Background: Preoperative glycemic control, as measured by HbA1c, is widely used in risk stratification for diabetic patients undergoing abdominal wall reconstruction (AWR). In a prior analysis, our group demonstrated that among diabetic patients undergoing open ventral hernia repair (VHR) with transversus abdominis release (TAR), preoperative HbA1c levels did not correlate with short-term wound morbidity. This study evaluates long-term outcomes in patients with poor preoperative glycemic control (HbA1c ≥ 8.5%) undergoing open AWR with TAR.

Methods: Adult diabetic patients with HbA1c ≥ 8.5% who underwent open, elective, clean VHR with concurrent TAR and permanent synthetic mesh at the Cleveland Clinic Center for Abdominal Core Health between January 2014 and January 2024 were identified from the Abdominal Core Health Quality Collaborative (ACHQC) and followed for a minimum of 12 months. Assessed outcomes included wound morbidity, mesh-related complications, and hernia recurrence. Threshold analysis using ROC methodology and logistic spline regression was performed to evaluate the discriminative capacity of HbA1c within the poor glycemic control range.

Results: Of 48 patients with HbA1c ≥ 8.5%, 46 (95.8%) completed long-term follow-up at a median of 22.3 months. Long-term SSOPI and partial mesh removal rates were 4.3% and 2.2%, respectively. Pragmatic hernia recurrence was observed in 4 patients (8.7%), all of whom had experienced early wound morbidity (4/4); three of the four had also undergone partial mesh excision or removal (3/4). No recurrences were documented in patients with uncomplicated postoperative courses. Threshold analysis yielded an AUC of 0.37, indicating no meaningful discriminative threshold within the observed HbA1c range.

Conclusion: Among diabetic patients with HbA1c ≥ 8.5% undergoing open AWR with TAR at a high-volume center, long-term wound and recurrence rates were within the range reported for general TAR cohorts. These descriptive findings, while limited by sample size and the absence of an internal comparator, support the hypothesis that preoperative HbA1c may have limited stand-alone discriminative capacity in this setting and warrant confirmation in adequately powered comparative analyses, including the longitudinal multi-stratum cohort currently ongoing at our institution.

Background: The goal was to identify risk factors for postoperative lower extremity deep vein thrombosis (DVT) in traumatic lower limb fracture patients and establish a nomogram prediction model for clinical risk assessment and management.

Methods: A total of 136 lower extremity traumatic fracture (LETF) patients admitted to the emergency surgery department were enrolled. Patients were divided into DVT and non-DVT groups based on postoperative color Doppler ultrasonography. Univariate and multivariable logistic regression analyses were performed to determine independent risk factors for DVT. A nomogram prediction model was constructed and validated using receiver operating characteristic curve analysis, calibration curve, and decision curve analysis (DCA).

Results: Among 136 patients, 52 developed DVT, while 84 did not. No significant differences were observed in age, gender, BMI, hypertension, coronary artery disease, time from injury to surgery, operative duration, or American Society of Anesthesiologists score (all p > 0.05). However, diabetes prevalence, intraoperative transfusion rate, hip versus tibiofibular fracture distribution, injury severity score (ISS) score ≥ 25, hemoglobin, hematocrit, fibrinogen (FIB), and D-Dimer (D-D) levels differed significantly (all p < 0.05). Thromboelastography (TEG) revealed significantly higher maximum amplitude (MA) and α-angle, but lower clot formation time (K) value in the DVT group (all p < 0.001). Multivariable analysis identified hip fracture, ISS ≥ 25, elevated FIB, elevated D-D, increased MA, and decreased K as independent risk factors (all p < 0.05). The nomogram demonstrated excellent predictive performance (area under the curve = 0.89, 95% confidence interval: 0.77 - 1.00), good calibration (Hosmer-Lemeshow test p > 0.05), and clinical utility on DCA.

Conclusions: The TEG-based nomogram incorporating clinical features effectively predicts postoperative DVT risk in traumatic fracture patients, facilitating early identification of high-risk individuals and personalized pro-phylaxis to mitigate DVT incidence and improve outcomes.

