Diabetic neuropathy (DN), a long-term and progressive complication of diabetes mellitus, impairs approximated half of patients with diabetes and affects the quality of life considerably because of pain, sensory deficiency, and motor deficits. Traditional treatment including anticonvulsants, antidepressants, and opioids derived agentshas provided some non-specific symptomatic benefit without aiming at the underlying causes like oxidative stress, chronic inflammation, and mitochondrial dysfunction. Curcumin, resveratrol, quercetin, and ginsenosides are few of phytochemicals, that are multi-targeted and can be used as therapeutic agents in DN treatment due to their antioxidant, anti-inflammatory, neuroprotective, and anti-glycation properties. These molecules have the effect of modulating redox-sensitive pathways, like NF-KB, SIRT1 and Nrf2, improving mitochondrial activity, inhibiting pro-inflammatory cytokines (TNF-alpha, IL-6), and stimulating nerve regeneration through neurotrophic factors such as NGF and BDNF. Although they have a promising pharmacological profile, problems like low oral bioavailability, non-clinical standardization, and regulatory concerns hinder their adoption to clinical applications. The review also addresses the importance of large-scale and randomized clinical trials to confirm efficacy and develop uniform dosing regimens.

Diabetic foot wound healing is a significant challenge for diabetic patients. Tanshinone IIA (Tan IIA) is widely used in treating diabetes and related complications, but its role in diabetic foot wound healing remains unclear. The aim of the study is to investigate the mechanism of Tan IIA in diabetic foot wound healing.

Human umbilical vein endothelial cells (HUVECs) cultured in high-glucose medium were used to simulate diabetic pathological conditions. Cell viability and migration were detected by MTT and transwell assays while Annexin V-FITC/PI was used for apoptosis analysis. Measurement of nitric oxide (NO) and Endothelin-1 (ET-1) were performed by ELISA. The expression of vascular endothelial growth factor (VEGF), miR-499-5p and PDCD4 was calculated by RT-qPCR. Dual-luciferase reporter assay was used to validate the interaction of miR-499-5p and PDCD4.

Tan IIA protected high-glucose-treated HUVECs by enhancing cell viability and migration, reducing apoptosis and oxidative stress, and improving endothelial function. Similar effects were observed when miR-499-5p was upregulated. Knockdown of miR-499-5p abolished the protective effects of Tan IIA. PDCD4 was identified as a direct target of miR-499-5p.

Tanshinone IIA protects high glucose-induced HUVECs by enhancing viability, migration, and endothelial function, while reducing apoptosis and oxidative stress, via the miR-499-5p/PDCD4 axis.These in vitro findings support its potential in diabetic foot wound healing, pending in vivo validation.

Patients undergoing bariatric surgery have a substantially elevated risk of gallstone disease, both at baseline and as a consequence of rapid postoperative weight loss. The optimal management of biliary pathology identified at the time of bariatric surgery remains unsettled. We aimed to describe the clinical, radiological, surgical, and histopathological characteristics, and the short-term safety, of simultaneous laparoscopic cholecystectomy performed during bariatric surgery in patients with documented preoperative biliary pathology.

A single-center retrospective cohort of patients who underwent bariatric surgery in 2024 was analyzed. Of 692 bariatric procedures performed by a single surgical team, 117 patients with preoperative ultrasonography-confirmed gallstones or gallbladder polyps who underwent simultaneous laparoscopic cholecystectomy were included. Demographic, anthropometric, comorbidity, imaging, intraoperative, histopathological, and 30-day complication data were extracted from medical records. Only descriptive statistics were used; no concurrent control group was available, and no inferential testing was performed.

The cohort comprised 109 women (93.2%) with a mean age of 42.1 ± 10.5 years and a mean body mass index of 42.3 ± 6.4 kg/m². Hypertension (15.4%), asthma (10.3%), and diabetes mellitus (8.5%) were the most frequent comorbidities. Preoperative imaging revealed multiple gallstones in 63.2%, a single stone in 30.8%, and an isolated gallbladder polyp in 6.0%; the largest stone measured a median of 14 mm (range 3-43). Hepatic steatosis was present in 94.0% of patients and hepatomegaly in 42.7%. Sleeve gastrectomy was performed in 108 patients (92.3%) and gastric bypass in 9 (7.7%); concomitant hiatal hernia repair was carried out in 41 patients (35.0%) and revisional bariatric surgery in 8 (6.8%). Cholecystectomy was performed through the existing 5-mm epigastric liver-retractor port in every patient, with no additional trocar required and no conversion to open surgery. Histopathology demonstrated chronic cholecystitis in all specimens, with an associated cholesterol polyp in 62.4%. A single patient (0.9%) developed early postoperative bleeding that resolved with conservative management and transfusion; no surgical re-exploration was required, and 30-day mortality was zero.

