Nevin Manimala

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

J Proteome Res. 2026 May 12. doi: 10.1021/acs.jproteome.5c00852. Online ahead of print.

ABSTRACT

The transcription factor SOX10 is a central regulator of melanoma, influencing tumor initiation, progression, phenotypic plasticity, and therapeutic resistance, yet the protein-protein interactions underlying its function remain poorly defined. To address this, we conducted the first dedicated, comprehensive mapping of the human SOX10 (hSOX10) proximal protein interactome using miniTurbo (mT) proximity-dependent biotinylation coupled with mass spectrometry in A375 melanoma cells. Stable lines expressing N- or C-terminal mT-tagged hSOX10 fusion proteins at near-endogenous levels enabled the unbiased capture of proximal proteins in a native cellular context, identifying 847 melanoma-enriched candidate hSOX10 interactors. Stringent statistical filtering, contaminant frequency profiling, and subcellular localization context refined this to 180 high-confidence candidates, including known hSOX10 partners and previously unidentified candidates. Integration of orthogonal biological relevance criteria (functional enrichment and network context, transcriptomic coexpression with hSOX10, and genomic co-occurrence in melanoma) further refined the dataset to 124 biologically relevant candidates enriched for transcriptional regulators, cofactors, chromatin-modifying complexes, and associated pathways. These proteins were stratified using an evidence-based prioritization framework incorporating transcriptomic, genomic, and chromatin-based context without additional exclusion. Collectively, this work provides a high-confidence resource for the hSOX10 proximal protein interactome in melanoma and a framework for generating testable hypotheses regarding hSOX10-associated regulatory networks, melanoma biology, and therapeutic vulnerabilities.

PMID:42117278 | DOI:10.1021/acs.jproteome.5c00852

Folia Morphol (Warsz). 2026;85:e01726086. doi: 10.5603/fm.111746.

ABSTRACT

BACKGROUND: Understanding anatomical variation in the sacral hiatus (SH) is important for improving the safety and technical success of caudal epidural block (CEB), particularly by reducing the risk of inadvertent dural puncture. However, data linking external sacral landmarks to internal volumetric capacity remain limited, especially in Southeast Asian skeletal populations. This study evaluated the relationships between external SH-related surface parameters and internal volumetric measures, particularly half-cone and caudal space volumes, in Thai dry sacra from Northeastern Thailand.

MATERIALS AND METHODS: Forty-five Thai dry sacra were analyzed using 20 parameters, including SH dimensions (SH1-SH4), external sacral surface landmarks (ES5-ES20), and volumetric measurements. Associations among SH parameters, ES parameters, and volumetric measures were assessed using Pearson correlation analysis. Intra- and inter-rater reliability were also evaluated.

RESULTS: The most prevalent SH morphologies were the inverted-U and irregular shapes, each accounting for 17.78% of specimens. The hiatal apex was most commonly located at the S4 vertebral level (64.44%), followed by S3 (26.67%). The mean SH length was 22.02 ± 9.59 mm. No statistically significant relationship was identified between SH morphology and either internal volumetric parameter. In contrast, several external sacral surface parameters demonstrated moderate-to-strong positive correlations with volumetric capacity.

CONCLUSIONS: SH morphology was not associated with internal volumetric capacity, whereas the external sacral surface framework appeared to be more informative than the hiatus aperture itself. These findings suggest that selected posterior sacral surface dimensions may provide anatomically relevant indicators of internal capacity in osteological assessment related to CEB. Further imaging-based and clinical studies are needed to validate these findings.

PMID:42117261 | DOI:10.5603/fm.111746

Pediatr Blood Cancer. 2026 May 12:e70390. doi: 10.1002/1545-5017.70390. Online ahead of print.

ABSTRACT

BACKGROUND: Osteosarcoma (OS) and Ewing sarcoma (EWS) are the most common primary bone cancers in children, but acute thrombosis is poorly characterized in this population. Our study evaluated the rates of venous thromboembolism (VTE) and associated risk factors in pediatric patients with bone sarcomas treated over a 10-year period encompassing the emergence of COVID-19.

PROCEDURE: Data were obtained via EMR review for patients diagnosed with OS and EWS at Texas Children’s Hospital from 2014 to 2023. Statistical analyses were performed using Fisher’s exact, chi-square, and Wilcoxon rank-sum tests. Change in VTE rate prior to and after 2020 was compared using interrupted time series analysis.

RESULTS: Among 137 eligible patients, the majority were diagnosed with OS (n = 85, 62%) compared to EWS (n = 52, 38%). Twelve patients (8.8%) developed VTEs during primary cancer therapy. Femoral tumor location was associated with increased VTE occurrence (p = 0.016), and there was a trend toward increased VTE in OS (p = 0.13) and obese patients (p = 0.2). VTE rates increased after the emergence of COVID-19, although only one affected patient tested positive. The incidence rate ratio pre- and post-COVID-19 emergence (2014-2019 vs. 2020-2023) was 8.7 (95% CI: 2.29-56.61; p = 0.005). This increase in VTEs after 2020 was sustained.

CONCLUSION: Our cohort represents the largest population of pediatric patients with bone sarcomas studied to date. In our 10-year analysis, we observed a sustained increase in VTE events following the emergence of COVID-19. Additionally, our data suggest that subsets of this patient population, specifically obese patients with OS and femoral tumors, should be closely monitored for thrombosis.

PMID:42117248 | DOI:10.1002/1545-5017.70390

Psychol Health. 2026 May 12:1-19. doi: 10.1080/08870446.2026.2668116. Online ahead of print.

ABSTRACT

Trait mindfulness refers to one’s natural tendency to be aware of and attentive to present experiences. Although the trait has been associated with physical health, most studies have been cross-sectional and failed to account for confounding variables. The present study tested the longitudinal relationship between trait mindfulness and physical health symptoms. Undergraduate student participants completed four surveys over a period of 3 months, in which they reported their trait mindfulness, physical symptoms (e.g. fatigue, stomachache), and cold symptoms (sore throat, congestion). Additionally, participants answered questions to assess general health, recent perceived stress, and trait neuroticism. Initial enrolment included 409 participants with 288 at Time 2, 218 at Time 3, and the final wave including 172 participants. Findings indicated that those higher in trait mindfulness reported fewer symptoms across all time points, regardless of general health, recent stress, or neuroticism, t(395) = -6.75, p < 0.001. By examining associations across time and covarying related variables, this study underscores the importance of trait mindfulness in predicting health outcomes. It is the largest longitudinal investigation of trait mindfulness and physical health symptoms in emerging adults. Future studies should explore pathways through which mindfulness influences symptoms.

PMID:42117223 | DOI:10.1080/08870446.2026.2668116