To evaluate and identify urinary biomarkers for the early diagnosis and staging of diabetic kidney disease (DKD).

This study enrolled 200 participants, including healthy controls (NDM, n=50) and patients with type 2 diabetes. The diabetic patients were stratified by urinary albumin-to-creatinine ratio (ACR) into the following groups: normoalbuminuria (SDM, n=50), microalbuminuria (MADKD, n=50), and macroalbuminuria (ADKD, n=50). Utilizing an integrated multi-dimensional screening strategy, we systematically evaluated traditional urinary protein markers (urinary retinol-binding protein [URBP], urinary immunoglobulin G [UIgG], urinary transferrin [UTRF], urinary alpha-1-microglobulin [Uα1-MG], and urinary beta-2-microglobulin [Uβ2-MG]), 20 urinary amino acids, and urinary proteins identified via high-throughput mass spectrometry. Candidate proteins were validated by ELISA, and their diagnostic performance was assessed using ROC curve analysis, with ACR serving as the practical clinical reference.

Among the traditional urinary protein markers, UTRF and UIgG demonstrated excellent diagnostic value, with areas under the curve (AUC) of 0.926 and 0.916, respectively. Among the amino acids, PRO showed the best diagnostic performance (AUC = 0.746). However, when all 20 urinary amino acids were combined into a diagnostic model, it exhibited outstanding diagnostic value (AUC = 0.928), outperforming individual amino acids and even traditional protein markers. From the top 50 proteins identified in the proteomic screening, serpin family A member 1 (SERPINA1) was determined to be a key protein. Subsequent ELISA validation and ROC analysis further confirmed that SERPINA1 possesses outstanding diagnostic capability (AUC = 0.964, 95% CI: 0.936-0.990), significantly outperforming other candidate proteins, namely osteoclast-associated Ig-like receptor (OSCAR), contactin 1 (CNTN1), and CD58 molecule (CD58).

Traditional proteins, especially UTRF/UIgG, hold diagnostic value. The 20-amino-acid combination (AUC = 0.928) outperformed them. This study first systematically identifies urinary SERPINA1 as a highly promising DKD biomarker, offering a novel target for early diagnosis and precise management.

T2DM readmission risk factors may evolve across time windows, but this dynamic remains poorly understood.

This retrospective cohort study developed nine machine learning models to predict 30-day, 60-day, and 365-day readmission in 12,041 T2DM patients (with an additional 2,007 patients used for temporal validation of the 30-day and 60-day models). Feature selection was performed using LASSO and Boruta. SHAP analysis was used for interpretability, with temporal validation performed for short- and medium-term models.

ANN achieved the highest AUROC for 30-day and 60-day predictions. Random forest showed competitive performance for 365-day prediction. SHAP analysis revealed a dynamic evolution: age dominated the 30-day window; length of hospital stay and inflammatory markers (SII, SIRI) emerged as key predictors in the 60-day window; and diabetes-specific chronic complications dominated the 365-day window.

Model selection should be time window-specific: ANN for short/medium-term, random forest for long-term prediction. Risk factors shift from acute vulnerability to inflammatory burden and then to chronic complications, supporting dynamic risk monitoring in T2DM patients.

Diabetes mellitus encompasses disorders characterized by hyperglycemia due to pancreatic β-cell dysfunction. Type 2 diabetes (T2D) constitutes over 90% of cases, with a background of genetic, metabolic, and environmental risk factors. Knowing that sex differences impact insulin resistance and glycemic control, this review aims to identify differences in adherence to dietary patterns between women and men with T2D.

This systematic review aims to evaluate sex differences in dietary pattern adherence among individuals with T2D and the implications of these differences for glycemic control.

