Low Rate of AVN and Complications in Unstable SCFE With Epiphyseal-metaphyseal Discontinuity After Treatment With a Modified Dunn Procedure.

BACKGROUND: The risk of developing avascular necrosis (AVN) in the setting of an unstable slipped capital femoral epiphysis (SCFE) that is undergoing treatment with the modified Dunn procedure is not well understood. In addition, since the Loder classification of unstable is reportedly different than actual intraoperatively observed instability (that is, discontinuity between the femoral head epiphysis and proximal femoral metaphysis), the overall risk of developing AVN, as well as the potential complications of treatment of these patients with the modified Dunn procedure, are unknown. QUESTIONS/PURPOSES: To evaluate the modified Dunn procedure for the treatment of patients with epiphyseal-metaphyseal discontinuity, we asked: (1) What was the survivorship free from AVN at 10 years? (2) What was the survivorship free from subsequent surgery and/or complications at 10 years? (3) What were the clinical and patient-reported outcome scores? METHODS: In a retrospective analysis, we identified 159 patients (159 hips) treated with a modified Dunn procedure for SCFE between 1998 and 2020, of whom 97% (155 of 159) had documentation about intraoperatively observed epiphyseal-metaphyseal stability. Of those, 37% (58 of 155) of patients were documented to have intraoperatively observed epiphyseal-metaphyseal discontinuity and were considered eligible for inclusion, whereas 63% (97 of 155) had documented epiphyseal-metaphyseal stability and were excluded. No patients were lost to follow-up before the 2-year minimum. All patients were assessed for survival, but 7% (4 of 58) did not fill out our outcomes score questionnaire. This resulted in 93% (54 of 58) of patients who were available for outcome score assessment. Additionally, 50% (29 of 58) of patients had not been seen within the last 5 years; they are included, but we note that there is uncertainty about their status. The median (range) age at surgery was 13 years (10 to 16), and the sex ratio was 60% (35 of 58) male and 40% (23 of 58) female patients. Sixty-four percent (37 of 58) of patients were classified as acute-on-chronic, and 17% (10 of 58) of patients were classified as acute. Forty-seven percent (27 of 58) of patients presented with severe slips and 43% (25 of 58) of patients with moderate slips based on radiographic classification. All patients underwent surgical hip dislocation with the modified Dunn procedure to correct the slip deformity and provide stabilization. Complications and reoperations were assessed from a review of electronic medical records, and a Kaplan-Meier estimator was used to estimate survivorship free from complications and reoperations at 10 years. Clinical examination results and questionnaire responses were evaluated at minimum 2-year follow-up. RESULTS: Kaplan-Meier survivorship free from AVN was 93% (95% CI 87% to 100%) at 10 years. Survivorship free from any reoperation was 75% (95% CI 64% to 88%) at 10 years. In addition, survivorship free from complications, defined as development of AVN, reoperation, or a Sink Grade II complication or higher, was 57% (95% CI 45% to 73%) at 10 years. The median (range) Merle D'Aubigne Postel score was 18 (14 to 18) for the patients who did not develop AVN, and 12 (6 to 16) for the four patients who developed AVN (p < 0.001). The median modified Harris hip score was 100 (74 to 100) in the non-AVN cohort and 65 (37 to 82) in the AVN cohort (p = 0.001). Median HOOS total score was 95 (50 to 100) in the non-AVN cohort and 53 (40 to 82) in the AVN cohort (p = 0.002). CONCLUSION: Although the modified Dunn procedure is technically challenging, this study shows that in experienced hands, patients with who have demonstrated epiphyseal-metaphyseal discontinuity can be treated with a low risk of AVN and subsequent surgery. Referral of these patients to specialists who have substantial expertise in this procedure is recommended to improve patient outcomes. Prospective, long-term observational studies will help us identify these high-risk patients preoperatively and determine the long-term success of this procedure. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Do Osteochondroplasty Alone, Intertrochanteric Derotation Osteotomy, and Flexion-Derotation Osteotomy Improve Hip Flexion and Internal Rotation to Normal Range in Hips With Severe SCFE? - A 3D-CT Simulation Study.

