Nevin Manimala

Clin Transl Oncol. 2026 May 12. doi: 10.1007/s12094-026-04359-9. Online ahead of print.

ABSTRACT

PURPOSE: Gastric cancer (GC) remains a major global health burden, with poor survival rates. HER2 is a key biomarker for targeted therapy, but discordance between primary tumors and metastases may impact treatment decisions. This meta-analysis evaluated the prevalence and clinical relevance of HER2 status differences between primary gastric cancers and metastatic lesions.

METHODS: A systematic search of PubMed, Embase, and Cochrane was conducted for studies assessing HER2 status in matched primary and metastatic gastric cancer samples. Pooled proportions and 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analyses by metastatic site were performed. Statistical analyses were conducted using R software, version 4.2.3.

RESULTS: This meta-analysis included 3,515 patients across 20 studies. The pooled proportion of HER2-positive expression in primary gastric tumors was 13% (95% CI: 12-15%; I² = 68.7%), while HER2-negative tumors accounted for 74% (95% CI: 72%-76%; I² = 94.9%). In metastatic sites, the overall pooled proportion of HER2-positive lesions was 18% (95% CI: 16%-20%; I² = 77.3%), with notable variation across anatomical locations: 38% in lung metastases, 31% in liver metastases, 19% in lymph nodes, and 7% in peritoneum. Conversely, HER2-negative metastases accounted for 82% overall (95% CI: 80%-84%; I² = 78.2%), with proportions of 93% in peritoneum, 81% lymph nodes, 69% in liver metastases, and 62% in lung.

CONCLUSIONS: Significant heterogeneity in HER2 expression between primary and metastatic gastric cancer underscores the need for reassessment of HER2 status in metastatic sites. Relying solely on primary tumor samples may lead to underestimation of HER2 positivity and suboptimal therapeutic decisions. Incorporating site-specific HER2 testing into clinical practice may enhance patient selection for HER2-targeted therapies and improve treatment outcomes.

PMID:42118480 | DOI:10.1007/s12094-026-04359-9

Clin Exp Optom. 2026 May 12:1-9. doi: 10.1080/08164622.2026.2669529. Online ahead of print.

ABSTRACT

CLINICAL RELEVANCE: Quantitative assessment of pupillary dynamics provides an objective measure of autonomic and retinal function, with potential utility in the clinical evaluation of ocular and neurological conditions.

BACKGROUND: Increasing myopia severity may alter pupillary mechanisms, and smartphone-based pupillometry provides a non-invasive method to quantify these changes. The purpose of this study was to investigate alterations in static and dynamic pupillary parameters among emmetropes, low, moderate, and high myopia groups using smartphone-based pupillometry.

METHODS: This comparative study included 160 participants (40 per group) aged 18-35 years. Pupillary dynamics were recorded with the Reflex Pro application under standardised illumination. Parameters analysed were latency, constriction velocity, maximum constriction speed, constriction amplitude, release amplitude, constriction time, and average pupil diameter. Intergroup differences were assessed using one-way ANOVA followed by Tukey’s post hoc analysis, with p < 0.05 considered statistically significant.

RESULTS: Latency was significantly prolonged with increasing severity of myopia, ranging from 0.25 ± 0.05 s in emmetropes to 0.36 ± 0.08 s in high myopes (p < 0.001). Constriction velocity and maximum constriction speed showed progressive reduction, with high myopes exhibiting the slowest dynamics (2.9 ± 0.3 mm/s and 3.1 ± 0.3 mm/s, respectively; p < 0.001). Constriction amplitude and release amplitude also declined significantly across groups (p < 0.001). Constriction time was prolonged in high myopes (0.74 ± 0.09 s) compared to emmetropes (0.65 ± 0.08 s, p = 0.01). Average pupil diameter showed a trend towards increase in high myopes (5.8 ± 0.6 mm) but did not reach overall statistical significance (p = 0.06). Post hoc analysis confirmed that differences between emmetropes and high myopes were consistently significant for most parameters (p < 0.001).

CONCLUSION: Pupillary dynamics vary with myopia severity, with smartphone-based pupillometry offering a potential non-invasive assessment tool, though causality requires longitudinal validation.

PMID:42117369 | DOI:10.1080/08164622.2026.2669529

Vet Rec. 2026 May 12. doi: 10.1002/vetr.70736. Online ahead of print.

ABSTRACT

BACKGROUND: Floppy rabbit syndrome (FRS) is known as an idiopathic neurological condition with a peracute onset of tetraparesis. While there are several anecdotal reports mentioning this phenomenon, scientific literature on this subject is scarce. The aim of this study was to assess clinical and clinicopathological data as well as the outcome of patients with FRS.

