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PURPOSE: Few studies have systematically analyzed the structure and content of laboratory exome sequencing reports from the same patient. METHODS: We merged 8 variants from patients into "normal" exomes to create virtual patient-parent trios. We provided laboratories worldwide with the data and patient phenotype information (developmental delay, dysmorphic features, and cardiac hypertrophy). Laboratories analyzed the data and issued a diagnostic exome report. Reports were scored using a coding matrix developed from existing guidelines. RESULTS: In total, 41 laboratories representing 17 countries issued reports. Reporting of quality control statistics and technical information was poor (46.3%). Although 75.6% of the reports clearly stated the classification of all reported variants, few reports listed extensive evidence supporting variant classification. Only 53.1% of laboratories that reported unsolicited or secondary findings gave advice regarding health-related follow-up and 20.5% gave advice regarding cascade testing for relatives. Of the 147 variants reported, 105 (71.4%) were classified in agreement with classifications based on American College of Medical Genetics and Genomics/Association for Molecular Pathology and Association for Clinical Genomic Science guidelines. Concordance was higher for known pathogenic variants (86.3%) than for novel unpublished variants (56.8%). CONCLUSION: The considerable variability identified in the components that laboratories included in their reports and their classification of variants suggests that existing guidelines are not being used consistently with significant implications for patient care. ispartof: GENETICS IN MEDICINE vol:24 issue:6 pages:1306-1315 ispartof: location:United States status: published

Background and purpose — The Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) was analyzed to determine trends in use of primary total elbow arthroplasty (TEA), the types of prostheses used, primary diagnoses, reasons for and types of revision, and whether the primary diagnosis or prosthesis design influenced the revision rate. Patients and methods — During 2008–2018, 1,220 primary TEA procedures were reported of which 140 TEAs were revised. Kaplan–Meier estimates of survivorship were used to describe the time to first revision and hazard ratios (HR) from Cox proportional hazard models, adjusted for age and sex, were used to compare revision rates. Results — The annual number of TEAs performed remained constant. The 3 most common diagnoses for primary TEA were fracture/dislocation (trauma) (36%), osteoarthritis (OA) (34%), and rheumatoid arthritis (RA) (26%). The cumulative percentage revision for all TEAs undertaken for any reason was 10%, 15%, and 19% at 3, 6, and 9 years. TEAs undertaken for OA had a higher revision rate compared with TEAs for trauma (HR = 1.8, 95% CI 1.1–3.0) and RA (HR = 2.0, CI 1.3–3.1). The Coonrad-Morrey (50%), Latitude (30%), Nexel (10%), and Discovery (9%) were the most used prosthesis designs. There was no difference in revision rates when these 4 designs were compared. The most common reasons for revision were infection (35%) and aseptic loosening (34%). Interpretation — The indications for primary and revision TEA in Australia are similar to those reported for other registries. Revision for trauma is lower than previously reported.

Purpose To define the longitudinal rotation axis around which individual vertebrae rotate, and to establish the various extra- and intravertebral rotation patterns in thoracic adolescent idiopathic scoliosis (AIS) patients, for better understanding of the 3D development of the rotational deformity. Methods Seventy high-resolution CT scans from an existing database of thoracic AIS patients (Cobb angle: 46°–109°) were included to determine the vertebral axial rotation, rotation radius, intravertebral axial rotation, and local mechanical torsion for each spinal level, using previously validated image processing techniques. Results For all levels, the longitudinal rotation axis, from which the vertebrae rotate away from the midline, was localized posterior to the spine. The axis became closer to the spine at the apex: apex, r = 11.5 ± 5.1 cm versus two levels above (radius = 15.8 ± 8.5 cm; p p p Conclusion In AIS, the vertebrae rotate away around an axis that is localized posterior to the spine. The distance between this axis and the spine is minimal at the apex and increases gradually to the neutral zones. The vertebral axial rotation is accompanied by smaller amounts of intravertebral rotation and local mechanical torsion, which increases toward the apical region. The altered morphology and alignment are important for a better understanding of the 3D pathoanatomical development of AIS and better therapeutic planning for bracing and surgical intervention. Graphic abstract These slides can be retrieved under Electronic Supplementary Material.

