Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interfaces Versus Standard Management in the Treatment of Limb Amputation: A Systematic Review and Meta-Analysis.

Introduction: Painful neuromas are a common postoperative complication of limb amputation often treated with secondary reinnervation. Surgical reinnervation include Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interface (RPNI), and can be primary and secondary. The aim of this review is to assess the effects of primary TMR/RPNI at the time of limb amputation on the incidence and intensity of post-operative neuroma and pain. Methods: This review was registered a priori on PROSPERO (CRD42021264360). A search of the following databases was performed in June 2021: Medline, EMBASE, and CENTRAL. Unpublished trials were searched using clinicaltrials.gov. All randomized and non-randomized studies assessing amputation with a reinnervation strategy (TMR, RPNI) were included. Outcomes evaluated included the incidences of painful neuroma, phantom limb pain (PLP), residual limb pain (RLP), as well as severity of pain, and Pain intensity, behavior, and interference (PROMIS). Results: Eleven studies were included in this systematic review, and five observational studies for quantitative synthesis. Observational study evidence suggests that TMR/RPNI results in a statistically significant reduction in incidence, pain scores and PROMIS scores of PLP and RLP. Decreased incidence of neuromas favored primary TMR/RPNI, but this did not achieve statistical significance (p = 0.07). Included studies had moderate to critical risk of bias. Conclusion: The observational data suggests that primary TMR/RPNI reduces incidence, pain scores and PROMIS scores of PLP and RLP. Going forward, randomized trials are warranted to evaluate this research question, particularly to improve the certainty of evidence.

Introduction: Les névromes douloureux sont une complication postopératoire courante de l'amputation d'un membre qui est souvent traitée par réinnervation secondaire. La réinnervation chirurgicale inclut la réinnervation musculaire ciblée (TMR) et l'interface nerveuse périphérique régénérative (RPNI) qui peuvent être primaires ou secondaires. Le but de cette revue était d'évaluer les effets de la TMR/RPNI primaires au moment de l'amputation du membre sur l'incidence et l'intensité du névrome et de la douleur postopératoire. Méthodes: Cette revue a été enregistrée a priori sur PROSPERO (CRD42021264360). Une recherche a été réalisée en juin 2021 dans les bases de données suivantes : MEDLINE, EMBASE et CENTRAL. Les essais non publiés ont été recherchés à l'aide du site clinicaltrials.gov. Toutes les études randomisées et non randomisées évaluant l'amputation avec stratégie de réinnervation (TMR, RPNI) ont été incluses. L'évaluation des résultats a inclus l'incidence des névromes douloureux, des douleurs du membre fantôme (PLP), de douleur résiduelle du membre (RLP) ainsi que la sévérité de la douleur, l'intensité de la douleur, le comportement et l'interférence (PROMIS). Résultats: Onze études ont été incluses dans cette revue systématique et cinq études observationnelles pour la synthèse quantitative. Les données probantes d'étude observationnelle suggèrent que la TMR/RPNI entraîne une réduction statistiquement significative de l'incidence, des scores de douleur et des scores PROMIS des PLP et RLP. La baisse de l'incidence des névromes favorisait les TMR/RPNI primaires, mais sans atteindre la signification statistique (P = 0,07). Les études incluses comportaient des risques de biais modérés à critiques. Conclusion: Les données observationnelles suggèrent que les TMR/RPNI réduisent l'incidence, les scores de douleur et les scores PROMIS de PLP et RLP. La réalisation d'essais randomisés est justifiée pour aller de l'avant et évaluer cette question de recherche, en particulier pour améliorer la certitude des données probantes.

Efficacy and safety of tixagevimab/cilgavimab as passive immunisation against COVID-19 infections in patients with hematological malignancies.

