Category: Nevin Manimala

J Natl Cancer Inst. 2026 Aug 22:djag285. doi: 10.1093/jnci/djag285. Online ahead of print.

ABSTRACT

BACKGROUND: Anal cancer screening is recommended for people with HIV in the United States (US). Because HIV prevalence varies geographically, the distribution of anal cancer diagnoses occurring among people with HIV may also differ by geography. Characterizing geographic variation can help identify areas needing enhanced screening infrastructure and outreach.

METHODS: Using data from the HIV/AIDS Cancer Match Study, US cancer registries, and CDC’s National HIV Surveillance System, we estimated the proportion of incident anal squamous cell carcinomas (SCC) among people with HIV across the 50 states, the District of Columbia (DC), and major metropolitan statistical areas (MSAs).

RESULTS: During 2010-2019, an average of 2,160 anal SCC diagnoses occurred annually among males, 414 (20.1%; Uncertainty Interval [UI]=19.4%-20.6%) among males with HIV. Among females, 58 of an average 4,099 annual anal SCC diagnoses (1.4%; UI = 1.3%-1.5%) occurred among females with HIV. Geographic variation among males was substantial. California had the highest annual number of anal SCC diagnoses among males with HIV (70/239; 29.2% [UI = 26.7%-31.8%]), followed by New York (48/161; 29.8% [UI = 26.3%-33.4%]), Florida (42/182; 23.1% [UI = 20.3%-26.1%]), Texas (36/132; 27.0% [UI = 23.7%-30.4%]), and Georgia (20/80; 25.2% [UI = 20.9%-29.8%]). New York had the highest annual number of diagnoses among females with HIV (10/263; 3.7% [UI = 3.0%-4.5%]). Across MSAs, the highest burden was in New York-Jersey City-White Plains (57 diagnoses [UI = 43-73]), with several MSAs in California, Texas, and Florida also showing a high burden.

DISCUSSION: Geographic differences underscore the need for targeted anal cancer screening outreach and implementation.

PMID:42633606 | DOI:10.1093/jnci/djag285

Eur Spine J. 2026 Aug 23. doi: 10.1007/s00586-026-10276-w. Online ahead of print.

ABSTRACT

BACKGROUND: Spinal meningiomas (SM) are generally benign tumours with favourable surgical outcomes. However, their potential to impair sphincter function-particularly bladder control-remains insufficiently investigated. Bladder dysfunction, ranging from urge incontinence to complete urinary incontinence, may significantly impair quality of life and correlate with both neurological status and surgical outcomes.

OBJECTIVE: This study aimed to determine whether preoperative clinically reported urinary impairment is associated with disease severity in surgically treated spinal meningiomas. Secondary aims were to evaluate its relationship with symptom duration, neurological status, extent of resection, and follow-up functional outcome.

METHODS: From a multicentric cohort of 270 SM operated between 1976 and 2023, 165 cases were retrospectively analysed. Patients were stratified according to preoperative patient-reported urinary status. Neurological function was assessed using Frankel and McCormick scales, while extent of resection was classified according to Simpson grade. Associations were explored using group comparisons and Spearman correlation. Univariable and multivariable logistic regression analyses were performed to identify factors associated with urinary dysfunction. Model discrimination was assessed using ROC analysis, and an exploratory nomogram was generated from the final multivariable model.

RESULTS: Symptom duration was longer in patients with sphincter impairment (p < 0.001). Extent of resection differed between groups (p = 0.007). Neurological status was worse both preoperatively and at follow-up, as reflected by Frankel (p = 0.009 preoperatively; p = 0.018 at follow-up) and McCormick grades (p = 0.010 both preoperatively and at follow-up).

CONCLUSION: Patient-reported urinary dysfunction was associated with longer symptom duration and worse neurological status in spinal meningiomas, underlining its role as a clinically relevant marker of disease severity. These findings should be interpreted as associative rather than causal, and prospective studies with standardized neuro-urological assessment are required.

PMID:42633604 | DOI:10.1007/s00586-026-10276-w

Diabetologia. 2026 Aug 23. doi: 10.1007/s00125-026-06830-2. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: Nearly 40% of African adults with type 2 diabetes are lean (BMI <25 kg/m²). Emerging evidence suggests that type 2 diabetes in African individuals who are lean may represent a distinct phenotype driven by impaired insulin secretion rather than insulin resistance, raising concerns about treatment mismatch and divergent disease outcomes. We examined complication profiles in Africans with type 2 diabetes who are lean vs overweight/obese.

