Category: Nevin Manimala

Chin Clin Oncol. 2025 Jun;14(3):29. doi: 10.21037/cco-25-3.

ABSTRACT

BACKGROUND: The introduction of immune checkpoint inhibitors (ICIs) has enabled long-term survival for non-small cell lung cancer (NSCLC) patients. However, the proportion of patients achieving this is still low compared to patients with melanoma. Many NSCLC patients experience early progression (primary resistance) following ICI treatment, or relapse after initial responses (acquired resistance). While chemotherapy regimens, typically involving cytotoxic agents, are commonly used after ICI resistance, little evidence has been accumulated regarding the efficacy of ICI rechallenge. The aim of this study was to evaluate the efficacy of ICI rechallenge in patients who experienced failure of primary treatment with ICI-containing regimens. Additionally, we assessed whether the administration of local therapy prior to rechallenge influenced the efficacy of ICI rechallenge.

METHODS: We retrospectively reviewed the records of advanced NSCLC patients for whom response was evaluated as progressive disease (PD) after receiving an ICI-containing regimen as first-line therapy and underwent rechallenge with an ICI in Funabashi Municipal Medical Center between January 2020 and March 2024. We analyzed progression-free survival (PFS) and overall survival (OS) based on whether local therapy (including beyond PD with local therapy) was performed. PFS was compared using the Kaplan-Meier method, with statistical significance set at P<0.05 using log-rank testing.

RESULTS: The study included 20 patients, with 10 patients in the local therapy group and 10 in the no-local therapy group. No significant differences in patient characteristics were apparent between groups, although the no-local therapy group tended to show a higher number of organs with residual metastases at the time of rechallenge. When ICI rechallenge was administered after local therapy, median PFS was significantly longer in the local therapy group (9.0 months) than in the no-local therapy group (1.6 months, P=0.02), particularly in cases where radiation therapy was applied to the primary lesion just before rechallenge. However, no significant difference in OS was evident between the local treatment group (21.4 months) and the no-local treatment group (18.8 months; P=0.12).

CONCLUSIONS: Rechallenge with ICI following local therapy in NSCLC patients who developed resistance to ICIs may extend PFS, suggesting potential value as a therapeutic option.

PMID:40575966 | DOI:10.21037/cco-25-3

Cancer Res Treat. 2025 Jun 25. doi: 10.4143/crt.2025.377. Online ahead of print.

ABSTRACT

PURPOSE: Although non-coding RNAs (ncRNAs) have often been implicated in various cancers, their causal roles in acute (AML) and chronic myeloid leukemia (CML) remain unclear. Here, we conducted a genome-wide two-sample Mendelian randomization (MR) study to investigate the causal effects of a comprehensive set of ncRNAs on AML and CML.

MATERIALS AND METHODS: We used summary statistics of blood expression quantitative trait loci (eQTL) from the eQTLGen consortium (31,684 European participants) as exposure data. Genome-wide association study summary statistics from the FinnGen study (AML: 322 cases; CML: 303 cases) and UK Biobank (UKBB) (AML: 318 cases; CML: 153 cases) served as outcome data. The generalized inverse-variance weighted (GIVW) method was used as the primary MR method. Two additional MR methods (generalized MR-Egger and weighted median), sensitivity analyses, and the HEIDI test were further employed to support our findings.

RESULTS: Upregulated HCG22 and RP11-42I10.1 were causally linked to increased AML risk, while the GMDS-AS1 locus was positively associated with increased CML risk. We highlight these ncRNAs for their consistent significance across all three MR methods, with no evidence of bias in sensitivity analyses (F-test, Cochran’s Q-test, MR-Egger intercept, MR-PRESSO global test) and no indication of confounding from the HEIDI test. Primarily discovered in FinnGen (FDRGIVW<0.05), their significance was validated in UKBB (PGIVW<0.05). Upon validation with an independent linkage disequilibrium reference panel, they remained robust.

CONCLUSION: This study provides evidence of causal relationships between ncRNAs and two ML subtypes, notably highlighting HCG22 and RP11-42I10.1 in AML and the GMDS-AS1 locus in CML.

PMID:40575950 | DOI:10.4143/crt.2025.377

Euro Surveill. 2025 Jun;30(25). doi: 10.2807/1560-7917.ES.2025.30.25.2400624.

