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Diabetic Foot Ulcers: Pathophysiology, Immune Dysregulation, and Emerging Therapeutic Strategies
by
Misakyan, Yura
,
Venketaraman, Vishwanath
,
Gonzalez, Edgar
in
advanced glycation end products (AGEs)
,
Amputation
,
Angiogenesis
2025
Diabetic foot ulcers (DFUs) are among the most common and debilitating complications of diabetes mellitus (DM), affecting approximately 15–25% of patients and contributing to over 85% of non-traumatic amputations. DFUs impose a substantial clinical and economic burden due to high recurrence rates, prolonged wound care, and frequent hospitalizations, accounting for billions in healthcare costs worldwide. The multifactorial pathophysiology of DFUs involves peripheral neuropathy, peripheral arterial disease, chronic inflammation, and impaired tissue regeneration. Recent studies underscore the importance of immune dysregulation—specifically macrophage polarization imbalance, regulatory T cell dysfunction, and neutrophil impairment—as central mechanisms in wound chronicity. These immune disruptions sustain a pro-inflammatory environment dominated by cytokines, such as TNF-α, IL-1β, and IL-6, which impair angiogenesis and delay repair. This review provides an updated synthesis of DFU pathogenesis, emphasizing immune dysfunction and its therapeutic implications. We examine emerging strategies in immunomodulation, regenerative medicine, and AI-based wound technologies, including SGLT2 inhibitors, biologics, stem cell therapies, and smart dressing systems. These approaches hold promise for accelerating healing, reducing amputation risk, and personalizing future DFU care.
Journal Article
Effects of negative pressure wound therapy with instillation and dwell time (NPWTi‐d) versus NPWT or standard of care in orthoplastic surgery: A systematic review and meta‐analysis
2023
Negative pressure wound therapy (NPWT) is a wound‐dressing system that applies sub‐atmospheric pressure on the surface of a wound to promote healing. An evolution of this technology, NPWT with solution instillation and dwell time (NPWTi‐d), is increasingly being used to maximise wound closure and reduce failure rates. However, there is still a lack of evidence concerning its use in orthoplastic surgery. Therefore, the aim of this study is to compare NPWTi‐d with NPWT and standard of care for wound management in orthoplastic surgery. A comprehensive literature search using PubMed, Web of Science, and Cochrane databases up to 15 March 2022 was performed, including studies describing the outcomes of NPWTi‐d for traumatic/orthopaedic injuries. A meta‐analysis on the number of surgical debridements, as well as the rate of complete wound closure and complications was carried out, although for other outcomes, a descriptive statistic was applied. Risk of bias and quality of evidence were assessed using the Downs& Black's Checklist for Measuring Quality. Thirteen studies with a total number of 871 patients were included, in which NPWTi‐d demonstrated significantly higher primary wound closure and lower complication rates (P < .05). No difference in the number of surgical procedures required for final wound healing was observed. Moreover, five out of six studies showed better results for NPWTi‐d when the change of the bioburden and bacterial count of the wound were analysed. A singular study investigating the length of the hospital stay of patients treated with NPWTi‐d showed a reduction in the latter. The present meta‐analysis proves that NPWTi‐d is superior to NPTW or conventional dressings in orthoplastic wound care management, in terms of complete wound closure rate and the reduced number of complications. Still, the limited quality of the studies analysed shows that future randomised studies are needed to confirm the benefits and to identify the most appropriate recommendations for using NPWTi‐d in orthoplastic surgery, as well as to investigate the cost‐effectiveness of this wound‐dressing system.
Journal Article
Surgical Endoscopic Vacuum-assisted Closure Therapy (EVAC) in Treating Anastomotic Leakages After Major Resective Surgery of Esophageal and Gastric Cancer
by
VIRGILIO, EDOARDO
,
CECI, DIEGO
,
CAVALLINI, MARCO
in
Anastomosis, Surgical - adverse effects
,
Anastomotic leak
,
Anastomotic Leak - etiology
2018
Endoscopic vacuum-assisted closure therapy (EVAC) is a promising new technique for repairing upper gastrointestinal defects of different etiologies. As of 2018, however, no standardized recommendation exists. This article reviewed EVAC in treating anastomotic leakage following major resective surgery of esophageal (EC) and gastric cancer (GC).
Only English-language literature was investigated. Only studies or data on EC and GC were included. Seven popular search engines (PubMed, Web of Science, ScienceDirect, Scopus, Google Scholar, ResearchGate, PubFacts) were utilized.
