, Doi PA, White AD, Stek M, Jr., Saah A. Experience of healthcare workers taking postexposure prophylaxis after occupational HIV exposures: findings of the HIV Postexposure Prophylaxis Registry. Infect Control Hosp Epidemiol. 2000; 21(12):780-5.

19. Hiransuthikul N, Hiransuthikul P, Kanasuk Y. Human immunodeficiency virus postexposure prophylaxis for occupational exposure in a medical school hospital in Thailand. J Hosp Infect. 2007;67(4):344-9.

20. Ruxrungtham K CK, Chetchotisakd P, Chariyalertsak S, Kiertburanakul S, Putacharoen O, et al. Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2021/2022. Nonthaburi: Division of AIDS and STIs, Department of Disease Control; 2022.

21. Cresswell F, Asanati K, Bhagani S, Boffito M, Delpech V, Ellis J, et al. UK guideline for the use of HIV post-exposure prophylaxis 2021. HIV Med. 2022;23(5):494-545.

Untargeted Metabolomics Analysis using LC-MS- QTOF for Metabolite Profile Comparison between Patients with Myofascial Pain of Upper Trapezius Muscle versus Controls

Manmas Vannabhum, B.ATM., M.Sc.*, Kamontip Harnphadungkit, M.D.**, Pravit Akarasereenont, M.D., Ph.D.***, ****, Sompol Tapechum, M.D., Ph.D.*

*Department of Physiology, **Department of Rehabilitation Medicine,***Center of Applied Thai Traditional Medicine, ****Siriraj Metabolomics and Phenomics Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

ABSTRACT

Objective: This study aims to identify different biomarkers of Myofascial pain syndrome (MPS) using untargeted metabolomics screening.

Materials and Methods: In a case-control study, serum samples from MPS patients (n = 19) and healthy controls (n = 10) were analyzed using reverse-phase liquid chromatography and mass spectrometry quadrupole time-of

-flight (MS-QTOF). The resulted raw data was processed with Progenesis QI data analysis software. The HMBD database was used to identify the metabolites based on their fold change (>1.2), variable importance plot (>1) with P < 0.05. MetaboAnalyst 5.0 was used to generate metabolic network analysis for all identified metabolites.

Results: The MPS group reported significantly higher pain on visual analog scale when compared with control while most of the other routine blood chemical profiles were not different. Twenty-seven metabolites were analyzed and identified with untargeted metabolomics analysis which could distinguish MPS patients from healthy controls. Inosine and chenodeoxycholic acid were abundant in the MPS group, whereas the others were low. Metabolites were divided into three categories: lipids, nucleotides, and organic compounds. Possible MPS metabolites included lysoSM (sphingomyelin), lysoPC (lysophosphatidylcholine), lysoPE (lysophosphatidylethanolamine), triglyceride, and inosine.

Conclusion: These metabolite profiles, including glycerophospholipids mechanism and purine metabolism, indicate that the inflammatory process might be related to the mechanisms of MPS. A larger sample size, a different trigger point location, and modifications in therapy afterward should all be further explored.

Keywords: Myofascial pain; trigger point; metabolomics; untargeted metabolomics; mass spectrometry (Siriraj Med J 2022; 74: 792-803)

INTRODUCTION

Myofascial pain syndrome (MPS) is a type of musculoskeletal discomfort that is a widespread health issue and a cause of employee sick leave.1 The prevalence of MPS is approximately 85% of the population. A clinical

characteristic of MPS is the appearance of myofascial trigger points (TrPs). Trigger point is a hyperirritable muscular region accompanied by a sensitively detectable nodule in a taut band. The diagnostic criteria for identifying TrPs

Corresponding author: Sompol Tapechum E-mail: sompol.tap@mahidol.ac.th

Received 30 May 2022 Revised 29 September 2022 Accepted 11 October 2022 ORCID ID:http://orcid.org/0000-0003-3808-4935 http://dx.doi.org/10.33192/Smj.2022.94

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

are a taut band, a hypersensitive area, and referred pain.2 Trigger point also can cause spontaneous pain, referred pain, fatigue, reduced range of motion, and autonomic dysfunction, such as sweating or piloerection.3,4 Trigger point can form in a variety of locations throughout the body. The neck and shoulder are the most prevalent sites for TrPs. In a previous study, TrPs of the upper trapezius muscles were observed in more than 80% of chronic nonspecific neck pain patients.5 Trigger point could be triggered by overuse, muscle trauma, or psychological stress. The most typical causes include poor ergonomics, improper postural alignment, and continuous repetition of daily activities.6 However, the initiation of TrPs remains unclear.

