Patients with herpes zoster neuralgia (HZN) and comorbid diabetes mellitus (DM) often experience persistent pain that markedly undermines quality of life. Most of these patients respond poorly to oral anticonvulsants or conventional pulsed radiofrequency (PRF). Repeated application of high-voltage PRF may offer superior clinical benefits and improve patient satisfaction.

This retrospective study aimed to analyze the outcomes of single versus repeated high-voltage PRF for thoracic HZN in patients with DM.

We retrospectively analyzed data from 109 thoracic HZN patients with DM who underwent CT-guided high-voltage PRF targeting the thoracic selective dorsal root ganglia (DRG) during a one-week hospitalization period. Outcome measures included the incidence of clinically meaningful postherpetic neuralgia (PHN) and the HbA1c level at 12 weeks post-PRF, Numeric Rating Scale (NRS) score, Pittsburgh Sleep Quality Index (PSQI) score at baseline (pre-PRF) and 1, 4, 8, and 12 weeks following PRF (post-PRF), and the adverse events associated with PRF.

56 patients received the single high-voltage PRF group (one PRF session, Group SHV-PRF) and 53 patients received the repeated high-voltage PRF group (two PRF sessions, Group RHV-PRF). The incidence of clinically meaningful PHN at 12 weeks post-PRF was lower in group RHV-PRF than in group SHV-PRF (20.8%vs 41.1%, P < 0.05). NRS and PSQI scores were lower in group RHV-PRF than in group SHV-PRF at 1, 4, 8, and 12 weeks post-PRF (P < 0.05). The HbA1c level at 12 weeks post-PRF was lower in group RHV-PRF than in group SHV-PRF (P<0.05). No severe adverse events were recorded in either group.

Repeated high-voltage pulsed radiofrequency confers favorable therapeutic outcomes for thoracic herpes zoster neuralgia in patients with diabetes mellitus, with an acceptable safety profile.

Diabetes mellitus (DM) is a chronic metabolic disorder marked by hyperglycemia due to impaired insulin secretion and/or action. Conventional therapies are often limited by side effects, highlighting the need for alternative treatments. Natural products have gained interest as promising therapeutic agents. Spondias tuberosa Arruda (umbu), traditionally used in Brazilian folk medicine, exhibits pharmacological potential against metabolic diseases. This study evaluated organoprotective and antioxidant effects of S. tuberosa extract (ExSt) in streptozotocin (STZ)-induced diabetic rats through clinical, biochemical, histopathological evaluations, as well as analysis of oxidative stress-related markers. Fifty-two Wistar rats were divided into five groups: CT (nondiabetic control), DM (diabetic), EX (nondiabetic + ExSt), DMEX (diabetic + ExSt), and DMIN (diabetic + insulin). Diabetes was induced by STZ (50 mg/kg, i.p.), and treatments with ExSt (500 mg/kg, orally) or NPH insulin (10 IU, s.c.) were administered for 30 days. Diabetic rats exhibited hyperglycemia, polyphagia, polydipsia, weight loss, and increased transaminases (AST, ALT), along with hepatic and pancreatic alterations. Treatment with ExSt moderately reduced AST and ALT levels, strongly preserved pancreatic morphology, and attenuated hepatic glycogen depletion by 50% despite the maintenance of hyperglycemia. Additionally, ExSt downregulated TGF-β1 and TGF-β2 expression and modulated oxidative stress-related enzymes, indicating antioxidant and antifibrotic mechanisms. These findings demonstrate that S. tuberosa extract mitigates hepatic and pancreatic injury in experimental diabetes through modulation of oxidative enzymes and TGF-β signaling, supporting its potential as a natural therapeutic alternative derived from Brazil's biodiversity.

Simultaneous pancreas-kidney transplantation (SPK) is the optimal treatment for selected patients with type I diabetes mellitus (T1DM) and end-stage kidney disease, but intraoperative bleeding remains a major cause of morbidity. Methylene blue flush during back-table pancreas preparation may better help preemptively identify bleeding points and reduce complications.

