Category: Nevin Manimala

J Hazard Mater. 2026 Jul 16;515:143013. doi: 10.1016/j.jhazmat.2026.143013. Online ahead of print.

ABSTRACT

Although pesticide exposure occurs through multiple pathways and has been linked to diverse health outcomes, the overall evidence remains unclear. We systematically searched PubMed/MEDLINE, Embase, CINAHL, and Google Scholar up to November 20, 2025, for meta-analyses examining pesticide exposure and adverse health outcomes. We recalculated pooled estimates using random-effects models and converted all effect metrics to equivalent odds ratios with 95% confidence intervals. The quality of included reviews was assessed using AMSTAR 2, and the credibility of evidence was graded using predefined criteria (Class I to IV). A total of 53 meta-analyses covering 235 associations were included. Among the 77 main associations, 48.1% achieved statistical significance, of which 51.4% were supported by highly suggestive or suggestive evidence. Significant associations with pesticide exposure were observed across several health domains, particularly oncological, metabolic, neurological, and respiratory outcomes, with additional signals emerging in subgroup analyses. Particularly, exposures to organochlorine pesticides had increased odds of non-Hodgkin lymphoma. Exposure to dichlorodiphenyldichloroethylenes was associated with diabetes mellitus and non-Hodgkin lymphoma, while exposure to organochlorine insecticides was associated with hypothyroidism. Pesticide exposure was associated with childhood lower respiratory infections among respiratory outcomes. These findings identify priorities for prevention and highlight the need for better exposure assessment.

PMID:42485730 | DOI:10.1016/j.jhazmat.2026.143013

ESMO Open. 2026 Jul 22;11(8):108335. doi: 10.1016/j.esmoop.2026.108335. Online ahead of print.

ABSTRACT

BACKGROUND: Currently, three cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are approved in combination with endocrine therapy (ET) as first-line treatment of patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). The impact of homologous recombination repair (HRR) pathogenic variants (PV) on outcomes with first-line CDK4/6i plus ET in HR-positive/HER2-negative MBC remains uncertain.

PATIENTS AND METHODS: We conducted a multicenter, real-world, case-control study including 233 patients with HR-positive/HER2-negative MBC treated with first-line CDK4/6i and ET. Among them, 116 presented HRR PVs and 117 were matched controls with negative germline testing. The primary objective was to compare progression-free survival (PFS) and overall survival among germline-BRCA2 PV carriers, other HRR PV carriers, and controls. To minimize baseline differences in prognostic factors between PV carriers and controls, inverse probability of treatment weighting was applied. Molecular analyses in pre-CDK4/6i samples among patients with BRCA2 PV were carried out, including RAD51-foci, PAM50 intrinsic subtype, and RB1 loss of heterozygosity (LOH).

RESULTS: Among the included 233 patients, median age at diagnosis was 45 years (interquartile range 39-56) and 33% had de novo metastatic disease. Primary resistance to adjuvant ET was present in 10% and secondary resistance in 27%. After a median follow-up of 44 months, patients with germline-BRCA2 PVs (n = 67) had significantly shorter PFS [11 versus 27 months; adjusted hazard ratio (aHR) 2.73, 95% confidence interval (CI) 1.65-4.51, P < 0.001] compared with controls. Among patients with endocrine-sensitive disease, germline BRCA2 PV carriers had markedly shorter PFS (median PFS 12 versus 39 months; aHR 4.04; 95% CI 1.82-8.98, P < 0.001). Exploratory analyses revealed RB1 LOH before CDK4/6i-treatment in most evaluable BRCA2 tumors.

CONCLUSIONS: BRCA2 PVs were independently associated with poorer outcomes to first-line CDK4/6i plus ET in HR-positive/HER2-negative MBC compared with controls, especially relevant among patients with endocrine-sensitive disease. These findings suggest that patients with a germline PV in BRCA2 may require alternative first-line strategies.

PMID:42485699 | DOI:10.1016/j.esmoop.2026.108335

Cancer Treat Res Commun. 2026 Jul 22;48:101326. doi: 10.1016/j.ctarc.2026.101326. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited durable treatment options despite evolving multimodal and systemic strategies. Systemic inflammation has emerged as a clinically relevant determinant of outcomes in several cancers. The systemic immune-inflammation index (SII; platelet count x neutrophil count / lymphocyte count) integrates key circulating immune cell populations and may serve as an accessible prognostic biomarker in PDAC.

