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As of 2018, upwards of 42% of the United States adult population was considered obese based on Body Mass Index (BMI) scales. With the annual number of total joint replacements increasing, this study aimed to evaluate the impact BMI has on anatomic total shoulder arthroplasty (aTSA) outcomes.This was a retrospective analysis of 128 shoulders requiring primary aTSA. Patients were stratified into three cohorts based on their BMI at surgery: under/normal weight (BMI ≤25.0), overweight (BMI25,0 ≤30.0), and obese (BMI30.0). BMI was separately analyzed as a continuous variable. Clinical endpoints were range of motion scores, including forward elevation, external rotation, and internal rotation and patient reported outcomes, including Visual Analog Scale scores, American Shoulder and Elbow Surgeons scores, and the Simple Shoulder Test. Survivorship curves were calculated using Kaplan-Meier analysis.44, 50, and 34 patient shoulders were in the under/normal weight (U/NW), overweight, and obese cohorts respectively. The mean follow-up time was 11.4 years. The U/NW cohort had more females (73%) compared to the overweight (34%; p=0.0030) and obese (35%; p=0.0015) groups; no differences were seen in revision rates. BMI was negatively correlated with age at surgery (r = -0.19, p=0.014); it was not correlated with any of the six postoperative clinical endpoints. All three cohorts saw significant improvements in forward elevation, external rotation, internal rotation, VAS, ASES, and SST when compared preoperatively to postoperatively (p0.001). There were no significant differences between the three cohorts with respect to postoperative range of motion. Postoperative ASES scores were higher for the overweight cohort (82.6 ± 18.6) compared to both the U/NW (63.0 ± 25.1) and obese cohorts (70.5 ± 26.8) (p0.001). The overweight cohort also had higher SST (p=0.0012) postoperative scores compared to the U/NW and obese cohorts; VAS scores were comparable between groups (p=0.12). The non-obese (BMI30) group (n=94) showed 5-year, 10-year, and 15-year implant survival of 98.9%, 94.9%, and 83.9%, respectively compared to 97.1%, 93.7%, and 87.0% in the obese (BMI≥30) group (n=34). The log rank test revealed no significant difference in survival curves (p=0.82).To our knowledge, this is the longest follow-up study analyzing clinical endpoints stratified by BMI for aTSA. We saw that patients with a higher BMI required shoulder replacement at a significantly younger age. However, we also report that regardless of BMI all patients saw significant improvements in patient reported outcomes and range of motion scores postoperatively.

Objective Rotator cuff repair (RCR) is one of the most common arthroscopic procedures. Our investigation aims to quantify the impact that the COVID-19 pandemic had on RCR, specifically on patients with acute, traumatic injuries. Methods Institutional records were queried to identify patients who underwent arthroscopic RCR between March 1st to October 31st of both 2019 and 2020. Patient demographic, preoperative, perioperative, and postoperative data were collected from electronic medical records. Inferential statistics were used to analyze data. Results Totals of 72 and of 60 patients were identified in 2019 and in 2020, respectively. Patients in 2019 experienced shorter lengths of time from MRI to surgery (62.7 ± 70.5 days versus 115.7 ± 151.0 days; p = 0.01). Magnetic resonance imaging (MRI) scans showed a smaller average degree of retraction in 2019 (2.1 ± 1.3 cm versus 2.6 ± 1.2 cm; p = 0.05) butnodifference in anterior toposterior tear size between years (1.6 ± 1.0 cm versus 1.8 ± 1.0 cm; p = 0.17). Less patients in 2019 had a tele-health postoperative consultation with their operating surgeon compared with 2020 (0.0% versus 10.0%; p = 0.009). No significant changes in complications (0.0% versus 0.0%; p > 0.999), readmission (0.0% versus 0.0%; p > 0.999), or revision rates (5.6% versus 0.0%; p = 0.13) were observed. Conclusion From 2019 to 2020, there were no significant differences in patient demographics or major comorbidities. Our data suggests that even though the time from MRI to surgery was delayed in 2020 and telemedicine appointments were necessary, RCR was still performed in a time in early complications. Level of Evidence III. Resumo Objetivo Oreparodomanguitorotador (RMR) é um dos procedimentos artroscópi-cos maiscomuns. Nossapesquisavisaquantificar o impacto da pandemia de COVID-19 sobre o RMR, especificamente em pacientes com lesões agudas e traumáticas. Métodos Os prontuários institucionais foram consultados para identificação de pacientes submetidos ao RMR artroscópico entre 1° de março e 31 de outubro de 2019 e de 2020. Dados demográficos, pré-operatórios, perioperatórios e pós-operatórios dos pacientes foram coletados de prontuários eletrônicos. Os dados foram analisados por estatística inferencial. Resultados Totais de 72 ede60pacientes foramidentificados em 2019 e 2020, respectivamente. Os pacientes de 2019 apresentaram menor intervalo entre a ressonância magnética (RM) e a cirurgia (62,7 ± 70,5 dias versus 115,7 ± 151,0 dias; p = 0,01). Os exames de RM mostraram menor grau médio de retração em 2019 (2,1 ± 1,3 cm versus 2,6 ± 1,2 cm; p = 0,05), mas nenhuma diferença foi observada na extensão anteroposterior da laceração entre os anos (1,6 ± 1,0 cm versus 1,8 ± 1,0 cm; p = 0,17).Em 2019,o número de pacientes atendidos por seus cirurgiões em consultas pós-operatórias por telemedicina foi menor em comparação com 2020 (0,0% versus 10,0%; p = 0,009). Não foram observadas alterações significativas nas taxas de complicação (0,0% versus 0,0%; p > 0,999), de readmissão (0,0% versus 0,0%; p > 0,999) ou de revisão (5,6% versus 0,0%; p = 0,13). Conclusão Não houve diferenças significativas nos dados demográficos dos pacientes ou nas principais comorbidades entre 2019 e 2020. Nossos dados sugerem que, embora o intervalo entre a RM e a cirurgia tenha sido maior em 2020 e tenha havido necessidade de consultas por telemedicina, o RMR ainda foi realizado em tempo hábil e sem alterações significativas nas complicações precoces. Nível de Evidência III.

