Search Results (1,348)

Background: Wound complications and unplanned revision surgery remain common after soft tissue sarcoma (STS) resection. Established risk models focus on patient- and tumour-related factors, while the role of operative and perioperative variables is less well defined. Methods: This retrospective single-centre study included 95 patients undergoing STS resection between 2021 and 2025. Associations with unplanned revision surgery were evaluated using univariate and exploratory multivariable logistic regression analyses. Receiver operating characteristic (ROC) analysis assessed the discriminatory performance of postoperative drainage output. Results: Unplanned revision surgery occurred in 23 patients (24%). On univariate analysis, several intraoperative and postoperative variables were associated with revision, whereas most patient- and tumour-related factors were not statistically significant. In multivariable analysis, intraoperative crystalloid administration was the only intraoperative factor associated with unplanned revision (OR 1.45 per 500 mL, 95% CI 1.05–2.02; p = 0.026). Among postoperative parameters, drainage output remained associated with revision (OR 1.45 per 100 mL, 95% CI 1.15–1.82; p = 0.005). In patients without planned secondary reconstruction, drainage output showed good exploratory discriminatory performance (AUC 0.927), with a cutoff of 925 mL providing high specificity (94.4%) with acceptable sensitivity (75%). Conclusions: In this cohort, unplanned revision was more frequently associated with markers of surgical complexity, including higher intraoperative crystalloid administration, and the early postoperative course, particularly drainage output. Drainage output appears to reflect an evolving complication rather than an independent predictor and may serve as an early clinical warning signal. Findings are hypothesis-generated and require external validation. Full article

Background/Objectives: Klebsiella pneumoniae complex, Escherichia coli, and Enterobacter cloacae complex are considered the most prevalent carbapenemase-producing (CP) Enterobacterales in Spain. However, temporal changes in carbapenemase distribution, clonal diversity, and the mobile genetic elements (MGEs) involved in their dissemination have not been systematically characterised in our region. To address this knowledge gap, this study investigated the epidemiology of these organisms over a seven-year period. Methods: CP Enterobacterales isolates recovered between 2019 and 2025 from rectal screening swabs and clinical specimens (blood, urine, respiratory, wound, and sterile fluid samples) were included. All 297 isolates underwent phenotypic characterisation. Carbapenemase detection and sequence type (ST) assignment were performed for the 282 isolates available for molecular analysis. Following the gradual implementation of long-read whole-genome sequencing (WGS) beginning in 2022, MGEs associated with carbapenemase dissemination were characterised, and selected high-risk clones were analysed by SNP-based phylogenetic analysis. Results: Fifty isolates were recovered from ICU admission rectal screening, and 247 from clinical samples. Although the proportion of CP Enterobacterales among Enterobacterales isolates remained stable throughout the study period, significant changes were observed between 2019 and 2022 and between 2023 and 2025 in carbapenemase types, with a statistically significant increase in metallo-β-lactamases (MBLs) (p < 0.001), as well as in species distribution. Furthermore, predominant plasmid replicons associated with the dissemination of MBL genes were characterised. A K. pneumoniae ST147 clone co-harbouring bla_OXA-48 and bla_NDM-1 emerged and expanded significantly during the study period (p < 0.05). In addition, an ST225 NDM-1 clone was identified. SNP-based phylogenetic analysis revealed distinct genetic clusters within both lineages. Conclusions: Temporal shifts in the epidemiology of CP Enterobacterales, including the emergence and expansion of high-risk clones, were observed. High-resolution genomic analyses provided additional insight into the genetic relationships among circulating lineages. Full article

