Association of Posterior Tibial Slope With Outcomes After Multiligamentous Knee Reconstruction for Knee Dislocation Grades 2 to 4.

Background: Patients with isolated anterior cruciate ligament (ACL) reconstruction have demonstrated an increased risk of ACL graft failure and lower patient-reported outcome (PRO) scores when increased posterior tibial slope (PTS) is present. However, there is a paucity of literature evaluating the effect of PTS on outcomes after combined bicruciate multiligamentous knee reconstruction. Purpose: To determine whether differences exist for graft failure rates or PRO scores based on PTS after combined bicruciate multiligamentous knee reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: All patients who underwent combined ACL and posterior cruciate ligament (PCL) reconstruction between 2000 and 2020 at our institution were identified. Exclusion criteria were age <18 years, knee dislocation grade 5 injuries, concomitant osteotomy procedures, and <2 years of clinical follow-up. Demographic and outcomes data were collected from our prospectively gathered multiligamentous knee injury database. Lysholm and International Knee Documentation Committee (IKDC) scores were analyzed in relation to PTS. Outcomes were compared for patients with a PTS above and below the mean for the total cohort, PTS >12° versus <12°, positive versus negative Lachman test at follow-up, and positive versus negative posterior drawer test at follow-up. Results: A total of 98 knees in 98 patients were included in the study, with a mean clinical follow-up of 5.1 years (median, 4.6 years; range, 2-16 years). The mean PTS was 8.7° (range, 0.4°-16.9°). Linear regression analysis showed no significant correlation between PTS and IKDC or Lysholm scores. Patients with a PTS above the mean of 8.7° trended toward lower IKDC (P = .08) and Lysholm (P = .06) scores. Four patients experienced ACL graft failure and 5 patients experienced PCL graft failure. There were no differences in graft failure rates or PRO scores for patients with a PTS >12°. Patients with a positive Lachman test trended toward higher PTS (9.6° vs 8.5°, P = .15). Conclusion: In this series of bicruciate multiligamentous knee reconstructions at midterm follow-up, no differences in graft failures, complications, reoperations, revisions, or PRO scores based on PTS were identified. Patients with a positive Lachman test were found to have a slightly higher PTS, although this did not reach statistical significance.

Minimally Invasive Quadriceps Tendon Anterior Cruciate Ligament Reconstruction Using the Quadriceps Tendon Harvest Guide System.

Anterior cruciate ligament (ACL) reconstruction using the quadriceps tendon (QT) autograft is an increasingly utilized technique that confers less donor site morbidity and comparable outcomes to other historically used graft options. The graft harvest and implantation process present vast variability-particularly regarding the achievement of adequate graft site visualization, consistently attaining a uniform and appropriately sized graft, and subsequent reconstruction of the ACL with the all-soft tissue graft. The purpose of this Technical Note and video is to describe and demonstrate minimally invasive quadriceps tendon autograft harvesting using the Quadriceps Tendon Harvest Guide System (QUADTRAC), and its subsequent implantation within a single-bundle ACL reconstruction with suspensory fixation.

Adipose tissue macrophages secrete small extracellular vesicles that mediate rosiglitazone-induced insulin sensitization.

The obesity epidemic continues to worsen worldwide, driving metabolic and chronic inflammatory diseases. Thiazolidinediones, such as rosiglitazone (Rosi), are PPARγ agonists that promote 'M2-like' adipose tissue macrophage (ATM) polarization and cause insulin sensitization. As ATM-derived small extracellular vesicles (ATM-sEVs) from lean mice are known to increase insulin sensitivity, we assessed the metabolic effects of ATM-sEVs from Rosi-treated obese male mice (Rosi-ATM-sEVs). Here we show that Rosi leads to improved glucose and insulin tolerance, transcriptional repolarization of ATMs and increased sEV secretion. Administration of Rosi-ATM-sEVs rescues obesity-induced glucose intolerance and insulin sensitivity in vivo without the known thiazolidinedione-induced adverse effects of weight gain or haemodilution. Rosi-ATM-sEVs directly increase insulin sensitivity in adipocytes, myotubes and primary mouse and human hepatocytes. Additionally, we demonstrate that the miRNAs within Rosi-ATM-sEVs, primarily miR-690, are responsible for these beneficial metabolic effects. Thus, using ATM-sEVs with specific miRNAs may provide a therapeutic path to induce insulin sensitization.

Long-term Outcomes of Primary Hip Arthroscopy: Multicenter Analysis at Minimum 10-Year Follow-up With Attention to Labral and Capsular Management.

