Category: Nevin Manimala

JAMA Netw Open. 2025 Aug 1;8(8):e2528924. doi: 10.1001/jamanetworkopen.2025.28924.

ABSTRACT

IMPORTANCE: Owing to a high prevalence of obesity, Pacific Islander individuals in the US are at higher risk for preterm birth (PTB), but outcomes after PTB remain understudied. Existing literature suggests that associations between prepregnancy obesity and neonatal mortality stratified by gestational age (GA) are modest or null, which may be a result of overlooked stratification bias.

OBJECTIVE: To estimate the association between prepregnancy body mass index (BMI) and neonatal death (NND) following PTB by different degrees of prematurity in US Pacific Islander neonates using birth-based and fetuses-at-risk (FAR) approaches.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used 2014 to 2018 data files from the National Center for Health Statistics for Pacific Islander singletons born at 22 to 41 weeks’ GA without congenital anomalies. The 2 at-risk populations were PTBs (for the birth-based approach) and all identified pregnancies resulting in live birth (for the FAR approach). Analyses were finished in March 2023.

MAIN OUTCOMES AND MEASURES: The primary outcome was NND following PTB stratified by GA intervals (22-27 weeks, 22-31 weeks, and 22-36 weeks). Cox proportional hazards models were used and stratified by GA at birth.

RESULTS: Among 55 975 mother-neonate dyads (27 320 [48.8%] female neonates), the mean (SD) maternal age was 27.8 (5.8) years, and the mean (SD) gestational age of all neonates was 38.5 (1.9) weeks. The PTB prevalence was 9.3% (5192 neonates), and the neonatal mortality rate was 20.4 deaths per 1000 PTBs by the birth-based approach and 1.9 deaths per 1000 live-born pregnancies by the FAR approach. Among extreme PTBs (22-27 weeks), using the FAR approach, associations between prepregnancy obesity and NND following PTB were evident for obesity class I (adjusted hazard ratio [aHR], 2.31; 95% CI, 1.12-4.79) and class II (aHR, 2.82; 95% CI, 1.24-6.41). These associations were attenuated using the birth-based approach (obesity class I aHR, 1.33; 95% CI, 0.61-2.87; class II aHR, 1.73; 95% CI, 0.71-4.28).

CONCLUSIONS AND RELEVANCE: In this cohort study of US Pacific Islander individuals, according to the FAR approach, prepregnancy obesity class I and II were associated with an increased rate of NND following PTB, yet these associations may be overlooked when analyses use the birth-based approach. This is likely because prepregnancy BMI affects GA at birth, which, in turn, may have its own confounded association with NND, leading to stratification bias and attenuated associations between prepregnancy BMI and NND using the birth-based approach. The FAR approach offers an alternative that may highlight important risk factors for key perinatal outcomes.

PMID:40856998 | DOI:10.1001/jamanetworkopen.2025.28924

Int J Cancer. 2025 Aug 26. doi: 10.1002/ijc.70108. Online ahead of print.

ABSTRACT

Men have a higher risk than women for most cancers affecting both sexes. Since taller stature is associated with increased cancer risk and men are, on average, taller than women, we investigated to what extent adult body height, as a proxy for stem cell number, explains the elevated cancer risk in men. This population-based cohort study linked adult height information from Swedish conscripts, mothers, and passports to the National Cancer and Cause of Death Registers (1960-2011). We used mediation survival analysis to estimate the proportion of the association between male sex and site-specific cancer risk mediated by adult height, our main outcome. Statistical significance was assessed using two-sided tests with a .05 significance level. Among 6,156,659 adults, we observed 285,778 non-sex-specific cancer cases. Male sex was significantly associated with cancer risk at 33 of 39 sites, and greater height with increased risk at 27 of 39 sites. Height mediated 0.5%-100% of the excess male cancer risk, with the highest proportions for salivary gland cancer, colon cancer, melanoma, and acute myeloid leukemia. The effects of height and its mediated effect were most consistent for malignancies with weak or no established environmental risk factors. These findings indicate that a substantial proportion of the excess cancer risk in men may be explained by height. This highlights the role of stochastic biological processes linked to height, as well as genetic and early-life determinants of height, in contributing to sex differences in cancer risk, beyond influences of adult lifestyle and environmental exposures.

