Nevin Manimala

Am J Physiol Heart Circ Physiol. 2026 Jan 19. doi: 10.1152/ajpheart.00950.2025. Online ahead of print.

ABSTRACT

Left ventricular (LV) flow state is associated with unfavorable outcome in patient with severe aortic stenosis. However, there is little information on its impact on long-term prognosis in a population without valvular disease. To examine the impact of LFS on all-cause mortality in multi-ethnic population we analyzed 4398 asymptomatic participants without clinical cardiovascular disease undergoing cardiac magnetic resonance (CMR) in the Multi-Ethnic Study of Atherosclerosis. LV stroke volume index (SVi), LVEF and myocardial contraction fraction (MCF) were measured. LV flow states were classified as normal flow state (NFS, SVi >35 ml/m²), low-flow state (LFS, 30-34 ml/m²) and very low-flow state (VLFS: SVi <30 ml/m²). Clinical data were collected at enrollment. Participants were followed up for a median of 14.2 years. All-cause and cardiovascular disease mortalities were used as primary endpoints. All-cause mortality was 16.2% and cardiovascular disease mortality 3.5%. VLFS and LFS groups had more cardiovascular risk factors and lower cardiac performance than NFS. The relationship between all-cause mortality and SVi was “L-shape with the “breakpoint” at 33.5ml/m2 for a statistical significance (p=0.009). All-cause mortality was significantly associated with LFS after adjusted for age, sex, LVEF, and LV mass index with hazard ratio (HR) 1.81, 95% CI: 1.31-2.49 for VLF and HR: 1.21, 95% CI: 0.95-1.54 for LFS with overall p value 0.001). The highest cardiovascular disease mortality was seen in VLFS.

PMID:41553736 | DOI:10.1152/ajpheart.00950.2025

BJS Open. 2025 Dec 29;10(1):zraf152. doi: 10.1093/bjsopen/zraf152.

ABSTRACT

BACKGROUND: Enhanced recovery after surgery is associated with improved clinical outcomes and cost savings. Comparisons between studies and settings are challenging owing to variable data collection and definitions. The objective of this study was to explore variation in compliance with enhanced recovery after surgery and outcomes across surgery types and countries using a standardized database.

METHODS: This international retrospective cohort study included adult patients who underwent surgical procedures (colorectal, gynaecological, pancreatic, hepatic, breast reconstruction, head and neck, urological, pulmonary), treated with enhanced recovery after surgery recorded in a standardized database between January 2017 and September 2021. The primary outcomes, length of hospital stay and complications, and the exposure variable, compliance with enhanced recovery after surgery, were captured from the standardized database. Patient demographic characteristics and surgical complexity were abstracted and considered as co-variates. Negative binomial and logistic regression analyses were used to model outcomes as a function of enhanced recovery after surgery compliance score.

RESULTS: The cohort included 12 134 patients (from Canada, the Netherlands, and Switzerland) who had median age of 63 years and underwent colorectal (59%) or gynaecological (19%) surgery. The median compliance with enhanced recovery after surgery differed by country (Canada 78.6%, the Netherlands 67.7%, Switzerland 80.0%). Each 1-unit increase in enhanced recovery after surgery compliance score corresponded to reduced length of hospital stay across all operations, by 0.94 (95% confidence interval (c.i.) 0.85 to 1.04) days in Canada, 1.03 (0.85 to 1.20) days in the Netherlands, and 1.55 (1.12 to 1.97) days in Switzerland. Each 1-unit increase in enhanced recovery after surgery compliance score corresponded to a 29 (95% c.i. 25 to 33)% reduction in odds of experiencing a severe complication across all operations in Canada, a 22 (14 to 31)% reduction in the Netherlands, and a 5 (2 to 8)% reduction in Switzerland.

CONCLUSION: Using a standardized database, this study confirmed that enhanced recovery after surgery compliance is associated with reduced length of hospital stay and complications in an international multisurgical cohort.

PMID:41553734 | DOI:10.1093/bjsopen/zraf152

Public Health Rep. 2026 Jan 19:333549251404847. doi: 10.1177/00333549251404847. Online ahead of print.

ABSTRACT

OBJECTIVE: Most people in the United States are unaware that alcohol causes cancer and increases heart disease risk. Warning labels on alcohol containers can increase knowledge about these harms. Yet, it is unclear if Americans support this policy. We assessed attitudes toward cancer and heart disease warning labels on alcohol containers.

