Indian Journal of Medical Research最新文献

Background & objectivesGender-affirming hormone therapy may alter body composition and muscle strength, which may impact participation in sports and other activities. These changes are important to decide whether transgender should have separate categories of competition. MethodsWe conducted this prospective study, to assess the body composition using bioelectrical impedance analysis muscle strength and serum irisin levels at baseline and at 12 months following gender affirming hormone therapy in transgender individuals. The comparisons were done in both cis mode and trans mode. ResultsA total of 32 transfemales and 22 transmales were included in the study. Among transwomen, there was an increase in total subcutaneous fat (9.2%) and visceral fat (11.3 %) (P<0.001 in both cis and trans mode comparison) and a decrease in muscle mass (7.7%) (P=0.033 and P<0.001 in cis and trans mode, respectively) and muscle strength at all sites (P<0.001). Among transmen, there was a decrease in total subcutaneous fat (5.9%) (P<0.001 for both cis and trans mode comparison) and an increase in muscle mass (7.2 %) (P<0.001 for trans mode only) and muscle strength except shoulder abduction on right side (P<0.001). No significant changes were observed in irisin levels following hormonal therapy. Interpretation & conclusionsGender affirming hormonal therapy leads to body fat redistribution after twelve months of hormone therapy with significant alterations in muscle mass and strength among both transmen and transwomen. Irisin, an adipomyokine produced through muscle contraction, did not correlate with muscle mass or fat mass on follow up.

Background & objectives Dialysis is a therapeutic intervention where it is essential to consider patients' quality of life (QOL) as a key aspect of care. This study aims to assess the QOL of patients and identify factors affecting QOL in patients undergoing dialysis. Methods A cross-sectional analytical study was conducted among 140 participants undergoing dialysis at a tertiary care hospital in South India. Data on socio-demographic characteristics, history of co-morbid conditions, and details regarding the duration and type of dialysis were collected. QOL was assessed using the European Quality of Life assessment instrument, the EuroQOL 5-Dimensional 5-Level (EQ-5D-5L) questionnaire. Results The mean age of the participants was 41 yr (SD±12). Of 140 participants, 96 (68.6%) were men; 80 (57.1%) resided in rural areas. Hypertension was the most common co-existing condition, present in (n=136; 97%) participants. In the QOL assessment, participants reported a total of 86 distinct health states. The most frequently reported states were 11111 (8.6%) and 11121 (2.9%). The health state associated with the poorest quality of life was 55544, reported by one study participant. A majority of participants (86.4%) experienced pain or discomfort, and more than three-fourths (78.6%) reported difficulty performing their usual activities. The mean EQ-5D utility score was 0.581 (95% CI: 0.522-0.639), and the mean EQ Visual Analogue Scale (EQ VAS) score was 49.0 (95% CI: 46.6-51.3). Patients undergoing haemodialysis (0.714) reported a significantly higher quality of life compared to those on peritoneal dialysis (0.512), with a P value of 0.005. Interpretation & conclusions The mean utility score among participants undergoing dialysis reflects a compromised quality of life.

Results from a recent Phase 3 clinical trial (DESTINY-Breast04) established the efficacy of the antibody-drug conjugate, trastuzumab deruxtecan (T-DXd) in patients with metastatic breast cancer with immunohistochemistry (IHC) score 1+ or 2+ and without in situ hybridization amplification, defining a new category of metastatic breast cancer known as human epidermal growth factor receptor 2 (HER2)-low. Across studies of patients with primary or metastatic breast cancer, approximately 50 per cent have HER2-low tumours, thereby emphasizing the importance of accurately identifying these tumours. Results from the DESTINY-Breast06 trial further corroborated the DESTINY-Breast04 results showing T-DXd as a new standard of care for patients with HER2-low and HER2-ultralow (defined as IHC score 0 with membrane staining) metastatic breast cancer following one or more lines of hormone therapy. Differentiating between HER2 IHC scores 0 and 1+ shows significant interobserver variability, possibly because the low scores did not have any clinical relevance until now. To establish a standardized approach in scoring of HER2-low tumours in India, a panel of experts comprising histopathologists, molecular pathologists, and clinicians met to discuss guidelines on HER2 testing. The identification of HER2-low expression depends on multiple methodological pre-analytical and analytical variables, including sample handling, fixation, processing, antigen clones, staining methodology, and substrates. The panel also focused on the challenges in the interpretation of HER2-low status. Challenges in the pre-analytical and analytical phases could be addressed by rigorous quality control procedures and training the pathologists. In the post-analytical phase, the subjective mode of HER2 assessment and HER2 intratumoural heterogeneity in HER2-low breast cancer are factors that influence HER2-low assessment. The panel recommended robust standard operating procedures to overcome these challenges. The central point of discussion was to implement clear guidelines, careful supervision of pre-analytical and analytical issues, and specialized training for accurate HER2 testing that would help select patients eligible for novel therapies.