BACKGROUND: Severe slipped capital femoral epiphysis (SCFE) leads to femoroacetabular impingement and restricted hip motion. We investigated the improvement of impingement-free flexion and internal rotation (IR) in 90 degrees of flexion following a simulated osteochondroplasty, a derotation osteotomy, and a combined flexion-derotation osteotomy in severe SCFE patients using 3D-CT-based collision detection software. METHODS: Preoperative pelvic CT of 18 untreated patients (21 hips) with severe SCFE (slip-angle>60 degrees) was used to generate patient-specific 3D models. The contralateral hips of the 15 patients with unilateral SCFE served as the control group. There were 14 male hips (mean age 13±2 y). No treatment was performed before CT. Specific collision detection software was used for the calculation of impingement-free flexion and IR in 90 degrees of flexion and simulation of osteochondroplasty, derotation osteotomy, and combined flexion-derotation osteotomy. RESULTS: Osteochondroplasty alone improved impingement-free motion but compared with the uninvolved contralateral control group, severe SCFE hips had persistently significantly decreased motion (mean flexion 59±32 degrees vs. 122±9 degrees, P <0.001; mean IR in 90 degrees of flexion -5±14 degrees vs. 36±11 degrees, P <0.001). Similarly, the impingement-free motion was improved after derotation osteotomy, and impingement-free flexion after a 30 degrees derotation was equivalent to the control group (113± 42 degrees vs. 122±9 degrees, P =0.052). However, even after the 30 degrees derotation, the impingement-free IR in 90 degrees of flexion persisted lower (13±15 degrees vs. 36±11 degrees, P <0.001). Following the simulation of flexion-derotation osteotomy, mean impingement-free flexion and IR in 90 degrees of flexion increased for combined correction of 20 degrees (20 degrees flexion and 20 degrees derotation) and 30 degrees (30 degrees flexion and 30 degrees derotation). Although mean flexion was equivalent to the control group for both (20 degrees and 30 degrees) combined correction, the mean IR in 90 degrees of flexion persisted decreased, even after the 30 degrees combined flexion-derotation (22±22 degrees vs. 36 degrees±11, P =0.009). CONCLUSIONS: Simulation of derotation-osteotomy (30 degrees correction) and flexion-derotation-osteotomy (20 degrees correction) normalized hip flexion for severe SCFE patients, but IR in 90 degrees of flexion persisted slightly lower despite significant improvement. Not all SCFE patients had improved hip motion with the performed simulations; therefore, some patients may need a higher degree of correction or combined treatment with osteotomy and cam-resection, although not directly investigated in this study. Patient-specific 3D-models could help individual preoperative planning for severe SCFE patients to normalize the hip motion. LEVEL OF EVIDENCE: III, case-control study.

Association of pregnancies with risk of multiple sclerosis.

BACKGROUND: Pregnancies have an impact on the disease course of multiple sclerosis (MS), but their relationship with MS risk is yet unclear. OBJECTIVE: To determine the relationships of pregnancies and gynecological diagnoses with MS risk. METHODS: In this retrospective case-control study, we assessed differences in gynecological International Classification of Diseases, 10th Revision (ICD-10) code recording rates between women with MS (n = 5720), Crohn's disease (n = 6280), or psoriasis (n = 40,555) and women without these autoimmune diseases (n = 26,729) in the 5 years before diagnosis. RESULTS: Twenty-eight ICD-10 codes were recorded less frequently for women with MS as compared to women without autoimmune disease, 18 of which are pregnancy-related. After adjustment for pregnancies, all codes unrelated to pregnancies were still negatively associated with MS. In a sensitivity analysis excluding women with evidence for possible demyelinating events before diagnosis, all associations were more pronounced. In comparison to women with psoriasis, most associations could be confirmed; that was not true in comparison to women with Crohn's disease. CONCLUSION: Our findings provide evidence for a possible protective effect of pregnancies on MS risk likely independent of or in addition to a previously suggested reversed causality. The negative associations of gynecological disorders with disease risk need further investigation. The associations might be shared by different autoimmune diseases.

High prevalence of hip lesions secondary to arthroscopic over- or undercorrection of femoroacetabular impingement in patients with postoperative pain.

OBJECTIVES: To compare the prevalence of pre- and postoperative osseous deformities and intra-articular lesions in patients with persistent pain following arthroscopic femoroacetabular impingement (FAI) correction and to identify imaging findings associated with progressive cartilage damage. METHODS: Retrospective study evaluating patients with hip pain following arthroscopic FAI correction between 2010 and 2018. Pre- and postoperative imaging studies were analyzed independently by two blinded readers for osseous deformities (cam-deformity, hip dysplasia, acetabular overcoverage, femoral torsion) and intra-articular lesions (chondro-labral damage, capsular lesions). Prevalence of osseous deformities and intra-articular lesions was compared with paired t-tests/McNemar tests for continuous/dichotomous data. Association between imaging findings and progressive cartilage damage was assessed with logistic regression. RESULTS: Forty-six patients (mean age 29 ± 10 years; 30 female) were included. Postoperatively, 74% (34/46) of patients had any osseous deformity including 48% (22/46) acetabular and femoral deformities. Ninety-six percent (44/46) had an intra-articular lesion ranging from 20% (9/46) for femoral to 65% (30/46) for acetabular cartilage lesions. Prevalence of hip dysplasia increased (2 to 20%, p = 0.01) from pre- to postoperatively while prevalence of cam-deformity decreased (83 to 28%, p < 0.001). Progressive cartilage damage was detected in 37% (17/46) of patients and was associated with extensive preoperative cartilage damage > 2 h, i.e., > 60° (OR 7.72; p = 0.02) and an incremental increase in postoperative alpha angles (OR 1.18; p = 0.04). CONCLUSION: Prevalence of osseous deformities secondary to over- or undercorrrection was high. Extensive preoperative cartilage damage and higher postoperative alpha angles increase the risk for progressive degeneration. KEY POINTS: • The majority of patients presented with osseous deformities of the acetabulum or femur (74%) and with intra-articular lesions (96%) on postoperative imaging. • Prevalence of hip dysplasia increased (2 to 20%, p = 0.01) from pre- to postoperatively while prevalence of a cam deformity decreased (83 to 28%, p < 0.001). • Progressive cartilage damage was present in 37% of patients and was associated with extensive preoperative cartilage damage > 2 h (OR 7.72; p = 0.02) and with an incremental increase in postoperative alpha angles (OR 1.18; p = 0.04).