Several options exist for the management of irreparable rotator cuff tears without advanced arthritic changes. Tendon transfer poses technical challenges and has limited but promising outcomes data. Newer procedures such as balloon spacers and bursal acromial reconstruction are currently being investigated as a reproducible solution to this challenging problem. Ultimately the decision to continue with conservative measures, use one of the aforementioned techniques, or proceed with reverse shoulder arthroplasty remains a decision to be made in the context of patient's unique demands and provider comfort with the various modalities of treatment.

Introduction The purpose of this investigation was to determine the impact of simulator practice on task completion time, radiation use, success rate, and overall quality in a simulation of placing a distal locking screw. Methods This was a prospective, randomized control trial with one-to-one randomization and parallel group design. Twenty-eight volunteer novice trainees (medical and premedical students) participated. Using the TraumaVision Virtual Reality Simulator (Swemac, Sweden), subjects performed locking screw placement using the "perfect circle" technique. All subjects underwent a pretest and posttest on the simulator. The simulator group completed three additional simulator training sessions. The primary outcome variables were simulator-collected task completion time, success rate, radiation exposure time, and overall score. Results No notable difference existed between groups for pretest completion time, radiation use, success rate, or overall score. No notable difference in posttest radiation use or overall procedure score was found between groups. A significant difference existed in posttest total completion time (trained = 251.2 ± 103.4; control = 497.3 ± 223.1; P = 0.001) and success rate (64.3% versus 100%; P = 0.041) between groups. In addition, a significant difference existed in variance between groups for completion time (P = 0.029). Conclusions These findings suggest that independent simulator practice leads to improved speed and success rates; however, radiation use and overall score do not improve in the same manner. The design of simulator-based curriculum must be tailored to specific educational objectives and ultimately validated in the clinical setting.

The spatial organization of the genome plays a critical role in cell-specific biological functions such as gene expression. Existing genome-wide technologies reveal a dynamic interplay between chromatin looping and gene regulation, but the mechanisms by which regulatory interactions between genetic elements are established or maintained remain unclear. Here, we present CLOuD9, a CRISPR-based technology that can create de novo, pairwise chromatin interactions in cells. This technique for chromatin loop reorganization employs dCas9-targeting and ABI1-PYL heterodimerization. It is reversible, but can also establish epigenetic memory under certain conditions, which provides a way to dissect gene regulation mechanisms.

Fat grafting can reduce radiation‐induced fibrosis. Improved outcomes are found when fat grafts are enriched with adipose‐derived stromal cells (ASCs), implicating ASCs as key drivers of soft tissue regeneration. We have identified a subpopulation of ASCs positive for CD74 with enhanced antifibrotic effects. Compared to CD74− and unsorted (US) ASCs, CD74+ ASCs have increased expression of hepatocyte growth factor, fibroblast growth factor 2, and transforming growth factor β3 (TGF‐β3) and decreased levels of TGF‐β1. Dermal fibroblasts incubated with conditioned media from CD74+ ASCs produced less collagen upon stimulation, compared to fibroblasts incubated with media from CD74− or US ASCs. Upon transplantation, fat grafts enriched with CD74+ ASCs reduced the stiffness, dermal thickness, and collagen content of overlying skin, and decreased the relative proportions of more fibrotic dermal fibroblasts. Improvements in several extracellular matrix components were also appreciated on immunofluorescent staining. Together these findings indicate CD74+ ASCs have antifibrotic qualities and may play an important role in future strategies to address fibrotic remodeling following radiation‐induced fibrosis., CD74⩲ adipose‐derived stromal cells express multiple growth factors with antifibrotic activity. These cells decrease production of collagen type 1 by TGF‐B1 stimulated fibroblasts, and when used to enrich fat grafts, they promote remodeling of radiation‐induced fibrosis in the overlying skin.CD74⩲ adipose‐derived stromal cells express multiple growth factors with antifibrotic activity. These cells decrease production of collagen type 1 by TGF‐B1 stimulated fibroblasts, and when used to enrich fat grafts, they promote remodeling of radiation‐induced fibrosis in the overlying skin.

Purpose: Osteoarthritis (OA) of the knee is a debilitating, expensive, and prevalent disease, and interest in the non-surgical management of knee OA has grown recently. Our objective was to systema...

To identify variables associated with operative duration and intraoperative or perioperative complications after primary anterior cruciate ligament reconstruction (ACLR).Surgeons who performed a minimum of 20 arthroscopic cases per month were recruited for participation through the Arthroscopy Association of North America from 2011 through 2013. All participants agreed to voluntarily submit data for 6 months of consecutive knee and shoulder arthroscopy cases. Only subjects coded for ACLR were analyzed, whereas revision cases were excluded. ACLRs were subdivided into isolated ACLR, ACLR with minor concomitant procedures, and ACLR with major concomitant procedures. Patient, surgeon, and surgical variables were analyzed for their effect on operative duration and complications.One hundred thirty-five orthopaedic surgeons participated, providing 1,180 primary ACLRs (399 isolated ACLRs, 441 ACLRs plus minor procedures, and 340 ACLRs plus major procedures). Most surgeons were in private practice (72.8%). Most patients were male patients (58.8%), and the mean body mass index (BMI) was 26.2 ± 5.1. The overall mean operative duration was 95.9 ± 42.0 minutes (isolated ACLRs, 88.4 ± 36.8 minutes; ACLRs plus minor concomitant procedures, 90.1 ± 37.6 minutes; and ACLRs plus major concomitant procedures, 118.5 ± 112.4 minutes;Increasing patient age, private practice, ambulatory surgery center setting, and surgeon experience are associated with a shorter operative duration for ACLR. Although an increasing number of arthroscopic knee procedures performed by surgeons correlated with fewer complications, only increasing patient BMI significantly predicted odds of complications.Level IV, prognostic case series.

