Mihai-Codrin Constantinescu

Background/Objectives: Bromelain-based enzymatic debridement (NexoBrid^®) is an established tissue-preserving alternative to tangential excision in deep partial-thickness burns. Its clinical efficacy is supported by randomised trials, but its systemic effects are inconsistently described and its effects at tissue level in humans are largely unknown. The objective was to synthesise the human evidence on both domains and to determine, as a prespecified endpoint, whether any study has evaluated them in the same patients. Methods: PubMed, Embase and Scopus were searched between 2016 and 2026 using two stream-specific strategies that shared their intervention and population blocks and differed only in their outcome block: Stream A, clinical outcomes reported with systemic biological parameters; Stream B, clinical outcomes reported with histopathological findings. Eligible studies were original human investigations published in the last ten years. Risk of bias was assessed with ROBINS-I and the JBI checklists, and the synthesis was narrative, following PRISMA 2020 and SWiM. Results: Of 559 records, twelve studies were included: ten in Stream A (970 patients) and two in Stream B (nine patients); no study identified by the present search met the criteria of both. C-reactive protein and procalcitonin were significantly higher after enzymatic than after surgical debridement throughout the first week, and, in the single study that analysed the treated area as a continuous exposure, the probability of a post-debridement coagulation alteration rose with the area treated (odds ratio 1.158 per percentage point of body surface). Early fever occurred in 14% of patients and predicted later wound infection. Both histological studies were purely qualitative: neither reported a thickness, a percentage or a cell count, and neither reported any laboratory value. Conclusions: Enzymatic debridement is associated with a measurable systemic response whose proposed mechanisms are all statements about tissue that has never been examined. The two literature fields describe the same process at two levels of observation, in different patients and at incompatible times. No validated instrument exists for quantifying the human burn biopsy after debridement.

Background: Management of surgically treated hand trauma varies according to injury characteristics, referral pathways, and institutional practice, particularly regarding postoperative antibiotic therapy and wound cleansing. This study compared injury patterns, management strategies, and early postoperative outcomes between two European referral centers and evaluated reported practice through a parallel surgeon survey. Methods: We conducted a retrospective two-center cohort study including 360 adults undergoing surgical treatment for hand trauma between April 2024 and March 2025 in Le Mans, France (n = 270), and Iași, Romania (n = 90). Injury mechanisms, anatomical involvement, postoperative antibiotic use and duration, wound irrigation and cleansing practices, follow-up, and postoperative infection were compared. Because the cohorts differed substantially in case mix, a secondary sensitivity analysis was performed using the Romanian acute-injury subgroup (n = 63). A parallel anonymous survey included 70 French and 40 Romanian surgeons involved in hand trauma care. Results: Injury mechanisms differed between centers (p < 0.001), with powered-tool or machinery injuries occurring in 34.4% of Romanian and 15.6% of French patients. The Romanian cohort also had higher frequencies of tendon injury (90.0% vs. 30.7%), neurovascular involvement (57.8% vs. 14.1%), joint involvement (23.3% vs. 12.2%), and associated fracture (27.8% vs. 5.2%; all p ≤ 0.016). Continued postoperative antibiotics were administered to 97.8% of Romanian and 55.2% of French patients (p < 0.001). Among treated patients, 1- to 3-day courses predominated in Romania (85.2% vs. 16.2%; p < 0.001). Wound-cleansing practices also differed substantially. Among patients with documented follow-up, postoperative infection was identified in 3/90 Romanian patients (3.3%) and 3/171 French patients (1.8%; p = 0.418). In the Romanian acute-injury subgroup, infection occurred in 1/63 patients (1.6%). Survey responses also demonstrated variation in postoperative antibiotic duration and perceptions of existing recommendations. Conclusions: Substantial center-level variation was observed in case mix, postoperative antibiotic prescribing, treatment duration, and wound-cleansing practices. Few postoperative infections were documented among patients with available follow-up; however, differences in eligibility criteria, injury complexity, and follow-up completeness preclude conclusions regarding comparative treatment effectiveness. Survey findings provided complementary evidence of variability in reported practice rather than validation of the center-level clinical findings. Prospective multicenter studies using standardized injury classification and follow-up are needed to develop more consistent, risk-based approaches to antimicrobial and wound management in hand trauma.

Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe, potentially life-threatening mucocutaneous reactions classified based on body surface area (BSA) involvement: SJS affects less than 10% BSA, SJS/TEN overlap affects 10–30% BSA, and TEN affects more than 30% BSA. The mortality rates range from 4.8–9% for SJS to 14.8–48% for TEN. Treatment remains controversial, with corticosteroids and intravenous immunoglobulin (IVIg) being the most debated therapeutic options. While some studies suggest IVIg may block Fas-mediated keratinocyte apoptosis, meta-analyses have shown conflicting results regarding mortality benefit. Case presentation: We describe two patients from opposite ends of the SJS/TEN spectrum, managed in a burn unit with different therapeutic approaches. The first patient, a 47-year-old man with systemic lupus erythematosus, developed TEN with approximately 35% body surface area involvement, complicated by sepsis and rhabdomyolysis; he was treated with systemic corticosteroids and intravenous immunoglobulin (IVIg, 0.4 g/kg/day for 3 days). The second patient, a 66-year-old woman, developed SJS attributed to amoxicillin–clavulanic acid and was treated with systemic corticosteroids alone. Both patients achieved complete re-epithelialization without major sequelae. Conclusions: These two cases illustrate the clinical heterogeneity of the SJS/TEN spectrum and the central role of early recognition, prompt withdrawal of the culprit drug, transfer to a specialized unit, and multidisciplinary supportive care. Given the substantial differences between the two patients in age, sex, comorbidities, culprit drugs, and disease severity, no comparative or causal inference regarding the relative efficacy of the two treatment strategies can be drawn; no efficacy claim is made for either therapeutic approach; this report is descriptive, and the two cases are presented as contrasting rather than comparable.

Background: The Meek micrografting technique remains an important option in burn reconstruction, particularly when donor sites are limited. By expanding a small split-thickness skin graft into a regularly spaced micrograft array, the method can achieve expansion ratios well beyond those of conventional meshed grafting. This systematic review aims to synthesize the clinical evidence on the Meek technique, its technical evolution since 1958, and its performance relative to mesh grafting across the full spectrum of burn severity. Methods: A systematic review of the surgical literature was conducted according to PRISMA 2020 recommendations. Searches were performed in PubMed, Scopus, and Web of Science from 1958 to 2026, using combinations of the terms Meek technique, Meek micrografting, microdermagrafting, burns, wound coverage, and skin graft expansion. Eligible studies included clinical outcome reports, comparative analyses with mesh grafting, randomized controlled trials, and technical modifications of the Meek method. Results: The search yielded 412 records, of which 15 unique publications met inclusion criteria and were synthesized, including a 2025 intra-patient randomized controlled trial conducted in a mixed wound population. Reports documented the evolution of the Meek technique from its original description in 1958 to contemporary refinements, while clinical studies reported expansion ratios of 1:2 to 1:9 and variable graft-take estimates, often around or above 80% in extensive burns. At the 1:2–1:3 expansion ratios studied, however, the only completed randomized controlled trial found mesh grafting superior to Meek micrografting for graft take and short-term scar quality, indicating that the relative advantage of Meek is most consistent in donor-site-limited injuries requiring high expansion ratios rather than a universal benefit. Conclusions: The Meek technique remains a reproducible and valuable strategy for burn reconstruction when donor sites are critically limited, but current randomized evidence does not support its routine use over mesh grafting within the population and expansion ratios studied, and the available evidence does not establish a universal TBSA threshold for selecting between the two techniques. Future research should prioritize randomized comparisons across a wider range of burn sizes and standardized long-term scar outcome reporting.

Background/Objectives: Circumferential deep dermal burns generate progressive sub-eschar pressure with risk of burn-induced compartment syndrome (BICS). Bromelain-based enzymatic debridement is a proposed non-surgical decompressive strategy, but the temporal kinetics of intracompartmental pressure (ICP) normalization and their relationship to burn depth are poorly characterized. We explored these kinetics and introduce, as an exploratory descriptive concept, the Enzymatic Decompression Half-Time (EDT₅₀), mapping the ICP normalization curve stratified by Laser Doppler Imaging (LDI) burn depth. Methods: In this single-center retrospective study, 31 adults with circumferential deep dermal burns (IIb, TBSA ≤ 20%) treated with NexoBrid^® were analyzed. ICP was measured at five time points (T0–T24 h) and LDI at T0 and T24 h. Subgroup analyses were treated as descriptive because several subgroups were small. Results: ICP declined progressively with no rebound (repeated-measures ANOVA, p < 0.001). EDT₅₀ appeared depth-dependent (high-flux 2.1 h; low-flux 5.9 h). No patient developed clinical BICS (0/31; 95% CI 0–11%). Pre-treatment LDI flux correlated negatively with ICP (r = −0.71) and EDT₅₀ (r = −0.64). Conclusions: In this small cohort, enzymatic debridement was associated with progressive ICP normalization without clinical compartment syndrome. These hypothesis-generating findings require prospective validation; established BICS remains an absolute indication for surgical escharotomy.