Limited Hip Flexion and Internal Rotation Resulting From Early Hip Impingement Conflict on Anterior Metaphysis of Patients With Untreated Severe SCFE Using 3D Modelling.

INTRODUCTION: Slipped capital femoral epiphysis (SCFE) is the most common hip disorder in adolescent patients that can result in complex 3 dimensional (3D)-deformity and hip preservation surgery (eg, in situ pinning or proximal femoral osteotomy) is often performed. But there is little information about location of impingement.Purpose/Questions: The purpose of this study was to evaluate (1) impingement-free hip flexion and internal rotation (IR), (2) frequency of impingement in early flexion (30 to 60 degrees), and (3) location of acetabular and femoral impingement in IR in 90 degrees of flexion (IRF-90 degrees) and in maximal flexion for patients with untreated severe SCFE using preoperative 3D-computed tomography (CT) for impingement simulation. METHODS: A retrospective study involving 3D-CT scans of 18 patients (21 hips) with untreated severe SCFE (slip angle>60 degrees) was performed. Preoperative CT scans were used for bone segmentation of preoperative patient-specific 3D models. Three patients (15%) had bilateral SCFE. Mean age was 13±2 (10 to 16) years and 67% were male patients (86% unstable slip, 81% chronic slip). The contralateral hips of 15 patients with unilateral SCFE were evaluated (control group). Validated software was used for 3D impingement simulation (equidistant method). RESULTS: (1) Impingement-free flexion (46±32 degrees) and IRF-90 degrees (-17±18 degrees) were significantly ( P <0.001) decreased in untreated severe SCFE patients compared with contralateral side (122±9 and 36±11 degrees).(2) Frequency of impingement was significantly ( P <0.001) higher in 30 and 60 degrees flexion (48% and 71%) of patients with severe SCFE compared with control group (0%).(3) Acetabular impingement conflict was located anterior-superior (SCFE patients), mostly 12 o'clock (50%) in IRF-90 degrees (70% on 2 o'clock for maximal flexion). Femoral impingement was located on anterior-superior to anterior-inferior femoral metaphysis (between 2 and 6 o'clock, 40% on 3 o'clock and 40% on 5 o'clock) in IRF-90 degrees and on anterior metaphysis (40% on 3 o'clock) in maximal flexion and frequency was significantly ( P <0.001) different compared with control group. CONCLUSION: Severe SCFE patients have limited hip flexion and IR due to early hip impingement using patient-specific preoperative 3D models. Because of the large variety of hip motion, individual evaluation is recommended to plan the osseous correction for severe SCFE patients. LEVEL OF EVIDENCE: Level III.

Minimal Out-Toeing and Good Hip Scores of Severe SCFE Patients Treated With Modified Dunn Procedure and Contralateral Prophylactic Pinning at Minimal 5-year Follow up.

BACKGROUND: Slipped capital femoral epiphyses (SCFE) is associated with out-toeing of the foot and external rotation gait. But it is unknown if SCFE patients treated with the modified Dunn procedure have out-toeing at follow up.Therefore, we used instrumented gait analysis and questioned (1) do severe SCFE patients treated with a modified Dunn procedure have symmetrical foot progression angle (FPA) compared with contralateral side and compared with asymptomatic volunteers (2) what is the prevalence of out-toeing gait and what are the outcome socres at follow up. METHODS: Gait analysis of 22 patients (22 hips) treated with an unilateral modified Dunn procedure for severe SCFE (slip angle >60 degrees, 2002 to 2011) was retrospectively evaluated. Of 38 patients with minimal 5-year follow up, 2 hips (4%) had avascular necrosis of the femoral head and were excluded for gait analysis. Twenty-two patients were available for gait analysis at follow up (mean follow up of 9±2 y). Mean age at follow up was 22±3 years. Mean preoperative slip angle was 64±8 degrees (33% unstable slips) and decreased postoperatively (slip angle of 8±4 degrees). Gait analysis was performed with computer-based instrumented walkway system (GAITRite) to measure FPA with embedded pressure sensors. Patients were compared with control group of 18 healthy asymptomatic volunteers (36 feet, mean age 29±6 y). RESULTS: (1) Mean FPA of SCFE patients (3.6±6.4 degrees) at follow up was not significantly different compared with their contralateral side (5.6±5.5 degrees) and compared with FPA of controls (4.0±4.5 degrees). (2) Of the 22 SCFE patients, most of them (19 hips, 86%) had normal FPA (-5 to 15 degrees), 2 patients had in-toeing (FPA<-5 degrees) and 1 had out-toeing (FPA >15 degrees) and was not significantly different compared with control group. (3) Mean modified Harris hip score (mHHS) was 93±11 points, mean Hip Disability and Osteoarthritis Outcome Score (HOOS) score was 91±10 points. Three patients (14%) had mHHS <80 points and walked with normal FPA. The 2 patients with in-toeing and one patient with out-toeing had mHHS >95 points. CONCLUSIONS: Patients with severe SCFE treated with modified Dunn procedure had mostly symmetrical FPA and good hip scores at long term follow up. This is in contrast to previous studies. Although 1 patient had out-toeing and 2 patients had in-toeing at follow up, they had good hip scores. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Revision of a Failed Primary Total Hip Arthroplasty following Excessive Reaming with a Medial Cup Protrusion.