Monoclonal antibodies, as tixagevimab/cilgavimab, have been introduced as prophylaxis against COVID-19 infections in high-risk populations. However, data on efficacy are limited. This study investigates efficacy and tolerability of tixagevimab/cilgavimab in hematological patients under real-life conditions. Tixagevimab/cilgavimab was administered to 155 hematological patients (March-August 2022) at two Austrian centres. S/RBD-antibody assessments were performed before (T0), four weeks (T1), and six months (T2) after application. Side effects, the occurrence of COVID-19 infections, and the course of S/RBD-antibody titres were analysed retrospectively in relation to clinical variables. 155 hematological patients, who refused tixagevimab/cilgavimab, were included as a control group to compare the frequency of COVID-19 infections. Of all immunised patients (52.3% males; 91% triple vaccinated), 25.8% had a COVID-19 breakthrough infection (76% mild) compared to 43.9% in the control group. Patients with chronic lymphocytic leukaemia (CLL)/lymphoma were at highest risk of a COVID-19 infection (OR = 2.21; 95% CI 1.05-4.65; p = 0.037). After immunisation, a steep increase in median antibody levels (1193.4BAU/ml, IQR 0-2318.94) was observed in 67.8%, followed by a rapid decrease between T1 and T2 (465.95BAU/ml, IQR 0-1900.65.3) with the greatest declines in CLL/lymphoma (848.7BAU/ml, IQR 0-1949.6, p = 0.026). Side-effects occurred in 21.2% (CTCAE I/II). These real-world data indicate that S/RBD antibodies respond rapidly after passive immunisation in all hematological patients without safety concerns. Given the rapid decline in S/RBD antibodies, early booster immunisations should be considered for future scenarios in this vulnerable group.

Reporting bias in breast reconstruction clinical trials: Which and when clinical trials get published.

BACKGROUND: Reporting bias refers to the phenomenon in which the reporting of research findings is influenced by the nature of the results. Without the totality of evidence, clinical practice may be misguided. The objective of this work was to examine the extent of reporting bias in clinical trials of breast reconstruction surgery. METHODS: We searched and extracted data from all completed breast reconstruction clinical trials published in ClinicalTrials.gov from database inception to August 2020. Investigators sought to identify published full manuscripts of the registered trials. The primary outcome was classified as positive or nonpositive and trials were classified as industry or nonindustry funded. Time to publication in a peer-reviewed journal was computed and compared using time-to-event analysis. Trial characteristics associated with publication were evaluated using logistic regression. RESULTS: A total of 156 clinical trials were identified, of which, 53 trials were published. The median time to publication was 22 months (IQR, 13-35 months). Industry-funded studies were associated with a longer time to publication (HR = 2.4, p = 0.023) and publication in lower-impact journals (OR = 3.7, p = 0.048). Randomized clinical trials were associated with faster times to publication than nonrandomized studies (aHR = 3.2, p = 0.030). Statistical significance and the effect size were not associated with time to publication. CONCLUSIONS: We found no evidence that industry-funded trials were more likely to report a positive primary outcome. However, industry-funded trials were associated with a longer time to publication and publication in lower-impact journals.

RHOAL57V drives the development of diffuse gastric cancer through IGF1R-PAK1-YAP1 signaling.

Cancer-associated mutations in the guanosine triphosphatase (GTPase) RHOA are found at different locations from the mutational hotspots in the structurally and biochemically related RAS. Tyr42-to-Cys (Y42C) and Leu57-to-Val (L57V) substitutions are the two most prevalent RHOA mutations in diffuse gastric cancer (DGC). RHOAY42C exhibits a gain-of-function phenotype and is an oncogenic driver in DGC. Here, we determined how RHOAL57V promotes DGC growth. In mouse gastric organoids with deletion of Cdh1, which encodes the cell adhesion protein E-cadherin, the expression of RHOAL57V, but not of wild-type RHOA, induced an abnormal morphology similar to that of patient-derived DGC organoids. RHOAL57V also exhibited a gain-of-function phenotype and promoted F-actin stress fiber formation and cell migration. RHOAL57V retained interaction with effectors but exhibited impaired RHOA-intrinsic and GAP-catalyzed GTP hydrolysis, which favored formation of the active GTP-bound state. Introduction of missense mutations at KRAS residues analogous to Tyr42 and Leu57 in RHOA did not activate KRAS oncogenic potential, indicating distinct functional effects in otherwise highly related GTPases. Both RHOA mutants stimulated the transcriptional co-activator YAP1 through actin dynamics to promote DGC progression; however, RHOAL57V additionally did so by activating the kinases IGF1R and PAK1, distinct from the FAK-mediated mechanism induced by RHOAY42C. Our results reveal that RHOAL57V and RHOAY42C drive the development of DGC through distinct biochemical and signaling mechanisms.

"Facekit"-Toward an Automated Facial Analysis App Using a Machine Learning-Derived Facial Recognition Algorithm.