METHODS: A systematic search of PubMed was performed for studies published up to 11 April 2025. Eligible full-text English studies reported hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) according to SII (typically high versus low SII, defined by a study-specific cutoff). Pooled HRs were calculated using an inverse-variance random-effects model. Heterogeneity was assessed using Cochran’s Q and the I² statistic. Small-study effects were evaluated by funnel plot inspection and Egger’s regression test.

RESULTS: Seventeen studies (18 datasets) comprising 4218 patients were included. Elevated SII was associated with worse OS (pooled HR 1.58, 95% CI 1.19 – 2.08; p < 0.01). Between-study heterogeneity was substantial (I² = 89.9%). Funnel plot inspection did not suggest major asymmetry, and Egger’s test did not provide statistical evidence of small-study effects (p = 0.072).

CONCLUSIONS: Elevated SII is associated with poorer overall survival and represents a practical prognostic biomarker derived from routine laboratory testing. Considerable heterogeneity across studies-likely driven by differences in case mix, treatment context, and SII cutoff definitions-underscores the need for standardized thresholds and prospective, harmonized validation studies.

PMID:42485687 | DOI:10.1016/j.ctarc.2026.101326

BJS Open. 2026 Jul 3;10(4):zrag095. doi: 10.1093/bjsopen/zrag095.

ABSTRACT

BACKGROUND: Postoperative hypoparathyroidism is the most common complication after total thyroidectomy, and is associated with impaired quality of life and increased long-term healthcare use. Indocyanine green fluorescence imaging enables real-time intraoperative assessment of parathyroid perfusion, potentially improving gland preservation. However, its cost-effectiveness in routine surgical practice has not been formally evaluated.

METHODS: A model-based cost-effectiveness analysis was conducted comparing angiography-guided thyroidectomy with conventional thyroidectomy from the perspective of the Spanish National Health System. A state-transition Markov model simulated long-term outcomes for adults undergoing thyroidectomy, incorporating the incidence of transient and permanent hypoparathyroidism, health-related quality-adjusted life-years, and direct medical costs. The model used contemporary surgical data, included a 35-year time horizon, and discounted costs and effects at 3.5% annually. Probabilistic and deterministic sensitivity analyses were used to assess parameter and structural uncertainty. Cost-effectiveness was judged at a willingness-to-pay threshold of €30 000 per quality-adjusted life-year.

RESULTS: Angiography-guided thyroidectomy was associated with lower lifetime healthcare costs (€563.7 million versus €613.2 million) and greater health benefits (310 997 versus 299 107 quality-adjusted life-years), yielding a gain of 11 889 quality-adjusted life-years and €49.5 million in cost savings. Angiography-guided thyroidectomy dominated conventional thyroidectomy in all sensitivity analyses, with an incremental net monetary benefit of €406.2 million (95% uncertainty interval €381.7 million to €431.5 million). Scenario and joint probabilistic analyses confirmed robustness under alternative utility values and surgical outcomes.

CONCLUSION: Angiography-guided thyroidectomy may be a cost-saving innovation within publicly funded healthcare systems by reducing the incidence and chronic burden of postoperative hypoparathyroidism. These findings support broader adoption of fluorescence-guided surgery and underscore the need for real-world implementation studies to validate cost-effectiveness, and inform training and procurement strategies.

PMID:42485666 | DOI:10.1093/bjsopen/zrag095

Arthritis Care Res (Hoboken). 2026 Jul 22. doi: 10.1002/acr.80121. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate whether extending the American College of Rheumatology (ACR)-recommended monitoring interval for complete blood count and liver function tests in patients receiving methotrexate (MTX) affects timely detection of medication-related toxicity.

METHODS: We conducted an observational cohort analysis of 14,199 laboratory encounters from 2,439 patients receiving MTX with at least two measurements of alanine aminotransferase (ALT), aspartate aminotransferase (AST), white blood cell (WBC) count, hematocrit (HCT), mean corpuscular volume (MCV), and/or platelet (PLT) count. Fibrosis-4 (FIB-4) scores were calculated when possible. Changes between consecutive measurements were plotted against time between encounters. Monitoring intervals of 3 months (45-135 days) and 6 months (135-225 days) were compared. After propensity score matching, we assessed incident clinically relevant abnormalities.

RESULTS: Testing frequency showed no meaningful correlation with changes in ALT, AST, WBC, HCT, MCV, PLT, or FIB-4 (all R² < 0.01). Mean laboratory changes did not differ meaningfully between monitoring intervals. Patients monitored every 135-225 days were equally or less likely to develop incident abnormal results than those monitored every 45-135 days; most odds ratios were not statistically significant (p > 0.05). Patients in the 6-month group were less likely to develop ALT >1×ULN (OR 0.72 [0.52-0.99]) or MCV >100 fL (OR 0.67 [0.46-0.96]).

