Surrogate indices such as the triglyceride-glucose (TyG) index are widely used to estimate insulin resistance (IR), yet their ability to discriminate incident gestational diabetes mellitus (GDM) in early gestation remains suboptimal. This study evaluated whether the previously developed composite metabolic index GLM7 was correlated with subsequent GDM in Korean singleton pregnant women.

In this study, we analyzed 582 singleton pregnancies from a Korean pregnancy registry. Multivariable logistic regression and restricted cubic splines (RCS) were used to evaluate the association between GLM7 and GDM. Discriminative performance was assessed by receiver operating characteristic (ROC) curve analysis, and pairwise comparisons were performed using DeLong's test. Robustness was assessed through sensitivity analyses, subgroup analyses, and E-value calculations.

In the fully adjusted model, GLM7 was independently associated with incident GDM (OR 14.27, 95% CI 5.01-40.67; p < 0.001). RCS analysis showed no evidence of departure from linearity (p for non-linearity = 0.266). The association persisted across sensitivity and subgroup analyses. The E-value of 28.03 suggested that only a very strong unmeasured confounder could nullify the observed association. ROC analysis revealed an AUC of 0.839 (95% CI 0.767-0.912) for GLM7. Pairwise DeLong comparisons showed significantly higher AUCs for GLM7 than for HOMA-IR and for first-trimester fasting plasma glucose (FPG), while differences compared with the TyG index, fatty liver index (FLI), and hepatic steatosis index (HSI) were not statistically significant. Within this cohort, the optimal GLM7 threshold was 6.932, yielding 77.8% sensitivity and 78.2% specificity.

GLM7 was independently associated with subsequent GDM.

Intractable neovascular glaucoma (NVG), secondary to retinal ischemia, responds poorly to traditional surgery due to postoperative neovascularization and scarring. Intravitreal ranibizumab(IVR) swiftly alleviates neovascularization to enable subsequent treatment, yet its long-term efficacy remains unclear.

This study sought to evaluate the ranibizumab-surgery combination therapy in NVG and describe clinical characteristics of surgical failure cases.

This retrospective propensity score matching (PSM) cohort study enrolled 62 patients (62 eyes) with NVG between August 2022 and August 2024. Using 1:1 nearest-neighbor PSM, 31 eyes received preoperative IVR plus conventional surgery (study group), while 31 underwent surgery alone (control group). Over 12 months of follow-up, the primary endpoint was the 12-month surgical success rate; secondary outcomes included IOP, BCVA, postoperative NVI status, and complications. IOP and BCVA were analyzed using linear mixed-effects models, and clinical characteristics of the failure cases were described descriptively.

After PSM, baseline characteristics were generally comparable between groups, with residual imbalances noted for glaucoma stage and angle status. The study group showed significantly lower IOP at all postoperative visits (P < 0.05). The 12-month surgical success rate was numerically higher in the study group (93.5% vs. 77.4%). Secondary outcomes, including BCVA improvement and favorable NVI-free status, were more favorable in the study group, while the difference in overall complications did not reach statistical significance. Among the 9 failure cases, the majority had poor baseline BCVA, diabetes mellitus, and advanced glaucoma stage.

In this retrospective matched cohort, adjunctive IVR was associated with more favorable IOP control and NVI-free status, whereas the difference in the 12-month surgical success rate, although numerically higher, did not reach statistical significance. Given the exploratory nature of this single-center study, larger prospective studies are warranted to confirm these findings.

This retrospective matched cohort study suggests that perioperative ranibizumab may be associated with more favorable IOP control and NVI-free status, although the 12-month surgical success rate did not reach statistical significance. These findings are exploratory and require confirmation in larger prospective studies.

This retrospective cohort study included 700 pregnant women who underwent antenatal check-ups and delivered at the Fourth Hospital of Shijiazhuang from January 2022 to December 2023, aiming to investigate the associations of second°trimester serum magnesium, phosphorus, and calcium with adverse pregnancy outcomes including gestational diabetes mellitus (GDM), anemia, and preterm birth. Mineral indicators were measured at 24-28 weeks of gestation, and baseline data were collected.

Mann-Whitney U test was adopted to compare the serum mineral levels among women with different pregnancy outcomes, multivariable logistic regression and ROC curve analysis was utilized to further explore the correlations.

After adjusting for potential confounders, magnesium, phosphorus, and calcium levels were correlated with GDM risk, with magnesium and calcium exerting statistically significant protective effects against GDM while high phosphorus serving as a statistically significant GDM risk factor. High calcium was also negatively associated with the risks of anemia and preterm birth whereas high phosphorus was positively linked to preterm birth risk.