BACKGROUND: Hip arthroscopy is rapidly advancing, with positive published outcomes at short- and midterm follow-up; however, available long-term data remain limited. PURPOSE: To evaluate outcomes of primary hip arthroscopy at a minimum 10-year follow-up at 2 academic centers by describing patient-reported outcomes and determining reoperation and total hip arthroplasty (THA) rates. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients with primary hip arthroscopy performed between January 1988 and April 2013 at 2 academic centers were evaluated for postoperative patient-reported outcomes-including the visual analog scale, Tegner Activity Scale score, Hip Outcome Score Activities of Daily Living and Sport Specific subscales, modified Harris Hip Score, Nonarthritic Hip Score, 12-item International Hip Outcome Tool, surgery satisfaction, and reoperations. RESULTS: A total of 294 patients undergoing primary hip arthroscopy (age, 40 ± 14 years; 66% women; body mass index, 27 ± 6) were followed for 12 ± 3 years (range, 10-24 years) postoperatively. Labral debridement and repair were performed in 41% and 59% of patients, respectively. Of all patients who underwent interportal capsulotomy, 2% were extended to a T-capsulotomy, and 11% underwent capsular repair. At final follow-up, patients reported a mean visual analog scale at rest of 2 ± 2 and with use of 3 ± 3, a 12-item International Hip Outcome Tool of 68 ± 27, a Nonarthritic Hip Score of 81 ± 18, a modified Harris Hip Score of 79 ± 17, and a Hip Outcome Score Activities of Daily Living of 82 ± 19 and Sport Specific subscale of 74 ± 25. The mean surgical satisfaction was 8.4 ± 2.4 on a 10-point scale, with 10 representing the highest level of satisfaction. In total, 96 hips (33%) underwent reoperation-including 65 hips (22%) converting to THA. THA risk factors included older age, higher body mass index, lower lateral center-edge angle, larger alpha angle, higher preoperative Tönnis grade, as well as labral debridement and capsular nonrepair (P≤ .039). Patients undergoing combined labral and capsular repair demonstrated a THA conversion rate of 3% compared with 31% for patients undergoing combined labral debridement and capsular nonrepair (P = .006). Labral repair trended toward increased 10-year THA-free survival (84% vs 77%; P = .085), while capsular repair demonstrated significantly increased 10-year THA-free survival (97% vs 79%; P = .033). CONCLUSION: At a minimum 10-year follow-up, patients undergoing primary hip arthroscopy demonstrated high satisfaction and acceptable outcome scores. In total, 33% of patients underwent reoperation-including 22% who underwent THA. Conversion to THA was associated with patient factors including older age, higher Tönnis grade, and potentially modifiable surgical factors such as labral debridement and capsular nonrepair.

Influence of Concomitant Meniscal Allograft Transplantation on Midterm Outcomes After Osteochondral Allograft Transplantation: A Comparative Matched-Pair Analysis.

