Frontiers in Endocrinology最新文献

{"title":"Disproportionate reporting of euglycaemic and diabetic ketoacidosis with SGLT-2 inhibitors across expanding cardiorenal indications: a cross-database study of FAERS and JADER.","authors":"Jinqian Chen, Deyin Wang, Xiaochuan Duan, Jianbo Wang, Zhenyu Zhao, Xiaolong Xing","doi":"10.3389/fendo.2026.1957734","DOIUrl":"10.3389/fendo.2026.1957734","url":null,"abstract":"<p><p>SGLT-2 inhibitors are now used beyond type 2 diabetes (T2DM) in heart failure (HF) and chronic kidney disease (CKD), where glucose is monitored less routinely. Whether their established ketoacidosis signal-particularly euglycaemic diabetic ketoacidosis (euDKA)-is maintained as the indications expand, and whether it reproduces across independent reporting systems, is untested. We analysed the US FAERS (2020Q1-2026Q1) and Japanese JADER using one pipeline. Signals required consensus across four methods (ROR, PRR, IC, EBGM/EB05). Analyses were run overall, within report-level indication strata [T2DM, HF, CKD, off-label type 1 diabetes (T1DM)] and against an active comparator (DPP-4 inhibitors), with two pre-specified negative controls, time-to-onset modelling and sensitivity analyses. The DKA signal met four-method consensus within every indication stratum, including HF and CKD, and was highest in off-label T1DM; it was therefore maintained, not diluted, as indications expanded. Overall RORs were 67.4 (95% CI 65.7-69.2) in FAERS and 112.3 (104.8-120.3) in JADER. SGLT-2 inhibitors accounted for 85.8% (FAERS) and 91.7% (JADER) of all euDKA reports, though euDKA was only 4.1% and 7.8% of SGLT-2 inhibitor reports. Both negative controls were null in both databases. Median time-to-onset was 60 days (Weibull β=0.48, 95% CI 0.46-0.50). Across two independent reporting systems, the SGLT-2 inhibitor ketoacidosis signal was maintained across the expanding cardiorenal indications, with euDKA concentrated within this class and early onset. Ketone-based assessment is warranted when ketoacidosis is suspected, particularly soon after initiation. As a disproportionality analysis, these are hypothesis-generating signals that cannot establish incidence, relative risk, or causality.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1957734"},"PeriodicalIF":5.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The metabolic-inflammatory axis in chronic heart failure: integrating the NLR and TyG index for recent-onset atrial fibrillation prediction via machine learning and mediation analysis.","authors":"Chenglong Yao, Xinmei Liu, Runjia Liu, Dongdong Su, Kai Yang, Ling Yao, Hongfan Qiu, Bingjie Wang, Xuemei Hou, Jianming Yao, Yuerong Jiang, Haixia Li","doi":"10.3389/fendo.2026.1831904","DOIUrl":"10.3389/fendo.2026.1831904","url":null,"abstract":"<p><strong>Introduction: </strong>Recent-onset atrial fibrillation (AF) is a common complication of chronic heart failure (CHF), potentially involving both inflammatory and metabolic dysregulation. This study aimed to develop and externally validate an interpretable machine learning (ML) model for predicting recent-onset AF in patients with CHF and to explore the relationships among inflammatory dysregulation, metabolic dysregulation, and recent-onset AF.</p><p><strong>Methods: </strong>In this retrospective multicenter study, 4,872 hospitalized patients with CHF from Guang'anmen Hospital and Xiyuan Hospital were included, with external validation performed in 277 additional patients. Demographic, clinical, and laboratory variables, including the triglyceride-glucose (TyG) index and neutrophil-to-lymphocyte ratio (NLR), were analyzed. Nine ML algorithms were compared for AF prediction. Model interpretability was assessed using SHapley Additive exPlanations (SHAP). Segmented regression was used to examine nonlinear threshold effects, and mediation analysis was performed to explore the immunometabolic pathway linking TyG, NLR, and AF.</p><p><strong>Results: </strong>The Extra Trees model performed best, achieving an area under the receiver operating characteristic curve of 0.853 in the training cohort and 0.766 in the external validation cohort. NLR showed a nonlinear association with AF risk, with a steeper increase below 4.24, whereas TyG showed a threshold-dependent J-shaped relationship, with the risk increasing significantly above 5.91. The combination of TyG and NLR further improved model discrimination. Mediation analysis suggested that the estimated indirect association through NLR accounted for a substantial proportion of the observed association between TyG and AF.