Background: Thyroid carcinoma (THCA), especially papillary thyroid carcinoma (PTC), remains clinically challenging because recurrence and metastasis occur in a subset of patients. SMDT1 is an essential regulator of the mitochondrial calcium uniporter complex that may influence tumor progression, but its role in thyroid carcinoma is unclear. This study investigated the expression, clinical significance, and biological functions of SMDT1 in thyroid carcinoma. Methods: Public databases were used to analyze SMDT1 expression, diagnostic value, prognostic relevance, co-expression networks, functional enrichment, protein interactions, and immune infiltration. SMDT1 expression was validated in 50 paired PTC and adjacent non-tumorous tissues. In vitro SMDT1 overexpression was performed in PTC cell lines, followed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting (WB), CCK-8, colony formation, wound healing, and transwell assays. Results:SMDT1 was significantly downregulated in thyroid carcinoma tissues, PTC tissues, and PTC cell lines. Low SMDT1 expression was associated with lymph node metastasis and shorter disease-free survival. Functional analyses linked SMDT1 with mitochondrial calcium transport, oxidative phosphorylation, apoptosis, cellular senescence, and immune infiltration, including CD8⁺ T cells and activated NK cells. SMDT1 overexpression significantly suppressed PTC cell proliferation, colony formation, migration, and invasion. Conclusions:SMDT1 may function as a tumor suppressor in thyroid carcinoma and has potential diagnostic and prognostic value. Its effects may involve mitochondrial calcium homeostasis, metabolic regulation, and immune microenvironment remodeling. Full article

Vitamin C (L-ascorbic acid) is an essential micronutrient involved in collagen biosynthesis, redox regulation, immune function, endothelial biology, carnitine synthesis, neurotransmitter metabolism, and non-heme iron absorption. Dietary reference values are designed primarily to prevent deficiency in general populations, but vulnerability to low-vitamin C status may increase during trauma, surgery, chronic inflammation, malignancy, metabolic disease, smoking, poor intake, environmental exposure, and tissue repair. This narrative review synthesizes mechanistic, pharmacokinetic, clinical, and safety evidence on vitamin C as a stress-responsive micronutrient. Evidence is reviewed across tissue repair and wound healing, orthopedic recovery and selected complex regional pain syndrome risk contexts, fatigue, neuropsychiatric vulnerability, cancer-supportive care, vascular homeostasis, dermatologic biology, and preliminary microbiota–gut–brain axis hypotheses. The strength of evidence differs substantially across domains: biochemical functions and deficiency correction are well established, whereas benefits of supraphysiologic oral supplementation in vitamin C-replete patients remain uncertain. Oral nutritional supplementation is distinguished from intravenous pharmacologic ascorbate, with attention to route, formulation, dose division, gastrointestinal tolerance-limited adjustment, and safety monitoring. Because evidence for high-dose oral supplementation remains limited and condition-specific, such use should be individualized, time-limited, and clinician-monitored rather than presented as a population-level recommendation or evidence-defined therapeutic target. Taken together, the clinical value of vitamin C depends on baseline status, patient vulnerability, route, formulation, dosing interval, clinical endpoint, and safety review. Full article

The escalating prevalence of bacterial infections has intensified the search for innovative antimicrobial strategies, particularly for infected wound management. Chondroitin sulfate (CS), a naturally occurring glycosaminoglycan with established biocompatibility, presents an attractive scaffold for developing metal ion-functionalized biomaterials. This study reports the fabrication of chondroitin sulfate–copper complex (CSCu) and chondroitin sulfate–zinc complex (CSZn) through an ion exchange method, wherein Cu²⁺ and Zn²⁺ ions bind to the groups of carboxylate, sulfate, or N-acetyl from the CS backbone. The resulting complexes exhibited copper or zinc loading capacities of about 6.6% and demonstrated potent antibacterial activity against E. coli and S. aureus. The integration of CSCu or CSZn with sodium alginate yielded a hydrogel system with a higher apparent viscosity, possessing injectability and spreadability on the skin surface and a porous three-dimensional internal structure conducive to wound healing applications. In a murine model of S. aureus-infected full-thickness wounds, topical application of CSCu and CSZn hydrogels substantially accelerated wound closure, achieving 97.46% and 98.11% healing, respectively, by day 10. Additionally, treatment with CSCu or CSZn hydrogels significantly attenuated systemic inflammatory responses, as reflected in lowered serum TNF-α, IL-1β, and IL-6 alongside increased IL-10. Histological evaluation confirmed enhanced re-epithelialization and stratum spinosum formation in treated wounds. These findings establish CSCu and CSZn as a promising bioactive agent for addressing bacterial wound infections through a dual mechanism of direct antibacterial action and immunomodulatory effects, offering a valuable alternative to conventional antibiotic therapies. Full article