BACKGROUND: Osteochondral allograft transplantation (OCAT) is an accepted knee joint-preserving treatment strategy for focal osteochondral lesions that is often conducted in combination with meniscal allograft transplantation (MAT). Despite its frequent and simultaneous utilization, there remains a lack in the literature reporting on outcomes and failure rates after concomitant procedures. PURPOSE: To determine (1) the midterm clinical success rate after OCAT+MAT in comparison with a matched-pair cohort undergoing isolated OCAT, (2) whether patient-specific and procedural variables influence the risk of failure, and (3) patient-reported outcome measures over time. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A single-center matched-pair cohort study was conducted investigating outcomes in patients who underwent OCAT of the medial or lateral femoral condyle with and without MAT between 2004 and 2020. Patients were matched 1:1 by age (±5 years), sex (male or female), body mass index (±5), and grouped Kellgren and Lawrence grade (grades 0-1 or 2-4). The minimum follow-up time was 2 years. Radiographic variables (International Cartilage Regeneration & Joint Preservation Society [ICRS] grade and Kellgren and Lawrence grade) were assessed preoperatively and at follow-up. Subjective patient-reported outcome measures (Lysholm score, Knee injury and Osteoarthritis Outcome Score [KOOS] including subscores, International Knee Documentation Committee [IKDC] score, and visual analog scale score) were collected preoperatively and at follow-up. Clinical failure was defined as revision surgery for graft failure or conversion to total knee arthroplasty. Patient-reported, clinical, and radiographic outcomes were compared between groups. RESULTS: In total, 66 patients (33 treated with isolated OCAT, 33 treated with OCAT+MAT; 57.6% male) with a mean age of 26.3 years (range, 18-62 years) were followed for a mean of 5.6 years (minimum, 2 years; range, 24-218 months). The 2 cohorts showed no difference in Kellgren and Lawrence grade postoperatively (P = .59). There was a significantly higher ICRS grade detected at follow-up in the OCAT+MAT group (2.81 ± 1.10) compared with the OCAT group (2.04 ± 0.96) (P < .05). There were no statistically significant differences between the groups regarding reoperation rate (OCAT: n = 6; OCAT+MAT: n = 13; P = .116), time to reoperation (OCAT: 46.67 ± 47.27 months vs OCAT+MAT: 28.08 ± 30.16 months; P = .061), and failure rate (OCAT: n = 4 [12.1%] vs OCAT+MAT: n = 5 [15.2%]; P = .66). In the OCAT+MAT group, an increase of tibial slope by 1° conferred a 1.65-fold increase in the hazard for failure over decreased slope (hazard ratio, 1.65; 95% CI, 1.10-2.50; P < .05). The overall survival rate was 86% at a mean follow-up of 5.6 years. Patient-reported outcome scores were significantly improved at the final follow-up compared with preoperative status. No significant differences were seen between groups with respect to subjective IKDC, Lysholm, Tegner, and KOOS results, except for the KOOS Symptoms subscale score, which was significantly higher in the OCAT+MAT group than in the OCAT group (mean difference, 14.6; P < .05) and did exceed the minimal clinically important difference threshold of 10.7. CONCLUSION: Midterm results after isolated OCAT and OCAT+MAT show high rates of healing and sustainable subjective improvement of knee function and quality of life. However, it should be noted that the difference in reoperation rate and time to reoperation between the groups is arguably clinically important and that lack of statistical significance may be because of low power. These results imply that isolated OCAT is an efficient joint-preserving treatment that can be combined with MAT in well-selected patients with meniscal insufficiency without negative influence on global clinical outcomes.

Dynamic enhancer landscapes in human craniofacial development.

The genetic basis of human facial variation and craniofacial birth defects remains poorly understood. Distant-acting transcriptional enhancers control the fine-tuned spatiotemporal expression of genes during critical stages of craniofacial development. However, a lack of accurate maps of the genomic locations and cell type-resolved activities of craniofacial enhancers prevents their systematic exploration in human genetics studies. Here, we combine histone modification, chromatin accessibility, and gene expression profiling of human craniofacial development with single-cell analyses of the developing mouse face to define the regulatory landscape of facial development at tissue- and single cell-resolution. We provide temporal activity profiles for 14,000 human developmental craniofacial enhancers. We find that 56% of human craniofacial enhancers share chromatin accessibility in the mouse and we provide cell population- and embryonic stage-resolved predictions of their in vivo activity. Taken together, our data provide an expansive resource for genetic and developmental studies of human craniofacial development.

Minimum 10-Year Outcomes of Matrix-Induced Autologous Chondrocyte Implantation in the Knee: A Systematic Review.

BACKGROUND: Matrix-induced autologous chondrocyte implantation (MACI) is an established cell-based therapy for the treatment of chondral defects of the knee. As long-term outcomes are now being reported in the literature, it is important to systematically review available evidence to better inform clinical practice. PURPOSE: To report (1) subjective patient-reported outcomes (PROs) and (2) the rate of graft failure, reoperation, and progression to total knee arthroplasty (TKA) after undergoing MACI of the knee at a minimum 10-year follow-up. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A comprehensive search of Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus from 2008 to September 15, 2022, was conducted in the English language. Study eligibility criteria included (1) full-text articles in the English language, (2) patients undergoing a MACI within the knee, (3) clinical outcomes reported, and (4) a minimum 10-year follow-up. RESULTS: In total, 168 patients (99 male, 69 female; mean age, 37 years [range, 15-63 years]; mean body mass index, 26.2 [range, 18.6-39.4]) representing 188 treated chondral defects at a minimum 10-year follow-up after MACI were included in this review. Significant and durable long-term improvements were observed across multiple PRO measures. Follow-up magnetic resonance imaging (MRI), when performed, also demonstrated satisfactory defect fill and an intact graft in the majority of patients. The all-cause reoperation rate was 9.0%, with an overall 7.4% rate of progression to TKA at 10 to 17 years of follow-up. CONCLUSION: At a minimum 10-year follow-up, patients undergoing MACI for knee chondral defects demonstrated significant and durable improvements in PROs, satisfactory defect fill on MRI-based assessment, and low rates of reoperation and TKA. These data support the use of MACI as a long-term treatment of focal cartilage defects of the knee.