A single-center, single-blinded, prospective randomized control trial was conducted at Westmead Hospital over 30 mo. Sixty participants were randomized to receive either crystalloid (n = 33) or methylene blue (MB) flush (n = 27) during pancreas preparation before implantation. The primary outcome was intraoperative bleeding.

There was no significant difference in intraoperative blood loss with the use of MB flush (433 ± 385 mL versus 588 ± 382 mL; P = 0.10). The MB group required significantly lower intraoperative blood transfusions (7% versus 27%, P = 0.032) but higher postoperative transfusions within 7 d (81% versus 58%, P = 0.038). No significant differences were observed in length of stay, reoperation rates, delayed graft function, readmission rates, graft loss, or mortality. Early graft loss and pancreatectomy were lower in the MB group (4% versus 12%) without reaching statistical significance (P = 0.206).

MB flush did not significantly reduce intraoperative blood loss but reduced intraoperative transfusion requirements, while increasing postoperative blood transfusion requirements, indicating a temporal shift in bleeding pattern. Graft outcomes were unaffected. Further studies should explore mechanisms and evaluate long-term outcomes.

Abdominal Compartment Syndrome (ACS) is a catastrophic complication following complex hernia repair, particularly in patients with Type 2 Diabetes Mellitus (T2DM) who exhibit a phenotype of "metabolic vulnerability." The interplay between preoperative nutritional depletion, chronic hyperglycemia, and systemic inflammation remains poorly understood in this context. Current risk assessment tools rely heavily on anatomical metrics and often fail to capture the synergistic impact of immuno-metabolic fragility. We aimed to develop and prospectively temporally validate a dynamic nomogram that integrates immuno-nutritional markers with surgical variables to predict ACS in diabetic patients.

We conducted a two-stage, prospective temporal validation study involving 555 diabetic patients undergoing elective complex hernia repair at a tertiary referral center. Phase I (January 2015 to December 2021) comprised a retrospective derivation cohort (N = 461) that was randomly split into a training set (n = 323) and an internal testing set (n = 138) to identify predictors and construct the model. Phase II (January 2022 to December 2024) established a prospective temporal validation cohort (N = 94) to verify model performance in a real-world clinical setting at the same institution. We utilized determining factors including the Hernia Sac Volume to Abdominal Cavity Volume (HSV/ACV) ratio, Nutritional Risk Screening 2002 (NRS-2002), Systemic Inflammatory Response Index (SIRI), and Glycated Hemoglobin (HbA1c). The primary endpoint was the development of ACS within 7 days postoperatively. Pre-specified sensitivity analyses included LASSO penalized regression with bootstrap optimism correction (1,000 resamples), modeling of all continuous predictors as restricted cubic splines, and comparison of nested models (anatomical-only vs. anatomical + metabolic vs. full nomogram) by decision curve analysis, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

