Clinics (Sao Paulo, Brazil)最新文献

{"title":"Gastrointestinal bleeding in hepatocellular carcinoma under systemic therapy: Real-world incidence and clinical predictors.","authors":"Leonardo G Da Fonseca, Lucas Takeshi Ikeoka, Eduardo Kim Sampaio, Thamires Haick Martins da Silveira, Victor Junji Yamamoto, Marina Acevedo Zarzar de Melo, Paulo Marcelo Hoff, Jorge Sabbaga","doi":"10.1016/j.clinsp.2026.101155","DOIUrl":"10.1016/j.clinsp.2026.101155","url":null,"abstract":"<p><strong>Objective: </strong>Gastrointestinal (GI) bleeding is a major complication in patients with advanced Hepatocellular Carcinoma (HCC), particularly among those with underlying portal hypertension. Although systemic therapy has improved survival outcomes, real-world data regarding the incidence, predictors, and clinical impact of GI bleeding remain limited. This study aimed to evaluate the incidence, risk factors, and prognostic implications of GI bleeding in patients with advanced HCC receiving sorafenib.</p><p><strong>Methods: </strong>This retrospective cohort study included 439 patients with advanced HCC between 2009 and 2025. Time-to-event analyses were performed from treatment initiation. The cumulative incidence of GI bleeding and bleeding-related mortality was estimated using competing-risk methods. Incidence rates were calculated per 100 Person-Years (PY), and adjusted incidence rate ratios were estimated using multivariable Poisson regression. Predictors of GI bleeding were further evaluated using multivariable logistic regression.</p><p><strong>Results: </strong>Baseline endoscopy was performed in 56% of patients, of whom 58% had evidence of portal hypertension. The incidence rate of GI bleeding was 5.6 per 100 PY (95% Confidence Interval [95% CI 4.6-6.8]), with cumulative incidence rates of 10.57% (95% CI 7.85-14.16) at 6-months and 23.06% (95% CI 18.60-28.38) at 12-months. Esophagogastric varices, splenomegaly, vascular invasion, and prior GI bleeding were independently associated with increased bleeding risk. Based on these predictors, a simple additive risk score ranging from 0 to 4 was developed and demonstrated progressive increases in predicted bleeding probability across risk categories, supporting its potential utility for clinical risk stratification. GI bleeding was associated with poor outcomes, with a median survival time of 11-days after the event and a bleeding-related mortality rate of 75.5%.</p><p><strong>Conclusion: </strong>GI bleeding is a frequent and highly lethal complication in patients with advanced HCC. These findings highlight the importance of risk assessment, endoscopic evaluation, and preventive strategies in this population.</p>","PeriodicalId":520594,"journal":{"name":"Clinics (Sao Paulo, Brazil)","volume":"81 ","pages":"101155"},"PeriodicalIF":2.4,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between early improvements in atherogenic lipids and reported dietary changes after RYGB: a pilot exploratory analysis in women with type 2 diabetes.","authors":"Gabriela de Oliveira Lemos, Ana Paula Aguiar Prudêncio, Renato H Nakagawa Santos, João Valentini Neto, Aline Marcadenti, Regina Mara Fisberg, Helena Menezes, Steven B Heymsfield, Raquel Susana Torrinhas, Dan Linetzky Waitzberg","doi":"10.1016/j.clinsp.2026.101125","DOIUrl":"10.1016/j.clinsp.2026.101125","url":null,"abstract":"<p><strong>Introduction: </strong>Roux-en-Y Gastric Bypass (RYGB) is considered a metabolic surgery due to its early effects on obesity-related dysfunctions, including dyslipidemia. However, some studies suggest that these improvements may be reproduced by dietary changes, primarily calorie restriction. We evaluated whether early post-RYGB changes in dietary intake are associated with improvements in the plasma lipid profile in women with Type 2 Diabetes (T2D).</p><p><strong>Methods: </strong>We analyzed retrospective paired data from women in the SURMetaGIT cohort at baseline and 3-months after RYGB. Dietary intake was assessed by 7-day food records, summarized as F&V (Fruits/legumes/Vegetables) and HFSS (high-fat/sugar/sodium) food groups, and quantified for energy, macronutrients, and fiber using Nutrabem®. Usual intake was estimated using the Multiple Source Method and adjusted for energy. Plasma lipids included total cholesterol, LDL-c, HDL-c, non-HDL-c, VLDL, and triglycerides. Paired comparisons, correlations, and multivariable linear regression were used to evaluate associations between dietary changes and lipid outcomes.