Medial Collateral Ligament Reconstruction of the Knee: The Modified Marx Technique With Adjustable-Loop Femoral Fixation and Posteromedial Corner Plication.

The medial collateral ligament serves as the primary stabilizer to valgus stress on the medial side of the knee and is the most commonly injured ligament in the knee. Medial collateral ligament reconstruction can provide improved stability and clinical outcomes for patients. Advancements in techniques, including the use of an adjustable-length-loop suspensory fixation device through a longitudinal incision, have been introduced in recent years. The purpose of this Technical Note and video is to provide a minimally invasive method for medial collateral ligament reconstruction with adjustable-loop femoral fixation and posteromedial corner plication.

Outcomes of Shoulder Instability Surgery in Competitive Wrestlers: Outcomes, Reoperations, and Return to Play at 5 Years' Mean Follow-up.

BACKGROUND: Wrestling is a physically demanding sport with young athletes prone to traumatic shoulder instability and a paucity of data evaluating the results of shoulder instability surgery (SIS). PURPOSE: To assess reoperation rates, patient-reported outcomes, and return to wrestling (RTW) after SIS in a cohort of competitive wrestlers. STUDY DESIGN: Case series; Level of evidence, 3. METHODS: All competitive wrestlers with a history of shoulder instability and subsequent surgery at a single institution between 1996 and 2020 were identified. All directions of shoulder instability (anterior shoulder instability [ASI], posterior shoulder instability [PSI], and traumatic multidirectional shoulder instability [TMDI]) were analyzed. Exclusions included revision SIS and <2 years of follow-up. Athletes were contacted for determination of complications, RTW, and Western Ontario Shoulder Instability Index scores. RESULTS: Ultimately, 104 wrestlers were included with a mean age at initial instability of 16.9 years (range, 12.0-22.7 years), mean age at surgery of 18.9 years (range, 14.0-29.0 years), and a mean follow-up of 5.2 years (range, 2.0-22.0 years). A total of 58 (55.8%) wrestlers were evaluated after a single shoulder instability event, while 46 (44.2%) sustained multiple events before evaluation. ASI was the most common direction (n = 79; 76.0%), followed by PSI (n = 14; 13.5%) and TMDI (n = 11; 10.6%). Surgical treatment was most commonly an arthroscopic soft tissue stabilization (n = 88; 84.6%), with open soft tissue repair (n = 13; 12.5%) and open bony augmentation (n = 3; 2.9%) performed less frequently. RTW occurred in 57.3% of wrestlers at a mean of 9.8 months. Recurrent instability was the most common complication, occurring in 18 (17.3%) wrestlers. Revision SIS was performed in 15 (14.4%) wrestlers. Across the entire cohort, survivorship rates free from recurrent instability and revision surgery were 90.4% and 92.5% at 2 years, 71.9% and 70.7% at 5 years, and 71.9% and 66.5% at 10 years, respectively. Preoperative recurrent instability was an independent risk factor for postoperative recurrent instability (hazard ratio, 3.8; 95% CI, 1.33-11.03; P = .012). CONCLUSION: Competitive wrestlers with multiple dislocations before initial clinical evaluation were 3.8 times more likely to experience postoperative recurrent instability. Patients should be counseled that despite SIS, only 57.3% returned to wrestling after surgery.

Minimally Invasive Quadriceps Tendon Harvest for Anterior Cruciate Ligament Reconstruction Using the Quadriceps Tendon Harvest Guide (QUADTRAC) System and Repair Augmentation With a Bioinductive Implant.

Quadriceps tendon autografts are an increasingly popular choice for anterior cruciate ligament (ACL) reconstruction, with decreased donor-site morbidity alongside good patient outcomes. Although harvesting of the tendon can be done in a minimally invasive fashion, this introduces some difficulty with visualization and consistency of graft sizing. The purpose of this Technical Note and video is to provide a method of quadriceps tendon autograft harvesting using the Quadriceps Tendon Harvest Guide System (QUADTRAC) in a single-bundle ACL reconstruction.

Survivorship of 157 Arthroscopic Meniscal Allograft Transplants Using Bone Fixation at a Mean of 7 Years and Prognostic Factors Analysis.

