-
CD4+ T cell subset imbalance contributes to diabetic kidney disease progression: immunopathological mechanisms and targeted therapeutic strategies.1 week agoDiabetic kidney disease (DKD) is one of the most common microvascular complications of diabetes and a leading cause of end-stage renal disease. Recently, immune and inflammatory mechanisms have been recognized as critical in the pathogenesis of DKD, among which CD4+ T cell subset imbalance serves as a key contributor to renal inflammation and fibrosis. This narrative review synthesizes evidence from PubMed, Web of Science, and EMBASE (inception to March 2026) to provide a comprehensive overview of the immunopathological roles and molecular regulatory networks of major CD4+ T cell subsets, including T helper type 1, T helper type 2, T helper type 17 and regulatory T cells, in mediating renal injury through signature cytokines and signaling pathways. We also discuss the regulatory effects of hyperglycemia, hypoxia and lipid disorders on CD4+ T cell function, as well as the crosstalk between renal resident cells and CD4+ T cells via pathways such as programmed death-1/programmed death ligand-1 and nuclear factor-kappa B in amplifying inflammatory responses. Moreover, we outline current therapeutic strategies targeting CD4+ T cells, including traditional Chinese herbs, biologic agents, nonsteroidal mineralocorticoid receptor antagonists, sodium-glucose cotransporter 2 inhibitors and stem cell therapy, and evaluate their potential and limitations in balancing T cell subsets and alleviating renal injury. Although these approaches show promise, translating them into precise immunotherapy for DKD will require deeper mechanistic insight and rigorous clinical validation.DiabetesCare/Management
-
In situ devalvulated small saphenous vein for distal popliteal-peroneal and popliteal-posterior tibial bypass in patients with chronic limb-threatening ischemia: A multicenter case series.1 week agoPatients with chronic limb-threatening ischemia (CLTI) who have exhausted conventional endovascular strategies and lack an adequate great saphenous vein represent a challenging subgroup with limited limb salvage options. We evaluated the feasibility, durability, and clinical outcomes of distal popliteal-peroneal and popliteal-posterior tibial bypasses performed using an in situ devalvulated small saphenous vein (SSV) through a posterior prone approach.
A multicenter, retrospective-prospective observational case series was conducted across participating vascular centers. Consecutive patients undergoing distal popliteal-peroneal or popliteal-posterior tibial bypass using an in situ devalvulated SSV between January 2023 and December 2025 were included. Eligible patients presented with CLTI, absence of a suitable great saphenous vein, previous failed distal bypasses, and/or local infectious or anatomical conditions precluding a standard medial approach. Procedures were performed in the prone position through a posterior exposure. The primary end point was limb salvage at 12 months. Secondary end points included technical success, primary/primary-assisted/secondary patency, wound healing, amputation-free survival, and perioperative complications.
A total of 11 patients were included. The mean age was 77 ± 11 years, and 73% were male. Diabetes mellitus was present in 100%, chronic kidney disease in 91%, and 36% were dialysis dependent. According to the Rutherford classification, 91% presented with tissue loss. Previous failed ipsilateral revascularization had occurred in 100% of limbs. Target vessels included the distal peroneal artery in four limbs and the retromalleolar/inframalleolar posterior tibial artery in seven limbs. Technical success was achieved in 100% of procedures. Thirty-day mortality was 0%, whereas early graft thrombosis occurred in 27.7%. At 12 months, primary, primary-assisted, and secondary patency rates were 63.6%, 72.7%, and 72.7%, respectively. Limb salvage was achieved in 72.7% of patients. Complete wound healing occurred in 100% after a median time of 6 weeks. Freedom from major adverse limb events was 72.7%.
Posterior popliteal-distal bypass using an in situ devalvulated SSV represents a valuable limb salvage strategy in highly selected patients with CLTI lacking conventional revascularization options. This technique allows the use of an entirely autologous conduit while avoiding hostile medial leg exposures. Acceptable patency and limb salvage outcomes can be achieved despite extreme anatomical complexity and previous treatment failures.DiabetesCare/Management -
Drug-induced hyperglycemia in obstetrics: key offending drugs, mechanisms, and practical management.1 week agoDrug-induced hyperglycemia is an important metabolic complication that may arise when medications disrupt insulin secretion, insulin sensitivity, or glucose homeostasis. In obstetric practice, several commonly used drugs, including glucocorticoids, progesterone, antihypertensive agents, tocolytic drugs, and immunosuppressants, may impair glycemic control to varying degrees, and prolonged exposure may even lead to drug-induced diabetes mellitus. These effects are particularly important in pregnant women with pregestational diabetes, gestational diabetes, obesity, or other risk factors for dysglycemia.
