Siriraj Medical Journal

Cancer Immunotherapy: Challenges and Advancements in CAR T Cell Technology

Pa-thai Yenchitsomanus — Wed, 01 May 2024 00:00:00 +0700

Cancer, characterized by uncontrolled cell proliferation, poses a major global health threat, as evident in the 2022 World Health Organization-International Agency for Research on Cancer report, recording 20 million new cases and 9.7 million deaths worldwide. Thailand alone reported 183,000 new cases and 118,000 fatalities, underscoring the need for tailored prevention, early detection, and treatment strategies. Conventional therapies like surgery, radiation, and chemotherapy, while effective in early stages, face limitations in advanced cases, prompting the development of targeted therapies and immunotherapy, notably chimeric antigen receptor (CAR) T cell therapy. CAR T cell therapy employs genetic engineering to create receptors recognizing cancer-specific antigens. Despite successes in hematological malignancies, challenges such as toxicities, relapse, and high costs persist. Ongoing research, led by the Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), focuses on advancing fourth- and fifth-generation CAR T cell technologies. SiCORE-CIT's fourth-generation CAR T cells exhibit potent anti-tumor activity against various cancers, surpassing second-generation counterparts. Their innovative fifth-generation "Siriraj fifth-generation CAR T cells" secrete anti-PD-L1 scFv, showing potential for diverse cancer applications, highlighting the transformative impact of ongoing research. Successful applications of fifth-generation CAR T cells in B-cell leukemia, lymphoma, and multiple myeloma underscore their transformative potential. This emphasizes the critical role of continuous research in refining therapeutic approaches for both hematologic and solid malignancies. The ongoing exploration and development in this domain have the potential to revolutionize cancer treatment paradigms, significantly contributing to alleviating the global health burden associated with this complex disease.

The Role of Lactate-based Serum Tests for Prediction of 30-day Mortality in Hospitalized Cirrhotic Patients with Acute Decompensation: A Prospective Cohort Study

Nattaporn Kongphakdee, Phubordee Bongkotvirawan, Sith Siramolpiwat — Mon, 01 Apr 2024 00:00:00 +0700

Objective: Cirrhotic patients with acute decompensation are associated with high short-term mortality. The prognostic performance of venous lactate (VLAC) for mortality prediction in these patients has not been well established. This study aimed to evaluate the role of several lactate-based serum tests for prediction of 30-day mortality in these patients.

Materials and Methods: Cirrhotic patients with acute decompensation were prospectively enrolled. VLAC on admission and at 6, 12, and 24 hours were determined. Lactate clearance (LAC-Cl), MELD-lactate, and MELD-lactate clearance (MELD-ΔLA) at each timepoint were calculated and compared between 30-days survivors and non-survivors.

Results: 74 patients were included (age 69±13 years, 66.2% male, MELD 18.3±7). The main indications for admission were infection (67.6%) and gastrointestinal bleeding (18.9%). The 30-day mortality rate was 29.7%. Initial VLAC was significantly higher in non-survivors (9.7±8 vs. 3.61±1.79 mmol/L, P<0.001). In addition, VLAC at 6, 12, 24 hours, MELD-Lactate and MELD-ΔLA scores were significantly higher in non-survivors. Based on ROC analysis, the VLAC, MELD-Lactate, and MELD-ΔLA at 6 hours were reliable predictors of 30-day mortality (AUROC 0.79, 0.86, and 0.86, respectively). However, compared to MELD score (AUROC 0.81), no significant difference was found.

Conclusion: In hospitalized cirrhotic patient with acute decompensation, VLAC, MELD-Lactate and MELD-ΔLA at 6 hours are simple, and reliable predictors for 30-day mortality.

Urine Liver-Type Fatty Acid Binding Protein; Biomarker for Diagnosing Acute Kidney Injury and Predicting Mortality in Cirrhotic Patients

Mon, 01 Apr 2024 00:00:00 +0700

Objective: To determine impact of urine liver-type fatty acid binding protein (uL-FABP) and urine neutrophil gelatinase-associated lipocalin (uNGAL), which were biomarkers linked to acute kidney injury (AKI), in AKI diagnosis and prediction of 28-day mortality among hospitalized cirrhotic patients.

Materials and Methods: We prospectively enrolled hospitalized cirrhotic patients at a tertiary care university hospital between June 2018 and November 2019. The uL-FABP, uNGAL, and plasma NGAL (pNGAL) were collected within 48 hours of admission. Cutoff values of biomarkers for diagnosing AKI derived from receiver operating characteristic (ROC) curve. Logistic regression analysis was used to identify independent factors for 28-day mortality.