BACKGROUND: Meniscal allograft transplantation (MAT) is an accepted and effective treatment option in the context of unsalvageable menisci, particularly in young and active patients. It has been shown to reduce pain and improve knee function in previously symptomatic patients. However, there is still limited knowledge about the long-term survival rates of allografts, the durability of clinical results, and the influence of patient-specific parameters, such as leg alignment, tibial slope, and preoperative International Cartilage Regeneration & Joint Preservation Society (ICRS) grade. PURPOSE: To determine (1) the long-term clinical success rate after MAT with bony fixation in a large, single-center cohort of consecutive patients, and (2) if patient-specific and procedural variables influence the clinical, anatomic, and subjective outcomes and risk of failure. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Data on 185 consecutive knees undergoing MAT in a single institution were prospectively collected and screened for inclusion in this study. The minimum follow-up time was 2 years. Radiographic variables (ICRS grade and Kellgren-Lawrence grade) were assessed preoperatively and at follow-up. Subjective patient-reported outcome measures (PROMs) (Lysholm score, Knee injury and Osteoarthritis Outcome Score [KOOS] including subscores, International Knee Documentation Committee [IKDC] score, and visual analog scale [VAS] score) were collected preoperatively and at follow-up. Clinical failure was defined as revision surgery due to graft failure or conversion to total knee arthroplasty. Anatomic failure was considered a tear covering >20% of the allograft, any peripheral tear, and unstable peripheral fixation leading to dislocation of the graft. Subjective failure was defined as Lysholm score ≤65. Preoperative tibial slope and leg alignment were assessed. Survival analyses were performed using the Kaplan-Meier estimate. Univariate and multivariate analyses were performed to determine risk factors for clinical and anatomic failure. RESULTS: A total of 157 knees met inclusion criteria. After a mean follow-up time of 7 ± 3.5 years, 127 (80.9%) knees were free of clinical, anatomic, and subjective failure. Fourteen (8.9%) knees experienced clinical failure, 26 (16.6%) knees were identified as having experienced anatomic failure, and 13 (8.3%) patients experienced subjective failure with a reported Lysholm score of ≤65 at a mean follow-up of 7 years. Concurrent osteochondral allograft transplantation was identified as a predictor of both clinical (hazard ratio [HR], 4.55; 95% CI, 1.46-14.17; P = .009) and anatomic (HR, 3.05; 95% CI, 1.34-6.92; P = .008) failure. Cartilage damage of ICRS grade 3 or 4 of the index compartment conveyed an increased risk for clinical (HR, 3.41; 95% CI, 1.05-11.01; P = .04) and anatomic (HR, 3.04; 95% CI, 1.31-7.11; P = .01) failure. High-grade cartilage damage preoperatively (HR, 10.67; 95% CI, 1.037-109.768; P = .046), patient age >25 years (HR, 5.44; 95% CI, 0.120-246.070; P = .384), and a body mass index >30 (HR, 2.24; 95% CI, 0.748-6.705; P = .149) were associated with subjective failure. PROMs including KOOS and IKDC were significantly improved at final follow-up compared with preoperative scores across all measurements (P < .005). CONCLUSION: MAT showed good to excellent clinical results at a mean follow-up of 7 years. Low ICRS lesion grade was associated with a higher clinical and anatomic survival rate. Patients with concurrent OCA transplantation are at a higher risk of clinical and anatomic failure, but still report significantly improved PROMs. These results suggest that MAT has a lasting beneficial effect both in isolation and in complex cases with ≥1 concurrent procedures.

Combined Single-Shot Infiltration Between the Popliteal Artery and Capsule of the Knee and Adductor Canal Block With Bupivacaine, Dexmedetomidine, and Dexamethasone for Total Knee Arthroplasty: A Propensity-Matched Analysis.

Background: To investigate if combined single-shot adductor canal blockade (ACB) and infiltration between the popliteal artery and capsule of the knee (IPACK) provide better postoperative pain management compared to ACB alone for patients undergoing unilateral total knee arthroplasty (TKA). Methods: This retrospective cohort study included adult patients who underwent primary, unilateral TKA. Patients were separated into 2 cohorts: single-shot ACB alone (performed with bupivacaine 0.25%) and combined single-shot ACB + IPACK (performed with bupivacaine 0.25%, dexmedetomidine 1 mg/kg, and dexamethasone 4 mg). Patients were propensity-matched 1:1. The primary study outcome was total opioid consumption converted to morphine milligram equivalents (MME) per eight-hour interval and postoperative day. Secondary outcomes included pain scores, length of stay, ambulation distance, return to emergency department, hospital readmission, and 30-day adverse events. Results: One hundred eighty patients were identified, of which propensity matching used 71% to yield 64 patients receiving ACB alone and 64 receiving combined ACB + IPACK. Combined ACB + IPACK had significantly lower total summative MME throughout the entire postoperative stay (P = .002) and cumulatively after the first 24 hours (P < .001). Combined ACB + IPACK also had lower mean pain scores for 0-8 hours (P = .005) and 8-16 hours (P = .009) postoperatively. There were no significant differences in secondary outcomes. Conclusions: Combined single-shot ACB + IPACK block was associated with lower total narcotic intake and mean pain scores during most of the immediate postoperative period following primary, unilateral TKA compared to ACB alone. Implementing longer-acting, single-shot ACB + IPACK for TKA can balance effective and more selective pain management with early rehabilitation.