We systematically reviewed the literature from major databases over the past decade on the association between commonly used obstetric medications and hyperglycemia, with a focus on glucocorticoids, beta-adrenergic agonists, tacrolimus, nifedipine, and indomethacin. Evidence from clinical studies, case reports, and mechanistic investigations was summarized.
Among the drugs reviewed, glucocorticoids, beta-adrenergic agonists, and tacrolimus showed relatively prominent diabetogenic effects, mainly through increased insulin resistance, β-cell dysfunction, and reduced insulin secretion. In contrast, nifedipine and indomethacin appeared to have less clinically significant effects on blood glucose. The use of high-risk agents during pregnancy was associated with a higher incidence of hyperglycemia and increased complexity of glycemic management.
Early identification of high-risk drugs and high-risk patients, together with individualized glucose monitoring and timely intervention, may reduce related complications and improve medication safety during pregnancy. Further prospective studies are warranted to define safe thresholds across different gestational stages and maternal conditions.DiabetesCare/Management -
Charcot Neuroarthropathy: Identification and Classification Using Artificial Intelligence (AI).1 week agoCharcot neuroarthropathy (CN) is a rare but severe complication of diabetes mellitus, characterized by progressive bone and joint destruction that may lead to foot deformity and limb loss. Accurate anatomical classification using Brodsky's system is essential for clinical decision-making but often depends on specialist interpretation, which may not be accessible in all healthcare settings. Artificial intelligence (AI), particularly deep learning, has emerged as a promising tool to support clinicians by automating the detection and classification of complex radiological patterns.
Neural network (NN) models with varying architectures were developed using a retrospective dataset comprising 234 X-rays from consecutive patients diagnosed with and without CN who received treatment at the Foot and Ankle Department of a tertiary care institute. All X-rays were retrieved from the hospital's PACS and annotated under the supervision of a senior foot and ankle consultant. The algorithm was trained to automatically detect the affected region and classify CN according to the Brodsky anatomical classification. The resulting algorithm was then validated on two sets of unseen datasets of 23 X-rays (internal test) and 15 X-rays (external test). The reference standard for classification was the assessment made by a senior foot and ankle surgeon, and model performance was evaluated against this reference standard.
Among the 23 X-rays included in the internal test, 18 had Charcot neuroarthropathy (target condition present) and 5 did not have the condition (target condition absent). The classification model achieved an accuracy of 93.39% on unseen data, while the segmentation model demonstrated 96.85% accuracy in both validation and testing. The AI predictions showed 91.3% agreement with expert-assigned Brodsky classifications, successfully identifying and localizing affected anatomical regions across diverse cases. For external validation, the model was evaluated on an independent dataset comprising 15 X-rays, of which 14 were correctly classified, corresponding to a 93.3% agreement with expert labels.
The proposed AI system offers a reliable and accurate method for diagnosing and classifying CN from radiographs, even in resource-limited environments. By recognizing global versus localized destruction patterns, it can help distinguish CN from conditions such as osteomyelitis, supporting earlier diagnosis and improved clinical outcomes. However, given the limited dataset, the current model should be regarded as a feasibility study, and larger multicenter datasets with increased number of observers for validation are needed to enhance its generalizability and clinical applicability.DiabetesCare/Management -
Development and validation of a LASSO-selected machine learning prediction pipeline for predicting coronary artery calcification in a health check-up population.1 week agoCoronary artery calcification (CAC) screening in young, asymptomatic populations is clinically valuable but constrained by CT radiation and cost. We developed and calibrated a parsimonious, interpretable machine learning model using routine health check-up variables to identify CAC-positive individuals suitable for early preventive lifestyle counseling.
A total of 4,465 participants were randomly divided into a training set (n = 3,125) and a testing set (n = 1,340) using stratified sampling based on CAC status. Candidate predictors included demographic characteristics, clinical history, anthropometric measurements, blood pressure, and laboratory indices. Least absolute shrinkage and selection operator (LASSO) regression was applied in the training set for feature selection, followed by the construction of a class-weighted and probability-calibrated logistic regression model. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, the Hosmer-Lemeshow test, decision curve analysis (DCA), and SHAP interpretation.