Background & objectives Sickle cell disease (SCD) is a monogenic disorder characterised by aberrant haemoglobin production, leading to haemolytic anaemia and vaso-occlusive crises. Genetic variations and altered expression of cell adhesion molecules (CAMs) are implicated in disease pathogenesis. This cross-sectional study investigated the association between single nucleotide polymorphisms (SNPs) in the SELP, SELE, ICAM-1, and VCAM-1 genes and their protein levels in individuals with SCD. Methods A total of 140 individuals with SCD were recruited. Plasma levels of P-selectin, E-selectin, ICAM-1 and VCAM-1 were measured by ELISA method alongside a control group (n=10). The selected SNPs of SELP, SELE, ICAM-1, and VCAM-1 genes were identified through Sanger sequencing method. Results The expression of adhesion molecules were found to be significantly higher in SCD group as compared to control. Furthermore, the results showed significant associations between SNPs, SELE: c.109+138A>C (P<0.0001), SELE: c.422-25T>C (P<0.0001), and SELE: c.529+15T>C (P=<0.0001) with vaso-occlusive crises even after Bonferroni correction (corrected P=0.0025). Interpretation & conclusions Significant correlation observed between SELP, SELE, and VCAM-1 levels suggests complex interactions of these markers that may influence disease progression and identify potential therapeutic targets for managing SCD complications. Further studies are warranted to validate these findings in larger cohorts and explore the functional implications of the observed genetic and molecular associations in SCD.

Radioprotectors are agents that protect normal tissues from the harmful effects of radiation during cancer treatment. Combining these protective agents with advanced radiotherapy techniques such as stereotactic body radiotherapy (SBRT) and proton therapy offers a promising strategy to enhance therapeutic efficacy while minimizing normal tissue toxicity. However, despite extensive research and the identification of numerous potential radioprotectors, only a few have made it into clinical practice. It is primarily because the transition from laboratory research to clinical application faces significant challenges. These include adverse side effects, lack of tissue specificity, complex regulatory requirements, and the high cost of development and implementation. Addressing these challenges requires a multifaceted approach. Streamlined regulatory pathways and increased funding for translational research can further accelerate the clinical adoption of these agents. This paper reviews the landscape of radioprotector research, examining the biological mechanisms, clinical trials, and challenges that have limited the clinical translation of many promising agents. This review underscores the critical need for continued research and innovation to bridge the gap between experimental radioprotectors and viable clinical treatments, aiming to enhance the therapeutic ratio of radiotherapy in oncology.