The study population exhibited a high baseline metabolic burden, with a mean body-mass index of 31.2 kg/m² and a mean HbA1c of 7.9%. Multivariable logistic regression identified seven independent predictors: HSV/ACV ratio ≥ 0.25 (Odds Ratio [OR], 2.75; 95% Confidence Interval [CI], 1.60-4.85), use of tension reduction procedures (OR, 2.45), operative time > 200 min (OR, 2.12), BMI ≥ 30 kg/m² (OR, 1.88), NRS-2002 score ≥ 3 (OR, 2.18), SIRI ≥ 1.6 (OR, 1.98), and HbA1c ≥ 6.0% (OR, 1.65). A positive correlation between SIRI and nutritional risk (Spearman ρ = 0.42, P < 0.001) was observed, consistent with an immuno-nutritional axis. The nomogram demonstrated good and stable discrimination, with an Area Under the Curve (AUC) of 0.89 (95% CI, 0.85-0.93) in the training cohort, 0.86 in the internal testing cohort, and 0.84 (95% CI, 0.77-0.91) in the prospective temporal validation cohort. Comprehensive calibration assessment in the prospective cohort showed a calibration slope of 0.91 (95% CI 0.74-1.08), calibration intercept of -0.09 (-0.31 to 0.13), Brier score 0.112, and a non-significant Hosmer-Lemeshow test (P = 0.45). Bootstrap-based internal validation (1,000 resamples) yielded an optimism-corrected C-index of 0.87 and a calibration slope of 0.93. Risk stratification categorized patients into low, intermediate, and high-risk groups, yielding ACS incidence rates of 1.0%, 10.1%, and 72.7%, respectively (P < 0.001). Compared with the anatomical-only baseline model, the full nomogram achieved an NRI of 0.31 (95% CI 0.18-0.44) and an IDI of 0.094 (95% CI 0.061-0.127), both P < 0.001. The high-risk phenotype was associated with significantly greater postoperative fluid sequestration, prolonged intensive care unit stays, and increased 30-days mortality.

The integration of immuno-nutritional markers (SIRI, NRS-2002) and glycemic control with anatomical parameters provides a temporally validated tool with good and stable discrimination for ACS in diabetic patients. Its principal clinical utility lies in reliable risk exclusion (negative predictive value 95.5% in the prospective temporal validation cohort), supporting safe rule-out of low-risk patients, while the more modest positive predictive value (46.4%) indicates that a high score should prompt enhanced surveillance and individualized decision-making rather than constitute a deterministic indication for pre-emptive open-abdomen management.

Hidradenitis suppurative (HS) is a chronic inflammatory skin disorder characterized by deep-seated nodules, abscesses, sinus tract formation, and scarring. Growing evidence has begun to support the notion that HS not only is a local follicular disorder but also has strong associations with metabolic dysfunction. The metabolic abnormalities seen in patients with HS include obesity, insulin resistance, metabolic syndrome, adipose-mediated inflammation, and altered cytokine signaling. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a class of drugs currently used to lower blood glucose in patients with type 2 diabetes mellitus (T2DM). However, recent studies have provided evidence that SGLT2i can alter multiple immunometabolic mediators, including reducing nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome activity, lowering pro-inflammatory cytokine levels, and improving insulin resistance. The purpose of this review was to determine whether SGLT2i can alter mechanisms involved in the development of HS through their anti-inflammatory and metabolic effects. Using Web of Science and PubMed, a literature review was conducted to compile studies on HS, metabolic dysfunction, and the anti-inflammatory effects of SGLT2is. The current evidence indicates that the metabolic and inflammatory pathways targeted by SGLT2is contribute to the development of HS, including the NLRP3 inflammasome, cytokine production, and adipose-related inflammation. The evidence supporting this is largely mechanistic; therefore, future clinical studies are needed to determine whether SGLT2i use in HS can provide significant improvement. However, with current therapies targeting downstream inflammatory mediators, SGLT2i and potentially other metabolic therapies may be promising adjunctive therapies by targeting upstream metabolic drivers that amplify these mediators.

Chronic diabetic wounds suffer from persistent oxidative stress, unresolved inflammation, and impaired neovascularization, with limited effective therapies.

We developed a biomimetic nanocomposite (PEG-HS/TiO₂) combining antioxidant TiO₂ with sustained-release honeysuckle. In vitro, we evaluated ROS scavenging, cellular senescence, VEGF expression, and macrophage polarization. In vivo, we assessed wound closure, neovascularization, collagen remodeling, and inflammatory markers in a diabetic mouse model.

