Peceleganan Spray for the Treatment of Skin Wound Infections: A Randomized Clinical Trial.

Importance: Peceleganan spray is a novel topical antimicrobial agent targeted for the treatment of skin wound infections. However, its efficacy and safety remain unclear. Objective: To assess the safety and efficacy of peceleganan spray for the treatment of wound infections. Design, Setting, and Participants: This multicenter, open-label, phase 3 randomized clinical trial recruited and followed up 570 adult patients diagnosed with secondary open wound infections from 37 hospitals in China from August 23, 2021, to July 16, 2022. Interventions: Patients were randomized to 2 groups with a 2:1 allocation. One group received treatment with 2% peceleganan spray (n = 381) and the other with 1% silver sulfadiazine (SSD) cream (n = 189). Main Outcomes and Measures: The primary efficacy outcome was the clinical efficacy rate (the number of patients fulfilling the criteria for efficacy of the number of patients receiving the treatment) on the first day following the end of treatment (day 8). The secondary outcomes included the clinical efficacy rate on day 5 and the bacterial clearance rate (cases achieving negative bacteria cultures after treatment of all cases with positive bacteria cultures before treatment) on days 5 and 8. The safety outcomes included patients' vital signs, physical examination results, electrocardiographic findings, blood test results, and adverse reactions. Results: Among the 570 patients randomized to 1 of the 2 groups, 375 (98.4%) in the 2% peceleganan treatment group and 183 (96.8%) in the 1% SSD control group completed the trial (n = 558). Of these, 361 (64.7%) were men, and the mean (SD) age was 48.6 (15.3) years. The demographic characteristics were similar between groups. On day 8, clinical efficacy was achieved by 339 patients (90.4%) in the treatment group and 144 (78.7%) in the control group (P < .001). On day 5, clinical efficacy was achieved by 222 patients (59.2%) in the treatment group and 90 (49.2%) in the control group (P = .03). On day 8, bacterial clearance was achieved by 80 of 334 patients (24.0%) in the treatment group and in 75 of 163 (46.0%) in the control group (P < .001). On day 5, bacterial clearance was achieved by 55 of 334 patients (16.5%) in the treatment group and 50 of 163 (30.7%) in the control group (P < .001). The adverse events related to the application of peceleganan spray and SSD cream were similar. Conclusions and Relevance: This randomized clinical trial found that peceleganan spray is a safe topical antimicrobial agent with a satisfactory clinical efficacy rate for the treatment of skin wound infections, while the effectiveness of bacterial clearance remains uncertain. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100047202.

Reconstruction of multiple long digital and hand defects using the multilobed anterolateral thigh perforator flap.

OBJECTIVE: This study investigated the reconstruction of multiple long digital and hand defects using the multilobed anterolateral thigh perforator flap. METHODS: From January 2018 to January 2021, 14 patients (hands) with multiple long digital defects were treated using the multilobed anterolateral thigh perforator flap. The mean age of the patients was 35 years (range, 18-55 years). The mean size (length × width) of the defects was 12.3 × 10.6 cm (range, 9 × 7 cm-16 × 12 cm). The mean size of the flap was 13.7 × 12.1 cm (range, 11 × 8 cm-19 × 14 cm). The total active motion was compared to the opposite side (100% normal, excellent; 75%-99% normal, good; 50%-74% normal, fair; <50% normal, poor). RESULTS: In this series, 12 flaps survived completely. Partial flap necrosis occurred in 2 patients but healed with wound care. The mean follow-up period was 28 months (range, 25-34 months). Based on the total active motion scoring system, we got 1 excellent, 7 good, 7 fair, and 1 poor result. A second surgery to separate the digits was not required. CONCLUSION: Multiple digital and hand defects can be reconstructed simultaneously using the multilobed anterolateral thigh perforator flap, allowing a length-to-width ratio of greater than 1.5:1 to resurface long digital defects. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.

Efficacy and Safety of PL-5 (Peceleganan) Spray for Wound Infections: A Phase IIb Randomized Clinical Trial.