Intracellular cobalamin metabolism (ICM) defects can be present as autosomal recessive or X-linked disorders. Parenteral hydroxocobalamin (P-OHCbl) is the mainstay of therapy, but the optimal dose has not been determined. Despite early treatment, long-term complications may develop. We have analyzed the biochemical and clinical responses in five patients with early onset of different types of ICM defects (cblC: patients 1-3; cblA: patient 4; cblX: patient 5) following daily P-OHCbl dose intensification (DI). In patient 4, P-OHCbl was started at age 10 years and in patient 5 at age 5 years. OHCbl was formulated at either, 5, 25, or 50 mg/mL. P-OHCbl was intravenously or subcutaneously (SQ) delivered, subsequently by placement of a SQ injection port except in patient 4. In all patients, homocysteine and methylmalonic acid levels, demonstrated an excellent response to various P-OHCbl doses. After age 36 months, patients 1-3 had a close to normal neurological examination with lower range developmental quotient. In patient 3, moderate visual impairment was present. Patient 4, at age 10 years, had normal renal, visual and cognitive function. In cblX patient 5, epilepsy was better controlled. In conclusion, P-OHCbl-DI caused an excellent control of metabolites in all patients. In the three cblC patients, comparison with patients, usually harboring identical genotype and similar metabolic profile, was suggestive of a positive effect, in favor of clinical efficacy. With P-OHCbl-DI, CblA patient has been placed into a lower risk to develop renal and optic impairment. In cblX patient, lower P-OHCbl doses were administrated to improve tolerability., SCOPUS: ar.k, info:eu-repo/semantics/published

Purpose: It is not yet known if unicompartmental knee arthroplasty (UKA) patients are more likely to return to work sooner or have improved ability to work (i.e., workability) than total knee arthroplasty (TKA) patients. The following questions were addressed: patients were assessed to determine: (1) whether they returned to work sooner following UKA compared to TKA; (2) whether UKA patients had better WORQ function scores compared to TKA patients; and (3) if UKA patients have higher workability scores and greater satisfaction regarding workability than TKA patients. Methods: A multicenter retrospective cohort study was performed that included patients at least 2 years after having undergone either UKA or TKA surgery and on the condition that patients had been in work in the 2 years prior to surgery. Time period between stopping work and returning to work was assessed; the WORQ scores (0 = worst–100 = best) and the Work Ability Index (WAI = 0–10) and reported satisfaction with work ability. Results: UKA patients (n = 157, median 60 years, 51% male) were compared to TKA patients (n = 167, median 60 years, 49% male) (n.s.). Of the 157 UKA patients, 115 (73%) returned to work within 2 years compared to 121 (72%) of TKA patients (n.s.). More UKA patients return to work within 3 months (73% versus 48%) (p < 0.01). WORQ scores improved similarly in both groups. The WAI was also comparable between the groups. Dissatisfaction with workability was comparable (UKA 15% versus TKA 18% (n.s.). Conclusion: TKA and UKA patients have similar WORQ, WAI, and satisfaction scores. However, in this study population, UKA patients to return to work after surgery significantly sooner than TKA patients, which improves their quality of life and allows them to participate actively in society. This information can help health care providers and patients weigh-up the pros and cons and choose the best treatment and timing for patients in the working population. Level of evidence: III.

Introduction In this study, we describe the distribution of placenta delivery and the incidence of postpartum hemorrhage in both spontaneous placental delivery and manual removal of the placenta. Methods A retrospective study was performed of 7603 singleton vaginal deliveries of a gestational age over 32 weeks, registered between September 2011 and 2016. We calculated the incidence of postpartum hemorrhage (≥1000 mL blood loss) per 10-minute duration of the third stage. The odds ratio for developing postpartum hemorrhage was assessed, adjusted for risk factors. The incidence of postpartum hemorrhage was compared between women that did and did not receive manual removal of placenta. Results The median duration of the third stage was 10 minutes (interquartile range 7-16 minutes). The median amount of blood loss was 300 mL (200-400 mL). The overall incidence of postpartum hemorrhage was 8.5%. With every additional 10 minutes of third-stage duration, the risk of developing postpartum hemorrhage significantly increased. In a third stage longer than 60 minutes, the incidence of postpartum hemorrhage was 21.2% without manual removal of the placenta and 70.3% with manual removal. Conclusions The incidence of postpartum hemorrhage increases significantly from 10 to 19 minutes into the third stage. Women with the removal of the placenta had a significantly higher percentage of postpartum hemorrhage. The optimal timing for manual removal of the placenta should be investigated in a carefully designed randomized controlled trial to examine whether earlier manual removal of placenta lowers the incidence and limits the severity of postpartum hemorrhage.