The protocol was developed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies published until July 2026 will be identified by searching the following electronic databases: MEDLINE, Scopus, Cochrane Library, and Web of Science. Three investigators will independently screen articles based on titles and abstracts followed by a thorough analysis of selected full-text articles of interest. Articles on T2D and dietary pattern scores that include biological sex data will be included. The estimation of risk of bias will be performed using the Standard Quality Assessment Criteria for Evaluating Primary Research Papers From a Variety of Fields. To synthesize the results, a narrative analysis will be performed based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework.

The search strategy was developed and refined between July 2025 and July 2026 through scoping and pilot searches. The comprehensive database search will be conducted in August 2026, covering records from database inception to July 2026. Study selection and data extraction are expected to be completed by December 2026, with publication anticipated in late 2027.

This systematic review will provide a comprehensive overview of the role of sex in dietary adherence among individuals with T2D. Identifying sex-specific and gender differences may inform the development of tailored nutritional strategies and interventions aimed at improving glycemic outcomes. Ultimately, this work highlights the importance of incorporating sex-based approaches in the management of T2D to optimize long-term health outcomes.

PROSPERO CRD42024340213; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024340213.

DERR1-10.2196/98958.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with infertility, and frozen-thawed embryo transfer (FET) has become a mainstream assisted reproductive technology for PCOS patients. Two primary endometrial preparation protocols are widely used for FET: ovulation induction cycles and artificial cycles (AC). However, the comparative clinical efficacy, maternal outcomes, and perinatal outcomes of these two protocols in PCOS women remain inconsistent in existing literature, highlighting the need for large-scale cohort studies to provide evidence-based guidance. This study aimed to investigate whether clinical, maternal, and perinatal outcomes following FET differ between ovulation induction cycles and artificial cycles in women with PCOS.

This was a retrospective cohort study conducted at a public fertility center in China. A total of 3,255 PCOS women who underwent FET between January 2018 and December 2023 were included. After propensity score matching (1:1), 530 patients in the ovulation induction group were compared with 530 patients in the artificial cycle group. The primary outcome was live birth rate. Secondary outcomes included clinical pregnancy, miscarriage, maternal outcomes, and perinatal outcomes.

After PSM, the ovulation induction group exhibited a significantly higher live birth rate than the artificial cycle group (57.5% vs. 51.3%; odds ratio [OR] 1.3, 95% confidence interval [CI] 1.0-1.7). The ovulation induction group also had a lower miscarriage rate (11.1% vs. 15.8%; OR 0.7, 95% CI 0.4-0.9). Regarding maternal outcomes, the ovulation induction group was associated with a significantly elevated risk of gestational diabetes mellitus (GDM) (17.6% vs. 9.0%; OR 2.2, 95% CI 1.4-3.4; P < 0.01). In singleton pregnancies, the ovulation induction group showed a reduced risk of large for gestational age (LGA) infants compared to the artificial cycle group (22.7% vs. 36.9%; OR 0.5, 95% CI 0.3-0.7; P < 0.01).

Within the limitations of a retrospective design and single-center setting, this study shows that in PCOS women undergoing FET, ovulation induction cycles were associated with higher live birth rates and lower risks of miscarriage and LGA infants in singleton pregnancies. However, this protocol is associated with an increased risk of GDM. These findings provide valuable evidence for individualizing endometrial preparation protocols in PCOS patients undergoing FET, balancing efficacy and maternal safety.

Type 2 diabetes mellitus has multiple treatment options and high healthcare costs. In Japan, DPP-4 inhibitors have been widely used, but since 2022 the pharmacotherapy algorithm has shifted: DPP-4 inhibitors and biguanides for BMI < 25 kg/m 2 , and biguanides and SGLT2 inhibitors for BMI ≥ 25 kg/m 2 . However, real-world factors influencing prescribing decisions between biguanides and SGLT2 inhibitors remain unclear.

This study investigates factors influencing the choice between biguanides and SGLT2 inhibitors in clinical practice. We also compare glycemic efficacy and medication persistence while accounting for baseline characteristics.