Avascular necrosis (AVN) of the humeral head is a debilitating pathology that can be managed with an array of treatments depending on disease staging. Humeral head arthroplasty for AVN has demonstrated good short-term improvements in pain and range of motion, but the published long-term outcomes data are limited. The objective of this study was to report long-term survivorship and outcomes for patients undergoing hemiarthroplasty (HA) or total shoulder arthroplasty (TSA) for the treatment of AVN of the humeral head.The practice of one fellowship-trained shoulder surgeon was queried for the surgical treatment of AVN of the humeral head via appropriate International Classification of Diseases, Ninth and Tenth Revision, codes. Sixteen shoulders that met inclusion criteria were identified. Demographics included the radiographic stage, age, sex, American Society of Anesthesiologists (ASA) score, and body mass index. The primary endpoint was survivorship of the implant. Secondary endpoints were range of motion in forward elevation, internal and external rotation, visual analog scale for pain, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form score, and the Simple Shoulder Test score.Of the 16 shoulders included in the study, 10 underwent HA and 6 underwent TSA. The TSA cohort was significantly older (mean 60.5 vs. 44.2, P = .005), with a higher mean ASA score (mean 3.0 vs. 2.13, P = .02) than the HA group. The 10-year survivorship rates were 88.9% for HA and 80% for TSA with no significant difference between groups. Survivorship data were available for a mean 13.0 ± 5.6 years' follow-up in the HA group and 13.8 ± 4.8 years in the TSA group. When compared to one another, the results between HA and TSA only differed in internal rotation, which was statistically significantly improved in the TSA group compared with HA (2.3 ± 2.6 compared with -3.0 ± 5.0, P = .03).The survivorship of both TSA and HA for the treatment of AVN was at least 80% at 10 years. Secondary endpoints, such as range of motion, pain, and shoulder function, improved significantly postoperatively in each cohort and were similar between the 2 groups, except for internal rotation, which had improved significantly more in the TSA group than in HA. Both TSA and HA are viable options for the treatment of AVN, each with durable long-term survival.

SummaryCongenital heart defects, the most common birth disorders, are the clinical manifestation of anomalies in fetal heart development - a complex process involving dynamic spatiotemporal coordination among various precursor cell lineages. This complexity underlies the incomplete understanding of the genetic architecture of congenital heart diseases (CHDs). To define the multi-cellular epigenomic and transcriptional landscape of cardiac cellular development, we generated single-cell chromatin accessibility maps of human fetal heart tissues. We identified eight major differentiation trajectories involving primary cardiac cell types, each associated with dynamic transcription factor (TF) activity signatures. We identified similarities and differences of regulatory landscapes of iPSC-derived cardiac cell types and their in vivo counterparts. We interpreted deep learning models that predict cell-type resolved, base-resolution chromatin accessibility profiles from DNA sequence to decipher underlying TF motif lexicons and infer the regulatory impact of non-coding variants. De novo mutations predicted to affect chromatin accessibility in arterial endothelium were enriched in CHD cases versus controls. We used CRISPR-based perturbations to validate an enhancer harboring a nominated regulatory CHD mutation, linking it to effects on the expression of a known CHD gene JARID2. Together, this work defines the cell-type resolved cis-regulatory sequence determinants of heart development and identifies disruption of cell type-specific regulatory elements as a component of the genetic etiology of CHD.

The acronym PHACE stands for the co-occurrence of posterior brain fossa malformations, hemangiomas, arterial anomalies, cardiac defects, and eye abnormalities. The majority of patients have a segmental hemangioma and at least one developmental structural anomaly. The etiology and pathogenesis are unknown. Here we discuss the candidate causative genes identified in a de novo analysis of whole genome sequencing of germline samples from 98 unrelated trios in which the probands had PHACE, all sequenced as part of the Gabriella Miller Kids First Pediatric Research Program. A g:Profiler pathway analysis of the genes with rare, de novo variants suggested dysregulation of the RAS/MAPK and PI3K/AKT pathways that regulate cell growth, migration, and angiogenesis. These findings, along with the developmental anomalies and the vascular birthmark, support including PHACE within the RASopathy family of syndromes.

Background Tobacco carcinogens have adverse effects on bone health and are associated with inferior outcomes following orthopedic procedures. The purpose of this study was to assess the impact tobacco use has on readmission and complication rates following shoulder arthroplasty. Methods The 2016–2018 National Readmissions Database was queried to identify patients who underwent anatomical, reverse, and hemi-shoulder arthroplasty. ICD-10 codes Z72.0 × (tobacco use disorder) and F17.2 × (nicotine dependence) were used to define “tobacco-users.” Demographic, 30-/90-day readmission, surgical complication, and medical complication data were collected. Inferential statistics were used to analyze complications for both the cohort as a whole and for each procedure separately (i.e. anatomical, reverse, and hemiarthroplasty). Results 164,527 patients were identified (92% nontobacco users). Tobacco users necessitated replacement seven years sooner than nonusers ( p Conclusion Comparatively, tobacco users required surgical correction earlier in life and had higher rates of readmission, revision, and complications in the short term following their shoulder replacement. However, when controlling for tobacco usage as an independent predictor of adverse outcomes, these aforementioned findings were lost for the cohort as a whole. Overall, these findings indicate that shoulder replacement in general is a viable treatment option regardless of patient tobacco usage at short-term follow-up, but this conclusion may vary depending on the replacement type used.

