Therapeutic Potential and Challenges of Mesenchymal Stem Cell-Derived Exosomes for Peripheral Nerve Regeneration: A Systematic Review.

Gap injuries to the peripheral nervous system result in pain and loss of function, without any particularly effective therapeutic options. Within this context, mesenchymal stem cell (MSC)-derived exosomes have emerged as a potential therapeutic option. Thus, the focus of this study was to review currently available data on MSC-derived exosome-mounted scaffolds in peripheral nerve regeneration in order to identify the most promising scaffolds and exosome sources currently in the field of peripheral nerve regeneration. We conducted a systematic review following PRISMA 2020 guidelines. Exosome origins varied (adipose-derived MSCs, bone marrow MSCs, gingival MSC, induced pluripotent stem cells and a purified exosome product) similarly to the materials (Matrigel, alginate and silicone, acellular nerve graft [ANG], chitosan, chitin, hydrogel and fibrin glue). The compound muscle action potential (CMAP), sciatic functional index (SFI), gastrocnemius wet weight and histological analyses were used as main outcome measures. Overall, exosome-mounted scaffolds showed better regeneration than scaffolds alone. Functionally, both exosome-enriched chitin and ANG showed a significant improvement over time in the sciatica functional index, CMAP and wet weight. The best histological outcomes were found in the exosome-enriched ANG scaffold with a high increase in the axonal diameter and muscle cross-section area. Further studies are needed to confirm the efficacy of exosome-mounted scaffolds in peripheral nerve regeneration.

[Management of patients with complex ear deformities]. / Prise en charge des patients présentant des déformations complexes du pavillon de l'oreille.

Complex ear reconstruction requires specialized multidisciplinary care. Most patients present with microtia, often associated with hearing disorders. The management of these disorders is a priority, and reconstruction of the external ear remains optional. Nowadays, auricular reconstruction is based on the subcutaneous implantation of either autologous cartilage or an allogeneic implant. Autologous reconstruction requires highly specialized surgical expertise and involves harvesting rib cartilage but carries a lower risk of exposure compared to allogeneic implants. Both techniques yield good results with a high success rate and have a positive impact on the social functioning and daily life of patients.

La reconstruction complexe du pavillon auriculaire nécessite une prise en charge multidisciplinaire spécialisée. La majorité des patients nécessitant ce geste présentent une microtie, souvent associée à des troubles de l'audition. La prise en charge de ceux-ci est prioritaire et la reconstruction du pavillon reste facultative. Aujourd'hui, la reconstruction du pavillon se base sur l'implantation sous-cutanée d'une maquette de cartilage autologue ou d'un implant allogène. La reconstruction autologue demande une expertise chirurgicale hautement spécialisée et nécessite un prélèvement de cartilage costal mais présente un risque d'exposition inférieur par rapport à l'implant allogène. Les deux techniques permettent d'atteindre de bons résultats avec un taux de réussite élevé et un effet positif sur le fonctionnement social et le quotidien des patients.

Distally based peroneus brevis flap: Reconstruction of complex soft-tissue defects with bony infection of the lateral malleolus.

BACKGROUND: Managing wounds of the lateral malleolus is challenging owing to limited nearby tissues and possibly injured or inadequate vessels for free flaps, especially in case of underlying infections. Moreover, free flaps require specialized skills and are not suitable for every patient. Therefore, identifying reliable local alternatives is crucial. This retrospective study investigated the efficacy and safety of the distally based peroneus brevis muscle flap in treating complex and infected soft-tissue defects of the lateral malleolus. MATERIALS AND METHODS: A retrospective medical chart review of all patients who underwent a distally based peroneus brevis muscle flap reconstruction in the context of an infected lateral malleolus defect at Geneva University Hospitals between October 2020 and January 2024 was performed. RESULTS: Ten patients underwent lateral malleolus reconstruction using a distally based peroneus brevis muscle flap primarily to address post-traumatic infections. Flap coverage was performed within 4 weeks of infection onset for post-traumatic cases, alongside antibiotic treatment. The defects were moderate in size, with a median width of 2.5 cm and length of 5.5 cm. There were no complete or partial flap failures. All patients regained the ability to walk within 5 days after surgery. CONCLUSIONS: The distally based peroneus brevis muscle flap was efficient in managing complex and infected soft-tissue defects of the lateral malleolus, with control of infection in all patients and minimal donor-site morbidity.