This retrospective cohort study used the Millennium Medical Record Database, primarily capturing care from large hospitals. Adults aged ≥ 18 years who received a first prescription of a biguanide or a SGLT2 inhibitor between July 2019 and April 2023 were included. Patients were categorized as 1st-line or 2nd-line therapy. Confounding was addressed using coarsened exact matching with classification tree modeling. HbA1c changes were analyzed using mixed models for repeated measures, and persistence using Kaplan-Meier methods.

A total of 1925 patients were included. In the 1st-line cohort (n = 1440), key selection factors were diuretic use, lipid-modifying agents, and baseline HbA1c. At 24 weeks, HbA1c decreased in both groups (biguanide: -1.37 percentage points, 95% CI -1.48 to -1.26; SGLT2 inhibitor: -1.16 percentage points, 95% CI -1.29 to -1.02); the between-group difference was -0.21 percentage points (95% CI -0.38 to -0.04). Persistence at 48 weeks was 47.0% (95% CI 42.7-51.2) for biguanides and 56.2% (95% CI 51.2-61.2) for SGLT2 inhibitors. In the 2nd-line cohort (n = 485), selection factors were baseline HbA1c, BMI, and diuretic use. HbA1c decreased at 24 weeks (biguanide: -2.26 percentage points, 95% CI -2.47 to -2.05; SGLT2 inhibitor: -1.79 percentage points, 95% CI -2.04 to -1.54); the between-group difference was -0.47 percentage points (95% CI -0.80 to -0.15). Persistence at 48 weeks was 51.8% (95% CI 45.2-58.4) for biguanides and 49.4% (95% CI 40.3-58.6) for SGLT2 inhibitors.

In Japanese patients with type 2 diabetes, treatment selection was mainly associated with concomitant cardiovascular medication use. BMI influenced choice, particularly in the 2nd-line setting, but was not the predominant determinant. Biguanides were associated with greater HbA1c reductions. In intention-to-treat analyses, persistence over 48 weeks was higher with SGLT2 inhibitors in the 1st-line cohort, while persistence was comparable in the 2nd-line cohort.

The aim of the present study was investigating the relationship between thyroid hormone levels and cognitive function in Parkinson's disease (PD).

431 PD patients were continuously enrolled from The First Affiliated Hospital of Kunming Medical University between January 2019 and December 2024. This study classified PD patients into PDNC and PDMCI groups based on the PDMCI diagnostic criteria defined by MDS. Clinical information including age, gender, length of illness, BMI, education, and levodopa equivalent daily dose (LEDD), and the presence of underlying diseases such as hypertension and diabetes mellitus were collected from all subjects, and all subjects completed the assessment of UPDRS-III score, H-Y staging, MMSE, MoCA (Beijing version), HAMA, and HAMD scale and underwent the evaluation of thyroid hormone serum T3, T4, FT3, FT4, TSH, TG, TMab, and aTG levels. The differences in general clinical data and thyroid hormone levels between the two groups were compared, and the correlation between thyroid hormone levels and each clinical data and different cognitive domains was analyzed.

Patients in the PDMCI group were older, had a higher proportion of females, had a longer disease duration but fewer years of education, and had higher UPDRS-III, H-Y staging, HAMA, HAMD scores, and LEDDs and lower TSH (all p < 0.05) than those in the PDNC group, but there were no statistically significant differences in comorbidities or thyroid-related markers. In PD patients, FT3 levels were negatively correlated with age, HAMA score, HAMD score, and H-Y staging; FT3 levels were positively correlated with the total MoCA score (p < 0.05) and attention (r = 0.165, p = 0.001), and this association remained independent and significant after multivariate adjustment and multiple-testing correction. The dose-response relationship between TSH levels and cognitive scores shows a clear inverted U-shape.

This study suggests that thyroid hormone dysregulation may be associated with cognitive function in Parkinson's disease patients, though this relationship requires further investigation to confirm. This highlights the need for future research to evaluate whether therapeutic modulation of thyroid function could influence cognitive outcomes during the progression of Parkinson's disease.