Background: LMNA , a gene encoding A-type lamin proteins (abbreviated as lamin A), is one of the most frequently mutated genes in dilated cardiomyopathy (DCM). The molecular mechanisms underlying cardiomyocyte dysfunction in LMNA -related DCM remain elusive, translating to the lack of disease-specific therapies. Lamin A has been shown to play a critical role in genome organization via interactions with the chromatin at specific regions called lamina-associated domains (LADs). However, little is known about whether DCM-causing LMNA mutations rearrange the genome conformation and chromosome accessibility. The overarching goal of this study is to define the role of genome organization in LMNA -related DCM. Methods: LMNA -related DCM was modeled in vitro using cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) from DCM patients carrying a frameshift mutation in the LMNA gene (c. 348_349insG; p. K117fs) and isogenic controls. We combined genome-wide single cell functional genomic and epigenomic mapping analyses to define the gene regulation and cis-regulatory interactions in isogenic iPSC-CMs. Results: Single-cell RNA-seq revealed global gene dysregulation in LMNA mutant compared to isogenic control iPSC-CMs. The homeodomain transcription factor PRRX1 was significantly upregulated in mutant cells. We showed that LAD integrity is disrupted at the PRRX1 locus in mutant iPSC-CMs. In agreement, DNA fluorescence in situ hybridization (FISH) revealed that the PRRX1 locus loses peripheral association and relocates towards the transcriptionally active nuclear interior in mutant iPSC-CMs. Correspondingly, single-cell assay for transposase accessible chromatin (ATAC)-seq showed increased chromatin co-accessibility at the PRRX1 locus, providing a plausible explanation for ectopic activation of PRRX1 in LMNA mutant iPSC-CMs. Conclusion: Our data suggest that LMNA haploinsufficiency disrupts the structure of LADs, leading to ectopic promoter interactions and altered gene expression in LMNA -related DCM iPSC-CMs. We identified PRRX1 as a promising candidate locus linking changes in LAD organization with gene dysregulation in LMNA -related DCM.

Accumulation of trimethylation of histone H3 at lysine 4 (H3K4me3) on immune-related gene promoters underlies robust transcription during trained immunity. However, the molecular basis for this remains unknown. Here we show three-dimensional chromatin topology enables immune genes to engage in chromosomal contacts with a subset of long noncoding RNAs (lncRNAs) we have defined as immune gene–priming lncRNAs (IPLs). We show that the prototypical IPL, UMLILO, acts in cis to direct the WD repeat-containing protein 5 (WDR5)–mixed lineage leukemia protein 1 (MLL1) complex across the chemokine promoters, facilitating their H3K4me3 epigenetic priming. This mechanism is shared amongst several trained immune genes. Training mediated by β-glucan epigenetically reprograms immune genes by upregulating IPLs in manner dependent on nuclear factor of activated T cells. The murine chemokine topologically associating domain lacks an IPL, and the Cxcl genes are not trained. Strikingly, the insertion of UMLILO into the chemokine topologically associating domain in mouse macrophages resulted in training of Cxcl genes. This provides strong evidence that lncRNA-mediated regulation is central to the establishment of trained immunity. This study shows that immune-related genes are primed for transcription by proximal lncRNAs. One such lncRNA, UMLILO, directs the WDR5–MLL1 complex to CXCL chemokine promoters, facilitating H3K4me3 deposition.

Purpose To compare differences in the contour of the anterior and posterior glenoid in 3-dimensional computed tomography reconstructions as a reason for variability in estimating glenoid bone loss. Methods Three reviewers digitally placed 11 points (1 at 6 o'clock, 5 from 3 to 6 o'clock, and 5 from 6 to 9 o'clock) along the inferior half of glenoid 3-dimensional computed tomography reconstructions of 32 cadaveric specimens. A best-fit circle for the whole glenoid was determined from all 11 points. The anterior 6 points determined an anterior-based circle, as for estimation of posterior bone loss. The posterior 6 points determined a posterior-based circle, as for estimation of anterior bone loss. The area and radii were determined for all circles. Individual intraclass correlations were used to evaluate reliability. Paired t-tests and Wilcoxon signed rank tests were used to compare areas and radii of the anterior and posterior circles relative to the best-fit glenoid circle. Significance was defined as P Results There was good-to-excellent inter-rater reliability for the overall best-fit circle (intraclass correlation coefficient [ICC] = 0.97 [95% confidence interval (CI), 0.95-0.99]), anterior circle (ICC = 0.82 [95% CI, 0.71-0.90]), and posterior circle (ICC = 0.78 [95% CI, 0.65-0.88]). The average area of the posterior-based circle was significantly greater than the area of the best-fit circle for the intact glenoid (111% [95% CI, 104.3%-117.7%]; P = .0016). The average radius of the posterior-based circle was significantly larger than the radius of the intact glenoid (105% [95% CI, 101.7%-108.3%]; P = .0042). There were no significant differences between the average area (96% [95% CI, 89.0%-103.0%]; P = .16) and average radius (97% [95% CI, 93.5%-100.5%]; P = .19) for the anterior-based circle relative to the actual whole glenoid. Conclusions Estimation of anterior glenoid bone loss based on the normal posterior glenoid rim may overestimate glenoid bone loss because of differences in the contour of the anterior and posterior glenoid, whereas estimations of posterior glenoid bone loss based on the anterior rim did not differ significantly from the intact glenoid. Clinical Relevance A circle based on the remaining intact portion of the injured glenoid may lead to an inaccurate estimate of glenoid bone loss.

