Insulin resistance (IR) contributes to osteoporosis (OP) by impairing bone microarchitecture, posing significant fragility-fracture risk in patients with type 2 diabetes mellitus (T2DM). The triglyceride-glucose (TyG) index and its anthropometry-adjusted derivatives (TyG-body mass index [BMI], TyG-waist circumference [WC]) are simple IR surrogates that may aid OP risk stratification. This study evaluated TyG, TyG-BMI and TyG-WC as independent predictors for OP in T2DM.

In a retrospective cohort of 568 patients with T2DM (36 OP cases), baseline clinical, laboratory (HbA1c, haemoglobin [HGB], high-density lipoprotein cholesterol [HDL], serum calcium [Ca]) and bone-metabolism (procollagen type 1 N-terminal propeptide [P1NP], osteocalcin [OC], bone-specific alkaline phosphatase [BAP]) data were analyzed. Candidate covariates were selected by least absolute shrinkage and selection operator (LASSO) regression with variance inflation factors (VIF) screening. Because the events-per-variable ratio was low (≈4), three Firth's penalised-likelihood logistic regression models were fitted for TyG, TyG-BMI or TyG-WC as the primary analysis. Discrimination was assessed by the area under the receiver-operating-characteristic curve (AUC) with 95% confidence intervals (CIs) and pairwise DeLong tests.

All three indices were significantly higher in OP than non-OP patients (all P < 0.001). After Firth-penalised adjustment, only remained independently associated with TyG-WC (OR 1.004; 95% CI 1.001-1.008; P = 0.013); TyG (P = 0.075) and TyG-BMI (P = 0.105) showed positive but non-significant associations. Higher HbA1c, OC and BAP increased the odds of OP, while male sex and higher HGB were protective. Discrimination was high and similar across models (apparent AUCs: 0.896 [TyG], 0.887 [TyG-BMI] and 0.901 [TyG-WC], with no DeLong-significant difference between indices.

Among the three IR surrogates, only TyG-WC was independently associations with OP in T2DM, although overall discrimination was comparable across indices. TyG-WC may serve as low-cost adjuncts for identifying diabetic patients at elevated OP risk, pending prospective external validation.

The first 1000 days of life, spanning from conception to the end of the second postnatal year, represent a critical developmental window during which environmental and metabolic exposures exert long-lasting effects on offspring health. Among these exposures, maternal and early-life hyperglycemia have emerged as major determinants of metabolic programming and future cardiometabolic disease risk. Increasing evidence suggests that hyperglycemic exposure during this vulnerable period induces complex alterations in placental function, fetal endocrine adaptation, epigenetic regulation, and postnatal metabolic homeostasis, thereby predisposing offspring to obesity, insulin resistance, type 2 diabetes mellitus, and neurodevelopmental disturbances later in life. This review summarizes current evidence regarding the mechanistic pathways linking hyperglycemia during the first 1000 days to adverse metabolic outcomes. We discuss the role of maternal hyperglycemia in placental dysfunction, oxidative stress, inflammation, and altered nutrient transport, as well as its effects on fetal pancreatic development, adipogenesis, and insulin signaling. Particular emphasis is placed on emerging evidence implicating epigenetic modifications, mitochondrial dysfunction, microbiome alterations, and endocrine dysregulation in developmental programming. We further examine the impact of neonatal and early infant metabolic exposures on growth trajectories, adiposity, neurodevelopment, and long-term cardiometabolic health. Finally, we highlight current knowledge gaps and potential opportunities for early intervention, including optimized glycemic control during pregnancy, nutritional modulation, breastfeeding promotion, and precision prevention strategies targeting high-risk mother-infant dyads. A deeper understanding of the biological mechanisms underlying hyperglycemia-induced metabolic programming may facilitate the development of preventive approaches aimed at reducing the intergenerational transmission of metabolic disease.

To investigate the predictive value of preoperative inflammatory-nutritional status and stone complexity for composite adverse outcomes following percutaneous nephrolithotomy (PCNL), and to develop a clinical risk stratification model.