METHODS: We analysed harmonised, individual-level cross-sectional data from two large, well-characterised African cohorts (Africa America Diabetes Mellitus study, n=2790; Research on Obesity and Diabetes among African Migrants study, n=541; total n=3331) of adults with type 2 diabetes from Ghana, Nigeria and Kenya. Participants were classified as lean (BMI <25 kg/m²) or overweight/obese (BMI ≥25 kg/m²). Robust Poisson regression, adjusted for age, sex, education and treatment, assessed associations with retinopathy, chronic kidney disease, stroke, hypertension and 10-year cardiovascular disease risk. Cohort-specific estimates were pooled using random effects, followed by mediation analysis examining contributions of lifestyle and metabolic markers to observed differences.

RESULTS: Type 2 diabetes in Africans who are lean was characterised by lower beta cell function and low insulin levels. Compared with individuals who are overweight/obese, adults who are lean showed a higher prevalence of retinopathy (pooled prevalence ratio [pPR] 1.36 [95% CI 1.13, 1.63]) and stroke (pPR 1.41 [95% CI 1.01, 1.99]), but lower hypertension (pPR 0.77 [95% CI 0.71, 0.85]) and 10-year cardiovascular disease risk (pPR 0.85 [95% CI 0.74, 0.97]). Chronic kidney disease prevalence did not differ between groups. Body fat percentage accounted for most differences (up to 92%).

CONCLUSIONS/INTERPRETATION: Complication patterns in Africans with type 2 diabetes who are lean vs overweight/obese follow divergent paths. In Africa, where nearly 24 million people have type 2 diabetes, two-fifths of whom are lean, our findings add to growing evidence that lean type 2 diabetes may be a distinct phenotype, underscoring the urgent need for investigation into better-targeted management for this large, potentially mistreated, population.

PMID:42633598 | DOI:10.1007/s00125-026-06830-2

Neuromodulation. 2026 Jul 17:S1094-7159(26)01305-X. doi: 10.1016/j.neurom.2026.07.641. Online ahead of print.

ABSTRACT

BACKGROUND: Peripheral magnetic stimulation therapy (PMST) has emerged as a promising, noninvasive alternative to the traditional treatment approaches for urinary incontinence (UI). This systematic umbrella review aimed to synthesize the available secondary literature to provide a definitive, high-level overview of PMST’s efficacy, safety parameters, and clinical utility.

MATERIALS AND METHODS: A systematic overview was conducted following the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. An a priori protocol was registered via the International Prospective Register of Systematic Reviews (PROSPERO), and systematic literature screening was performed using Rayyan. The Joanna Briggs Institute critical appraisal checklist was utilized to evaluate the methodological quality of the included systematic reviews and meta-analyses. Primary study overlap across the portfolio was structurally mapped and mathematically quantified using the Corrected Covered Area (CCA) formula. The certainty of the synthesized evidence across key clinical end points was evaluated using the narrative GRADE framework. Data extraction was restricted strictly to the systematic review components.

RESULTS: Fifteen systematic reviews and meta-analyses were included. Citation matrix analysis revealed a Corrected Covered Area (CCA) of 3.64%, demonstrating a slight overlap and confirming that the synthesized secondary evidence base is non-redundant. Synthesized data revealed a consistent frequency-specific pattern across the included reviews, whereby higher-frequency protocols (35-50 Hz) were most commonly applied to pelvic floor muscle recruitment in stress urinary incontinence, whereas lower-frequency protocols (10-15 Hz) were more frequently used for urgency urinary incontinence and overactive bladder. However, these observations represent prevailing treatment approaches rather than a validated therapeutic paradigm. Relative to sham/placebo configurations, PMST yielded statistically and clinically significant improvements in objective leakage metrics (pad tests) and subjective symptom indices (ICIQ-SF, Health-Related Quality of Life). Safety data demonstrated a remarkable tolerability profile, with adverse events limited to mild, transient, and self-limiting symptoms (eg, local tingling, mild soreness, or increased stool frequency), with no severe complications reported. Methodological quality across the evidence base was highly polarized, with 25% of reviews scoring high and the remainder classified as moderate or low due to deficits in comprehensive database search strings or formal primary study risk-of-bias monitoring.