CONCLUSION: Extending routine MTX monitoring from every 3 months to every 6 months was not associated with more severe abnormalities or delayed detection of toxicity, suggesting quarterly testing may be more frequent than necessary and could be reconsidered to reduce cost and patient burden.

PMID:42485655 | DOI:10.1002/acr.80121

J Vet Intern Med. 2026 Jul 1;40(4):aalag139. doi: 10.1093/jvimsj/aalag139.

ABSTRACT

BACKGROUND: Middle ear abnormalities are frequently observed in brachycephalic dogs due to their anatomical variation, and the prevalence of these abnormalities may be influenced by modern breed popularity.

HYPOTHESIS/OBJECTIVES: We hypothesized that 10% of dogs with signs of neurologic disease will have incidental otitis media (OM) and that brachycephalic breeds will have a higher occurrence of OM.

ANIMALS: Three hundred eighty client-owned dogs that underwent magnetic resonance imaging (MRI) of the head for any signs of neurologic disease.

METHODS: Retrospective, single-institution study. Prevalence of any kind of otitis and association with dog clinical signs were analyzed using standard multinomial formulas and Fisher’s exact test. Signalment variables with P-values less than .1 but with no zero counts on bivariable analysis were included in a multivariable logistic regression model. Statistical significance was set to P < .05.

RESULTS: Of the dogs in this study, 60 (15.7%) had otitis of any kind. Among these, 15 (3.9%) were diagnosed with otitis of any kind as the primary cause of their clinical signs, all of which were affected by OM and all but one had otitis interna (OI). Forty-five (45/380, 11.8%) were classified with incidental otitis of any kind. The most common form of otitis was OM in 54 dogs (54/380, 14.2%). French Bulldogs were the most common breed reported (32/380, 8.4%) and 18 (56%) had evidence of 1 or more types of otitis: 5 causative and 13 incidental.

CONCLUSION AND CLINICAL IMPORTANCE: Otitis media is commonly an incidental finding in dogs undergoing MRI of the head, especially in brachycephalic breeds. French Bulldogs are more frequently affected. These findings can help guide diagnostic and treatment approaches for dogs with neurologic disease.

PMID:42485624 | DOI:10.1093/jvimsj/aalag139

Hum Vaccin Immunother. 2026 Dec;22(1):2701546. doi: 10.1080/21645515.2026.2701546. Epub 2026 Jul 22.

ABSTRACT

A systematic literature review was conducted to build a comprehensive evidence base of qualitative/quantitative studies to identify barriers and enablers influencing maternal immunization (MI). Searches of seven databases on 20/10/2023 and 26/10/2023 yielded 87,367 records. Two reviewers performed full-text screening of 484 records. English-language articles from countries that had national recommendations for pertussis-containing maternal vaccines and reported on maternal vaccine acceptance, trust, and hesitancy were eligible. Overall, 184 studies were included. Barriers involving individual and group influences like lack of knowledge and reduced awareness of MI, pre-existing anti-vaccination beliefs and attitudes, and perceived concerns about vaccine safety and efficacy were the most prominent. Proactive communication and recommendations from healthcare professionals and public health authorities were major enablers, alongside trusting the information provided by healthcare professionals. Our results show that vaccine hesitancy is a complex phenomenon. Addressing both practical and perceptual barriers to MI might increase vaccination coverage among pregnant individuals.

PMID:42485609 | DOI:10.1080/21645515.2026.2701546

JCO Glob Oncol. 2026 Jul;12(7):e2500254. doi: 10.1200/GO-25-00254. Epub 2026 Jul 22.

ABSTRACT

PURPOSE: To assess willingness of patients with cancer to participate in observational studies (OBS) and clinical trials (CT) and to examine the factors influencing their decision to join CT.

METHODS: A cross-sectional study using a systematic sampling strategy was conducted from December 2023 to June 2024. Data were collected directly from patients and their medical charts. Logistic regression was performed to identify significant predictors of patients’ willingness to participate in CT.