Background: Burn wound healing is a complex biological process requiring coordinated interactions among inflammatory cells, keratinocytes, fibroblasts, endothelial cells, extracellular matrix components, and neural structures. Increasing evidence suggests that sensory nerves actively regulate tissue repair through modulation of inflammation, angiogenesis, epithelial regeneration, and tissue remodeling. However, the role of sensory innervation in burn wound healing remains incompletely understood. The aim of this study was to investigate the effects of sensory denervation on healing of experimental second- and third-degree burns in rats. Methods: Thirty-two adult male Wistar albino rats were randomly allocated into four groups: denervated second-degree burns (Group 1), denervated third-degree burns (Group 2), innervated second-degree burns (Group 3), and innervated third-degree burns (Group 4). Bilateral T5–T7 sensory denervation was performed microsurgically in denervated groups. Standardized contact burns were subsequently created. Histopathological assessment of inflammation, neovascularization, epithelialization, fibroblast proliferation, and collagen deposition was performed on postoperative days 3, 7, 14, and 21. Results: Sensory denervation adversely affected multiple parameters of burn wound healing. Delayed epithelialization, impaired fibroblast proliferation, and reduced collagen deposition were most pronounced in denervated third-degree burns. Significant differences were identified between denervated and innervated wounds, particularly during proliferative and remodeling phases of healing. Conclusions: Sensory denervation significantly delays burn wound healing, particularly following third-degree thermal injury. Intact sensory innervation appears essential for successful epithelial regeneration, fibroblast activation, and extracellular matrix remodeling. Full article

Hydrocolloid-based and hydrocolloid-dominant hybrid matrices have developed from conventional rheology modifiers into functional platforms for pharmaceutical and cosmetic delivery. This review focuses on systems in which hydrocolloid chemistry, hydration, ionisation, bioadhesion, and network architecture determine swelling, mechanical behaviour, biocompatibility, and controlled release. The discussion covers alginate, chitosan, hyaluronic acid, pectin, carrageenan, dextran, gellan gum, collagen, cellulose derivatives, and selected hybrid architectures in which synthetic or semi-synthetic components provide a defined responsive function. Rather than treating all smart polymers as a single class, the review compares how pH, enzymatic, redox/ROS, thermo-responsive, magnetic, optical, ultrasound-mediated, and multi-trigger mechanisms operate within hydrocolloid-rich matrices. Pharmaceutical examples are considered across oral, transdermal, injectable depot, wound-healing, and regenerative applications, while cosmetic and cosmeceutical systems are discussed in relation to active stabilisation, dermal residence, barrier support, and personalised skincare. By linking material class, trigger mechanism, route of administration, and translational constraints, the review identifies the main advantages of hydrocolloids as delivery matrices as well as their current limitations, including burst release, modest mechanical strength, hydrophobic-drug loading challenges, sterilisation sensitivity, source variability, and regulatory complexity. Full article

Biofilm formation of ESKAPE pathogens creates a major problem in healthcare-associated infections, and nutrient supply significantly contributes to biofilm structure and bacterial survival. An understanding of how various nutritional environments influence polymicrobial biofilm dynamics is important for the development of targeted antimicrobials. In the present work, biofilm formation of ESKAPE pathogens was tested under three different nutritional environments—nutrient broth with no supplementation (NB; minimal), nutrient broth with supplementation of 2% glucose + 2% sucrose (NB+G+S; moderate), and Brain Heart Infusion supplemented with 2% glucose + 2% sucrose (BHI-G+S; Rich). Furthermore, we studied the effect of bacterial mixtures on biofilm features in each medium. Standard ATCC strains of Staphylococcus aureus (S), Enterococcus faecalis (E), Klebsiella pneumoniae (K), and Pseudomonas aeruginosa (P) were grown alone or in combination as mono-, dual-, tri-, and tetra-species. Biofilm formation was determined by crystal violet spectrophotometric assay (n = nine biological replicates, with three technical replicates each). LIVE/DEAD staining and confocal laser scanning microscopy (CLSM) were used for samples with absorbance values > 0.5, including 3-D architectural analysis of viability using ImageJ software. Biofilm height was quantified by using the ZEN depth code tool. Statistical analysis included one-way ANOVA with Tukey’s post hoc test (p < 0.05), and unpaired t-tests were performed when applicable to compare variables. Biofilm formation was drastically increased in rich medium compared to moderate and minimal NB. The tetra-species cocktail SKEP reached the highest biofilm dry weight in BHI+G+S and greater elevation/viability compared to NB+G+S, whereas P. aeruginosa monospecies exhibited an opposite trend (greater elevation in NB+G+S than BHI+G+S). Interestingly, the E. faecalis and P. aeruginosa group exhibited strong biofilm characteristics in a range of nutritional environments. Confocal analysis showed structurally distinct biofilms: dense, vertical biofilms in BHI+G+S and sparse, horizontal patterns in NB+G+S. Nutrient composition significantly impacts polymicrobial biofilm formation, with nutrient-rich conditions (BHI+G+S) supporting robust viable three-dimensional structures, particularly within complex bacterial communities. These observations are of potential significance with respect to biofilm formation in hospital settings, such as in wounds, and may be used in strategies against the targeted intervention of polymicrobial infections. Full article