A total of 29 studies (17 retrospective, six prospective and six case reports) with a total of 209 patients. Range of anastomotic leakage closure was 66.7-100%. Anastomotic stricture was the most frequent long-term related complication (18 cases).
EVAC appears to be an extremely useful treatment for postsurgical anastomotic leakage in patients with EC/GC. Almost all kinds of anastomotic leakage (silent to symptomatic, small to large) seem to be amenable to this technique.
Journal Article
No closure of the linea alba cervicalis reduces complications in endoscopic thyroidectomy
2025
The benefits of not suturing the linea alba cervicalis and using negative pressure wound therapy after endoscopic thyroidectomy have attracted increasing attention. Therefore, this study aims to determine whether the non-closure of the linea alba cervicalis after endoscopic thyroidectomy can significantly reduce postoperative complications and evaluate the application of NPWT to prevent cavity-related complications. A retrospective analysis was performed. 142 patients were enrolled and divided into two groups, including 71 individuals in the improvement group (no suture of the linea alba cervicalis) and 71 in the conventional group (suture the linea alba cervicalis). Then, the general clinical data and operative indicators were analyzed and compared between the two groups using SPSS 26.0 software. Statistical significance was recognized with
P
< 0.05. The improvement group showed a lower incidence of neck edema (3/71,4.2% vs. 10/71,14.1%) and a lower score on the Visual Analogue Scale (VAS) 5 days after the operation (3 ± 1.2 vs. 4 ± 1.3) between the two groups (
P
< 0.05), and there is no significant difference in the overall incidence of postoperative complications between the two groups (
P
>0.05). No closure of the linea alba cervicalis is safe and feasible after endoscopic thyroidectomy via chest-breast approach, with significantly less incidence of neck edema and lower neck discomfort. In addition, NPWT, providing a novel tool to reduce the occurrence of cavity-related complications in current clinical practice, can be used in whether or not to suture the linea alba cervicalis, which is safe and effective.
Journal Article
Temporal Regulation of Early-Stage Cytokine Expression in Diabetic Wound Healing Under Negative Pressure Wound Therapy
2025
Negative pressure wound therapy (NPWT) is widely recognized for its efficacy in treating diabetic wounds, but the mechanisms involved in the wound healing process remain unclear. By examining changes in blood cytokine levels as molecular signaling precursors, we aim to provide a comprehensive cytokine profile to support adjunctive therapy research and clinical applications. A diabetic mouse wound model was established to compare cytokine profiles between NPWT-treated and standard dressing groups, identifying key signaling candidates that may facilitate wound healing. By integrating normal mouse data with large-scale cytokine analysis, we developed a time-stratified NPWT approach to track acute-phase cytokine fluctuations in diabetic conditions. NPWT did not significantly enhance coagulation-related cytokine expression but effectively reduced inflammation, albeit with a delayed regulatory effect compared to wild-type mice. A one-sided binomial test revealed that NPWT advanced the cytokine expression peak from 16 to 2 h, partially restoring the early healing pattern seen in normal mice and suggesting its potential role in modulating early-stage wound repair. These findings provide novel insights into early cytokine regulation during wound healing and highlight the potential of NPWT to inform therapeutic strategies. This refined monitoring approach may contribute to improved clinical decision-making and support enhanced wound management in diabetic patients.
Journal Article
Negative pressure wound therapy for emergency laparotomy incisions: A national database propensity matched study
by
Argandykov, Dias
,
Velmahos, George C.
,
Kaafarani, Haytham M.A.
in
Abscesses
,
Aneurysms
,
Chronic obstructive pulmonary disease
2024
Surgical site infections (SSI) are a common complication of laparotomy incisions. The role of Negative Pressure Wound Therapy (NPWT) in preventing SSIs has not yet been explored in a nationwide analysis. We aimed to evaluate the association of the prophylactic use of NPWT with SSIs in patients undergoing an emergency laparotomy procedure.
We conducted a retrospective cohort study using the National Surgery Quality Initiative Program (NSQIP) database from 2013 to 2020. We included patients ≥18 years undergoing an emergency laparotomy. We performed a 1:1 propensity matching adjusting for patient age, sex, race, ethnicity, BMI, comorbid conditions, ASA status, diagnosis, preoperative factors and laboratory variables, procedure type, wound class, and intraoperative variables. We compared NPWT with standard dressings in two patient populations: 1. patients with completely closed (skin and fascia) laparotomy incisions and 2. patients with partially closed (fascia only) laparotomy incisions. Our primary outcome was the rate of incisional SSI. Secondary outcomes included the type of SSI, postoperative 30-day complications, postoperative hospital length of stay, and discharge disposition.