Background and Objectives: Atraumatic intrapelvic protrusion of the acetabular component following excessive reaming of the acetabulum with a far medial positioning of the cup is a rare, but serious complication of a total hip arthroplasty (THA). This study analyzes the factors contributing to this uncommon complication and presents the outcome after the revision surgery using the Ganz reinforcement ring combined with a bone graft and plating of the posterior column and/or screws for the anterior column. Materials and Methods: A retrospective case series study with seven patients (four males, mean age 76 ± 10 years (60−86)) that underwent a revision THA within 24 ± 17 days (5−60) after an atraumatic periprosthetic acetabular fracture with a medial cup protrusion was performed. All fractures were reconstructed with a Ganz reinforcement ring and bone graft with a mean follow-up of 1.7 ± 1.7 years (0.5−5). Radiographs were evaluated for the following: (i) cup positioning immediately after the primary THA and the revision surgery, (ii) cup migration in the follow-up, and (iii) fracture healing. Results: The position of the acetabular component as assessed on the postoperative radiographs after the index surgery and before the complete medial cup protrusion showed a cup placement beyond the ilioischial line indicative of a fracture of the medial wall. The revision surgery with the reconstruction of the medial wall with a Ganz reinforcement ring combined with a bone graft restored in the presented cases the center of rotation in the horizontal direction with a statistical significance (p < 0.05). During the follow-up, there was no aseptic loosening with the relevant cup migration or significant change in the position of the acetabular cup at the final follow-up (p > 0.05) after the revision. All seven fractures and bone grafts realized a bone union until the latest follow-up. Conclusions: Following excessive reaming, the acetabular component was placed too far medially and resulted in an intrapelvic cup protrusion. An unstable cup following a fracture of the medial wall was evident on the immediate postoperative radiographs. In the case of the medial wall perforation with an intrapelvic cup protrusion after the primary THA, the reconstruction with a Ganz reinforcement ring was a successful treatment option resulting in the fracture healing and a stable cup positioning. Surgeons should be aware of that rare and probably underreported complication and restore the anatomic center of rotation by treating the defect intraoperatively.

Magnetization-prepared 2 Rapid Gradient-Echo MRI for B1 Insensitive 3D T1 Mapping of Hip Cartilage: An Experimental and Clinical Validation.

Background Often used for T1 mapping of hip cartilage, three-dimensional (3D) dual-flip-angle (DFA) techniques are highly sensitive to flip angle variations related to B1 inhomogeneities. The authors hypothesized that 3D magnetization-prepared 2 rapid gradient-echo (MP2RAGE) MRI would help provide more accurate T1 mapping of hip cartilage at 3.0 T than would 3D DFA techniques. Purpose To compare 3D MP2RAGE MRI with 3D DFA techniques using two-dimensional (2D) inversion recovery T1 mapping as a standard of reference for hip cartilage T1 mapping in phantoms, healthy volunteers, and participants with hip pain. Materials and Methods T1 mapping at 3.0 T was performed in phantoms and in healthy volunteers using 3D MP2RAGE MRI and 3D DFA techniques with B1 field mapping for flip angle correction. Participants with hip pain prospectively (July 2019-January 2020) underwent indirect MR arthrography (with intravenous administration of 0.2 mmol/kg of gadoterate meglumine), including 3D MP2RAGE MRI. A 2D inversion recovery-based sequence served as a T1 reference in phantoms and in participants with hip pain. In healthy volunteers, cartilage T1 was compared between 3D MP2RAGE MRI and 3D DFA techniques. Paired t tests and Bland-Altman analysis were performed. Results Eleven phantoms, 10 healthy volunteers (median age, 27 years; range, 26-30 years; five men), and 20 participants with hip pain (mean age, 34 years ± 10 [standard deviation]; 17 women) were evaluated. In phantoms, T1 bias from 2D inversion recovery was lower for 3D MP2RAGE MRI than for 3D DFA techniques (mean, 3 msec ± 11 vs 253 msec ± 85; P < .001), and, unlike 3D DFA techniques, the deviation found with MP2RAGE MRI did not correlate with increasing B1 deviation. In healthy volunteers, regional cartilage T1 difference (109 msec ± 163; P = .008) was observed only for the 3D DFA technique. In participants with hip pain, the mean T1 bias of 3D MP2RAGE MRI from 2D inversion recovery was -23 msec ± 31 (P < .001). Conclusion Compared with three-dimensional (3D) dual-flip-angle techniques, 3D magnetization-prepared 2 rapid gradient-echo MRI enabled more accurate T1 mapping of hip cartilage, was less affected by B1 inhomogeneities, and showed high accuracy against a T1 reference in participants with hip pain. © RSNA, 2021.