</p><p><strong>Conclusions: </strong>An interpretable ML framework identified the immune-metabolic axis as an important predictive component of recent-onset AF in CHF. NLR and TyG are inexpensive, clinically accessible biomarkers that may improve early risk stratification and identify a high-risk phenotype characterized by concurrent metabolic stress and inflammation. Trial registration: ChiCTR (ITMCTR2025001576).</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1831904"},"PeriodicalIF":5.7,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148826614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prehospital glucagon-like peptide-1 receptor agonists are not associated with reduced inpatient opioid exposure but with shorter hospital length of stay after total joint arthroplasty.","authors":"Noam Vaknin, Chen Seidenberg, Eric Sitton, Pierre Singer, Ruth Mishali, Hila Vidal, Michal Slevin-Kish","doi":"10.3389/fendo.2026.1918370","DOIUrl":"https://doi.org/10.3389/fendo.2026.1918370","url":null,"abstract":"<p><strong>Aims: </strong>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been hypothesized to confer anti-inflammatory, antinociceptive, and anti-addictive benefits. We aimed to investigate their impact on acute perioperative pain and opioid use after total joint arthroplasty (TJA).</p><p><strong>Methods: </strong>A retrospective cohort study analyzed 14,375 hip or knee arthroplasties performed between January 2018 and February 2026, which included 882 patients on chronic preoperative GLP-1RA therapy. Using 1:1 propensity-score matching without replacement, 786 GLP-1RA users were matched to 786 non-users (total n=1,572) based on demographics, surgery type, and chronic medication use.</p><p><strong>Results: </strong>In the matched cohort, chronic GLP-1RA use was not associated with reduced inpatient opioid administration (adjusted difference -0.18; 95% CI, -0.74 to 0.38; p=0.53) or corrected postoperative morphine milligram equivalents (MME) (-2.79 MME; 95% CI, -6.95 to 1.37; p=0.19). When normalized to hospitalization time, the difference in inpatient opioid exposure was not statistically significant (+0.073 MME/hour; 95% CI, -0.003 to 0.149; p=0.059). Average visual analog scale (VAS) pain scores also showed no significant difference (-0.094; p=0.15). However, GLP-1RA users demonstrated a consistently shorter length of stay (LOS) (adjusted difference -10.41 hours; 95% CI, -13.97 to -6.85; p<0.001).</p><p><strong>Conclusions: </strong>Chronic preoperative GLP-1RA therapy was not associated with reduced inpatient opioid exposure or improved early postoperative pain control following TJA. Nevertheless, GLP-1RA use was consistently associated with shorter hospital LOS. Prospective studies are needed to determine whether this finding reflects improved recovery pathways or residual confounding and to evaluate the impact of GLP-1RAs on longer-term postoperative outcomes and opioid utilization.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1918370"},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Graves' disease and bone mineral density: a meta-analysis and UK Biobank.","authors":"Mengchu Wu, Jie Wang, Yunlin Lu, Mengting Yuan, Jiangxun Ji, Junhao Liang, Jiarui Cui, Hongyu Wang, Hongbin Xu, Tianpeng Liu, Yi Shen, Furui Fu, Senjie Shi, Qi Shi, Libing Shen, Dezhi Tang, Chunchun Yuan, Yongjun Wang","doi":"10.3389/fendo.2026.1794055","DOIUrl":"https://doi.org/10.3389/fendo.2026.1794055","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the association between Graves' disease (GD) and bone mineral density by integrating a meta-analysis with a large-scale cross-sectional analysis in the UK Biobank.</p><p><strong>Methods: </strong>We systematically searched PubMed, Web of Science, and Cochrane Library for cohort and cross-sectional studies. The pooled findings were then examined in the UK Biobank using multivariable linear regression models with adjustment for age, BMI, lifestyle factors, vitamin D, calcium, and sex.</p><p><strong>Results: </strong>The meta-analysis (14 studies, 3,643 participants) showed that GD patients had significantly lower bone mineral density than controls (Mean Difference = -0.09, 95% CI [-0.10, -0.07], <i>P</i> < 0.001) and higher serum calcium (Standard Mean Difference = 0.37, 95% CI [0.18, 0.57], <i>P</i> = 0.023). However, substantial between-study heterogeneity was observed (I² = 92.1%), indicating considerable variation across studies. Meta-regression and subgroup analyses identified postmenopausal women, older age (>50 years), and lower BMI as key factors amplifying the association. In the UK Biobank (n = 42374), after rigorous adjustment for all covariates, the association was substantially attenuated and remained statistically significant only at the ribs (<i>P</i> < 0.05), while other skeletal sites, including the lumbar spine and femoral neck, showed no significant differences.