Diabetic wounds are often infected with microbes, which perpetuate inflammation, and stall wound healing. The bacterium Group B Streptococcus (GBS) is frequently isolated from diabetic wounds; however, little is known about how GBS adapts to survive in this niche. Previously, we found that GBS acquires stable mutations in the major two-component system CovRS during murine diabetic wound infection that result in increased pigmentation. Here, we further characterize these pigmented variants and determine the consequences on GBS survival. Using a murine model of wound infection, we find that covRS mutants arise specifically in diabetic hosts and are selected for across multiple GBS backgrounds. Whole genome sequencing of pigmented isolates revealed mutations in both covR and covS, with most isolates having a single nucleotide insertion or deletion in the covR promoter region. Phenotypic analysis of murine-acquired mutants reveals enhanced traits associated with virulence, including increased hemolytic activity, host cell cytotoxicity, and elevated nuclease activity. While our previous and current study indicated that engineered covR deletion mutants do not exhibit increased survival in the diabetic wound, we observe that a pigmented isolate survived better than wild-type during co-infection with Enterococcus faecalis, another frequently isolated wound pathogen. Finally, we find that depletion of neutrophils reduces the frequency of covRS mutant variants that arise in the population. Our work highlights the emergence of covRS mutations in GBS, and the consequences of these variations are associated with enhanced virulence and competitive fitness, underscoring the importance of these regulatory changes in the context of diabetic wounds.

Objective: Early postoperative wound complications remain a significant challenge following posterior lumbar spine surgery. The C-reactive protein to albumin ratio (CAR) has emerged as a promising biomarker for systemic inflammation and nutritional status. This study aimed to evaluate the predictive value of preoperative CAR for postoperative wound complications in patients undergoing posterior lumbar spine surgery.

Methods: We retrospectively reviewed 420 patients who underwent posterior lumbar spine surgery at our institution. Patients were divided into a case group (N = 140, with wound complications) and a control group (N = 280, without wound complications). Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for early postoperative wound complications. Subgroup analyses were further conducted based on surgical strategy (interbody fusion vs. without interbody fusion) and surgical extent (number of levels >3 vs. ≤ 3).

Results: Patients in the case group had significantly greater BMI, aCCI scores, ASA scores, blood loss, operative duration, and drain retention time compared to the control group (all P < 0.05). The proportions of diabetes mellitus and allogeneic blood transfusion were also significantly higher in the case group compared to controls (all P < 0.05). Notably, the proportion of patients with a high preoperative CAR (≥0.9) was significantly greater in the case group than in the control group (35.0% vs. 25.0%, P = 0.032). Multivariate logistic regression analysis revealed that a CAR ≥0.9 was an independent predictor of postoperative wound complications (fully adjusted OR: 1.753, 95% CI: 1.089-2.822, P = 0.021). In stratified analyses, CAR remained a robust predictor in patients undergoing interbody fusion (OR: 1.802, P = 0.011) and multilevel surgery (OR: 1.816, P = 0.010). However, CAR was not significantly associated with complications in patients undergoing surgery without interbody fusion (P = 0.726).

Conclusion: Preoperative CAR is a valuable and independent biomarker for predicting early postoperative wound complications after posterior lumbar spine surgery. Its predictive utility is particularly significant in more complex procedures, such as interbody fusion and long-segment surgeries. Preoperative assessment of CAR may facilitate personalized risk stratification and clinical optimization to improve surgical outcomes.

Introduction: Diabetic foot ulcers (DFUs) are severe complications that cause frequent lower extremity amputations. Timely diagnosis is crucial for effective clinical management. Although deep learning approaches improve detection, the models often struggle to capture different lesion scales. Furthermore, opaque algorithmic decisions often lower medical trust. Therefore, this study introduces DFU-GCNet for robust and interpretable ulcer classification.

Methods: The proposed architecture merges inception modules with global context blocks. This combination extracts multi-scale features from different wound sizes and simultaneously models broad spatial dependencies across tissue regions. Thus, it effectively distinguishes pathology from surrounding healthy skin. We evaluate this framework using the Kaggle DFU dataset. We integrate explainable AI techniques to ensure clinical transparency. GradCAM++, Local Interpretable Model-Agnostic Explanations, and SHapley Additive exPlanations are used to provide high-resolution diagnostic heatmaps and confirm that the network prioritizes clinically relevant wound boundaries.

Results: The model achieved a superior classification accuracy of 97.16%, with an F1-score of 0.9715 and a Matthews correlation coefficient of 0.9437. DFU-GCNet demonstrated decisive superiority compared with standardized modern baselines such as VGG16 and EfficientNet.

Discussion: The findings indicate that DFU-GCNet is a highly reliable automated screening instrument.