PMID:40856995 | DOI:10.1002/ijc.70108

Environ Sci Process Impacts. 2025 Aug 26. doi: 10.1039/d5em00511f. Online ahead of print.

ABSTRACT

The Mongolian Plateau grasslands constitute a vital ecological barrier in inland Asia. Within these ecosystems, the mineral-associated soil fraction (<53 μm, MASF) is the dominant component, and its iron (Fe) oxides play a pivotal role in mediating carbon (C), nitrogen (N), and phosphorus (P) cycling. Using sequential chemical extraction, we quantified seven Fe fractions (Fe_ex, Fe_carb, Fe_ox1, Fe_ox2, Fe_mag, Fe_prs, and Fe_U) within the MASF across the plateau. The relative abundance of these fractions followed the sequence: Fe_U > Fe_prs > Fe_ox2 > Fe_ox1 > Fe_mag > Fe_carb > Fe_ex. The combined Fe_ox1 and Fe_ox2 fractions, representing highly reactive Fe (Fe_HR), constituted 6.82-55.77% of total iron (FeT), identifying them as the dominant Fe_HR components. Both Fe fraction abundance and inorganic phosphorus extracted by sequential extraction (IP_SE) decreased significantly along the grassland gradient: meadow steppe > typical steppe > desert steppe. This parallel decline underscores the key regulatory role of Fe (hydr)oxides in governing P fractionation and bioavailability within the MASF. Multivariate statistical analyses revealed soil physicochemical properties as the primary drivers of Fe_HR variability, explaining 64.52% of the variance, followed by climatic factors (18.6%) and vegetation factors (11.7%). IP_SE drivers exhibited a similar hierarchy, suggesting a coupled geochemical cycling mechanism between Fe_HR and IP_SE. This study provides fundamental geochemical insights into Fe fractionation within the MASF, advancing analytical approaches for understanding elemental cycling and ecological processes in Mongolian Plateau grasslands.

PMID:40856992 | DOI:10.1039/d5em00511f

J Endocrinol Invest. 2025 Aug 26. doi: 10.1007/s40618-025-02582-9. Online ahead of print.

ABSTRACT

PURPOSE: A sharp increase in diabetes-related mortality has been registered during the pandemic. Although immigrants are known to suffer from a higher prevalence of diabetes than host populations, data on diabetes-related mortality in pandemic years among immigrants are lacking.

METHODS: All deaths with any mention of diabetes (multiple causes of death-MCOD) among subjects aged 20-64 years were extracted from the Italian National Cause of Death Register in the years 2019-2021. Directly age-standardized mortality rates (2013 European standard population) were computed. Standardized mortality ratios (SMR) for different immigrant groups were estimated with expected numbers based on rates registered among Italian citizens.

RESULTS: Overall age-standardized mortality rates related to diabetes increased by 30% in 2020 compared to 2019, remaining high in 2021. Before the pandemic, large differences were observed across different immigrant groups; during the pandemic, the mortality disadvantage versus the native population widened among those already at increased risk. Among female immigrants, SMR in 2021 were 1.9 (95% Confidence Interval 1.1-2.8) in North Africans, 4.4 (2.5-6.3) in Sub-Saharan Africans and 2.8 (1.6-4.1) in South Asians.

CONCLUSION: Surveillance based on MCOD is warranted to assess if the large differences in diabetes-related mortality observed across different populations living in Italy will reduce in the next years.

PMID:40856980 | DOI:10.1007/s40618-025-02582-9

J Cancer Educ. 2025 Aug 26. doi: 10.1007/s13187-025-02715-x. Online ahead of print.