</p><p><strong>Conclusion: </strong>This dual-evidence approach provides suggestive, rather than definitive, evidence that GD is associated with reduced BMD. The meta-analysis suggested widespread BMD reductions in GD patients. However, due to the limited number of confirmed GD cases, the fully adjusted UK Biobank analysis adopted a broader exposure definition of hyperthyroidism and observed a nominally statistically significant association only at the ribs, with no significant differences detected at other skeletal sites. Given the limited replication of the meta-analysis findings and the high heterogeneity observed in the meta-analysis, we advocate for a risk-stratified approach to BMD screening that prioritizes postmenopausal women, older adults, and individuals with low BMI, rather than routine screening for all GD patients. These findings underscore the need for prospective studies with standardized protocols to clarify the skeletal impact of GD and to guide evidence-based bone health management.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1794055"},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The gut microbiome in polycystic ovary syndrome: mechanistic pathways and therapeutic potential of microbiota-targeted interventions.","authors":"Farah Elhennawy, Basmalah Naji, Alexandra E Butler","doi":"10.3389/fendo.2026.1900535","DOIUrl":"https://doi.org/10.3389/fendo.2026.1900535","url":null,"abstract":"<p><p>Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine disorders worldwide, affecting 6-13% of reproductive-aged women and exerting a profound metabolic, reproductive and psychological toll. Emerging evidence suggests that the gut microbiome may be a potentially critical, yet under-recognized, contributor to the pathophysiology of PCOS. Alterations in microbial composition and function appear to influence hormonal imbalance, metabolic dysfunction and inflammatory processes that characterize the condition. However, much of the current evidence remains associative or derived from preclinical models, and the causal nature of these relationships is only beginning to be established through approaches such as Mendelian randomization. This literature review examines the evolving relationship between the gut microbiome and PCOS through a mechanism-guided, evidence-stratified framework, with particular focus on how microbiota-targeted interventions - including prebiotics, probiotics, synbiotics, dietary modifications and fecal microbiota transplantation, may modulate gut health and mitigate symptom severity. Across the reviewed studies, microbiome-targeted supplementation was associated with improvements in insulin sensitivity, reductions in systemic inflammation and favorable hormonal changes, although the strength of evidence varies across outcomes and intervention types. Importantly, PCOS heterogeneity, including differences in body mass index (BMI), insulin resistance status and phenotype, may influence both gut microbiota composition and therapeutic response, underscoring the need for phenotype-stratified research. These findings suggest that targeting the gut microbiome may serve as a promising adjunct to conventional PCOS management. Though further rigorous, long-term clinical trials are needed to advance both understanding and clinical translation.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1900535"},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral blood inflammatory indices across thyroid functional states in Graves' disease: associations with liver biochemical abnormalities and hyperthyroid relapse.","authors":"Wenjie Sun, Hui Chen","doi":"10.3389/fendo.2026.1863070","DOIUrl":"https://doi.org/10.3389/fendo.2026.1863070","url":null,"abstract":"<p><strong>Background: </strong>Graves' disease is an organ-specific autoimmune disorder driven by thyrotropin receptor antibody (TRAb) and accompanied by persistent immune and inflammatory activation. Peripheral blood inflammatory indices are readily available and have been increasingly used to assess inflammation in autoimmune diseases. However, their clinical significance in Graves' disease across different thyroid functional states is unknown.