Precision Drug Repurposing: A Deep Learning Toolkit for Identifying 34 Hyperpigmentation-Associated Genes and Optimizing Treatment Selection.

BACKGROUND: Hyperpigmentation is a skin disorder characterized by a localized darkening of the skin due to increased melanin production. When patients fail first line topical treatments, secondary treatments such as chemical peels and lasers are offered. However, these interventions are not devoid of risks and are associated with postinflammatory hyperpigmentation. In the quest for novel therapeutic potentials, this study aims to investigate computational methods in the identification of new targeted therapies in the treatment of hyperpigmentation. METHODS: We used a comprehensive approach, which integrated text mining, interpreting gene lists through enrichment analysis and integration of diverse biological information (GeneCodis), protein-protein association networks and functional enrichment analyses (STRING), and plug-in network centrality parameters (Cytoscape) to pinpoint genes closely associated with hyperpigmentation. Subsequently, analysis of drug-gene interactions to identify potential drugs (Cortellis) was utilized to select drugs targeting these identified genes. Lastly, we used Deep Learning Based Drug Repurposing Toolkit (DeepPurpose) to conduct drug-target interaction predictions to ultimately identify candidate drugs with the most promising binding affinities. RESULTS: Thirty-four hyperpigmentation-related genes were identified by text mining. Eight key genes were highlighted by utilizing GeneCodis, STRING, Cytoscape, gene enrichment, and protein-protein interaction analysis. Thirty-five drugs targeting hyperpigmentation-associated genes were identified by Cortellis, and 29 drugs, including 16 M2PK1 inhibitors, 11 KRAS inhibitors, and 2 BRAF inhibitors were recommended by DeepPurpose. CONCLUSIONS: The study highlights the promise of advanced computational methodology for identifying potential treatments for hyperpigmentation.

Amputated Digit Replantations: Critical Digit Ischemia Timing, Temperature, and Other Predictors of Survival.

INTRODUCTION: A common consideration for replantation success is the ischemia time following injury and the preservation temperature. A classic principle within the hand surgery community describes 12 hours of warm ischemia and 24 hours of cold ischemia as the upper limits for digit replantation; however, these limits are largely anecdotal and based on older studies. We aimed to compare survival data from the large body of literature to aid surgeons and all those involved in the replantation process in hopes of optimizing success rates. METHODS: The PubMed database was queried on April 4th, 2023, for articles that included data on digit replantation survival in terms of temperature of preservation and ischemia time. All primary outcomes were analyzed with the Mantel-Haenszel method within a random effects model. Secondary outcomes were pooled and analyzed using the chi-square statistic. Statistical analysis and forest plot generation were completed with RevMan 5.4 software with odds ratios calculated within a 95% confidence interval. RESULTS: Our meta-analysis identified that digits preserved in cold ischemia for over 12 hours had significantly higher odds of replantation success than the amputated digits replanted with 0-12 hours of warm ischemia time ( P ≤ 0.05). The odds of survival in the early (0-6 hours) replantation group were around 40% greater than the later (6-12 hours) replantation group ( P ≤ 0.05). Secondary outcomes that were associated with higher survival rates included a clean-cut amputation, increased venous and arterial anastomosis, a repair that did not require a vein graft, and replants performed in nonsmokers ( P ≤ 0.05). DISCUSSION: Overall, these findings suggest that when predicting digit replantation success, time is of the essence when the digit has yet to be preserved in a cold environment. This benefit, however, is almost completely diminished when the amputated digit is appropriately maintained in a cold environment soon after injury. In conclusion, our results suggest that there is potential for broadening the ischemia time limits for digit replant survival outlined in the literature, particularly for digits that have been stored correctly in cold ischemia.

Repair of Sciatic Nerve Defect in Rats With Acellular Nerve Allograft Carrying Vascular Endothelial Cells.

BACKGROUND: Acellular nerve allografts (ANAs) were developed to replace the autologous nerve grafts (ANGs) to fill the peripheral nerve defects. Poor vascularization relative to ANGs has been a limitation of application of ANAs. METHODS: A total of 60 female Sprague-Dawley rats were assigned 3 groups. The rats in A group received ANGs, the rats in B group received ANAs, and the rats in C group were transplanted with ANA carrying endothelial cells (ANA + ECs). In the 1st, 2nd, 4th, and 12th postoperative weeks, 5 rats were selected from each group for evaluating sciatic function index (SFI), electrophysiology, maximum tetanic force recovery rate, tibialis anterior muscle weights recovery rate, and microvessel density. In the 12th postoperative week, the nerves were harvested and stained with toluidine blue and observed under an electron microscope to compare nerve fibers, myelin width, and G-ratio. RESULTS: All the rats survived. In the first and second postoperative weeks, more microvessels were found in the ANA + EC group. In the 12th postoperative week, the nerve fibers were more numerous, and G-ratio was smaller in the C group compared with the B group. The compound muscle action potential and maximum tetanic force recovery rate in the tibialis anterior muscle in the C group were better than those in the B group in the 12th postoperative week. The A group showed better performances in electrophysiology, maximum tetanic force, muscle wet weight, and nerve regeneration. CONCLUSION: ANA + ECs can promote early angiogenesis, promoting nerve regeneration and neurological function recovery.