LASSO selected 13 predictors: sex, age, pulse, systolic blood pressure (SBP), diastolic blood pressure (DBP), hypertension (HTN), diabetes mellitus (DM), low-density lipoprotein cholesterol (LDL-C), serum creatinine (Scr), serum uric acid (SUA), non-alcoholic fatty liver disease (NAFLD), smoking, and drinking. The final model achieved an AUC of 0.816 in the training set and 0.771 (95% CI, 0.713-0.824) in the testing set. At the optimal classification threshold, the testing-set sensitivity, specificity, accuracy, PPV, NPV, F1 score, Brier score, and AUPRC were 0.726, 0.689, 0.691, 0.102, 0.981, 0.179, 0.042, and 0.147, respectively. Calibration was acceptable in both cohorts. DCA suggested positive net benefit within a low threshold probability range relevant to preventive counseling and further cardiovascular risk assessment. SHAP analysis identified age, sex, hypertension, pulse, and NAFLD as the most influential predictors.
The LASSO-selected and calibrated logistic regression model demonstrated acceptable discrimination and calibration for CAC positivity in an internally validated health check-up cohort. Its potential use should be interpreted as preliminary risk stratification rather than clinical implementation, and independent multicenter external validation is required before the model can be recommended for routine clinical use.DiabetesCare/Management -
Metabolic reprogramming in diabetic panvascular disease: Molecular mechanism and therapeutic strategies.1 week agoDiabetes mellitus substantially increases the risk of cardiovascular, cerebrovascular, renal, retinal and peripheral vascular complications. These are collectively referred to as diabetic panvascular disease. A traditional approach that treats each complication separately is no longer sufficient. An emerging framework places metabolic reprogramming at its center. This review examines how the diabetic environment, including hyperglycemia, insulin resistance, and dyslipidemia, rewires core metabolic pathways in vascular cells. Major changes include the diversion of glucose through the polyol, hexosamine and AGE-PKC axes, lipotoxicity resulting from excessive fatty acids, disruption of amino acid networks such as BCAA and one-carbon metabolism, mitochondrial dysfunction with increased mtROS production, and epigenetic modifications that drive metabolic memory. These interconnected abnormalities promote oxidative stress and chronic inflammation, which in turn lead to endothelial dysfunction, atherosclerosis, microvascular rarefaction, and end-organ damage in the heart, brain, kidney, retina, and peripheral nerves. We also describe the current therapeutic landscape, ranging from established agents such as metformin, SGLT2 inhibitors, GLP-1 receptor agonists, RAAS blockers, and anti-VEGF therapies to emerging mechanism-based strategies including aldose reductase inhibitors, glucokinase activators, PKC, RAGE, NOX, and NLRP3 inhibitors, miRNA modulators, and exosome therapy. Finally, we highlight unmet needs and future directions. These may include multi-omics guided precision phenotyping, cross-organ causal inference, single-cell metabolic flux technologies, and adaptive clinical trial designs. By shifting from a glucose-centric to a metabolic reprogramming-centric paradigm, this review aims to provide a roadmap for developing more targeted therapies for diabetic panvascular disease.DiabetesCare/Management
-
Hemorrhagic sellar lesion mimicking pituitary adenoma apoplexy: MRI follow-up suggesting Rathke cleft cyst.1 week agoRathke cleft cysts (RCCs) are benign epithelial sellar and suprasellar lesions arising from remnants of Rathke pouch. Although typically incidental and asymptomatic, intracystic hemorrhage is rare and may mimic pituitary adenoma apoplexy. We report a 19-year-old woman presenting with one week of progressive severe headache. CT demonstrated sellar enlargement with suprasellar extension. MRI showed a hemorrhagic sellar lesion centered in the pars intermedia/posterior pituitary with fluid-fluid levels, dependent T2 hypointense components, susceptibility-related signal loss, and suprasellar extension abutting the optic chiasm, without nodular enhancement. Neurologic, ophthalmologic, and endocrinologic evaluations were unremarkable. Conservative management with corticosteroids and observation was pursued. Follow-up MRI at 3 months demonstrated markedly decreased pituitary enlargement with evolution into a small residual nonenhancing pars intermedia cyst, suggesting a hemorrhagic RCC. Recognition of this rare entity may support conservative management and avoid surgery in clinically stable patients.CancerCardiovascular diseasesAccessCare/ManagementAdvocacy
-
From "passive burden-bearing" to "active benefit-gaining": exploring the psychological growth paths of female caregivers of advanced lung cancer patients.1 week agoThis study aimed to explore the benefit-finding experiences of female caregivers of patients with lung cancer, focusing particularly on their positive psychological adaptations throughout the caregiving process. The findings are expected to inform the development of more targeted and effective nursing interventions.