Neuro-driven skin regeneration represents an emerging paradigm in wound healing that integrates peripheral nerve repair with functional skin restoration. Hydrogels serve as versatile platforms for supporting such dual tissue regeneration, owing to their biocompatibility, tunable physicochemical properties, and ability to mimic the extracellular matrix. Recent advances have enabled the development of multifunctional hydrogels that combine biophysical and biochemical cues-including conductive materials, bioactive molecules, and exosomes-to create healing microenvironments that promote nerve growth, angiogenesis, and tissue repair, particularly in challenging conditions such as diabetic ulcers and chronic wounds. This review examines the molecular mechanisms underlying neural regulation of wound healing, focusing on sensory neuron-derived factors, neuro-immune crosstalk, neurovascular integration, and the emerging role of neurogenic exosomes as central signaling hubs. Furthermore, design principles for hydrogel materials-including natural, synthetic, and composite systems-are explored alongside smart responsive hydrogels that adapt to dynamic wound environments, thereby enabling controlled therapeutic delivery. Current trends integrating wearable bioelectronics, artificial intelligence (AI), and bioengineered scaffolds are discussed in the context of real-time monitoring and personalized therapy. While neurogenic hydrogels show significant promise for clinical translation, their development requires rigorous preclinical validation and well-designed human trials. Beyond skin regeneration, these materials hold potential for nerve repair, bone healing, and cardiac tissue engineering, highlighting their versatility as therapeutic solutions across diverse physiological systems. Future efforts should focus on leveraging AI to optimize hydrogel formulations, advancing stem cell-based therapies, and establishing standardized metrics for treatment efficacy.

Diabetes impairs wound healing due to hyperglycemia-induced vascular dysfunction. This condition triggers mitochondrial impairment, leading to ferroptosis in endothelial cells. While mesenchymal stromal cells (MSCs) can promote tissue repair through intercellular mitochondrial transfer, strategies to enhance their mitochondrial-donating capacity under hyperglycemic conditions remain underdeveloped. Mesenchymal condensation endows MSCs with enhanced regenerative potential and greater mitochondrial functionality. Microcarrier-based three-dimensional (3D) dynamic culture systems mimicking this process offer a promising strategy. However, effectively shielding donor MSCs from hyperglycemia-induced oxidative stress remains a key challenge in microcarrier design. Here, we engineered a glucose-responsive antioxidant biomaterial-based 3D dynamic culture system using chitosan-formylphenylboronic acid (CS-FPBA) microcarriers combined with stem cells from human exfoliated deciduous teeth (SHED) to generate native-like SHED (N-SHED). This system provides a protective niche for transplanted SHED through glucose-triggered antioxidant microcarrier degradation while simultaneously enhancing mitochondrial function and intercellular transfer. Consequently, N-SHED attenuated endothelial ferroptosis, promoted angiogenesis, and accelerated diabetic wound healing in vivo. This study presents a native-like cell culture platform that amplifies the therapeutic efficacy of MSCs by enhancing their mitochondrial-donating capacity. With strong translational potential, this strategy not only advances MSCs-based therapy for diabetic wounds but also offers a novel framework for mitochondrial-targeted regenerative medicine.

[This corrects the article DOI: 10.3389/fnut.2026.1807919.].

Introduction: Early re-operation secondary to postoperative surgical site infection (SSI) in lumbar microdiscectomy, although rare, poses significant morbidity and healthcare burden.

Research question: Given the variable performance of traditional statistical and machine learning (ML) models in predicting this outcome, this study aimed to develop and validate a ML model to accurately predict 30-day re-operation following SSI in patients undergoing lumbar microdiscectomy.

Material and methods: De-identified patient data were obtained from American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), focusing on patients with microdiscectomy. After applying inclusion criteria, 79,870 eligible cases were analyzed, of which 462 (0.6%) experienced re-operation following SSI. A nested cross-validation pipeline with Bayesian optimization was implemented using extreme gradient boosting (XGBoost) combined with Synthetic Minority Over-sampling Technique (SMOTE), and multiple classification thresholds were evaluated. Model interpretability was assessed through SHapley Additive Explanations (SHAP) to identify the most influential predictors.

Results: The final model achieved an area under the receiver operating characteristic curve of 0.996, with accuracy consistently at 0.993 and sensitivity of 0.924-0.985 across thresholds. Specificity remained at 0.993, while the positive predictive value fluctuated modestly (0.436-0.437), and the negative predictive value was 1.000. SHAP analysis highlighted any SSI, race, smoking status, diabetic status, and revised Risk Analysis Index scores as top predictors influencing re-operation risk.

Discussion and conclusion: An optimized ML approach incorporating synthetic data augmentation yielded high predictive performance for an infrequent yet critical complication of lumbar microdiscectomy. These findings underscore the potential of data-driven models to enhance perioperative risk stratification and support targeted preventive strategies.