ABSTRACT

Cancer rehabilitation remains underutilized despite its value in addressing survivorship-related impairments. Early exposure to interdisciplinary cancer care, including oncology and physical medicine and rehabilitation (PM&R), is limited, particularly for students underrepresented in medicine (URiM). This study evaluated the impact of a novel interdisciplinary workshop introducing oncology and cancer rehabilitation, designed specifically to address the persistent educational and workforce disparities faced by URiM students. A half-day, in-person workshop was conducted in April 2025 at a medical school in New York City. The curriculum included lectures, case-based learning, a procedural suturing session, and a mentorship panel. Pre- and post-workshop surveys assessed self-reported knowledge and confidence in oncology, cancer rehabilitation, and clinical skills. Data were analyzed using descriptive statistics and unpaired t-tests. Of 160 pre-workshop survey respondents, 94 attended, with 73 completing post-workshop surveys (77.6% response rate). Over half of participants identified as URiM (53.3%). Significant improvements (p < 0.001) were observed across key domains, including confidence in cancer diagnosis (5.6 to 58.9%), understanding oncologist responsibilities (18.1 to 68.5%), oncology-PM&R collaboration awareness (8.8 to 71.2%), and procedural confidence in suturing (12.5 to 63.0%). A single-day interdisciplinary workshop significantly improved knowledge and confidence in oncology and cancer rehabilitation among high school students. Such targeted early-exposure initiatives could enhance diversity, address educational disparities, and improve awareness in the cancer care workforce.

PMID:40856965 | DOI:10.1007/s13187-025-02715-x

Int J Clin Pharm. 2025 Aug 26. doi: 10.1007/s11096-025-01989-x. Online ahead of print.

ABSTRACT

INTRODUCTION: Breast cancer is the most prevalent malignancy in women worldwide. Docetaxel-based chemotherapy is commonly used for treatment, but its clinical application is often constrained by hematologic toxicity, particularly severe bone marrow suppression. The early identification of high-risk patients is essential to prevent complications and optimize therapeutic outcomes. Machine learning offers advanced capabilities for risk prediction by capturing complex patterns beyond those of traditional statistical models.

AIM: This study aimed to identify the risk factors associated with bone marrow suppression in breast cancer patients receiving docetaxel-based chemotherapy, and to develop and validate predictive models using machine learning algorithms.

METHOD: This retrospective case-control study included 119 patients with breast cancer treated with docetaxel-based chemotherapy at the Hainan Hospital of Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, from January 2020 to December 2024. Patients were divided into bone marrow suppression (n = 57; WHO grades II-IV) and non-suppression (n = 62; grades 0-I) groups based on WHO toxicity criteria. Multivariate logistic regression was used to identify independent risk factors. Three prediction models, logistic regression, random forest, and AdaBoost, were constructed and evaluated. A five-fold cross-validation with 50 repetitions was performed to ensure model stability and reliability.

RESULTS: Multivariate analysis revealed that a low baseline lymphocyte count (OR = 4.95, 95% CI 1.62-17.0), decreased white blood cell (WBC) count (OR = 0.62, 95% CI 0.40-0.9), and reduced prealbumin level (OR = 0.98, 95% CI 0.97-0.99) were significantly associated with severe bone marrow suppression (all p < 0.05). Among the models, AdaBoost achieved the best overall performance (AUC = 0.81; specificity = 94%; accuracy = 77%). The random forest model showed the highest sensitivity (83%), while logistic regression was more interpretable but demonstrated a lower predictive ability (AUC = 0.69).

CONCLUSION: Pretreatment lymphocyte count, WBC count, and prealbumin level are reliable predictors of docetaxel-induced bone marrow suppression. The AdaBoost model demonstrates high specificity (94%) in identifying low-risk patients, supporting accurate risk stratification and personalized care in breast cancer treatment.

PMID:40856959 | DOI:10.1007/s11096-025-01989-x

Cardiovasc Drugs Ther. 2025 Aug 26. doi: 10.1007/s10557-025-07764-4. Online ahead of print.

ABSTRACT

PURPOSE: Homozygous Familial Hypercholesterolemia (HoFH) is a rare and life-threatening genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and early-onset atherosclerotic cardiovascular disease. Lomitapide, a microsomal triglyceride transfer protein (MTP) inhibitor, decreases LDL-C independent of LDL receptor function, providing an alternative treatment in this population. We aimed to evaluate the efficacy and safety of lomitapide in patients with HoFH through a systematic review and meta-analysis of available clinical evidence.