Background: High tibial osteotomy (HTO) is increasingly used in young and physically active patients with knee osteoarthritis. These patients have high expectations, including return to sport (RTS). By retaining native knee structures, a return to highly knee-demanding activities seems possible. However, evidence on patient-related outcomes, including RTS, is sparse. Also, time to RTS has never been described. Furthermore, prognostic factors for RTS after HTO have never been investigated. These data may further justify HTO as a surgical alternative to knee arthroplasty. Purpose: To investigate the extent and timing of RTS after HTO in the largest cohort investigated for RTS to date and to identify prognostic factors for successful RTS. Study Design: Case-control study; Level of evidence, 3. Methods: Consecutive patients with HTO, operated on between 2012 and 2015, received a questionnaire. First, pre- and postoperative sports participation questions were asked. Also, time to RTS, sports level and frequency, impact level, the presymptomatic and postoperative Tegner activity score (1-10; higher is more active), and the postoperative Lysholm score (0-100; higher is better) were collected. Finally, prognostic factors for RTS were analyzed using a logistic regression model. Covariates were selected based on univariate analysis and a directed acyclic graph. Results: We included 340 eligible patients of whom 294 sufficiently completed the questionnaire. The mean follow-up was 3.7 years (± 1.0 years). Out of 256 patients participating in sports preoperatively, 210 patients (82%) returned to sport postoperatively, of whom 158 (75%) returned within 6 months. We observed a shift to participation in lower-impact activities, although 44% of reported sports activities at final follow-up were intermediate- or high-impact sports. The median Tegner score decreased from 5.0 (interquartile range [IQR], 4.0-6.0) presymptomatically to 4.0 (IQR, 3.0-4.0) at follow-up ( P < .001). The mean Lysholm score at follow-up was 68 (SD, ± 22). No significant differences were found between patients with varus or valgus osteoarthritis. The strongest prognostic factor for RTS was continued sports participation in the year before surgery (odds ratio, 2.81; 95% CI, 1.37-5.76). Conclusion: More than 8 of 10 patients returned to sport after HTO. Continued preoperative sports participation was associated with a successful RTS. Future studies need to identify additional prognostic factors.

Background Context: One of the characteristics of reported observations in adolescent idiopathic scoliosis (AIS) is that the thoracic spine is longer anteriorly than posteriorly, more pronounced around the apex than the transitional zones. This reversal of the normal kyphotic anatomy of the thoracic spine is related to questions of etiopathogenesis of AIS. The changes in the anatomy of the anterior column have been described rather in detail; however, the role of the posterior spinal column and the laminae has so far not been elucidated. If the posterior column exhibits a longitudinal growth disturbance, it could act as a tether, leading to a more or less normal anterior column with a deformed and shorter posterior aspect of the spine. So far, it has remained unclear whether this anterior-posterior length discrepancy is the result of relative anterior lengthening or relative posterior shortening, and which tissues (bone, disc, intervertebral soft tissue) are involved. Purpose: The present study aimed to compare the discrepancy of the anterior-posterior length of the spinal column in the “true” midsagittal plane of each vertebra in patients with idiopathic scoliosis versus controls, using three-dimensional computed tomography (CT) scans. Study Design/Setting: This is a cross-sectional study. Patient Sample: The sample consisted of computed tomography scans of 80 patients with moderate to severe AIS (Cobb angle: 46°–109°) before scoliosis navigation surgery and 30 non-scoliotic age-matched controls. Outcome Measures: The height of the osseous and non-osseous structures from anterior to posterior in the “true” midsagittal plane has been determined: the anterior side of the vertebral body and disc, the posterior side of the vertebral body and disc, the lamina and interlaminar space and the spinous process and interspinous space, as well as the height ratios between the anterior column and posterior structures of the primary thoracic and lumbar AIS curves and corresponding levels in non-scoliotic controls. Methods: Semiautomatic software was used to reconstruct and measure the parameters in the true midsagittal plane of each vertebra and intervertebral structure that are rotated and tilted in a different way. Results: In AIS, the anterior height of the thoracic curve was 3.6±2.8% longer than the posterior height, 2.0±6.1% longer than the length along the laminae, and 8.7±7.1% longer than the length along the spinous processes, and this differed significantly from controls (−2.7±2.4%, −7.4±5.2%, and +0.7±7.8%; p

