Nevin Manimala

Am J Clin Nutr. 2026 Apr 3:101305. doi: 10.1016/j.ajcnut.2026.101305. Online ahead of print.

ABSTRACT

BACKGROUND: Prebiotic fiber supplementation increases calcium absorption but its long-term effects on bone mass are mixed in children and adolescents.

OBJECTIVES: To determine the effect of one-year soluble corn fiber (SCF) supplementation compared to Placebo (maltodextrin; Main comparison), with or without calcium (calcium gluconate; Secondary comparison) on bone mineral content (BMC) and density (BMD) in children and adolescents with low habitual calcium intake through a randomized clinical trial. We hypothesized that SCF supplementation will result in higher bone mass.

METHODS: Healthy children and adolescents (9-14 years old) with usual low calcium intake were recruited and randomized for 1 year to SCF (12 g/d) or Placebo (12 mg/d), with or without calcium (600 mg/d). Bone mass was measured using dual energy x-ray absorptiometry (DXA) at baseline, 6 months and 12 months. Results are shown as mean±SD. Statistical analyses included linear mixed-effects and analysis of variance.

RESULTS: 213 participants were recruited and 177 were randomized. Most were White (41.3%), Hispanic (69.5%) and with healthy weight (74.0%). Girls had significantly higher Tanner score (3.10±1.20) compared to boys (2.30±1.20; p<0.001) and a significantly higher body fat % (p<0.05), therefore, results were stratified by sex. Among completers (n=151), whole-body BMC and BMD significantly increased from baseline to 6-months and to 12-months. In girls, 1-year gain in whole-body BMC was higher with SCF (216.3±138.3 g or 18.8%) compared to Placebo (139.9±84.0 g, 12.9%) after adjusting for age, Tanner stage, height velocity, weight velocity, lean mass velocity, fat mass velocity, and compliance (p<0.05). Similar results were found for BMD in girls. This was not observed in boys or when calcium supplementation was added.

CONCLUSIONS: 1-year supplementation with SCF resulted in a higher whole-body BMC and BMD compared to Placebo in girls only. This effect could have potential long-term benefits on bone mass acquisition in girls.

CLINICALTRIALS: GOV: NCT02916862; https://clinicaltrials.gov/study/NCT02916862 CLINICALTRIALS.

GOV REGISTRATION: NCT02916862.

PMID:41936980 | DOI:10.1016/j.ajcnut.2026.101305

J Equine Vet Sci. 2026 Apr 3:105880. doi: 10.1016/j.jevs.2026.105880. Online ahead of print.

ABSTRACT

BACKGROUND: Immune-mediated keratitis (IMMK) is a chronic inflammatory corneal disease in horses. Long-term topical therapy with cyclosporine is often impractical, highlighting the need for sustained-release alternatives.

AIMS/OBJECTIVES: To assess clinical response, tolerability, and duration of effect of episcleral silicone matrix cyclosporine implants (ESMC) in horses with presumed IMMK.

METHODS: Medical records of 12 horses (14 eyes) treated between 2019 and 2023 were retrospectively reviewed. IMMK subtypes were classified as epithelial (n = 3 eyes), anterior stromal (n = 9), or mid-stromal (n = 2). Collected data included treatment success or failure, complications, and duration of therapeutic effect. Statistics were applied with non-parametric testing.

RESULTS: No local or systemic adverse effects were observed. All epithelial IMMK eyes (3/3) achieved treatment success, with a median duration of therapeutic effect of 698 days (interquartile range – IQR 375). Seven of nine anterior stromal eyes presented successful outcome, with median duration of therapeutical effect of 104 days (IQR 88). Two eyes failed, requiring enucleation or surgical management. Both eyes with mid-stromal IMMK were classified as failure, with a median duration of therapeutic effect of 39 days (IQR 3). Significant differences in the duration of therapeutic effect were detected between epithelial and anterior stromal (p = 0.04) and between epithelial and mid-stromal subtypes (p = 0.03). No correlation was found between the number of implants and the duration of therapeutic effect (p = 0.7).