METHODS: This retrospective study included pet rabbits that presented with a peracute progressive symmetric lower motor neuron tetraparesis characterised by generalised weakness in all four limbs and decreased muscle tone and spinal reflexes. History, clinical signs, laboratory results, treatment and outcome were analysed.

RESULTS: The data revealed nine rabbits with non-ambulatory tetraparesis resembling FRS. Otherwise, the rabbits presented clinically unremarkably. All the animals showed significantly increased serum creatine kinase (CK) concentrations. Eight out of nine rabbits fully recovered within a short period.

LIMITATIONS: The study is limited by the small number of patients and the absence of muscle biopsy results and electromyography.

CONCLUSION: FRS can be clearly diagnosed due to its typical consistent clinical presentation and neurological examination. Clinical pathology, including the determination of serum CK concentrations, may aid in differentiating FRS from other diseases. FRS is typically self-limiting idiopathic neuromuscular disease that does not require specific treatment; therefore, euthanasia should be avoided.

PMID:42117365 | DOI:10.1002/vetr.70736

Vet Rec. 2026 May 12. doi: 10.1002/vetr.70741. Online ahead of print.

ABSTRACT

BACKGROUND: Large language models (LLMs) are emerging as decision-support tools in human medicine; however, their evaluation in veterinary anaesthesiology remains limited.

METHODS: We retrospectively analysed 225 anonymised feline and canine cases (American Society of Anaesthesiologists [ASA] classifications 1‒5) from Atatürk University Veterinary Hospital. ChatGPT-4o, ChatGPT-5 and Gemini 2.5 Pro independently assigned ASA classifications and generated anaesthetic protocols using standardised prompts. Protocol adequacy was evaluated for all cases, regardless of ASA classification agreement, by two experienced veterinary anaesthesiologists using a four-point scale. Statistical analyses included Friedman and Bonferroni-adjusted Wilcoxon tests, effect sizes and inter-panelist reliability (assessed by quadratic-weighted Cohen’s kappa and intraclass correlation coefficient).

RESULTS: ChatGPT-5 achieved the highest ASA classification accuracy (53.3%), followed by ChatGPT-4o (46.7%) and Gemini 2.5 Pro (30.7%). The performance was strongest for ASA 3‒5, whereas ASA 1 cases were frequently misclassified, mainly due to ASA overestimation. ChatGPT-5 generated the most clinically sufficient anaesthetic protocols, outperforming the other models.

LIMITATIONS: The retrospective, single-centre design and inclusion of only feline and canine cases may limit generalisability.

CONCLUSIONS: LLMs can generate clinically relevant ASA classifications and anaesthetic protocols in veterinary anaesthesiology, although performance varies across models. However, expert oversight remains essential.

PMID:42117364 | DOI:10.1002/vetr.70741

Curr Cardiol Rev. 2026;22(3):e1573403X351298. doi: 10.2174/011573403X351298250717031928.

ABSTRACT

INTRODUCTION: There are strong guidelines regarding the importance of SGLT-2 inhibitors (SGLT2i) in reducing mortality in patients with heart failure with reduced ejection (HFrEF). However, the role of SGLT2i in the management of patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) remains ambiguous.

METHODS: A systematic review and meta-analysis of SGLT2i randomized controlled trials (RCTs) in HFpEF and HFmrEF, with and without diabetes was conducted (Prospero ID – CRD42023464479). Databases including Clinicaltrials.gov, PubMed, Biomed Central, Scopus, and Science Direct were searched from 2018 to 2024. Hospitalization due to heart failure (HFH) with HFpEF and HFmrEF was the primary outcome analyzed, followed by a subgroup analysis of HFH in HFpEF only. Secondary outcomes analyzed included cardiovascular (CV) death, all-cause mortality, and serious adverse effects.

RESULTS: In seven RCTs involving 31,057 participants, meta-analysis using random effects models showed that SGLT2i treated patients had a statistically significant reduction in HFH risk (OR=0.74, p<0.00001) compared to placebo or standard of care (SOC). A subgroup analysis, in HFpEF only patients, also showed a statistically significant reduction (OR=0.72, p<0.0001) in HFH odds. Statistical analysis of secondary outcomes showed a statistically non-significant difference in CV death risk (OR=0.92, p=0.13), all-cause mortality (OR=0.94, p=0.13), and any serious adverse events (OR=0.92, p=0.10).