RESULTS: A total of 367 patients participated, 58.9% were females, and 59.8% had stage IV disease. Most participants (81%) had a performance status (PS) of 0-1, with only 1.9% having prior experience with a CT and 9% with OBS. Willingness to join OBS was higher than willingness to join CT (64% v 31.6%, P < .001). Key barriers included fear of side effects (61.6%), lack of information (46.3%), and concerns about the investigational product (41.6%). Motivators were having their treating physician as the principal investigator (42.5%) and prior human testing of the product (40.6%). Patients who underwent surgery or believed that their physical or psychological condition is unsuitable for trials were less likely to participate (P < .05, odds ratio [OR], 0.30, 0.38, 0.37, respectively). Patients with a friend or relative who had joined a trial were more willing to participate (P < .05, OR, 3.48).

CONCLUSION: The results highlight a low level of willingness to participate in CT. Some barriers could be avoided during the study design phase. Discrepancies between patients’ self-assessed PS and physicians’ evaluations may lower the enrollment rates. Encouraging patients who have participated in CTs to share their experiences with the family and friends could significantly improve the community’s willingness to join CT.

PMID:42485596 | DOI:10.1200/GO-25-00254

JCO Glob Oncol. 2026 Jul;12(7):e2600203. doi: 10.1200/GO-26-00203. Epub 2026 Jul 22.

ABSTRACT

PURPOSE: Lung cancer remains the leading cause of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) have become the standard of care for stage IV non-small cell lung cancer (NSCLC). In 2021, Lebanon experienced a severe economic collapse that resulted in major shortages of immunotherapy and treatment interruptions. The aim of this study was to explore the potential impact of immunotherapy shortage on progression-free survival (PFS).

METHODS: This retrospective multicenter study included patients with newly diagnosed stage IV NSCLC treated between January 2019 and December 2020 (control group) and between October 2021 and December 2022 (crisis group). The primary end point was PFS, defined from treatment initiation to progression according to RECIST 1.1 criteria or death. Kaplan-Meier survival curves were generated, and differences were assessed using log-rank test.

RESULTS: A total of 500 medical records were reviewed; 158 eligible patients were included (73 control, 85 crisis). The total cohort included 60.8% men with a mean age of 69.7 years. Among immunotherapy recipients, 44.0% received full-dose therapy (dose density ratio = 1.0), 41.4% received 50%-99% of standard dose (dose density ratio = 0.50-0.99), and 14.7% received <50% (dose density ratio = <0.50). The median PFS was 6.33, 12.86, and 10.23 months, respectively; no statistically significant difference was observed (P = .132).

CONCLUSION: Despite a statistically significant reduction in immunotherapy dose density during the economic crisis, no statistically significant difference in PFS was detected between the precrisis and crisis groups. These findings suggest that reduced immunotherapy dosing may not be associated with inferior short-term survival outcomes in stage IV NSCLC, although the study was not designed or powered to establish equivalence.

PMID:42485593 | DOI:10.1200/GO-26-00203

JCO Oncol Pract. 2026 Jul 22:OP2501431. doi: 10.1200/OP-25-01431. Online ahead of print.

ABSTRACT

PURPOSE: Adherence to operative standards and thorough documentation of surgical technique are critical, particularly in multidisciplinary clinical trials. We sought to evaluate variability in the performance and documentation of oncologically relevant aspects of technical surgery among patients enrolled in Alliance A021501, a phase 2 National Clinical Trials Network randomized clinical trial of neoadjuvant therapy for borderline resectable pancreatic adenocarcinoma.

METHODS: We reviewed the primary operative and pathology reports of all enrolled patients who underwent complete pancreatic resection. Operative techniques and pathologic end points with potential to influence recurrence and survival were evaluated.

RESULTS: Fifty-one of 126 study participants (40.5%) underwent complete pancreatectomy. The extent of lymphadenectomy was documented in 36 (70.6%) operative reports, and 5 (9.8%) reports outlined the specific lymph node stations removed. Periadventitial dissection of the superior mesenteric artery was described in 25 of 50 (50.0%) operative reports. Immediate histopathologic analysis of the hepatic duct and pancreatic parenchyma margins was documented in 29 of 50 (58.0%) and 32 of 49 (65.3%) reports, respectively, and presence or absence of residual disease following resection was documented in 9 of 51 (17.6%) reports. Specimen orientation was documented in 19 of 51 (37.3%) pathology reports, and 30 of 49 (61.2%) pathology reports stated the distance between the tumor and final SMA margin.

CONCLUSION: Even in this rigorously controlled, multicenter, randomized pancreatic cancer clinical trial, performance of key elements of technical surgery was inconsistent, and documentation was incomplete. Standardization of technique and documentation in clinical trials and within clinical practice should be addressed to improve quality assurance and trial interpretability.

PMID:42485590 | DOI:10.1200/OP-25-01431