These findings demonstrate that second-trimester serum magnesium, phosphorus, and calcium levels are associated with GDM, providing clinical evidence for glycemic control interventions and individualized nutritional guidance during pregnancy.

Type 2 diabetes mellitus (T2DM) increases the risk of sarcopenia, which independently contributes to bone fragility, especially among the elderly. Bone mineral content (BMC) is a parameter that helps in the assessment and monitoring of bone mass. This study aims to identify the correlation between BMC and sarcopenia in hospitalized patients with T2DM.

A total of 1,135 inpatients admitted with T2DM in this study and classified into two groups (sarcopenia and non-sarcopenia group). A comparative analysis of clinical data and body composition was performed between the two groups. A multivariable logistic regression model was used to assess the independent association of BMC with sarcopenia.

The sarcopenia group showed a lower BMC level than the non-sarcopenia group (P < 0.001). The BMC level was correlated with a history of sarcopenia (P < 0.001). The receiver operator characteristic (ROC) curve analysis showed a medium ability of BMC in predicting sarcopenia (area under the ROC curve=0.760). The optimal cut-off level for BMC to predict sarcopenia was found to be < 2.86 kg. Finally, in the multivariable logistic regression model, a BMC level < 2.86 kg was significantly associated with sarcopenia [odds ratio (OR) = 4.994, 95% confidence interval [CI] 3.130-7.967, P < 0.001]. Additional analyses revealed that lower BMC level was associated with an increased risk of sarcopenia irrespective of the subgroup of age (including elderly group and non-elderly group).

Our results confirmed that in hospitalized patients with T2DM, BMC levels are inversely associated with sarcopenia and may therefore serve as a biomarker for sarcopenia discrimination. But additional studies are needed to confirm and further elucidate our results.

CD70 deficiency, mostly recognized by immune dysregulation, hemophagocytic lymphohistiocytosis, lymphoproliferation, and malignancy, was recently associated with severe and accelerated diabetes in mice. Such a causal relationship is not previously reported in humans. The aim of this study is to describe the first case of CD70 deficiency manifesting with severe onset type 1 diabetes mellitus (T1DM). Changes to glycemic control following hematopoietic stem cell transplantation and accompanying autoimmunity are defined. Immunophenotype analysis, next-generation-primary immunodeficiency panel analysis, and Sanger sequencing were conducted. Then, segregation analysis and functional studies were carried out for validation of the homozygous missense variant in CD70. Following confirmation of CD70 deficiency, hematopoietic stem cell transplantation (HSCT) was carried out. A comprehensive review of clinical history, alongside biochemical and immunologic investigations, was carried out to identify the natural history as well as immune and endocrine phenotypes. Presentation of severe-onset T1DM with severe diabetic ketoacidosis, multiorgan dysfunction, and unexplained findings during follow-up (recurrent diabetic ketoacidosis episodes, unexplained recurring skin lesions, and celiac disease) prompted an evaluation for underlying etiology, and CD70 deficiency was diagnosed. Timely HSCT was curative for CD70 deficiency. Following HSCT, glycemic control was improved (median HbA1c: 8.1% [7.6-8.6] vs 6.5% [5.8-7.0]), total daily insulin dose was reduced from 0.85 to 0.62 U/kg/d, and recurrent episodes of diabetic ketoacidosis ceased. It was concluded that, a homozygous missense variant in CD70, causing CD70 deficiency, may be associated with severe onset T1DM, confirming the significance of intact CD27/CD70 co-stimulation in the prevention of pancreatic β-cell autoimmunity. The CD27/CD70 pathway represents a potential target for immunotherapy trials in T1DM.

Tubulointerstitial fibrosis predicts irreversible kidney function loss in diabetic kidney disease (DKD), but adipose-derived signals that shape fibrogenesis are poorly defined. Here, we show that perirenal fat (PRF), an adipose depot contiguous with the kidney, is enriched for β₃-adrenergic receptor (ADRB3) and that ADRB3 expression is reduced in human DKD and male mouse DKD models. In db/db and streptozotocin/high-fat diet mice, increased PRF mass associates with albuminuria and serum creatinine, whereas PRF removal attenuates tubular lipid accumulation, mitochondrial injury and fibrosis. Brown adipocyte-lineage ADRB3 deletion enlarges PRF and increases adipocyte TNFα release by suppressing Bcat2-dependent branched-chain amino-acid catabolism through CREB1/METTL3-mediated m6A regulation. ADRB3 activation or PRF-restricted ADRB3 restoration reduces PRF inflammation and renal fibrosis, while iBAT-restricted restoration does not reproduce this renal protection. These findings identify a PRF ADRB3-Bcat2/BCAA-TNFα pathway that contributes to diabetic renal fibrosis.