</p><p><strong>Results: </strong>Post-RYGB, patients exhibited a significant decrease in pro-atherogenic lipids. These changes did not correlate with variations in energy, macronutrient, or food-group intake. Conversely, HDL-c showed an independent positive association with phytosterols (β = 0.34, 95% CI: 0.10-0.59; p = 0.007) and a negative association with trans fatty acid intake (β = -0.44, 95% CI:0.82 to -0.06; p = 0.025).</p><p><strong>Conclusion: </strong>Early pro-atherogenic lipid improvements in women with T2D after RYGB showed no association with changes in reported energy macronutrient or broad food group intake. Nevertheless, trends in HDL-c were associated with intake of phytosterols and trans fatty acids, suggesting a potential role for dietary counseling to optimize HDL-c after RYGB.</p>","PeriodicalId":520594,"journal":{"name":"Clinics (Sao Paulo, Brazil)","volume":"81 ","pages":"101125"},"PeriodicalIF":2.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13594641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific differences in the anatomical localization and severity of coronary artery disease: differential impact of conventional cardiovascular risk factors.","authors":"Nurgül Keser, Yetkin Korkmaz, Selami Doğan, Mehmet Şeker, Samet Yavuz, Mert Babaoğlu, Almina Erdem, İrem Yılmaz, Mustafa Oğuz, Akın Torun, Lutfullah Orhan, Mehmet Uzun","doi":"10.1016/j.clinsp.2026.101149","DOIUrl":"10.1016/j.clinsp.2026.101149","url":null,"abstract":"<p><strong>Background: </strong>Sex differences in coronary artery disease (CAD) are well recognized. Whether conventional cardiovascular risk factors (CVRFs) exert differential effects on anatomical localization and stenosis severity on coronary arteries (CA) remains uncertain. We aimed to evaluate sex-specific associations between major CVRFs and CA involvement.</p><p><strong>Methods: </strong>We analyzed 978 patients undergoing coronary angiography (CAG) between 2017-2023. Sex, age, hypertension (HT), diabetes mellitus (DM), history of CAD (HCAD), smoking, Syntax scores (SS), lipid parameters and creatinine levels were assessed. Segment-based coronary involvement was evaluated using correlation and multivariable regression analyses.</p><p><strong>Results: </strong>Women were older (p < 0.001), had higher rates of HT (p = 0.001), DM (p = 0.026) and higher total cholesterol (p = 0.001), LDL-C (p = 0.001) and HDL-C levels (p = 0.001). In contrast HCAD (p = 0.001), smoking (p = 0.009) and SS (p < 0,01) were higher in men. HT was associated with circumflex (Cx) (p = 0.029) and right coronary artery (RCA) (p = 0.002) involvement in women; with proximal left anterior descending artery (LAD) (p = 0.024) involvement in men. DM showed significant associations with LAD (p = 0.001), 1st diagonal (Dg) (p = 0.003), Cx: (p = 0.001) and RCA (p = 0.001) territories in women. HCAD was associated with proximal LAD (p = 0.013), CX (p = 0.006) and RCA (p = 0.016) in men; proximal LAD (p = 0.047), CX (p = 0.014) and RCA (p = 0.009) in women. Lipid parameters had no association with CA involvement in either sex after adjustment. Creatinine levels were associated with RCA and CX involvement in women and with LMCA and proximal LAD territories in men.</p><p><strong>Conclusion: </strong>CVRFs exert sex-specific effects on CA, highlighting the importance of sex aware risk stratification in CAD.</p>","PeriodicalId":520594,"journal":{"name":"Clinics (Sao Paulo, Brazil)","volume":"81 ","pages":"101149"},"PeriodicalIF":2.