Tag: pubmed

J Cachexia Sarcopenia Muscle. 2025 Oct;16(5):e13743. doi: 10.1002/jcsm.13743.

ABSTRACT

BACKGROUND: Polytrauma patients with an Injury Severity Score (ISS) ≥ 16 have a high mortality rate. Early identification of patients at risk of mortality is key. Different risk stratification models are available; however, body composition on third lumbar computed tomography (L3 CT) is not routinely used. The aim of this study is to determine the effect of CT body composition on 1-year mortality in adult polytrauma patients.

METHODS: Body composition analysis (L3 CT) was performed on 593 adult polytrauma patients. The associations with 1-year mortality were assessed using uni- and multivariable logistic regression analysis. As a sensitivity analysis, 1-year mortality was analysed using Kaplan-Meier survival curves, log-rank tests and Cox regression.

RESULTS: The study population was predominantly male (69.5%), with a mean age of 55 (±20) years and an average BMI of 25.34 kg/m² (±4.07). Comorbidities were present in 327 (55.4%) patients, with an average Charlson Comorbidity Index (CCI) of 2.07 points (±2.1). The mean ISS score was 27.59 (±11.06); 323 (54.5%) patients had an ISS ≥ 25 points. Age, CCI, ISS, skeletal muscle index and skeletal muscle radiation attenuation (OR 1.053, 5.713, 3.711, 0. 563 and 0.533, respectively; p < 0.001), subcutaneous adipose tissue radiation attenuation (SATRA OR 1.253, p = 0.028) and visceral adipose tissue index (OR 1.242, p = 0.038) were significantly associated with 1-year mortality. In multivariable logistic regression, age, ISS and SATRA remained statistically significantly associated with 1-year mortality (OR 1.062, p < 0.001; OR 4.761, p < 0.001; OR 1.396, p = 0.009).

CONCLUSIONS: This study demonstrated that subcutaneous adipose tissue radiation attenuation on emergency trauma CT scans is significantly associated with 1-year mortality in adult polytrauma patients. Additionally, we found a significant effect of age and ISS on 1-year mortality. Incorporating body composition analysis could lead to a better selection of patients at risk for 1-year mortality and aid in treatment decision-making.

PMID:41078117 | DOI:10.1002/jcsm.13743

J Cardiovasc Electrophysiol. 2025 Oct 13. doi: 10.1111/jce.70135. Online ahead of print.

ABSTRACT

INTRODUCTION: Cannabis use is significantly increasing worldwide yet its cardiovascular effects and arrhythmogenic potential remain unclear. As legalization expands, it is critical to understand public health risks and clinical implications. This study evaluates the relationship between cannabis use and the risk of arrhythmias using a large, real-world dataset.

METHODS: This retrospective cohort study utilized deidentified electronic health records from 68 U.S. healthcare organizations within the TriNetX network. A total of 210 817 adult cannabis users were identified and matched 1:1 with 210 817 ibuprofen users using propensity score matching across 17 baseline variables, including demographics, cardiovascular risk factors, and medication use. The primary outcomes were incident diagnoses of atrial fibrillation/flutter (AF/AFL), paroxysmal tachycardia, premature beats, and ventricular tachycardia/fibrillation (VT/VF). Outcomes were assessed using Cox proportional hazards models and Kaplan-Meier survival analyses.

RESULTS: Cannabis use was significantly associated with an increased risk of multiple arrhythmias compared to ibuprofen use. The incidence of AF/AFL was 1895 versus 1332 cases (HR = 1.549, 95% CI: 1.444-1.662, p < 0.001). Paroxysmal tachycardia occurred in 1065 versus 672 patients (HR = 1.791, 95% CI: 1.626-1.973, p < 0.001), and premature beats in 1135 versus 745 patients (HR = 1.739, 95% CI: 1.585-1.908, p < 0.001). The most pronounced relative risk was observed for VT/VF, with 97 versus 35 cases (HR = 3.078, 95% CI: 2.089-4.533, p < 0.001). All associations remained statistically significant after adjustment, and Kaplan-Meier curves demonstrated lower arrhythmia-free survival in cannabis users across all endpoints.