Long-term Outcomes After Surgical Reconstruction of Multiligamentous Knee Injuries: Results at Minimum 10-Year Follow-up.

Background: Multiligamentous knee injuries (MLKIs) are devastating injuries with concomitant injuries that complicate treatment and recovery. Short-term studies have shown satisfactory patient outcomes after surgical treatment; however, evaluations of long-term outcomes remain scarce. Purpose: To evaluate long-term outcomes after surgically reconstructed MLKIs and further investigate the relationship between patient age on clinical outcomes. Study Design: Case series; Level of evidence, 4. Methods: A total of 55 knees (age, 36 ± 11 years; 24% female subjects) who underwent surgical reconstruction for MLKI between 1992 and 2013 met the study inclusion criteria and were evaluated with postoperative patient-reported outcomes (PROs) including International Knee Documentation Committee (IKDC) score, Lysholm score, visual analog scale (VAS) for pain, Forgotten Joint Score, subjective improvement ratings and surgery satisfaction, and Tegner activity scores. PRO scores, revision, and conversion to arthroplasty were analyzed using descriptive statistics, linear regression, Wilcoxon rank-sum, and Fisher exact tests. Results: At final follow-up (mean, 15 ± 5 years; range, 10-31 years), 67% of the cohort reported subjective improvement in their knee, and 82% reported satisfaction with their surgery. Compared with preoperative scores, there were significant improvements in postoperative VAS pain at rest in the full cohort, age ≤30-year cohort, and age >30-year cohort (4 ± 1 vs 2 ± 2; 4 ± 1 vs 2 ± 3; 4 ± 1 vs 1 ± 2, respectively; P≤ .029 for all) but significant reductions in Tegner scores (6 ± 3 vs 4 ± 2; 7 ± 2 vs 5 ± 2; 5 ± 2 vs 3 ± 1; P≤ .003 for all). Younger patients had higher postoperative Tegner scores than older patients (5 ± 2 vs 3 ± 1, respectively; P = .003), but no other differences in PROs were observed based on age. At a mean 15-year follow-up, 3.6% of the cohort underwent revision ligament surgery and 10.9% required arthroplasty. Conclusion: The majority of the cohort reported modest subjective improvement and were satisfied with their surgery. Gradual but expected age-related decreases in Tegner scores were observed, and some patients demonstrated continued symptomatic and functional limitations, but mean PRO scores remained satisfactory. Revision surgery and conversion to arthroplasty were not commonly required.

Satisfactory Clinical Outcomes and Continuance of Sports After Hip Arthroscopic Labral Repair in Young Competitive Athletes at Minimum 8.5-Year Follow-Up.

PURPOSE: To evaluate long-term patient-reported outcomes and achievement rates of patient acceptable symptomatic state (PASS) in young athletes undergoing hip arthroscopy, and to report long-term sports continuance and reoperation. METHODS: Inclusion criteria consisted of age <24 years at surgery, femoroacetabular impingement undergoing primary hip arthroscopy with labral repair, and participation in sport with intent to return to sport after surgery. The enrollment period was from April 2009 to June 2014. Modified Harris Hip Scores (mHHS), Hip Outcome Score (HOS), HOS Activities of Daily Living (HOS-ADL), and HOS Sport (HOS-Sport) were collected preoperatively, 2 years' postoperatively, and final follow-up. Patients were evaluated for PASS achievement, reoperation, and sports participation. RESULTS: Forty-two hips in 37 patients (11 male, 26 female, age: 17.7 ± 2.1 years, range 13.6-23.0, body mass index 22.8 ± 2.9, range 17.6-33.7) met inclusion criteria and were followed for 10.0 ± 1.3 years (range 8.5-13.0) postoperatively. Mean mHHS, HOS-ADL and HOS-Sports outcome scores at minimum 8.5 years were 82.2 ± 12.9, 89.6 ± 10.9, and 81.8 ± 16.4, respectively, with significant (P < .001) postoperative improvements. Thirty survey respondents (83%) met PASS for mHHS, 27 (75%) for HOS-ADL, and 24 (67%) for HOS-Sports. At minimum 8.5-year follow-up, only 9 of 37 (24%) cited their hip as the reason for stopping sport. Of the remaining patients, 17 of 28 (61%), continued playing their initial sport. There was no difference in patient-reported outcomes between patients who endorsed sports continuance and patients who did not report sports continuance and did not cite their hip as a reason (P ≥ .229). At final follow-up, 4 hips (10%) had undergone subsequent surgical intervention at a mean of 4.8 ± 3.3 years (range 1.0-8.4) postoperatively. CONCLUSIONS: Durable mid-term outcomes and satisfactory PASS achievement rates are observed in young amateur athletes undergoing primary hip arthroscopy. At minimum 8.5-year follow up, approximately 1 in 4 patients discontinue their sports due to hip related reasons. LEVEL OF EVIDENCE: Level IV, case-series.