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular risk estimation using the steno type 1 risk engine in Brazilian individuals with type 1 diabetes: a multicenter cross-sectional study.","authors":"Marília Brito Gomes, Fernanda Oliveira Braga de Albuquerque, Alessandra Matheus, Luiz Henrique Canani, Adriana Costa Forti, Reine Marie Chaves, Elizabeth João Pavin, Renan Montenegro Junior, Sergio A Dib, João S Felicio, Rosangela Roginski Réa, Marcia Nery, Carlos Antonio Negrato, Luana Casari Silva","doi":"10.1016/j.clinsp.2026.101082","DOIUrl":"10.1016/j.clinsp.2026.101082","url":null,"abstract":"<p><strong>Objective: </strong>To assess the 5- and 10-year Cardiovascular Disease (CVD) risk among Brazilian patients with Type 1 Diabetes (T1D) using the Steno Type 1 Risk Engine (ST1RE), and to evaluate the prevalence of clinical CVD, analyzing traditional and non-traditional risk factors.</p><p><strong>Material and methods: </strong>This was a cross-sectional multicenter study conducted in 13 public clinics in 11 Brazilian cities, involving 1,760 patients. The ST1RE was used in patients without previous CVD (n = 1,300).</p><p><strong>Results: </strong>The prevalence of CVD was 2.1%, with ischemic heart disease being the most common. These patients were older, had higher age at T1D diagnosis, and longer diabetes duration when CVD was diagnosed. According to ST1RE 10-year risk, 70.7% were classified as low, 18.0% as moderate, and 11.3% as high risk without differences regarding sex. A lower use of cardioprotective drugs was noted in patients with moderate/high 10-year ST1RE in relation to guidelines recommendations. Higher age at diagnosis, presence of retinopathy, elevated high-sensitivity C-reactive protein, and uric acid levels were associated to moderate/high ST1RE risk.</p><p><strong>Conclusions: </strong>Almost 30% of our patients had moderate/high ST1RE risk and were undertreated for CVD risk factors. This highlights the need to establish strategies to improve cardiovascular and diabetes management risk in routine clinical practice.</p>","PeriodicalId":520594,"journal":{"name":"Clinics (Sao Paulo, Brazil)","volume":"81 ","pages":"101082"},"PeriodicalIF":2.4,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematological parameters in patients with chronic pain on long-term dipyrone therapy followed in a tertiary hospital: a retrospective cohort study.","authors":"Gibran E Harcha Munoz, Felipe Chiodini Machado, Heleno de Paiva Oliveira, Maria F de Paula Ferreira, Áquila Lopes Gouvêa, Hazem Adel Ashmawi","doi":"10.1016/j.clinsp.2026.101124","DOIUrl":"10.1016/j.clinsp.2026.101124","url":null,"abstract":"<p><strong>Background: </strong>Chronic pain is a significant public health problem, with high prevalence and substantial impact on quality of life and costs in healthcare, particularly in the context of ongoing opioid abuse crises in many countries. Chronic pain management often involves a multimodal approach. Dipyrone or metamizole has been used widely for several decades as a non-opioid analgesic. Despite its effectiveness, concerns regarding potential side effects, such as agranulocytosis, have led to its ban in several countries. This study aimed to describe changes in erythrocyte, leukocyte, neutrophil, and platelet counts among patients with chronic pain receiving dipyrone therapy for longer than six months.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using data manually collected from medical records of patients treated at the Pain Outpatient Clinic of a tertiary hospital in Brazil, between 2012 and 2022. The research was registered and approved by the institutional ethical Committee. A total of 1,880 adult patients with chronic pain of different causes who received well documented continuous dipyrone therapy for at least six months. Blood counts before dipyrone use and at the end of dipyrone therapy were evaluated. A control group of chronic pain patients not exposed to dipyrone was not available, which represents a major limitation. Statistical analyses such as paired t-tests, Pearson correlations, and multivariate regression were performed to assess changes in blood cell counts, identify any relationships with dipyrone dosage, therapy duration, and other factors.</p><p><strong>Results: </strong>The mean age of the study population was 58.7 years, with a mean duration of dipyrone therapy of 6.5 years. Statistically significant decreases were observed in neutrophil, leukocyte, and platelet counts from baseline to follow-up; however, these reductions were not clinically relevant and within normal established laboratory reference values. No severe hematological or severe drug reaction such as agranulocytosis were observed. A limited multivariable model did not identify clinically meaningful associations between prescribed dipyrone dose or treatment duration and blood count changes.