Integrative single-cell analysis of cardiogenesis identifies developmental trajectories and non-coding mutations in congenital heart disease.

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 contrasted regulatory landscapes of iPSC-derived cardiac cell types and their in vivo counterparts, which enabled optimization of in vitro differentiation of epicardial cells. Further, we interpreted sequence based deep learning models of cell-type-resolved chromatin accessibility profiles to decipher underlying TF motif lexicons. De novo mutations predicted to affect chromatin accessibility in arterial endothelium were enriched in congenital heart disease (CHD) cases vs. controls. In vitro studies in iPSCs validated the functional impact of identified variation on the predicted developmental cell types. This work thus defines the cell-type-resolved cis-regulatory sequence determinants of heart development and identifies disruption of cell type-specific regulatory elements in CHD.

Socioeconomic Factors Including Patient Income, Education Level, and Health Insurance Influence Postoperative Secondary Surgery and Hospitalization Rates Following Hip Arthroscopy.

PURPOSE: To evaluate a large cross-sectional sample of patients utilizing administrative database records and analyze the effects of income, insurance type, and education level on outcomes after hip arthroscopy, including 2-year revision surgery, conversion to total hip arthroplasty (THA), and 90-day hospitalizations. METHODS: Current Procedural Terminology codes were used to query the PearlDiver Mariner database from October 2015 to January 2020 for patients undergoing hip arthroscopy with a minimum 2-year follow-up. Patients were categorized by mean family income in their zip code of residence (MFIR), health insurance type, and educational attainment in their zip code of residence (EAR). Two-year revision arthroscopy, conversion to THA, and 90-day hospital readmissions or emergency department (ED) visits were analyzed along socioeconomic strata. RESULTS: Multivariate analysis of 33,326 patients revealed that patients with MFIR between $30,000 and $70,000 had lower odds of 2-year revision arthroscopy (odds ratio [OR], 0.63; P < .001), THA conversion (OR, 0.76; P = .050), and 90-day readmission (OR, 0.53; P = .007) compared to MFIR >$100,000. Compared to patients with commercial insurance, patients with Medicare had lower odds of revision arthroscopy (OR, 0.60; P = .035) and THA conversion (OR, 0.46, P < .001) but greater odds of 90-day readmission (OR, 1.74; P = .007). Patients with Medicaid had higher odds of 90-day ED visits (OR, 1.84; P < .001). Patients with low EAR had higher odds of revision arthroscopy (OR, 1.42; P = .005) and THA conversion (OR, 1.58; P = .002) compared to those with high EAR. CONCLUSIONS: Following hip arthroscopy, patients residing in areas with lower mean family income were less likely to undergo reoperations and readmissions. Medicare patients showed lower reoperation but higher readmission odds, while Medicaid patients showed higher odds of ED visits. Additionally, higher educational attainment in the zip code of residence is protective against future reoperation. LEVEL OF EVIDENCE: Level III, retrospective case series.

Does body mass index influence long-term outcomes after anatomic total shoulder arthroplasty?

BACKGROUND: As of 2018, upwards of 42% of the US 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. METHODS: This was a retrospective analysis of 128 shoulders requiring primary aTSA. Patients were stratified into 3 cohorts based on their BMI at surgery: underweight/normal weight (U/NW; BMI ≤25.0), overweight (25.0 < BMI ≤ 30.0), and obese (BMI >30.0). 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 (VAS) scores, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores, and the Simple Shoulder Test (SST). Survivorship curves were calculated using Kaplan-Meier analysis. RESULTS: Forty-four, 50, and 34 patient shoulders were in the 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 with the overweight (34%; P = .0030) and obese (35%; P = .0015) groups; no differences were seen in revision rates. BMI was negatively correlated with age at surgery (r = -0.19, P = .014); it was not correlated with any of the 6 postoperative clinical endpoints. All 3 cohorts saw significant improvements in forward elevation, external rotation, internal rotation and VAS, ASES, and SST scores when compared preoperatively to postoperatively (P < .001). There were no significant differences between the 3 cohorts with respect to postoperative range of motion. Postoperative ASES scores were higher for the overweight cohort (82.6 ± 18.6) compared with both the U/NW (63.0 ± 25.1) and obese cohorts (70.5 ± 26.8) (P < .001). The overweight cohort also had higher SST (P = .0012) postoperative scores compared with the U/NW and obese cohorts; VAS scores were comparable between groups (P = .12). The nonobese (BMI <30) group (n = 94) showed 5-, 10-, 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 = .82). CONCLUSION: 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.

Survivorship of total shoulder arthroplasty vs. hemiarthroplasty for the treatment of avascular necrosis at greater than 10-year follow-up.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Epigenomics: Technologies and Applications.