Giredestrant and everolimus target the estrogen receptor (ER) pathway and the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway, respectively, which are implicated in endocrine-therapy resistance.

In this phase 3, open-label, randomized trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who had disease progression or recurrence after receipt of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor plus endocrine therapy. Patients were assigned, in a 1:1 ratio, to receive giredestrant plus everolimus (each given orally) or standard endocrine therapy (i.e., exemestane, fulvestrant, or tamoxifen) plus everolimus. The primary end point was investigator-assessed progression-free survival, evaluated first among patients with ESR1-mutated tumors and then in the overall trial population.

Overall, 373 patients underwent randomization, with 183 assigned to the giredestrant-everolimus group and 190 to the standard therapy-everolimus group. Among 207 patients with ESR1-mutated tumors, the median progression-free survival was 10.0 months with giredestrant-everolimus and 5.5 months with standard therapy-everolimus (hazard ratio for disease progression or death, 0.38; 95% confidence interval [CI], 0.27 to 0.54; P<0.001). In the overall population, the median progression-free survival was 8.8 months with giredestrant-everolimus and 5.5 months with standard therapy-everolimus (hazard ratio, 0.56; 95% CI, 0.44 to 0.71; P<0.001). Adverse events occurred in 98.9% of patients who received giredestrant-everolimus and in 96.8% of those who received standard therapy-everolimus. The most common adverse events were stomatitis (in 47.3% of giredestrant-everolimus recipients and 48.9% of standard therapy-everolimus recipients), diarrhea (in 26.9% and 22.6%, respectively), and anemia (in 23.6% and 21.0%).

An all-oral giredestrant-everolimus regimen led to significantly longer progression-free survival than standard endocrine therapy-everolimus among patients with ER-positive, HER2-negative advanced breast cancer who had received a CDK4/6 inhibitor previously, mainly in patients with ESR1-mutated tumors. The incidence of adverse events was similar in the two groups. (Funded by Genentech; evERA Breast Cancer ClinicalTrials.gov number, NCT05306340.).

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a complex and dose-limiting toxicity of cancer treatment leading to increased disability and reduced quality of life. Inconsistent use of outcome measures in previous studies have limited our ability to identify clinical risk factors for CIPN. This study aimed to use a comprehensive multimodal battery of neuropathy assessment to investigate the association between clinical variables and CIPN in individuals treated with neurotoxic cancer treatment.

We conducted a cross-sectional, multisite study of individuals who had received neurotoxic treatments from oncology centers in Australia (taxanes, platinum, vinca alkaloids, bortezomib, and thalidomide). CIPN was assessed through clinical grading, neurologic evaluation (Total Neuropathy Score [TNS], sural nerve conduction studies), and patient-reported outcome measure (European Organization for Research and Treatment of Cancer Quality of Life Chemotherapy-Induced Peripheral Neuropathy Questionnaire [EORTC-CIPN20]). Clinical variables included demographic (age, sex), metabolic (body mass index [BMI], diabetic status), and medical history (preexisting peripheral neuropathy, prior neurotoxic treatment). Dose information was extracted from clinical notes to identify dose modification of neurotoxic treatments due to CIPN. Least absolute shrinkage and selection operator (LASSO) regression was used to identify candidate variables, followed by multivariable regression to construct final models. The results were presented as odds ratio (OR) or β (95% CI).

The study included 901 individuals (median age 61 [interquartile range 19] years, 66% female) assessed 12 (median; interquartile range 18) months postneurotoxic treatment. In total, 37% had moderate-to-severe CIPN (n = 337, clinical grade ≥2), and 31% required dose modification due to CIPN. Multivariable logistic regression identified female sex (OR 1.7, 95% CI 1.2-2.5) to be associated with dose-limiting CIPN. Post-treatment CIPN was evaluated using multiple assessment tools. Patient-reported neuropathy was associated with older age (β = 3.9, 95% CI 2.0-5.7), diabetes (β = 3.3, 95% CI 0.1-6.5), higher BMI (overweight β = 3.1 [95% CI 0.9-5.2], obese β = 3.8 [95% CI 1.4-6.2]), and prior neurotoxic treatment (β = 5.1, 95% CI 1.3-8.9). Similar factors were associated with neurologic evaluation (TNS, sural amplitude). Clinical grading was associated with age (OR 3.0, 95% CI 2.2-4.2), higher BMI (overweight OR 2.1 [95% CI 1.5-3.0], obese OR 1.6 [95% CI 1.1-2.4]), and prior neurotoxic treatment (OR 2.9, 95% CI 1.2-6.8). Variables associated with severe CIPN (defined as highest quartile scores or moderate/severe clinical grading) across all assessment tools included older age (EORTC-CIPN20 OR 1.9 [95% CI 1.3-2.6], TNS OR 3.2 [95% CI 2.2-4.8], clinical grading OR 1.8 [95% CI 1.3-2.4]), and prior neurotoxic treatment (EORTC-CIPN20 OR 1.9 [95% CI 1.0-3.4], TNS OR 2.0 [95% CI 1.1-3.7], clinical grading OR 2.1 [95% CI 1.2-3.7]).