</p><p><strong>Methods: </strong>In this retrospective study, 687 patients with Graves' disease were enrolled. Five peripheral blood inflammatory indices were calculated, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune-inflammation value (PIV). Patients were stratified and compared according to thyroid functional status. Because sex distribution differed among the groups, sex-adjusted median regression models were additionally fitted, and group-by-sex interactions were examined. Correlation analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis were used to evaluate associations of these indices with clinical characteristics, liver biochemical abnormalities, and hyperthyroid relapse. The outcome models were internally validated using bootstrap resampling and repeated 10-fold cross-validation.</p><p><strong>Results: </strong>Sex distribution differed significantly among the thyroid functional groups. After adjustment for sex, MLR, SIRI, and PIV remained significantly higher in the overt hyperthyroid group than in the subclinical hyperthyroid and euthyroid groups. In patients with overt hyperthyroidism, MLR was positively correlated with age, FT3, FT4, ALT, and AST (r_s = 0.152-0.206, all <i>P</i> < 0.05). Multivariable logistic regression identified TRAb, hemoglobin, and standardized MLR as independent factors associated with liver biochemical abnormalities, and the resulting model showed limited-to-moderate discrimination (apparent AUC, 0.703; optimism-corrected AUC, 0.692; cross-validated AUC, 0.680). Among the five inflammatory indices, PIV showed the highest individual discrimination for hyperthyroid relapse (AUC, 0.734). The TRAb-PIV model showed relatively good internal discrimination (apparent AUC, 0.815; optimism-corrected AUC, 0.805; cross-validated AUC, 0.788).</p><p><strong>Conclusion: </strong>Compared with NLR and SII, the monocyte-containing indices MLR, SIRI, and PIV showed clearer differences across thyroid functional states in Graves' disease and may provide complementary inflammation-related information. Among them, MLR was associated with liver biochemical abnormalities, whereas PIV showed potential adjunctive value for hyperthyroid relapse risk assessment.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1863070"},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From explainability to clinical actionability: translating artificial intelligence models into decision support for endocrine disease management.","authors":"Tianqiang Wu, Wenpin Cai, Zhixiang Li","doi":"10.3389/fendo.2026.1887643","DOIUrl":"https://doi.org/10.3389/fendo.2026.1887643","url":null,"abstract":"<p><p>Artificial intelligence (AI) models are increasingly reported in endocrine disease management, but clinical value cannot be inferred from discrimination, model complexity, or explainability alone. This narrative review synthesizes evidence from diabetes and diabetic kidney disease (DKD), thyroid disease, polycystic ovary syndrome (PCOS; with attention to the proposed polyendocrine metabolic ovarian syndrome, PMOS, terminology transition), and obesity/GLP-1-based metabolic management through an actionability framework. We define clinical actionability as the link between a meaningful endocrine prediction and transparent reporting, bias and applicability appraisal, external or temporal validation, calibration, threshold-based utility, interpretable output, workflow integration, fairness assessment, and post-deployment monitoring. Diabetes/DKD provides a comparatively broad evidence base, including decision-support examples, non-invasive triage, calibration, decision-curve analysis, and early deployment-oriented work. Thyroid AI increasingly reports validation and clinical-utility metrics for nodule triage, biopsy decisions, and risk prediction, but prospective workflow evidence remains limited. PCOS/PMOS AI addresses diagnostic and reproductive-endocrine gaps, yet requires broader phenotype alignment, fairness analysis, and multi-setting validation during the PMOS terminology transition. Obesity/GLP-1 evidence now includes response-prediction, benefit-stratification, treatment-intensification, persistence, and remote-care examples, but it does not establish AI-guided treatment selection, adherence/tolerability prediction, or monitoring. Across modules, differences lie less in headline discrimination metrics, including the area under the receiver operating characteristic curve (AUC), than in validation, utility, workflow, fairness, and monitoring evidence. Endocrine AI should move from explainable prediction toward decision support that can be interpreted, thresholded, acted on, monitored, and revised in clinical workflows.