Indian Journal of Medical Research最新文献

Background & objectives Genetic instability is frequent in tumour cells and might occur due to an imbalance of homologous recombination (HR). HR is a crucial mechanism of DNA double-strand break (DSB) repair that depends on the formation and resolution of Holliday junctions for genomic stability maintenance. The SMC6 complex with SMC5 is involved in DSB repair. We sought to investigate the association between SMC6 expression, genomic instability, and prognosis of breast cancer. Methods This was an observational retrospective cohort study. We assessed SMC6 expression and copy number variation (CNV) data measured by qRT-PCR and whole-genome comparative genomic hybridization in 33 women with breast cancer who are non-carriers of BRCA1/BRCA2 mutations. According to nuclear staining, the SMC6 protein expression was evaluated on a tissue microarrayer containing 481 samples classified as SMC6low (negative/weak) or SMC6high (moderate/strong). Results SMC6low tumours tend to show higher CNV. SMC6high group presented poorer disease-free survival than the SMC6low group (P=0.050), mainly for the luminal subtype (P=0.005). SMC6low/ERpos were protective biomarkers for recurrence. Interpretation & Conclusions There is a possible association between SMC6 expression and relapse of breast cancer, also suggesting that SMC6 abnormal expression may indicate tumour genetic instability in breast cancer.

Background & objectives The effects of COVID-19 on neonatal and perinatal outcomes and infant development in low- and middle-income countries have not been well studied. Our study aimed to explore the effect of maternal COVID-19 infection on pregnancy, neonatal outcomes, and development of infants. Methods We conducted a retrospective cohort study on women exposed to and not exposed to COVID-19 during pregnancy and their infants (exposed and comparison cohort, respectively). Data were collected through hospital records and interview of mothers. Outcomes included stillbirth, preterm birth, low birth weight, admission to special newborn care unit (SNCU) and attainment of age-appropriate developmental milestones till one year of age. We conducted propensity score matching analysis to address any selection bias. Results Exposure to SARS-CoV-2 was associated with a higher risk of stillbirths [adjusted odds ratio (aOR) 2.63; 95% confidence interval (CI) 1.39, 4.96] and admission to SNCU (aOR 2.57; 95% CI 1.85, 3.58) after adjusting for pregnancy and birth-related covariates. Risk of illness among babies born to COVID-positive mothers was higher [relative risk (RR) 4.23; 95% CI 3.14, 5.69; P<0.001]. Age of attainment of developmental milestones were similar between both cohorts. Interpretation & conclusions Women who contracted COVID-19 in pregnancy were at higher risk of stillbirths, and their babies were more likely to be admitted to the SNCU as compared to their COVID-negative counterparts. There were no clinically meaningful differences between babies of both cohorts in the age at which developmental milestones were attained.

Background & objectives The clinical manifestation of dengue results from a complex and finely balanced interaction between the dengue virus (DENV) and the host immune responses, particularly excessive inflammation driven by pro-inflammatory cytokines. Vitamin D is an essential modulator of antiviral innate immunity, capable of reducing cytokine production and viral replication in vitamin D3-differentiated monocyte-derived macrophages (D3-MDM). It also downregulates inflammatory miRNAs, including miRNA-155. This study aimed to investigate serum levels of 25-hydroxyvitamin D [25(OH)D], cytokine production, and the expression of microRNA-155 (miRNA-155) in patients with dengue. Methods Serum samples were collected from 98 dengue-positive patients categorised as dengue without warning signs, dengue with warning signs, or severe dengue, along with 10 healthy individuals as controls. Clinical and laboratory data were also analysed. Results Serum 25(OH)D levels were significantly higher in dengue without warning as compared to other two categories. Although dengue with warning signs patients exhibited higher 25(OH)D levels than those with severe dengue, both groups showed a significant reduction compared to healthy controls. In contrast, miRNA-155 expression was highest in the severe dengue group, followed by dengue with warning signs, dengue without warning signs, and controls. A significant negative correlation was observed between serum 25(OH)D levels and miRNA-155 expression. Lower 25(OH)D concentrations were associated with elevated TNF-α, IL-6, and IFN-γ levels, particularly in patients with warning signs and severe dengue. Interpretation & conclusions These findings suggest a relationship between vitamin D status, miRNA-155 expression, and immune activation during dengue infection. The inverse correlation between 25(OH)D and miRNA-155 highlights their potential as disease severity and progression biomarkers in patients infected by dengue virus.