The current study used theories on expertise development (the holistic model of image perception and the information reduction hypothesis) as a starting point to identify and explore potentially relevant process measures to monitor and evaluate expertise development in radiology residency training. It is the first to examine expertise development in volumetric image interpretation (i.e., CT scans) within radiology residents using scroll data collected longitudinally over five years of residency training. Consistent with the holistic model of image perception, the percentage of time spent on full runs, i.e. scrolling through more than 50% of the CT-scan slices (global search), decreased within residents over residency training years. Furthermore, the percentage of time spent on question-relevant areas in the CT scans increased within residents over residency training years, consistent with the information reduction hypothesis. Second, we examined if scroll patterns can predict diagnostic accuracy. The percentage of time spent on full runs and the percentage of time spent on question-relevant areas did not predict diagnostic accuracy. Thus, although scroll patterns over training years are consistent with visual expertise theories, they could not be used as predictors of diagnostic accuracy in the current study. Therefore, the relation between scroll patterns and performance needs to be further examined, before process measures can be used to monitor and evaluate expertise development in radiology residency training.

It has been brought to the publisher s attention that the two subparts A and B of Figure 5 were inadvertently swapped in the article with DOI: 10.1055/s-0040-1721027 published on November 23, 2020. The corrected figure appears as follows. (Figure Presented).

Summary Objective Knee Image Digital Analysis (KIDA) is standardized radiographic analysis software for measuring osteoarthritis (OA) characteristics. It was validated in mild OA, but used for severe OA as well. The current goal was to evaluate the performance of KIDA in severe OA. Design Of 103 patients, standardized radiographs were performed before and one and 2 years after treatment for severe OA. All radiographs were evaluated on subchondral bone density, joint space width (JSW), osteophytes, eminence height, and joint angle, twice within years by the same observer. Part of the radiographs were randomly selected for reevaluation twice within 1 month and evaluation by another observer. The intraclass correlation coefficient (ICC), smallest detectable difference (SDD) and coefficient of variation (CV) were calculated; the SDD and CV were compared to those in mild OA. The relation of severity with KIDA parameters and with observer differences was calculated with linear regression. Results Intra-observer ICCs were higher in the 98 severe radiographs reanalyzed within 1 month (all >0.8) than the 293 reanalyzed within years (all >0.5; most >0.8) and than inter-observer ICCs (all >0.7). SDDs and CVs were smaller when reanalyzed within a month and comparable to those in mild OA. Some parameters showed bias between readings. Severity showed significant relation with osteophytes and JSW parameters, and with the observer variation in these parameters (all P Conclusions KIDA is a well-performing tool also for severe OA. In order to decrease variability and SDDs, images should be analyzed in a limited time frame and randomized order.

Additional file 3: Table S13. GenBank accession numbers.

Additional file 2: Supplementary Figures S1-S5. Fig. S1. Dendrogram of hnRNPs based on multiple sequence alignment of canonical amino acid sequences. Colors match those seen in Fig. 2. NDD hnRNPs are shown in black boxes. Fig. S2. Pathogenicity assessment of variation in hnRNPs. A) Gene Variation Intolerance Ranking (GeVIR), loss-of-function observed/expected upper bound fraction (LOEUF), and Variation Intolerant Region Loss-of-Function (VIRLoF) percentiles. Average LOEUF percentile is significantly higher for NDD HNRNPs (n = 13) compared to other HNRNPs (n = 15). B) Average fold change for GeVIR, LEOUF, and VIRLoF for autosomal dominant (AD) and autosomal recessive (AR) variants. Average LEOUF fold change for AD mutations is significantly higher for NDD HNRNPs compared to other HNRNPs, with the AD VIRLoF fold change trending in the same direction. The AR LEOUF fold change is trending towards being significantly higher among other HNRNPs compared to NDD HNRNPs. One-way t-test. * p