CONCLUSION: PMST appears to be a safe and potentially effective therapeutic option for the management of urinary incontinence and may be considered either as a standalone treatment or as an adjunct to conventional physical therapy. However, the interpretation and clinical application of these findings are limited by considerable heterogeneity in stimulation protocols, patient populations, and outcome measures; variable methodological quality among the included reviews; and the scarcity of long-term follow-up data exceeding six months.

PMID:42633592 | DOI:10.1016/j.neurom.2026.07.641

J Allergy Clin Immunol Pract. 2026 Feb;14(2):404-414.e1. doi: 10.1016/j.jaip.2025.10.015. Epub 2025 Oct 25.

ABSTRACT

BACKGROUND: Mucus plugs are common in severe eosinophilic asthma and contribute to airway obstruction. Interleukin (IL)-13 drives goblet cell hyperplasia and mucus overproduction, and IL-5 activates eosinophils, increasing mucus viscosity. Mepolizumab, an anti-IL-5 monoclonal antibody, reduces eosinophilic inflammation, but its effect on mucus plugs is unclear.

OBJECTIVE: To evaluate the effectiveness of mepolizumab in reducing mucus plugs and their association with biomarkers and clinical outcomes.

METHODS: This prospective study included 47 severe eosinophilic asthma patients treated with mepolizumab for 12 months. High-resolution computed tomography was used to quantify mucus plugs using the Mucus Plug Score (MPS, range 0-20). Demographic and clinical data were collected at baseline and after 12 months. Correlations between MPS and clinical variables were assessed. The most commonly used definitions of clinical remission were also evaluated.

RESULTS: Mepolizumab significantly reduced MPS from 4 (3-7) to 1 (0-2) (P < 0.0001) after 12 months of treatment. At baseline, patients with high MPS (≥4) had higher blood eosinophil counts and sputum eosinophils, more frequent exacerbations, and worse lung function. Reductions in MPS were significantly correlated with decreases in blood eosinophil counts (r = 0.40; P = .0488), sputum eosinophils (r = 0.58; P = .0376), and OCS dose (r = 0.38; P = .0372), and with increases in FEV₁% (r = -0.37; P = .0425). Clinical remission was more frequent in patients with lower MPS (0-3), although this difference was not statistically significant.

CONCLUSIONS: Mepolizumab effectively reduces mucus plug burden and is associated with improvements in inflammatory biomarkers and clinical outcomes. These results support mucus plugs as a promising imaging biomarker in severe eosinophilic asthma, warranting confirmation in larger, controlled studies.

PMID:42633588 | DOI:10.1016/j.jaip.2025.10.015

J Natl Cancer Inst. 2026 Aug 22:djag291. doi: 10.1093/jnci/djag291. Online ahead of print.

ABSTRACT

BACKGROUND: Synthetic control arms (SCAs) derived from historical trial data can complement randomized controlled trials (RCTs), particularly in oncology where feasibility, ethical, and cost constraints may limit conventional trial designs. However, their validity for overall survival (OS) remains uncertain. We evaluated the feasibility and limitations of constructing SCAs from the ARCAD metastatic colorectal cancer (mCRC) database across multiple treatment lines.

METHODS: Seven landmark RCTs representing first-, second-, and third-line settings were selected. External control arms were constructed from ARCAD individual patient-level data using propensity score matching based on key clinical and biological variables from a validated ARCAD prognostic score, with adjustment for geographic region and time era when needed. A prespecified two-step benchmarking framework assessed: (1) control-arm OS reproducibility and (2) virtual trial comparisons between matched synthetic controls and original RCT experimental arms. Agreement was evaluated using hazard ratios (HRs) and Z-tests.

RESULTS: A total of 28,022 patients met the inclusion criteria. ARCAD-derived SCAs were successfully constructed for all selected RCTs and closely reproduced control-arm OS. After matching, baseline characteristics were well balanced, with minimal differences between included and excluded patients. Virtual trials showed concordant treatment-effect estimates with the original RCTs, with a median absolute HR deviation of 0.05 and no significant differences by Z-tests (P>.05). Survival outcomes were consistently reproduced across treatment lines.

CONCLUSION: ARCAD-derived SCAs reliably reproduced control-arm OS and benchmark treatment-effect estimates from landmark RCTs in mCRC. Despite limitations related to residual confounding and missing data, this framework supports benchmarking, trial design, and exploratory analyses when conventional control arms are impractical.