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1887643"},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and validation of a diagnostic model for type 2 diabetes mellitus comorbid with metabolic dysfunction-associated steatotic liver disease based on routine serological indicators: a retrospective case-control study.","authors":"Lihong Wu, Shuang Wang, Ning Yang, Renjun Li, Shui Jin","doi":"10.3389/fendo.2026.1891690","DOIUrl":"https://doi.org/10.3389/fendo.2026.1891690","url":null,"abstract":"<p><strong>Objective: </strong>The prevalence of type 2 diabetes mellitus (T2DM) with concurrent Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is high. However, simple, efficient and non-invasive diagnostic tools based on routine serological indicators are lacking. This study aims to construct and validate a simple diagnostic model using routine serological indicators.</p><p><strong>Methods: </strong>A retrospective case-control study is conducted, enrolling 470 patients with T2DM. They are randomly stratified into a training set and a validation set at a 7:3 ratio. Independent predictive factors are identified using univariate and multivariate logistic regression. Diagnostic performance is assessed via receiver operating characteristic (ROC) curves. A nomogram diagnostic model is constructed and evaluated using ROC curves, calibration curves and decision curve analysis. For external validation, an additional 300 T2DM patients are recruited.</p><p><strong>Results: </strong>Body mass index (BMI), fasting C-peptide, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), urea and alanine aminotransferase (ALT) are independent predictors of comorbid T2DM and MASLD. The area under the curve (AUC) of this model in the training set, internal validation set and external validation set is 0.921, 0.913 and 0.830, respectively. The calibration curve closely approximates the ideal diagonal line and decision curve analysis (DCA) demonstrates significant clinical net benefit across a broad range of threshold probabilities.</p><p><strong>Conclusion: </strong>This model enables high-precision diagnosis of T2DM with MASLD using routinely available serological indicators, avoiding invasive procedures and exhibiting strong potential for clinical translation. Future studies should validate its generalizability in multicenter prospective cohorts to promote its use as a routine screening tool for MASLD in T2DM patients.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1891690"},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The estradiol-to-periovulatory follicle ratio (E2/N16) as a marker of follicular endocrine efficiency and embryological outcomes in ART cycles.","authors":"Claudio Maurizio Maria Brigante, Ilaria Caliari, Roberta Iemmello, Silvana Gippone, Diletta Guglielmi, Beatrice Dal Canto, Mario Romano Mignini Renzini","doi":"10.3389/fendo.2026.1866946","DOIUrl":"https://doi.org/10.3389/fendo.2026.1866946","url":null,"abstract":"<p><strong>Background: </strong>Controlled ovarian stimulation (COS) in assisted reproductive technology (ART) is traditionally assessed using quantitative parameters, particularly the number of retrieved oocytes. However, these measures may not fully capture the endocrine efficiency of the periovulatory follicular cohort.</p><p><strong>Objective: </strong>To evaluate the association between the estradiol-to-periovulatory follicle ratio (E2/N16) and embryo yield, and to investigate its relationship with serum progesterone concentrations and ovarian stimulation characteristics.</p><p><strong>Methods: </strong>This retrospective observational cohort study included 2,831 ART cycles performed between January 2022 and February 2025. E2/N16 was calculated by dividing serum estradiol concentration by the number of periovulatory follicles (≥16 mm) on the day of trigger. The primary outcome was viable embryo yield per cycle. E2/N16 was analyzed as a continuous variable and by quartiles. Multivariable models were adjusted for female age, body mass index, anti-Müllerian hormone, number of retrieved oocytes, total FSH dose, and trigger type. Restricted cubic splines with formal tests of non-linearity and sensitivity analyses were also performed.