Negative Pressure Wound Therapy versus Conventional Dressing in Lower Limb Fractures: Systematic Review and Meta-analysis.

Gustilo 3 lower limb fractures represent a significant challenge because of high complication risk. Two management strategies are commonly used for wound coverage until final closure: negative pressure wound therapy (NPWT) and conventional wound dressing (CWD), also described as standard wound coverage without subatmospheric pressure. Understanding their relative effectiveness is essential to improve patient outcomes. The aim of this systematic review and meta-analysis was to compare the efficacy of NPWT and CWD in Gustilo 3 lower limb fracture management, with a focus on overall rates, superficial infection, and deep infection rates. A systematic review of medical research databases was conducted in accordance with PRISMA guidelines. Studies comparing NPWT with CWD for Gustilo 3 fractures were included. Data extraction and quality assessment were performed. Treatment with CWD was associated with significantly higher rates of overall infection [pooled risk ratio (RR): 0.33; 95% confidence interval (CI): 0.14-0.51] and pooled risk difference (RD: 0.27; 95% CI: 0.15-0.38), superficial infection (pooled RR: 0.35; 95% CI: 0.04-0.66), and deep infection (pooled RR: 0.20; 95% CI: 0.02-0.38) compared with NPWT treatment. Overall infection rate remained significantly higher in the CWD group after analyzing only open tibia fractures (pooled RR: 0.35; 95% CI: 0.21-0.48). Nonunion rate was significant higher in the CWD group (pooled RR: 0.30; 95% CI: 0.00-0.59). Flap failure rate was similar in both groups (pooled RR: 0.09; 95% CI: -0.05 to 0.23). NPWT appears to be a reasonable option for wound management in Gustilo 3 lower limb fractures in terms of infection rates.

Medial Femoral Condyle Free Flap: A Systematic Review and Proportional Meta-analysis of Applications and Surgical Outcomes.

Background: Recalcitrant bone nonunion and osseous defect treatment is challenging and often requires vascularized bone transfer. The medial femoral condyle flap has become an increasingly popular option for reconstruction. The study aims at reviewing its different applications and synthesizing its surgical outcomes. Method: A systematic review including all studies assessing surgical outcomes of free medial femoral condyle flap for bone reconstruction in adults was conducted on January 31, 2023. Flap failure and postoperative complications were synthesized with a proportional meta-analysis. Results: Forty articles describing bony reconstruction in the head and neck, upper limb, and lower limb areas were selected. Indications ranged from bony nonunion and bone defects to avascular bone necrosis. Multiple flaps were raised as either pure periosteal, cortico-periosteal, cortico-cancellous-periosteal, or cortico-chondro-periosteal. A minority of composite flaps were reported. Overall failure rate was 1% [95% confidence interval (CI), 0.00-0.08] in head & neck applications, 4% in the lower limb (95% CI, 0.00-0.16), 2% in the upper limb (95% CI, 0.00-0.06), and 1% in articles analyzing various locations simultaneously (95% CI, 0.00-0.04). Overall donor site complication rate was 4% (95% CI, 0.01-0.06). Major reported complications were: femoral fractures (n = 3), superficial femoral artery injury (n = 1), medial collateral ligament injury (n = 1), and septic shock due to pace-maker colonization (n = 1). Conclusion: The medial femoral condyle flap is a versatile option for bone reconstruction with high success rates and low donor site morbidity.

Sensory and pain outcomes of neurotized skin-grafted free gracilis muscle flaps for lower extremity reconstruction.