Early revision surgery after elective anterior cervical discectomy and fusion (ACDF) is uncommon but clinically important, as it may reflect early mechanical failure, procedure-related morbidity, or postoperative complications requiring repeat operative intervention. Contemporary national data specifically evaluating predictors of early revision after elective ACDF remain limited. The purpose of this study was to determine the incidence of revision surgery requiring readmission within 90 days after elective ACDF and to identify baseline clinical and index-admission postoperative factors associated with this outcome.

A retrospective cohort study was performed using the Nationwide Readmissions Database from 2020 to 2022. Adult patients undergoing elective ACDF were identified using ICD-10-PCS procedure codes. Cases associated with trauma, malignancy, non-elective indications, or infection as the indication for the index ACDF hospitalization were excluded. Index procedures performed between January and September were included to allow complete 90-day follow-up. The primary outcome was early revision spinal surgery requiring readmission within 90 days of the index hospitalization, defined by readmission procedure codes for revision fusion, decompression, or hardware removal. Secondary outcomes included 90-day all-cause readmission and readmission resource utilization. Univariate comparisons were performed using t tests and chi-square testing. Multivariable logistic regression models were used to identify independent associations with early revision surgery.

A total of 30,696 patients undergoing elective ACDF were included. Mean age was 57.7 ± 12.6 years, and 51.7% were female. Within 90 days, 2,198 patients (7.2%) were readmitted and 303 patients (1.0%) underwent early revision spinal surgery requiring readmission. Patients requiring early revision were older than those who did not undergo revision (60.9 ± 11.3 vs. 57.6 ± 12.6 years, p < 0.001), and were more likely to have hypertension (61.1% vs. 45.1%, p < 0.001) and congestive heart failure (3.0% vs. 1.2%, p = 0.005). Diabetes mellitus was more frequent in the early revision group but was not statistically significant on univariate analysis (26.4% vs. 22.7%, p = 0.132) and was not independently associated with revision in the multivariable model (OR 0.98, 95% CI 0.75-1.28; p = 0.879). On multivariable analysis, age (OR 1.016, 95% CI 1.006-1.026; p = 0.002), hypertension (OR 1.85, 95% CI 1.45-2.37; p < 0.001), and congestive heart failure (OR 2.99, 95% CI 1.48-6.07; p = 0.002) were independently associated with early revision. In a separate model of index-admission postoperative complications, dysphonia (OR 3.96, 95% CI 1.69-9.28; p = 0.002) and surgical site infection (OR 15.95, 95% CI 4.75-53.56; p < 0.001) were associated with revision surgery within 90 days.

In this national cohort of elective ACDF procedures, early revision surgery requiring readmission within 90 days occurred in 1.0% of patients. Older age, hypertension, and congestive heart failure were independently associated with increased revision risk, while dysphonia and surgical site infection recorded during the index admission were associated with subsequent early revision. Diabetes mellitus was evaluated but was not independently associated with early revision. Because procedure-level details, surgical level, laterality of approach, implant-related factors, and same-hospitalization reoperations were not fully available in the NRD, these findings should be interpreted as associations rather than causal determinants of early surgical failure.

Level III.

Tirzepatide, a first-in-class dual GIP/GLP-1 receptor agonist, was approved by the FDA for type 2 diabetes mellitus (2022) and chronic weight management (2023). Despite superior efficacy in trials, its real-world safety profile remains incompletely characterised. This study aimed to characterise tirzepatide's post-marketing safety signals using the FAERS database.

FAERS reports listing tirzepatide as the primary suspected drug were extracted (Q2 2022-Q4 2025). Disproportionality analysis used four algorithms (ROR, PRR, IC, EBGM). Adverse events were coded using MedDRA terminology. Time-to-onset and comparative analyses versus semaglutide were conducted.