The aim of this two-centre RCT was to compare pre- and post-operative radiological, clinical and functional outcomes between patient-specific instrumentation (PSI) and conventional instrumented (CI) unicompartmental knee arthroplasty (UKA). It was hypothesised that both alignment methods would have comparable post-operative radiological, clinical and functional outcomes.One hundred and twenty patients were included, and randomly allocated to the PSI or the CI group. Outcome measures were peri-operative outcomes (operation time, length of hospital stay and intra-operative changes of implant size) and post-operative radiological outcomes including the alignment of the tibial and femoral component in the sagittal and frontal plane and the hip-knee-ankle-axis (HKA-axis), rate of adverse events (AEs) and patient-reported outcome measures (PROMs) pre-operatively and at 3, 12 and 24 months post-operatively.There was a statistically significant difference (p 0.05) in alignment of the femoral component in the frontal plane in favour of the CI method. No statistically significant differences were found for the peri-operative data or in the functional outcome at 2-year follow-up. In the PSI group, the approved implant size of the femoral component was correct in 98.2% of the cases and the tibial component was correct in 60.7% of the cases. There was a comparable rate of AEs: 5.1% in the CI and 5.4% in the PSI group.The PSI method did not show an advantage over CI in regard of positioning of the components, nor did it show an improvement in clinical or functional outcome. We conclude that the possible advantages of PSI do not outweigh the costs of the MRI scan and the manufacturing of the PSI.Randomised controlled trial, level I.

Anteromedial osteoarthritis (AMOA) is a common wear pattern in primary osteoarthritic knees. In patients with bone-on-bone disease, the most appropriate surgical intervention is still a matter of debate. Knee arthroplasty is a well-accepted treatment to relieve symptoms and regain function. Unfortunately, satisfaction is limited, especially related to activities. A cross-sectional study was performed among patients treated with total knee arthroplasty (TKA) and unicondylar arthroplasty (UKA) to determine if the osteoarthritis wear pattern or type of prosthesis affects knee-specific function scores and satisfaction related to activities. All UKA patients (N = 100) were treated for AMOA. Based on radiological assessment of the wear pattern, TKA patients were divided into two groups: TKA for AMOA (N = 68) and true TKA (N = 99). The Knee injury and Osteoarthritis Outcomes Score (KOOS), new Knee Society score (KSS), anterior knee pain scale, visual analog scales (VASs) for satisfaction about activities, and net promoter score were collected. After 2 years' follow-up, the anterior knee pain scale and VAS satisfaction showed significantly better scores for patients treated with TKA for AMOA compared with the true TKA group. Also in the KOOS subscales, some differences were seen in favor of the TKA for AMOA group. The new KSS was not in favor of a specific wear pattern, but patients with AMOA treated with UKA performed better on the symptoms subscale compared with patients treated with TKA. In conclusion, patients treated with TKA for AMOA showed better knee-specific function scores and satisfaction scores compared with patients treated with TKA for other wear patterns, and only slight differences were found between both the AMOA groups (TKA for AMOA and UKA). Thus, the radiologic assessment of wear patterns might be useful to take into account the shared decision-making process, when discussing expectations, timing, and outcomes with knee osteoarthritis patients considering knee arthroplasty. When AMOA is present, it might be beneficial to choose UKA over TKA.

BACKGROUND: Knee arthroplasty (KA) is increasingly performed in relatively young, active patients. This heterogeneous patient population often has high expectations, including work resumption and performance of knee-demanding leisure-time activities. Goal attainment scaling (GAS) may personalize rehabilitation by using patient-specific, activity-oriented rehabilitation goals. Since unmet expectations are a leading cause of dissatisfaction after KA, personalized rehabilitation may improve patient satisfaction. We hypothesized that, compared with standard rehabilitation, GAS-based rehabilitation would result in younger, active patients having higher satisfaction regarding activities after KA. METHODS: We performed a single-center randomized controlled trial. Eligible patients were