BACKGROUND: Skin-grafted free gracilis muscle flaps are commonly used for lower extremity reconstruction. However, the loss of sensory function may lead to increased patient morbidity. This study prospectively analyzed the sensory and neuropathic pain outcomes of neurotized skin-grafted free gracilis muscle flaps used for the reconstruction of lower extremity defects. METHODS: Patients undergoing lower extremity reconstructions between 2020 and 2022 with neurotized skin-grafted free gracilis muscle flaps were prospectively enrolled. Sensation was assessed at 3, 6 and 12 months postoperatively using monofilaments, two-point discrimination, a vibration device, and cold and warm metal rods. Sensations were tested in the center and periphery of the flaps, as well as in the surrounding skin. The contralateral side served as the control. Patients completed the McGill pain questionnaire to evaluate patient-reported neuropathic pain. RESULTS: Ten patients were included. At 12 months postoperatively, monofilament values improved by 44.5% compared to that of the control site, two-point discrimination, cold detection, warmth detection, and vibration detection improved by 36.2%, 48%, 50%, and 88.2%, respectively, at the reconstructed site compared to those at the control site. All sensory tests were significantly better than 3 and 6 months values (p < 0.05), but remained significantly poorer than the control site (p < 0.05). Sensation in the central flap areas were similar to peripheral flap areas throughout the follow-up period (p > 0.05). The surrounding skin reached values similar to the control site at 12 months (p > 0.05). Moreover, 50% of patients reported neuropathic pain at 3 months postoperatively, 40% at 6 months, and 0% at 12 months (p < 0.05). CONCLUSION: Mechanical detection, vibration detection, temperature detection, and two-point discrimination significantly improved over time but without reaching normal sensory function at 12 months postoperatively. Neuropathic pain resolved at 12 months.

Role of Oxygen and Its Radicals in Peripheral Nerve Regeneration: From Hypoxia to Physoxia to Hyperoxia.

Oxygen is compulsory for mitochondrial function and energy supply, but it has numerous more nuanced roles. The different roles of oxygen in peripheral nerve regeneration range from energy supply, inflammation, phagocytosis, and oxidative cell destruction in the context of reperfusion injury to crucial redox signaling cascades that are necessary for effective axonal outgrowth. A fine balance between reactive oxygen species production and antioxidant activity draws the line between physiological and pathological nerve regeneration. There is compelling evidence that redox signaling mediated by the Nox family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases plays an important role in peripheral nerve regeneration. Further research is needed to better characterize the role of Nox in physiological and pathological circumstances, but the available data suggest that the modulation of Nox activity fosters great therapeutic potential. One of the promising approaches to enhance nerve regeneration by modulating the redox environment is hyperbaric oxygen therapy. In this review, we highlight the influence of various oxygenation states, i.e., hypoxia, physoxia, and hyperoxia, on peripheral nerve repair and regeneration. We summarize the currently available data and knowledge on the effectiveness of using hyperbaric oxygen therapy to treat nerve injuries and discuss future directions.

Successful Treatment of SIADH after Removal of Ruptured Breast Implants.

Local adverse reactions to breast implants and systemic reactions, mostly autoinflammatory, are numerously described in the literature. A patient presented at our institution with severe neurologic symptoms, including confusion and phasic troubles due to severe hyponatremia as part of syndrome of inappropriate antidiuretic hormone secretion (SIADH). Common etiologies for SIADH, primarily malignancy and central nervous system disturbances, have been ruled out by imaging. On the computed tomography scan of the thorax and abdomen, several masses were found in the pectoral region, inferior to the sternum and in the left axilla that were biopsied and verified as silicone. While evaluating the patient's medical history, the patient remembered having undergone breast augmentation with silicone implants several decades ago. The only explanation left for the persisting SIADH was her ruptured silicone implants, causing an inflammatory systemic reaction. Literature was searched, and one abstract was found, in which a woman presenting with SIADH was treated successfully after removal of her silicone breast implants. We offered the same treatment to our patient, and siliconomas were removed through a bilateral inframammary approach as well as axillary on the left. There were no complications encountered. Postoperatively, the patient's hyponatremia improved and normalized 1 month later even without hydric restriction. This potential form of etiology and treatment of SIADH is a novelty in the medical literature. Surgical removal of dispersed silicone is presumed to be the cure for this syndrome. It represents a diagnosis of exclusion after more life-threatening causes, such as central nervous system disturbances and malignancies, have been ruled out.