CIPN is a significant toxicity that affects patients' ability to receive anticancer therapies and continues to affect long-term survivorship. We identified clinical variables that are readily available at beginning of treatment, which suggest increasing susceptibility to developing dose-limiting, post-treatment, and severe CIPN.

Evidence on the associations of polyunsaturated fatty acid (PUFA) intake and sleep patterns with lung cancer remains inconsistent. We aimed to examine these associations in southwest China and to explore whether the association between sleep patterns and lung cancer differed according to dietary PUFA intake.

We conducted a matched case-control study in Chongqing, southwest China, from August 22, 2023, to September 30, 2024. Each lung cancer case was matched to two controls by age group (<45, 45-65, or >65 years) and sex. Dietary PUFA intake was assessed using a validated semi-quantitative food frequency questionnaire (SQFFQ), and sleep patterns were evaluated using a composite healthy sleep score based on five sleep characteristics. Multivariable conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

A total of 322 lung cancer cases and 644 matched controls were included. In continuous analyses, each 1-g/day increase in omega-3 PUFA intake was associated with lower odds of lung cancer (OR = 0.82, 95% CI: 0.70-0.96). In tertile-based analyses, participants in the highest versus lowest intake tertiles had lower odds of lung cancer across all three PUFA types (omega-3 PUFAs: OR = 0.50, 95% CI: 0.32-0.78; omega-6 PUFAs: OR = 0.50, 95% CI: 0.31-0.80; total PUFAs: OR = 0.48, 95% CI: 0.30-0.79). Favorable sleep patterns were also associated with lower odds of lung cancer compared with unfavorable sleep patterns (OR = 0.59, 95% CI: 0.40-0.87). Although lower stratum-specific ORs were observed in the higher omega-3 PUFA intake stratum, the multiplicative interaction tests were not statistically significant.

Higher dietary omega-3 PUFA intake and favorable sleep patterns were each associated with lower odds of lung cancer in this matched case-control study. Associations for omega-6 and total PUFA intake were observed in tertile-based analyses but were not consistent across modeling approaches. These observational findings require confirmation in prospective studies.

Postoperative recurrence after hepatic resection for hepatocellular carcinoma (HCC) remains frequent. Readily available biomarkers that integrate host inflammatory, immune, and nutritional statuses may improve risk stratification. In this study, we evaluated the prognostic significance of the preoperative C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index in patients who underwent resection for primary HCC.

This retrospective, single-center study included 611 patients who underwent hepatic resection for primary HCC between 2004 and 2022. The CALLY index was defined as (albumin × lymphocytes)/(CRP × 104). Patients were classified into high (≥ 2.2) and low (< 2.2) CALLY index groups. Clinicopathological factors, disease-free survival (DFS), and overall survival (OS) were compared. Prognostic factors were assessed using Cox proportional hazards models, and propensity-score matching was performed.

The low CALLY index group had lower albumin levels, higher CRP and alpha-fetoprotein levels, larger tumors, and more severe postoperative complications than the high CALLY index group. Patients with low CALLY index had significantly worse DFS and OS than those with high CALLY index. Multivariate analysis identified that the low CALLY index was independently associated with worse DFS (hazard ratio (HR), 1.86; 95% confidence interval (CI), 1.40-2.47; P < 0.0001) and OS (HR, 1.93; 95% CI, 1.37-2.72; P = 0.0002). After propensity-score matching, the low CALLY index group continued to have significantly poorer DFS and OS rates than the high CALLY index group.

The preoperative CALLY index was independently associated with DFS and OS after hepatic resection for primary HCC. This simple biomarker may help identify patients at a high risk of recurrence and poor survival.