The mechanism of MPS and the pathogenesis of TrPs are not completely understood. In the TrP region, hypercontracture of the sarcomere was discovered.6,7 Ultrasound techniques can also be used to determine anatomical and physiological changes relating to TrPs. In the non-TrP region, the tissue echo strength is the same as the surrounding structures or tissues. The TrP region shows solid tissue and a reduction in blood flow. It revealed a localized stiffness region of TrPs.8 According to the integrated theory, it originated with excessive acetylcholine release from the motor endplate.9 Increased acetylcholine release results in metabolic stress and an energy crisis. A deficit of energy causes longer sarcomeres to shorten, reducing blood and oxygen supply.6 In addition, local hypoxia produces physiological abnormalities and cell stress; myokines, inflammatory cytokines, and neurotransmitters, such as bradykinin, substance P, tumor necrosis factor α, interleukin 1β (IL-1β), interleukin 6, serotonin, and norepinephrine, are produced.10-12 The release of biochemical substances produces pain-activating nociceptors and alters autonomic regulation. This change produces tissue sensitivity and contributes to the persistence of the TrPs and MPS.6

Metabolomics is an omics analytical technique that identifies thousands of low-molecular-weight compounds using high-throughput technology.13 It can be used for detecting metabolites representing human phenotypes in normal and pathological states and also suggesting the pathophysiological processes. It is widely used to identify biomarkers in biological samples that are relevant to disease biomarkers, pharmaceutical development, nutrition, and physiological process. Biomarkers illustrate why disease risk factors and etiologies have changed.14 The mapping of biomarkers in the metabolic pathway enables diseases to be addressed.15 Previous studies have found systemic changes in the metabolite profiles of patients suffering from nonspecific neck-shoulder pain

and chronic widespread pain. Several metabolite changes suggest the relation with lipid metabolism and energy consumption.16 Because there is no solid evidence of MPS pathogenesis, untargeted metabolomics research was performed to discover different metabolites of MPS. The objectives of this study are to (1) investigate possible differences in metabolomics profiles between MPS patients and a control group, and (2) analyze the pathways associated with MPS patients. It could be used to explore alterations in a variety of biochemical pathways, as well as to understand further about pathophysiology and treatments.

MATERIALS AND METHODS

Subjects

Twenty-nine subjects aged between 18 and 65 years were recruited at Siriraj Hospital, Bangkok, Thailand (10 control subjects and 19 MPS patients). The MPS group was recruited based on the diagnosis with myofascial pain of the upper trapezius muscle.4 The followings criteria were considered for the MPS to be eligible for the study:

• Severity of pain greater than 40 on a visual analog scale for at least 3 months

• Presence of at least 1 TrP in the upper trapezius muscle identified by palpation that included palpable taut bands with local hypersensitivity and referral pain Patients with other musculoskeletal diseases, tumors, psychological problems, metabolic diseases, pregnancy or lactation, previous neck or shoulder pain therapies or medicine, history of alcohol abuse and smoking, and abnormal liver or renal function at the time of screening were all excluded from the study. Healthy control subjects were non-MPS with the same exclusion criteria as those

of the MPS group.

The study was approved by the Siriraj Institutional Review Board at Faculty of Medicine Siriraj Hospital, Mahidol University (Si259/2017).

Sample collection

Fasting blood samples were collected between 7 and 9 am to reduce variation in sample collection. Basal clinical laboratory profiles were assessed by central laboratory of the Siriraj Hospital. For metabolomics analysis, the blood was obtained in BD Vacutainer serum blood collection tubes (Becton Dickinson, Franklin Lakes, New Jersey) to initiate clotting. After centrifugation for 10 minutes at 4,500g at 4°C, the supernatant was collected, aliquoted, and kept at −80°C until analysis. The sample collection was performed in accordance with good clinical practice, which included ethical and safety considerations.

Sample preparation for metobolomics analysis

The MPS and healthy control samples were analyzed in random order. The protocol was modified from a previous study for metabolic profiling of serum using LCMS.17 Serum samples were retrieved from the –80°C freezer and allowed to thaw on ice. After that, 50 µL of 1 ng/µL mixed internal standard solution (l-phenylalanine [13CC8H11N1O2], caffeine [13CC7H10N4O2], cholic acid [D4C24H36O5]) was added to a 200 µL serum sample. Serum samples were extracted by adding 600 µL of methanol. The samples were continuously mixed at 4°C for 15 minutes at 2000 revolutions per minute using a Multitube vortexer (BenchMixer; Benchmark Scientific Inc, Sayreville, New Jersey) and then frozen for 1 hour at −80°C. The samples were then centrifuged for 15 minutes at 4°C at 15,800g. Then, the supernatant was collected and dried in a speed vac (CentriVap Mobile System Console, Labconco, USA) for 300 mins at 30°C. After completely dry, samples were store at -80°C for analysis.