CONCLUSION: Episcleral silicone matrix cyclosporine implants were well tolerated in horses with presumed IMMK. The treatment showed high success rates in epithelial and anterior stromal subtypes, but poor outcomes in mid-stromal subtype. The therapeutic effect was longest in epithelial IMMK, suggesting implant efficacy may vary with disease subtype.

PMID:41936975 | DOI:10.1016/j.jevs.2026.105880

J Equine Vet Sci. 2026 Apr 3:105877. doi: 10.1016/j.jevs.2026.105877. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: The DMRT3 gene, often referred to as the “gait keeper,” plays a key role in controlling alternative gaits in horses, such as tölt and pace. This study aimed to determine the frequency of known and to screen for potential novel polymorphisms within the second exon of the DMRT3 gene.

DATA COLLECTION: A total of 244 blood or hair samples were collected from representative individuals of the six horse breeds: gaited (Icelandic Horse, French Trotter), non-gaited (Arabian Horse, Malopolski Horse), and pony breeds (Welsh Pony, Shetland Pony).

RESEARCH METHODS: The second exon of the DMRT3 gene analyzed using Sanger sequencing. Detected polymorphisms were annotated and classified using Ensembl and NCBI databases. Allele frequencies and genotype distributions were statistically compared between breeds and breeding populations. Putative novel variants were further analysed using in silico approaches to predict their potential structural and functional consequences at the protein level.

RESULTS: Six polymorphisms were identified, including three novel variants. The known stop-gain variant c.902C>A (DMRT3_Ser301STOP) was confirmed in Icelandic Horses and French Trotters, with significant genotype differences between two French Trotter studs (p < 0.05). A novel 18-nucleotide in-frame duplication (c923_943dup; Ala297_Ala302dup) was found exclusively in Shetland Ponies. Additionally, a missense variant (c.967T>A; p.Tyr323Asn) and a synonymous change (c.855T>C) were detected in non-gaited breeds. In silico analyses suggested no major structural impact of the identified variants on the predicted DMRT3 protein.

CONTRIBUTIONS: This study confirms the distribution of the DMRT3_Ser301STOP allele in gaited breeds and identifies novel polymorphisms in DMRT3. It expands current knowledge by identifying population- and breed-specific variants, suggesting a broader genetic influence on locomotor traits beyond gaited horses. The findings support the continued identification of DMRT3 as a molecular marker in equine locomotion research and selective breeding.

PMID:41936970 | DOI:10.1016/j.jevs.2026.105877

Ann Allergy Asthma Immunol. 2026 Apr 3:S1081-1206(26)00148-1. doi: 10.1016/j.anai.2026.03.026. Online ahead of print.

ABSTRACT

BACKGROUND: Anti-Interleukin 5/Rα (IL5/Rα) for severe asthma has demonstrated marked reductions in systemic corticosteroid use. However, little is known about the long-term total (inhaled and systemic) corticosteroid exposure.

OBJECTIVE: Estimate total corticosteroid exposure reduction and prevalence of corticosteroid remission over five years of anti-IL5/Rα therapy for severe asthma.

METHODS: All Danish adults initiating anti-IL5/Rα for severe asthma during 2016-2019 were followed for five years. Corticosteroid exposure was assessed annually using national registries, and changes were estimated using mixed models. Corticosteroid remission was defined as no systemic corticosteroid exposure and low-to-moderate daily inhaled corticosteroid doses.

RESULTS: In total, 253 patients were included (median age 57, 51% female). At baseline, 33% were using daily maintenance oral corticosteroids. The year prior to biologic therapy, median total corticosteroid exposure was 3,604mg (3,404, 3,803) prednisolone equivalents. Year one, total corticosteroid exposure was reduced by 25.2% (13.4, 36.9) increasing to a reduction of ∼45% years three through five. Systemic corticosteroids accounted for the majority of reductions, with decreases of 32.8% (21.1-44.6) during the first year and ∼60% during later years. For inhaled corticosteroids, statistically significant reductions were observed during year four at -149.7mcg (-13.7, -285.7) budesonide-equivalents and -189.1mcg (-23.2, -355.1) during year five. During later treatment years, inhaled corticosteroids represented the main source of corticosteroid exposure. An annual average of 23% achieved corticosteroid remission, while only 2.4% achieved five-year sustained corticosteroid remission.