PMID:42633557 | DOI:10.1093/jnci/djag291

Pak J Pharm Sci. 2026 Nov 1;39(11):3554-3565. doi: 10.36721/PJPS.2026.39.11.328.1.

ABSTRACT

BACKGROUND: Lung cancer is the most common pulmonary malignancy. WHO data show that its incidence and mortality are rising globally, severely threatening public health.

OBJECTIVES: This study aims to investigate the regulatory effect of Jolkinolide B (JB) on lung cancer A549 cells and to preliminarily explore the potential molecular mechanisms underlying its anti-lung cancer effects.

METHODS: In this study, A549 lung adenocarcinoma cells were used to investigate the anti-lung cancer effects of JB. CCK-8 and colony formation assays were performed to evaluate cell proliferation. Molecular docking and molecular dynamics simulation were applied to verify the binding between JB and JAK2, while Western blot was used to detect the expression of JAK2/STAT3 pathway-related proteins. Flow cytometry, immunofluorescence and Western blot were employed to explore the regulatory roles of JB in cell apoptosis and cycle. In addition, a nude mouse xenograft model was established and HE staining and immunohistochemistry were used to verify the in-vivo efficacy of JB. All data were statistically analyzed using GraphPad Prism and SPSS.

RESULTS: The results demonstrated that JB inhibited A549 cell proliferation in a dose‑dependent manner with an IC50 of 39.34 μM at 24 h. JB bound stably to JAK2 (PDB: 7RN6) with a binding free energy of -8.33 kcal/mol and suppressed the JAK2/STAT3 pathway. JB significantly promoted apoptosis and induced G1‑phase arrest via regulating P21, Cyclin D1, BAX, Caspase 3, PARP1 and Bcl‑2. In-vivo, JB reduced tumor growth in a dose‑dependent manner, induced tumor cell necrosis and downregulated p‑JAK2 and p‑STAT3 expression.

CONCLUSION: Jolkinolide B can significantly inhibit the proliferation of human lung adenocarcinoma A549 cells. Its mechanism of action is closely related to inducing cell cycle arrest and promoting cell apoptosis. The above effects may be partially achieved by inhibiting the JAK2/STAT3 pathway. In animal experiments, JB also significantly inhibits the growth of lung cancer transplanted tumors.

PMID:42633541 | DOI:10.36721/PJPS.2026.39.11.328.1

Pak J Pharm Sci. 2026 Nov 1;39(11):3535-3542. doi: 10.36721/PJPS.2026.39.11.326.1.

ABSTRACT

BACKGROUND: Chemotherapy-induced leukopenia is a common dose-limiting toxicity that compromises treatment continuity and increases the risk of infection. Current pharmacological interventions are often associated with adverse effects, highlighting the need for safe and effective supportive strategies. Guiqi crucian carp decoction (GQCCD), a traditional dietary therapy derived from the concept of medicine-food homology, has been used to replenish qi and nourish blood; however, its hematopoietic protective effects have not been systematically evaluated.

OBJECTIVES: This study aimed to investigate the hematopoietic and immunoprotective effects of GQCCD in a rat model of chemotherapy-induced leukopenia.

METHODS: A leukopenia model was established in rats using 5-fluorouracil (5-FU). Rats were divided into a blank control group, model group, positive control group (batyl alcohol) and GQCCD-treated group. Peripheral blood parameters, including white blood cell (WBC), neutrophil (NE UT), lymphocyte (LYMPH) and monocyte (MONO) counts, were measured at different time points. Thymus and spleen indices were calculated and histopathological examinations of bone marrow, spleen and thymus were performed.

RESULTS: 5-FU administration induced significant leukopenia, accompanied by reduced thymus and spleen indices and marked histopathological damage in immune organs and bone marrow. Compared with the model group, GQCCD treatment significantly increased WBC and NEUT counts and MONO percentage (P < 0.01), along with significant improvements in thymus and spleen indices (P < 0.01). Histopathological analysis revealed substantial restoration of bone marrow and immune organ structures. No statistically significant improvement in LYMPH counts was observed.

CONCLUSION: GQCCD effectively alleviated chemotherapy-induced leukopenia in rats by restoring peripheral blood parameters, improving immune organ indices and ameliorating bone marrow and immune organ damage. These findings support the potential of GQCCD as a complementary dietary therapy for managing chemotherapy-related myelosuppression.