We included 65,803 patients with completely closed incisions of whom 387 patients received NPWT. There was no significant difference in the rate of total SSIs (13.4 % vs. 11.9 %; p = 0.52) in the matched population of 387 pairs. We included 7285 patients with partially closed incisions of whom 477 patients received NPWT. There was no significant difference in the rate of total SSIs (3.6 % vs. 4.4 %; p = 0.51) in the matched population of 477 pairs. Secondary outcomes did not differ significantly in either group.
The rate of SSIs was not significantly different when prophylactic NPWT was used compared to standard dressings for patients with a closed or partially closed laparotomy incision.
•In patients with skin and fascial closure, use of NPWT was not associated with lower rates of surgical site infections.•In patients with fascial closure only, use of NPWT was not associated with lower rates of surgical site infections.•There was no difference in secondary outcomes in patients with laparotomy incisions receiving NPWT versus standard dressings.
Journal Article
The Underlying Mechanisms and Role of Negative Pressure Wound Therapy in Chronic Diabetic Wound Healing: A Systematic Review and Meta‐Analysis
2026
Although Negative Pressure Wound Therapy (NPWT) has been increasingly used in wound care to improve impaired healing, there is little scientific evidence supporting its role and underlying biomolecular mechanisms. Aims of the present study are to provide a quantitative analysis of recent literature investigating NPWT in diabetic wound healing focusing on healing duration, wound closure, hospitalisation period and complications, and qualitative insight into studies analysing biomolecular mechanisms. The systematic review and meta‐analysis were conducted following PRISMA guidelines (PROSPERO: CRD42024524813). 21 studies published in PubMed, Cochrane Library, EMBASE between 2019 and 2024 were included. Clinical studies indicated NPWT was superior to standard care dressings (SCD), promoting faster wound healing with significantly reduced hospitalisation times by 7.8 days (95% CI: −14.2 to −1.4, p = 0.017), and significantly reduced complications rates, particularly major and minor amputations (95% CI: −10.2 to −1.3, p = 0.01). Mechanistic in vitro and animal studies highlighted NPWT can reduce local inflammation, oxidative stress, support angiogenesis and improve scarring, essential components of normal healing. Although studies suggest NPWT is more effective than SCD for diabetic wound healing, the paucity of studies, small cohorts and scarce outcomes consistency make defining clear conclusions challenging. There is still more evidence required to fully understand NPWT's role in the complex diabetic wound healing. Highlights NPWT can help reduce diabetic wound healing times and patient hospitalisation time when compared to standard care dressings. Across literature, NPWT was found to significantly reduce risk of major and minor amputations. In vitro and in vivo studies indicated NPWT can support angiogenesis and reduce local inflammation and oxidative stress and improve scarring, mechanisms associated with normal healing pathways. Future studies should report more standardise analysis timepoints and outcome measures and incorporate deeper molecular investigations to better understand the mechanisms of wound healing, chronicity and role of NPWT in diabetic.
Journal Article
Negative Pressure Wound Therapy as a Key Strategy in the Management of Severe Diabetic Foot Ulcers in Septic Frail Patients: A Case Series
by
Malerba, Silvia
,
Skokowski, Jaroslaw
,
Pirski, Maria Ignacy
in
Aged
,
Aged, 80 and over
,
Amputation
2026
Diabetes mellitus represents a major global health challenge, with over 537 million adults currently affected worldwide. Among its complications, diabetic foot ulcers remain a leading cause of morbidity, hospitalization and amputation, imposing a significant socioeconomic burden. Effective management requires a multidisciplinary approach integrating surgical, medical and rehabilitative expertise. Negative pressure wound therapy has demonstrated clinical efficacy in promoting granulation tissue formation, accelerating wound healing, and reducing infection rates compared with conventional dressings. This case series presents the management of four frail, septic patients with severe diabetic foot ulcers treated between 2023 and 2025 in an academic surgical department. All patients required surgical intervention, including debridement or partial amputation, combined with negative pressure wound therapy and, in selected cases, revascularization or skin grafting. One case utilized an electrospun nanofiber dressing which enhanced wound granulation and shortened healing time. Outcomes varied according to systemic comorbidities, vascular status and glycemic control; however, NPWT consistently supported wound stabilization and preparation for definitive closure. These findings reinforce the essential role of interdisciplinary collaboration and advanced wound technologies in the treatment of complex diabetic foot infections, particularly in frail or septic patients, and highlight the potential of nanofiber‐based dressings as adjunctive therapies in comprehensive diabetic foot care. Negative pressure wound therapy (NPWT) consistently supported wound stabilization and granulation in frail septic patients with severe diabetic foot ulcers. Multidisciplinary management, including surgical, vascular, and metabolic optimization, remains central to limb‐salvage strategies in complex diabetic foot infections. Frailty, rather than chronological age, emerged as a critical determinant of clinical trajectory and healing potential in septic surgical patients. Electrospun nanofiber dressings may enhance wound healing dynamics, representing a promising adjunct in advanced diabetic foot care.