The transplant cohort of the German center for infection research (DZIF Tx-Cohort): study design and baseline characteristics.

Infectious complications are the major cause of morbidity and mortality after solid organ and stem cell transplantation. To better understand host and environmental factors associated with an increased risk of infection as well as the effect of infections on function and survival of transplanted organs, we established the DZIF Transplant Cohort, a multicentre prospective cohort study within the organizational structure of the German Center for Infection Research. At time of transplantation, heart-, kidney-, lung-, liver-, pancreas- and hematopoetic stem cell- transplanted patients are enrolled into the study. Follow-up visits are scheduled at 3, 6, 9, 12 months after transplantation, and annually thereafter; extracurricular visits are conducted in case of infectious complications. Comprehensive standard operating procedures, web-based data collection and monitoring tools as well as a state of the art biobanking concept for blood, purified PBMCs, urine, and faeces samples ensure high quality of data and biosample collection. By collecting detailed information on immunosuppressive medication, infectious complications, type of infectious agent and therapy, as well as by providing corresponding biosamples, the cohort will establish the foundation for a broad spectrum of studies in the field of infectious diseases and transplant medicine. By January 2020, baseline data and biosamples of about 1400 patients have been collected. We plan to recruit 3500 patients by 2023, and continue follow-up visits and the documentation of infectious events at least until 2025. Information about the DZIF Transplant Cohort is available at https://www.dzif.de/en/working-group/transplant-cohort .

A Cam Morphology Develops in the Early Phase of the Final Growth Spurt in Adolescent Ice Hockey Players: Results of a Prospective MRI-based Study.

BACKGROUND: Cam morphologies seem to develop with an increased prevalence in adolescent boys performing high-impact sports. The crucial question is at what age the cam morphology actually develops and whether there is an association with an aberration of the shape of the growth plate at the cam morphology site. QUESTIONS/PURPOSES: (1) What is the frequency of cam morphologies in adolescent ice hockey players, and when do they appear? (2) Is there an association between an extension of the physeal growth plate and the development of a cam morphology? (3) How often do these players demonstrate clinical findings like pain and lack of internal rotation? METHODS: A prospective, longitudinal MRI study was done to monitor the proximal femoral development and to define the appearance of cam morphologies in adolescent ice hockey players during the final growth spurt. Young ice hockey players from the local boys' league up to the age of 13 years (mean age 12 ± 0.5 years) were invited to participate. From 35 players performing on the highest national level, 25 boys and their parents consented to participate. None of these 25 players had to be excluded for known disease or previous surgery or hip trauma. At baseline examination as well as 1.5 and 3 years later, we performed a prospective noncontrast MRI scan and a clinical examination. The three-dimensional morphology of the proximal femur was assessed by one of the authors using radial images of the hip in a clockwise manner. The two validated parameters were: (1) the alpha angle for head asphericity (abnormal > 60°) and (2) the epiphyseal extension for detecting an abnormality in the shape of the capital physis and a potential correlation at the site of the cam morphology. The clinical examination was performed by one of the authors evaluating (1) internal rotation in 90° of hip and knee flexion and (2) hip pain during the anterior impingement test. RESULTS: Cam morphologies were most apparent at the 1.5-year follow-up interval (10 of 25; baseline versus 1.5-year follow-up: p = 0.007) and a few more occurred between 1.5 and 3 years (12 of 23; 1.5-year versus 3-year follow-up: p = 0.14). At 3-year follow-up, there was a positive correlation between increased epiphyseal extension and a high alpha angle at the anterosuperior quadrant (1 o'clock to 3 o'clock) (Spearman correlation coefficient = 0.341; p < 0.003). The prevalence of pain on the impingement test and/or restricted internal rotation less than 20° increased most between 1.5-year (1 of 25) and the 3-year follow-up (6 of 22; 1.5-year versus 3-year follow-up: p = 0.02). CONCLUSION: Our data suggest that a cam morphology develops early during the final growth spurt of the femoral head in adolescent ice hockey players predominantly between 13 to 16 years of age. A correlation between an increased extension of the growth plate and an increased alpha angle at the site of the cam morphology suggests a potential underlying growth disturbance. This should be further followed by high-resolution or biochemical MRI methods. Considering the high number of cam morphologies that correlated with abnormal clinical findings, we propose that adolescents performing high-impact sports should be screened for signs of cam impingement, such as by asking about hip pain and/or examining the patient for limited internal hip rotation. LEVEL OF EVIDENCE: Level I, prognostic study.

The Acetabular Wall Index Is Associated with Long-term Conversion to THA after PAO.