Background/Objectives: Thermal injuries represent a significant global health burden, often complicated by hypertrophic scarring, chronic inflammation, and delayed re-epithelialization. While Mesenchymal Stem Cell (MSC) transplantation has shown promise, its clinical translation is hindered by risks of tumorigenicity and immunological concerns. This study evaluates the efficacy of cell-free Extracellular Vesicle (EV) therapy—derived from both mammalian MSCs and plant sources (PDNVs)—as standardized, off-the-shelf alternatives. This study synthesizes evidence focusing on re-epithelialization velocity, angiogenic activity, and anti-fibrotic outcomes, while assessing the impact of second-generation delivery scaffolds on therapeutic durability. Methods: Conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (CRD420261305379), this review interrogated PubMed, Scopus, Embase, and Web of Science for studies published between 2015 and 2026. Eligible studies included in vivo animal models of thermal injury using purified vesicles from mammalian MSC sources or plant-derived nanovesicles compared with placebo, standard care, or untreated controls. Data were synthesized narratively; methodological quality was appraised using the SYRCLE risk of bias tool and compliance with MISEV guidelines. Results: Synthesis of 50 studies revealed that vesicle-based interventions consistently accelerate wound closure and improve histological healing. Mammalian ADSC-derived vesicles demonstrated superior anti-fibrotic effects via the miR-192-5p and miR-125b-5p axes, while hUC-MSC vesicles attenuated systemic inflammatory signaling via miR-181c. Plant-derived nanovesicles (PDNVs) showed potent antioxidant and re-epithelialization effects, with emerging potential as engineered genetic carriers. Crucially, advanced delivery systems, including bioactive hydrogels and microneedle patches, were repeatedly associated with improved local retention and more durable effects than bolus injections. Conclusions: Vesicle-based therapies show consistent pro-healing signals in preclinical models, suggesting source-dependent profiles: MSC-derived vesicles excel in immunomodulation and anti-fibrotic remodeling, while PDNVs provide a scalable, low-immunogenicity platform. As a cell-free strategy, these therapies circumvent the safety risks of live cell transplantation. This review identifies a critical shift toward second-generation delivery scaffolds to overcome the clearance crisis of topical applications, emphasizing the need for harmonized MISEV-aligned characterization in future clinical translation.

Background: NexoBrid^® (NXB; MediWound Ltd., Yavne, Israel) (anacaulase-bcdb) is a bromelain-based enzymatic debriding agent approved for eschar removal in burn care. Despite widespread clinical use, histological evidence of tissue-level changes after enzymatic debridement remains limited. This systematic review aimed to evaluate preclinical and clinical studies describing histological findings following bromelain-based enzymatic debridement of thermal burns. Methods: Following PRISMA 2020 guidelines, we performed parallel systematic searches of preclinical (animal) and clinical (human) studies across PubMed, Embase, CENTRAL, Web of Science, and Scopus. Included studies reported thermal burns treated with bromelain-based enzymatic debridement and tissue biopsies with histological analysis. Quality was assessed using the SYRCLE Risk of Bias Tool (preclinical) and JBI Critical Appraisal Checklists (clinical). Results: Six preclinical studies (five porcine, one rat) met inclusion criteria. Findings included: selective eschar removal with dermal preservation; protection of the zone of stasis (67% partial- vs. 100% full-thickness necrosis; p = 0.05); viable dermal thickness of 1.1 ± 0.7 mm; and accelerated re-epithelialization (7.4 ± 0.8 vs. 9.1 ± 2.1 days; p < 0.05). Only two clinical studies (n = 9 patients) met the inclusion criteria: one case series (n = 8) and one case report. Clinical findings showed upper dermal homogenisation with preserved deep dermis, vascular congestion correlating with pinpoint bleeding, and pseudoeschar formation via transepidermal elimination. Conclusions: Preclinical evidence supports selective enzymatic debridement with dermal preservation. However, clinical histological data are limited to nine patients after over 13 years of use. This highlights a critical translational gap and underscores the need for prospective clinical histological studies.