Journal Article
The use of negative pressure wound therapy following stoma reversal: a systematic review and meta-analysis of randomized controlled trials
by
Creavin, Ben
,
McCormick, Paul
,
Previsic, Iva Pranjic
in
Clinical trials
,
Complications
,
Demographics
2025
Introduction
Stoma reversal is a contaminated surgery with many patients experiencing significant wound complications that contribute to patient morbidity. It is believed that the use of prophylactic negative pressure wound therapy (NPWT) may enhance wound healing and help reduce the risk of developing surgical site infections (SSI). However, there is conflicting research regarding its effectiveness following stoma reversal. Our systematic review aims to evaluate the available randomized data to determine if the use of prophylactic NPWT after stoma reversal improves the duration of wound healing and reduces rates of postoperative complications.
Methods
A comprehensive search of literature published up to January 2025 was conducted using the following databases: PubMed, Embase, Medline, and Cochrane Library. The included trials were randomized controlled trials that investigated the effect of NPWT following stoma reversal. The primary outcome was the time to complete wound healing. Secondary outcomes included the incidence of wound complications, SSI, hematomas, and the length of hospital stay.
Results
Six randomised control trials were included, with 332 patients, of which 171 of these underwent NPWT. There was a significant reduction in time to complete wound healing (OR − 2.53, 95% CI − 3.82 to − 1.24,
p
= 0.0001,
I
2
= 45%) and wound healing at 42 days (OR 0.36, 95% CI 0.14 − 0.88,
p
= 0.03,
I
2
= 0%) in the NPWT group. There was no significant difference in any wound complications (OR 0.72, 95% CI 0.23–2.28,
p
= 0.58,
I
2
= 42%), SSI rates (OR 0.95, 95% CI 0.27–3.29,
p
= 0.94,
I
2
= 38%) or haematoma rates (OR 0.21, 95% CI 0.03–1.27,
p
= 0.09,
I
2
= 0%) between the groups. There was no significant difference in length of stay (OR − 0.02, 95% CI − 1.21–1.18,
p
= 0.98,
I
2
= 66%).
Conclusion
The use of NPWT after stoma reversal significantly reduces the time needed for complete wound healing while maintaining a comparable rate of wound complications and length of hospital stay. Therefore, NPWT may be valuable in optimizing postoperative recovery and enhancing patient outcomes.
Journal Article
Surgical limits, pitfalls, and potential solutions in kyphectomy in myelomeningocele: three cases and systematic review of the literature
by
Nasto, Luigi Aurelio
,
De Marco, Raffaele
,
Piatelli, Gianluca
in
Child
,
Child, Preschool
,
Female
2024
Objectives
To describe surgical treatment of 3 cases of severe and progressive thoracolumbar kyphosis in myelomeningocele and provide a systematic review of the available literature on the topic.
Methods
Medical records and pre- and post-operative imaging of 3 patients with thoracolumbar kyphosis and myelomeningocele were reviewed. A database search was performed for all manuscripts published on kyphectomy and/or surgical treatment of kyphosis in myelomeningocele. Patients’ information, preoperative kyphosis angle, type of surgery, levels of surgery degrees of correction after surgery and at follow-up, and complications were reviewed for the included studies.
Results
Three cases underwent posterior vertebral column resection (pVCR) of 2–4 segments at the apex of the kyphosis (kyphectomy). Long instrumentation was performed with all pedicle screws constructed from the thoracic spine to the pelvis using iliac screws. According to literature review, a total of 586 children were treated for vertebral kyphosis related to myelomeningocele. At least one vertebra was excised to gain some degree of correction of the deformity. Different types of instrumentation were used over time and none of them demonstrated to be superior over the other.
Conclusion
Surgical treatment of progressive kyphosis in myelomeningocele has evolved over the years incorporating all major advances in spinal instrumentation techniques. Certainly, the best results in terms of preservation of correction after surgery and less revision rates were obtained with long construct and screws. However, complication rate remains high with skin problems being the most common complication. The use of low-profile instrumentation remains critical for treatment of these patients.
Journal Article