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.

Ursolic acid inhibits human dermal fibroblasts hyperproliferation, migration, and collagen deposition induced by TGF-ß via regulating the Smad2/3 pathway.

Hypertrophic scar (HS) is a skin condition characterized by excessive fibrosis with disordered collagens from skin fibroblasts, which causes abnormal esthetic and even functional symptoms, thereby affecting millions of people. Ursolic acid (UA) is widely used in skincare and exerts anti-fibrotic effects. The present study aimed to delve into the impact of UA on HS and the mechanism. Fibroblasts (FBs) were incubated with TGF-ß to investigate physiological characteristics compared with FBs isolated from normal skin (NSFBs) and hyperplastic scars (HSFBs). TGF-ß-incubated FBs were subjected to treatment with UA (0-20 µM). The expressions of Vimentin, α-SMA, Collagen I, and Collagen III were examined using immunofluorescence, RT-qPCR, and western blot. Cell viability, proliferation, apoptosis, migration, and contractility were examined by CCK-8, EdU, Annexin V-FITC/PI, Transwell, and collagen gel contraction assays, respectively. The activation of Smad2/3 signaling was also determined by western blot. The binding sites for UA of TGF-ßR1 (ALK5) were predicted by the Autodock tool. Compared with NSFBs, the cell proliferation, migration, and contractility of both HSFBs and TGF-ß-incubated FBs were all significantly up-regulated. UA markedly impaired the TGF-ß-induced increase in cell proliferation, migration, and contractility, α-SMA, collagen I, and Collagen III expression of FBs. UA significantly inhibited the phosphorylation levels of Smad2/3 in TGF-ß-incubated FBs with no influence on TGF-ßR1 and TGF-ßR2 expressions, which might be because of the binding of UA to the catalytic domain of ALK5 protein. UA attenuated TGF-ß1-induced hyperproliferation, migration, and collagen deposition in FBs via regulating the Smad2/3 pathway.

The epidemiology and prognosis of patients with massive burns: A multicenter study of 2483 cases.

OBJECTIVE: Epidemiological features of massively burned patients in China remains unclear. This study was designed to investigate the epidemiological characteristics and evaluate the burn index (BI) and other risk factors associated with the prognosis of massively burned patients. METHODS: Data of patients with ≥30% total body surface area burned admitted in 2014 were retrieved from 106 burn centers in the mainland of China. Information of epidemiological features and the outcome were collected for retrospective analysis. RESULTS: A total of 2483 massively burned patients were included in this study, with a male-to-female ratio of 2.29:1, the mean age of 49.23±16.67 years, mean TBSA of 55.53±21.39% and the mean BI of 39.75±21.59. Scald accounted for 81.07% of the injuries in children, while flame accounted for 66.89% and 74.31% of the injuries in adults and seniors. Approximately 17.76% of the patients were admitted to the local burn center after 6h of injury, and the wound areas of 1154 (46.48%) patients were covered with folk remedies. The mortality was 9.79%, and the area under the receiver operating characteristic (ROC) curve for BI was 0.941 (95% CI, 0.929-0.954). When the value of BI was above a threshold of 29 in the 0-14 years age group, 43.5 in the 15-59 years age group and 35.5 in the 60 years or older age group, the mortality increased significantly. Multivariate logistic regression analyses showed that the odds ratio (OR) of death increased 6% with an increase in the BI of 1.0. Patients older than 60 years, the admission time longer than 6h after-injury (adjusted OR, 1.797; 95% CI, 1.179-2.740; adjusted p<0.001), and patients with a combined inhalation injury (adjusted OR, 6.649; 95% CI, 4.517-9.789; adjusted p<0.000), were at higher risk of death. CONCLUSIONS: There are etiological characteristics of the different age groups that should be considered for prevention. BI can be a reliable index of prognosis in severely burned patients. The results of the study showed that a large BI, elderly age, delayed admission after injury and combined inhalation injury are the main risk factors for extensively burned patients.