DISCUSSION: This meta-analysis demonstrates that SGLT2i significantly reduce the risk of heart failure hospitalization in patients with preserved and mildly reduced ejection fraction, regardless of diabetes status. While reductions in cardiovascular and all-cause mortality, as well as serious adverse events, were observed, these did not reach statistical significance. These findings align with emerging evidence suggesting a broader cardioprotective role for SGLT2i across the heart failure spectrum, although further studies are needed to clarify their mortality benefit and long-term safety in HFpEF and HFmrEF populations.

CONCLUSION: This meta-analysis found a significant reduction in HFH with the use of SGLT2i in patients with HFpEF and HFmrEF. Secondarily, there was a statistically non-significant reduction in allcause mortality, CV death risk, and serious adverse events with the use of SGLT2i.

PMID:42117353 | DOI:10.2174/011573403X351298250717031928

J Pharm Pract. 2026 May 12:8971900261450730. doi: 10.1177/08971900261450730. Online ahead of print.

ABSTRACT

Pharmacists have been shown to improve HbA1c reduction among medically underserved Type 2 diabetes mellitus (T2DM) patients when compared to standard of care. However, there is limited literature exploring the difference in prescribing patterns between these 2 cohorts. This study evaluated the impact of pharmacy-driven T2DM management utilizing a collaborative practice agreement (CPA) compared to usual care at a family medicine clinic by comparing HbA1c reduction and prescribing patterns. This single-center, retrospective chart review identified patients with an HbA1c >9% within a 1-year period. Patients had to be at least 18 years of age, have a diagnosis of T2DM, and have a repeat HbA1c measurement documented within 6 months of baseline HbA1c. In total, 307 charts were reviewed with 126 patients included (provider, n = 70; pharmacist, n = 56). A significantly greater reduction in HbA1c was found in the pharmacist group (-2.61% ± 2.22% vs -1.87% ± 1.97%, P = 0.03), and the pharmacist group achieved statistically significantly higher percentages of patients achieving HbA1c <7% (23% vs 11%, P = 0.04) and <8% (50% vs 33%, P = 0.03). Prescribing of basal insulin was significantly higher in the pharmacist group (55% vs 33%, P = 0.011), while prescribing of other medication classes was similar between cohorts. Pharmacist-driven management of T2DM in a medically underserved population resulted in greater HbA1c reduction and more basal insulin utilization compared to the provider-managed group. Low usage of GLP-1 agonists and SGLT2 inhibitors was noted in both groups.

PMID:42117347 | DOI:10.1177/08971900261450730

Mult Scler. 2026 May 12:13524585261444243. doi: 10.1177/13524585261444243. Online ahead of print.

ABSTRACT

BACKGROUND: People with multiple sclerosis (PwMS) have an elevated risk of macrovascular disease that may be underestimated by vascular risk calculators (VRCs) validated in the general population.

OBJECTIVES: This study evaluated, recalibrated and externally validated five commonly used VRCs for PwMS using population-based data from England, 1987-2023.

METHODS: PwMS and matched controls were identified from Clinical Practice and Research Datalink (CPRD) GOLD (calibration) and CPRD Aurum (validation). Exposure variables included multiple sclerosis (MS) status and risk factors as defined in Atherosclerotic Cardiovascular Disease, Framingham Risk Score (FRS), FRS-BMI (body mass index), QRESEARCH risk estimator version 3 score and Systematic Coronary Risk Evaluation version 2 score (SCORE2). Model performance was assessed using Somers’ D statistic, area under the receiver operating characteristic (ROC) curve and Hosmer-Lemeshow chi-square test. VRCs with ROC < 0.70 in PwMS were recalibrated using Cox regression, incorporating MS status. Ten-fold cross-validation was used to estimate Somers’ D.

RESULTS: Calibration: 9411 PwMS and 57,805 controls; validation: 45,934 PwMS and 278,452 controls. Discrimination declined with standard thresholds (e.g. SCORE2 sensitivity in PwMS, 30.0%). Only FRS-BMI retained all significant predictors and was successfully recalibrated, improving discrimination (Somers’ D = 0.815 vs. 0.792; Δ = 0.023) and showing good calibration. External validation showed modest gain (Somers’ D = 0.716; Δ = 0.003).

CONCLUSION: These findings underscore the limitations of general-population VRCs in PwMS and support the development of MS-specific vascular risk models.

PMID:42117333 | DOI:10.1177/13524585261444243

J Rural Health. 2026 Mar;42(2):e70164. doi: 10.1111/jrh.70164.

ABSTRACT

PURPOSE: This study aims to examine rural-urban differences in the prevalence of three measures of one domain of social determinants of heath, economic security, in a national sample of children.