Clinical data of 386 patients with renal calculi who underwent PCNL at the Cangzhou Central Hospital between January 2021 and December 2024 were retrospectively analyzed. Composite adverse outcomes were defined as the occurrence of any of the following: postoperative fever (temperature >38 °C), systemic inflammatory response syndrome (SIRS), requirement for blood transfusion, or complications of Clavien-Dindo grade ≥ II. Preoperative inflammatory-nutritional status was assessed using the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI), while stone complexity was quantified using the Guy's grading system and the S. T. O. N. E. nephrolithometry score. Multivariate logistic regression analysis was performed to identify independent risk factors, and a risk stratification model was constructed based on the number of these factors.

Among the 386 patients, 121 (31.3%) experienced composite adverse outcomes postoperatively. Multivariate logistic regression analysis identified diabetes mellitus (OR = 2.41, 95% CI: 1.32-4.41, p = 0.004), preoperative urinary tract infection (OR = 3.27, 95% CI: 1.58-6.78, p = 0.001), NLR ≥ 3.5 (OR = 2.18, 95% CI: 1.35-3.52, p = 0.001), PNI < 45 (OR = 2.03, 95% CI: 1.22-3.38, p = 0.006), Guy's grade ≥ III (OR = 2.67, 95% CI: 1.56-4.56, p < 0.001), and S. T. O. N. E. score ≥8 (OR = 3.14, 95% CI: 1.89-5.22, p < 0.001) as independent risk factors for composite adverse outcomes after PCNL. Receiver operating characteristic (ROC) curve analysis indicated that ≥3 risk factors was the optimal cutoff for predicting composite adverse outcomes, with a sensitivity of 78.5%, specificity of 75.2%, and an area under the curve (AUC) of 0.837 (95% CI: 0.791-0.883). Patients were stratified into low-risk (0-2 factors), intermediate-risk (3-4 factors), and high-risk (≥5 factors) groups, with corresponding incidence rates of composite adverse outcomes of 12.5, 34.6, and 68.4%, respectively (p < 0.001).

Preoperative inflammatory-nutritional status (NLR, PNI) and stone complexity (Guy's grading system, S. T. O. N. E. score) are independent predictors of composite adverse outcomes after PCNL. The risk stratification model based on the number of risk factors is simple and reliable, and can effectively identify high-risk patients, providing a basis for precise perioperative management.

Diabetic foot ulcer (DFU) affects up to 34% of diabetic patients, with a 1-year recurrence rate of approximately 40%. This review primarily focuses on type 2 diabetes mellitus (T2DM), the most common form of diabetes associated with DFUs. Emerging evidence shows that gut microbiota critically influences DFUs healing through immune modulation (e.g., Treg/Th17 balance), regulation of inflammatory responses via short-chain fatty acids (SCFAs) that inhibit NF-κB, the gut-immune-skin axis, and systemic effects of microbial metabolites. Microbiota-targeted interventions-probiotics, prebiotics, fecal microbiota transplantation, and dietary strategies-can restore microbial balance and reduce inflammation, thereby promoting DFUs healing. These findings provide a mechanistic foundation for microbiome-based therapies and guide future clinical research.

Citrullination and deamidation are post-translational modifications (PTMs) increasingly recognized as important contributors to neoepitope formation in type 1 diabetes (T1D). Under inflammatory and endoplasmic reticulum stress conditions, beta cells activate calcium-dependent peptidylarginine deiminase and transglutaminase enzymes, leading to self-protein modification, altered peptide charge and HLA-binding properties, thereby generating neoepitopes that can be recognized by autoreactive CD4⁺ and CD8⁺ T cells. Accumulating evidence from both murine and human studies demonstrates that immune responses against citrullinated and deamidated beta cell proteins are present and increase with disease progression, supporting a role in epitope spreading rather than disease initiation. Although both PTMs are biochemically analogous, their kinetics and regulation are distinct: citrullination appears as an earlier and partly intrinsic response of stressed beta cells, whereas deamidation is more closely associated with sustained inflammation and later disease stages. In parallel, reduced PTM-generating enzyme expression in the thymus may limit central tolerance to modified epitopes, facilitating escape of autoreactive T cells. In this review, we summarize current insights into the biochemical and immunological roles of citrullination and deamidation in T1D, with emphasis on their temporal regulation, contribution to neoepitope formation, and potential as therapeutic targets, highlighting key findings from our own work in the field.