Context: Locally advanced fungating breast cancer complicated by hemorrhage or infection represents a complex clinical condition that often requires a rapid and coordinated multidisciplinary approach. Although international guidelines, such as those developed by ESMO and NCCN, provide well-defined principles for the management of locally advanced breast cancer, they offer limited recommendations regarding the management of complicated fungating forms. Methods: We conducted a structured narrative review of the literature using the PubMed, Scopus, and Web of Science databases, including studies published between December 2019 and March 2026. Studies addressing locally advanced breast cancer and fungating forms complicated by hemorrhage or infection were included. Results: Available data are heterogeneous and derive primarily from case reports, small case series and retrospective studies. Systemic therapy remains the cornerstone of oncologic control; however, the presence of acute complications often necessitates prioritization of local interventions depending on the patient’s clinical stability. Hemorrhage may be managed through arterial embolization, hemostatic dressings or radiotherapy, whereas infection requires local wound care and targeted antibiotic therapy. These interventions aim to control acute symptoms and stabilize patients, thereby facilitating the subsequent integration of oncologic treatment. Emergency surgical intervention is reserved for selected cases, particularly when conservative measures fail to control bleeding or in the presence of persistent sepsis. Conclusions: The management of fungating breast cancer should be individualized and guided by the clinical presentation within a multidisciplinary team setting rather than by a rigid therapeutic sequence. This paper proposes a pragmatic, symptom-oriented clinical framework integrating all currently available therapeutic modalities (systemic therapy, radiotherapy, interventional radiology, surgery, and supportive care) with the aim of supporting decision-making in complex clinical scenarios. Full article

Background/Objectives: Hand phlegmons are rapidly progressive bacterial soft-tissue infections that may lead to severe functional impairment, repeated surgical interventions, and prolonged hospitalization if diagnosis and treatment are delayed. Although Gram-positive skin flora are considered the predominant pathogens, microbiological findings and clinical severity may vary considerably depending on the extent of infection and host factors. Methods: This single-center retrospective study analyzed 100 patients surgically treated for hand phlegmons at a university hospital between 2020 and 2025. Clinical data included demographics, portal of entry, microbiological findings, inflammatory markers, antibiotic therapy, number of surgical procedures, and length of hospital stay. Pathogens were classified according to Gram stain characteristics, and statistical analyses were performed using nonparametric methods and correlation analyses. Results: The cohort consisted of 69 male and 31 female patients with a mean age of 50.5 ± 20.9 years. Mean hospital stay was 12.9 days (range 1–77), and patients underwent an average of 2.18 surgical procedures (range 0–11). Wounds and bite injuries represented the most common portals of entry, although many cases lacked a clearly identifiable cause. Microbiological cultures were negative in 62% of cases. Among positive cultures, Gram-positive organisms predominated (84.2%), with Staphylococcus aureus and Streptococcus pyogenes representing the most frequent pathogens. MRSA was detected in three patients and was associated with significantly more surgical procedures (p = 0.04) and a tendency toward prolonged hospitalization. Admission CRP levels differed significantly according to Gram stain classification (p = 0.008) and correlated positively with both length of hospital stay (r = 0.431, p < 0.001) and number of surgical interventions (r = 0.272, p = 0.006). Patients with microbiologically confirmed infections required significantly more operative procedures than patients without pathogen detection (p < 0.001). Empiric antibiotic therapy primarily consisted of ampicillin/sulbactam, cefuroxime, and clindamycin, followed by oral therapy with amoxicillin–clavulanate or clindamycin. Conclusions: Hand phlegmons remain clinically challenging infections characterized by heterogeneous presentation, frequent culture-negative findings, and substantial surgical burden. Gram-positive pathogens continue to predominate, while resistant organisms such as MRSA may be associated with more complex clinical courses. Elevated inflammatory markers at admission correlate with prolonged hospitalization and increased operative requirements, suggesting their potential value as indicators of disease severity. Early diagnosis, prompt surgical debridement, and individualized antimicrobial therapy remain essential for infection control and preservation of hand function. Full article

