Citations

Abstract Background and aims This post hoc analysis evaluated the corticosteroid-sparing effects of risankizumab (RZB) therapy in patients with moderate-to-severe ulcerative colitis in the phase 3 induction and maintenance studies, INSPIRE and COMMAND. Methods Patients were randomized (2:1) to 12 weeks of intravenous RZB or placebo (PBO) induction therapy; responders to intravenous RZB were randomized (1:1:1) to receive subcutaneous RZB 180 mg, 360 mg, or PBO (RZB withdrawal) maintenance therapy. Baseline corticosteroid doses were maintained during induction, with a mandatory taper beginning at maintenance week 0. Efficacy outcomes were evaluated by baseline corticosteroid use at induction week 12, while corticosteroid-free clinical and endoscopic outcomes were assessed at maintenance week 52 among the overall population and among patients on corticosteroids at baseline. Safety was also assessed. Results At baseline, 35.7% (348/975) of patients were taking corticosteroids. At induction week 12, greater rates were observed for clinical, endoscopic, and patient-reported outcomes in RZB 1200 mg-treated patients compared with PBO, regardless of baseline corticosteroid use. RZB 180 mg and 360 mg treatment resulted in higher corticosteroid discontinuation rates (RZB 180 mg 64.9% [48/74]; RZB 360 mg 54.2% [32/59]; PBO [withdrawal] 36.8% [25/68], P ≤ .01) and corticosteroid-free clinical, endoscopic, and patient-reported outcomes at week 52, compared with PBO (withdrawal). The rates of treatment-emergent adverse events were similar regardless of baseline corticosteroid use during induction and maintenance. Conclusions The efficacy of RZB induction therapy was independent of corticosteroid use, with high rates of corticosteroid-free outcomes observed in the overall population and among patients with baseline corticosteroid use, reaffirming the potential of RZB to serve as a corticosteroid-sparing therapy for patients with ulcerative colitis. Clinicaltrial.gov numbers NCT03398148 and NCT03398135

Background: Cognitive change is an important factor in understanding dementia. Estimating effects of exposures on cognitive change requires choosing an analytical timescale, typically time on study or current age. There is limited consensus regarding timescale choice in epidemiologic cognitive aging research. Methods: Using a coordinated analytic approach in 10 cohorts of older adults, we evaluated whether estimated effects of two exposures on memory change differed depending on timescale (time on study or current age). We modeled effects of apolipoprotein-E (APOE) ε4 genotype (a time-invariant exposure) and diabetes (a potentially time-varying/acquired exposure evaluated at baseline) using mixed-effects models with linear and nonlinear time specifications for both timescales. Results: Among APOE ε4 carriers, model-estimated memory scores at baseline (time on study timescale) or at each cohort’s median baseline age (current age timescale) were lower, and the average rate of decline was faster than among APOE ε4 noncarriers. Model-estimated memory scores at baseline or at median baseline age were generally similar across baseline diabetes status, with variability across cohorts in the diabetes-memory change association. In some cohorts, trends in diabetes-memory change associations differed in direction across timescales. Conclusions: Timescale was largely inconsequential for estimated effects of APOE genotype, but yielded differences in estimated diabetes effects, raising questions about the appropriate scale. The current age scale may be problematic because diabetes was measured heterogeneously in age across individuals, a common issue in aging cohorts. Our work demonstrates approaches to evaluate alternative timescales, including in multicohort analyses, and highlights potential implications for estimated exposure effects on cognitive change.

Abstract Introduction: Periacetabular osteotomy (PAO) is a complex procedure historically requiring inpatient stay. There is increased emphasis for these to be performed on an outpatient basis by insurance companies. The purpose of this study was to investigate the proportion of various surgical listing classifications (outpatient, outpatient-overnight, inpatient), the incidence of subsequent denial/request for additional documentation for approval of inpatient stay, and to characterize the average length of stay (LOS) following PAO. Methods: A retrospective chart review was performed to identify all PAOs, performed by four participating surgeons, at a single academic institution over a two-year period. The initial listing status as an outpatient-overnight or inpatient procedure was identified. Whether a preoperative peer review was required for approval of inpatient listings as well as if additional documentation was necessary to convert outpatient-overnight listings to inpatient stays were also recorded. Results: A total of 140 PAOs amongst 117 patients were performed with 25 (17.9%) initially listed as an inpatient stay and 115 (82.1%) listed as outpatient-overnight. Of the 25 PAOs listed as inpatient, 2 (8.0%) required a preoperative peer review process to justify or clarify listing status. The average LOS was 1.9 ± 1.4 days with 55.7% (78/140) of PAOs staying two or more nights in the hospital. Only 6 PAOs (4.3%) went home the same day as surgery. Of the 115 PAOs listed as an outpatient-overnight, 53 (46.1%) converted to an inpatient stay. Conclusion: Over half of PAOs performed required inpatient stay beyond outpatient-overnight status. Preoperative peer-to-peer review for inpatient stay approval was modestly frequent (8% of inpatient listings), and all conversions to inpatient required additional service documentation to support status conversion. Understanding trends in postoperative hospitalizations and LOS might allow for better informed partnerships between surgeons and insurance companies creating more efficient pre-authorizations, billing practices, and expected patterns of patient care and discharge.

