Muscle fibers lacking dystrophin undergo a long-term alteration of Ca2+ homeostasis, partially caused by a leaky Ca2+ release ryanodine (RyR) channel. S48168/ARM210, an RyR calcium release channel stabilizer (a Rycal compound), is expected to enhance the rebinding of calstabin to the RyR channel complex and possibly alleviate the pathologic Ca2+ leakage in dystrophin-deficient skeletal and cardiac muscle. This study systematically investigated the effect of S48168/ARM210 on the phenotype of mdx mice by means of a first proof-of-concept, short (4 wk), phase 1 treatment, followed by a 12-wk treatment (phase 2) performed in parallel by 2 independent laboratories. The mdx mice were treated with S48168/ARM210 at two different concentrations (50 or 10 mg/kg/d) in their drinking water for 4 and 12 wk, respectively. The mice were subjected to treadmill sessions twice per week (12 m/min for 30 min) to unmask the mild disease. This testing was followed by in vivo forelimb and hindlimb grip strength and fatigability measurement, ex vivo extensor digitorum longus (EDL) and diaphragm (DIA) force contraction measurement and histologic and biochemical analysis. The treatments resulted in functional (grip strength, ex vivo force production in DIA and EDL muscles) as well as histologic improvement after 4 and 12 wk, with no adverse effects. Furthermore, levels of cellular biomarkers of calcium homeostasis increased. Therefore, these data suggest that S48168/ARM210 may be a safe therapeutic option, at the dose levels tested, for the treatment of Duchenne muscular dystrophy (DMD).—Capogrosso, R. F., Mantuano, P., Uaesoontrachoon, K., Cozzoli, A., Giustino, A., Dow, T., Srinivassane, S., Filipovic, M., Bell, C., Vandermeulen, J., Massari, A. M., De Bellis, M., Conte, E., Pierno, S., Camerino, G. M., Liantonio, A., Nagaraju, K., De Luca, A. Ryanodine channel complex stabilizer compound S48168/ARM210 as a disease modifier in dystrophin-deficient mdx mice: proof-of-concept study and independent validation of efficacy.

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Background: Free flap reconstruction of the lower limb following trauma often suffers higher complication rates than other areas of the body. The choice of muscle or fasciocutaneous free flap is an area of active debate. Methods: A systematic review of EMBASE, MEDLINE, Pubmed, and Cochrane register from inception to January 10, 2022 was performed. Articles were assessed using the methodological index for non-randomized studies (MINORS) instrument. The primary outcome was to assess and compare the major surgical outcomes of partial or total flap failure, re-operation, and amputation rates. Results: Seventeen studies were included. All studies were retrospective in nature, of level three evidence, and published between 1986 and 2021. The most common muscle and fasciocutaneous free flaps used were latissimus dorsi flap (38.1%) and anterolateral thigh flap (64.8%), respectively. Meta-analysis found no significance difference in rates of total flap failure, take-back operations, or limb salvage, whereas partial flap failure rate was significantly lower for fasciocutaneous flaps. The majority of studies found no significant difference in complication rates, osteomyelitis, time to fracture union, or time to functional recovery. Most, 82.4% (14/17) of the included studies were of high methodological quality. Conclusions: The rate of total flap failure, re-operation, or limb salvage is not significantly different between muscle and fasciocutaneous free flaps after lower limb reconstruction following trauma. Partial flap failure rates appear to be lower with fasciocutaneous free flaps. Outcomes traditionally thought to be managed better with muscle free flaps, such as osteomyelitis and rates of fracture union, were comparable.