Single-cell analysis of chromatin accessibility in the adult mouse brain.

Recent advances in single-cell technologies have led to the discovery of thousands of brain cell types; however, our understanding of the gene regulatory programs in these cell types is far from complete1-4. Here we report a comprehensive atlas of candidate cis-regulatory DNA elements (cCREs) in the adult mouse brain, generated by analysing chromatin accessibility in 2.3 million individual brain cells from 117 anatomical dissections. The atlas includes approximately 1 million cCREs and their chromatin accessibility across 1,482 distinct brain cell populations, adding over 446,000 cCREs to the most recent such annotation in the mouse genome. The mouse brain cCREs are moderately conserved in the human brain. The mouse-specific cCREs-specifically, those identified from a subset of cortical excitatory neurons-are strongly enriched for transposable elements, suggesting a potential role for transposable elements in the emergence of new regulatory programs and neuronal diversity. Finally, we infer the gene regulatory networks in over 260 subclasses of mouse brain cells and develop deep-learning models to predict the activities of gene regulatory elements in different brain cell types from the DNA sequence alone. Our results provide a resource for the analysis of cell-type-specific gene regulation programs in both mouse and human brains.

Long-Term Outcomes of Primary Hip Arthroscopy With Labral Repair for Femoroacetabular Impingement: Results at Minimum 9-Year Follow-up.

Background: Hip arthroscopy continues to advance and become increasingly commonly performed. With the evolution of techniques and instrumentation, labral repair rather than debridement has emerged as the treatment of choice for labral pathology. There remains a lack of data on long-term outcomes after labral repair. Purpose: To (1) evaluate long-term patient-reported outcomes of primary hip arthroscopy with labral repair for femoroacetabular impingement, (2) report achievement rates of Patient Acceptable Symptom State (PASS) and minimal clinically important difference (MCID), and (3) investigate rates of reoperation and progression to total hip arthroplasty (THA). Study Design: Case series; Level of evidence, 4. Methods: Prospectively collected data were reviewed for patients who underwent primary hip arthroscopy with labral repair between 2010 and 2013. Patients' medical records were reviewed for demographic characteristics, intraoperative findings, reoperation, and progression to THA. Patients were assessed pre- and postoperatively using the following scales: visual analog scale (VAS) for pain; Tegner activity scale; modified Harris Hip Score (mHHS); 12-item International Hip Outcome Tool (iHOT-12); Hip Outcome Score-Activities of Daily Living (HOS-ADL); HOS-Sport-Specific Subscale (HOS-SSS); and Non-Arthritic Hip Score. Patients were also surveyed for satisfaction, subjective improvement, and level of function. Results: A total of 32 patients (n = 24 women; n = 8 men) with a mean age of 27.7 years (range, 13.6-51 years) were evaluated for a mean of 9.4 years (range, 9-12.1 years). Patients achieved significant mean improvements in VAS pain at rest of 2 points, VAS pain with use of 1.9, mHHS of 19.9 points, iHOT-12 of 33.5 points, HOS-ADL of 17.4 points, and HOS-SSS of 29.5 points (P≤ .015 for all). Eleven patients (34.4%) underwent reoperation and 4 (12.5%) progressed to THA during the study period. At the final follow-up, the MCID achievement rate was ≥68%, the PASS achievement rates ranged from 39% to 65%, and the mean patient satisfaction was 8.1 on a 1 to 10 scale, with 10 denoting most satisfied. Conclusion: Patients demonstrated significant postoperative improvements in pain, mHHS, iHOT-12, HOS-ADL, and HOS-SSS scores at 9 years postoperatively. The all-cause reoperation rate was 34.4%, and 12.5% of patients progressed to THA.