Background & objectives Pseudomonas aeruginosa is a leading cause of bacterial keratitis, known for its rapid progression, severe corneal damage, and resistance to treatment. Existing animal models exist to study disease mechanisms and therapeutic options require specialised conditions or complex procedures. This study aimed to develop a simplified, cost-effective, and reproducible murine model of P. aeruginosa keratitis using Swiss albino mice for translational research applications. Methods Four female Swiss albino mice (6-8 wk old) were maintained under standard conditions. Baseline ocular evaluation was done using a handheld slit lamp. The left corneas were abraded with a sterile 26G needle and inoculated topically with 10 μL of P. aeruginosa (1.0 × 10⁶ CFU/mL, ATCC 19660). The right eyes served as uninfected controls. Clinical signs were assessed on days 1, 2, and 3 using a standardised 0-4 scoring scale. Infection was confirmed through culture, biochemical tests, and PCR targeting the exotoxin A gene. Statistical analysis was performed using one-way ANOVA with Tukey's post hoc test. Results All infected eyes developed progressive keratitis marked by lid swelling, corneal haze, and stromal involvement. Control eyes remained unaffected. Clinical scores increased significantly over time (P< 0.05). Culture and molecular analyses confirmed successful infection. Interpretation & conclusions This simplified Swiss albino mouse model effectively mimics human P. aeruginosa keratitis and enables cost-efficient study of pathogenesis and therapeutic testing. It can facilitate standardised ophthalmic infection research.

Background & objectives While originator anti-tumour necrosis factor (TNF) agents have demonstrated good efficacy in the management of axial spondyloarthritis, the therapeutic equivalence and safety profile of their Indian biosimilars remain uncharacterised. This study aimed to evaluate the efficacy and safety of adalimumab biosimilar in patients diagnosed with axial spondyloarthritis. Methods This retrospective, single-centre observational study from India assessed the efficacy and safety of adalimumab biosimilar in axial spondyloarthritis patients with high disease activity. We recorded baseline characteristics, swollen/tender joint counts, and Bath ankylosing spondylitis disease activity index (BASDAI) scores at 0, 12, and 24 wk. The primary outcome was the percentage of patients achieving a BASDAI50 response at 12 wk; adverse events were also monitored. Results The study included 96 axial spondyloarthritis patients (84 male, mean age 29.1 yr) and showed that adalimumab biosimilar was efficacious, with 54per cent achieving BASDAI50 response at 12 weeks and 70 per cent at 24 wk. Mean BASDAI significantly improved from 5.8 at baseline to 2.9 at 12 wk and 2.3 at 24 wk. Safety concerns were minimal, though two patients developed tuberculosis despite prophylaxis. Most patients accessed the biosimilar through government funding, and dose spacing was attempted in a few. Interpretation & Conclusions Adalimumab biosimilar is efficacious in patients with axial spondyloarthritis without major safety concerns.

Background & objectives Lung cancer is the most diagnosed cancer and leading cause of cancer deaths. We assessed regional patterns in incidence, mortality, morphology, and mortality-to-incidence ratio across 57 populations, along with tobacco and alcohol use in India. We also estimated time-trends (average annual percent change: AAPC) by gender and age, and forecasted to 2030. Methods We used age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) (per 105 population) estimated AAPC via joinpoint regression and applied auto-regressive integrated moving average (ARIMA) model to forecast rates. Results Higher incidence of lung cancer among men was observed in the south, north and north-east regions of India. Highest ASIR was in Srinagar (39.5) and highest ASMR in Aizawl (27.1). Among women, highest rates were observed in the north-east, particularly in Aizawl (ASIR:33.7, ASMR:23.2). Tobacco use among women remains low outside the north-east, correlating with the patterns of lung cancer. Mortality to incidence ratio was low (<30%) except in a few populations. An increasing-trend in incidence was noted, with the highest AAPC in Thiruvananthapuram (women:6.7) and Dindigul (men:4.3). Adenocarcinoma has emerged as the dominant subtype over 25 yr, with higher prevalence among women, especially in Bengaluru (56.0%). Large-cell carcinoma increased notably in Delhi. By 2030, ASIRs are projected to range from 1.8 (Barshi) to 33.1 (Kollam) in men, and 1.9 (Barshi) to 8.1 (Bengaluru) in women. Interpretation & conclusion The burden of lung cancer in India shows regional disparities, with more adenocarcinoma, especially among women. Incidence is projected to rise, while low mortality to incidence ratio suggests underreported mortality, underscoring the need for better death reporting. Region-specific research beyond tobacco use is essential.