A total of 123 145 reports (251 435 individual adverse events) were included. Females accounted for 62.30%, with a mean age of 53.7 years. Major signals included medication errors, injection-site reactions and gastrointestinal disorders. Novel unlabelled signals included eructation, hunger, food craving and starvation ketoacidosis. Compared with semaglutide, tirzepatide showed lower reporting odds of vomiting, constipation and decreased appetite. Among reports with valid onset data, median time to onset was 13 days, with 67.1% occurring within 30 days.

This FAERS study characterises tirzepatide safety signals in real-world practice. Medication errors and injection-site reactions were the strongest signals. Several novel signals warrant further investigation. Among reports with complete onset data, most adverse events were reported early after treatment initiation, suggesting the importance of closer monitoring during the first month of therapy.

To analyze the outcomes of multiple endocrine neoplasia type 1 (MEN1) patients after distal pancreatectomy (DP) for pancreatic neuroendocrine neoplasm (P-NENs) with a specific attention to postoperative complications and long-term survival.

MEN1 patients from the French MEN1 cohort who underwent DP for P-NENs between 1990 and 2022 were included in the study. Early and late postoperative complications, secretory control, pancreatic disease-free and overall survival were assessed.

Out of 62 patients included, 41 (66%) underwent DP for a non-functioning P-NENs, 14 (23%) for insulinomas, 4 (6%) for a VIPoma and 3 (5%) for a glucagonoma. Median follow-up was 84 months (range: 12-335). No death within the 90 postoperative days was observed. Clavien-Dindo grade III-V postoperative complications occurred in 16% of the patients (n=11). Fourteen patients (23%) developed pancreatic fistulas. Twenty-four patients (39%) developed diabetes mellitus and 8 patients (13%) developed pancreatic exocrine insufficiency. The secretory control rate was 90%. Mean age at death was 56±10.9years. Five-year and ten-year overall survival was 93.0% [CI (85-100)], and 86.7% [CI (76.2-98.5)]. Ten-year liver metastasis-free survival was significantly shorter when DP was performed for non-functioning P-NENs compared to insulinomas 60.4% [CI (47-79)] versus 83.3% [CI (68-87)] (P=0.007).

Distal pancreatectomy in MEN1 patients is a safe surgical procedure with an acceptable morbidity and a very low postoperative mortality. Further studies are needed to standardize the extent of lymph node removal when distal pancreatectomy is performed in MEN-1 patients.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated cardiovascular and metabolic benefits individually; however, the comparative effectiveness of combination therapy versus monotherapy in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) remains incompletely characterized.

We conducted three pairwise target trial emulations using the TriNetX Research Network. Adults with MASLD and T2DM initiating GLP-1 RA plus SGLT2i combination therapy, GLP-1 RA monotherapy, or SGLT2i monotherapy were identified. Primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE), and composite liver outcomes. Propensity score matching (PSM) (1:1) was performed for each pairwise comparison. Cox proportional hazards regression with Bayesian hierarchical bias-effect (BHBE) correction was utilized to address residual confounding.

Following PSM, 42423 combination versus 42 423 GLP-1 RA, 40349 combination versus 40 349 SGLT2i, and 51 826 GLP-1 RA versus 51 826 SGLT2i patients were analyzed. Combination therapy significantly reduced all-cause mortality versus SGLT2i monotherapy (hazard ratio [HR] 0.522, 95% confidence interval [CI] 0.488-0.559), with probable benefit after bias correction (corrected HR 0.655, posterior probability 92.4%; credible interval includes the null). Combination therapy demonstrated increased MACE risk versus GLP-1 RA (HR 1.106, 95% CI 1.045-1.170), remaining significant after correction (corrected HR 1.111). Composite liver outcomes favored combination therapy versus SGLT2i (corrected HR 0.907, probability of benefit 81.9%).

GLP-1 RA and SGLT2i combination therapy significantly reduced mortality and liver outcomes versus SGLT2i monotherapy in MASLD with T2DM; however, increased MACE risk versus GLP-1 RA monotherapy warrants consideration in management decisions.