A qualitative phenomenological approach was employed, with sample size determined by the principle of data saturation. From November to December 2024, 12 female caregivers of hospitalized lung cancer patients were purposively recruited from a tertiary hospital in Shenzhen, Guangdong Province. Data were collected through semistructured, in-depth interviews and analyzed using Colaizzi's seven-step method. MAXQDA 22.0 software was utilized to facilitate data organization, coding, and thematic analysis.
Twelve participants aged 30-75 years were included in the study. Analysis of the interview data generated four major themes and six subthemes: (1) reflections on the meaning of life (drawing strength in adversity, reconstructing life meaning), (2) enhancement of caregiving competence (improved disease-related knowledge, strengthened caregiving role), (3) multifaceted support (perceived family support, perceived social support), and (4) adoption of positive coping strategies.
Female caregivers of patients with lung cancer demonstrated clear benefit-finding experiences throughout the caregiving process. These findings underscore the importance of supporting caregivers in developing adaptive coping strategies, strengthening caregiving skills, and addressing both the physical and psychological needs of patients. Facilitating positive psychological adjustment and mobilizing supportive resources can not only promote patient self-management and well-being but also enhance caregivers' perceived benefits and reduce caregiving stress.CancerChronic respiratory diseaseAccessCare/ManagementAdvocacy -
Continuous infusion of granulocyte colony-stimulating factor is associated with an advantage in neutrophil recovery in pediatric oncologic disorders.1 week agoThe use of intensified chemotherapy has significantly improved overall survival (OS) and relapse-free survival (RFS) in cancer patients. However, it also increases the risk of chemotherapy-induced neutropenia (CIN). Granulocyte colony-stimulating factor (G-CSF) is commonly used to hasten neutrophil recovery, but limited research has focused on the superiority of different routes of G-CSF administration.
This was a randomized, prospective, single-institution study. Twenty-eight participants were enrolled and randomly assigned to experimental and control arms in a 1:1 ratio. At the end of the study, 20 cases were eligible for statistical analysis. The primary endpoint was the duration from the onset of neutropenia to steady neutrophil recovery. Secondary endpoints included the safety profile, 7-day emergency return rate, and the occurrence of infectious or febrile events.
The mean duration from CIN to neutrophil recovery was 6.2 days in the intravenous drip (IVD) group and 7.6 days in the intravenous injection (IVI) group (P = 0.0068). The mean difference between the two groups was 1.4 days. A significantly lower incidence of febrile neutropenia (FN) was observed in the IVD group compared to the IVI group (15% vs. 50%, P = 0.0407). Adverse effects (AEs) were comparable between the two groups.
The IVD route of G-CSF administration leads to faster neutrophil recovery and reduces the risk of FN. All evaluable AEs are comparable between the two groups. These findings suggest that the IVD route may be a preferable option for optimizing supportive care in cancer patients with CIN.CancerAccessCare/ManagementAdvocacy -
Linvoseltamab outcomes by frailty status in patients with relapsed/refractory multiple myeloma: a subgroup analysis of the LINKER-MM1 study.1 week agoThere is a paucity of data in frail patients with multiple myeloma (MM) receiving bispecific antibodies (bsAbs). In LINKER-MM1 (NCT03761108), linvoseltamab (human BCMA×CD3 bsAb) demonstrated high response rates and a generally manageable safety profile in relapsed/refractory (RR)MM. This LINKER-MM1 post hoc analysis evaluated outcomes of linvoseltamab 200 mg in patients categorized for frailty using the International Myeloma Working Group Frailty Proxy (IMWG-FP), Simplified Frailty Score (SFS), and patient-reported frailty phenotype (PRFP). As of July 23, 2024, 117 patients received linvoseltamab (median follow-up: 21.3 months). The percentage of frail patients varied by measure: IMWG-FP, 27.4%; SFS, 26.5%; and PRFP, 20.5% (8/4 patients were excluded due to missing IMWG-FP/PRFP scores, respectively). Objective response rates in non-frail and frail groups, respectively, were: IMWG-FP, 72.7% and 65.6%; SFS, 69.8% and 74.2%; PRFP, 73.0% and 62.5%. Incidence of Grade 3/4 treatment-emergent adverse events was consistent across non-frail and frail groups (IMWG-FP: 72.7% and 75.0%; SFS%: 73.3% and 74.2; PRFP: 74.2% and 70.8, respectively). Clinical outcomes were consistent in non-frail and frail groups, indicating a favorable risk-benefit profile for linvoseltamab in the frail patients with RRMM from LINKER-MM1. Continued evaluation of linvoseltamab in frail patients with RRMM in clinical trials and real-world settings is warranted.CancerCardiovascular diseasesAccessCare/Management