ABSTRACT

BACKGROUNDRespiratory syncytial virus (RSV) is a major cause of morbidity in older adults.AIMWe aimed to investigate the epidemiology of RSV in adults in five European countries and one region before and during the COVID-19 era.METHODSWe conducted a retrospective analysis using national hospital admission data from Denmark, England, Finland, the Netherlands, Scotland and regional prospective surveillance data from the Spain-Valencia region. We included patients aged ≥ 18 years hospitalised for respiratory tract infections (RTIs) 2016-2023 and assessed RSV-coded and laboratory-confirmed hospitalisations, intensive care unit (ICU) admissions and mortality.RESULTSHospitalisations associated with RSV varied by country and year but increased with increasing age regardless of the use of RSV-coded or RSV-confirmed data, the country or year. The highest hospitalisation rates were in patients aged ≥ 85 years. We found that RSV-coded hospitalisations underestimated the case numbers when compared with laboratory-confirmed cases by an average of 1.9 (standard deviation (SD): ± 0.9). Admissions to ICU associated with RSV in England and CFR in England and Finland displayed different patterns post-COVID-19 pandemic peak but were not notably higher compared with RTI admissions.CONCLUSIONOur findings reveal a consistency of RSV hospital admission patterns between European countries in the study period, with higher incidence rates among older patients. The differences between the numbers of RSV-coded and laboratory-confirmed cases highlight the critical need for improved surveillance, diagnostic practices and coding guidelines to better assess the incidence. Our findings could be vital for guiding public health strategies, particularly with the introduction of RSV vaccines for older adults.

PMID:40575911 | DOI:10.2807/1560-7917.ES.2025.30.25.2400624

Rev Esp Enferm Dig. 2025 Jun 27. doi: 10.17235/reed.2025.11305/2025. Online ahead of print.

ABSTRACT

BACKGROUND: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is linked to poor sleep quality, though evidence remains inconsistent. This meta-analysis aimed to evaluate sleep quality in IBD patients and its association with disease activity.

METHODS: We systematically searched databases up to February 2025 for studies reporting sleep quality in IBD. Outcomes included pooled prevalence of poor sleep, odds ratios (ORs), and standardized mean differences (SMDs) comparing IBD patients to controls, UC vs CD, and active vs inactive disease. Heterogeneity was assessed using Cochran’s Q and I² statistics.

RESULTS: Fifty-five studies were included. Poor sleep prevalence was 60% in IBD, 52% in UC, 56% in CD, and 68% in active IBD. IBD patients had higher odds of poor sleep than controls (OR: 1.90, 95% CI: 1.38-2.61; SMD: 0.61, 95% CI: 0.32-0.89). No differences emerged between UC and CD (OR: 0.93; SMD: -0.04). Active IBD patients showed elevated poor sleep risk versus those in remission (OR: 2.09, 95% CI: 1.50-2.90), driven by CD (OR: 2.40, 95% CI: 1.42-4.05). SMDs for active vs inactive disease were 0.49 (IBD overall), 0.40 (UC), and 0.73 (CD).

CONCLUSION: Poor sleep is highly prevalent in IBD, particularly during active disease, with significantly higher rates than in healthy controls. Sleep quality did not differ between UC and CD. Addressing poor sleep in IBD management and exploring underlying mechanisms are crucial for improving patient outcomes.

PMID:40575902 | DOI:10.17235/reed.2025.11305/2025

Rev Esp Enferm Dig. 2025 Jun 27. doi: 10.17235/reed.2025.11389/2025. Online ahead of print.

ABSTRACT

BACKGROUND: This study analyses mortality trends in early-onset gastrointestinal cancers (EOGIC, <50 years) in Spain between 1999 and 2023, comparing them with those of late-onset cancers (≥50 years).

METHODS: Data from the Spanish National Institute of Statistics were used to calculate age-standardised mortality rates. Joinpoint regression was applied to identify trend changes, reporting average annual percentage change (AAPC) and annual percentage change (APC), with 95% confidence intervals.

RESULTS: EOGIC mortality declined across most cancer sites and in both sexes. Among men, the largest decreases were observed in oesophageal (-5.6%) and stomach cancers (-4.0%), followed by liver (-3.7%) and colon (-3.2%). In women, oesophageal cancer showed the greatest reduction (-4.3%), followed by colon (-2.6%), stomach (-2.2%), rectal and liver cancers. Pancreatic cancer mortality remained stable in younger women but began to decline from 2007 onwards (-1.2%). In adults aged 50 and over, trends were more variable: pancreatic cancer mortality increased (men: +1.0%; women: +1.6%), while stomach cancer mortality declined (men: -3.3%; women: -2.9%). Colon cancer showed steeper declines from 2011-2012. Liver, rectal and other digestive cancers showed modest decreases. Oesophageal cancer mortality declined in men but remained stable in women.