METHODS: A comprehensive search was conducted in PubMed, Scopus, and Web of Science through March 2025. Observational studies and clinical trials reporting on lipid profile changes and safety outcomes in HoFH patients receiving lomitapide were included. Outcomes were pooled using random-effects models, and heterogeneity was assessed using the I² statistic.

RESULTS: Eight studies comprising both adult and pediatric patients (n = 209) were included. Lomitapide significantly reduced LDL-C levels by 49.27%, total cholesterol by 46.05%, and apolipoprotein B by 51.01%. Reductions were also observed in triglycerides, VLDL-C, and non-HDL-C. HDL-C remained relatively unchanged. Adverse events were mostly gastrointestinal, with a 14% discontinuation rate. The overall quality of studies ranged from fair to good.

CONCLUSIONS: Lomitapide demonstrates substantial efficacy in reducing LDL-C and other atherogenic lipids in HoFH patients, with an acceptable safety profile. These findings support its role as an adjunctive therapy in this population, though further randomized controlled trials are warranted to validate long-term safety and effectiveness.

PMID:40856940 | DOI:10.1007/s10557-025-07764-4

Mol Diagn Ther. 2025 Aug 26. doi: 10.1007/s40291-025-00812-7. Online ahead of print.

ABSTRACT

Cardiovascular aging is a complex biological process involving progressive cellular and molecular changes that impair heart and vascular function. This review evaluates both fundamental mechanisms and therapeutic strategies, focusing on how recent advances in pharmacology, gene therapy, and regenerative medicine can be translated into clinical practice to mitigate age-related cardiovascular decline. We conducted a comprehensive analysis of peer-reviewed studies from 2000 to 2023, examining molecular pathways of cardiovascular aging and their modulation through pharmacological, genetic, and lifestyle interventions. The review prioritized clinical trials, translational research, and meta-analyses to assess therapeutic efficacy and safety. Current evidence highlights the effectiveness of senolytic drugs such as dasatinib and quercetin in reducing age-related cardiovascular dysfunction, while rapamycin and metformin show promise in improving cardiac longevity through metabolic regulation. Gene therapies, including clustered regularly interspaced short palindromic repeats (CRISPR)-based interventions, demonstrate potential in preclinical models for cardiac regeneration. Stem cell therapies and nanotechnology-based drug delivery systems are emerging as innovative approaches to enhance tissue repair. In addition, lifestyle modifications such as Mediterranean diet adherence and exercise significantly improve vascular health in aging populations. However, challenges remain in drug delivery, patient-specific responses, and long-term safety of novel therapies. The integration of targeted pharmacological treatments, advanced regenerative techniques, and personalized lifestyle interventions represents a transformative approach to managing cardiovascular aging. Future research should focus on optimizing therapeutic combinations, refining delivery methods, and validating biomarkers for clinical monitoring. A multidisciplinary strategy combining these advances will be essential to improve cardiovascular outcomes in aging populations.

PMID:40856932 | DOI:10.1007/s40291-025-00812-7

Jpn J Ophthalmol. 2025 Aug 26. doi: 10.1007/s10384-025-01265-5. Online ahead of print.

ABSTRACT

PURPOSE: This study evaluated the efficacy and safety of initially implanted PreserFlo MicroShunt (PMS) in Japanese patients with exfoliation glaucoma (XFG). Using propensity score matching, intraocular pressure (IOP) control rates were compared between patients with XFG and primary open-angle glaucoma (POAG).

STUDY DESIGN: Retrospective observational study.

METHODS: This study reviewed 31 eyes of 31 patients with XFG who underwent initial PMS implantation with mitomycin C. IOP, medication scores, and corneal endothelial cell density (CECD) were assessed preoperatively and at up to 6 months postoperatively. Kaplan-Meier analysis was used to estimate the 6-month survival rate, defined as an IOP reduction of > 20% from baseline and an IOP < 15 mmHg. The incidences of needling, reoperation, and complications were also assessed. IOP control was compared between XFG and propensity-score-matched POAG patients using the log-rank test.