METHODS: This was a cross-sectional study (2022-2023) of the National Survey of Children’s Health. Primary exposures included rurality and child and caregiver characteristics. Three economic stability outcomes were whether a child experienced housing instability, food insecurity, and/or income inadequacy (having a hard time getting by on family income). We used bivariate analyses and multivariable regressions analyses to examine the association between rurality and measures of economic stability. All analyses were weighted with survey sampling to generate nationally representative estimates.

FINDINGS: In the weighted multivariable regression analysis, adjusting for child and caregiver characteristics, rural children had higher odds of housing instability (aOR 1.20; 95% CI 1.07-1.34), food insecurity (aOR 1.47; 95% CI 1.22-1.78), and income inadequacy (aOR 1.32; 95% CI 1.18-1.48), compared to urban children.

CONCLUSIONS: Rural children and their families are experiencing everyday challenges in housing, food access, and the ability to get by on their income, which are all shown to have ramifications on their health. Child advocates, policymakers, and program developers must consider these factors when developing programs and policies for families residing in rural America.

PMID:42117331 | DOI:10.1111/jrh.70164

J Rural Health. 2026 Mar;42(2):e70163. doi: 10.1111/jrh.70163.

ABSTRACT

PURPOSE: Efforts to generalize findings from the Environmental influences on Child Health Outcomes (ECHO) Cohort across rural and urban areas are challenged by limitations in both sample composition and the classification schemes used to define place. We evaluated how rural-urban stratification affects the interpretation and generalizability of preterm birth (PTB) prevalence proportions in the ECHO Cohort compared to national benchmarks.

METHODS: We used a population data science approach to compare bootstrap estimates of PTB prevalence in ECHO (2017-2019, 2020-2022) to county-level prevalence from the National Center for Health Statistics, stratified by rural-urban classification (RUCC, UIC, NCHS), race/ethnicity, education, and income. We applied post-stratification weights and conducted sensitivity analyses.

FINDINGS: Overall PTB prevalence in ECHO was statistically similar to that in US live births. Estimates varied by rural-urban classification scheme but showed no consistent directional difference. Stratifying by race and education revealed variability in PTB differences and gaps in subgroup representation within the analytic sample. Post-stratification increased PTB estimates slightly and stabilized rural estimates. Two predominantly rural cohort sites strongly influenced rural means; excluding one reversed the direction of rural-urban difference while excluding the other increased it. Supplemental analyses showed regional variability in PTB prevalence and suggested that living above 130% of the federal poverty level may be protective.

CONCLUSIONS: Rural-urban stratification alone, without accounting for the context of rural places, limits generalizability and may obscure differences between samples drawn from large cohort studies and the broader population. Context-aware stratification may improve validity and equity in population health research.

PMID:42117321 | DOI:10.1111/jrh.70163

Int Wound J. 2026 May;23(5):e70935. doi: 10.1111/iwj.70935.

ABSTRACT

Venous leg ulcers (VLUs) are common, difficult to heal, and prone to recurrence. Malnutrition and impaired nitric-oxide-dependent microcirculation may contribute to recalcitrance. Arginine-enriched oral nutritional supplements (ONS) improve healing in other wound types, but data in VLUs is limited. We conducted a prospective single-arm study evaluating arginine-enriched ONS (L-arginine 4.5 g, vitamins C, E) as an adjunct to evidence-based standard care (compression, debridement, infection control and venotonic/hemorheologic agents). Adults with recalcitrant VLUs received daily ONS for 8 weeks. Primary outcome was change in ulcer area; secondary outcomes included complete healing, adverse events and exploratory correlations. Ten patients with chronic VLUs were enrolled. Median prior duration of conventional therapy before ONS was substantial at 32.5 months. From baseline to week 8, mean ulcer area decreased significantly from 30.5 to 21.4 cm² (p = 0.024), representing a mean reduction of 32.8% (p = 0.012). Eight patients had reductions in ulcer size, with one patient achieving complete epithelisation. Two patients showed minimal improvement. There were no gastrointestinal side effects reported. Arginine-enriched ONS, when added to compression-centred multimodal care, was associated with clinically and statistically significant reductions in VLU area. Findings support nutritional optimisation-including arginine-enriched ONS-as a pragmatic adjunct for recalcitrant VLUs; larger randomised controlled trials are warranted. Clinical relevance: In malnourished or slow-to-heal VLU patients, a short course of arginine-enriched ONS may accelerate closure and can be delivered alongside routine outpatient wound care and compression.

PMID:42117292 | DOI:10.1111/iwj.70935