METHODS: In May 2024, we surveyed 1095 adults (aged ≥18 y) participating in AmeriSpeak, a nationally representative panel of the US noninstitutionalized civilian adult population. We analyzed support for warning labels overall and by sociodemographic characteristics by using descriptive statistics weighted to represent the US population.

RESULTS: Overall, 4 in 10 respondents supported cancer or heart disease warning labels on alcohol containers. Fewer than 10% opposed warning labels; many were neutral. More young adults (aged 18-29 y; 57.9% [95% CI, 44.6%-70.0%]) than older adults (aged ≥60 y; 36.0% [95% CI, 30.3%-42.1%]) supported cancer warning labels (P = .04). More women (50.8%; 95% CI, 45.0%-56.6%) than men (40.5%; 95% CI, 34.1%-47.2%) supported heart disease warning labels (P = .03).

CONCLUSIONS: Most people in the United States are neutral about or support cancer and heart disease warning labels on alcohol containers. Leveraging warning labels is a cost-effective way to inform the public about alcohol’s link to cancer and heart disease.

PMID:41553719 | DOI:10.1177/00333549251404847

Minerva Endocrinol (Torino). 2026 Jan 19. doi: 10.23736/S2724-6507.25.04276-9. Online ahead of print.

ABSTRACT

BACKGROUND: Prenatal exposure to dioxin, a known endocrine disruptor, after the Seveso accident of 1976 has been associated with thyroid dysfunction, metabolic syndrome and semen quality reduction. Experimental exposure to dioxin in utero produced epigenetic endocrine modifications associated with reduction of semen quality, while in men epigenetic effects are not known. Our objective was to study, by a case control approach, the long-term epigenetic effects of prenatal dioxin exposure in 38 men whose mothers had been exposed to high doses of dioxin, serum median 52.0 ppt at exposure, and therefore who were exposed in utero, median 24.7 ppt at pregnancy, vs. 41 unexposed men.

METHODS: Bisulfite-converted DNA was hybridized onto illumina Infinium Methylation EPIC BeadChip and methylation differences were studied at both individual probe (DMPs) and gene region (DMRs) levels.

RESULTS: We identified hypomethylation of the SPAG1 gene region and a slightly hypermethylated region containing genes of the HOXA family associated with thyroid and skeletal development. An elevated level of epigenetic drift was noted in the exposed group potentially contributing to disease risk. Epigenetic age acceleration did not show significant association with in-utero dioxin exposure. Additionally, we found heightened neutrophils and diminished natural killer cells in blood of dioxin exposed men.

CONCLUSIONS: These observations are the first in the literature and align with the long-term semen quality reduction and alteration of thyroid homeostasic mechanisms reported in children exposed in utero to dioxin in Seveso. The actual dioxin background serum levels, 1.0-2.0 ppt, are much lower than those associated to these effects.

PMID:41553716 | DOI:10.23736/S2724-6507.25.04276-9

Adv Ther. 2026 Jan 19. doi: 10.1007/s12325-025-03447-6. Online ahead of print.

ABSTRACT

INTRODUCTION: While the therapeutic options for Crohn’s disease (CD) have broadened swiftly, direct comparative evidence on treatment efficacy remains limited. This study explored the relative efficacy and safety of available treatments based on current evidence.

METHODS: A network meta-analysis (frequentist random-effect model) evaluated comparative efficacy of licensed advanced therapies for CD using data on efficacy of maintenance therapy from fully published, randomised, controlled phase 3/3b studies with 48-64-week follow-up periods and placebo or active comparator controls, identified through a systematic literature review (PROSPERO number CRD42023413752). Intravenous (IV) and subcutaneous (SC) infliximab, SC adalimumab, IV and SC vedolizumab, SC ustekinumab, SC risankizumab, and oral upadacitinib were included. Clinical remission and endoscopic response rates attained through maintenance regimens were assessed according to line of use (e.g., first-line and second-or-later line). Safety (serious adverse event rates) was also compared.

RESULTS: Data from nine randomised controlled trials were analysed. SC infliximab 120 mg every 2 weeks (q.2.w.) exhibited the highest risk difference (95% confidence interval) vs. placebo in both first-line and second-or-later-line maintenance treatment for achieving clinical remission (0.38 [0.23-0.53] and 0.51 [0.19-0.83], respectively; 14 and 12 comparator arms, respectively), and endoscopic response (0.39 [0.29-0.49] and 0.35 [0.07-0.63], respectively; 5 comparator arms) compared with other treatments. Differences between therapies did not reach statistical difference. Safety was comparable among treatments in terms of rates of serious adverse events.