</p><p><strong>Conclusions: </strong>In this large cohort of chronic pain patients on long-term dipyrone therapy, only mild and clinically insignificant variations in hematological parameters were observed, and no cases of agranulocytosis were identified. However, the absence of an unexposed control group of chronic pain patients and the lack of systematic data on concomitant medications preclude attributing these observed changes to dipyrone alone.</p>","PeriodicalId":520594,"journal":{"name":"Clinics (Sao Paulo, Brazil)","volume":"81 ","pages":"101124"},"PeriodicalIF":2.4,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standardizing cervical canal morphometry: A step toward improved clinical reproducibility.","authors":"Larissa Tozetti, Carlos Fernando Pereira da Silva Herrero, Vitória Argenti Perez, Talis Nascimento Miranda Freitas, Denise Marques Costa Pereira da Silva, Mariana Demetrio de Sousa Pontes, Thabata Pasquini Soeira","doi":"10.1016/j.clinsp.2026.101049","DOIUrl":"10.1016/j.clinsp.2026.101049","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to establish a comprehensive protocol for assessing the morphometric parameters of the cervical vertebral canal using Magnetic Resonance Imaging (MRI) and to evaluate the interobserver reliability of these measurements.</p><p><strong>Methods: </strong>A descriptive study was conducted to evaluate the diameter and area of the cervical vertebral canal through MRI scans of 20 patients. Two independent observers performed the measurements, and interobserver reliability was assessed using Intraclass Correlation Coefficients (ICC).</p><p><strong>Results: </strong>The study detailed an effective method for evaluating both the diameter and area of the cervical vertebral canal, demonstrating excellent interobserver reproducibility for diameter measurements (ICC > 0.969) and good reproducibility for area measurements (ICC > 0.893).</p><p><strong>Conclusion: </strong>This protocol provides a standardized approach for measuring the cervical vertebral canal parameters, enhancing the evaluation of stenosis, and supporting precise clinical decision-making. The protocol is clear, reproducible, and adaptable for use in other research settings and clinical practices.</p>","PeriodicalId":520594,"journal":{"name":"Clinics (Sao Paulo, Brazil)","volume":"81 ","pages":"101049"},"PeriodicalIF":2.4,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between body mass index and peak expiratory flow rate and the mediating role of hand grip strength: evidence from CHARLS.","authors":"Xiaonan Zhang, Haowei Jin, Sheng Zhou","doi":"10.1016/j.clinsp.2026.101091","DOIUrl":"10.1016/j.clinsp.2026.101091","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the mediating role of Hand Grip Strength (HGS) in the relationship between Body Mass Index (BMI) and Peak Expiratory Flow (PEF) among Chinese middle-aged and elderly adults without diagnosed lung disease.</p><p><strong>Method: </strong>This cross-sectional study utilized data from the 2015 China Health and Retirement Longitudinal Study (CHARLS). HGS, BMI, and PEF were assessed through standardized measurements. Logistic regression models were applied to evaluate the associations of BMI and HGS with reduced PEF, defined as PEF%pred < 80%. Mediation analysis was conducted to explore the relation between BMI and PEF%pred via HGS.</p><p><strong>Result: </strong>A total of 8784 participants were included in the analysis, with 671 classified as having reduced PEF (PEF%pred < 80%). Higher BMI and greater HGS were each associated with significantly lower odds of reduced PEF (per 1-unit increase in BMI: OR = 0.970, 95% CI: 0.946-0.993; per 1 kg increase in HGS: OR = 0.961, 95% CI: 0.952-0.970), implying that lower BMI and lower HGS are related to increased risk. Mediation analysis indicated that HGS statistically mediated the association between BMI and PEF%pred; however, the absolute indirect effect size was very small (indirect effect = 0.003, 95% CI: 0.003-0.004), corresponding to a negligible change in PEF%pred.