Background: Trimalleolar ankle fractures are complex injuries associated with high complication rates and poorer outcomes, particularly in elderly and medically comorbid patients. While open reduction and internal fixation (ORIF) remains the standard treatment, alternative strategies such as tibiotalocalcaneal arthrodesis (TTCA) have been increasingly explored for high-risk populations.

Methods: A retrospective cohort study was performed using the TriNetX Research Network. Adult patients undergoing operative treatment for trimalleolar fractures were identified and stratified by procedure (TTCA versus ORIF). Propensity score matching (1:1) was performed to balance demographics and comorbidities, including age, sex, obesity, tobacco use, osteoporosis, diabetes, dementia, and peripheral vascular disease. Outcomes were assessed at 90 days, 1 year, and 2 years. Primary outcomes included secondary surgery (revision procedures, irrigation and debridement, hardware removal, and below-knee amputation). Secondary outcomes included 90-day infection and wound dehiscence. Risk ratios with 95% confidence intervals were calculated, with p < 0.05 considered significant.

Results: After matching, 210 patients were included in each group. At 90 days, infection and wound complication rates were similar between TTCA and ORIF cohorts. TTCA was associated with significantly higher rates of secondary surgery at 1 year (28.1% vs 17.1%; RR 1.64, p = 0.007) and 2 years (31.4% vs 21.0%; RR 1.50, p = 0.015). Irrigation and debridement was also more frequent in the TTCA cohort at 1 year (RR 2.25, p = 0.012) and 2 years (RR 2.23, p = 0.009). In sensitivity analysis of closed fractures, findings remained consistent, with higher secondary surgery rates in the TTCA group.

Conclusion: In this large propensity-matched study, TTCA may be associated with a higher incidence of secondary surgery-particularly irrigation and debridement-compared with ORIF at one and two years postoperatively, while early wound complication rates were similar. These findings may be influenced by residual confounding despite propensity matching.

Background: Obstructive sleep apnea (OSA) is common in type 2 diabetes (T2D) and may contribute to its chronic complications. Whether STOP-Bang-defined OSA risk is associated with diabetic foot ulcer (DFU) severity and outcome remains unclear. We compared STOP-Bang score between T2D patients with and without DFU and explored the association between OSA risk and DFU severity and healing.

Methods: We conducted an observational study with a cross-sectional matched case-control comparison including 73 T2D patients with DFU and 73 T2D controls without DFU, matched by age, HbA1c, BMI and smoking. At the study visit, STOP-Bang-defined OSA risk was assessed as a continuous score and categorized as low versus moderate/high risk. In the DFU group, ulcer severity was graded at the same visit with the WIfI classification, and time to healing and amputation was recorded during clinical follow-up. Multivariable logistic regression identified predictors of moderate-to-high amputation risk.

Results: In unadjusted analyses, DFU patients had higher STOP-Bang score than controls (4.3 ± 2.0 vs. 3.2 ± 2.2, p=0.004) and more often intermediate/high OSA risk (83.6% vs. 60.3%, p=0.002), although these differences were attenuated after accounting for sex imbalance. Among DFU patients, higher ulcer severity was associated with moderate/high STOP-Bang-defined OSA risk (97.1 vs. 71.8%; p=0.004). Median healing time was longer in those with moderate/high versus low STOP-Bang-defined OSA risk (120.0 vs. 65.0 days, p=0.032). In multivariable analysis, WIfI ulcer severity was associated with male sex, higher STOP-Bang category and poorer metabolic control.

Conclusion: STOP-Bang-defined OSA risk was associated with greater DFU severity and delayed wound healing. Incorporating OSA risk stratification into routine assessment of patients with DFU may help identify individuals at higher risk of poor outcomes.

Diabetes is a major global public health challenge. Diabetic foot ulcer (DFU), one of its most severe complications, imposes a substantial economic burden and severely impairs patients' quality of life. Current treatment strategies often yield suboptimal outcomes, underscoring the urgent need for novel therapeutic approaches. Adipose-derived stem cell exosomes (ADSC-Exos) have emerged as a promising cell-free therapy with significant clinical potential. This review integrates the mechanisms through which ADSC-Exos facilitate diabetic wound healing with the phases of wound healing. It elucidates that ADSC-Exos function by alleviating oxidative stress, modulating inflammation, promoting angiogenesis, stimulating cell proliferation and migration, and suppressing excessive fibrosis. Additionally, this study organizes insights into how delivery strategies based on smart materials (e.g., hydrogels and bioscaffolds) and the latest physical modalities can overcome bottlenecks in clinical translation. This review aims to provide an integrated perspective for developing next-generation DFU therapies.