Introduction: Multiple tools have been developed for facial feature measurements and analysis using facial recognition machine learning techniques. However, several challenges remain before these will be useful in the clinical context for reconstructive and aesthetic plastic surgery. Smartphone-based applications utilizing open-access machine learning tools can be rapidly developed, deployed, and tested for use in clinical settings. This research compares a smartphone-based facial recognition algorithm to direct and digital measurement performance for use in facial analysis. Methods: Facekit is a camera application developed for Android that utilizes ML Kit, an open-access computer vision Application Programing Interface developed by Google. Using the facial landmark module, we measured 4 facial proportions in 15 healthy subjects and compared them to direct surface and digital measurements using intraclass correlation (ICC) and Pearson correlation. Results: Measurement of the naso-facial proportion achieved the highest ICC of 0.321, where ICC > 0.75 is considered an excellent agreement between methods. Repeated measures analysis of variance of proportion measurements between ML Kit, direct and digital methods, were significantly different (F[2,14] = 6-26, P<<.05). Facekit measurements of orbital, orbitonasal, naso-oral, and naso-facial ratios had overall low correlation and agreement to both direct and digital measurements (R<<0.5, ICC<<0.75). Conclusion: Facekit is a smartphone camera application for rapid facial feature analysis. Agreement between Facekit's machine learning measurements and direct and digital measurements was low. We conclude that the chosen pretrained facial recognition software is not accurate enough for conducting a clinically useful facial analysis. Custom models trained on accurate and clinically relevant landmarks may provide better performance.

Introduction : Il existe de multiples outils pour procéder aux mesures et à l'analyse des caractéristiques faciales à l'aide des techniques d'apprentissage machine de la reconnaissance faciale. Cependant, il reste plusieurs défis à relever avant qu'ils soient utiles en contexte clinique de chirurgie reconstructive et de chirurgie plastique. Des applications pour téléphone intelligent faisant appel à des outils d'apprentissage machine en libre accès peuvent être rapidement mises au point, déployées et mises à l'essai dans un cadre clinique. Dans la présente étude, les chercheurs comparent un algorithme de reconnaissance faciale sur téléphone intelligent pour effectuer les mesures directes et numériques nécessaires lors de l'analyse faciale. Méthodologie : Facekit est une application pour appareil photo de téléphone Android qui fait appel à ML Kit, une application de vision par ordinateur en libre accès créée par Google. Au moyen du module de repères faciaux, les chercheurs ont mesuré quatre proportions faciales chez 15 sujets en santé et les ont comparées aux mesures de surface directe et aux mesures numériques à l'aide de la corrélation intraclasse et de la corrélation de Pearson. Résultats : La mesure de la proportion nasofaciale a obtenu le coefficient de corrélation intraclasse (CCI) le plus élevé, à 0,321, où un CCI supérieur à 0,75 est considéré comme une excellente corrélation entre les méthodes. Des analyses de variance répétées des mesures de proportion entre le ML Kit, la méthode directe et la méthode numérique différaient considérablement (F[2,14] = 6 à 26, p<<0,05). Les mesures Facekit des ratios entre les mesures orbitale, orbitonasale, naso-orale et naso-faciale avaient une faible corrélation globale et étaient corrélées avec les mesures directes et numériques (R<<0,5, CCI<<0,75). Conclusion : Facekit est une application pour appareil photo de téléphone intelligent visant à analyser rapidement les caractéristiques faciales. La concordance entre les mesures d'apprentissage machine de Facekit et les mesures directes et numériques était faible. Les chercheurs concluent que le logiciel de reconnaissance faciale préentraîné n'est pas assez précis pour procéder à une analyse faciale utile sur le plan clinique. Des modèles personnalisés formés à des repères précis et pertinents sur le plan clinique donneront peut-être un meilleur rendement.

Gender Equality in Plastic Surgery Training: A Canadian Nationwide Cross-sectional Analysis.