CONCLUSION: Cannabis use was associated with an increased risk of multiple arrhythmias, particularly atrial fibrillation and ventricular arrhythmias. These findings highlight the need for further research on the cardiovascular effects of cannabis and reinforce the importance of patient counseling regarding its potential arrhythmogenic risks.

PMID:41078108 | DOI:10.1111/jce.70135

Aging Cell. 2025 Oct 13:e70265. doi: 10.1111/acel.70265. Online ahead of print.

ABSTRACT

While preclinical studies suggest that Phosphodiesterase 5 (PDE5) inhibition may reduce cognitive impairment, findings from observational studies on whether PDE5 inhibitors reduce Alzheimer’s disease (AD) risk have been inconsistent. We performed a two-sample cis-Mendelian Randomisation (MR) analysis to estimate the causal effect of PDE5 inhibition on AD risk. The analysis was performed across four different genome-wide association studies (GWAS) of AD to enhance reliability through triangulation. Additionally, a sex-stratified MR analysis using data from UK Biobank was performed to assess potential sex-specific effects. No evidence of a causal association between PDE5 inhibition and AD risk was found in the main analyses. Similar findings were obtained in the sex-stratified analysis. Our study uses genetic data to triangulate the evidence and suggests that PDE5 inhibitors are unlikely to decrease the risk of AD. Further research is needed to thoroughly understand the impact of PDE5 inhibitors on the risk of Alzheimer’s disease.

PMID:41078087 | DOI:10.1111/acel.70265

Genome Biol Evol. 2025 Oct 13:evaf194. doi: 10.1093/gbe/evaf194. Online ahead of print.

ABSTRACT

NUPTs are DNA sequences of plastid origin present in plant nuclear genomes to varying, though typically low, amounts. It is assumed that they are continuously formed and, due to their potentially mutagenic effect, removed at a constant turnover rate, which should result in an exponential decay of their age distributions and a negative correlation between age and size. However, these assumptions are based on analysis from a limited number of species and have never been explicitly tested. To gain insight into the mechanisms driving the origin and evolution of NUPTs, here we surveyed the plastid and nuclear genomes of 30 species representing the main angiosperm (flowering plants) lineages. By modeling the distribution of ages and sizes, examining their linear arrangement across the plastid genome, and statistically assessing spatial biases with respect to other genomic features, we showed that NUPTs are i) formed by both continuous and episodic mechanisms; ii) unevenly represented across the plastid genome; iii) consistently associated with certain classes of RNA genes, in particular rRNA, tRNA and regulatory RNA genes; iv) differentially contributing to structural genes; and v) closer than expected to different superfamilies of transposons in a species-specific manner. Our results reveal the unexpected complexity in the mechanisms driving the origin of NUPTs, which do not only involve their continuous formation but also episodic, highlight their role as a major source of non-coding RNA genes and other genomic features and provide a more complete picture of the different drivers of evolutionary change at the genome level.

PMID:41078074 | DOI:10.1093/gbe/evaf194

Dig Dis. 2025 Oct 13:1-20. doi: 10.1159/000548588. Online ahead of print.

ABSTRACT

INTRODUCTION: Green tea polyphenols (GTPs) and aspirin were demonstrated to be novel candidates for cancer chemoprevention. This study aimed to investigate effects of GTPs and aspirin on esophageal diseases.

METHODS: This non-randomized prospective cohort study recruited participants from January 2012 to January 2013, who self-reported long-term GTPs intake, aspirin intake and no medicine use in questionnaire and underwent gastroscopy. Regression was defined as any reversal of process from normal epithelium to esophageal high-grade intraepithelial neoplasia. The primary outcome was regression rates after a one-year follow-up.

RESULTS: A total of 159, 151,160 participants self-reported GTPs intake, aspirin intake, and no medication. After one year, 78, 81, and 83 participants received follow-up endoscopy in GTPs, aspirin, and control groups, respectively. There was no statistically significant difference in baseline pathology between the final cohort and lost to follow-up group. The average age of participants was 50.11  5.62 years old, consisting of 42 female and 200 male. The regression rates of esophageal precursor diseases were 68%, 55%, and 48% in GTPs, aspirin, and control groups, respectively (P = 0.036). Analyzing esophagitis subgroup, the regression rate of GTPs group (43/69, 62%) was significantly higher than aspirin group (32/67, 48%) and control group (27/70, 39%) (P = 0.019). One person experienced nausea for GTPs (1/159) and one person experienced gastrointestinal bleeding in the aspirin group (1/151).