</p><p><strong>Results: </strong>Viable embryo yield progressively decreased across increasing E2/N16 quartiles, from 2.09 to 1.77 embryos per cycle (p < 0.001). After multivariable adjustment, including trigger type, higher E2/N16 remained independently associated with lower embryo yield (β = -0.000218; 95% CI, -0.000427 to -0.000010; p = 0.040). The spline showed no statistically significant departure from linearity (P for non-linearity = 0.449), despite a modest initial rise followed by a decline. The association with serum progesterone was significantly non-linear (P for non-linearity = 0.009), with a U-shaped pattern. After exclusion of cycles with two or fewer periovulatory follicles, the association with embryo yield was attenuated but remained directionally consistent.</p><p><strong>Conclusions: </strong>The estradiol-to-periovulatory follicle ratio (E2/N16) was independently associated with embryo yield and provided information complementary to conventional quantitative measures of ovarian response. Its relationship with progesterone was non-monotonic, indicating that E2/N16 should not be interpreted as a simple linear marker of ovarian steroidogenesis. Prospective studies are required to validate its clinical utility and define how it might contribute to the assessment of ovarian stimulation in ART.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1866946"},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of sarcopenia and muscle attenuation with clinical outcomes in patients with diabetic foot: a systematic review and meta-analysis.","authors":"Li Yang, Lei Wang, Jiaqi Yang, Yang Li, Xuan Li, Bing Wu, Ting Yin, Yi Zhao","doi":"10.3389/fendo.2026.1894356","DOIUrl":"https://doi.org/10.3389/fendo.2026.1894356","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Diabetic foot (DF) represents a severe and disabling complication of diabetes, closely linked to ulceration, amputation, functional impairment, and an elevated risk of death. Sarcopenia is a syndrome marked by progressive declines in muscle mass and function. Emerging evidence suggests a possible link between DF and sarcopenia. Nonetheless, a systematic evaluation of the influence of sarcopenia on adverse clinical outcomes in individuals with DF remains unavailable. The present investigation aims to systematically assess and quantitatively synthesize the association of sarcopenia and muscle attenuation with clinical outcomes in those with DF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A systematic search of Embase, Cochrane, PubMed, Web of Science, SinoMed, China National Knowledge Infrastructure, Wanfang, and VIP databases was conducted from their inception through December 2025. Observational studies enrolling DF individuals aged ≥ 18 years and comparing clinical prognoses between those with and without sarcopenia and muscle attenuation were included. The primary outcomes comprised rates of mortality and amputation. Secondary outcomes encompassed ulcer severity. The NHLBI was adopted for risk-of-bias evaluation. Given substantial between-study heterogeneity, a narrative synthesis was prioritized, with meta-analyses implemented for outcomes amenable to quantitative pooling.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Eighteen studies (9 cross-sectional, 4 prospective cohort, 4 retrospective cohort, and 1 retrospective case-control studies) comprising 2,888 individuals were included, of which 9 contributed to the meta-analysis. The meta-analysis revealed that, relative to those without sarcopenia and muscle attenuation, DF individuals with comorbid sarcopenia exhibited an elevated risk of all-cause mortality (HR = 2.38, 95% CI: 1.63-3.48), an association with amputation (OR = 2.11, 95% CI: 1.32-3.38), and a higher proportion of severe ulcers (Wagner grade 4-5) (RR = 1.69, 95% CI: 1.31-2.17).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Impaired muscle health was associated with a higher risk of all-cause mortality, higher odds of amputation, and a greater prevalence of severe ulcers in patients with DF. Because the available evidence is observational and heterogeneous, these findings should be considered hypothesis-generating and should not yet be used to support prognostic screening or clinical risk-stratification decisions. Future prospective cohort investigations are necessary to further clarify the temporal relationship and underlying mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding and registration: &lt;/strong&gt;This study was supported by the Ningxia Natural Science Foundation (Grant Number: 2025AAC030725). This systematic review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD420251247873).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Sy","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1894356"},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}