Introduction: One of the important factors in achieving gender equity is ensuring equitable surgical training for all. Previous studies have shown that females get significantly lower surgical exposure than males in certain surgical specialties. Gender gap in surgical exposure has never been assessed in plastic surgery. To that end, the goal of this study was to assess if there are any differences in plastic surgery training between male and female residents. Methods: A survey was sent to all plastic surgery residency programs in Canada to assess the No. of surgeries residents operated on as a co-surgeon or primary assistant during their training. The survey also assessed career goals, level of interest in the specialty, and subjective perception of gender bias. Results: A total of 89 plastic surgery residents (59.3% participation rate) completed the survey and were included in the study. The average No. of reconstructive cases residents operated on as a co-surgeon or primary assistant was 245 ± 312 cases. There was no difference in either reconstructive or aesthetic surgery case logs between male and female residents (p > .05). However, a significantly larger proportion of females (39%) compared to males (4%) felt that their gender limited their exposure to surgical cases and led to a worsening of their overall surgical training (p < .001). Finally, a larger proportion of male residents were interested in academic careers while a larger proportion of female residents were interested in a community practice (p = .024). Conclusion: While there is no evidence of differences in the volume of logged cases between genders, female surgical residents still feel that their respective gender limits their overall surgical training. Gender inequalities in training should be addressed by residency programs.

Introduction: L'un des facteurs importants pour atteindre l'égalité des genres est d'assurer une formation chirurgicale équitable pour tous. Des études antérieures ont montré que les femmes ont une exposition significativement moindre à la chirurgie que les hommes dans certaines spécialités chirurgicales. L'écart entre genres pour l'exposition à la chirurgie n'a jamais été évalué en chirurgie plastique. À cette fin, la présente étude a eu pour objectif d'évaluer s'il y avait des différences dans la formation à la chirurgie plastique entre les résidents masculins et féminins. Méthodes: Une enquête a été envoyée à tous les programmes canadiens de résidence en chirurgie plastique pour évaluer le nombre d'interventions auxquelles les résidents ont participé en tant que co-chirurgien ou assistant principal au cours de leur formation. L'enquête a également évalué les objectifs de carrière, le niveau d'intérêt dans la spécialité et la perception subjective d'un biais lié au genre. Résultats: En tout, 89 résidents en chirurgie plastique (taux de participation de 59,3 %) ont répondu à l'enquête et ont été inclus dans l'étude. Le nombre moyen de cas de chirurgie reconstructrice au cours desquelles les résidents sont intervenus en tant que co-chirurgien ou principal assistant était de 245 ± 312 cas. Il n'y a pas eu de différence entre les journaux de cas, qu'il s'agisse de chirurgie reconstructrice ou de chirurgie esthétique entre résidents masculins et féminins (P > 0,05). Cependant, un nettement plus grand pourcentage de femmes (39 %) que d'hommes (4 %) estimait que leur genre limitait leur exposition à des cas chirurgicaux et résultait dans une aggravation de leur formation globale à la chirurgie (P < 0,001). Enfin, un plus grand pourcentage de résidents masculins était intéressé par une carrière universitaire alors qu'un plus grand pourcentage de résidentes était intéressé par une pratique dans la communauté (P = 0,024). Conclusion: Bien qu'il n'y ait pas de données probantes étayant des différences de volume des cas consignés entre les genres, les résidentes féminines en chirurgie pensent encore que leur genre limite leur formation chirurgicale. Les inégalités entre genres devraient être abordées par les programmes de résidence.

Use of Digital Stethoscope to Measure Heart Rate in Birds: Comparison of Different Counting Methods Using Phonocardiograms.

The high cardiac contractility of birds poses a challenge to traditional cardiac auscultation, particularly for the accurate determination of heart rate (HR). The objectives of this study were to 1) evaluate the feasibility of using phonocardiograms of adequate length and quality to assess HR in different avian species with a commercially available digital stethoscope, 2) compare 5 counting methods, including 2 direct reading methods (manual counting and using a semiautomatic computerized algorithm as a reference method) and 3 listening methods (progressive mental counting, counting by 10s, and counting with a smartphone application tap counter), and 3) obtain the HR in selected birds and identify a correlation between body weight and HR in different avian species. An inverse correlation on a logarithmic scale was identified between the mean body weight and HR in 60 different bird species (n = 211; R = -0.72, P < 0.0001). Manual reading of phonocardiograms was the most reliable method and had the highest agreement with the reference method; this was followed by the counting by 10s method, the tapping method, and the progressive mental counting method, which was the least reliable. The agreement levels for the different methods were comparable for HRs <200 beats per minute (bpm) in birds weighing >1 kg. For HRs >500 bpm in birds weighing <150 g, only the reading method maintained a good agreement level. A digital stethoscope can be a useful tool for accurately determining the HR in birds, including very small species with high HRs.