RESULTS: At 6 months, the mean IOP had decreased significantly, from 22.3 ± 6.6 to 14.7 ± 6.6 mmHg, and the medication score had declined from 4.5 to 1.4. CECD decreased from 2127 to 1902 cells/mm², although this was not statistically significant. The complete success rate (without any glaucoma medications or intervention) was 48%. Postoperative complications included anterior chamber hemorrhage and choroidal detachment. Needling was performed in nine eyes (29.0%), and additional surgery was performed in five eyes (16.1%). Compared to POAG patients (11.9 mmHg), XFG patients had higher postoperative IOP (14.8 mmHg) and higher medication scores (0.5 vs 1.4, p = 0.04) and a lower success rate (62.2% vs 41.7%).

CONCLUSIONS: PMS in Japanese patients with XFG resulted in a significant IOP reduction over 6 months, with a relatively favorable safety profile. However, its efficacy was slightly inferior to that in POAG, implying potential differences in PMS responsiveness between glaucoma subtypes.

PMID:40856918 | DOI:10.1007/s10384-025-01265-5

Am J Clin Dermatol. 2025 Aug 26. doi: 10.1007/s40257-025-00977-1. Online ahead of print.

ABSTRACT

BACKGROUND: Erythrodermic psoriasis (EP) is a severe and rare variant of psoriasis. Clinical features include scaling and erythema affecting more than 75% of body surface area, associated with systemic symptoms such as lymphadenopathy, arthralgia, fever, fatigue, dehydration, serum electrolyte disturbances, and tachycardia, making this condition a potentially life-threatening disease. Differential diagnosis can be challenging, encompasses atopic dermatitis, cutaneous adverse drug reaction, and advanced cutaneous lymphoma. Following a correct diagnostic framing, appropriate systemic treatment must be initiated. Unfortunately, there are no recent up-to-date guidelines and standardized treatment options for EP are still lacking.

OBJECTIVE: To review the current reported systemic treatment options for EP.

METHODS: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and based on a search in MEDLINE, PubMed, Scopus, and Cochrane Library for articles in English from first available publication to 9 November 2024.

RESULTS: In all, 145 studies were included in the review. Case reports and case series are the main available work, reporting heterogeneous outcomes and effectiveness with nonbiologic and biologic systemic agents. Among non-biologic systemic treatments, methotrexate and cyclosporin are the most widely reported as treatment for EP, showing clinical response in over 60% of cases, with cyclosporine offering a faster onset of action and being suitable for acute management. Available randomized controlled trials include patients with EP treated with etretinate, infliximab, certolizumab-pegol (CZP), Ixekizumab, guselkumab, risankizumab, and deucravacitinib. However, these trials were not specifically designed for erythrodermic psoriasis, and the sample size of EP patients included is limited, resulting in reduced statistical power and limiting the reliability of the findings. Among TNF-α inhibitors, infliximab is the most reported agent, with data on 103 patients. Certolizumab pegol (CZP) also showed promising results, with PASI 75 achieved in over 80% of patients at 52 weeks. A retrospective analysis comparing infliximab, adalimumab, etanercept, ustekinumab, and efalizumab found TNF-α inhibitors to be superior to other biologic classes. Regarding IL-17 inhibitors, secukinumab is the second most frequently studied biologic, with 93 patients reported. It demonstrated rapid efficacy, achieving PASI 75 in more than 80% of patients by week 8. A head-to-head comparison with ixekizumab showed comparable outcomes. Among IL-23 inhibitors, risankizumab led to PASI 90 in over 75% of patients at week 16, suggesting high efficacy despite more limited data.

CONCLUSIONS: Non-biologic systemic drugs appear to be a rational first-line therapy, with cyclosporine showing good results in managing the acute phase and methotrexate being effective in maintaining remission. In the case of contraindications or treatment failure of traditional systemic therapies, among biologic drugs, the rapidity of action, safety, and limited evidence of efficacy are in favor of IL-17 inhibitors and risankizumab. However, the findings we report are limited by the evidence available in current literature, which is characterized by low statistical power.

PMID:40856907 | DOI:10.1007/s40257-025-00977-1