CONCLUSIONS: GTPs, rather than aspirin, was associated with esophagitis remission compared with the control group. The benefits of GTPs on esophageal precursor diseases make it a promising health supplement.

PMID:41078050 | DOI:10.1159/000548588

Med Princ Pract. 2025 Oct 11:1-23. doi: 10.1159/000548894. Online ahead of print.

ABSTRACT

OBJECTIVE: Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease that usually responds to corticosteroids ± azathioprine (AZA). However, some patients are intolerant or refractory to first-line therapy and require second-line immunosuppression. Mycophenolate mofetil (MMF) and tacrolimus (TAC) are commonly used alternatives, although comparative evidence is limited. This systematic review and meta-analysis evaluated the efficacy and safety of MMF and TAC in adult AIH patients who failed first-line therapy.

METHODS: A systematic search of six databases identified 16 eligible studies (n = 705), including retrospective cohorts and one case series. Study quality was assessed using the Newcastle-Ottawa Scale and the MMS (methodological quality and synthesis of case series and case reports) tool.

RESULTS: Biochemical remission was achieved in 56% of MMF-treated patients, rising to 66% with ≥6 months follow-up. TAC showed a pooled remission rate of 66%, increasing to 67% when defined by transaminase normalization. MMF was particularly effective in azathioprine-intolerant patients, while TAC showed better outcomes in steroid-refractory patients. Adverse events differed: MMF was most often associated with gastrointestinal intolerance, whereas TAC was linked to tremor, hypertension, diabetes, and renal impairment. However, statistical analysis showed wide confidence intervals, and there was considerable heterogeneity across studies.

CONCLUSION: Both MMF and TAC are effective second-line therapies for AIH. MMF appears safer and better tolerated in azathioprine-intolerant patients, while tacrolimus showed a modest advantage in efficacy over mycophenolate in steroid-refractory cases. Given the limitations of current evidence, including small sample sizes, heterogeneity, and lack of randomized controlled trials, treatment choice should be individualized until higher-quality data are available.

PMID:41078044 | DOI:10.1159/000548894

Am J Nephrol. 2025 Oct 10:1-13. doi: 10.1159/000548738. Online ahead of print.

ABSTRACT

INTRODUCTION: Parathyroid hormone (PTH) induces browning of adipose tissue, leading to increased resting energy expenditure and loss of adipose and muscle tissues in animal models of kidney failure. However, its clinical significance in humans remains unclear. This study aimed to investigate whether PTH-lowering therapy with upacicalcet, a novel injectable calcimimetic, affects serum albumin levels as a surrogate marker of protein-energy wasting in patients on hemodialysis with secondary hyperparathyroidism (SHPT).

METHODS: This was a post-hoc analysis of a phase 3, double-blind, placebo-controlled study of upacicalcet for the treatment of SHPT in patients on hemodialysis. Participants were randomized in a 2:1 ratio to receive either upacicalcet or placebo after each hemodialysis session for 24 weeks. Longitudinal changes in serum albumin levels were compared between groups using mixed-effects models for repeated measures. The rate of change (slope) in serum albumin over time was also estimated using a linear mixed-effects model.

RESULTS: A total of 99 patients in the upacicalcet group and 46 patients in the placebo group were included in the analysis. While serum albumin levels tended to decline in the placebo group, they remained relatively stable in the upacicalcet group, with a significant treatment-by-time interaction. In the linear mixed-effects model, the slope was less steep in the upacicalcet group than in the placebo group, although the between-group difference (0.09 g/dL per year; 95% CI, -0.04 to 0.23) did not reach statistical significance.

CONCLUSION: These findings raise the hypothesis that PTH suppression with upacicalcet mitigates the gradual decline in serum albumin levels over time. Further studies are warranted to investigate the long-term impact of PTH control on protein-energy wasting and related clinical outcomes.

PMID:41078042 | DOI:10.1159/000548738

Acta Cytol. 2025 Oct 9:1-18. doi: 10.1159/000548613. Online ahead of print.