Radiographic Measurements of Internal Organs in Rhode Island Red Hybrid Hens (Gallus gallus domesticus) and Their Evolution During Egg Formation.

Backyard poultry hens are becoming very popular as pets, and thus the demand for treating the individual chicken is increasing. Few basic diagnostic techniques commonly used in small animal practice have been evaluated in this species. At the moment, there is no study in backyard hens describing radiographic measurements of internal organs contrary to psittacine birds or birds of prey. Moreover, the effect of egg laying on these measurements has not been studied in avian species even though it could affect radiographic measurements depending on the stage of egg formation. This is of particular concern in laying hens since they are able to lay on a daily basis. Thirteen adult hens and 3 juvenile Rhode Island red hybrid hens (Gallus gallus domesticus) were used to evaluate which organs can be reliably measured and to provide preliminary reference values for clinically healthy chickens. Additionally, whole body radiographs were collected every 2 hours over 24 hours in 5 adult hens to study the evolution of these measurements throughout egg formation. Organs that could be clearly delimitated on radiographs were measured, and the only organs that could be reliably measured were the heart and liver silhouettes. These measurements were significantly higher in adult compared to juvenile hens (P = 0.024). Among the different organ ratios, heart width: total liver width ratio was the only significantly different measurement and was higher in juvenile hens (P = 0.024). Hepatic silhouette measurements and ratios were found to increase over time (P < 0.02) but did not follow the progress of egg mineralization. Eggshell thickness was found to be a promising parameter to evaluate the stage of egg formation, and thus should be taken into account when trying to establish reference intervals for radiographic measurements of internal organs in laying hens.

Effect of Hooding on Physiological Parameters During Manual Restraint in Rhode Island Red Hybrid Hens (Gallus gallus domesticus).

Manual handling of chickens is required for many veterinary, research, and breeding procedures. This study aimed to assess the changes in physiological parameters over time during manual restraint of chickens, as well as the effect of hooding on these parameters. Heart rate, heart rate variability, respiratory rate, and body temperature were measured every 3 minutes for 15 minutes during manual restraint in 13 adult laying hens (Gallus gallus domesticus). Heart rate variability was significantly higher in hooded hens than in nonhooded hens (P= 0.003) but was not significant over time. Hooded hens were also found to have significantly lower heart rate (P = 0.043) and respiratory rate (P = 0.042) compared to nonhooded hens. Heart rate and respiratory rate significantly decreased over time, independent of the use of the hood (P = 0.008; P = 0.01, respectively). Temperature was found to increase significantly (P = 0.001) over time for both groups. Overall, hooding increased heart rate variability, a factor associated with a lower stress level, and decreased heart rate and respiratory rate. In conclusion, these data suggest that the use of the hood reduces stress levels in birds during manual restraint. Therefore, the use of the hood is encouraged for short (less than 15 minutes) painless procedures, such as physical examination or radiographic acquisition.

The appropriateness and quality of patient-reported outcome measures (PROMs) in plastic surgery randomized controlled trials: A systematic review.

BACKGROUND: Patient-reported outcome measures (PROMs) quantify patient perspectives to measure outcomes that matter to patients. The aim of this study was to assess the reporting of appropriateness and quality of PROM selection in plastic surgery randomized controlled trials (RCTs). METHODS: MEDLINE, Embase, and CENTRAL were searched from January 1, 2000, to June 5, 2022, to identify published RCTs within the plastic surgery literature. Included studies were categorized as follows: 1) a clearly defined patient-reported primary outcome; 2) a primary outcome could be inferred; or 3) no clear or implied primary outcome. The Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) database was consulted to assess the available literature on the PROMs. RESULTS: There were 130 plastic surgery RCTs identified. Of the 43 studies with a clear or inferred primary outcome, the percentage of studies that commented with supporting references on the PROM's appropriateness for the population, disease/condition, and outcome were 20.9% (n = 9/43), 18.6% (n = 8/43), and 27.9% (n = 12/43), respectively. The percentage of studies that commented on the PROM's validity, reliability, and responsiveness with supporting references were 34.9% (n = 15/43), 14.0% (n = 6/43), and 11.7% (n = 5/43), respectively. There were 21 unique PROMs identified; 28.6% (n = 6/21) were available in the COSMIN database. CONCLUSION: The majority of plastic surgery RCTs assessing patient-reported primary outcomes lack transparency surrounding PROM selection and quality. We recommend investigators conducting plastic surgery clinical research report explicitly why they used a particular PROM and support its appropriateness and psychometric properties with supporting references. Finally, they should familiarize themselves with the COSMIN initiative.