Introduction: While global burden is underappreciated, traumatic wounds account for 23 million annual emergency department visits in the United States, accounting for trillions in medical costs and work and quality of life loss. We hypothesized that the use of intact fish skin grafts (IFSGs) would result in faster time to obtain a graftable wound bed compared to a synthetic matrix (SM). Methods: This retrospective analysis of patients with full-thickness acute traumatic wound was conducted on a matched sample of patients receiving IFSG versus SM. We hypothesized that there would be at least a 10-day difference between the two treatments. Two surgeons reviewed electronic charts for primary outcomes. Incomplete charts were excluded. For sensitivity analysis, both simple linear regression and generalized linear mixed models were utilized to adjust the primary outcome to potential confounders. Results: Data were reviewed for 80 patients. The final cohort included 38 patients [IFSG (n = 12) and SM (n = 26)]. Demographics were not different between groups. The mean age was 42.4 ± 20.7 years, with 62.2% being male and equal proportions having burns treated vs. another traumatic wound. The most common site was the lower extremity. All IFSG patients had negative pressure wound therapy (NPWT) placed at the time of implantation vs. 50% of SM (p = 0.001). The SM group had a larger TBSA (p < 0.001) and wound size (p = 0.001). Differences were subsequently used to adjust primary outcomes via regression. Patients with IFSG had faster time to a graftable wound bed compared to SM (mean ± SD: 13.9 ± 5.3 vs. 29.1 ± 10.3, p < 0.001). Neither wound size, burn severity, presence of infection, nor use of NPWT significantly altered the inference. Conclusions: In this paired sample, the use of IFSG as a dermal template for full-thickness traumatic injuries was associated with faster time to obtain a graftable wound bed compared to an SM. However, regression analysis alone is not enough to conclude that the same difference would exist in a prospectively controlled experiment, which should be performed. Full article

Background/Objectives: Total nasal reconstruction has long represented a formidable surgical challenge. To date, no universally accepted, evidence-based protocol for nasal reconstruction exists to guide clinical practice. This study introduces a novel technique for comprehensive, three-layer nasal reconstruction. Specifically, the approach entails (1) reconstruction of the nasal mucosal lining using a free radial forearm flap; (2) provision of robust structural support via an exogenous extended framework; and (3) restoration of the external nasal skin using an expanded forehead flap. Methods: Ten patients underwent reconstruction for full-thickness nasal defects, all achieving successful structural and functional restoration. All surgical procedures were completed successfully, with operative durations ranging from 6.5 to 10.5 h. One patient developed an infection involving the rib cartilage graft. Following thorough debridement, the radial forearm free flap healed uneventfully. A second patient experienced postoperative vascular compromise of the flap. Intraoperative exploration revealed inadequate perfusion; immediate microsurgical revision—including adjustment of recipient vessels and/or re-anastomosis—successfully restored flap viability. Results: Primary wound healing was achieved in all patients within 10–22 days. All patients completed a follow-up of 12–36 months (mean: 21.5 months). Both patients and the surgical team rated postoperative nasal aesthetics as satisfactory. Objective functional assessments—including anterior rhinomanometry and peak nasal inspiratory flow—demonstrated no clinically significant impairment in nasal airflow. Conclusions: This surgical strategy for reconstructing the three-layer nasal architecture in patients with total nasal defects represents a rational and clinically viable approach—offering a valuable reference for rhinoplasty surgeons performing such complex reconstructions. Full article