Propionyl-l-carnitine mitigates ischemia-reperfusion injury in rat epigastric island flaps.

Background: Ischemia-reperfusion injury presents a substantial concern in various medical scenarios, notably in reconstructive surgery involving tissue flaps. Despite reports on the protective benefits of Propionyl-l-carnitine against ischemia-reperfusion injury, a thorough assessment of its efficacy in epigastric island flap models is currently lacking. Methods: Sixteen male Sprague-Dawley rats underwent epigastric island flap surgery and were divided into two groups: a Propionyl-l-carnitine group that received intraperitoneal Propionyl-l-carnitine prior to ischemia induction and a sham group that received saline treatment. A comprehensive evaluation was performed including macroscopic, biochemical and histological assessments encompassing measurements of flap survival areas, lipid peroxidation (malondialdehyde), glutathione, myeloperoxidase, nitric oxide and peripheral neutrophil counts. Results: The Propionyl-l-carnitine group demonstrated significantly increased flap survival areas when compared to the sham group. Administration of Propionyl-l-carnitine led to reduced malondialdehyde levels and elevated glutathione levels indicating a reduction in oxidative stress. Furthermore, the Propionyl-l-carnitine group exhibited lower myeloperoxidase levels, higher nitric oxide levels and reduced peripheral neutrophil counts, suggesting a decrease in the inflammatory response. Histopathological analysis revealed decreased levels of inflammation, necrosis, polymorphonuclear leukocyte infiltration and edema in the Propionyl-l-carnitine group. Additionally, vascularity was enhanced in the Propionyl-l-carnitine group. Conclusion: This study provides compelling evidence that Propionyl-l-carnitine administration effectively mitigates the deleterious effects of ischemia-reperfusion injury in epigastric island flaps. This is substantiated by the improved flap survival, diminished oxidative stress and inflammation, as well as the enhanced vascularity observed. Propionyl-l-carnitine emerges as a promising therapeutic intervention to enhance tissue flap survival in reconstructive surgery, warranting further exploration through larger-scale investigations.

Post-mastectomy Breast Reconstruction With Gas vs Saline Tissue Expanders: Does the Fill Type Matter?

The most common reconstruction technique following mastectomy is a 2-stage technique that involves tissue expansion followed by definitive implant-based reconstruction (IBR). Tissue expanders (TEs) have classically used saline for initial fill; however, TEs with an initial gas fill (GTE)-including the CO2-based AeroForm (AirXpanders, San Francisco, CA) TE and TEs initially filled with atmospheric air-have been increasingly used in the past decade. We aimed to compare the outcomes in breast reconstruction for tissue expanders initially filled with saline vs gas. PubMed was queried for studies comparing gas- and saline-filled tissue expanders (STEs) used in IBR. A meta-analysis was performed on major postoperative outcomes and the required expansion and definitive reconstruction time. Eleven studies were selected and included in the analysis. No significant differences existed between tissue expansion with GTEs vs STEs for 11 of the 13 postoperative outcomes investigated. Out of the complications investigated, only the risk of infection/cellulitis/abscess formation was significantly lower in the GTE cohort (odds ratio 0.62; 95% CI, 0.47 to 0.82; P = .0009). The time to definitive reconstruction was also significantly lower in the GTE cohort (mean difference [MD], 45.85 days; 95% CI, -57.80 to -33.90; P < .00001). The total time to full expansion approached significance in the GTE cohort (MD, -20.33 days; 95% CI, -41.71 to 1.04; P = .06). A cost analysis considering TE cost and infection risk determined that GTE use saved a predicted $2055.34 in overall healthcare costs. Surgical outcomes for both fill types were predominantly similar; however, GTEs were associated with a significantly decreased risk of postoperative infection compared to saline-filled TEs. GTEs could also reduce healthcare expenditures and require less time until definitive reconstruction after placement.

Risk Factors Associated With Misdiagnosis of Digital Glomus Tumor: A Retrospective Cohort Study.