Visceral Haemoproteus minutus Infection in a Major Mitchell's Cockatoo (Lophochroa leadbeateri).

A 1-year-old major Mitchell's cockatoo (Lophochroa leadbeateri) was presented for evaluation of weakness, diarrhea with undigested seeds in the droppings, and weight loss. Leukocytosis with severe heterophilia, monocytosis, and lymphocytosis was noted on the complete blood count. Altered plasma biochemical parameters included a slight increase in creatine kinase and mild hypoproteinemia. Two blood smears before and after 2 days of treatment revealed mild polychromasia and anisocytosis but no blood parasites. Radiographic and computed tomographic imaging of the cockatoo were helpful in identifying airsacculitis, pneumonia, and gastrointestinal motility disorders. The patient died 5 days after treatment for the presenting clinical problems. On the gross postmortem examination, dark red foci in the ventricular muscle layers and 1-3-mm white foci in the myocardium, opaque air sacs, and dark lungs were identified. Histopathologic examination of submitted tissue samples found severe granulomatous ventriculitis and myocarditis with intralesional Haemoproteus species megalomeronts. Qualitative polymerase chain reaction testing for the cytochrome b (cyt b) gene performed on pooled heart, liver, kidney, and intestinal tissues identified 99.5% homology to Haemoproteus minutus. This case report demonstrates the expansion of the geographic range of H minutus to France and potentially to Belgium, which may compromise breeding and conservation of Australian parrots living outdoors. Challenging diagnosis, rapid disease progression, and the absence of validated treatment protocols for psittacine patients suggest that the use of preventive measures to reduce the presence of insect vectors such as hippoboscid flies and biting midges (Culicoides) should be considered. Haemoproteus minutus should be considered and potentially screened by polymerase chain reaction testing on blood samples, especially in the case of highly susceptible avian species (eg, Australian parrots in Europe) that present with sudden weakness, heterophilic leukocytosis, and monocytosis associated with mild anemia.

Opioid Consumption After Upper Extremity Surgery: A Systematic Review.

There is currently an overprescription of opioids, which may result in abuse and diversion of narcotics. The aim of this systematic review was to investigate opioid prescription practices and consumption by patients after upper extremity surgery. This review was registered a priori on Open Science Framework (osf.io/6u5ny) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A search strategy was performed using MEDLINE, Embase, PubMed, and Cochrane Central Register of Controlled Trials databases (from their inception to October 17, 2021). Prospective studies investigating opioid consumption of patients aged 18 years or older undergoing upper extremity surgeries were included. The Risk of Bias in Nonrandomized Studies of Interventions and Risk of Bias 2.0 tools were used for quality assessment. In total, 21 articles met the inclusion criteria, including 7 randomized controlled trials and 14 prospective cohort studies. This represented 4195 patients who underwent upper extremity surgery. Most patients took less than half of the prescribed opioids. The percentage of opioids consumed ranged from 11% to 77%. There was moderate to severe risk of bias among the included studies. This review demonstrated that there is routinely excessive opioid prescription relative to consumption after upper limb surgery. Additional randomized trials are warranted, particularly with standardized reporting of opioid consumption and assessment of patient-reported outcomes.