</p><p><strong>Conclusion: </strong>Both low BMI and reduced grip strength are significantly associated with greater odds of reduced PEF in Chinese middle-aged and elderly adults. Although HGS mediates part of the statistical association between BMI and PEF, the clinical significance is limited due to the small effect size. These results do not support specific muscle-strengthening interventions based on this finding alone, and caution should be exercised in clinical interpretation.</p>","PeriodicalId":520594,"journal":{"name":"Clinics (Sao Paulo, Brazil)","volume":"81 ","pages":"101091"},"PeriodicalIF":2.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and internal validation of a nomogram for predicting grade B/C hemorrhage after pancreaticoduodenectomy.","authors":"Siqing Yi, Jisheng Zhu, Ziyi Ye, Zhichao Li, Zulong Wang, Jiang Wei, Weidong Xiao","doi":"10.1016/j.clinsp.2026.101134","DOIUrl":"10.1016/j.clinsp.2026.101134","url":null,"abstract":"<p><strong>Objective: </strong>Postpancreatectomy Hemorrhage (PPH) is a severe complication after Pancreaticoduodenectomy (PD). This study aims to investigate the predictors and develop a nomogram to predict grade B/C PPH.</p><p><strong>Methods: </strong>Data were collected from patients who underwent PD at the Department of General Surgery of the First Affiliated Hospital of Nanchang University from January 2016 to December 2023. These patients were then randomly divided into a training set and a validation set. Logistic regression analysis was performed to investigate the predictors and develop a nomogram. The model's discriminative ability was evaluated using the Area Under Curve (AUC) of the receiver operating characteristic, calibration was evaluated using calibration curves, clinical utility was evaluated using decision curve analysis, and generalizability was evaluated by examining model's performance in the validation set. SHapley Additive exPlanations (SHAP) were used to interpret feature contributions and visualize the model's decision logic.</p><p><strong>Results: </strong>Preoperative Prothrombin Time (PT), preoperative Total Bilirubin (TB) (≥171 μmol/L), Postoperative Pancreatic Fistula (POPF), and Postoperative Biliary Fistula (POBF) were independent predictors of grade B/C PPH. The AUC values were 0.848 and 0.721 in the training set and the validation set, respectively. The model demonstrated satisfactory discriminative ability, calibration, clinical utility, and generalizability. SHAP indicated that POPF was the most influential predictor.</p><p><strong>Conclusions: </strong>Preoperative PT, preoperative TB (≥ 171 μmol/L), POPF, and POBF were identified as independent predictors of grade B/C PPH, and SHAP indicated the importance of POPF. The nomogram based on these predictors can help clinicians predict grade B/C PPH.</p>","PeriodicalId":520594,"journal":{"name":"Clinics (Sao Paulo, Brazil)","volume":"81 ","pages":"101134"},"PeriodicalIF":2.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum human epididymis protein 4 and long-term mortality in U.S. women: a nationally representative cohort study.","authors":"Yu-Wei Fang, Hsuan-Cheng Lin, Chikang Wang, Chien-Yu Lin","doi":"10.1016/j.clinsp.2026.101133","DOIUrl":"10.1016/j.clinsp.2026.101133","url":null,"abstract":"<p><strong>Purpose: </strong>Serum Human Epididymal secretory protein E4 (HE4) is a biomarker in gynecologic oncology and is increasingly linked to fibrosis and adverse outcomes across organ systems; however, its population-level prognostic value beyond cancer and advanced organ failure remains unclear.</p><p><strong>Patients and methods: </strong>We analyzed women aged ≥ 20-years in the National Health and Nutrition Examination Survey (NHANES) 2001-2002 cycle with serum HE4 (unweighted n = 2200; weighted population ≈46.9 million) linked to mortality outcomes through 2019.