OBJECTIVE: To assess the safety and efficacy of antimicrobial peptide PL-5 (Peceleganan) spray in the treatment of wound infections. BACKGROUND: Antimicrobial peptide PL-5 spray is a novel topical antimicrobial agent. METHODS: We conducted a multicenter, open-label, randomized, controlled phase IIb clinical trial to evaluate the efficacy and safety of PL-5 spray, as compared with silver sulfadiazine, in patients with skin wound infections. The primary efficacy outcome was the clinical efficacy rate on the first day after ending the treatment (D8). The secondary efficacy outcome was the clinical efficacy rate on the fifth day posttreatment (D5), the bacteria clearance rate, and the overall efficacy rate at the mentioned 2 time points. The safety outcomes included adverse reactions and pharmacokinetic analysis posttreatment. RESULTS: A total of 220 patients from 27 hospitals in China were randomly assigned to 4 groups. On D8, the efficacy rate was 100.0%, 96.7%, 96.7% for the 1‰ PL-5, 2‰ PL-5, 4‰ PL-5 groups, respectively, as compared with 87.5% for the control group. The efficacy rate among the 4 groups was significantly different ( P <0.05). On D5, the efficacy rate was 100.0%, 93.4%, 98.3% for the 1‰ PL-5, 2‰ PL-5, 4‰ PL-5 groups, respectively, as compared with 82.5% for the control group. The efficacy rate among the 4 groups was significantly different ( P <0.05). The blood concentration of PL-5 was not detectable in pharmacokinetic analysis. No severe adverse event related to the application of PL-5 was reported. CONCLUSIONS: Antimicrobial peptide PL-5 spray is safe and effective for the treatment of skin wound infections. TRIAL REGISTRATION: ChiCTR2000033334.

Screening and analysis of differentially expressed circRNAs and miRNAs in chronic diabetic extremity wounds.

Increasing studies have shown that circular RNAs (circRNAs) and microRNAs (miRNAs) are related to the development of endocrine and metabolic diseases. However, there are few reports on the expression of circRNAs and miRNAs and their related co-expression and the expression of competitive endogenous RNA (ceRNA) in diabetic chronic refractory wounds. In this study, we compared the differential expression of circRNAs and miRNAs in diabetes chronic refractory wounds and normal skin tissues by high-throughput gene sequencing, and screened the differentially expressed circRNAs and miRNAs. Five abnormally expressed circRNAs and seven abnormally expressed miRNAs were detected by reverse transcription quantitative polymerase chain reaction PCR (RT-qPCR)to verify the results of RNA sequencing. We applied gene ontology (GO) to enrich and analyze dysregulated genes and elucidated their main functions via the Kyoto encyclopedia of genes and genomes analysis (KEGG). We constructed coding noncoding gene co-expression networks and ceRNA networks based on significantly abnormally expressed genes. According to the results of coding noncoding gene co-expression network analysis, hsa_circRNA_104175, hsa_circRNA_ 001588, hsa_circRNA_104330, hsa_circRNA_ 100141, hsa_circRNA_103107, and hsa_ circRNA_102044 may be involved in the regulation of the chronic intractable wound healing process in diabetes mellitus. This is particularly true in the regulation of vascular smooth muscle contraction-related pathways and the actin cytoskeleton, which affect the healing of chronic intractable wounds in diabetes. MiR-223-5p, miR-514a-3p, miR-205-5p, and miR-203-3p, which each have a targeting relationship with the above circRNAs, regulate the metabolism of nitrogen compounds in wound tissue by regulating NOD-like receptor signaling pathways, signaling pathways regulating the pluripotency of stem cells, microRNAs in cancer, and ECM-receptor interaction. This study showed circRNAs, miRNAs, and their network are associated with the development of chronic intractable wounds in diabetes, and our research identified the goals for new molecular biomarkers and gene therapy.

Epidemiological and Clinical Characteristics of 5,569 Pediatric Burns in Central China From 2013 to 2019.

Background: Pediatric burns of all the ages are prevalent worldwide, posing a severe health risk to children. This study aims to examine pediatric burns' clinical characteristics and epidemiology in central China. Methods: The pediatric patients of the Burn Research Center, Department of the First People's Hospital of Zhengzhou City from 2013 to 2019 were retrospectively studied and the relevant data were collected from the hospitalized medical records [e.g., demographic, etiology, length of stay (LOS), age, gender, burn area and depth, number of surgeries, cost, and outcome]. Results: A total of 5,569 pediatric burn patients were included, accounting for 43.9% of the total burn population. Electric burns represented a relatively small proportion (1.17%) but were more likely to lead to disabilities or death than scalds (90.63%) and flames (5.12%). The median age was 2 years [interquartile range (IQR): 1-4] and the boys/girls ratio ranged from 1.3:1 to 1.6:1. The most commonly burnt anatomic sites were the limbs (38.3%), with a median %TBSA (total body surface area) of 6 (IQR: 4-10). The complications of shock and pneumonia accounted for 7.6 and 19.2%, respectively. The peak months of pediatric burns included January, May, and August and the rural/urban ratio reached 1.61:1. The percentage of burn wounds treated surgically increased considerably from 2013 to 2019 (3.8 vs. 37.8%). The median hospital LOS was 15 days (IQR: 8-28 days), with the three high-risk factors (e.g., more surgeries, more %TBSA, full-thickness skin burns). The median cost of hospitalization was 1,511 USD (IQR: 848-2,648 USD) and the main risk factors consisted of full-thickness burns, more %TBSA, longer LOS, and more surgical procedures. Among all the patients, LA50 was 78.63% (95% CI = 75.12-83.45) and the overall mortality reached 0.1% since seven deaths were recorded. Conclusion: Scalds, flames, contact, and chemicals are the main causes of burns among children aged 1-5 years in central China. Accordingly, various prevention strategies should be employed depending upon the cause of the burn.