Incidence Trends of Melanoma of the Lower Limbs and Hips in the United States: A Surveillance, Epidemiology, and End Results Analysis 2000-2019.

BACKGROUND/AIM: No specific studies on the changes in the incidence of melanoma in the lower limbs and hips have been performed. This article aimed to examine trends in incidence rates of melanoma of the lower extremities in the U.S. PATIENTS AND METHODS: Data from the SEER program provided by the National Cancer Institute were used to examine trends in melanoma incidence from 2000 to 2019. Data analysis was performed from October to December 2022. RESULTS: A total of 192,327 cases of melanoma of the lower limbs and hips were diagnosed from 2000 to 2019 and included in our study. The incidence rate increased from 9.78 to 13.65 cases per 100,000 person-year and by an average annual percent change (AAPC) of 2% (95%CI=1.4-2.9%). The incidence increased by an AAPC of 2.1% in men and 1.7% in women. The incidence among people under 50 remained stable but increased among those over 50 years. Localized stage disease was the only stage where a continuously increasing incidence was observed, with an AAPC of 1.7% (95%CI=0.9-2.5%). Lentiginous melanoma showed the highest incidence trend rate with an AAPC of 2.3% (95%CI=1.0-3.5%). CONCLUSION: The incidence rate of melanoma in the lower limbs and hips increased between 2000 and 2019, with a higher incidence in men, reversing the previously described trend of higher incidence among women. However, incidence among people under 50 remained stable, suggesting the efficacy of prevention campaigns in this population.

Oncoplastic reduction mammoplasty: Systematic review and proportional meta-analysis of surgical outcomes.

BACKGROUND: Breast-conserving surgery is the standard of care for early-stage breast cancer but can often result in unsatisfactory cosmetic outcomes. Oncoplastic surgery aims to address these issues by combining local excision with plastic surgery techniques to improve oncologic and esthetic outcomes. By incorporating breast reduction techniques into cancer surgery, wider margins of excision can be achieved, leading to enhanced oncological safety and reduced recurrence rates without causing significant asymmetry. This systematic review and meta-analysis aims to provide an updated understanding of the surgical outcomes associated with oncoplastic reduction mammoplasty. METHODS: A systematic review of the literature was conducted according to PRISMA guidelines. Articles reporting post-operative outcomes following the oncoplastic reduction mammoplasty were included. A proportional meta-analysis of post-operative complications was performed to obtain their proportions and 95% Confidence Intervals (CIs). RESULTS: Eighteen studies met the inclusion criteria, representing a total of 2711 oncoplastic reduction mammoplasty procedures in 2680 patients. The overall complication rate was 20% (95% CI: 15-25%). The positive margin rate following oncoplastic reduction mammoplasty was 11% (95% CI: 6-17%). The re-excision rate was 6% (95% CI: 3-12%). The completion mastectomy rate was 3% (95% CI: 2-6%). CONCLUSIONS: Oncoplastic reduction mammoplasty is a safe and effective alternative to mastectomy and traditional breast-conserving surgery in the treatment of early-stage breast cancers.

Reverse Abdominoplasty in a Patient Presenting with Subcostal Nephrectomy Scar and Transverse Muscle Incisional Hernia.

Abdominoplasty and its different approaches have been widely described to improve abdominal wall contour. However, the role of reverse abdominoplasty, a less commonly performed technique, and its indications are not fully understood. Recent advances in the understanding of the vascular supply to the anterior abdominal wall have made this technique more popular, but there is still limited information available in the literature. In this report, we present the case of a 52-year-old woman who underwent a reverse abdominoplasty using an existing subcostal scar from a previous nephrectomy. No surgical complications were observed, and the patient achieved both aesthetic and functional improvement after 6 months of follow-up. Reverse abdominoplasty can be a reliable option for maintaining adequate blood supply and achieving a satisfactory cosmetic result in cases where there is a pre-existing subcostal scar.