CONCLUSIONS: The current NMA integrating recently updated phase 3 data in CD indicated that no single treatment significantly outperformed others in achieving clinical remission and endoscopic response, although SC infliximab 120 mg q.2.w exhibited highest numerical efficacy as both a first-line and second-or-later-line maintenance treatment in adult patients with moderate-to-severe CD.

PMID:41553714 | DOI:10.1007/s12325-025-03447-6

Adv Ther. 2026 Jan 19. doi: 10.1007/s12325-025-03470-7. Online ahead of print.

ABSTRACT

INTRODUCTION: Three previous publications have reported real-world comparative effectiveness of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) and budesonide/glycopyrrolate/formoterol fumarate (BUD/GLY/FORM) in patients with chronic obstructive pulmonary disease (COPD) in the USA. This subgroup analysis assessed treatment with FF/UMEC/VI and BUG/GLY/FORM in patients with COPD who stepped up from dual therapy, stratified by number of prior exacerbations and class of prior dual therapy.

METHODS: Propensity score (PS)-weighted patients identified within healthcare claims from the Komodo Research database were used to compare annualized rates and time to first moderate-severe COPD exacerbation between FF/UMEC/VI and BUD/GLY/FORM initiators stepping up from dual therapy, stratified by the type of dual therapy (long-acting muscarinic antagonist plus long-acting β₂-agonist [LAMA/LABA] or inhaled corticosteroid [ICS] plus LABA) and by prior (none or ≥ 1) COPD exacerbation. Results are presented as events per patient year (PPY) and rate ratio (RR) with 95% confidence intervals (CIs).

RESULTS: Approximately 14,000 patients contributed to this analysis, 10,093 FF/UMEC/VI and 3926 BUD/GLY/FORM initiators. Baseline characteristics were well balanced following PS weighting. Step-up to FF/UMEC/VI was associated with a statistically significant reduction in moderate-severe exacerbations compared with step-up to BUD/GLY/FORM irrespective of exacerbation history: no prior exacerbation, n = 7235, 0.48 vs 0.56 PPY, RR [95% CI] 0.86 [0.77, 0.95], P = 0.003; ≥ 1 prior exacerbation, n = 6784, 1.14 vs 1.41 PPY, RR [95% CI] 0.81 [0.74, 0.87], P < 0.001. Step-up to FF/UMEC/VI was also associated with a statistically significant reduction in moderate-severe exacerbations compared with step-up to BUD/GLY/FORM across both subgroups of prior dual therapy: LAMA/LABA, n = 5717, 0.71 vs 0.95 PPY; RR [95% CI] 0.75 [0.67, 0.83], P < 0.001; ICS/LABA, n = 8302, 0.85 vs 0.99 PPY; RR [95% CI] 0.86 [0.79, 0.93], P < 0.001.

CONCLUSION: Patients newly initiating FF/UMEC/VI following prior treatment with ICS/LABA or LAMA/LABA experienced a significantly lower rate of moderate-severe COPD exacerbations than those newly initiating BUD/GLY/FORM irrespective of number of prior exacerbations or prior dual therapy class.

PMID:41553713 | DOI:10.1007/s12325-025-03470-7

Dermatol Ther (Heidelb). 2026 Jan 19. doi: 10.1007/s13555-025-01647-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Atopic dermatitis (AD) is a complex disease with clinical heterogeneity. Nemolizumab is a novel interleukin (IL)-31 receptor alpha inhibitor that has demonstrated efficacy in managing moderate-to-severe AD. However, there are no head-to-head trials that compare nemolizumab with other anti-IL-4/13 monoclonal antibodies (mAbs). To support clinical decision-making, the comparative efficacy and safety of nemolizumab versus other advanced systemic therapies, in combination with topical treatments, were estimated using network meta-analyses (NMAs).

METHODS: Randomized controlled trials (RCTs) investigating advanced systemic therapies for moderate-to-severe AD in adolescents (12-17 years) and adults (≥ 18 years) were identified through a systematic literature review (searches conducted 31 March 2025, CRD42023492392). The trial results were analyzed in fixed- and random-effects Bayesian NMA models. Outcomes included ≥ 75% improvement in the Eczema Area Severity Index (EASI-75), an Investigator’s Global Assessment (IGA) score of 0 or 1 (IGA success), treatment-emergent adverse events, and discontinuations due to adverse events. Analyses for all endpoints were conducted at week 16. This publication presents a targeted comparison of licensed anti-IL mAbs.