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This is an Open Journal Systems article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. AbstractPurpose: The purpose of this study is to identify if the previously reported declining interest in surgery amongst medical students persists, and also to provide more descriptive analysis of trends by surgical specialty and medical school. Our hypothesis is that the previously reported decreasing interest in surgery remains constant for some surgical disciplines. Methods:The Canadian Resident Matching Service and the Association of Faculties of Medicine of Canada provided data for this study. Several metrics of interest in surgery, including overall application trends, applications by discipline, and rankings by school of graduation were evaluated. Descriptive statistics and linear regression modeling were used. Results:Between 2007 and 2017 the number of non-surgical residency positions and Canadian medical graduates increased significantly. However, the number of surgical residency positions and applications to surgical programs did not change significantly. The number of rankings to orthopedic and vascular surgery decreased significantly. Likewise, applicants to general, orthopedic, plastic, otolaryngology, and vascular surgery decreased significantly. Vascular surgery saw a significant decrease in first choice rankings. Total rankings to surgical programs increased significantly at McGill, with no significant change at other Canadian institutions. Conclusions:The findings of this study suggest that while the number of applicants to surgical residency positions has been consistent, it is not keeping pace with the growing number of both CMGs and non-surgical residency Canadian Medical Education Journal 2019 xx positions. Furthermore, by using other measures of medical student interest in surgical specialties, such as the total number of rankings to a specialty through the residency matching process, the total number of applicants applying to a surgical discipline and the total number of first choice ranks that each surgical discipline received, we have demonstrated that there is a possible declining interest in some surgical disciplines Résumé Objectif : Cette étude vise à établir s'il persiste un déclin de l'intérêt pour la chirurgie parmi les étudiants en médecine, etfournir une analyse plus descriptive des tendances par spécialité chirurgicale et par faculté de médecine. Notre hypothèse est que le déclin précédemment rapporté de l'intérêt pour la chirurgie reste constant pour certaines disciplines chirurgicales.Méthodes : Le Service canadien de jumelage des résidents et l'Association des facultés de médecine du Canada ont fourni les données pour la présente étude. Plusieurs paramètres d'intérêt en chirurgie ont été évalués, dont les tendances globales des demandes d'admission, les demandes par discipline et les classements p...

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Background: Metastatic lesions to the hand or wrist are rare and can mimic inflammatory and benign processes such as gout and infections. This often leads to misdiagnosis, underreporting, and delays in treatment. The purpose of this study was to examine all known cases of metastasis to the hand or wrist available in the literature and to analyze demographic trends, metastasis characteristics, and clinical course, and provide recommendations for management. Methods: An online systematic review of MEDLINE, Embase, PubMed, and the Cochrane Library from inception to January 7, 2022, was completed. Studies outlining the care of a patient with acrometastases of the hand were included. Data extracted included age, sex, site of primary tumor and metastasis, presence of other metastases, time from primary diagnosis to acrometastasis diagnosis, misdiagnosis, treatment, and survival. Results: Between 1889 and present, 871 lesions were described in 676 patients who met the inclusion criteria. There was no predilection for hand dominance or site of previous trauma. The mean age among patients was 59.5 (1.5-91) years, and male sex was more common (64.6%). The most common primary cancer source was the lung (39.2%), followed by the kidney (10.8%). The distal phalanx was the most frequently cited tumor location (33.7%). Mean survival after diagnosis of acrometastasis was 6.3 months (0.25-50) ± 11.5 months. Conclusion: Acrometastasis remains an uncommon presentation of metastatic disease with poor prognosis. Treatment currently focuses on pain management and optimizing functional outcomes. Our review led to the development of 7 treatment recommendations when managing these patients.

Objective To assess the effect the Pre-clerkship Residency Exploration Program (PREP) had on student career interest and improving understanding of physical medicine and rehabilitation (PMR). Design During a 2-week program, students were exposed to a PMR elective, workshop, career presentation, and panel discussion with PMR residents. Interest and understanding were assessed using pre- and postprogram questionnaires. Setting PREP was held at a Canadian medical school during the summer between the second and third years of undergraduate medical training. Participants Second-year medical student participants (N=40) (26 women and 14 men, aged 20 to >30 y) were randomly selected from 74 applicants at a Canadian medical school. Interventions Of the 40 program participants, 20 participated in a PMR elective and specialty-specific workshop. The full cohort of 40 participants participated in the PMR career presentation and PMR resident panel discussion. Main Outcome Measure Primary outcome measure was an increase in understanding of the PMR specialty. Results Understanding of the roles and responsibilities of physiatrists increased significantly, with larger trends in those with greater exposure time. After PREP, comfort level in common PMR procedures also significantly increased. Higher exposure time was correlated with an increased top 3 career selection. Student interest in PMR did not significantly change after the program. Conclusion Although no statistically significant effects were found from the 2-week PREP in this population in terms of career choice, benefits were found in the participants comfort with PMR procedures and understanding the roles and responsibilities of physiatrists. A brief exposure as part of a 2-week summer elective is beneficial for career decision planning and may be feasible to implement in medical curricula.