Abstract Background: Osteochondral allograft and autograft transplantation for femoral head defects have emerged as promising treatments for concomitant cartilage and subchondral bone injuries in young patients. The purpose of this study was to evaluate the clinical and radiological outcomes of patients who underwent osteochondral allograft or autograft transplantation for femoral head defects and access any risk factors that may lead to conversion to THA. Methods: All patients who underwent osteochondral allograft or autograft transplantation for femoral head defects were analyzed. All patients had symptomatic femoral head osteochondral defects identifiable on advanced imaging such as computed tomography or magnetic resonance imaging. Clinical outcomes were assessed at final follow-up with the modified Harris Hip Score (mHHS), Hip Outcome Score – Activities of Daily Living (HOS-ADL), Hip Outcome Score – Sport-Specific Subscale (HOS-SSS), and International Hip Outcome Tool (iHOT-12). Additionally, patients were assessed radiographically preoperatively and at a final postoperative visit using anterior-posterior and lateral radiographs for osteoarthritis using Tönnis grading. Results: A total of 27 patients were included in this study (19 osteochondral allograft transplantation, 8 osteochondral autograft transplantation). The overall mean follow-up was 4.7 years. The average mHHS, HOS-ADL, HOS-SSS, and iHOT-12 for the allograft cohort were 86.7, 92.8, 81.4, and 79.0, respectively, while for the autograft cohort it was 87.6, 92.7, 83.1, and 82.0, respectively. For the allograft cohort, there were a total of 5 reoperations (26.3%) consisting of 4 THA at a mean of 1.9 years and 1 trochanteric osteotomy nonunion at 0.7 year. For the remaining allograft patients who did not undergo treatment failure, only one (6.7%) had radiographic osteoarthritis progression. None of the patients in the autograft cohort underwent THA. Overall, conversion to THA was 14.8%. Conclusion: Osteochondral allograft and autograft transplantation for femoral head defects demonstrated overall favorable clinical outcomes and conversion to THA at mean 5-year follow-up and should be considered for patients with focal femoral head defects.

Abstract Introduction: Labral injury at the time of open and arthroscopic hip preservation surgery for symptomatic femoroacetabular impingement (FAI) is managed with debridement versus refixation by the treating surgeon based on tear pattern, tissue quality, and hip morphology. While refixation has been favored based on mid-term outcomes in some series, differences in the long-term patient reported outcomes (PROMS) have not been defined in well-designed and matched prospective series. Methods: This study consisted of a prospective, multi-center cohort that underwent primary surgical treatment for symptomatic FAI. Patients were included if they underwent corrective osteoplasty and a labral refixation or a labral debridement procedure. Using a ratio of 1:1, hips with labral refixation and labral debridement were matched by age, sex, and surgical approach. Postoperative assessments were conducted at a minimum 8 years after surgery using PROMS and assessment of reoperations. Results: A total of 237 hips (n=188 labral refixation, n=49 labral debridement) met the inclusion criteria for the current study. 48 hips from the labral refixation and 48 hips from debridement groups with mean follow-up of 10.3±1.7 years and 10.6±2.1 years respectively were included. No significant differences were observed in the femoral head, acetabular cartilage grade, or labral grade between the groups. The mHHS improved 19.8±19.6 and 23.4±16.8 from baseline to the final follow-up in the labral refixation and debridement groups, respectively (p=0.43). There were no significant differences in PROMS between the labral refixation and debridement groups. Overall, 66% and 76% of the labral refixation and debridement groups achieved the MCID for the mHHS respectively (p=0.30). There were more revision surgeries with labral refixation than with debridement (10.4% vs. 2.1%, p=0.09), but more conversions to total hip replacement in the labral debridement group (8.3% vs. 4.2%, p=0.38), but neither of these differences were statistically significant. Discussion: Both labral refixation and debridement are effective with durable improvement in PROMS at a mean of 10 years in a prospective cohort of patients treated surgically for symptomatic FAI. No significant differences in baseline or final PROMS were observed, and similar rates of revision and conversion to hip replacement were observed in the debridement and refixation groups.