The advent of high-throughput epigenome mapping technologies has ushered in a new era of multiomics where powerful tools can now delineate and record different layers of genomic output. Integrating various components of the epigenome from these multiomics measurements allows the interrogation of cellular heterogeneity in addition to the discovery of molecular connectivity maps between the genome and its functional output. Mapping of chromatin accessibility dynamics and higher-order chromatin structure has enabled new levels of understanding of cell fate decisions, identity, and function in normal development, physiology, and disease. We provide a perspective on the progress of the epigenomics field and applications and anticipate an even greater revolution in our understanding of the human epigenome for years to come.

Molecular mechanisms of long noncoding RNAs.

Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. Here we discuss the emerging archetypes of molecular functions that lncRNAs execute-as signals, decoys, guides, and scaffolds. For each archetype, examples from several disparate biological contexts illustrate the commonality of the molecular mechanisms, and these mechanistic views provide useful explanations and predictions of biological outcomes. These archetypes of lncRNA function may be a useful framework to consider how lncRNAs acquire properties as biological signal transducers and hint at their possible origins in evolution. As new lncRNAs are being discovered at a rapid pace, the molecular mechanisms of lncRNAs are likely to be enriched and diversified.

Clinical Outcomes of Revision Osteochondral Allograft Transplantation.

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.

Clinical Outcomes of Osteochondral Allograft Transplantation for Secondary Treatment of Osteochondritis Dissecans of the Knee in Skeletally Mature Patients.

PURPOSE: To report clinical outcomes of osteochondral allograft transplantation (OCA) for skeletally mature patients with osteochondritis dissecans (OCD) lesions of the knee in whom prior surgical intervention has failed, and to describe return-to-sport (RTS) rates and any predictive demographic or preoperative variables associated with a higher likelihood to RTS. METHODS: Patients who underwent OCA by a single surgeon (B.J.C.) between October 1, 2002, and November 30, 2014, for a diagnosis of OCD with a minimum of 2 years' follow-up were included. Demographic, surgical history, operative, and postoperative data points including RTS were analyzed for all patients collectively, with subanalysis to identify any demographic and operative variables associated with the ability to RTS. Failure was defined as revision OCA, gross appearance of graft failure on second-look arthroscopy, or conversion to arthroplasty. RESULTS: We identified 41 consecutive patients (43 knees), with 37 patients (39 knees, comprising 26 male and 13 female knees) available for clinical follow-up at an average of 7.29 ± 3.30 years. There was significant improvement (P < .05) in all patient-reported outcome scores, with the exception of the Short Form 12 mental subscale (P = .910). Most patients (81.6%) reported being either mostly satisfied or completely satisfied at final follow-up. Of patients self-identifying as athletes preoperatively (n = 22), 18 (81.8%) achieved RTS at an average of 14.0 ± 8.7 months. Athletes with failure to RTS had a significantly greater body mass index (RTS, 24.68 ± 3.67; no RTS, 27.82 ± 0.69; P = .005). Subsequent surgery was performed in 14 patients (35.9%), and primary OCA failed in 2 patients at an average of 6.2 ± 3.8 years. CONCLUSIONS: OCA is a successful secondary surgical treatment for OCD of the knee in skeletally mature patients and leads to clinically meaningful improvements in patient-reported outcome scores and high patient satisfaction and RTS rates in low-level athletes at an average of 7.29 years' follow-up. Athletes with failure to RTS were found to have a significantly higher body mass index. Although reoperation may be common after OCA (35.9%), the failure rate is low (5.1%) in this series. LEVEL OF EVIDENCE: Level IV, case series.

Utility of Modern Arthroscopic Simulator Training Models: A Meta-analysis and Updated Systematic Review.

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.

A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression.

The genome is extensively transcribed into long intergenic noncoding RNAs (lincRNAs), many of which are implicated in gene silencing. Potential roles of lincRNAs in gene activation are much less understood. Development and homeostasis require coordinate regulation of neighbouring genes through a process termed locus control. Some locus control elements and enhancers transcribe lincRNAs, hinting at possible roles in long-range control. In vertebrates, 39 Hox genes, encoding homeodomain transcription factors critical for positional identity, are clustered in four chromosomal loci; the Hox genes are expressed in nested anterior-posterior and proximal-distal patterns colinear with their genomic position from 3' to 5'of the cluster. Here we identify HOTTIP, a lincRNA transcribed from the 5' tip of the HOXA locus that coordinates the activation of several 5' HOXA genes in vivo. Chromosomal looping brings HOTTIP into close proximity to its target genes. HOTTIP RNA binds the adaptor protein WDR5 directly and targets WDR5/MLL complexes across HOXA, driving histone H3 lysine 4 trimethylation and gene transcription. Induced proximity is necessary and sufficient for HOTTIP RNA activation of its target genes. Thus, by serving as key intermediates that transmit information from higher order chromosomal looping into chromatin modifications, lincRNAs may organize chromatin domains to coordinate long-range gene activation.

