Experimental Cranial Nerve Models in the Rat.

BACKGROUND: The intricacies of nerve regeneration following injury have prompted increased research efforts in recent years, with a primary focus on elucidating regeneration mechanisms and exploring various surgical techniques. While many experimental animals have been used for these investigations, the rat continues to remain the most widely used model due to its cost-effectiveness, accessibility, and resilience against diseases and surgical/anesthetic complications. A comprehensive evaluation of all the experimental rat models available in this context is currently lacking. METHODS: We summarize rat models of cranial nerves while furnishing descriptions of the intricacies of achieving optimal exposure. RESULTS: This review article provides an examination of the technical exposure, potential applications, and the advantages and disadvantages inherent to each cranial nerve model. CONCLUSION: Specifically in the context of cranial nerve injury, numerous studies have utilized different surgical techniques to expose and investigate the cranial nerves in the rat.

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.

Surgical Management of Postoperative Nipple Necrosis After Inverted Nipple Correction: Experiences From a Series of 25 Cases.

INTRODUCTION: The inverted nipple is a condition that affects approximately 10% of women and can have negative cosmetic and psychological implications. Surgical correction is a common approach to address this concern; however, this method can lead to complications, such as nipple necrosis. As comprehensive guidelines are currently lacking for postoperative nipple necrosis management, this study reports our experience in the management of postoperative nipple necrosis following initial attempt at surgical management. METHODS: A retrospective chart review was conducted and included female patients who experienced postoperative nipple necrosis after inverted nipple correction between 2018 and 2021. Cases of recurrent nipple retraction following partial necrosis and cases of complete nipple necrosis were evaluated. Recurrent nipple retraction was managed using various inverted nipple correction techniques, while complete necrosis required a modified C-V flap for nipple reconstruction. RESULTS: A total of 25 patients with a total of 42 affected nipples were included. Thirteen cases (26 nipples) experienced recurrent nipple retraction following partial necrosis, while 12 cases (16 nipples) exhibited complete necrosis. No significant predictive variables for these complications were found. Notably, all patients achieved successful healing following single-stage surgical repair. At 6 months postoperation, the treated nipples exhibited satisfactory healing and appearance and an absence of infection or papillary necrosis. Seven reconstructed nipples showed a mean loss of projection (2.7 ± 0.98) compared with only 2 nipples in the inverted nipple correction group. CONCLUSIONS: Distinguishing between recurrent nipple retraction after partial necrosis and complete nipple necrosis is crucial and should be taken into consideration when managing patients following inverted nipple correction.

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.

Principles and clinical applications of transcutaneous laser-assisted drug delivery: A narrative review.

Introduction: Transcutaneous laser-assisted drug delivery (LADD) is recognized as a developing therapy for skin disorders. Method: Current literature was reviewed to summarize current applications for LADD. Discussion: 12 clinical applications for this therapy are currently reported. Conclusion: LADD has potential for wide application in skin disorder treatment. Lay Summary: Laser assisted drug delivery improves drug bioavailability for treatment of skin disorders. This technique is being assessed clinically in disorders ranging from skin cancers to alopecia.

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.

Burn Injury-related Growth Factor Expressions and Their Potential Roles in Burn-related Neuropathies.

In the context of burn injury, growth factors (GFs) play a significant role in mediating the complex local and systematic processes that occur. Among the many systemic complications that arise following a burn injury, peripheral neuropathy remains one of the most common. Despite the broad understanding of the effects GFs have on multiple tissues, their potential implications in both wound healing and neuropathy remain largely unexplored. Therefore, this review aims to investigate the expression patterns of GFs prominent during the burn wound healing process and explore the potential contributions these GFs have on the development of burn-related peripheral neuropathy.

Professor Thomas Gibson and the Nobel Prize.

ABSTRACT: Professor Thomas Gibson collaborated in seminal clinical studies that contributed to a Nobel Prize later being awarded to Professor Peter Medawar.

Sophocles and the Wound of Philoctetes.

ABSTRACT: The dramatic story of the Greek hero Philoctetes encompasses a psychological concept of healing and a chronic wound that can be understood as a chronically infected traumatic pseudoaneurysm.

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.