BACKGROUND: Periacetabular osteotomy (PAO) has been shown to be a valuable option for delaying the onset of osteoarthritis in patients with hip dysplasia. Published studies at 30 years of follow-up found that postoperative anterior overcoverage and posterior undercoverage were associated with early conversion to THA. The anterior and posterior wall indices are practical tools for assessing AP coverage on standard AP radiographs of the pelvis pre-, intra-, and postoperatively. However, no study that we know of has evaluated the relationship between the postoperative anterior and posterior wall indices and survivorship free from arthroplasty. QUESTIONS/PURPOSES: In a study including patients after PAO for developmental dysplasia of the hip (DDH), we evaluated whether the acetabular wall index is associated with conversion to THA in the long-term after PAO. We asked: (1) Is an abnormal postoperative anterior wall index associated with conversion to THA after PAO? (2) Is an abnormal postoperative posterior wall index associated with conversion to THA after PAO? (3) Are there other factors associated with joint replacement after PAO? METHODS: This retrospective study involved pooling data of PAO for DDH from two previously published sources. The first series (1984-1987) comprised the very first 75 PAOs for symptomatic DDH performed at the inventor's institution. The second (1997-2000) comprised a series of PAOs for symptomatic DDH completed at the same institution 10 years later. No patient was lost to follow-up. Fifty hips (44 patients) were excluded for predefined reasons (previous surgery, substantial femoral pathomorphologies, poor-quality radiographs), leaving 115 hips (102 patients, mean age 29 ± 11 years, 28% male) for analysis with a mean follow-up of 22 ± 6 years. One observer not involved in patient treatment digitally measured the anterior and posterior wall indices on postoperative AP pelvic radiographs of all patients. All patients were contacted by mail or telephone to confirm any conversion to THA and the timing of that procedure relative to the index procedure. We performed univariate and multivariate Cox regression analyses using conversion to THA as our endpoint to determine whether the anterior and posterior wall indices are associated with prosthetic replacement in the long-term after PAO. Thirty-one percent (36 of 115) of hips were converted to THA within a mean of 15 ± 7 years until failure. The mean follow-up duration of the remaining patients was 22 ± 6 years. RESULTS: A deficient anterior wall index was associated with conversion THA in the long-term after PAO (adjusted hazard ratio 10 [95% CI 3.6 to 27.9]; p < 0.001). Although observed in the univariate analysis, we could not find a multivariate association between the posterior wall index and a higher conversion rate to THA. Grade 0 Tönnis osteoarthritis was associated with joint preservation (adjusted HR 0.2 [95% CI 0.07 to 0.47]; p = 0.005). Tönnis osteoarthritis Grades 2 and 3 were associated with conversion to THA (adjusted HR 2.3 [95% CI 0.9 to 5.7]; p = 0.08). CONCLUSION: A deficient anterior wall index is associated with a decreased survivorship of the native hip in the long-term after PAO. Intraoperatively, in addition to following established radiographical guidelines, the acetabular wall indices should be measured systematically to ascertain optimal acetabular fragment version to increase the likelihood of reconstructive survival after PAO for DDH. LEVEL OF EVIDENCE: Level III, therapeutic study.

Metadata Correction: Patient Empowerment During the COVID-19 Pandemic by Ensuring Safe and Fast Communication of Test Results: Implementation and Performance of a Tracking System.

[This corrects the article DOI: 10.2196/27348.].

Patient Empowerment During the COVID-19 Pandemic by Ensuring Safe and Fast Communication of Test Results: Implementation and Performance of a Tracking System.

BACKGROUND: Overcoming the COVID-19 crisis requires new ideas and strategies for online communication of personal medical information and patient empowerment. Rapid testing of a large number of subjects is essential for monitoring and delaying the spread of SARS-CoV-2 in order to mitigate the pandemic's consequences. People who do not know that they are infected may not stay in quarantine and, thus, risk infecting others. Unfortunately, the massive number of COVID-19 tests performed is challenging for both laboratories and the units that conduct throat swabs and communicate the results. OBJECTIVE: The goal of this study was to reduce the communication burden for health care professionals. We developed a secure and easy-to-use tracking system to report COVID-19 test results online that is simple to understand for the tested subjects as soon as these results become available. Instead of personal calls, the system updates the status and the results of the tests automatically. This aims to reduce the delay when informing testees about their results and, consequently, to slow down the virus spread. METHODS: The application in this study draws on an existing tracking tool. With this open-source and browser-based online tracking system, we aim to minimize the time required to inform the tested person and the testing units (eg, hospitals or the public health care system). The system can be integrated into the clinical workflow with very modest effort and avoids excessive load to telephone hotlines. RESULTS: The test statuses and results are published on a secured webpage, enabling regular status checks by patients; status checks are performed without the use of smartphones, which has some importance, as smartphone usage diminishes with age. Stress tests and statistics show the performance of our software. CTest is currently running at two university hospitals in Germany-University Hospital Ulm and University Hospital Tübingen-with thousands of tests being performed each week. Results show a mean number of 10 (SD 2.8) views per testee. CONCLUSIONS: CTest runs independently of existing infrastructures, aims at straightforward integration, and aims for the safe transmission of information. The system is easy to use for testees. QR (Quick Response) code links allow for quick access to the test results. The mean number of views per entry indicates a reduced amount of time for both health care professionals and testees. The system is quite generic and can be extended and adapted to other communication tasks.