Despite a vast literature on the role of macrophages in wound healing, the role of dermal monocyte (Mo)-derived antigen presenting cells (APC) has received scant attention. Using scRNAseq and flow cytometry, we identify a population of APC that is prominent in wounds of non-diabetic mice but is reduced in wounds of diabetic mice. Using adoptive transfer experiments and Ccr2 knockout mice, we demonstrate that wound APC are derived primarily from Mo and that the diabetic wound environment inhibits differentiation of Mo into APC. We also show that Mo-specific Irf4 knockout mice exhibit reduced differentiation of Mo into APC, decreased levels of IL-27 and numbers of activated Treg cells in wounds. and impaired wound healing. Importantly, adoptive transfer of bone marrow Mo that express Irf4 into wounds of Mo-specific Irf4 knockout mice rescued levels of wound APC and activated Treg, as well as wound healing. Local administration of recombinant IL-27 into wounds of these mice also rescued levels of activated Treg in wounds, along with wound healing, Together, these findings identify a novel pathway in which IRF4 induces Mo differentiation into APC in wounds, which in turn produce IL27 that activates Treg to promote healing. This pathway is impaired in wounds of diabetic mice, which provides a novel target to improve diabetic wound healing.

To evaluate the effectiveness of multidisciplinary offloading versus standard care on one-year diabetic foot ulcer recurrence, amputation, mortality, and functional recovery. In this prospective cohort study, 232 patients with healed diabetic foot ulcers were stratified into a control group (76 patients) or an intervention group (156 patients) receiving offloading modalities ranging from felt padding to custom-made therapeutic footwear. Assignment was based on shared decision-making considering biomechanical needs and economic feasibility. Primary outcomes included recurrence, amputation, and mortality. Secondary outcomes assessed quality of life, working ability, and ankle function. The intervention group demonstrated significantly lower recurrence (10.9% vs. 25.0%; p = 0.007) and mortality (3.2% vs. 14.5%; p = 0.004). Multivariable analysis identified offloading as independently protective against recurrence (odds ratio 0.35) and mortality (odds ratio 0.24). Amputation rates did not differ significantly after adjustment. Functionally, the intervention group achieved superior recovery in quality of life, working ability, and ankle scores (p < 0.001). Subgroup analysis indicated that customized therapeutic footwear yielded the lowest complication rates and highest patient satisfaction. Multidisciplinary offloading significantly reduces recurrence and mortality while restoring physical function. Although financial barriers influence device selection, customized therapeutic footwear offers the optimal balance of biomechanical protection and functional outcomes.

Diabetic wounds present a formidable clinical challenge due to a self-amplifying network of hyperglycemia-driven microenvironmental dysregulation, including hypoxia, oxidative stress, chronic inflammation, and persistent infection. Existing therapies fail to integrate mechanical support with dynamic, holistic regulation of this complex milieu, leaving intertwined biological and material challenges unresolved. Here, we report a multifunctional protein hydrogel membrane, GOX@MnO₂/CLP-EGF@BSA (GM/CEB), designed to actively remodel the diabetic wound niche. The hydrogel is constructed via topological chain entanglement of bovine serum albumin (BSA), incorporating a genetically encoded collagen-like protein fused with epidermal growth factor (CLP-EGF) for sustained regenerative signaling, and embedding a GOX@MnO₂ dual-enzyme cascade that converts glucose into oxygen while scavenging reactive oxygen species. This hierarchical, protein-based hydrogel membrane is mechanically robust and biodegradable, enabling continuous, integrated modulation of the hyperglycemia-driven pathological microenvironment. In a S. aureus-infected diabetic wound model, GM/CEB significantly accelerated healing by alleviating hypoxia and promoting macrophage polarization. Concurrently, GM/CEB activated EGFR-associated signaling pathways (PI3K/AKT/mTOR), thereby enhancing tissue regeneration and restoring dermal architecture. Taken together, this hybrid multifunctional protein-based hydrogel membrane, characterized by high toughness and a fully proteinaceous matrix, represents a new generation of protein-based biomaterials, holding strong potential as a skin substitute to provide an integrated platform for infection control, immune modulation, and functional tissue regeneration in complex wound repair. STATEMENT OF SIGNIFICANCE: Chronic wounds represent a paradigmatic failure of biomaterials design, where static scaffolds cannot adapt to dynamically evolving pathological microenvironments. Here, we introduce a protein-based hydrogel membrane that departs from conventional crosslinked systems by leveraging topological chain entanglement as the primary structural principle, coupled with an embedded enzyme-like cascade to actively reprogram the wound milieu. This integration enables simultaneous mechanical resilience and spatiotemporally adaptive regulation of oxidative stress, immunity, and regeneration. By shifting from passive support to active microenvironmental control, this work establishes a new design paradigm for protein biomaterials and advances the conceptual foundation for treating complex tissue pathologies.