CONCLUSION: EOGIC mortality in Spain declined steadily over the study period, whereas trends in late-onset cancers were more irregular. These findings highlight the need for age-specific cancer prevention and control strategies.

PMID:40575889 | DOI:10.17235/reed.2025.11389/2025

Hypertension. 2025 Jun 27. doi: 10.1161/HYPERTENSIONAHA.125.24664. Online ahead of print.

ABSTRACT

BACKGROUND: With aging, frailty and hypertension become increasingly prevalent comorbidities in the older population. Therefore, the aim of the study is to identify effective druggable targets for these conditions.

METHODS: We performed a 2-sample Mendelian randomization analysis to assess the causal effects of 2532 druggable genes on frailty, hypertension, systolic blood pressure and diastolic blood pressure. RNA expression profiling data and single-cell RNA sequencing were performed for validation. Mediation Mendelian randomization analysis was conducted to identify possible mediators participating in the effects of target genes on outcomes. Molecular docking was used to identify potential drugs.

RESULTS: After screening, the expression of Glutathione peroxidase 1 (GPX1) in whole blood was found to positively correlate with hypertension (β, 0.308 [95% CI, 0.266-0.349]; P=3.40×10^-48) and frailty index (β, 0.172 [95% CI, 0.141-0.204]; P=1.21×10^-26), which was validated by RNA expression profiling data. Mediation Mendelian randomization analysis indicated that glycine and carnitine/ergothioneine mediated the effects of GPX1 on hypertension and frailty. Single-cell RNA sequencing further validated the mediating effects of glycine metabolism and carnitine transport at the cellular level. Moreover, GPX1 expression in mononuclear phagocytes was associated with upregulated inflammatory responses and immune activation. Molecular docking analysis identified biochanin A and epigallocatechin gallate as potential agents for GPX1 with high affinity.

CONCLUSIONS: Collectively, GPX1 is a potential therapeutic target for mitigating both frailty and hypertension.

PMID:40575858 | DOI:10.1161/HYPERTENSIONAHA.125.24664

Neuroreport. 2025 Jun 24. doi: 10.1097/WNR.0000000000002190. Online ahead of print.

ABSTRACT

BACKGROUND: Rhegmatogenous retinal detachment (RRD) is known to induce functional alterations in the gray matter regions associated with vision. However, the impact of RRD on the white matter (WM) connectome remains largely unexplored.

METHODS: We applied graph theory to evaluate the functional network topology of the WM connectome in RRD patients. A support vector machine (SVM) classifier, combined with SHapley Additive exPlanations (SHAP), was then employed to distinguish RRD patients from healthy controls (HCs) and to identify key brain regions driving model predictions.

RESULTS: Compared to HCs, RRD patients exhibited significant disruptions in both global and nodal network topology. Network-based statistics identified 23 subnetworks with altered connectivity. Notably, the integration of SVM and SHAP analyses revealed that betweenness centrality (Bc) was the most discriminative topological feature, achieving an area under the curve of 0.9211.

CONCLUSION: These findings suggest that RRD disrupts critical hubs within the central visual and higher-order cognitive networks, leading to characteristic network reorganization. Moreover, Bc shows promise as an early neuroimaging biomarker for RRD. Overall, our results advance the understanding of neuroadaptive changes in RRD and support the clinical application of network topological metrics in early diagnosis.

PMID:40575857 | DOI:10.1097/WNR.0000000000002190

J Cardiovasc Med (Hagerstown). 2025 Jun 24. doi: 10.2459/JCM.0000000000001759. Online ahead of print.

ABSTRACT

INTRODUCTION: Transcatheter patent foramen ovale (PFO) closure has emerged as the therapeutic gold standard in patients with a PFO-related stroke. New-onset atrial fibrillation appears as an early complication of this procedure. Our study aims to evaluate if the MVP (Morphology-Voltage-P wave duration) ECG risk score calculated before PFO closure might be a valuable predictor of early postprocedural atrial fibrillation occurrence.