PEG-HS/TiO₂ achieved sustained HS release over 72 hours. It scavenged superoxide and H₂O₂, reduced endothelial ROS by approximately 89%, suppressed senescence markers, and restored VEGF expression (>7-fold increase vs. H₂O₂ control). The nanocomposite shifted macrophages from M1 to M2 phenotype, increasing the CD206/CD86 ratio. In vivo, PEG-HS/TiO₂ accelerated wound closure (76% wound area reduction by day 7 vs. 18% in Sham), enhanced CD31+ vessels (6.3-fold vs. Sham), improved collagen organization, reduced M1 macrophages by 85% and IL-1β by 73%, increased IL-10 by 3.1-fold, and lowered systemic CRP and PCT.

PEG-HS/TiO₂ breaks the diabetic wound pathology cycle through ROS neutralization, anti-senescence, and macrophage immunometabolic reprogramming, representing a promising strategy for diabetic wound management.

Opportunistic cardiac chamber volumetry derived from coronary artery calcium (CAC) scans using the AI-CVD platform predicts heart failure (HF) independent of conventional risk factors. Type 2 diabetes mellitus (T2DM), which classifies individuals as Stage A HF, is associated with chamber enlargement; however, the HF risk associated with chamber enlargement in the absence of T2DM has not been characterized.

We analyzed left atrial (LA) and left ventricular (LV) volumes and mass, indexed to body surface area, using AI-CVD chamber volumetry of 7585 asymptomatic participants in the pooled cohort of Multi-Ethnic Study of Atherosclerosis (MESA) and Framingham Heart Study (FHS) second, and third generation (MESA & FHS; mean age 62.7 ± 14.6 years, 48.6 % male, 10.6 % with T2DM). Chambers were classified as enlarged (≥95th) or normal (<50th percentile). Cox regression and Kaplan-Meier analyses with log-rank tests were performed.

Over a median follow-up of 17.1 years, 438 HF events occurred. Individuals without T2DM, with enlarged chambers had HF incidence rates comparable to or higher than individuals with T2DM and normal chambers: LA volume 16.4 vs 8.7 (p = 0.001), LV volume 8.1 vs 8.9 (p = 0.66), and LV mass 10.1 vs 8.9 (p = 0.55) per 1000 person-years. After multivariable adjustment, compared with normal chambers, enlarged LA (HR 2.5[1.9-3.3]), LV (HR 3.5[2.3-5.4]), and LV mass (HR 3.2[2.2-4.9]) remained independently associated with HF in individuals without T2DM.

AI-derived cardiac chamber enlargement measured in CAC scans is associated with HF incidence in individuals without T2DM, supporting its potential utility in HF risk stratification.

To evaluate and compare the efficacy, safety, and immunogenicity of a synthetic semaglutide injection (Test semaglutide) with Wegovy (Reference semaglutide) injection for weight management.

This randomized, Phase III, non-inferiority study included adults with obesity or overweight with or without comorbidities from 21 centers in India. A total of 270 patients with body mass index ≥ 30 kg/m² or ≥ 27 kg/m² with the presence of at least one of the weight-related comorbidities (hypertension, dyslipidemia or type 2 diabetes mellitus) were randomized (2:1) to receive either Test semaglutide (N = 177) or Reference semaglutide injection (N = 90) once weekly with dose escalation from 0.25 to 2.4 mg. The primary endpoint was percentage change in bodyweight from baseline to Week 24.

Out of 267 randomized patients, 246 completed the study. At Week 24, mean percent weight change from baseline was -13.8% ± 4.28% in Test and -14.1% ± 4.11% in Reference groups with least-squares mean difference of 0.26% (95% CI: -0.86% to 1.39%), meeting the criterion for non-inferiority. The proportion of patients with ≥ 5% and ≥ 10% weight loss were 96.40% and 80.60% in Test, and 98.80% and 80.00% in Reference groups, respectively at Week 24. Improvements in body mass index, waist circumference, SF-36 total score, and glycemic parameters were comparable between groups. Treatment-emergent adverse events were reported in 72.30% and 76.70% in the Test and Reference groups, respectively, with gastrointestinal events being the most common.

Test synthetic semaglutide was found to be non-inferior to Reference semaglutide in weight management with or without comorbidities.