Return to Sports After Total Hip Arthroplasty: A Survey Among Members of the European Hip Society.

BACKGROUND: The study's aim was to summarize the recommendations given by members of the European Hip Society (EHS) regarding sport activities after total hip arthroplasty (THA). METHODS: Members of the EHS were invited to complete an online web-based questionnaire including recommendations for 47 sports disciplines. The questions regarding the specific sports were also divided into 4 subcategories: "allowed," "allowed when experienced," "not allowed", and "no opinion." Four intervals for resuming the sports activities after THA were evaluated: within 6 weeks after THA, 6 to 12 weeks after THA, 12 weeks to 6 months after THA, and more than 6 months after THA. Consensus on resuming sports was analyzed. RESULTS: A total of 150 (32.9%) EHS members participated in the survey. Agreement was found for 5 sports activities in the first 6 weeks after THA, for 10 activities, 6 to 12 weeks after surgery, for 26 activities, 3 to 6 months after THA, and for 37 of 47 activities, 6 months after surgery. Sports activities which were not allowed after THA were handball, soccer and football, basketball, full contact sports, and martial arts. CONCLUSION: This is the first report describing the recommendations of European hip arthroplasty surgeons on resuming sport activity after THA. Most physical activities were allowed for the patients 6 months after THA. The experience of the patient in performing a distinct sport activity did not influence the recommendations to return to former sports activities. European surgeons are progressively mitigating restrictions to sports after THA. Further studies should evaluate the effects of this trend on patients' outcome and implant survival.

Ablation of neuronal ADAM17 impairs oligodendrocyte differentiation and myelination.

Myelin, one of the most important adaptations of vertebrates, is essential to ensure efficient propagation of the electric impulse in the nervous system and to maintain neuronal integrity. In the central nervous system (CNS), the development of oligodendrocytes and the process of myelination are regulated by the coordinated action of several positive and negative cell-extrinsic factors. We and others previously showed that secretases regulate the activity of proteins essential for myelination. We now report that the neuronal α-secretase ADAM17 controls oligodendrocyte differentiation and myelin formation in the CNS. Ablation of Adam17 in neurons impairs in vivo and in vitro oligodendrocyte differentiation, delays myelin formation throughout development and results in hypomyelination. Furthermore, we show that this developmental defect is, in part, the result of altered Notch/Jagged 1 signaling. Surprisingly, in vivo conditional loss of Adam17 in immature oligodendrocytes has no effect on myelin formation. Collectively, our data indicate that the neuronal α-secretase ADAM17 is required for proper CNS myelination. Further, our studies confirm that secretases are important post-translational regulators of myelination although the mechanisms controlling CNS and peripheral nervous system (PNS) myelination are distinct.

The Molecular-Container Calabadion-2 Prevents Methamphetamine-Induced Reinstatement in Rats: A Potential Approach to Relapse Prevention?

BACKGROUND: Reexposure to methamphetamine with a single "priming dose" can trigger intense cravings and precipitate relapse in methamphetamine-dependent individuals. The acyclic cucurbit[n]uril "molecular container" calabadion-2 shows a high affinity to bind and sequester methamphetamine in vitro and attenuates its locomotor-stimulating effect in rats. The present study investigates whether pretreatment with calabadion-2 is sufficient to prevent the reinstatement of drug seeking by a priming dose of methamphetamine in rats. METHODS: Male Long-Evans rats were trained to self-administer i.v. methamphetamine (0.06 mg/kg/infusion). Following 10 days of stable self-administration, rats underwent extinction training and were subsequently tested on a multi-phase reinstatement procedure. Drug-primed reinstatement sessions (0.3 mg/kg methamphetamine, i.v.) were preceded by either saline or calabadion-2 (130 mg/kg). Additional reinstatement tests were conducted after administration of yohimbine (1.0 mg/kg, i.v.) to define the pharmacological specificity of calabadion-2. RESULTS: Pretreatment with calabadion-2 significantly attenuated methamphetamine-induced reinstatement of responding. Cal2 did not affect drug-seeking behavior stimulated by the pharmacological stressor yohimbine, indicating a mechanism of action specific to methamphetamine. CONCLUSIONS: These results demonstrate the effectiveness of calabadion-2 in a preclinical model relapse-like behavior. With further structural optimization, molecular containers may provide a novel and efficacious pharmacokinetic approach to relapse prevention for methamphetamine-dependent individuals.

Dioxygen Binding to all 3d, 4d, and 5d Transition Metals from Coupled-Cluster Theory.

Understanding how transition metals bind and activate dioxygen (O2 ) is limited by experimental and theoretical uncertainties, making accurate quantum mechanical descriptors of interest. Here we report coupled-cluster CCSD(T) energies with large basis sets and vibrational and relativistic corrections for 160 3d, 4d, and 5d metal-O2 systems. We define four reaction energies (120 in total for the 30 metals) that quantify O-O activation and reveal linear relationships between metal-oxygen and O-O binding energies. The CCSD(T) data can be combined with thermochemical cycles to estimate chemisorption and physisorption energies for each metal from metal oxide embedding energies, in good correlation with atomization enthalpies (R2 =0.75). Spin-geometry variations can break the linearities, of interest to circumventing the Sabatier principle. Pt, Pd, Co, and Fe form a distinct group with the weakest O2 binding. R2 up to 0.84 between surface adsorption energies and our energies for MO2 systems indicate relevance also to real catalytic systems.