Diabetes mellitus (DM) is a multifactorial metabolic disorder characterized by chronic hyperglycemia due to impaired insulin secretion and/or action. A severe complication is delayed wound healing, particularly diabetic foot ulcers, associated with defective angiogenesis, neuropathy, persistent inflammation, and increased infection risk. Biodegradable, biocompatible biomaterials have gained attention as advanced platforms for tissue regeneration. Polyhydroxyalkanoates (PHAs), microbial-derived biopolymers, are promising for wound healing. This study evaluated the therapeutic efficacy of PHAs derived from high-rate algal pond (HRAP) microalgae using a streptozotocin (STZ)-induced diabetic rat model. HRAP microalgal biomass was used for polyhydroxybutyrate (PHB) extraction via solvent precipitation. Purified PHB was blended with polycaprolactone (PCL) to fabricate electrospun nanofiber scaffolds containing different algal extract concentrations (PHB-1, PHB-2, PHB-3). Structural characterization was performed by NMR and GC-MS. Diabetes was induced in male Wistar rats with a high-fat diet followed by STZ (30 mg/kg). Full-thickness excisional wounds were created and topically treated for 12 days. Wound healing progression was assessed by wound contraction, histopathology, and qRT-PCR analysis of IL-6, TNF-α, and MMP-1. GC-MS confirmed hydroxyalkanoate monomers, validating PHB biosynthesis. Scanning electron microscopy showed uniform, well-defined nanofiber morphology. PHB-based scaffolds significantly accelerated wound closure compared with untreated diabetic controls. Histology revealed enhanced re-epithelialization, dermal regeneration, reduced inflammatory infiltration, and reappearance of hair follicles. Gene expression analysis showed anti-inflammatory effects, with IL-6, TNF-α, and MMP-1 reduced by 67.99%, 74.01%, and 59.60%, respectively. PHB-based nanofiber scaffolds improved diabetic wound healing through combined regenerative and anti-inflammatory actions, supporting sustainable PHB as a promising biomaterial for advanced wound dressings.

This study aimed to examine the independent and combined impacts of diabetes mellitus (DM), and substance use on the risk of accidental injuries in a nationwide population-based cohort in Taiwan. Using Taiwan's National Health Insurance Research Database (NHIRD), two retrospective cohorts were analyzed. The DM cohort (2000-2013) included 31,424 patients with DM and 94,272 age-, sex-, and index-year-matched controls. The substance uses cohort (2013-2022) included 324,648 substance users and an equal number of matched controls. Injury outcomes were classified as traffic accidents, falls, burns and fires, brain injuries, suicide, and drowning. Cox proportional hazards models were applied to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs), and Kaplan-Meier analyses were used for descriptive visualization of cumulative injury risk, and interaction was formally assessed using Cox regression models. Patients with DM exhibited a 1.702-fold higher risk of injury compared to non-DM individuals, while substance users demonstrated a 1.444-fold higher risk compared to non-users. Among substance users, the highest risks were found for suicide (aHR = 10.287), intentional injury (aHR = 2.453), and falls (aHR = 1.742). Female sex, low income, major illness, and comorbidities (stroke, hypertension, hyperlipidemia) further amplified injury risk. Both DM and substance use were independently associated with increased injury risk. In joint-effects analyses, individuals with both DM and substance use had the highest injury risk among the four exposure groups (non-DM/non-user, DM only, substance use only, and DM + substance use). The multiplicative interaction between DM and substance use was statistically significant. Results were consistent in sensitivity analyses restricted to unintentional injuries. DM and substance use independently elevate the risk of accidental and intentional injuries; their coexistence is associated with the highest injury risk that markedly increases injury susceptibility. Integrating chronic disease management with substance use prevention and behavioral interventions may reduce injury-related morbidity and mortality in high-risk populations.

Purpose: To describe characteristics and outcomes of humeral shaft nonunion.

Methods: Adult patients diagnosed with humeral shaft nonunion at one Level 1 trauma center from December 2000-July 2020 were retrospectively reviewed. Independent samples t-test was used for continuous variables, and chi squared or fishers exact test for categorical. P < 0.05 was considered significant.