Results: We enrolled 109 cirrhotic patients in derivative cohort, 41.3% had AKI. Median uL-FABP, uNGAL, and pNGAL levels in AKI group were higher than non-AKI group: 8.1 vs. 2.8 ng/mL (p=0.002), 40.5 vs. 10.1 ng/mL (p<0.001), and 195.7 vs 81.4 ng/mL (p=0.001), respectively. Areas under the ROC curve of uL-FABP, uNGAL, and pNGAL for AKI diagnosis were 0.68, 0.73 and 0.68, respectively. Also, all biomarkers were significantly higher in mortality group. Multivariate analysis showed that the only independent predictor for 28-day mortality was uL-FABP ≥ 4.68 ng/mL (odd ratio 4.15, p=0.02).

Conclusion: UL-FABP, uNGAL, and pNGAL are associated with AKI in hospitalized cirrhotic patients. Moreover, uL-FABP ≥ 4.68 ng/mL was a significant independent predictor for 28-day mortality.

Validity and Reliability of the Thai version of the International Consultation on Incontinence Questionnaire – Female Lower Urinary Tract Symptoms Long Form (ICIQ-FLUTS LF) and Its Correlation with the IPSS

Parm Tohroonglert, Valeerat Swatesutipan — Wed, 01 May 2024 00:00:00 +0700

Objective: Incontinence Modular Questionnaire on Female Lower Urinary Tract Symptoms Long form (ICIQ-FLUTS LF) is a robust psychometric tool to assess the severity of lower urinary tract symptoms (LUTS) in women. A Thai language version of the ICIQ-FLUTS LF is available, but it had not been validated yet. This study aimed to validate the ICIQ-FLUTS LF questionnaire in Thai and to identify the correlation between the ICIQ-FLUTS LF and the IPSS.

Materials and Methods: We recruited 130 females, 50 with LUTS were recruited from patients visiting the Urology Clinic to assess the test with known group validity. They completed the ICIQ-FLUTS LF twice, two weeks apart, and the IPSS once. Meanwhile, 80 without LUTS (control group) were recruited from relatives of the patients to increase the consistency of the statistical analysis, completed the ICIQ-FLUTS LF. Then validity and reliability were determined using statistical analysis.

Results: Convergent validity showed a moderate correlation between ICIQ-FLUTS LF and IPSS for both storage and voiding symptoms, with Pearson’s correlation coefficient 0.49, 0.66; P<0.001, respectively. Construct validity, using the Wilcoxon signed-rank test, demonstrated statistically significant difference between the target group and the control group (P<0.001). The Thai version of the ICIQ-FLUTS LF showed good internal consistency, with Cronbach’s alpha coefficients 0.76-0.79 and Test–retest reliability strong, with weighted kappa values 0.63 to 0.90.

Conclusion: The Thai version of the ICIQ-FLUTS LF shows good validity and reliable measures of females with LUTS, and is simple to use. This questionnaire in the Thai version can be used in clinical practice and academic research.

Factors Predicting Psychological Well-being among Survivors of Breast Cancer in A Tertiary Care Hospital, Thailand

Wed, 01 May 2024 00:00:00 +0700

Objective: The primary aim of this study was to examine predicting the effect of stress, social support, self-efficacy, and resilience on psychological well-being in breast cancer survivors

Materials and Methods: This predictive analysis for the descriptive cross-sectional study was conducted by the theoretical underpinning of resilience and population consisted of eligible breast cancer survivors receiving care at an outpatient clinic within a tertiary hospital setting. The data collecting was proceeded through self-administered questionnaires in line with convenient sampling. The analytical approach encompassed descriptive statistics, Pearson’s correlation coefficient, and multiple linear regression.

Results: Emanating from the study included the recruitment of 123 participants, with stress, social support, and resilience collectively elucidating 43% of the variance in psychological well-being among breast cancer survivors. Notably, resilience emerged as the most influential predictor (β=.33), followed by stress (β=-.27) and social support (β=.26), all of which significantly contributed to the prediction of psychological well-being.

Conclusion: Resilience, stress, and social support were three predictors of psychological well-being among survivors of breast cancer in this study. Recommendations extend to the integration of strategies that foster resilience and social support, while concurrently mitigating stress levels through activities and programs aimed at augmenting the psychological well-being of breast cancer survivors in the future.