RESULTS: Twenty-two RCTs were included in the NMA. When measuring response through EASI-75 and IGA success, no statistically significant differences were observed between nemolizumab and all other anti-IL mAbs in CsA-experienced adults or CsA-naïve adolescents. In CsA-naïve adults, only lebrikizumab demonstrated statistically superior efficacy against nemolizumab. Nemolizumab demonstrated a comparable safety profile with other available treatments.

CONCLUSIONS: The results of this study suggest that compared with other anti-IL mAb therapies for the treatment of moderate-to-severe AD, nemolizumab has similar efficacy in achieving EASI-75 and IGA success, and a comparable safety profile. This is in addition to nemolizumab’s well-demonstrated efficacy in improving itch. Nemolizumab may be particularly beneficial in clinical settings where patients and physicians are seeking to manage AD with a well-tolerated therapeutic.

PMID:41553701 | DOI:10.1007/s13555-025-01647-0

Environ Sci Pollut Res Int. 2026 Jan 19. doi: 10.1007/s11356-026-37394-8. Online ahead of print.

ABSTRACT

Climate change is a critical global challenge driven by rising greenhouse gas emissions, particularly carbon dioxide CO $_2^{}$ . Accurate forecasting of CO $_2^{}$ emissions is essential for developing effective mitigation strategies. This study focuses on modeling and forecasting CO $_2^{}$ emissions in Iraq based on data from 1937 to 2023, incorporating climatic variables such as temperature and precipitation as exogenous variables to enhance forecast accuracy using multiple models, including traditional time series ARIMAX, Feedforward Neural Networks (FNN), Recurrent Neural Networks (RNN), and hybrid FNN-RNN. ARIMAX requires the assumption of linearity, FNN alone can model complex nonlinear interactions for each observation, while the RNN capture temporal relationships in sequential data. The hybrid configuration combining FNN and RNN models provides a learning of both linear and nonlinear structures. Empirical results indicate that the hybrid FNN-RNN model outperforms other models using key evaluation metrics, including $R^2$ , MSE, RMSE, and MAE. The hybrid model shows that both training and validation losses decrease steadily and converge to very low values without overfitting. The close alignment of the two curves indicates good generalization, and the slight dip in validation loss suggests effective regularization. Additionally, the study forecasts a significant 9.18% rise in Iraq’s CO $_2^{}$ emissions over the 5 years from 2024 to 2028, and the forecast showed its highest recorded value in 2028. These findings may support policymakers in designing more accurate and proactive emission control strategies. While focused on climatic variables, the model offers a strong basis for future research to focus on socioeconomic factors such as GDP and population growth.

PMID:41553698 | DOI:10.1007/s11356-026-37394-8

J Autism Dev Disord. 2026 Jan 19. doi: 10.1007/s10803-025-07205-z. Online ahead of print.

ABSTRACT

PURPOSE: In low- and middle-income countries (LMICs), where the majority of children with developmental disorders live, access to early, specialized interventions is highly limited. While studies from high-income countries show that tailored early intervention can be effective in learning new skills, there remains a lack of evidence-based approaches specifically designed for the realities of LMICs.

METHODS: The study included 50 preschoolers, 25 of whom (mean age = 52.4 months) participated in an individualized developmental and behavioral program combined with parent education in addition to preschool attendance over a six-month period. The remaining 25 children (mean age = 50.5 months) attended only preschool. The intervention averaged 2.9 h per week (range: 2.1-4 h) and targeted age-appropriate developmental goals. Additionally, parents received an average of 0.6 h per week (range: 0.2-0.7 h) of education to support the generalization of skills to daily life.

RESULTS: Children who received the individualized developmental and behavioral intervention combined with parent education in addition to preschool made statistically significant progress across all developmental areas compared to those who attended only preschool.

CONCLUSION: These findings highlight the potential of locally adapted, evidence-based, low-intensity interventions, combined with parent education, to improve outcomes for children with developmental disorders, including autism, in LMICs.

PMID:41553659 | DOI:10.1007/s10803-025-07205-z

J Autism Dev Disord. 2026 Jan 19. doi: 10.1007/s10803-026-07221-7. Online ahead of print.

NO ABSTRACT

PMID:41553658 | DOI:10.1007/s10803-026-07221-7