Results: 59 patients (age 59.83 ± 17.71; 56.14 female; BMI 29.54 ± 8.5) had comorbidities included 32.70% current smoking, 14.30% alcohol use disorder, 21.40% hypothyroidism, 14.30% diabetes. 6 had open fractures; 42 (71.19%) were initially treated nonoperatively. 21 patients were diagnosed with atrophic nonunion, 4 with hypertrophic, and 28 with oligotrophic. 43 nonunions were treated surgically, 11 nonoperatively; the remainder were lost to follow up. 9 had positive cultures at revision. Those with negative revision cultures healed sooner (198 ± 177.54 vs. 451.25 ± 314.377 days, p = 0.034). 41 patients were treated with bone graft at revision. 42 patients (77.78%) required only one revision before radiographic healing; 12 required > 1. Patients with > 1 revision had longer follow-up (846.25 ± 624.75 vs. 358 ± 261.65 days, p < 0.001) and were slower to heal (433 ± 388.75 vs. 202.21 ± 157.38 days, p = 0.028); other factors were not significant on comparison.

Conclusion: Humeral shaft nonunion remains a complex clinical problem. In this analysis, positive cultures at time of initial revision were found to significantly delay healing. Use of bone graft at time of revision was not significantly associated with faster healing or decreased likelihood of requiring > 1 revision procedure.

Diabetic foot ulcer (DFU) remains difficult to heal due to disrupted endogenous bioelectricity together with persistent infection, inflammation, and oxidative stress. Reinstating wound bioelectricity therefore represents an attractive therapeutic strategy, and thermoelectric materials are particularly suited to this purpose by harvesting the natural skin-air temperature gradient without external power input. Here, a self-powered ionic thermoelectric dual-network hydrogel is developed to simultaneously reconstruct wound bioelectric cues and remodel the hostile DFU microenvironment. The hydrogel generates wound-relevant microcurrents under physiological temperature gradients, while luteolin and Zn^{2 +} are incorporated as complementary bioactive modules to suppress bacterial burden and excessive inflammation, thereby establishing a pro-regenerative niche. Meanwhile, the catechol-containing dual-network architecture imparts strong wet adhesion and robust mechanical stability for conformal wound coverage. Mechanistically, this study provides, to our knowledge, the first evidence that thermoelectric stimulation reprograms fibroblast repair behavior through bioelectric transduction into a Ca^{2 +}/calmodulin-dependent phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinase (Erk) signaling network. The hydrogel exhibits broad-spectrum antibacterial activity, immunomodulatory effects, and pro-angiogenic capacity in vitro, and accelerates wound healing by 66.84% in diabetic rats. This work establishes a self-powered strategy that integrates bioelectric restoration with microenvironment remodeling for DFU repair.

Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes and weight loss, with well known gastrointestinal side effects including nausea, vomiting, and delayed gastric emptying. While mucosal injuries such as Mallory Weiss tears have been reported, full thickness esophageal perforation has not previously been described. We report the first documented case of Boerhaave's syndrome associated with GLP-1 RA use, highlighting the potential for rare but life threatening complications following abrupt reinitiation at high doses.

Case presentation: A previously healthy woman in her 50s presented with vasopressor dependent shock and respiratory failure requiring intubation following severe nausea, emesis, and acute chest pain. She had restarted semaglutide at the maximum 2.4 mg weekly dose the day prior to symptom onset, after several months off therapy and without dose titration. Imaging revealed pneumomediastinum and bilateral pleural effusions. Esophagram confirmed a contained esophageal perforation. She was managed with endoscopic stent placement, nasojejunal feeding, and chest tube drainage, followed by clinical improvement and discharge. Two months later, she was readmitted with necrotizing pneumonia. Imaging and endoscopy revealed an esophagopleural fistula, abscess, and migrated stent. She underwent left thoracotomy, abscess drainage, decortication, and wedge resection of necrotic lung. The perforation site was reinforced with an intercostal muscle flap, and a PEG tube was placed. Postoperatively, at 10-month follow up she was on a regular diet, PEG tube removed, and esophagus was healed on EGD. She was advised to permanently discontinue GLP-1 RAs.

Conclusions: This case underscores a previously unreported but serious complication of GLP-1 RA therapy, transmural esophageal rupture, likely precipitated by drug induced gastroparesis and forceful emesis. Restarting semaglutide at a high dose without titration after a prolonged interruption likely increased vulnerability to injury. Clinicians should maintain a high index of suspicion for esophageal complications in patients presenting with chest pain and vomiting during GLP-1 RA initiation or reinitiation. Early multidisciplinary management is crucial to optimizing outcomes in this rare but life-threatening scenario.