Objective To define patient demographics, preoperative, and intraoperative surgical variables associated with successful or failed repair of bucket-handle meniscal tears. Design All patients who underwent arthroscopic repair of a bucket-handle meniscus tear at a single institution between May 2011 and July 2016 with minimum 6-month follow-up were retrospectively identified. Patient demographic, preoperative (including imaging), and operative variables were collected and evaluated. A Kaplan-Meier curve was generated to demonstrate meniscus repair survivorship. Results In total, 75 patients (78 knees) with an average age of 26.53 ± 10.67 years met inclusion criteria. The average follow-up was 23.41 ± 16.43 months. Fifteen knees (19.2%) suffered re-tear of the repaired meniscus at an average 12.24 ± 9.50 months postoperatively. Survival analysis demonstrated 93.6% survival at 6 months, 84.6% survival at 1 year, 78.4% survival at 2 years, and 69.9% survival at 3 years. There was significant improvement from baseline to time of final follow-up in all patient-reported outcome ( P < 0.05) except Marx score ( P = 0.933) and SF-12 Mental Subscale ( P = 0.807). The absence of other knee pathology (including ligament tear, contralateral compartment meniscal tear, or cartilage lesions) noted intraoperatively was the only variable significantly associated with repair failure ( P = 0.024). Concurrent anterior cruciate ligament reconstruction (vs. no concurrent anterior cruciate ligament reconstruction) trended toward significance ( P = 0.059) as a factor associated with successful repair. Conclusions With the exception of the absence of other knee pathology (including ligament tear, contralateral compartment meniscal tear, or cartilage lesions) noted intraoperatively, no other variables were significantly associated with re-tear. The results are relatively durable with 84.6% survival at 1 year. Surgeons should attempt meniscal repair when presented with a bucket-handle tear.

Purpose To determine the utility of modern arthroscopic simulators in transferring skills learned on the model to the operating room. Methods A meta-analysis and systematic review of all English-language studies relevant to validated arthroscopic simulation models using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines from 1999 to 2016 was performed. Data collected included the specific simulator model, the joint used, participant demographic characteristics, participant level of training, training session information, type and number of tasks, pre- and post-training assessments, and overall outcomes of simulator performance. Three independent reviewers analyzed all studies. Results Fifty-seven studies with 1,698 participants met the study criteria and were included. Of the studies, 25 (44%) incorporated an arthroscopic training program into the study methods whereas 32 (56%) did not. In 46 studies (81%), the studies' respective simulator models were used to assess arthroscopic performance, whereas 9 studies (16%) used Sawbones models, 8 (14%) used cadaveric models, and 4 (7%) evaluated subject performance on a live patient in the operating room. In 21 studies (37%), simulator performance was compared with experience level, with 20 of these (95%) showing that clinical experience correlated with simulator performance. In 25 studies (44%), task performance was evaluated before and after simulator training, with 24 of these (96%) showing improvement after training. All 4 studies that included live-patient arthroscopy reported improved operating room performance after simulator training compared with the performance of subjects not participating in a training program. Conclusions This review suggests that (1) training on arthroscopic simulators improves performance on arthroscopic simulators and (2) performance on simulators for basic diagnostic arthroscopy correlates with experience level. Limited data suggest that simulator training can improve basic diagnostic arthroscopy skills in vivo. Level of Evidence Level IV, systematic review of Level I through IV studies.

Background: Microfracture is an effective surgical treatment for full-thickness cartilage defects of the knee; however, little is known regarding long-term outcomes after microfracture in the shoulder. Purpose: To present long-term clinical outcomes of patients undergoing microfracture of full-thickness articular cartilage defects of the glenohumeral joint. Study Design: Case series; Level of evidence, 4. Methods: Sixteen consecutive patients (17 shoulders) were retrospectively reviewed who underwent arthroscopic microfracture of the humeral head and/or glenoid surface, with or without additional procedures between 2001 and 2008 and with a minimum follow-up of 8.5 years. All patients completed pre- and postoperative surveys containing the visual analog scale, American Shoulder and Elbow Surgeons form, and Simple Shoulder Test. Complications and reoperations were analyzed. Failure was defined by biological resurfacing or conversion to arthroplasty. Results: Of the original 16 patients (17 shoulders), 13 patients (14 shoulders) were available for mean follow-up at 10.2 ± 1.8 years after microfracture (range, 8.5-15.8 years), for an overall clinical follow-up rate of 82%. The patients (6 men, 7 women) were 36.1 ± 12.9 years old at time of microfracture. The average size of humeral head defects was 5.20 cm2 (range, 4.0-7.84 cm2), and the average size of glenoid defects was 1.53 cm2 (range, 1.0-3.75 cm2). Four patients (4 shoulders) underwent at least 1 reoperation, and 3 were considered to have structural failures. The average time to failure was 3.7 years after microfracture (range, 0.2-9.6 years). The overall survival rate was 76.6% at 9.6 years. For these patients, there were statistically significant improvements in visual analog scale, Simple Shoulder Test, and American Shoulder and Elbow Surgeons scores as compared with preoperative values at long-term follow-up ( P < .05 for all), without any significant change from short-term (mean, 2.3 years) to long-term (mean, 10.2 years) follow-up. There was no significant difference in Single Assessment Numeric Evaluation or Short Form–12 Physical or Mental scores between short- and long-term follow-up. When compared with short-term follow-up, in which 2 patients had already failed, 1 additional patient progressed to failure at 9.6 years after the original microfracture. Two patients (2 shoulders) were considered to have clinical failure. Owing to the overall number of failures (3 structural failure and 2 clinical failure), the total long-term success rate of glenohumeral microfracture is 66.7% in the current study. Conclusion: Treating full-thickness symptomatic chondral defects of the glenohumeral joint with microfracture can result in long-term improved function and reduced pain for some patients. However, in this case series, 21.4% of patients required conversion to arthroplasty