Simultaneous laparoscopic cholecystectomy can be incorporated into bariatric surgery in patients with imaging-confirmed biliary pathology with a low short-term complication rate and without the need for an additional trocar in this single-team series. Prospective, multicenter, randomized studies remain necessary to define the optimal management of asymptomatic gallstone disease at the time of bariatric surgery.

Clinical guidelines recommend next-generation sequencing (NGS) before initiation of first-line (1L) therapy as the standard of care for patients with advanced non-small cell lung cancer (aNSCLC). This study examined the impact of timing of molecular testing in relation to treatment initiation on overall survival (OS) to help inform clinical decision making for aNSCLC treatment.

This retrospective cohort study analyzed the Flatiron Health aNSCLC deidentified database from 2019 to 2021. Patients with aNSCLC and 1L systemic therapy were grouped into three cohorts based on timing of testing: (1) up-front NGS; (2) up-front non-NGS genomic testing; and (3) NGS after 1L therapy initiation. Kaplan-Meier analysis and Cox Proportional Hazards models were used to compare OS from the date of aNSCLC diagnosis between cohorts.

Overall, 13,139 patients with aNSCLC treated with systemic therapy were identified, including 6,210 patients with up-front tumor NGS, 2,697 patients with up-front non-NGS testing, and 2,824 patients with NGS after 1L initiation. A higher proportion of patients with up-front NGS received targeted therapy compared with patients with NGS after 1L initiation (22.6% v 14.8%, P < .0001). Median OS was significantly longer (20.9 months) with up-front NGS compared with up-front non-NGS (17.5 months) and NGS testing after 1L (18.2 months, P < .005). Multivariable analyses suggest that OS benefits associated with up-front NGS were primarily attributable to treatment.

NGS testing before 1L therapy was observed to be associated with earlier use of targeted therapy and longer survival when compared with other testing strategies. Future studies are warranted given the rapidly evolving treatment landscape in aNSCLC.

The phenotypic and morphologic heterogeneity of tumor vasculature in colorectal cancer (CRC) has been increasingly recognized; however, its clinical importance remains unclear.

To examine whether specific tumor vascular features are associated with CRC-specific mortality.

The prospective cohort incident-tumor biobank method (PCIBM) was used to analyze data from the Nurses' Health Study and the Health Professionals Follow-up Study, in which 4476 incident CRC cases were documented and resected tumor tissue specimens were collected. Immunofluorescence staining was conducted from July 30 to August 14, 2024, and data analyses were performed between December 2024 and June 2025.

Tumor vascular features were assessed by in situ multispectral immunofluorescence. The study used an in situ multispectral immunofluorescence assay targeting ACKR1 (atypical chemokine receptor 1), CD34 (cluster of differentiation 34), CD36 (cluster of differentiation 36), KDR (kinase insert domain receptor), LAMB1 (laminin subunit β1), MADCAM1 (mucosal addressin cell adhesion molecule 1), and KRT (keratin) combined with machine learning to characterize tumor vasculature. The vessels were morphologically classified as micro, collapsed, patent, and irregular. Multivariable-adjusted Cox proportional hazards regression models were used to assess CRC mortality.

CRC-specific mortality assessed using multivariable adjusted Cox proportional hazards regression models.

Tumor vessels were successfully analyzed in 837 patients with CRC (median [IQR] age at diagnosis, 69 [63-75] years; 466 [56%] female). During a median (IQR) follow-up of 11.8 (8.7-14.7) years for censored cases, there were 628 all-cause deaths, including 263 CRC-specific deaths. Multivariable-adjusted CRC-specific mortality hazard ratios were 0.39 (95% CI, 0.25-0.60; P for trend <.001) for overall CD34+ vessel density in quartile 4 (vs quartile 1), 0.48 (95% CI, 0.31-0.74; P for trend = .004) for micro CD34+ vessel proportion in quartile 4, 1.58 (95% CI, 1.07-2.32; P for trend = .004) for CD34+CD36+ vessel proportion highest category (vs lowest category), and 1.78 (95% CI, 1.22-2.61; P for trend <.001) for CD34+LAMB1+ vessel proportion highest category.