Reconstruction of Giant Defects Due to Electrical and Radiation Burns in the Lower Leg with Free Anterolateral Thigh Flaps.

The purpose of this study was to introduce reconstruction of giant soft tissue defects of the lower leg caused by high-voltage electrical burns and radiation burns using the free anterolateral thigh (ALT) flap. From March 2017 to January 2018, 6 patients who sustained high-voltage electrical burns and 2 patients who sustained ulcerated radiation burns were reconstructed using the free ALT flap. The mean size of the defects was 19 cm × 32 cm (range, 18 cm × 22 cm to 30 cm × 36 cm). The mean size of the flaps was 22 cm × 34 cm (range, 20 cm × 24 cm to 32 cm × 38 cm). All flaps survived completely. The mean preoperative Functional Analysis Technique Evaluation score was 62 (range, 43 to 74). The mean follow-up period was 16 months (range, 12 to 18 months). At the final follow-up, the mean postoperative score was 90 (range, 86 to 94). The mean improvement was 33% (range, 17% to 54%) with 4 excellent and 4 good results. For extensive, high-voltage electrical, and radiation burns encompassing the lower leg, early treating the giant soft tissue defects with a free ALT flap produces good functional outcomes without significant complications.

Topically administered rhGM-CSF affects PPARß expression in the stasis zone.

Using a rat comb thermal damage model, we investigated the effects of topically administered recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on peroxisome proliferator-activated receptor PPARß expression. We created bilateral comb scald models on the backs of fifty Sprague-Dawley rats. The left sides of the backs served as the experimental group and the right sides served as the control group. The experimental group received topically applied rhGM-CSF hydrogel and the control group did not. The survival situations of the stasis zones were compared between the experimental and control groups on the 1st, 3rd, 7th, 14th and 21st post-burn days. Tissues from the surviving stasis zones of both groups were collected at different time-points. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting were used to detect the PPARß mRNA and protein expression levels. Immunohistochemical methods were applied to detect the localization of PPARß protein expression. The results showed that, first, the tissue viability numbers for the stasis zones of the experimental group were significantly increased compared with those of the control group. Second, RT-PCR revealed that the PPARß mRNA expression first increased and then gradually declined in both groups. At all time-points, the expression level in the experimental group was increased compared with that in the control group and the highest expression levels were observed in both groups on the 3rd post-burn day. Third, western blot analysis revealed that the PPARß protein expression in both groups increased after thermal damage and then gradually decreased. PPARß protein expression in the experimental group was greater than that in the control group, and the highest expression quantities in both groups were observed on the 3rd post-burn day. In conclusion, rhGM-CSF hydrogel effectively promotes the expression of PPARß, and the hydrogel had a specific protective effect for the stasis zone.

[STUDY ON MODIFICATION OF BIOMATERIALS OF ACELLULAR BOVINE PERICARDIUM WITH DIFFERENT CROSSLINKING REAGENTS].

OBJECTIVE: To investigate the effects of modification of acellular bovine pericardium with 1-ethyl-3-(3- dinethylami-nopropyl) carbodimide (EDC)/N-hydroxysuccininide (NHS) or genipin and find out the best crosslinking reagent. METHODS: The cellular components of the bovine pericardiums were removed. The effects of decellularization were tested by HE staining. The acellular bovine pericardiums were crosslinked with EDC/NHS (EDC/NHS group) or genipin (genipin group). The properties of the crosslinked acellular matrix were evaluated by scanning electron microscope (SEM), matrix thickness, crosslinking index, mechanical property, denaturation temperature, enzymatic degradation, and cytotoxicity test before and after the crosslinking. Acellular bovine pericardium (ABP group) or normal bovine pericardium (control group) were harvested as controls. RESULTS: SEM showed that collagen fibers were reticulated in bovine pericardial tissues after crosslinked by EDC/NHS or genipin, and relative aperture of the collagen fiber was from 10 to 20 µm. The thickness and denaturation temperature of the scaffolds were increased significantly after crosslinking with EDC/NHS or genipin (P < 0.05), while there was no significant difference between EDC/NHS group and genipin group (P > 0.05). The difference had no statistical significance in crosslinking index between EDC/NHS group and genipin group (t = 0.205, P = 0.218). The degradation rate in EDC/NHS group and genipin group was significantly lower than that in ABP group and control group (P < 0.05). Elastic modulus and fracture stress in EDC/NHS group and genipin group were significantly lower than those in ABP group (P < 0.05), but there was no significant difference among EDC/NHS group, genipin group, and control group (P > 0.05). The break elongation in EDC/NHS group and genipin group were significantly increased than those in ABP group and control group (P < 0.05). The difference had no statistical significance in stability and mechanical properties between EDC/NHS group and genipin group (P > 0.05). Cytotoxicity of genipin crosslinked tissue (grade 1) were much lower than that of EDC/NHS (grade 2) at 5 days. CONCLUSION: Acellular bovine pericardium crosslinked with genipin has better biocompatibility than EDC/NHS.