CONCLUSION: Over five years, anti-IL5/Rα treatment significantly reduced total corticosteroid exposure. Reductions were driven by marked reductions in systemic corticosteroid exposure, whereas modest reductions in inhaled corticosteroid exposure were observed.

PMID:41936962 | DOI:10.1016/j.anai.2026.03.026

Ann Allergy Asthma Immunol. 2026 Apr 3:S1081-1206(26)00146-8. doi: 10.1016/j.anai.2026.03.024. Online ahead of print.

ABSTRACT

BACKGROUND: Treatment which reduces systemic corticosteroid (SCS)-related adverse effects but maintains disease control is of broad public health importance.

OBJECTIVE: To evaluate the effect of mepolizumab versus chronic-SCS use on SCS-related adverse effects in patients with severe asthma.

METHODS: This retrospective, longitudinal cohort study (GSK ID: US 218950) used claims data from the Optum Clinformatics Data Mart database from November 2014 – December 2022. Eligible patients (aged ≥12 years with ≥2 asthma diagnostic claims), had ≥2 mepolizumab claims (mepolizumab-treated cohort) or ≥6 months continuous SCS use (chronic-SCS-treated cohort). Inverse probability of treatment weighting was used to balance cohort characteristics.

PRIMARY OUTCOME: SCS-related adverse effects.

SECONDARY OUTCOMES: exacerbation frequency, SCS/oral corticosteroid (OCS) use, healthcare resource utilization (HCRU), and costs (excluding cost of therapy).

RESULTS: Overall, 1,219 (mepolizumab-treated) and 835 (chronic-SCS-treated) patients with severe asthma were included (median follow-up 12 months). Cohorts were well-balanced after weighting (mean age 63-65 years, 66% female). The mepolizumab-treated cohort had significant reductions in overall, acute, and chronic-SCS-related adverse effects (rate ratio [RR] [95% confidence interval] 0.80 [0.70-0.92], 0.63 [0.47-0.84], 0.80 [0.70-0.92], respectively) versus the chronic-SCS-treated cohort; SCS dose reduction of 4.7 mg/day corresponds to a 20% reduction in SCS-related adverse effects (p=0.002). Similar trends were observed in exacerbation rates, HCRU, and medical costs, although not all reached statistical significance.

CONCLUSION: Mepolizumab treatment reduced acute and chronic corticosteroid effects in patients with severe asthma versus chronic-SCS use, suggesting avoidance of corticosteroid use can lead to measurable regression of SCS-associated adverse effects and more favorable disease trajectory.

PMID:41936961 | DOI:10.1016/j.anai.2026.03.024

J Hepatol. 2026 Apr 3:S0168-8278(26)00199-6. doi: 10.1016/j.jhep.2026.03.044. Online ahead of print.

NO ABSTRACT

PMID:41936952 | DOI:10.1016/j.jhep.2026.03.044

JACC Adv. 2026 Apr 4;5(5):102708. doi: 10.1016/j.jacadv.2026.102708. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiac resynchronization therapy (CRT) failure leads to adverse remodeling and poor outcomes.

OBJECTIVES: The purpose of this study was to evaluate vericiguat effects on outcomes, mitochondrial function, and inflammation/oxidative stress in CRT nonresponders at 1 year.

METHODS: In this multicenter, observational prospective study, CRT nonresponders treated with vericiguat (n = 156) were compared with non-treated (n = 415). Mitochondrial function was assessed by technetium-99m-methoxyisobutylisonitrile uptake and metabolic profiling of peripheral blood mononuclear cells. Primary endpoint was the CRT responder rate at 1 year; secondary endpoints included heart failure (HF) hospitalizations, mitochondrial function, and inflammatory/oxidative stress markers. CRT responders showed ≥10% reduction in left ventricle end-systolic volume with improved functional status at follow-up. Statistical analysis included Student’s t-tests, chi-square tests, Fisher’s tests, linear mixed models, and Cox regression (significance P < 0.05).