Background & objectives Sickle cell anaemia (SCA) is a serious inherited blood disorder caused by mutations in the β-globin gene, leading to abnormal haemoglobin (HbS). Understanding the genetic diversity of SCA is important for improving diagnosis, treatment, and public health planning. Our aim was to systematically review and summarise the genetic variations associated with SCA in various populations, and to explore how these differences affect clinical outcomes and inform public health responses. Methods A systematic search was conducted across databases, including PubMed, Scopus, Cochrane, and Science Direct, for studies published between 1990 and 2025. A total of 62 studies were included, covering populations with a high prevalence of haemoglobinopathies. Results Significant genetic heterogeneity was identified. Common coinherited conditions included α- and β-thalassaemia, particularly in Saudi Arabia, Iran, and Sub-Saharan Africa, influencing haemoglobin levels and disease severity. Specific βS haplotypes (e.g. Benin, Bantu, Senegal) were regionally dominant, with some (e.g. Senegal) linked to higher foetal haemoglobin levels and milder symptoms. Genetic modifiers such as BCL11A and MYH9 variants were also found to affect disease expression. Public health screening programmes in countries like the UAE and India have achieved high coverage, but diagnostic and treatment challenges persist due to ongoing genetic and environmental variation. The Quantitative findings include regional dominance of βS haplotypes: Benin (29%), Bantu (3%), Senegal (1%), with the Senegal haplotype linked to higher foetal haemoglobin (HbF) levels (average 14.6%) and the Arab Indian haplotype (6.7%). Co-inheritance of β-thalassaemia was notably common in Saudi Arabia, Iran, and Sub-Saharan Africa. Interpretations & conclusions Tailored, genomically informed public health strategies are needed to address the diverse genetic landscape of SCA. Clinicians should incorporate genetic profiling and culturally appropriate counselling to improve care in affected populations. Variability in study design, sample size, and genetic reporting limited the ability to perform direct comparisons across regions.

Background & objectives Dynapenia, an age-related decline in muscle strength independent of muscle mass loss, is increasingly recognised as a predictor of functional decline and adverse health outcomes. This study aimed to investigate the prevalence and predictors of dynapenia among older adults with low skeletal muscle mass. Methods This hospital-based cross-sectional study included 128 participants aged ≥ 60 yr with low muscle mass determined using the EWGSOP-2 criteria. Assessments included handgrip strength using a Jamar dynamometer, a 4-meter gait speed test, the geriatric depression scale, and the clinical frailty scale. Pearson's correlation was used to assess the relationships between muscle strength parameters, gait speed, frailty scores, and depression scores, followed by multivariate logistic regression. Results Among individuals with low muscle mass, 66 (51.6%) had dynapenia [29 (43.9%) in females; 37 (56.06%) in males]. Handgrip strength strongly and positively correlated with knee extension strength [coefficient correlation (r) = 0.822, P<0.001] and moderately correlated with gait speed (r=0.414, P<0.001). Both strength parameters were inversely correlated with frailty scores (r=-0.367 and r=-0.316, respectively; P<0.001). Multivariable analysis identified female gender [Odds ratio (OR)=7.655, 95% confidence interval (CI): 1.616-36.264, P=0.010], lower socioeconomic status (P<0.001), and gait speed <0.8 m/s (OR=22.664, 95% CI: 2.952-174.010, P=0.003) as predictors of dynapenia. Depression was more prevalent in dynapenia patients [25.8% (n=17) vs. 3.2% (n=2), P<0.001]. Interpretations & conclusions The prevalence of dynapenia was 51.6 per cent among elderly with low muscle mass, with female sex, lower socioeconomic status, and reduced gait speed as significant correlates. Routine strength assessment is warranted in elderly with low muscle mass.

Background & objectives Brucellosis is a zoonotic infectious disease that affects both humans and animals, with diagnosis traditionally confirmed by bacteriological culture of blood or tissue samples. This study aimed to identify clinical, epidemiological, and laboratory parameters that predict culture positivity in brucellosis cases. Methods We conducted a retrospective, single-centre study including 130 patients with brucellosis diagnosed between January 2023 and December 2024. Patients were classified as bacteraemic (n=60) and non-bacteraemic (n=70). Demographic characteristics, clinical features, laboratory parameters, and treatment outcomes were compared between the two groups. Results Patients with bacteraemia had higher rates of summer admissions, more frequent exposure to animal husbandry, and shorter symptom duration. Clinical manifestations such as back pain, headache, weight loss, and abdominal pain were more common in them. Laboratory findings showed lower leukocyte and, neutrophil counts, lower haemoglobin, lower platelet counts, in bacteraemic patients. Erythrocyte sedimentation rate, C-reactive protein, alanine aminotransferase, and aspartate aminotransferase levels were significantly higher in bacteraemic vs non-bacteraemic patients. Receiver operating characteristic analysis indicated that AST had the highest diagnostic accuracy (AUC: 0.841, 95% CI: 0.758-0.924), with an optimal cut-off of 27.3 U/L, yielding 67.2 per cent sensitivity and 84.1 per cent specificity. Binary logistic regression analysis demonstrated that exposure history (OR=5.5), residence in a high-incidence geographic location (OR=10.0), and clinical features such as back pain (OR = 9.4), together with low haemoglobin and elevated AST levels, were independent predictors of blood culture positivity in brucellosis. Interpretation & conclusions It may be possible to predict bacteraemia in brucellosis by using a combination of epidemiology, clinical, and laboratory criteria.