Repair of lower extremity soft tissue defect with free musculo-cutaneous flaps bridging with healthy contralateral posterior tibial vessel / 中华整形外科杂志

<p><b>OBJECTIVE</b>To observe the clinical effects of free musculo-cutaneous flap bridging with contralateral posterior tibial vessel on repair of lower extremity soft tissue defect.</p><p><b>METHODS</b>From February 2006 to June 2013, 10 patients with soft tissue defect on lower shank and foot were included. The posterior tibial vessel on healthy lower extremity was chosen as recipient vessel and anastomosed with free latissimus dorsi musculo-cutaneous flap, or free latissimus dorsi musculo-cutaneous flap combined with thoracic-umbilical skin flap or anterolateral femoral musculo-cutaneous flap. The retrograde bridged flap was transposed to repair defect on contralateral lower shank and foot. The wound area ranged from 40 cm x 21 cm to 22 cm x 15 cm, with flap size from 48 cm x 26 cm to 25 cm x 18 cm. Meanwhile the defects on donor sites were covered with skin graft and both lower extremities were fixed with kirschner wires at middle tibia and calcaneus. The kirschner wires were removed at 4 weeks and pedicles were cut off 5-8 weeks postoperatively. Six patients received posterior tibial vessel reanastomosis at the same time of pedicle cutting.</p><p><b>RESULTS</b>All the 10 flaps survived and 3 patients received thinning of flaps due to excessive thickness. During the follow-up period of 3 months to 2 years follow up, the ambulatory function of injured legs recovered gradually with satisfactory appearance. The reanastomosed posterior tibial vessel on the healthy side was recovered.</p><p><b>CONCLUSIONS</b>Appropriate bridged musculo-cutaneous flaps is suitable for extensive soft tissue defect of lower shank and foot. It is a safe and effective method for limb salvage.</p>

[Multi-center clinical trial of FLAMIGEL (hydrogel dressing) for the treatment of residual burn wound].

OBJECTIVE: To evaluate the effect of FLAMIGEL (hydrogel dressing) on the repair of residual burn wound. METHODS: Sixty burn patients with residual wounds hospitalized in 6 burn units from November 2011 to May 2012 were enrolled in the multi-center, randomized, and self-control clinical trial. Two residual wounds of each patient were divided into groups T (treated with FLAMIGEL) and C (treated with iodophor gauze) according to the random number table. On post treatment day (PTD) 7 and 14, wound healing rate was calculated, with the number of completely healed wound counted. The degree of pain patient felt during dressing change was evaluated using the visual analogue scale (VAS). The mean numbers of wounds with score equal to zero, more than zero and less than or equal to 3, more than 3 and less than or equal to 6, more than 6 and less than or equal to 10 were recorded respectively. Wound secretion or exudate samples were collected for bacterial culture, and the side effect was observed. Data were processed with repeated measure analysis of variance, t test, chi-square test, and nonparametric rank sum test. RESULTS: Wound healing rate of groups T, C on PTD 7 was respectively (67 ± 24)%, (45 ± 25)%, and it was respectively (92 ± 16)%, (72 ± 23)% on PTD 14. There was statistically significant difference in wound healing rate on PTD 7, 14 between group T and group C (F = 32.388, P < 0.01). Ten wounds in group T and four wounds in group C were healed completely on PTD 7, with no significant difference between them (χ(2) = 0, P > 0.05). Forty-two wounds in group T and seven wounds in group C healed completely on PTD 14, with statistically significant difference between them (χ(2) = 42.254, P < 0.01). Patients in group T felt mild pain during dressing change for 37 wounds, with VAS score higher than zero and lower than or equal to 3. Evident pain was observed in patients of group C during dressing change for 43 wounds, and it scored higher than 3 and less than or equal to 6 by VAS evaluation. There was statistically significant difference in mean number of wounds with different grade of VAS score between group T and group C (Z = -4.638, P < 0.01). Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, E. coli, Baumanii, and Staphylococcus epidermidis were all detected in both groups, but there was no statistical difference between group T and group C (χ(2) = 0.051, P > 0.05). No side effect was observed in either of the two groups during the whole trial. CONCLUSIONS: FLAMIGEL can accelerate the healing of residual burn wounds and obviously relieve painful sensation during dressing change.