A comparative atlas of single-cell chromatin accessibility in the human brain.

Recent advances in single-cell transcriptomics have illuminated the diverse neuronal and glial cell types within the human brain. However, the regulatory programs governing cell identity and function remain unclear. Using a single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq), we explored open chromatin landscapes across 1.1 million cells in 42 brain regions from three adults. Integrating this data unveiled 107 distinct cell types and their specific utilization of 544,735 candidate cis-regulatory DNA elements (cCREs) in the human genome. Nearly a third of the cCREs demonstrated conservation and chromatin accessibility in the mouse brain cells. We reveal strong links between specific brain cell types and neuropsychiatric disorders including schizophrenia, bipolar disorder, Alzheimer's disease (AD), and major depression, and have developed deep learning models to predict the regulatory roles of noncoding risk variants in these disorders.

Colchicine for the Prevention of Recurrent Arrhythmia After Catheter Ablation of Atrial Fibrillation: Results of a Single-Center, Retrospective Study.

BACKGROUND: There is evidence to suggest that colchicine reduces the risk of recurrent atrial fibrillation (AF) after catheter ablation; however, the tolerability and safety of colchicine in routine practice is unknown. METHODS: Patients undergoing catheter ablation for AF who received colchicine after ablation were matched 1:1 to patients who did not by age, sex, and renal function. Recurrent AF was compared between groups categorically at 12 months and via propensity weighted Cox proportional hazards models with and without a 3-month blanking period. RESULTS: Overall, 180 patients (n = 90 colchicine and n = 90 matched controls) were followed for a median (Q1, Q3) of 10.3 (7.0, 12.0) months. Mean age was 65.3 ± 9.1 years, 33.9% were women, mean CHA2DS2-VASc score was 2.9 ± 1.5, and 51.1% had persistent AF. Most patients (70%) received colchicine 0.6 mg daily for a median of 30 days. In the colchicine group, 55 patients (61.1%) were receiving at least one known interacting medication with colchicine. After ablation, one patient required colchicine dose reduction and four patients required discontinuation. After adjusting for covariate imbalance using propensity weighting, no significant association between colchicine use and AF recurrence was identified (adjusted hazard ratio 0.94, 95% confidence interval [CI] 0.48-1.85; p = 0.853). No significant association was found between colchicine use and all-cause hospitalizations (adjusted odds ratio 0.74, 95% CI 0.28-1.96; p = 0.548). CONCLUSION: Despite the frequent presence of drug-drug interactions, a 30-day course of colchicine is well-tolerated after AF ablation; however, we did not observe any association between colchicine and lower rates of AF recurrence or hospitalization.

A super-enhancer-regulated RNA-binding protein cascade drives pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy in need of new therapeutic options. Using unbiased analyses of super-enhancers (SEs) as sentinels of core genes involved in cell-specific function, here we uncover a druggable SE-mediated RNA-binding protein (RBP) cascade that supports PDAC growth through enhanced mRNA translation. This cascade is driven by a SE associated with the RBP heterogeneous nuclear ribonucleoprotein F, which stabilizes protein arginine methyltransferase 1 (PRMT1) to, in turn, control the translational mediator ubiquitin-associated protein 2-like. All three of these genes and the regulatory SE are essential for PDAC growth and coordinately regulated by the Myc oncogene. In line with this, modulation of the RBP network by PRMT1 inhibition reveals a unique vulnerability in Myc-high PDAC patient organoids and markedly reduces tumor growth in male mice. Our study highlights a functional link between epigenetic regulation and mRNA translation and identifies components that comprise unexpected therapeutic targets for PDAC.

Human microglia maturation is underpinned by specific gene regulatory networks.

Microglia phenotypes are highly regulated by the brain environment, but the transcriptional networks that specify the maturation of human microglia are poorly understood. Here, we characterized stage-specific transcriptomes and epigenetic landscapes of fetal and postnatal human microglia and acquired corresponding data in induced pluripotent stem cell (iPSC)-derived microglia, in cerebral organoids, and following engraftment into humanized mice. Parallel development of computational approaches that considered transcription factor (TF) co-occurrence and enhancer activity allowed prediction of shared and state-specific gene regulatory networks associated with fetal and postnatal microglia. Additionally, many features of the human fetal-to-postnatal transition were recapitulated in a time-dependent manner following the engraftment of iPSC cells into humanized mice. These data and accompanying computational approaches will facilitate further efforts to elucidate mechanisms by which human microglia acquire stage- and disease-specific phenotypes.