The Effects of Tranexamic Acid in Breast Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Tranexamic acid (TXA) is used in trauma and surgical settings. Its role in reducing postoperative blood loss in breast surgery remains unclear. The primary objective of this study was to determine the effect of TXA on postoperative blood loss in breast surgery. METHODS: Searches of the PubMed, Ovid MEDLINE, Embase, CINAHL, and Cochrane Central Register of Controlled Trials databases were performed from inception to April 3, 2020. Inclusion criteria were any retrospective reviews, prospective cohort studies, and randomized controlled trials that administered TXA (topical or intravenously) in the context of breast surgery. Quality of studies were evaluated using the risk of bias in randomized trials tool and the risk of bias in nonrandomized studies of interventions tool. Data were pooled, and a meta-analysis was performed. RESULTS: In total, seven studies were included, representing 1226 patients (TXA, 632 patients; control, 622 patients). TXA was administered as follows: topically (20 mL of 25 mg/mL TXA intraoperatively; n =258 patients), intravenously (1 to 3 g perioperatively; n = 743 patients), or both (1 to 3 g daily up to 5 days postoperatively; n = 253 patients). TXA administration reduced hematoma formation in breast surgery (risk ratio, 0.48; 95% CI, 0.32 to 0.73), with no effect on drain output (mean difference, -84.12 mL; 95% CI, -206.53 to 38.29 mL), seroma formation (risk ratio, 0.92; 95% CI, 0.60 to 1.40), or infection rates (risk ratio, 1.01; 95% CI, 0.46 to 2.21). No adverse effects were reported. CONCLUSION: The use of TXA in breast surgery is a safe and effective modality with low-level evidence that it reduces hematoma rates without affecting seroma rates, postoperative drain output, or infection rates.

A comparison of skin grafts versus local flaps for facial skin cancer from the patient perspective: protocol for a feasibility study.

BRIEF ABSTRACT: This is a protocol to assess feasibility of conducting a prospective cohort study comparing local flaps versus skin grafts for surgical excision of skin cancer from the face. INTRODUCTION: Skin cancer is the most common malignancy worldwide and the face is one of the most common locations of occurrence. Surgical excision is the most popular treatment for small lesions of the face. Defects can be reconstructed using local flaps or skin grafts. There is a paucity of literature evaluating outcomes after skin cancer surgery from the patient's perspective using valid measurement tools. The purpose of this study is to assess the feasibility of conducting a prospective observational cohort study. The primary outcomes include recruitment rates, eligibility rate, compliance of intervention and rate of completion of the primary outcome (FACE-Q scales) at 3 months. Secondary outcomes include examining patient characteristic and FACE-Q score differences between local flaps to skin grafts and adverse events. METHODS AND ANALYSIS: This study is a prospective cohort study consisting of an anticipated 30 patients aged ≥18 years. The study population will consist of a consecutive sample of non-melanoma facial skin cancer patients undergoing a skin graft or local flap. Patients will be followed and evaluated with the FACE-Q questionnaire at 2 weeks, 3 months, 6 months and 1 year post-operation. The following criteria will determine success: patients who meet eligibility criteria >70%; recruitment rate >70%; compliance with intervention >90%; rate of completion of full-scale prospective study primary outcome (FACE-Q at 3 months) >80%; retention rate at 6-month follow-up visit >70%. DISCUSSION: The findings of this study will be used to guide the sample size calculation for a future, large-scale prospective study.Trial registration: ClinicalTrials.gov (NCT04842279).

Novel homozygous GLDC variant causing late-onset glycine encephalopathy: A case report and updated review of the literature.

Glycine encephalopathy (MIM #605899) is an autosomal recessive inborn error of metabolism caused by pathogenic variants in three genes GLDC, AMT, GCSH encoding glycine cleavage enzyme system. We report an 8-year-old boy with late-onset glycine encephalopathy who harbors a novel homozygous GLDC likely pathogenic variant c.707G > A p.(Arg236Gln). Polyhydramnios was noted at fetal ultrasound. He displayed global developmental delay, craniofacial dysmorphism, convulsions. Our report expands the phenotypic and genetic spectrum of late-onset nonketotic hyperglycinemia.

Breastfeeding Outcome and Complications in Females With Breast Implants: A Systematic Review and Meta-Analysis.

Breast augmentation is a commonly performed cosmetic procedure. We set out to determine whether there was any effect on breastfeeding in females after breast implants. The aim of this study was to perform a systematic review and meta-analysis of the current evidence on breastfeeding outcome and complications in females with breast augmentation. A systematic review was performed utilizing MEDLINE, EMBASE, and all evidence-based medicine reviews from their respective inception dates to November 7, 2022, to assess outcomes of breastfeeding in females with breast implants (PROSPERO ID: CRD42022357909). This review was in accordance with both the Cochrane Handbook for Systematic Review of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eleven studies (4 prospective and 7 retrospective) in total were included in the review. A total of 8197 out of 9965 (82.25%) patients were successfully able to breastfeed after breast implants. Of 5 studies that included a control group, 343,793 of 388,695 (88.45%) women without breast implants successfully breastfed. A meta-analysis of 5 comparative studies showed a significant reduction of breastfeeding in females with breast implants, n = 393,686, pooled odds ratio = 0.45 (95% CI, 0.38 to 0.53). Complications described included pain, mastitis, insufficient or excessive lactation, and nipple inversion. There may be impairment in ability to breastfeed for females who receive breast implants when compared with those without. Additional studies on the topic are needed to further clarify the relationship.