OBJECTIVE: Glomus tumors are benign with unique triad of symptoms; however, the delayed diagnosis of these tumors is common. We investigated the possible risk factors for the misdiagnosis of digital glomus tumors, with an aim to treat these patients on time. METHODS: We conducted a retrospective cohort study of 104 patients with digital glomus tumors from October 2009 to February 2021. Data pertaining to sex, age, tumor locations, symptoms, imaging modalities, and clinical departments visited by the patients were extracted and analyzed through logistic regression. RESULTS: The duration of delayed diagnosis ranged from 3 months to 40 years (mean, 5.5 ± 6.5 years). The total misdiagnosis and recurrence rate are 34.6% and 3.8%, respectively. On the multivariate logistic regression, the misdiagnosis of digital glomus tumor was significantly associated with the clinical departments visited by the patients ( P < 0.001). The risk of misdiagnosis of nonhand surgery department visit is 179.741-fold higher than that of hand surgery department visit. CONCLUSIONS: The misdiagnosis rate of digital glomus tumor was closely related to the clinical departments visited by the patients. Hand surgeons are the first choice for the treatment of the tumor.

Heterotopic Ossification in Burn Patients.

ABSTRACT: Heterotopic ossification (HO) is a known complication of burns. The incidence of this complication is low. The etiology is unclear, but experiment conducted about HO can be significant. Currently, there are still no targeted, effective preventive and therapeutic measures against it. In this study, the relevant literature is summarized to demonstrate the potential pathogenic mechanisms, diagnosis, prophylaxis, and treatment measures of HO in burn patients. Early diagnosis and treatment can be effective in improving the prognosis of patients.

Clinical Application of the Musculoperiosteal Iliac Flap for Osteonecrosis of the Femoral Head.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) often affects young, active patients, and the femoral head's preservation is the primary goal of treatment for this disease. Vascularized iliac crest bone grafting is one of the many vascularized procedures used in treating ONHF. In some cases, we selectively performed this procedure using the musculoperiosteal iliac flap with the ascending branch of the lateral femoral circumflex artery for ONFH treatment. METHODS: Twelve patients (12 hips) with nontraumatic femoral head necrosis underwent musculoperiosteal iliac flap transfer with the ascending branch of the lateral femoral circumflex artery. The Harris Hip Score (HHS), visual analog scale score, and double-hip X-ray findings were used to analyze hip function changes within 10 days preoperatively and 6 and 12 months postoperatively. RESULTS: The mean HHS increased from 52.33 ± 3.34 preoperatively to 65.92 ± 5.04 6 months postoperatively and 79.75 ± 3.84 12 months postoperatively, and the data showed a statistical significance difference between preoperative and postoperative (F = 131.90, P < 0.01). The HHS at 6 and 12 months after surgery were significantly different (P < 0.01). The visual analog scale score showed the same trend. The x-ray of hip joints at 6 and 12 months after surgery showed that the femoral heads' shape and contour were good, femoral heads did not collapse, and the transferred bone flaps healed well. CONCLUSIONS: Musculoperiosteal iliac flap transfer with the ascending branch of the lateral femoral circumflex artery may be an effective method with a high clinical success rate for treating young patients with early to midstage ONFH.

Practice Diversity and Burn Center Growth: A 10-Year Profile of a State's Only Burn Center.

BACKGROUND: Growth and sustainability of burn practices can be impaired by irregular patterns of patient presentations, resulting in uneven utilization of facilities and staff. Burn care itself may not engage the full capacities of members of burn care teams. To address these problems, we organized a burn and reconstruction center to provide statewide acute care as Mississippi's only burn unit, to fully integrate reconstructive surgery into management of burn patients, and to diversify practice based on plastic surgery scope of practice. The first 10 years of this unit were reviewed to evaluate the performance of this scheme. METHODS: Burn admissions to and surgical procedures at this unit between July 2009 and June 2019 were analyzed to quantify acute burn care, secondary reconstructive burn care, and categories of practice growth. RESULTS: The unit admitted 5469 acute burn patients with a mortality rate of 1.49%. Comparing year 10 to year 1 of practice, acute burn admissions increased 58%. Total operations increased 276%. Acute burn procedures increased 176%. Secondary burn procedures increased 405%. Nonburn procedures increased 352%, with the subset of nonburn hand surgery increasing 1062%. CONCLUSION: Acute burn admissions and procedures increased over this period, but greater growth was seen in secondary burn procedures and nonburn procedures, especially hand cases. Expansion of practice into areas within the overall skill sets of burn team members was an effective growth strategy.

Fungal Infection in Burn Patents: A Review of 36 Case Reports.