Diabetic nephropathy (DN) is a one of the common microvascular complication of diabetes that involves oxidative stress, inflammation, activation and overexpression of Nuclear factor kappa B (NF-κB), and chronic renal dysfunction. In this study, we evaluated the renoprotective role of perillaldehyde (PA) in protecting kidneys from diabetic nephropathy using in vitro and in vivo models of Streptozotocin-induced diabetic nephropathy. PA pre-treatment of NRK-52E cells under high-glucose conditions resulted in a significant reduction of reactive oxygen species formation, up-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2), suppression of Kelch-like ECH-associated protein 1 (Keap1), and elevation of antioxidant enzyme biomarkers, such as heme oxygenase 1, superoxide dismutase 1, and NAD(P)H dehydrogenase quinone 1. PA also inhibited the overexpression of NF-κB, inducible nitric oxide synthase, and poly (ADP-ribose) polymerase in high-glucose exposed NRK-52E cells. Administration of PA (35 and 70 mg/kg) to streptozotocin-induced diabetic rats showed beneficial effects on renal function parameters such as creatinine and blood urea nitrogen. PA treatment attenuated glomerular and tubular structural damage, as evidenced by H&E and PAS staining. At molecular level, PA was found to maintain the redox balance in the kidneys by stimulating the Nrf2/Keap1/HO-1 signalling pathway and inhibiting the NF-κB-dependent inflammatory response. Moreover, PA lowered lipid peroxidation and enhanced antioxidant status via reduction in MDA and elevation in GSH. The above results indicated that PA showed considerable reno-protective actions through coordinated regulation of both oxidative stress and inflammation pathways in experimental models of diabetic nephropathy.

Hilar lymph nodes with dense adhesion to the bronchus and pulmonary artery ("doornail" nodes) can be encountered unexpectedly during robot-assisted pulmonary resection. We report our experience managing these nodes and associated factors. This retrospective single-center cohort study included 1,185 patients undergoing robot-assisted pulmonary resection (March 2021-September 2024). Preoperative factors were analyzed using Firth penalized logistic regression in a clinically selected model (age, maximal voluntary ventilation [MVV], and tumor diameter). Operative time and blood loss were compared using robust regression models. Perioperative outcomes were compared descriptively between attempted separate dissection and en bloc stapling. Doornail hilar lymph nodes occurred in 48 of 1,185 patients (4.05%; 95% CI, 3.07-5.33%). Older age remained associated with this finding after adjusting for MVV and tumor diameter (adjusted OR per 10 years, 2.316; 95% CI, 1.533-3.596; P<0.001). Operative time was longer unadjusted (105 vs 92 min; P=0.027) but not after adjustment. Among these 48 patients, 45 (93.8%) received en bloc stapling with no blood loss exceeding 200 mL, transfusion, or prespecified in-hospital complication, whereas all 3 (6.3%) who underwent attempted separate dissection had substantial bleeding (700-2,400 mL), and 2 required transfusion. No conversion to thoracotomy occurred. Doornail hilar lymph nodes occurred in about 4% of patients; older age remained associated with this finding after adjusting for MVV and tumor diameter. Because strategy selection was non-random and groups differed in resection extent, comparative safety cannot be established; en bloc stapling after tissue thinning may be feasible when a node cannot be safely separated.

Although enhanced recovery after surgery (ERAS) has demonstrated benefits in various surgical specialties, evidence supporting its application in elective glioma craniotomies remains limited. This study compared the institutional ERAS pathway with conventional perioperative care in adults undergoing elective craniotomy for a single cerebral glioma. This retrospective cohort study (2019-2024) at a Thai university hospital enrolled patients aged ≥ 15 years with histologically confirmed gliomas. Propensity score matching (PSM; 1:1) addressed measured baseline confounding, and inverse probability of treatment weighting (IPTW) served as a sensitivity analysis. The primary outcomes were total hospital length of stay (LOS), intensive care unit (ICU) LOS, and postoperative LOS. Of 153 eligible patients (ERAS, n = 58; conventional, n = 95), PSM yielded 53 matched pairs. The ERAS group had shorter median total (9 vs. 12 days; p = 0.004) and postoperative (7 vs. 9 days; p = 0.037) LOS, with equivalent ICU LOS, hospitalization costs, and complication rates. The results of the IPTW analysis were directionally consistent. In multivariable logistic regression analyses, 2-hour preoperative carbohydrate loading (adjusted odds ratio [95% confidence interval] 5.98 [1.08-33.02], p = 0.040) and early oral fluid intake within postoperative 8 h (5.74 [1.22-26.96], p = 0.027) independently predicted a short postoperative LOS (< 7 days). Thus, ERAS was associated with shorter hospital stay without increased complications. Preoperative carbohydrate loading and early oral fluid intake were independently associated with a short postoperative LOS, identifying them as high-priority targets for a pragmatic, stepwise implementation strategy for ERAS in elective glioma craniotomies. Prospective multicenter studies are required to further optimize this pathway.