In this PCIBM-based study of patients with CRC, higher overall CD34+ vessel density was associated with better prognosis, whereas higher CD34+CD36+ and CD34+LAMB1+ vessel proportions were associated with worse prognosis. These findings suggest that tumor vasculature may have a role as a prognostic biomarker and potential therapeutic target.

Hodgkin lymphoma (HL) survivors face an elevated long-term risk of developing second primary malignancies (SPMs), yet accurate prediction tools remain scarce. This study aimed to develop and internally validate a machine learning-based prediction model for SPM risk in HL survivors using a competing risk framework.

We analysed 57,429 patients diagnosed with HL between 2006 and 2020 from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly divided into training (n = 40,201, 70%) and internal validation (n = 17,228, 30%) cohorts. A random survival forest (RSF) model was developed to predict SPM occurrence, with death without SPM treated as a competing event. Model performance was compared against the traditional Fine-Grey subdistribution hazard regression. Discrimination was assessed using time-dependent area under the receiver operating characteristic curve (AUC), and calibration was evaluated through calibration plots. Clinical utility was determined via decision curve analysis (DCA). SHapley Additive exPlanations (SHAP) analysis was employed to interpret the model.

During follow-up, 4,954 patients (8.6%) developed SPMs, while 9,750 (17.0%) died without SPM. The RSF model demonstrated superior discriminative ability compared to Fine-Grey regression across all time points: AUC at 3 years (0.721 vs. 0.549), 5 years (0.761 vs. 0.555), and 10 years (0.804 vs. 0.553). Calibration plots indicated good agreement between predicted and observed risks. DCA confirmed the RSF model provided greater net clinical benefit across a wide range of threshold probabilities. SHAP analysis identified age as the most influential predictor, followed by disease stage, radiotherapy status, race, sex, and chemotherapy.

The RSF-based machine learning model accurately predicts SPM risk in HL survivors within a competing risk framework, substantially outperforming traditional regression approaches. This interpretable prediction tool may facilitate personalised surveillance strategies and risk-adapted follow-up for HL survivors.

To map the scientific evidence on the use of the Neuman Systems Model (NSM) in the field of women's health.

A scoping review. The search was conducted from April to June 2024 in the Scopus, PubMed, Embase, Ovid, Web of Science, CINAHL, Biblioteca Virtual em Saúde, Biblioteca Digital Brasileira de Teses e Dissertações, ProQuest, and Google Scholar databases. Primary studies, reviews, editorials, opinion articles, letters, comments, and grey literature that used the model in women's health were included.

The model was used to assess stress related to procedures and motherhood, understand the experiences of patients with breast cancer, analyze violence, provide contraceptive counseling, and deliver health education regarding the female athlete triad. The model elements were identified in each setting studied; however, few studies used the model comprehensively.

NSM has provided a framework for practice in women's health, using the five variables to guide interventions directed toward health problems, strengthening lines of defense and resistance. It demonstrates potential as a theoretical framework in this field.

Progression-free survival (PFS) is a common primary endpoint in first-line epithelial ovarian cancer (EOC) trials; however, its relationship with overall survival (OS) remains uncertain. The patient-level PFS-OS association among individuals with BRCA wild-type advanced EOC treated with first-line platinum-based chemotherapy was evaluated.

This retrospective analysis pooled patient-level data from first-line advanced EOC historical trials sourced from the Medidata Enterprise Data Store. Eligible patients had BRCA wild-type disease and initiated platinum-based chemotherapy (index date) after primary debulking surgery or as neoadjuvant therapy before planned interval debulking surgery. The PFS-OS association was evaluated using Spearman's correlation (ρ) and landmark analyses at prespecified timepoints (9, 12, 15, and 18 months after index).