Melanoma of the Lower Limbs and Hips: A Surveillance, Epidemiology, and End Results Analysis of Epidemiology and Survival 2000-2019.

BACKGROUND/AIM: Melanoma, an aggressive skin cancer, poses a significant threat to patients' lives, with lower limbs and hips being among the most affected regions. Epidemiology and survival outcomes of patients with melanoma in the lower extremities were investigated and compared to other sites to better understand tumoral behavior and identify predictors of decreased survival. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to search for all skin melanoma cases between 2000 and 2019. Demographic, pathological, and therapeutic factors were compared between affected regions. Overall and disease specific survival were calculated and compared among subgroups. A multivariable analysis was conducted to identify independent prognostic factors. RESULTS: A total of 50,109 patients were diagnosed with melanoma in lower limbs and hips, while 224,121 patients had melanomas in other areas. More women (70.8%) and younger people (mean 55.2 years, SD 16.5) were affected with lower extremities melanoma, with better survival rates than other skin regions. Factors associated with better survival included female sex, younger age, horizontal growth pattern melanomas, and surgery with <1 cm margins. CONCLUSION: Melanoma affecting lower extremities is commonly diagnosed in young females. Prognosis depends on age, stage at diagnosis, and histologic subtype, but remains better compared to other locations.

Inferior gluteal artery perforator (IGAP) flap in autologous breast reconstruction: A proportional meta-analysis of surgical outcomes.

BACKGROUND: The inferior gluteal artery perforator (IGAP) flap is an alternative technique for autologous breast reconstruction. In contrast to other commonly used techniques, there is a paucity of literature on the safety and efficacy of the IGAP flap. The aim of this study was to perform a systematic literature review and meta-analysis of postoperative outcomes and complications associated with the IGAP in autologous breast reconstructions to validate its safety. METHODS: A systematic review of literature was performed following PRISMA guidelines. Articles reporting post-operative outcomes of IGAP flaps in autologous breast reconstruction were included. A proportional meta-analysis of post-operative complications was performed to obtain their proportions with 95% confidence intervals (CIs). RESULTS: Seven studies met the inclusion criteria, which represented a total of 239 IGAP flaps in 181 patients The total flap loss rate was 3% (95% CI 0-8%), partial flap loss rate was 2% (95% CI 0-4%), haematoma rate was 3% (95% CI 0-7%), overall donor-site complication rate was 15% (95% CI 5-28%), overall recipient-site complication rate was 24% (95% CI 15-34%), and the overall complication rate was 40% (95% CI 23-58%). CONCLUSIONS: This meta-analysis provides comprehensive knowledge on the safety and efficacy of the IGAP flap in autologous breast reconstruction. It evidences the IGAP flap in autologous breast reconstruction's overall safety and validates its role as an effective option in breast reconstruction.

Extensive skin necrosis following total hip arthroplasty performed through the direct anterior approach.

BACKGROUND: Total hip arthroplasty is a widely performed surgical procedure, which enables patients to regain mobility, alleviates pain, and improves overall quality of life. Periarticular multimodal drug infiltration (PAI) is increasingly being used as an effective postoperative pain management, decreasing the systemic consumption of opioids. Extensive postoperative skin necrosis without a deep joint infection as a complication of total hip arthroplasty with PAI has not yet been described. CASE PRESENTATION: A 71-year-old patient who underwent total hip arthroplasty of the right hip for primary osteoarthritis through the Direct Anterior Approach presented postoperatively a large area of necrotic skin at the incision. Joint infection was excluded. An extensive debridement was performed and the tissue defect was reconstructed by a pedicled anterolateral thigh flap. The skin maintained a satisfactory appearance at 1 year postoperatively, and the hip was pain-free with restored ranges of motion. The patient was able to walk with no support and without limitation. CONCLUSION: We address the possible risk factors, discuss the use of epinephrine in PAI and explore possible treatment options for such a complication.