Summary Introduction Peroral plication of the esophagus (POPE) can reduce sump size and improve symptoms in end-stage achalasia. However, its long-term efficacy and safety are unknown. Methods Patients with end-stage achalasia who underwent POPE at our institution (2016–2024) were identified. Data were abstracted for patient demographics, procedural details, and clinical and radiographic outcomes. Results Twelve patients underwent POPE. The technical success rate was 100%, with mean procedural time of 57 minutes and without adverse events. Symptomatic improvement occurred in 75% of patients (mean follow-up of 15 months), while 86% had radiographic improvement in sump size. Repeat POPE in 6 (50%) patients a mean of 2.6 years after index POPE and a third POPE in four (33%) patients a mean of 3.1 years later was performed, with similar technical success rates and outcomes to the index POPE. Conclusions POPE is a safe and repeatable long-term therapeutic option in end-stage achalasia.

Abstract Introduction: Low-dose computed tomography (CT) has been increasingly utilized in FAI due to its improved ability to characterize the complex and variable hip morphologies of FAI patients, compared to plain radiographs. This study defined FAI morphology between females and males as well as across adolescents, young adults, and older adults. Methods: A multi-center, prospective cohort of FAI patients undergoing primary arthroscopy was performed. Patients 14-45 years of age with idiopathic FAI were included. Low-dose CT was used for preoperative planning. Analysis focused on acetabular and femoral morphology and the differences between females/males and adolescents (A,14-18.9)/young adults (Y,19-24.9)/older adults (O,25+). Adolescents were the reference group during analysis. Results: There were 604 patients with CT data. Mean age was 24.9 years with 55.9% female. Males had more anterosuperior coverage (i.e. 64.2% vs 62.5% at 1:00), lower version (14.1° vs 18.0°), smaller femoral neck-shaft angles (130.9° vs 133.4°), and larger alpha angles (i.e. 72.1° vs 58.6° at 1:00) compared to females. Multivariable analysis demonstrated that females had associations with more femoral anteversion (OR: 1.05,CI: 1.03-1.07) and larger femoral neck-shaft angles (OR: 1.11,CI: 1.06-1.16). Males has associations with larger alpha angles at 1:00 (OR: 1.05,CI: 1.02-1.07) and 1:30 (OR: 1.03,CI: 1.00-1.06) as well as radial coverage at 1:00 (OR: 1.18,CI: 1.11-1.26). For females, adolescents had slightly less radial coverage at 2:00 (49.9%) compared to young (51.2%) and older adults (51.4%). Femoral neck-shaft angle decreased across age groups (A: 134.4°,Y: 133.0°,O: 132.7°). Alpha angles increased at 2:00 with age (A:54.6°,Y:55.3°,O:58.7°). Multivariable analysis had femoral neck-shaft angle decreasing for young (OR: 0.932,CI: 0.87) and older adults (OR:0.92,CI: 0.86-0.98) and it also had alpha angle at 1:15 increasing for young adults (OR: 1.03,CI: 1.00-1.06) and older adults (OR: 1.03,CI: 1.01-1.06). Males did not have any appreciable differences alpha angles, femoral version, or acetabular coverage across age groups. Conclusion: Differences in morphology identified on CT exist between females and males as well as across age groups for females. These differences may offer insight into disease pathomechanics between these patient populations. Further studies should confirm these findings and look at how they affect patient outcomes after treatment.

Abstract Background: Long-term outcomes of FAI surgery are critical to understand it’s hip preserving ability, yet few studies have reported mid to long-term survivorship following FAI surgery. The purpose of this study was to report rates of treatment failure after first-generation FAI surgery at an average 10- year follow-up. Methods: A prospective, multicenter cohort study assessed patients treated for FAI with hip arthroscopy or surgical dislocation by seven surgeons at four institutions from 2008 to 2012. Inclusion criteria included primary surgery and diagnosis of isolated cam or combined cam/pincer type FAI. At an average 10-year follow-up, 362/452 eligible hips (80.1%) achieved follow-up. Cox proportional hazards model was used to identify predictors of conversion to total hip arthroplasty (THA). Results: Three hundred and sixty two hips were evaluated at a mean of 10.0 ± 2.3 years follow-up. At time of final follow-up, 34 hips (9.2%) had undergone conversion to THA at a mean of 5.2 ± 3.1 years post-operatively. An additional 18 patients (4.9%) underwent non-arthroplasty revision preservation surgery at a mean of 2.0 ± 1.5 years post-operatively. The Kaplan Meier survivorship rates after 5 and 10 years of surgery were 94.9% and 95.2% for conversion to THA and 91 % and 95.2% for revision hip preservation. Older age (HR:1.06, CI: 1.01-1.10; p=0.009), BMI≥30 (HR:4.14, CI:1.52-11.24, p=0.005), male sex (HR:3.23, CI: 1.18-9.09, p=0.02), and lower baseline mHHS (HR:1.03, CI: 1.01-1.04, p=0.01) were significant predictors of conversion to THA. Conclusion: This study demonstrates that FAI surgery yields durable outcomes with the majority of patients (85.9%) not requiring revision surgery or conversion to total hip arthroplasty at an average 10 years. Age 30 years, male sex, and obesity were significantly associated with the risk of THA conversion.