[Changes in serum contents of interleukin-6 and interleukin-10 and their relation with occurrence of sepsis and prognosis of severely burned patients].

OBJECTIVE: To observe the changes in serum contents of interleukin-6 (IL-6) and interleukin-10 (IL-10) in patients with severe burn injury, and to investigate their relation with occurrence of sepsis and prognosis of patients. METHODS: One-hundred and sixty adult patients admitted into our hospital (1.0 ± 6.0) h after injury during March 2007 to March 2011 with massive and severe burns were enrolled in the investigation. Patients were divided into non-sepsis group (NS, n = 112), sepsis-survival group (SS, n = 36), and sepsis-deceased group (SD, n = 12) based on the occurrence of sepsis and death. Sepsis occurred on post burn day (PBD) 9 ± 5 in patients in the latter two groups. Patients died on PBD 18 ± 4 in SD group. Twenty healthy adult volunteers were chosen as healthy control group (HC). The age of subjects for observation among four groups, and total burn area and full-thickness burn area of patients among NS, SS, and SD groups were compared. Serum was isolated from blood samples collected from each patient every day from day of admission till PBD 20 to determine the contents of IL-6 and IL-10 by ELISA, and the same determinations were done in HC group. Data of trial subjects were processed with one-way analysis of variance. Data of IL-6 and IL-10 contents were processed with analysis of variance of repeated measure data and SNK method (q test). RESULTS: (1) There was no significant statistical difference among four groups in age (F = 2.090, P > 0.05). Total burn areas of patients in SS and SD groups were significantly larger than that in NS group (q test, with P values both below 0.05), and total burn area of patients in SD group was obviously larger than that in SS group (q test, P < 0.05). Full-thickness burn areas of patients in SS and SD groups were significantly larger than that in NS group (q test, with P values both below 0.05). (2) Serum contents of IL-6 of patients in NS, SS, and SD groups from PBD 1 to 20 were obviously higher than that of volunteers in HC group. There was no significant statistical difference among NS, SS, and SD groups in serum contents of IL-6 from PBD 1 to 7 (with F value from 0.188 to 2.897, P values all above 0.05). Serum content of IL-6 of patients in NS group decreased from PBD 4. Serum content of IL-6 of patients in SS group decreased gradually from PBD 13, but that in SD group increased continuously at the same time points. Serum contents of IL-6 of patients in NS group [(262 ± 25) pg/mL on PBD 8] were lower than those in SS group [(287 ± 38) pg/mL on PBD 8, q test, P < 0.05] and SD group [(299 ± 22) pg/mL on PBD 8, q test, P < 0.05] from PBD 8. Serum contents of IL-6 of patients in SS group [(300 ± 33) pg/mL on PBD 13] were obviously lower than those in SD group [(338 ± 22) pg/mL on PBD 13, q test, P < 0.05] from PBD 13. (3) Serum contents of IL-10 of patients in NS, SS, and SD groups were higher than that in HC group at each time point. There was no significant statistical difference among NS, SS, and SD groups in serum contents of IL-6 from PBD 1 to 5 (with F values from 1.802 to 2.538, P values all above 0.05). Serum content of IL-10 of patients in NS group was obviously lower than that of patients in SD group from PBD 6 (q test, P values all below 0.05). On PBD 8, serum content of IL-10 of patients in SS group [(54 ± 19) pg/mL] was obviously lower than that in SD group [(91 ± 23) pg/mL, q test, P < 0.05]. The sum of sensitivity (83.33%, 10/12) and specificity (91.67%, 33/36) minus 1 was maximum when the critical value of IL-10 content was set at 77 pg/mL based on the comparison between SS group and SD group in serum content of IL-10 on PBD 8. CONCLUSIONS: The occurrence and outcome of sepsis is related to burn area and depth when the patients are in similar age. Serum contents of IL-6 and IL-10 play important roles in the pathogenesis of sepsis after burn. IL-6 content in early stage shall not be used in predicting the prognosis of patients with sepsis. IL-10 continuously higher than 77 pg/mL in early stage forecasts unfavorable prognosis of patient.