Background/Objectives: The “bank-finger” or “spare-parts” principle offers an immediate reconstructive solution in mutilating hand injuries by repurposing viable tissues from non-salvageable digits to restore length, coverage, and function. Although described for decades, systematic evidence remains scarce. This study compared a single-center retrospective cohort with a systematic review of the specialized literature (2015–2025) to clarify the indications, reconstructive models, assessment of functional outcomes, and complication profiles associated with this technique. Methods: A retrospective analysis was performed on 35 adult patients treated for complex hand trauma between 2017 and 2024. It was compared with a systematic review of nine clinical studies identified across PubMed, Scopus, Embase, Web of Science, and Cochrane Library. Extracted variables included demographics, mechanisms of injury, type of tissues transferred, vascularization method, complications, and functional outcomes. Methodological quality was assessed using the Joanna Briggs Institute (JBI) criteria for case reports and case series. Results: Across 78 cases (43 from the literature and 35 institutional), vascularized fillet and osteo-cutaneous transfers constituted the predominant reconstructive approach, providing immediate skeletal stability and durable, sensate soft-tissue coverage. All flaps and grafts survived, and functional recovery was consistently favorable. In the retrospective cohort, standardized evaluation demonstrated excellent outcomes (mean DASH 14.6, MHQ 82.5, VAS 1.8). The overall complication rate remained below 10%, limited to transient venous congestion or mild postoperative stiffness. No infections, flap losses, or donor-site morbidity were reported. Conclusions: The bank-finger technique is a reliable, biologically efficient reconstructive strategy for acute mutilating hand trauma. When applied early and with appropriate tissue selection, it achieves outcomes comparable to conventional microsurgical options while avoiding additional donor-site morbidity. The present combined analysis highlights its reproducibility and underscores the need for prospective multicenter studies employing standardized functional metrics.

Alopecia areata (AA) is an autoimmune-mediated nonscarring alopecia with limited therapeutic options and frequent relapses. Exosomes, nanosized extracellular vesicles secreted by various cell types, have recently emerged as potential regenerative and immunomodulatory therapies. The aim of the study is to review the clinical and preclinical evidence regarding the efficacy and safety of EV-based therapies for alopecia areata. a systematic search of PubMed, Embase, Web of Science, and Cochrane Library was performed from 2020 to 2 October 2025. Inclusion criteria were original studies (clinical, preclinical, in vivo, in vitro) investigating exosome-derived interventions for AA. Outcomes of interest were hair regrowth, immune modulation, follicular regeneration, and safety. A total of 499 records were retrieved from electronic database searches. After deduplication and application of the inclusion/exclusion criteria, 40 studies met the eligibility criteria for the review. Of these, two were clinical studies (one retrospective cohort, one case report), while the remainder comprised five animal (in vivo) studies, six in vitro studies, and sixteen mixed translational studies (in vitro/in vivo ± clinical). Experimental studies reported hair coverage improvements of 50–99% and, in one instance, 30% regrowth in totalis and 16% in partialis, with nearly complete regrowth in incipient alopecia. Clinical reports noted density increases of 9–31 hairs per cm² (e.g., from 121.7 to 146.6 hairs/cm², p < 0.001) and improvements in hair count, length, and thickness. Several studies detailed activation of the Wnt/β-catenin pathway along with enhanced dermal papilla and hair follicle stem cell function, as well as anti-inflammatory effects. Reported safety profiles were favorable; when adverse events occurred, they were limited to mild, transient local reactions with no severe systemic issues. EV-based therapy is a novel and biologically plausible approach for AA, but robust randomized controlled trials (RCTs) are lacking. Standardization of small EV sources, doses, and delivery methods is essential before clinical translation.

Burn injury triggers a complex inflammatory cascade in which the interplay between pro- and anti-inflammatory mediators determines recovery or progression to sepsis, ventilator-associated pneumonia (VAP) or multi-organ dysfunction, and mortality. We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus for studies published between 2006 and 2024, identifying 1883 records. We conducted a comprehensive systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After screening and eligibility assessment, 24 studies covering both pediatric and adult populations met the inclusion criteria. Data on cytokines, acute-phase proteins, complement fragments, and systemic inflammatory indices were synthesized narratively. The evidence indicates that the inflammatory response to burn injury is not a linear sequence of events but a dynamic and unstable equilibrium, where outcomes are determined less by the initial magnitude of cytokine release and more by the persistence of dysregulated inflammation or failure of compensatory mechanisms.