METHODS: We enrolled all consecutive patients (aged 18-65 years) who underwent percutaneous PFO closure between July 2020 and August 2023. The MVP ECG risk score was calculated. Patients were reassessed with clinical and echocardiographic follow-up at 1 month and 6 months later, to assess the efficacy and safety of the procedure as well as atrial fibrillation occurrence. Patients were then divided into two groups according to the occurrence of early atrial fibrillation after PFO closure.

RESULTS: We enrolled 103 patients, 63.1% male (mean age 48.7 ± 10.6 years). At the end of follow-up, atrial fibrillation occurred in five patients (4.9%). When comparing groups with and without atrial fibrillation diagnosis at follow-up, there was a statistically significant difference in MVP ECG risk scores (3.0 versus 1.0; P = 0.001). At receiver operating characteristic analysis, the MVP ECG risk score showed good diagnostic accuracy in predicting the diagnosis of atrial fibrillation at follow-up [AUC: 0.90; 95% confidence interval (CI) 0.81-0.98]. In the multivariate Cox proportional hazard model, the MVP ECG risk score remained the only independent predictor of atrial fibrillation onset (hazard ratio 2.96; 95% CI 1.13-7.71; P = 0.03).

CONCLUSION: The MVP ECG risk score could be an independent predictor of early atrial fibrillation occurrence in patients undergoing percutaneous PFO closure.

PMID:40575851 | DOI:10.2459/JCM.0000000000001759

Ann Neurol. 2025 Jun 27. doi: 10.1002/ana.27304. Online ahead of print.

ABSTRACT

OBJECTIVE: Clonal hematopoiesis of indeterminate potential (CHIP) is an emerging risk factor for cardio-cerebrovascular diseases. This study aimed to investigate CHIP’s association with cerebrovascular or glymphatic changes in a community-based population.

METHODS: This study examined Chinese community cohort participants. CHIP mutations were identified through whole-exome sequencing. Intracranial arterial stenosis, silent brain infarcts, cerebral small vessel disease markers, and diffusion along the perivascular space index were identified by magnetic resonance imaging. The correlation between CHIP and neuroimaging outcomes was investigated through univariate and multivariate logistic/linear regression. The multivariate regression model was adjusted for cerebrovascular disease risk factors, including age, sex, body mass index, smoking status, hypertension, diabetes, and hyperlipidemia.

RESULTS: In total, 18.2% (224 out of 1,229) participants were identified as carriers of CHIP mutations. The prevalence of CHIP generally increases with age (p = 0.009). After adjusting for vascular risk factors using multivariate regression, CHIP mutations were found to be significantly associated with increased odds of large magnetic resonance imaging-defined infarcts (>15 mm; OR 3.20; 95% CI 1.18 to 8.43; p = 0.018), inversely associated with diffusion along the perivascular space (β = -0.02; 95% CI -0.04 to 0; p = 0.034), and showed a borderline association with intracranial arterial stenosis (OR 1.52; 95% CI 0.99 to 2.30; p = 0.053). Notably, no statistically significant correlations were observed between CHIP and cerebral small vessel disease markers or brain atrophy measures.

INTERPRETATION: CHIP was significantly associated with glymphatic dysfunction and large infarcts, and marginally associated with intracranial arterial stenosis. Further research is needed to elucidate the pathophysiology linking CHIP to cerebral covert changes. ANN NEUROL 2025.

PMID:40575838 | DOI:10.1002/ana.27304

Tidsskr Nor Laegeforen. 2025 Jun 17;145(8). doi: 10.4045/tidsskr.25.0025. Print 2025 Jun 24.

ABSTRACT

BACKGROUND: For patients with Crohn’s disease, surgery can be appropriate when medical treatment fails to adequately control the condition, or in cases of stenosis, fistulas or abscesses. We aimed to investigate the types of bowel surgery these patients undergo, as well as waiting times and the prevalence of serious complications.

MATERIAL AND METHOD: This is a retrospective observational study investigating the surgical treatment of Crohn’s disease at the University Hospital of North Norway, Tromsø, in the period 1 January 2013 to 31 December 2021.

RESULTS: A total of 179 patients were included in the study: 92 women and 87 men, with a median age of 44 years (interquartile range: 26-57). Of these, 151 patients (84 %) underwent elective surgery with a median waiting time of 89 days (interquartile range: 43-142), while 28 patients (16 %) underwent emergency surgery.

INTERPRETATION: There was considerable variation in the types of surgery performed on patients with Crohn’s disease in this cohort. The prevalence of complications was high and waiting times for surgical treatment were long.

PMID:40575820 | DOI:10.4045/tidsskr.25.0025