</p><p><strong>Results: </strong>Over a median 199.3-months of follow-up, 466 deaths occurred. Higher ln-HE4 levels were strongly associated with Chronic Kidney Disease (CKD) (Odds Ratio [OR = 2.07], 95% CI: 1.38-3.12) and history of lung disease (OR = 1.34, 95% CI: 1.06-1.71). In fully adjusted models, higher ln-HE4 was associated with all-cause mortality (Hazard Ratio [HR = 1.29], 95% CI: 1.03-1.63) and cancer mortality (HR = 1.60, 95% CI: 1.02-2.49). Chronic lower respiratory disease mortality showed a positive but imprecise association because of limited events (n = 25; HR = 3.16, 95% CI: 1.26-7.91). For diabetes mortality, the estimate was also imprecise and not statistically significant (n = 18; HR = 3.84, 95% CI: 0.92-16.00). Trends across quartiles were significant for all-cause (p for trend = 0.001) and cancer mortality (p for trend = 0.006). Sensitivity analyses were broadly consistent, although estimates for outcomes with few events should be interpreted cautiously.</p><p><strong>Conclusions: </strong>In a nationally representative cohort of U.S. women, higher serum HE4 was associated with increased risks of all-cause and cancer mortality. Associations with chronic lower respiratory disease and diabetes mortality were based on few events and should be interpreted cautiously. These results support HE4 as a potential population-level prognostic biomarker beyond oncology, warranting validation in other cohorts and mechanistic studies.</p>","PeriodicalId":520594,"journal":{"name":"Clinics (Sao Paulo, Brazil)","volume":"81 ","pages":"101133"},"PeriodicalIF":2.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers and arterial stiffness. A sub-analysis of the \"Exercise training in heart failure with reduced ejection fraction and permanent atrial fibrillation: A randomized clinical trial\".","authors":"Guilherme Veiga Guimarães, Veridiana Moraes D' Avila, Paulo Roberto Chizzola, Cristian Alvarez, Edimar Alcides Bocchi","doi":"10.1016/j.clinsp.2026.101142","DOIUrl":"10.1016/j.clinsp.2026.101142","url":null,"abstract":"<p><strong>Objective: </strong>Regular exercise improves outcomes in patients with Heart Failure (HF) and Atrial Fibrillation (AF), but its effects on inflammatory pathways and arterial stiffness in HF with Reduced Ejection Fraction (HFrEF) and permanent AF remain uncertain. This study examined the effects of a 12-week aerobic exercise program on biomarkers and arterial stiffness.</p><p><strong>Design and methods: </strong>This secondary analysis was derived from a parallel group randomized trial. We recruited 32 patients with HFrEF and permanent AF, randomizing 1:1 to an exercise group (n = 16) or a control group (n = 16). Six participants discontinued the protocol (two dropouts and one death per group), resulting in a final analyzed cohort of 26 patients who completed the study (13-per-group). The exercise group performed supervised aerobic training three times weekly for 12-weeks, while controls received usual care. Levels of BNP, ANP, IL-6, TNF-α, angiotensin II, and arterial stiffness by pulse wave velocity were measured at baseline and post-intervention.</p><p><strong>Results: </strong>Baseline characteristics were comparable. After 12-weeks, the exercise group showed significant reductions in BNP, ANP, IL-6, TNF-α, and angiotensin II, whereas the control group exhibited significant increases in ANP, IL-6, TNF-α, and angiotensin II. Arterial stiffness remained unchanged in the exercise group but increased in controls; however, the between-group difference was not statistically significant.</p><p><strong>Conclusion: </strong>A 12-week aerobic exercise program favorably modulated inflammatory and neurohormonal biomarkers in patients with HFrEF and permanent AF; however, its effect on arterial stiffness was less clear. Although arterial stiffness progressed in the control group and remained stable in the exercise group, the between-group difference in this change was not statistically significant. As these findings derive from a secondary analysis of a randomized trial, they should be interpreted with caution.</p>","PeriodicalId":520594,"journal":{"name":"Clinics (Sao Paulo, Brazil)","volume":"81 ","pages":"101142"},"PeriodicalIF":2.4,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148932491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}