Background & objectives Immunisation is a cornerstone of public health, significantly reducing vaccine-preventable disease (VPD) mortality. The World Health Organization-United Nations Children's Fund (WHO-UNICEF) effective vaccine management (EVM) initiative provides tools to enrich vaccine supply chains. This study evaluated the effectiveness of cold storage management in western part of India, using EVM criteria, comparing performance across districts with varying full immunisation coverage (FIC). Methods A cross-sectional study was conducted in six districts (3 high-FIC and 3 low-FIC). Data were collected from 90 service points (SPs) and six district vaccine stores (DVSs) using the WHO EVM tool and structured questionnaire with 204 stakeholders. Secondary data were obtained from vaccine management records and analysed to assess the performance of the vaccine supply chain. EVM criteria scores (e.g., temperature control, stock management) and category scores (e.g., infrastructure, maintenance) were compared to the global benchmark of 80 per cent. Descriptive statistics were used to summarise the data, while the Shapiro-Wilk test assessed normality. Depending on the distribution, independent samples t-tests or Mann-Whitney U tests were applied to compare EVM scores across relevant groups. Results Gujarat achieved strong scores across most EVM criteria, i.e., temperature control (99%), storage capacity (98%), maintenance (99%), and vaccine management (96%). Management Information System (MIS) and vehicle infrastructure had the lowest scores, with MIS scoring 79 per cent and vehicle infrastructure scoring 80 per cent, slightly below the WHO-recommended benchmark. High- and low-FIC districts showed no statistically significant differences in overall performance, as measured by the EVM composite score (mean EVM score difference: 1.75 percentage points, P>0.05). Category analysis highlighted high scores in buildings (95%), capacity (97%), and training (99%). Compared to earlier assessments, Gujarat demonstrated significant improvements in supply chain efficiency. Interpretation & conclusions Gujarat's vaccine supply chain has demonstrated substantial improvements, meeting or exceeding global benchmarks in most areas, though targeted improvements in MIS and vehicle infrastructure are necessary. The findings emphasise the importance of robust vaccine management systems for public health success.

Background & objectives Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterised by menstrual irregularities, hirsutism, acne, obesity, infertility, and other features adversely affecting the quality of life of women of childbearing age. Besides lifestyle modifications, limited pharmacological treatments have been used to manage the symptoms of PCOS. This meta-analysis was conducted to evaluate a novel pharmacological approach, sodium glucose cotransporter-2 inhibitors (SGLT2i), in PCOS. Methods Electronic databases were searched systematically for literature published before November 2024. Randomised controlled trials (RCTs) evaluating SGLT2i alone or in combination in women diagnosed with PCOS, based on the Rotterdam criteria, were included in the meta-analysis. Preclinical studies, and non-randomised trials, were excluded. Quality of studies was assessed using RoB 2.0. Meta-analysis was performed for change in anthropometry, reproductive hormone levels, glycaemic and cardiometabolic indices. Adverse events (AEs) were also compared between the SGLT2i and control groups, using RevMan 5.4.1. Mean difference using the inverse-variance method and 95% confidence interval was used as a measure of effect size of continuous variables, while odds ratio (OR)using the Mantel-Haenszel method (M-H) with 95% confidence interval was calculated to analyse dichotomous variables. P value less than 0.5 was the cut-off for significance. Trial sequential analysis (TSA) was conducted to test the conventional and required information size (RIS) boundaries. The meta-analysis was registered in PROSPERO (CRD42024608736). Results Five RCTs with 'low' risk of bias, including 205 patients with PCOS, receiving SGLT2i (empagliflozin, licogliflozin, dapagliflozin, and canagliflozin alone and in combination with metformin) or control (placebo, metformin, or exenatide) were evaluated in the meta-analysis. SGLT2i significantly reduced total testosterone (mean difference=-0.10 [-0.19, -0.01], P=0.03), free androgen index (mean difference = -0.61 [-1.16, -0.05], P=0.03), and homeostasis model assessment-estimated insulin resistance (HOMA-IR) (mean difference = -0.38 [-0.75, -0.02], P=0.04). Total cholesterol (mean difference=0.13 [0.01, 0.26], P=0.04) and low-density cholesterol (MD=0.18 [0.06, 0.31], P=0.003) increased with SGLT2i use. Genitourinary AEs were more common in the SGLT2i group (OR=10.88 [1.33, 89.14], P= 0.03). On performing TSA, the Z-curve did not cross the RIS boundary of 80 per cent power. Interpretation & conclusions The findings of this meta-analysis suggest that SGLT2i improves the hormonal and glycaemic indices in patients with PCOS. It can prove to be a safe alternative in patients not responding to or intolerant of standard pharmacological treatments.