Objective To critically evaluate the current basic science, translational, and clinical data regarding bone marrow aspirate concentrate (BMAC) in the setting of focal cartilage defects of the knee and describe clinical indications and future research questions surrounding the clinical utility of BMAC for treatment of these lesions. Design A literature search was performed using the PubMed and Ovid MEDLINE databases for studies in English (1980-2017) using keywords, including [“bone marrow aspirate” and “cartilage”], [“mesenchymal stem cells” and “cartilage”], and [“bone marrow aspirate” and “mesenchymal stem cells” and “orthopedics”]. A total of 1832 articles were reviewed by 2 independent authors and additional literature found through scanning references of cited articles. Results BMAC has demonstrated promising results in the clinical application for repair of chondral defects as an adjuvant procedure or as an independent management technique. A subcomponent of BMAC, bone marrow derived–mesenchymal stem cells (MSCs) possess the ability to differentiate into cells important for osteogenesis and chondrogenesis. Modulation of paracrine signaling is perhaps the most important function of BM-MSCs in this setting. In an effort to increase the cellular yield, authors have shown the ability to expand BM-MSCs in culture while maintaining phenotype. Conclusions Translational studies have demonstrated good clinical efficacy of BMAC both concomitant with cartilage restoration procedures, at defined time points after surgery, and as isolated injections. Early clinical data suggests BMAC may help stimulate a more robust hyaline cartilage repair tissue response. Numerous questions remain regarding BMAC usage, including cell source, cell expansion, optimal pathology, and injection timing and quantity.

An increasingly consumer-centric health insurance market has empowered patients to select the providers of their choice. There is a lack of studies investigating the rationale by which patients select a foot and ankle surgeon. In the present study, 824 consecutive new patients seeking treatment from 3 foot-ankle surgeons were consecutively administered an anonymous questionnaire prior to their first appointment. It included rating the importance of 15 factors regarding specialist selection on a 1 to 10 scale, with 10 designated “ Very important” and 1 designated “ Not important at all.” The remaining questions were multiple choice regarding patient perspectives on other surgeon aspects (appointment availability, waiting room times, clinic proximity, etc). Of 824 consecutive patients administered the survey, 305 (37%) responded. Patients rated board certification (9.24 ± 1.87) and on-site imaging availability (8.48 ± 2.37)—on a 1 to 10 scale, with 10 designated “Very important— as the 2 most important criteria in choosing a foot and ankle surgeon. Patients rated advertisements as least important. Among the patients, 91% responded that a maximum of 30 minutes should elapse between clinic check-in and seeing their physician; 61% responded that a maximum of 20 minutes should elapse between clinic check-in and seeing their physician. In the context of an increasingly consumer-driven paradigm of health care delivery and reimbursement, it is important to understand patients’ preferences in specialist selection.Levels of Evidence: Level III: Prospective questionnaire

Articular cartilage lesions of the tibial plateau are an uncommonly encountered clinical entity, and they have been comparatively less well studied than femoral condyle or patellofemoral defects. The management of these lesions is complicated by the challenging geometry, difficult surgical approach, and proximity to important anatomic structures, and thus, treating these lesions by previously established methods, such as osteochondral allograft transplantation or osteochondral autograft transfer, can be a technically challenging endeavor. These lesions remain readily available to undergo microfracture, and this is the preferred method of management in the senior author's practice. Although less technically difficult and less invasive than other techniques, microfracture is currently limited by concerns over the long-term durability of the method. Current research seeks to improve the quality of cartilage fill stimulated by microfracture, and adjunct techniques have become increasingly popular. In this technical report, we present a technique for arthroscopic treatment of an isolated tibial plateau defect with microfracture using a micronized allogeneic cartilage (BioCartilage; Arthrex, Naples, FL) and platelet-rich plasma adjunct.

Symptomatic articular cartilage lesions of the knee can be debilitating, particularly in athletic patient populations. For patients with focal articular chondral defects in the knee, fresh osteochondral allograft transplantation (OCA) has been shown to be an effective single-stage procedure, particularly for larger lesions (>2 cm 2 ) to restore the articular surface with hyaline cartilage. Indications for OCA continue to expand as a growing body of literature suggests good to excellent long-term clinical outcomes in appropriately selected patients as both a primary and salvage cartilage restoration procedure. In this review, a thorough summation of the most current literature regarding OCA in athletes, including associations between demographic and surgical variables and the ability to return to sport, and a detailed description of the senior author’s rehabilitation protocol with sport-specific considerations will be presented.

Although emerging evidence has identified an expanded role for nonoperative treatment of Achilles tendon ruptures, there remains a preference to treat young, active patients operatively to reduce the risk of rerupture and improve return to play. To ensure an adequate repair while minimizing risks for wound complications, the senior authors (B.J.C. and J.L.L.) prefer a limited open technique to repair. Additionally, we recommend a brief period of immobilization and nonweight bearing which is quickly followed by an early, active rehabilitation phase to balance the functional benefits of early loading with the risk of early reinjury. Recent literature has linked patient demographic factors, such as older age and elevated body mass index, to worse postoperative symptomatic outcomes. Although higher preoperative activity levels are correlated with improved postoperative functional outcomes, these patients report reduced satisfaction, likely attributable to unmet expectations of restored function. Because of the large loads placed on the Achilles tendon during certain athletic activities, these injuries can be very difficult for explosive athletes, such as jumpers or sprinters, to effectively return from, regardless of management approach.