ABSTRACT

INTRODUCTION: Hyperthyroidism-related epithelial hyperplasia is seldomly listed as a pitfall in thyroid cytology. Therefore, we focused on the cytomorphological characteristics of epithelial hyperplasia and compared these features with papillary thyroid carcinoma (PTC).

METHODS: Study group consisted of 76 patients (133 FNA specimens) histologically diagnosed with hyperthyroidism-related epithelial hyperplasia without a concomitant malignancy. The control group contained 21 histologically verified FNAs of PTCs. A total of 48 cytomorphological features were quantitatively evaluated.

RESULTS: Statistically significant differences between the study groups were discovered on the architectural, cellular, and nuclear levels. Nuclear features varied most: nuclear elongation, grooves, irregular nuclear membrane, pseudoinclusions, the presence of nucleoli or small eccentric nucleoli were clearly more common in PTC group.

CONCLUSION: Fine-needle aspiration referrals with clinical data and thyroid function test results can facilitate the interpretation of cytomorphological features and reduce the use of undetermined categories in cases of hyperthyroidism-related epithelial hyperplasia.

PMID:41078039 | DOI:10.1159/000548613

Conserv Biol. 2025 Oct 12:e70158. doi: 10.1111/cobi.70158. Online ahead of print.

ABSTRACT

The Natura 2000 (N2K) network of protected areas is one of the main tools for area-based conservation in the European Union (EU), yet its role in preserving plant biodiversity requires better understanding. We examined data kept in the European Vegetation Archive from over 1.2 million vegetation plots and obtained over 14.2 million plant species occurrences. To test the N2K network’s representativeness of plant species gamma diversity, we compared the number and percentage of native and conservation priority species in- and outside the N2K network throughout the EU and for individual countries, biogeographical regions, and combinations thereof. We then determined whether N2K sites hosted more species than sites outside the network with the species-area relationship. Overall, almost 90% of the native vascular plant species occurred at least once in the N2K network. Yet, significant variation exists across countries and biogeographical regions-from 0% of species in the Boreal region of Lithuania, to 98% in the Alpine region of Croatia-indicating that local N2K sites are not equally representative of the regional gamma diversity. Nonetheless, the N2K network contains more species than land outside the network when area is taken into account. The planned expansion of the N2K network, as mandated by the European Biodiversity Strategy for 2030, should prioritize areas with currently underrepresented elements of the EU vascular flora.

PMID:41077638 | DOI:10.1111/cobi.70158

Pharmacoepidemiol Drug Saf. 2025 Oct;34(10):e70235. doi: 10.1002/pds.70235.

ABSTRACT

PURPOSE: Observational comparative studies can be analyzed using intention-to-treat (ITT) (i.e., initial-treatment) or as-treated (AT) (i.e., per-protocol) approaches to estimate distinct treatment effects. Unfortunately, AT analyses have an increased vulnerability to selection bias from informative censoring. While methods for informative censoring adjustment are well established, the nuances of their implementation are less well documented.

METHODS: We compared marginal hazard ratios for all-cause mortality from ITT and AT analyses comparing new users of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in the clinical practice research datalink from 2019 to 2022 using inverse probability of treatment weights. We created inverse probability of censoring weights (IPCW) using (A) non-lagged and (B) lagged models to adjust for informative censoring in the AT analyses. We replicated analyses comparing acetylcholinesterase inhibitor and angiotensin receptor blocker initiators to assess the impact of IPCW in a different context.

RESULTS: We identified 335 469 SSRI initiators and 24 318 SNRI initiators. While AT estimates (HR: 1.50, 95% CI: 1.30-1.74) were further from the null than ITT estimates (HR: 1.22, 95% CI: 1.12-1.32), applying IPCW attenuated AT estimates using both lagged and non-lagged models (lagged HR: 1.24, 95% CI: 1.08-1.44; non-lagged HR: 1.16, 95% CI: 1.00-1.33). In the 337 981 antihypertensive initiators, however, IPCW did not influence AT estimates.

CONCLUSIONS: Younger patients were more likely to discontinue SSRIs than SNRIs, resulting in biased AT estimates closer to estimates in older patients. IPCW attenuated this bias, highlighting the utility of weighting when censoring is linked to patient characteristics.

PMID:41077625 | DOI:10.1002/pds.70235