RESULTS: At 1 year, vericiguat users vs those untreated had higher CRT responders’ rate [67/156 (42.9%) vs 51/415 (12.3%)] and lower HF hospitalizations [17/156 (11.1%) vs 114/415 (27.5%)], (P < 0.05). They had better NYHA functional class, higher left ventricular ejection fraction, and lower inflammatory/oxidative stress levels (P < 0.05). Reduced methoxyisobutylisonitrile washout, enhanced adenosine triphosphate (ATP) synthesis, and increased sirtuins3-6 expression were observed (P < 0.05). CRT-responders outcome was predicted by vericiguat (2.165; 95% CI: 1.512-4.623), sacubitril/valsartan (1.432; 95% CI: 1.020-2.885), and low-baseline ATP (0.265; 95% CI: 0.072-0.369); HF hospitalizations outcome was reduced by vericiguat (0.312; 95% CI: 0.195-0.497) and sacubitril/valsartan (0.672; 95% CI: 0.308-0.865) and increased by lower baseline ATP production (4.881; 95% CI: 1.945-8.507) and left ventricular ejection fraction (1.864; 95% CI: 1.209-2.871) at follow-up end.

CONCLUSIONS: In this small cohort of CRT nonresponders, vericiguat increased CRT response at 1 year, likely through improved mitochondrial function and reduced inflammatory/oxidative stress. Larger studies are needed to confirm these findings.

PMID:41936180 | DOI:10.1016/j.jacadv.2026.102708

Int J Pediatr Otorhinolaryngol. 2026 Apr 3;204:112816. doi: 10.1016/j.ijporl.2026.112816. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the clinical characteristics, causes of readmission, postoperative complications, and auditory outcomes of pediatric patients in whom otitis media with effusion (OME) was detected during cochlear implant (CI) surgery.

MATERIALS AND METHODS: This retrospective study reviewed medical records and audiological follow-up data of 461 ears from 243 patients who underwent CI surgery. Postoperative complications were analyzed in the entire cohort. For audiological outcome analysis, 25 ears with intraoperatively detected OME were compared with 25 randomly selected ears without OME and with similar clinical characteristics to ensure balanced group sizes and reduce potential confounding. Appropriate parametric tests were applied, and effect sizes were calculated using Cohen’s d and Cramér’s V.

RESULTS: There were no significant differences between the OME and control groups regarding age or gender distribution (p > 0.05). Pure-tone average and most audiological parameters did not differ significantly between groups. However, the Speech Recognition Threshold (SRT) was significantly lower in the OME group compared with the control group (p = 0.012, d = -0.741). Postoperative infection occurred more frequently in ears with OME than in those without (12.0% vs. 2.5%), and this difference was statistically significant (p = 0.035).

CONCLUSION: Although the presence of OME during CI surgery is associated with an increased risk of postoperative infection, the clinical effect size is limited. OME does not appear to adversely affect overall auditory performance. With appropriate perioperative management and follow-up, OME should not be considered an absolute contraindication for cochlear implantation in pediatric patients.

PMID:41936177 | DOI:10.1016/j.ijporl.2026.112816

J Epidemiol Popul Health. 2026 Apr 4;74(4):203366. doi: 10.1016/j.jeph.2026.203366. Online ahead of print.

ABSTRACT

INTRODUCTION: Firearm-related mortality remains a public health concern in the United States (US). This study examines firearm-related mortality trends in Pennsylvania from 2012 to 2023, with an emphasis on demographic disparities.

METHODS: Firearm-related mortality data was obtained from the Pennsylvania Enterprise Data Dissemination Informatics Exchange, categorizing deaths as intentional (suicide, homicide) or unintentional based on ICD-10 codes. Crude mortality rates were analyzed by sex, age, race/ethnicity, and county. Annual percentage changes were computed to assess trends, and statistical significance was determined using chi-square tests and linear regression models.