OBJECTIVES: The aims of this study were to review recent fungal infection case reports published, evaluate the treatment regimens and clinical outcomes, and provide recommendations for future management. METHODS: A review of case reports published over the last decade was conducted. PubMed was searched to collect the relevant citations using a combination of the key words ("burn," "burned," "burns," "fungal," "fungi," and "fungus") in title or abstract. Case series, reviews, guidelines, and experimental and non-English studies were excluded. Statistical analyses were performed using Microsoft Excel 2019. RESULTS: A total of 36 case reports encompassing a total of 44 burn patients with fungal infection were included in the final analysis. Ablative surgeries, including surgical excision, debridement, skin graft, vitrectomy, teeth extraction, valve replacement, or amputation, were performed in 38 cases after the suspicion or identification of fungal infection. Twenty-nine of them were eventually discharged, yielding a survival rate of 76.3%. In the remaining 6 cases, ablative surgery was not mentioned and 3 of them eventually died, yielding a survival rate of 50%. The total mortality was 27.27%. Among the 12 death cases, 1 was infected with Candida albicans, 1 with non-albicans Candida, 2 with Aspergillus spp, 2 with Fusarium spp, 4 with Zygomycetes, and 2 with other fungal species. CONCLUSIONS: The overall mortality of fungal wound infection is still high in burn patients around the world, especially those infected with non-Candida species. Early diagnosis of fungal infection, early initiation of appropriate antifungal therapy, and effective surgical intervention are key measures to improve the treatment effect and reduce the mortality of fungal infection in burn patients.

Cesarean Delivery in the Management of Pregnancy Complicated by Burn Injuries.

ABSTRACT: Two cases of cesarean delivery in the management of burn injuries in 2 pregnant patients are presented to illustrate current utilization of cesarean delivery for infant rescue in maternal burn care.

The Coverage of Soft-Tissue Defects Around the Foot and Ankle Using Free or Local Flaps: A Comparative Cohort Study.

BACKGROUND: The purpose of this study was to compare the reconstructive outcomes of soft-tissue defects around foot and ankle with local or free flaps and attempt to provide an optimal strategy for these patients in comparison with the conventional guidelines. METHODS: A retrospective review of all continuous patients with foot and ankle reconstruction using different flaps from 2010 to 2018 was performed. Based on the flap types, the patients were divided into 2 groups: local flap group and free flap group. Outcomes were assessed according to the flap survival rate, recipient complications, aesthetic outcomes, and donor-site complications. RESULT: A total of 130 flaps including 47 free flaps and 83 local flaps were collected. There was no difference in flap survival rate between the 2 groups; however, a significant difference in aesthetic outcomes was noted between them: the free flap group presented a better overall aesthetic outcomes in comparison with the local flap group in terms of color and contour match. Moreover, local flaps had more donor-site morbidities including the need for skin grafting and wound infection. CONCLUSIONS: Free flaps in wound coverage of foot and ankle can achieve better outcomes than local flaps in terms of recipient benefits and donor-site compromise with a comparable flap survival rate.

Efficacy of Infection Control Measures in Managing Outbreaks of Multidrug-Resistant Organisms in Burn Units.

BACKGROUND: Multidrug-resistant organisms (MDROs) pose a significant threat to severe burn victims and represents a clear epidemic hazard in burn units. Several infection control measures have been implemented to control and manage the outbreaks of MDRO. The efficiency of those measures, however, remains controversial and an area of debate. A systematic review was conducted to evaluate the efficacy of infection control measures and the necessity of closing burn units in dealing with MDRO outbreaks. METHODS: Peer-reviewed articles were identified using PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases, focusing on infection control measures to manage MDRO outbreaks in burn units. RESULTS: Twenty-one studies that reported MDRO outbreaks in burn units met the inclusion criteria. The outbreaks were successfully controlled with interventions in 17 units (81%), partially controlled in 1 unit (4.7%), and uncontrolled in 3 units (14.3%). Infection control measures were implemented by screening patient (19 units), screening health care worker (17 units), obtaining environmental cultures (16 units), providing ongoing staff education (13 units), cohort or isolation (17 units), preemptive barrier precautions (10 units), improving hand hygiene (15 units), and enhanced cleaning and environmental disinfection (17 units). Closure of burn units occurred in 8 units, with outbreaks controlled in 6 of the units (75%). The reasons for unit closure include decontamination (4 units; 50%), outbreak investigation (1 unit; 12.5%), and uncontrolled outbreaks (3 units; 37.5%). The incidence of infection was significantly decreased in 4 units after the closure but rose again after reopening in 1 of the units. In 3 units, the spread was halted by other control measures, including change of hydrotherapy facilities, identification of staff transmission, and unit structure remodeling. CONCLUSIONS: Proper infection control measures play an important role in managing MDRO outbreaks in burn units. Temporary closure of burn units may be necessary to control the spread of nosocomial, and this option should be considered when other measures are ineffective.