Among 487 patients (50.1% aged ≥65 years; 90.1% White; 63.7% International Federation of Gynecology and Obstetrics stage III; 54.6% ECOG-PS 0; 37.3% primary debulking surgery; 53.0% interval debulking surgery; median follow-up 3.4 years), the median PFS and OS were 15.6 months (95% CI, 13.8-16.8) and 42.1 months (95% CI, 37.8-45.7), respectively. The PFS-OS correlation (ρ) was 0.7 (95% CI, 0.6-0.8). Across all landmarks, progression-free patients experienced longer subsequent OS; at 15 months, the unadjusted HR was 0.29 (95% CI, 0.22-0.37). Associations remained after covariate adjustment and did not vary by best overall response, bevacizumab use, or surgical type/outcomes.

In this patient population, PFS demonstrated a consistently moderate, positive association with OS across multiple analytical approaches. These findings provide patient-level evidence that PFS is an informative early endpoint, although additional trial-level evaluations are needed to confirm PFS as a validated surrogate for OS in first-line EOC.

Infantile tumors are rare and different from those in older children in terms of anatomic site, histologic features, and behavior. Thus, they require adapted multimodality approaches for diagnosis and treatment. We aimed to evaluate the characteristics and outcomes of different tumor types in children under 1 year of age who were referred to the Hacettepe University Pediatric Oncology Department over 20 years. There were 515 infants, with a mean age of 6.1±3.4 months, diagnosed with malignant tumors. The male/female ratio was 1.15. Thirty-three (6.4%) of them were diagnosed in the newborn period. Prenatal diagnosis was made in 4.9% of the patients. The most common finding was a mass and symptoms related to the mass (81.6%). The mean time to diagnosis was 31.3±44.7 days. The most common histopathologic diagnoses were retinoblastomas (33.6%), neuroblastomas (27.1%), renal tumors (10.3%), and central nervous system (CNS) tumors (9.7%). Forty patients (7.8%) had congenital anomalies, genetic syndromes and diseases, and metabolic and immune deficiency disorders. Multimodal treatment was administered according to diagnosis, stage, and risk group. The 5-year overall survival (OS) was 86.6% in the whole group and 83.4% in newborns. The best 5-year OS (>91.5%) was observed for renal tumors, retinoblastomas, and neuroblastomas. Conversely, the lowest OS was observed for CNS tumors (52.5%). Our results contribute to a better understanding of the characteristics and outcomes of the tumors in this age group.

Breast cancer (BC) chemoprevention (CP) is highly effective in reducing invasive BC risk, yet uptake among eligible women at high risk remains critically low. Prior research has not adequately examined CP decision-making alongside other primary prevention therapies, such as statins, in the practical context of multimorbidity and polypharmacy.

To identify cognitive, emotional, and perceptual factors associated with accepting statins while declining or deferring breast cancer chemoprevention.

In this exploratory qualitative study, in-depth semistructured interviews were conducted at a single academic health system between December 2024 and June 2025 with women aged 40 to 79 years at elevated risk for BC. Interviews focused on experiences with and perceptions of both BC chemoprevention and statin therapy. Analysis used an iterative, team-based thematic approach supported by a novel hybrid artificial intelligence-human coding workflow.

The primary outcomes were themes identified through thematic analysis that explain systematic differences in patient acceptance of statins and deferral of CP agents.

Among 17 women with high risk for BC (mean [SD] age, 54.5 [10.6] years), 3 overarching categories of themes were identified: (1) risk framing, (2) trade-offs, and (3) pathway complexity. Statins were commonly framed as routine, low-burden, measurable interventions that fit easily into a familiar model of preventive care. In contrast, CP was often perceived as a high-burden, uncertainty-heavy, identity-relevant cancer treatment with benefits experienced as probabilistic, long-term, and invisible. This asymmetry was amplified by multimorbidity and polypharmacy, contributing to treatment fatigue and fragmented clinical pathways in which statins receive clear, prescriptive guidance; however, CP is offered through nondirective, complex discussions across multiple specialists.

In this qualitative study, the divergence in women's decisions about statins vs CP reflected a systematic interplay of drug-specific beliefs, emotional heuristics, and health system structures. These asymmetries may be addressed by reframing CP as a member of a family of preventive risk-reducing medications, presenting it as a reversible and time-limited trial, and embedding it in clearer, more integrated clinical communication with decision support, which may increase appropriate CP uptake among women at high risk.