Prospectively registered on the Clinical Trials Registry-India, CTRI/2025/04/085487 [Registered on: 24/04/2025], https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTIwNjMx&Enc=&userName=.

To characterize the epidemiology, microbiological spectrum, and antimicrobial resistance of infectious corneal ulcers in a Northern Portugal referral center and to identify predictors of severe structural outcomes in real-world practice.

Retrospective observational cohort study of consecutive infectious corneal ulcer episodes undergoing microbiological sampling (2014-2025). Baseline demographics, ocular and systemic risk factors, clinical severity markers (ulcer location, hypopyon), microbiologic results, organism groups, antimicrobial susceptibility and initial empiric therapy were recorded. The primary outcome was severe structural failure (corneal perforation and/or evisceration). Secondary outcomes included central corneal scarring and hospitalization. Descriptive microbiological endpoints included culture positivity, pathogen distribution, and antimicrobial susceptibility patterns. Predictors of severe outcome were assessed using multivariable logistic regression.

The study included 206 episodes (205 patients; mean age 54.6 ± 20.7 years). Microbiologic confirmation was obtained in 49.0% of episodes. Among microbiologically confirmed episodes, bacterial keratitis predominated (76.2%), followed by other/unspecified organisms (13.9%), polymicrobial infections (5.9%), and fungal keratitis (4.0%). The most frequent identified pathogens included Pseudomonas aeruginosa and Cutibacterium acnes, alongside PCR-detected HSV-1, coagulase-negative staphylococci, and Corynebacterium spp. Resistance was uncommon among isolates with available susceptibility data (fluoroquinolone 12%, aminoglycoside 9.1%, cephalosporin 5.9%); MDR occurred in 4.7%. Severe outcome occurred in 8.4% of episodes with available data. In multivariable analysis, hypopyon (aOR 6.85), systemic immunosuppression (aOR 4.89), and diabetes mellitus (aOR 2.50) independently predicted severe outcome.

In this cohort, severe corneal ulcer outcomes were primarily driven by baseline inflammatory severity and host vulnerability (hypopyon, immunosuppression, diabetes), while antimicrobial resistance and MDR were infrequent. Early risk stratification using these clinical and systemic factors may guide escalation and monitoring, alongside ongoing local resistance surveillance.

To investigate the modulatory role of NOTCH3 in renal inflammatory and fibrotic processes during diabetic nephropathy (DN), focusing on TLR4/NF-κB and TGF-β1/Smad3 signaling pathways. HK2 cells were stimulated with BSA to mimic diabetic conditions in vitro. To investigate the roles of TLR4/NF-κB and TGF-β1/Smad3 pathways, cells were treated with Resatorvid or LPS, and SB-431542 or TGF-β1, respectively. Also, HK2 cells were transfected with siRNA knockdown and pcDNA 3.1 overexpression vectors targeting NOTCH3. After treatments, cell viability, LDH release, inflammatory factors, apoptosis, and levels of fibrotic markers were analyzed. BSA stimulation upregulated NOTCH3 expression in HK2 cells. Silencing NOTCH3 enhanced viability and reduced LDH release, secretion of inflammatory factors, apoptosis, and fibrotic marker expression. Conversely, NOTCH3 overexpression exacerbated BSA-induced cellular injury, inflammatory responses, and fibrotic marker expression. NOTCH3 also enhanced activation of the TLR4/NF-κB and TGF-β1/Smad3 pathways, and inhibition of either pathway partially mitigated the effects of NOTCH3 overexpression. Furthermore, in NOTCH3 knockdown cells, co-treatment with downstream activators partially restored inflammatory and fibrotic responses, supporting the modulatory role of NOTCH3 in coordinating these signaling pathways. NOTCH3 modulates renal inflammation and fibrosis in BSA-stimulated HK2 cells via the TLR4/NF-κB and TGF-β1/Smad3 pathways, highlighting its potential as a modulator of inflammatory and fibrotic responses in DN.