Patient Understanding, Expectations, and Satisfaction Regarding Rotator Cuff Injuries and Surgical Management.

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.

Patient Understanding, Expectations, Outcomes, and Satisfaction Regarding Anterior Cruciate Ligament Injuries and Surgical Management.

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.

Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis.

Large intervening non-coding RNAs (lincRNAs) are pervasively transcribed in the genome yet their potential involvement in human disease is not well understood. Recent studies of dosage compensation, imprinting, and homeotic gene expression suggest that individual lincRNAs can function as the interface between DNA and specific chromatin remodelling activities. Here we show that lincRNAs in the HOX loci become systematically dysregulated during breast cancer progression. The lincRNA termed HOTAIR is increased in expression in primary breast tumours and metastases, and HOTAIR expression level in primary tumours is a powerful predictor of eventual metastasis and death. Enforced expression of HOTAIR in epithelial cancer cells induced genome-wide re-targeting of Polycomb repressive complex 2 (PRC2) to an occupancy pattern more resembling embryonic fibroblasts, leading to altered histone H3 lysine 27 methylation, gene expression, and increased cancer invasiveness and metastasis in a manner dependent on PRC2. Conversely, loss of HOTAIR can inhibit cancer invasiveness, particularly in cells that possess excessive PRC2 activity. These findings indicate that lincRNAs have active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.

Generalized benign cutaneous reaction to cytarabine.

BACKGROUND: Cytarabine-induced toxicity manifests as various cutaneous morphologies. A generalized papular purpuric eruption has not been well described. OBJECTIVES: We aimed to characterize a distinct cytarabine-related eruption. METHODS: We reviewed all cases of cytarabine-related toxicity with papular purpuric eruptions or violaceous erythema at the University of California, San Francisco between 2006 and 2011. RESULTS: Sixteen cases were identified. The eruption began as erythematous papules that evolved into coalescing purpuric papules and plaques. It had affinity for intertriginous areas, neck, ears, and scalp. Pruritus was common, but no systemic complications were documented. Thirteen patients (81.3%) developed the eruption after completion of chemotherapy. Differential diagnosis often included viral exanthem (62.5%), drug eruption (50%), and vasculitis (37.5%). Histopathology was nonspecific but commonly demonstrated sparse lymphocytic infiltrates, spongiosis, and/or red cell extravasation. Importantly, the eruption was neither predicted by past cytarabine exposure nor predictive of future recurrence. LIMITATIONS: This is a review of cases from a single institution. Observation was limited to acute hospitalization, however, charts were reviewed for subsequent reactions on rechallenge. CONCLUSIONS: The eruption described herein represents a specific skin-limited reaction to cytarabine. Awareness of its characteristic morphology, distribution, and timeline will aid in clinical diagnosis. Reassurance concerning its benign nature will prevent unnecessary intervention or cessation of chemotherapy.

A fibrous papule with abundant CD34-immunoreactive ganglion-like multinucleated giant cells: a case report and review of the literature.

Fibrous papules present clinically as benign, asymptomatic, dome-shaped, flesh colored papules on the face. Histologically, fibrous papules are characterized by fibrous stroma with fibroblasts and dilated blood vessels. Multiple variants of fibrous papules have been reported. Although scattered multinucleated cells in fibrous papules have been well described, we report a fibrous papule with abundant multinucleated ganglion-like giant cells that were immunoreactive with CD34. Recognition of such fibrous papule variants is important to avoid misdiagnosis as potentially more worrisome and/or aggressive melanocytic, soft tissue, or neural lesions that may require more aggressive treatment. Indeed, fibrous papules do not commonly appear on the differential diagnosis for lesions with multinucleated giant cells or ganglion-like cells and consideration should be given to their inclusion in the appropriate clinical setting.

Increased rate of out-of-network surgeon selection for hip arthroscopy compared to more common orthopedic sports procedures.