RESULTS: From 2012 to 2023 in Pennsylvania, there were 19,470 firearm-related deaths, including 11,520 suicides and 7446 homicides. Firearms accounted for 51.4% of all suicides (11,520 of 22,395) and 76.8% of all homicides (7446 of 9691). The proportion of firearm-related suicide was significantly higher among males compared to females (57.2% [10,151/17,740] vs 29.4% [1369/4654]; p < 0.001) and among Whites compared to Blacks (52.7% [10,514/19,939] vs 47.4% [655/1381]; p < 0.001). Among racial subgroups, the firearm-related suicide rate increased among Whites, Blacks, and Hispanics, however, the statistically significant increase over time occurred among Whites (p = 0.011) and Blacks (p < 0.001). The proportion of firearm-related homicide rate mortality was significantly higher among males compared to females (81.3% [6439/7924] vs 57.0% [1007/1766]; p < 0.001) and among Blacks compared to Whites (87.3% [5126/5875] vs 54.5% [1505/2760]). Subgroup analysis showed the highest rate increase was among Black males aged 40-59 years (122.7%).

CONCLUSIONS: Firearm-related mortality rates increased substantially in Pennsylvania in the past decade, with disparities observed in subgroup populations. Firearm safety policies, mental health support, and violence prevention programs are needed to reduce firearm-related mortality in Pennsylvania.

PMID:41936170 | DOI:10.1016/j.jeph.2026.203366

J Surg Res. 2026 Apr 4;321:523-530. doi: 10.1016/j.jss.2026.03.034. Online ahead of print.

ABSTRACT

INTRODUCTION: Reconstruction of complex incisional hernias can be technically challenging. Enterotomy (ENT) is infrequent in most abdominal wall reconstruction (AWR) cases, yet in complex, reoperative fields, bowel injury can be difficult to avoid. Data describing the incidence and outcomes of ENT in these operations remain limited.

METHODS: A prospective, tertiary hernia center database was queried for elective AWR. Outcomes following an operative ENT (small bowel) were compared with no ENT (non-ENT). Standard statistical analyses were performed. Kaplan-Meier analysis compared recurrence-free survival between groups.

RESULTS: Of 2687 patients, 41 (1.5%) patients sustained an ENT. ENT and non-ENT were similar in age, body mass index, and smoking status (all P > 0.05). Diabetes was more prevalent in non-ENT (9.8% versus 23.8%; P = 0.027). Though similar defect sizes (189.0 (133.0, 308.0) versus 160.0 (63.0, 286.0); P = 0.093), ENT had more recurrent hernias (68.3% versus 51.5%; P = 0.033). Most operations were performed open (95.1% versus 93.3%) with all mesh placed preperitoneal. Biologic mesh was used more frequently in ENT (68.3% versus 19.2%; P < 0.001). Fascial closure was achieved in most cases (100.0% versus 93.1%; P = 0.401). Delayed primary closure was performed more often in ENT (14.6% versus 5.9%; P = 0.021). ENT had longer operative times (227.0 (193.0, 284.0) versus 181.0 (138.0, 230.0) minutes; P < 0.001), length-of-stay (6.0 (5.0, 8.0) versus 5.0 (3.0, 6.0) days; P < 0.001), wound complications (36.6% versus 19.5%; P = 0.006) and hernia recurrence (12.2% versus 3.7%; P = 0.005). Mesh infection was not different (4.9% versus 1.3%; P = 0.108). ENT wound complications were significantly lower in biologic versus synthetic mesh (25.0% versus 61.5%; P = 0.024), but recurrence (7.1% versus 23.1%; P = 0.304) was similar. Both ENT mesh infections were in synthetic mesh. Average follow-up was similar (15.1 (2.7, 49.9) versus 11.3 (1.3, 51.3) months; P = 0.311).

CONCLUSIONS: ENT during AWR is rare but is associated with wound morbidity and hernia recurrence. Prevention of bowel injury and aggressive mitigation of wound morbidity are important to preserving long-term durability of AWR.

PMID:41936147 | DOI:10.1016/j.jss.2026.03.034