Mesenchymal Stem Cells in Nerve Tissue Engineering: Bridging Nerve Gap Injuries in Large Animals.

Cell-therapy-based nerve repair strategies hold great promise. In the field, there is an extensive amount of evidence for better regenerative outcomes when using tissue-engineered nerve grafts for bridging severe gap injuries. Although a massive number of studies have been performed using rodents, only a limited number involving nerve injury models of large animals were reported. Nerve injury models mirroring the human nerve size and injury complexity are crucial to direct the further clinical development of advanced therapeutic interventions. Thus, there is a great need for the advancement of research using large animals, which will closely reflect human nerve repair outcomes. Within this context, this review highlights various stem cell-based nerve repair strategies involving large animal models such as pigs, rabbits, dogs, and monkeys, with an emphasis on the limitations and strengths of therapeutic strategy and outcome measurements. Finally, future directions in the field of nerve repair are discussed. Thus, the present review provides valuable knowledge, as well as the current state of information and insights into nerve repair strategies using cell therapies in large animals.

Natural polysaccharides and their derivatives as potential medical materials and drug delivery systems for the treatment of peripheral nerve injuries.

Peripheral nerve repair following injury is one of the most serious problems in neurosurgery. Clinical outcomes are often unsatisfactory and associated with a huge socioeconomic burden. Several studies have revealed the great potential of biodegradable polysaccharides for improving nerve regeneration. We review here the promising therapeutic strategies involving different types of polysaccharides and their bio-active composites for promoting nerve regeneration. Within this context, polysaccharide materials widely used for nerve repair in different forms are highlighted, including nerve guidance conduits, hydrogels, nanofibers and films. While nerve guidance conduits and hydrogels were used as main structural scaffolds, the other forms including nanofibers and films were generally used as additional supporting materials. We also discuss the issues of ease of therapeutic implementation, drug release properties and therapeutic outcomes, together with potential future directions of research.

Cutaneous Melanoma of the Lip: A SEER Analysis of Epidemiology and Survival Outcomes With Focus on Surgery and Other Treatment Options.

BACKGROUND/AIM: Cutaneous melanoma of the lip (LM) is a rare malignancy with a low overall survival (OS). Few studies exist in the literature to aid its diagnosis and treatment. The purpose of this study was to assess the different treatment modalities by collecting cases from a single database and to provide current information on the epidemiologic characteristics of cutaneous lip melanoma. PATIENTS AND METHODS: The SEER database was searched for demographic, clinical-pathological, and therapeutic characteristics. The Kaplan-Meier model was used to analyze the overall survival (OS) of the study population, and survival curves were modelled. Univariable analysis between subgroups was carried out using the log-rank test. Surgery was further assessed with a multivariable cox regression, where the surgical procedure was adjusted for Breslow thickness. RESULTS: Patients aged 62.4 years on average, and 62.7% of them were males. A total of 386 melanomas of the cutaneous lip were identified. Mean OS was 155.1 months, median OS was 187 months, and 67.4% had localized disease. CONCLUSION: LM has a poor prognosis with a 5-year OS of 75.2%. Surgery remains the mainstay of treatment, with less invasive surgical approaches yielding a comparable overall survival to surgery with greater margins.

Demographic and Clinicopathological Factors as Predictors of Lymph Node Metastasis in Merkel Cell Carcinoma: A Population-Based Analysis.

Merkel cell carcinoma is an aggressive malignant skin tumor with high recurrence and low survival. Lymph nodal metastases are associated with a worse overall prognosis. Our aim was to assess how lymph node procedures and positivity are influenced by demographic, tumor, and treatment characteristics. The Surveillance, Epidemiology and End Results database was searched for all cases of Merkel cell carcinoma of the skin between 2000 and 2019. Univariable analysis was conducted using the chi-squared test with the aim of identifying differences in lymph node procedures and lymph node positivity for each variable. We identified 9182 patients, of which 3139 had sentinel lymph node biopsy/sampling, and 1072 had therapeutic lymph node dissection. Increasing age, increasing tumor size, and truncal location were associated with higher positive lymph node rates.