Osmotic pump maintains plasma concentrations of meloxicam for 6 days after orthopedic surgery in pigeons (Columba livia).

OBJECTIVE: To determine the plasma concentration of meloxicam delivered via an osmotic pump in pigeons undergoing orthopedic surgery and if an osmotic pump is a suitable alternative to repeated oral administration of this drug. ANIMALS: 16 free-ranging pigeons presented for rehabilitation with a wing fracture. PROCEDURES: An osmotic pump filled with 0.2 mL of 40 mg/mL meloxicam injectable solution was implanted subcutaneously in the inguinal fold of 9 pigeons under anesthesia for orthopedic surgery. The pumps were removed 7 days postsurgery. Blood samples were collected before pump implantation (time 0) and 3, 24, 72, and 168 hours after pump implantation in 2 pigeons in a pilot study then at 12, 24, 72, and 144 hours in the 7 pigeons of the main study. The blood of 7 other pigeons receiving meloxicam at 2 mg/kg, PO, every 12 hours was also sampled between 2 to 6 hours after the last meloxicam administration. Plasma meloxicam concentrations were measured via high-performance liquid chromatography. RESULTS: The plasma concentration of meloxicam was maintained at significant levels from 12 hours to 6 days after osmotic pump implantation. Median and minimum plasma concentrations in implanted pigeons were maintained at the same or higher level than those measured in pigeons that received meloxicam at a dose known to be analgesic in this species. No adverse effects attributable to either osmotic pump implantation and removal or meloxicam delivery were observed in this study. CLINICAL RELEVANCE: Plasma concentrations levels of meloxicam in pigeons implanted with osmotic pumps were maintained at a similar concentration or higher than the suggested analgesic meloxicam plasma concentration in this species. Thus, osmotic pumps could represent a suitable alternative to the frequent capture and handling of birds for analgesic drug administration.

Clinical validation of a ctDNA-Based Assay for Multi-Cancer Detection: An Interim Report from a Vietnamese Longitudinal Prospective Cohort Study of 2795 Participants.

The SPOT-MAS assay "Screening for the Presence Of Tumor by Methylation And Size" detects the five most common cancers in Vietnam by evaluating circulating tumor DNA in the blood. Here, we validated its performance in a prospective multi-center clinical trial, K-DETEK. Our analysis of 2795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location. We present a case report to support further using SPOT-MAS as a complementary method to achieve early cancer detection and provide the opportunity for early treatment.

Structural investigation of human cystine/glutamate antiporter system xc - (Sxc -) using homology modeling and molecular dynamics.

The cystine/glutamate antiporter system xc - (Sxc -) belongs to the SLC7 family of plasma membrane transporters. It exports intracellular glutamate along the latter's concentration gradient as a driving force for cellular uptake of cystine. Once imported, cystine is mainly used for the production of glutathione, a tripeptide thiol crucial in maintenance of redox homeostasis and protection of cells against oxidative stress. Overexpression of Sxc - has been found in several cancer cells, where it is thought to counteract the increased oxidative stress. In addition, Sxc - is important in the central nervous system, playing a complex role in regulating glutamatergic neurotransmission and glutamate toxicity. Accordingly, this transporter is considered a potential target for the treatment of cancer as well as neurodegenerative diseases. Till now, no specific inhibitors are available. We herein present four conformations of Sxc - along its transport pathway, obtained using multi-template homology modeling and refined by means of Molecular Dynamics. Comparison with a very recently released cryo-EM structure revealed an excellent agreement with our inward-open conformation. Intriguingly, our models contain a structured N-terminal domain that is unresolved in the experimental structures and is thought to play a gating role in the transport mechanism of other SLC7 family members. In contrast to the inward-open model, there is no direct experimental counterpart for the other three conformations we obtained, although they are in fair agreement with the other stages of the transport mechanism seen in other SLC7 transporters. Therefore, our models open the prospect for targeting alternative Sxc - conformations in structure-based drug design efforts.