Background/Objectives: Reconstruction of complex soft-tissue defects in the lower extremity remains a significant challenge in reconstructive surgery, necessitating reliable vascularized tissue coverage when local options are exhausted. Since 1984, the free ALT flap has been recognized for its versatility, consistent vascular anatomy and low donor-site morbidity. Methods: A two-pronged approach was used, consisting of a systematic review of 18 clinical studies (published 2015–2025, n > 3400) and a retrospective analysis of 20 patients treated for high-energy traumatic defects at a single center (2017–2021). Primary endpoints included flap survival, complication rates, and functional outcomes. Results: The retrospective cohort demonstrated a 90% flap survival rate, which was not significantly different from the figure of 92.4% reported in the literature (p = 0.661). The overall complication rate was 40%, significantly higher than the 7.4% literature average (p < 0.001). Most complications were localized wound-healing disorders, such as partial necrosis, associated with the zone of injury in trauma. Despite these complications, a 100% limb salvage rate was achieved. Good functional outcomes, defined as regaining weight-bearing capacity, were observed in 80% of patients, consistent with the literature benchmarks (84.8%, p = 0.532). Conclusions: Within the limitations of this retrospective cohort and systematic review, the findings suggest that the free ALT flap is a reliable option for lower-extremity reconstruction, providing high flap survival and favorable functional outcomes despite a relatively high rate of localized wound complications in complex trauma cases. Full article

Background/Objectives: Liver fibrosis, a wound-healing response to chronic liver injury characterized by excessive extracellular matrix (ECM) accumulation, represents a major global health burden with no approved anti-fibrotic therapies. Pien Tze Huang (PZH), an officially approved traditional Chinese medicine (NMPA Drug Approval No. Z35020243), has demonstrated hepatoprotective effects, yet its epigenetic mechanisms in fibrosis treatment remain unexplored. Methods: We performed the first integrated methylome–transcriptome–proteome analysis to investigate PZH’s anti-fibrotic mechanisms in a CCl₄-induced mouse model using reduced representation bisulfite sequencing (RRBS), RNA-seq, and TMT-labeled LC-MS/MS. Results: We identified 10,974 differentially methylated loci (DMLs) and 773 differentially expressed genes (DEGs) modulated by PZH treatment. Integration analysis revealed ANXA3 and CORO1A as candidate therapeutic targets exhibiting significant inverse methylation-expression correlations validated at both transcriptomic and proteomic levels. Notably, PZH treatment modulated the CRLF-CLCF1 cytokine complex and the EGR-3 transcription factor network (42/44 genes enriched), suggesting broad transcriptional reprogramming in fibrotic liver. Protein–protein interaction (PPI) analysis highlighted key gene pairs such as Dnmt1-Uhrf1, Cbfb-Runx1, and Col4a1-Col4a2, implicating PZH in epigenetic maintenance, transcription factor regulation, and ECM remodeling. Conclusions: These findings suggest mechanistic insights into PZH’s multi-target anti-fibrotic effects and offer a rationale for developing potential therapeutic targets for liver fibrosis. Full article

Postoperative wound healing complications present a major challenge in plastic and reconstructive surgery, prolonging recovery and impairing outcomes. Early risk identification is difficult due to complex interactions among clinical, laboratory, and molecular factors. This study developed and evaluated machine-learning (ML) models to predict wound healing outcomes and identify key complication predictors. Utilizing a dataset of 95 women and 76 variables (including hematological, biochemical, coagulation, and gene expression profiles), we evaluated several ML approaches, including Decision Tree, Extra Trees, Gaussian/Bernoulli Naive Bayes, Logistic Regression, and Support Vector Machine. Model performance was assessed via k-fold cross-validation, ROC analysis, and SHAP feature importance. Molecular markers (COL1A1, MMP9, MAPK1, MAPK8, IL10, and CCL2) emerged as the strongest predictors, whereas conventional clinical variables showed limited value. The models achieved high discriminative performance, with validation ROC–AUC values ranging from 0.903 to 0.913. Extra Trees and Gaussian Naive Bayes demonstrated the highest sensitivity for detecting complications (Recall = 0.820 ± 0.238 and 0.807 ± 0.246, respectively). These findings highlight the value of integrating molecular-genetic biomarkers with ML for personalized risk stratification and preventive care in reconstructive surgery. Full article