PMID:42633540 | DOI:10.36721/PJPS.2026.39.11.326.1

Cancer Control. 2026 Jan-Dec;33:10732748261481960. doi: 10.1177/10732748261481960. Epub 2026 Aug 23.

ABSTRACT

IntroductionThe optimal choice between docetaxel and abiraterone in combination with androgen deprivation therapy (ADT) for metastatic hormone-sensitive prostate cancer (mHSPC) remains uncertain due to the lack of direct randomized trials. Real-world data, particularly from developing countries, are limited. This study aimed to compare the effectiveness of docetaxel versus abiraterone in combination with ADT and to identify prognostic factors associated with survival outcomes in a Vietnamese population.MethodsWe conducted a retrospective cohort study of patients with mHSPC treated at Vietnam National Cancer Hospital between January 2021 and December 2025. Eligible patients received first-line ADT combined with either docetaxel or abiraterone acetate. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards models were applied to evaluate prognostic factors.ResultsBaseline characteristics were generally comparable. Abiraterone was associated with a higher rate of deep prostate-specific antigen (PSA) response at 6 months (PSA≤0.2 ng/mL: 43.7% vs. 16.7%, p=0.002). After a median follow-up of 28.6 months, the median OS was 41.4 months in the docetaxel group and 44.6 months in the abiraterone group. Median PFS was 23.6 and 29.6 months, respectively, with no statistically significant differences between groups. In multivariable analysis, baseline PSA>100 ng/mL (HR 1.98, p=0.01, 95% CI: 1.15-3.42) and PSA>0.2 ng/mL at 6 months (HR 3.93, p<0.001, 95% CI: 1.82-8.49) were independent predictors of worse PFS. PSA>0.2 ng/mL at 6 months was also associated with inferior OS (HR 2.66, p=0.03, 95% CI: 1.09-6.47).ConclusionIn this real-world Vietnamese cohort, docetaxel and abiraterone combined with ADT provided comparable survival outcomes in mHSPC. Although abiraterone achieved deeper PSA responses, this did not translate into a survival advantage. Baseline PSA and 6-month PSA response were strong prognostic factors, underscoring the clinical value of PSA kinetics in risk stratification and treatment monitoring.

PMID:42633534 | DOI:10.1177/10732748261481960

Actas Esp Psiquiatr. 2026 Aug 15;54(4):1245-1256. doi: 10.62641/aep.v54i4.2093.

ABSTRACT

BACKGROUND: To investigate the potential causal association between sex hormones and depression, a twosample mendelian randomization (MR) analysis was conducted.

METHODS: Summary statistics from Genome-wide Association Study (GWAS) on sex hormones and depression were collected. Sex-specific instruments were used to analyze seven sex hormones, including progesterone (PROG) and bioavailable testosterone (BAT). The inverse variance weighted (IVW) method was employed as the primary analysis, and sensitivity analyses were conducted to assess the robustness of the findings.

RESULTS: The IVW analysis revealed genetically significant association between PROG and depression (odds ratio (OR): 0.95, 95% confidence interval (CI): 0.92-0.98, p = 0.002), which remained significant after Bonferroni correction (p < 0.0036). A nominally significant association was observed for BAT (OR: 0.90, 95% CI: 0.82-1.00, p = 0.049) and depression; however, this association did not survive Bonferroni correction. Upon stratification by gender, these associations were no longer significant (p > 0.05). Furthermore, no substantial associations were observed between depression and other sex hormones, including total testosterone (TT), estradiol (E2), follicle-stimulating hormone, prolactin, and luteinizing hormone (p > 0.05). Leave-one-out analyses and funnel plots (indicating balanced pleiotropy), confirmed the reliability of these findings, supporting the robustness of the results. Significant heterogeneity was observed in seven exposures: E2_Female, TT_Male, TT_Both, BAT_Both, BAT_Male, BAT_Female, and TT_Female. Additionally, Mendelian Randomization Pleiotropy Residual Sum and Outlier (MR-PRESSO) analysis identified outliers for BAT_Both, BAT_Female, E2_Female, TT_Both, and TT_Female; however, excluding these outliers did not alter the results.

CONCLUSIONS: This study indicates a potential causal association between genetically predicted PROG levels and a decreased risk of depression. While BAT also suggested a potential protective effect, this association was considered suggestive after multiple testing correction and requires further validation.

PMID:42633530 | DOI:10.62641/aep.v54i4.2093