Existing research suggests that while some laboratories report variants of uncertain significance, unsolicited findings (UF), and/or secondary findings (SF) when performing exome sequencing, others do not.To investigate reporting differences, we created virtual patient-parent trio data by merging variants from patients into "normal" exomes. We invited laboratories worldwide to analyze the data along with patient phenotype information (developmental delay, dysmorphic features, and cardiac hypertrophy). Laboratories issued a diagnostic exome report and completed questionnaires to explain their rationale for reporting (or not reporting) each of the eight variants integrated.Of the 39 laboratories that completed the questionnaire, 30 reported the HDAC8 variant, which was a partial cause of the patient's primary phenotype, and 26 reported the BICD2 variant, which explained another phenotypic component. Lack of reporting was often due to using a filter or a targeted gene panel that excluded the variant, or because they did not consider the variant to be responsible for the phenotype. There was considerable variation in reporting variants associated with the cardiac phenotype (MYBPC3 and PLN) and reporting UF/SF also varied widely.This high degree of variability has significant impact on whether causative variants are identified, with important implications for patient care.

Background and purpose — Partial knee replacement (PKR) survival rates vary a great deal among registries and cohort studies. These discrepancies can largely be attributed to inappropriate indications of the PKR and low thresholds for revision, but also to the PKR volume. This study used Dutch Arthroplasty Register data to analyze whether absolute PKR or proportional PKR hospital volume is associated with the risk of revision. Patients and methods — 18,134 PKRs were identified in the Dutch Arthroplasty Register from 2007 to 2016. For each year, hospitals were divided into 4 groups based on the quartiles for the absolute volume (< 22, 22–36, 36–58 and > 58 PKRs per year) and the proportional volume (< 8.5, 8.6–14.2, 14.3–25.8 and > 25.8% PKRs). Kaplan–Meier survival analysis was performed to determine survival rates. A multivariable Cox regression adjusted for age category, sex, ASA score, year of surgery, diagnosis, unicondylar side, and type of hospital was used to estimate hazard ratios (HR) for revision. Results and interpretation — Proportional PKR volume did not, but absolute PKR volume did influence the risk of revision. The adjusted HR for hospitals with an absolute volume of 22–36 PKRs per year was 1.04 (95% CI 0.91–1.20), 0.96 (CI 0.83–1.10) for the hospitals with 36–58 PKRs, and 0.74 (CI 0.62–0.89) for hospitals with more than 58 PKRs compared with hospitals that had fewer than 22 PKRs per year. So, patients treated with a PKR in a high absolute volume hospital have a lower risk of revision compared with those treated in a low absolute volume hospital.

Background: Lateral epicondylitis (LE) most commonly affects the Extensor Carpi Radialis Brevis (ECRB) tendon and patients are generally treated with injection therapy. For optimal positioning of the injection, as well as an estimation of the surface area and content of the ECRB tendon to determine the volume of the injectable needed, it is important to know the exact location of the ECRB in relation to the skin as well as the variation in tendon length and location. The aim of this study was to determine the variation in location and size of the ECRB tendon in patients with LE. Methods: An observational sonographic evaluation of the ECRB tendon was performed in 40 patients with LE. The length of the ECRB tendon, distance from the cutis to the center of the ECRB tendon, the length of the osteotendinous junction at the epicondyle and the distance from cutis to middle of the osteotendinous junction were measured. Results: The average tendon length was 1.68cm (range 1.27-1.98; SD 0.177). Compared to women, the ECRB tendon of men was on average 0.12cm longer. Overall, the average distance from cutis to the center of the ECRB was 0.75cm (range 0.50-1.46cm; SD 0.210), the average length of the junction was 0.55cm (range 0.35-0.87; SD 0.130), and the distance from cutis to middle of the osteotendinous junction was 0.73cm (range 0.40-1.25cm; SD 0.210). Conclusion: The size and depth of the ECRB tendon in patients with LE is largely variable. While there are no studies yet suggesting sono-guided injection to be superior to that of blind injection, the anatomic variability of this study suggests that the accuracy of injection therapy for LE might be compromised when based solely on bony landmarks and therefore not fully reliable. As a result, there is value in further studies exploring the accuracy of the ultrasound guided injection techniques.