Invasive lobular carcinoma (ILC) of the breast typically affects older women. As a result, there is limited research on prognosis and prognostic factors in young women with ILC. Here we set out to determine the long-term outcome and prognostic factors of women under 40 years of age with lymph node-negative (N0), hormone-receptor positive (HR+)/human epidermal growth-factor receptor 2 negative (HER2-) ILC who did not receive adjuvant systemic treatment (chemo- and/or endocrine therapy).

Through the Netherlands Cancer Registry we selected all systemically untreated patients younger than 40 years with HR+/HER2-, N0, early breast cancer diagnosed in the Netherlands from 1989-2000. At the time, node-negativity was considered a favorable prognostic marker and guidelines recommended no adjuvant systemic therapy for this subgroup. Distant recurrence-free survival (DRFS), recurrence-free survival (RFS) and overall survival (OS) were assessed according to the STEEP criteria. Uni- and multivariable Cox proportional hazard models were used to assess prognosis, calculating hazard ratios (HR) with confidence interval (CI).

Of the n = 1138 selected patients, n = 95 were histologically classified as ILC and n = 805 as invasive breast cancer of no special type (BC-NST), n = 238 were classified as other breast cancer subtype. In ILC, tumor grade was not associated with DRFS/RFS or OS (HR for DRFS 1.40, 95%CI 0.42-4.63). However, the presence of lymphovascular invasion (LVI) (adjusted HR DRFS 2.81, 95%CI 1.14-6.94, p < 0.05) and multifocality (adjusted HR DRFS 3.28, 95%CI 1.49-7.22, p < 0.01) were. When comparing DRFS, RFS and OS in matched low-risk luminal A-like ILC vs. BC-NST, we observed a trend for worse 15-year survival in ILC (15-year DRFS 63% in ILC vs. 74% in BC-NST; HR 1.50, 95%CI 0.98-2.29, p = 0.06).

In these young patients with systemically untreated N0 ILC we show that grade was not prognostic at 15 years follow-up, whereas LVI and multifocality were. Furthermore, ILC had a numerically worse 15-year survival than matched luminal A-like BC-NST.

This study aims to describe the technical details of laser-assisted endoscopic pilonidal sinus treatment (LEPSIT), a method used for the first time in pediatric pilonidal sinus disease (PSD), and to report early-stage clinical outcomes in a pediatric cohort.

Clinical data of children under 18 years of age who underwent LEPSIT for PSD between November 2021 and July 2023 were retrospectively analyzed.

Of the 45 patients included, 19 (42.2%) were female, and 26 (57.8%) were male; the mean age at surgery was 15.2 ± 3.1 years, and the mean body mass index was 25.1 ± 3.2. Of the 45 patients, 35 presented with an acute pilonidal abscess at initial evaluation and had undergone abscess drainage prior to LEPSIT. Six patients had been previously operated on for pilonidal sinus disease at an external center prior to LEPSIT. Mean procedure duration was 30 ± 7.2 min. The mean visual analog scale (VAS) score at 6 h was 1.8, 24 h was 1,1 and the mean analgesic use was 1 ± 0.3 days. Successful treatment was achieved in 41 patients (91.1%) after a single procedure; 4 patients (8.9%) had recurrence, all of whom achieved cure after a second LEPSIT. Improvement was ultimately achieved in all 45 patients. Mean follow-up was 32.4 ± 11.3 months.

LEPSIT is an easy-to-administer, minimally painful (mean VAS score: 1.1), and minimally invasive treatment that shortens hospital stay and enables rapid return to daily activities. It is also a safe and well-tolerated option for recurrent PSD.