Background: The widespread adoption of GLP-1 receptor agonists such as semaglutide for weight loss has led to an increasing number of non-diabetic patients seeking body contouring procedures after pharmacologic weight reduction. However, concerns have emerged regarding postoperative complications potentially linked to GLP-1 therapy, particularly when continued up to the time of surgery.

Objectives: This retrospective cohort study aimed to evaluate the impact of preoperative semaglutide discontinuation timing on short-term postoperative outcomes in aesthetic lipoabdominoplasty.

Methods: Eighty patients who underwent primary lipoabdominoplasty were divided into four groups: continued semaglutide until surgery (Group A), 2-week discontinuation (Group B), 4-week discontinuation (Group C), and semaglutide-naïve controls (Group D). All patients were matched for age, BMI, and surgical technique. Postoperative complications within 30 days were assessed.

Results: Group A exhibited the highest complication rate (45%), including wound dehiscence, infection, and seroma formation. Group B showed moderate improvement (30% complication rate), while Group C demonstrated a significant reduction in adverse outcomes (10%), comparable to the control group (10%). Gastrointestinal intolerance and prolonged drain duration were also more frequent in patients with ongoing semaglutide use. No reoperations or readmissions occurred.

Conclusions: Continuation of semaglutide until surgery significantly increases postoperative complication risk in lipoabdominoplasty. A 4-week preoperative discontinuation period effectively normalizes outcomes, supporting its use as a safety measure in aesthetic surgery candidates. These findings emphasize the need for standardized perioperative management protocols for patients on GLP-1 therapy and underscore the importance of interdisciplinary coordination and nutritional assessment.

Level of evidence iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Diabetic foot ulcers (DFUs) are chronic, non-healing wounds that affect up to 34% of diabetic patients. DFUs are complicated by infection in nearly 60% of cases and frequently progress to amputation. DFU pathology is characterized by a persistent inflammatory state, impaired angiogenesis, and infection. This creates a complex microenvironment refractory to standard care, with fewer than 20% of DFUs healing within 8 weeks. In this review article, normal and pathophysiological processes of wound healing, current clinical management strategies, and adjunct therapeutics in the clinical pipeline are discussed, followed by recent advances in multifunctional bioengineered platforms. These platforms are categorized into three main systems: hydrogels, electrospun dressings, and 3D-bioprinted constructs, in addition to hybrid fabrication approaches and the integration of low-temperature plasma therapy as emerging multi-targeted strategies. For hydrogels, stimuli-responsive designs that respond to mechanical force, pH, glucose, and excess reactive oxygen species to actively modulate drug release and scaffold behavior are discussed. For electrospun scaffolds, strategies for controlled, multi-therapeutic delivery, including fiber blending, surface conjugation, and core-shell architectures are reviewed. Next, 3D bioprinting as a platform for patient-specific, cell-laden constructs is presented and covers major fabrication techniques and the emerging potential of handheld in situ bioprinters for accelerating clinical translation. Multi-targeted hybrid approaches that combine these platforms, along with the synergistic integration of low-temperature plasma therapy for broad-spectrum antimicrobial action, biofilm disruption, and immune modulation are emphasized. Unlike prior material-centric reviews, this review adopts a function-driven framework that organizes scaffold systems based on their ability to address key DFU pathologies, including infection, inflammation, impaired angiogenesis, and delayed healing, providing a more clinically relevant perspective. Finally, emerging directions such as artificial intelligence (AI)-guided design, in situ bioprinting, and recent clinical trends are discussed to bridge scaffold design with translational application. STATEMENT OF SIGNIFICANCE: Diabetic foot ulcers (DFUs) present a critical global health challenge characterized by a highly inflammatory microenvironment that remains refractory to standard care. This review elucidates the paradigm shift from passive wound dressings to "intelligent," multifunctional bioengineered scaffolds designed to actively modulate DFUs. We critically examine recent advances in stimuli-responsive hydrogels (pH-, glucose-, and reactive oxygen species-sensitive), mechanically active contractile patches, complex electrospun architectures, and 3D bioprinting. Furthermore, by integrating emerging technologies such as handheld in situ 3D bioprinting, low-temperature plasma therapy, and artificial intelligence-driven design, this work provides a roadmap for the next generation of precision biomaterials capable of overcoming specific biological barriers to regeneration in chronic wounds.