Quality control samples were utilized in the study to examine technical stability and repeatability. For quality control, 29 serum samples were pooled and extracted using the same methods as the individual samples.

Liquid chromatography and mass spectrometry quadrupole time-of-flight analysis

On the day of analysis, dried samples were reconstituted with 100 µL of water and shaken at 2000 revolutions per minute for 10 minutes at 4°C. The samples were centrifuged for 10 minutes at 4°C at 15,800g. The supernatant was transferred to a total recovery vial (Waters Corp, Milford, Massachusetts). Extracted serum samples were maintained the temperature at 4°C during analysis.

Extracted serum samples were analyzed using ultraperformance liquid chromatography system (Waters Corp, Wilmslow, United Kingdom) coupled with Synapt G2-Si QTOF mass spectrometer (Quadrupole Time- of-Flight; Waters Corp). The ultraperformance liquid chromatography system was performed using an Acquity HSS T3 column with a 100-mm length 2.1-mm internal diameter and 1.8 microns in particle size. The protocol for LCMS-QTOF analysis was modified from a previous study.17 The temperatures in the column and sample manager were 40°C and 4°C, respectively. The gradient elution was mobile phases A1 and B1 at a flow rate of

0.4 mL/min. In the mobile phase, solvents A and B were 0.1% formic acid in water (vol/vol) and 0.1% formic acid in MeOH (vol/vol), respectively. The elution gradient was as follows: initial conditions at 100% A1; from 1 to

16 minutes, increased to 100% B1; from 16 to 20 minutes, maintained at 100% B1; from 20 to 22 minutes, increased to 100% A1; and from 22 to 24 minutes, maintained at 100% A1.

For mass spectrometer, the instrument was used in resolution mode with the MSe data acquisition function with electrospray ionization in positive and negative ion modes. The parent ion’s trap collision energy was 6 electron volts (eV), whereas the fragmentation’s ramp trap collision energy was 15 to 40 eV. The capillary voltage was set to 3 kV, whereas the sampling cone voltage was set to 40 V. The desolvation gas temperature was set at 500°C, with the source temperature set at 150°C. The desolvation gas flow rate was set at 1000 L/h, whereas the cone gas flow rate was set at 50 L/h.

Biomarker identification and pathway analysis

Progenesis QI data analysis software (Nonlinear Dynamics, Newcastle, United Kingdom) was used to import and process the raw data. A search of the Human Metabolomics Database, HMDB 5.0 (https://hmdb.ca) was used to identify compounds. MetaboAnalyst 5.0 (www.metaboanalyst.ca) was used to perform metabolic network analysis on all chemical identifications.

Progenesis QI data analysis software (Nonlinear Dynamics, Newcastle, UK) was used to import and process the raw data. All of the samples were aligned to ensure that retention duration, mass measurements, isotopic composition, and fragmentation were all correct. The experiment comprised a between-subject design with an unpaired T-test for the different groups (CON versus MPS). The following criteria were used to select compounds: p-value < 0.05, fold change between two groups >1.2. The significant metabolites were selected.

Multivariate Analysis (MVA) and Univariate Analysis were used to examine all chemical values in normalized compound abundances (UVA). The scale was Pareto for principal component analysis (PCA) and orthogonal partial least-square discriminant analysis (OPLS-DA). S-plots were used to filter metabolites biomarkers when p (1) and p (corr) (1) from the OPLS-DA model were >

±0.04. The variable importance plot (VIP) > 1 was chosen. After matched the significant metabolites with selection biomarkers from S-plot. The metabolites biomarkers were searched from the online Human Metabolomics Database (HMDB 5.0). The precursor tolerance and fragmentation tolerance were both set to 20 ppm, with a retention time of less than 0.1 minute. When the isotope similarity was greater than 70%, the identification was confirmed.

MetaboAnalyst 5.0 (www.metaboanalyst.ca) was used to perform metabolic network analysis on all chemical identifications. Significant pathways had a p-value less than 0.05 and impact more than 0.05.

Statistical analysis

The metabolite profile was assessed using Multivariate Analysis and Univariate Analysis, as previously described. All demographic and other parameters were evaluated using SPSS software (PASW version 18; IBM Corp, Chicago, Illinois). To test the normalization of data distribution, the Shapiro-Wilk test was performed. An unpaired t test or Chi-square was used to compute the differences between groups. P < 0.05 was considered statistically significant.