Using electronegativity and hardness to test density functionals.

Density functional theory (DFT) is used in thousands of papers each year, yet lack of universality reduces DFT's predictive capacity, and functionals may produce energy-density imbalances. The absolute electronegativity (χ) and hardness (η) directly reflect the energy-density relationship via the chemical potential ∂E/∂N and we thus hypothesized that they probe universality. We studied χ and η for atoms Z = 1-36 using 50 diverse functionals covering all major classes. Very few functionals describe both χ and η well. η benefits from error cancellation, whereas χ is marred by error propagation from IP and EA; thus, almost all standard GGA and hybrid functionals display a plateau in the MAE at ∼0.2 eV-0.3 eV for η. In contrast, variable performance for χ indicates problems in describing the chemical potential by DFT. The accuracy and precision of a functional is far from linearly related, yet for a universal functional, we expect linearity. Popular functionals such as B3LYP, PBE, and revPBE perform poorly for both properties. Density sensitivity calculations indicate large density-derived errors as occupation of degenerate p- and d-orbitals causes "non-universality" and large dependency on exact exchange. Thus, we argue that performance for χ for the same systems is a hallmark of an important aspect of universality by probing ∂E/∂N. With this metric, B98, B97-1, PW6B95D3, MN-15, rev-TPSS, HSE06, and APFD are the most "universal" among the tested functionals. B98 and B97-1 are accurate for very diverse metal-ligand bonds, supporting that a balanced description of ∂E/∂N and ∂E2/∂N2, via χ and η, is probably a first simple probe of universality.

A rare IL33 loss-of-function mutation reduces blood eosinophil counts and protects from asthma.

IL-33 is a tissue-derived cytokine that induces and amplifies eosinophilic inflammation and has emerged as a promising new drug target for asthma and allergic disease. Common variants at IL33 and IL1RL1, encoding the IL-33 receptor ST2, associate with eosinophil counts and asthma. Through whole-genome sequencing and imputation into the Icelandic population, we found a rare variant in IL33 (NM_001199640:exon7:c.487-1G>C (rs146597587-C), allele frequency = 0.65%) that disrupts a canonical splice acceptor site before the last coding exon. It is also found at low frequency in European populations. rs146597587-C associates with lower eosinophil counts (ß = -0.21 SD, P = 2.5×10-16, N = 103,104), and reduced risk of asthma in Europeans (OR = 0.47; 95%CI: 0.32, 0.70, P = 1.8×10-4, N cases = 6,465, N controls = 302,977). Heterozygotes have about 40% lower total IL33 mRNA expression than non-carriers and allele-specific analysis based on RNA sequencing and phased genotypes shows that only 20% of the total expression is from the mutated chromosome. In half of those transcripts the mutation causes retention of the last intron, predicted to result in a premature stop codon that leads to truncation of 66 amino acids. The truncated IL-33 has normal intracellular localization but neither binds IL-33R/ST2 nor activates ST2-expressing cells. Together these data demonstrate that rs146597587-C is a loss of function mutation and support the hypothesis that IL-33 haploinsufficiency protects against asthma.

A comprehensive tool for creating and evaluating privacy-preserving biomedical prediction models.

BACKGROUND: Modern data driven medical research promises to provide new insights into the development and course of disease and to enable novel methods of clinical decision support. To realize this, machine learning models can be trained to make predictions from clinical, paraclinical and biomolecular data. In this process, privacy protection and regulatory requirements need careful consideration, as the resulting models may leak sensitive personal information. To counter this threat, a wide range of methods for integrating machine learning with formal methods of privacy protection have been proposed. However, there is a significant lack of practical tools to create and evaluate such privacy-preserving models. In this software article, we report on our ongoing efforts to bridge this gap. RESULTS: We have extended the well-known ARX anonymization tool for biomedical data with machine learning techniques to support the creation of privacy-preserving prediction models. Our methods are particularly well suited for applications in biomedicine, as they preserve the truthfulness of data (e.g. no noise is added) and they are intuitive and relatively easy to explain to non-experts. Moreover, our implementation is highly versatile, as it supports binomial and multinomial target variables, different types of prediction models and a wide range of privacy protection techniques. All methods have been integrated into a sound framework that supports the creation, evaluation and refinement of models through intuitive graphical user interfaces. To demonstrate the broad applicability of our solution, we present three case studies in which we created and evaluated different types of privacy-preserving prediction models for breast cancer diagnosis, diagnosis of acute inflammation of the urinary system and prediction of the contraceptive method used by women. In this process, we also used a wide range of different privacy models (k-anonymity, differential privacy and a game-theoretic approach) as well as different data transformation techniques. CONCLUSIONS: With the tool presented in this article, accurate prediction models can be created that preserve the privacy of individuals represented in the training set in a variety of threat scenarios. Our implementation is available as open source software.