Background: Demand for hip arthroscopy (HA) has increased, but shortfalls in HA training may create disparities in care access. This analysis aimed to (1) compare out-of-network (OON) surgeon utilization for HA with that of more common orthopedics sports procedures, including rotator cuff repair (RCR), partial meniscectomy (PM), and anterior cruciate ligament reconstruction (ACLR), (2) compare the HA OON surgeon rate with another less commonly performed procedure, meniscus allograft transplant (MAT), and (3) analyze trends and predictors of OON surgeon utilization. Methods: The 2013-2017 IBM MarketScan database identified patients under 65 who underwent HA, RCR, PM, ACLR, or MAT. Demographic differences were determined using standardized differences. Cochran-Armitage tests analyzed trends in OON surgeon utilization. Multivariable logistic regression identified predictors of OON surgeon utilization. Statistical significance was set to p < 0.05 and significant standardized differences were >0.1. Results: 410,487 patients were identified, of which 12,636 patients underwent HA, 87,607 RCR, 233,241 PM, 76,700 ACLR, and 303 MAT. OON surgeon utilization increased for HA, rising from 7.98 % in 2013 to 9.37 % in 2017 (p = 0.026). Compared to RCR, PM, and ACLR, HA was associated with higher likelihood of OON surgeon utilization. Usage of ambulatory surgery centers (ASCs) was predictive of higher OON surgeon rates along with procedure year, insurance plan type, and geographic region. HA performed in an ASC was 13 % less likely to have an OON surgeon (p = 0.047). Conclusion: OON surgeon utilization generally declined but increased for HA. HA was a predictor of OON surgeon status, possibly because HA is a technically complicated procedure with fewer trained in-network providers. Other predictors of OON surgeon status included ASC usage, PPO/EPO plan type, and Northeast geographic region. There is a need to improve access to experienced HA providers-perhaps with prioritization of HA training in residency and fellowship programs-in order to address rising OON surgeon utilization.

Super-enhancer interactomes from single cells link clustering and transcription.

Regulation of gene expression hinges on the interplay between enhancers and promoters, traditionally explored through pairwise analyses. Recent advancements in mapping genome folding, like GAM, SPRITE, and multi-contact Hi-C, have uncovered multi-way interactions among super-enhancers (SEs), spanning megabases, yet have not measured their frequency in single cells or the relationship between clustering and transcription. To close this gap, here we used multiplexed imaging to map the 3D positions of 376 SEs across thousands of mammalian nuclei. Notably, our single-cell images reveal that while SE-SE contacts are rare, SEs often form looser associations we termed "communities". These communities, averaging 4-5 SEs, assemble cooperatively under the combined effects of genomic tethers, Pol2 clustering, and nuclear compartmentalization. Larger communities are associated with more frequent and larger transcriptional bursts. Our work provides insights about the SE interactome in single cells that challenge existing hypotheses on SE clustering in the context of transcriptional regulation.

Assessment of Risk Factors and Rate of Conversion to Total Hip Arthroplasty Within 2 Years After Hip Arthroscopy Utilizing a Large Database of Commercially Insured Patients in the United States.

Background: The conversion rate of hip arthroscopy (HA) to total hip arthroplasty (THA) has been reported to be as high as 10%. Despite identifying factors that increase the risk of conversion, current studies do not stratify patients by type of arthroscopic procedure. Purpose/Hypothesis: To analyze the rate and predictors of conversion to THA within 2 years after HA. It was hypothesized that osteoarthritis (OA) and increased patient age would negatively affect the survivorship of HA. Study Design: Cohort study; Evidence level, 3. Methods: The IBM MarketScan database was utilized to identify patients who underwent HA and converted to THA within 2 years at inpatient and outpatient facilities between 2013 and 2017. Patients were split into 3 procedure cohorts as follows: (1) femoroacetabular osteoplasty (FAO), which included treatment for femoroacetabular impingement; (2) isolated debridement; and (3) isolated labral repair. Cohort characteristics were compared using standardized differences. Conversion rates between the 3 cohorts were compared using chi-square tests. The relationship between age and conversion was assessed using linear regression. Predictors of conversion were analyzed using multivariable logistic regression. The median time to conversion was estimated using Kaplan-Meier tests. Results: A total of 5048 patients were identified, and the rates of conversion to THA were 12.86% for isolated debridement, 8.67% for isolated labral repair, and 6.76% for FAO (standardized difference, 0.138). The isolated labral repair cohort had the shortest median time to conversion (isolated labral repair, 10.88 months; isolated debridement, 10.98 months; and FAO, 11.9 months [P = .034). For patients >50 years, isolated debridement had the highest rate of conversion at 18.8%. The conversion rate increased linearly with age. Factors that increased the odds of conversion to THA were OA, having an isolated debridement procedure, and older patient age (P < .05). Conclusion: Older patients and those with preexisting OA of the hip were at a significantly increased risk of failing HA and requiring a total hip replacement within 2 years of the index procedure. Younger patients were at low risk of requiring a conversion procedure no matter which arthroscopic procedure was performed.