ABSTRACTImmune thrombotic thrombocytopenic purpura (iTTP) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular occlusion secondary to acquired ADAMTS13 deficiency. Contemporary data regarding iTTP treatment practices in the US, including the use of caplacizumab, are lacking. We aimed to characterize the demographics and therapies, including medications and apheresis practices, in patients with iTTP in the US. We retrospectively analyzed iTTP cases at 15 sites in the US that provide comprehensive care for patients with iTTP. The time‐period assessed was from January 1, 2017 to December 31, 2021. Our primary objective was to analyze data by iTTP episode, inclusive of initial episodes and relapses. A total of 390 iTTP episodes were reported for 280 unique individuals (187 females, 93 males). Thirty‐day mortality was 3.7% (14/374), and 6‐month mortality was 7.4% (27/367). TPE details were reported for 343 episodes, among which 261 underwent at least one procedure (median 6, IQR 3–11). Among the 261 episodes with at least one therapeutic plasma exchange (TPE) performed, 82.0% (214/261) used only plasma. Caplacizumab was used either alone or in combination with other agents in 43 (11.0%) episodes. Management strategies for iTTP remain varied across centers in the US, with a variety of combinations for TPE replacement fluids and therapeutic agents, as well as limited use of caplacizumab. Further research and standardization of treatment regimens may further reduce mortality in this condition.

Abstract Introduction: Femoroacetabular impingement commonly causes labral and cartilage damage. Understanding what clinical and CT-morphological factors are associated with increased labral and acetabular cartilage damage may give insight into the FAI pathophysiology. The present study aims to identify factors associated with labral and cartilage damage. Method: This is a prospective, multicenter cohort of patients undergoing primary arthroscopy for treatment of symptomatic FAI. Enrollment was between 2020 and 2022. The current study investigated predictive factors of advanced labral damage (detachment or full-thickness tear length >4cm) and advanced acetabular cartilage damage (delamination or full-thickness defect ≥200mm2). Finally, we performed external validation for the previously reported RAPID score that predicts high-grade cartilage injury. Results: There were 647 patients in the cohort. For labral injuries, there were 384/647 (59.4%) detachments and 154/647 (23.8%) full-thickness defects, with labral tears ≥4cm was present in 100/558 (17.9%) hips. Older age (OR:1.04, p=0.002), males (OR:1.83,p=0.005), and larger alpha angles at 2:00 (OR:1.02,p=0.04) were associated with full-thickness labral injuries. Older age (OR:1.06,p<0.001) and larger alpha angles at 2:00 (OR:1.03,p=0.01) were associated with tears ≥4cm. 258/679 (38.0%) patients had delamination or full-thickness cartilage defects. Older age (OR:1.09,p<0.001), males (OR:1.91 p=0.003), decreased IRF (OR:0.95,p<0.001), higher femoral version (OR:1.02,p=0.04), and larger alpha angles at 1:30 (OR:1.06,p<0.001) were associated with delamination or defect cartilage injuries. Advanced acetabular cartilage damage ≥200mm2 was present in 109/679 (16.8%) hips and was associated with larger alpha angles at 2:00 (OR:1.07,p<0.001), decreased IRF (OR:0.95,p<0.001), and males (OR:2.52,p=0.002), and age (OR:1.05,p=0.002). For RAPID score external validation, we used our data for their model (sex, Tonnis OA Grade, radiographic alpha angle) and found an AUC of 0.685. With an adjusted model using CT alpha angles, AUC improved to 0.703. Our final model improved the AUC to 0.809 and included age, sex, IRF, femoral version, and CT alpha angles. Conclusion: FAI commonly has associated labral and cartilage injuries. The current study found multiple predictive factors for advanced labral and cartilage injuries as well as for larger lesions. A model including age, sex, IRF, femoral version, and CT alpha angles appears to best predict acetabular cartilage damage. Further research should investigate how these affect outcomes.