SUMMARY Our data suggest that, after a myocardial infarction, integrin-associated protein CD47 on cardiac myocytes is elevated. In culture, increased CD47 on the surface of dying cardiomyocytes impairs phagocytic removal by immune cell macrophages. After myocardial ischemia and reperfusion, acute CD47 inhibition with blocking antibodies enhanced dead myocyte clearance by cardiac phagocytes and also improved the resolution of cardiac inflammation, reduced infarct size, and preserved cardiac contractile function. Early targeting of CD47 in the myocardium after reperfusion may be a new strategy to enhance wound repair in the ischemic heart., Graphical Abstract

Rotator cuff injuries are among the most common in orthopaedics, with rotator cuff repair surgery consistently reported as one of the most commonly performed orthopaedic procedures. Patient satisfaction is becoming an increasingly important outcome metric as health care continues to evolve with regard to quality measures affecting physician reimbursement. Evidence supports that postoperative patient satisfaction, an important quality outcome metric, is highly influenced by preoperative patient expectations, which are in turn governed by patient knowledge and understanding. Many authors have delineated patient-, injury-, and surgery-specific variables associated with high preoperative expectations and satisfaction after rotator cuff surgery. Specifically, large rotator cuff tears, subscapularis tears, persistence of postoperative pain and dysfunction, worker's compensation cases, lower education level, and preoperative disability have been seen more frequently in patients reporting poor satisfaction. Others have reported variables associated with higher patient satisfaction such as being married, employed, and of older age at the time of surgery (>55 years old) predictive of higher satisfaction. Patient education preoperatively regarding details about the surgery and the postoperative plan both immediately after the procedure and for rehabilitation are critical in helping set patients' preoperative expectations that have a known effect on patients' subjective clinical outcomes.

Chromatin looping is key to gene regulation, yet no broadly applicable methods to selectively modify chromatin loops have been described. We have engineered a method for chromatin loop reorganization using CRISPR-dCas9 (CLOuD9) to selectively and reversibly establish chromatin loops. We demonstrate the power of this technology to selectively modulate gene expression at targeted loci., Chromatin looping plays an important role in gene regulation and the ability to manipulate loops would aid in understanding how this occurs. Here the authors present CLOuD9, a system that uses dimerized Cas9 complexes to selectively and reversibly establish chromatin loops.

Patient satisfaction has become an increasingly important outcome metric in orthopaedics and medicine in general as many initiatives at both the state and national levels aim to improve the efficiency and quality of health care. Anterior cruciate ligament injuries are among the most common injuries in orthopaedics, with anterior cruciate ligament reconstruction (ACLR) surgery consistently reported as one of the most frequently performed procedures by orthopaedic surgeons. Patient-reported outcomes are frequently used to evaluate outcomes from the patient's perspective, and many physicians also ask patients about their satisfaction with treatment. A growing volume of literature has investigated the relation between preoperative patient expectations and postoperative patient satisfaction. The quality of online resources, patient expectations for ACLR, and factors associated with and/or predictive of either poor or good to excellent outcomes after surgery are described. This article critically reviews the orthopaedic literature on this important topic and identifies variables that influence patient expectations and satisfaction to help treating physicians better counsel and evaluate patients and ultimately improve outcomes of and satisfaction with ACLR surgery.

Background Although error identification and recovery skills are essential for the safe practice of surgery, they have not traditionally been taught or evaluated in residency training. This study validates a method for assessing error identification and recovery skills in surgical residents using a thoracoscopic lobectomy simulator. Methods We developed a 5-station, simulator-based examination containing the most commonly encountered cognitive and technical errors occurring during division of the superior pulmonary vein for left upper lobectomy. Successful completion of each station requires identification and correction of these errors. Examinations were video recorded and scored in a blinded fashion using an examination-specific rating instrument evaluating task performance as well as error identification and recovery skills. Evidence of validity was collected in the categories of content, response process, internal structure, and relationship to other variables. Results Fifteen general surgical residents (9 interns and 6 third-year residents) completed the examination. Interrater reliability was high, with an intraclass correlation coefficient of 0.78 between 4 trained raters. Station scores ranged from 64% to 84% correct. All stations adequately discriminated between high- and low-performing residents, with discrimination ranging from 0.35 to 0.65. The overall examination score was significantly higher for intermediate residents than for interns (mean, 74 versus 64 of 90 possible; p = 0.03). Conclusions The described simulator-based examination with embedded errors and its accompanying assessment tool can be used to measure error identification and recovery skills in surgical residents. This examination provides a valid method for comparing teaching strategies designed to improve error recognition and recovery to enhance patient safety.

To characterize the generic behavior of open quantum systems, we consider random, purely dissipative Liouvillians with a notion of locality. We find that the positivity of the map implies a sharp separation of the relaxation timescales according to the locality of observables. Specifically, we analyze a spin-1/2 system of size l with up to n-body Lindblad operators, which are n local in the complexity-theory sense. Without locality (n=l), the complex Liouvillian spectrum densely covers a "lemon"-shaped support, in agreement with recent findings [S. Denisov et al., Phys. Rev. Lett. 123, 140403 (2019)PRLTAO0031-900710.1103/PhysRevLett.123.140403]. However, for local Liouvillians (n

To determine if physeal status or other preoperative or intraoperative variables influence the failure rate after arthroscopic reduction and internal fixation of osteochondritis dissecans (OCD) lesions in the knee.Consecutive patients undergoing screw fixation of osteochondral fragments from OCD by a single surgeon from 2005 to 2015 with a minimum 2-year follow-up were included. Demographic, preoperative imaging, and intraoperative data were analyzed to determine risk factors associated with failure, which was defined as the need for a revision reoperation or arthroplasty after initial OCD fixation.A total of 45 knees met the inclusion criteria, including 26 skeletally mature patients and 19 patients with incompletely closed physes on preoperative imaging. The mean ages of the skeletally mature and immature groups were 18.3 ± 2.5 years and 14.9 ± 2.2 years, respectively (P.001), and the mean body mass index values were 24.3 ± 3.6 and 23.2 ± 4.0, respectively (P = .432). We excluded 10 patients from the survivorship analysis because they had less than 2 years' follow-up. No statistically significant difference in failure rates was found between skeletally mature and immature individuals (30% and 40%, respectively; P = .721). The only factor significantly associated with fixation failure was undergoing a prior surgical procedure to address the OCD lesion (P = .038). Kaplan-Meier analysis showed rates of overall survivorship from revision reoperations of 88.6% at 1 year and 68.8% at 5 years.Outcomes after internal fixation of OCD fragments are guarded, with a fragment survival rate of 65.7% at a mean of 4.1 years' follow-up. No difference in fragment survival was noted in skeletally mature versus immature patients. The only independent risk factor identified for fixation failure was the number of previous operations. LEVEL OF EVIDENCE: Level IV, case series with subgroup analysis.

Pruritus is common in all age groups but is especially prevalent in the elderly due to senescence of the integumentary, immune, and nervous systems. In developing a treatment regimen, clinicians must consider the many potential therapeutic options for pruritus and how these interplay with common comorbidities and functional limitations of elderly patients. While the causes of pruritus are numerous, effective topical and systemic treatments are limited, especially in the elderly, due to the unique pharmacokinetics and pharmacodynamics of aging bodies. The major etiologies and treatment options for dermatitis and pruritus are reviewed, taking into account the challenges of local and systemic treatment in elderly patients.

Mutations in LMNA, the gene that encodes lamin A and C, causes LMNA-related dilated cardiomyopathy (DCM) or cardiolaminopathy. LMNA is expressed in endothelial cells (ECs); however, little is known about the EC-specific phenotype of LMNA-related DCM. Here, we studied a family affected by DCM due to a frameshift variant in LMNA Human induced pluripotent stem cell (iPSC)-derived ECs were generated from patients with LMNA-related DCM and phenotypically characterized. Patients with LMNA-related DCM exhibited clinical endothelial dysfunction, and their iPSC-ECs showed decreased functionality as seen by impaired angiogenesis and nitric oxide (NO) production. Moreover, genome-edited isogenic iPSC lines recapitulated the EC disease phenotype in which LMNA-corrected iPSC-ECs showed restoration of EC function. Simultaneous profiling of chromatin accessibility and gene expression dynamics by combining assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA sequencing (RNA-seq) as well as loss-of-function studies identified Kruppel-like factor 2 (KLF2) as a potential transcription factor responsible for the EC dysfunction. Gain-of-function studies showed that treatment of LMNA iPSC-ECs with KLF2 agonists, including lovastatin, rescued the EC dysfunction. Patients with LMNA-related DCM treated with lovastatin showed improvements in clinical endothelial dysfunction as indicated by increased reactive hyperemia index. Furthermore, iPSC-derived cardiomyocytes (iPSC-CMs) from patients exhibiting the DCM phenotype showed improvement in CM function when cocultured with iPSC-ECs and lovastatin. These results suggest that impaired cross-talk between ECs and CMs can contribute to the pathogenesis of LMNA-related DCM, and statin may be an effective therapy for vascular dysfunction in patients with cardiolaminopathy.

In the version of this article initially published, ‘+’ and ‘–’ labels were missing from the graph keys at the bottom of Fig. 8d. The error has been corrected in the HTML and PDF versions of the article.

Articular cartilage injury remains a challenging condition for orthopedic surgeons to address. While multiple treatment options exist and have reported improvement in patient symptoms, sustained and successful treatment of symptomatic chondral defects remains elusive in many cases. Physicians may define failure in a multitude of ways such as subsequent surgery, progression to arthroplasty, lack of improvement in outcome measures, lack of hyaline-like repair tissue, or poor appearance on imaging studies. This chapter reviews the current standards for defining treatment failure in order to address the importance of consistent and clear goals for treating cartilage injuries and understanding the outcome tools currently available.

Tibial plateau defects present a challenging clinical entity, as their location, geometry, and proximity to surrounding structures make them technically challenging to treat. Additionally, the literature on the management of tibial plateau cartilage defects is not well-developed. Techniques such as osteochondral allografts or autografts are technically complicated in these regions and should be approached with caution. Microfracture is a well-established technique that is technically simple and has low rates of complications, and it is well-suited for treating tibial plateau defects. However, concerns about the long-term outcomes of microfracture have been raised, likely secondary to the generation of fibrocartilage. Newer treatments that are available including BioCartilage (Arthrex, Naples, FL) and matrix-associated autologous chondrocyte implantation (MACI) may have promise in this technically demanding area.

Purpose To assess the survivorship, clinical outcomes, and radiographic outcomes of patients who have undergone revision osteochondral allograft (OCA) to the knee in a retrospective case series. Methods Nine patients who underwent revision OCA by the senior author between January 2003 and December 2015 with a minimum follow up of 2 years were reviewed retrospectively. Patients completed patient-reported outcome surveys containing the visual analog scale, the International Knee Documentation Committee, the Knee injury and Osteoarthritis Outcome Score, Lysholm score, and the Short-Form 12. Radiographic analysis included anteroposterior view graded via the Kellgren and Lawrence scale. Complications and reoperations were analyzed, with failure defined as conversion to arthroplasty. (Institutional review board 15050301.) Results One of 10 consecutive patients was lost to follow up, for an overall follow-up rate of 90% (5 males, 4 females); mean follow up, 4.53 ± 3.17 years. The median patient age at the time of revision OCA was 33 years (interquartile range [IQR], 8.6), the median defect size was 4.0 cm2 (IQR, 0), and the median time from index OCA to revision OCA was 2.9 years (IQR, 1.9). Five patients (50%) underwent subsequent surgery at a median of 1.92 years (IQR, 7.25), with 1 progressing to arthroplasty at 23 months after revision OCA, for an overall failure rate of 11%. There were no significant differences in any of the patient-reported outcome assessments compared with prerevision OCA (postindex OCA) values at final follow up (P > .05 for all). Similarly, there were no significant differences in Kellgren and Lawrence score before and after surgery (P = .1). Conclusions At a mean 4.5 years following revision OCA, there was an 89% graft survivorship rate in a series of 9 patients, with no statistical changes in the radiographic progression of arthritis. Level of Evidence Level IV, case series.