Citations

Abstract Background To protect minors’ future autonomy, professional organizations have historically discouraged returning predictive adult-onset genetic test results and carrier status to children. Recent clinical guidance diverges from this norm, suggesting that when minors have genomic sequencing performed for clinical purposes, parents and children should have the opportunity to learn secondary findings, including for some adult-onset conditions. While parents can currently opt in or out of receiving their child’s secondary findings, the American Society of Human Genetics Workgroup on Pediatric Genetic and Genomic Testing suggests including adolescents in the decision-making process. However, it is not clear what factors young people consider when given the opportunity to learn genetic findings for themselves. We are examining adolescents’, young adults’, and parents’ (if applicable) decisions about learning genomic information for the adolescent. Methods We are enrolling assenting (ages 13–17) adolescents and consenting (ages 18–21) young adults in a prospective genomic screening study to assess the choices they make about receiving individual genomic results. Participants use an online tool to indicate whether they want to learn their personal genetic risk for specific preventable, treatable, and adult-onset conditions, as well as carrier status for autosomal recessive conditions. We are examining 1) how choices differ between adolescent and young adult cohorts (as well as between adolescents/young adults and parents) and 2) decisional conflict and stability across study timepoints. Results are returned based on participants’ choices. Qualitative interviews with a subset of participants explore decisional stability, adolescent/young adult engagement with parents in decision-making, and the impact of learning pathogenic/likely pathogenic and carrier results. Discussion This study explores decision making and decision stability between adolescents and parents (where applicable), as well as the ethical implications and impact of return of clinical-grade genetic research results to adolescents and young adults. The results of this study will contribute empirical evidence to support best practices and guidance on engaging young people in genetic research studies and clinical care that offer return of results. Trial Registration: ClinicalTrials.gov Identifier: NCT04481061. Registered 22 July 2020.

Background: Ream-and-run arthroplasty can improve pain and function in patients with glenohumeral arthritis while avoiding the complications and activity restrictions associated with a prosthetic glenoid component. However, stiffness is a known complication after ream-and-run arthroplasty and can lead to repeat procedures such as a manipulation under anesthesia (MUA) or open surgical revision. The objective of this study was to determine risk factors associated with repeat procedures indicated for postoperative stiffness after ream-and-run arthroplasty. Methods: We conducted a retrospective review of our shoulder arthroplasty database to identify patients who underwent ream-and-run arthroplasty and determined which patients underwent subsequent repeat procedures (MUA and/or open revision) indicated for postoperative stiffness. The minimum follow-up was 2 years. We collected baseline demographic information and preoperative and 2-year patient-reported outcome scores and analyzed preoperative radiographs. Univariate and multivariate analyses determined the factors significantly associated with repeat procedures to treat postoperative stiffness. Results: There were 340 patients who underwent ream-and-run arthroplasty. The mean Simple Shoulder Test (SST) scores for all patients improved from 5.0 ± 2.4 preoperatively to 10.2 ± 2.6 postoperatively (p < 0.001). Twenty-six patients (7.6%) underwent open revision for stiffness. An additional 35 patients (10.3%) underwent MUA. Univariate analysis found younger age (p = 0.001), female sex (p = 0.034), lower American Society of Anesthesiologists (ASA) class (p = 0.045), posterior decentering on preoperative radiographs (p = 0.010), and less passive forward elevation at the time of discharge after ream-and-run arthroplasty (p < 0.001) to be significant risk factors for repeat procedures. Multivariate analysis found younger age (p = 0.040), ASA class 1 compared with class 3 (p = 0.020), and less passive forward elevation at discharge (p < 0.001) to be independent risk factors for repeat procedures. Of the patients who underwent open revision for stiffness, 69.2% had multiple positive cultures for Cutibacterium. Conclusions: Younger age, ASA class 1 compared with class 3, and less passive forward elevation in the immediate postoperative period were independent risk factors for repeat procedures to treat postoperative stiffness after ream-and-run arthroplasty. Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Myelin oligodendrocyte glycoprotein (MOG) antibody–associated disease (MOGAD) is an inflammatory demyelinating CNS condition characterized by the presence of MOG autoantibodies. We sought to investigate whether human MOG autoantibodies are capable of mediating damage to MOG-expressing cells through multiple mechanisms. We developed high-throughput assays to measure complement activity (CA), complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent cellular cytotoxicity (ADCC) of live MOG-expressing cells. MOGAD patient sera effectively mediate all of these effector functions. Our collective analyses reveal that (a) cytotoxicity is not incumbent on MOG autoantibody quantity alone; (b) engagement of effector functions by MOGAD patient serum is bimodal, with some sera exhibiting cytotoxic capacity while others did not; (c) the magnitude of CDC and ADCP is elevated closer to relapse, while MOG-IgG binding is not; and (d) all IgG subclasses can damage MOG-expressing cells. Histopathology from a representative MOGAD case revealed congruence between lesion histology and serum CDC and ADCP, and we identified NK cells, mediators of ADCC, in the cerebrospinal fluid of relapsing patients with MOGAD. Thus, MOGAD-derived autoantibodies are cytotoxic to MOG-expressing cells through multiple mechanisms, and assays quantifying CDC and ADCP may prove to be effective tools for predicting risk of future relapses.

Introduction Various clinical trials addressing large core acute ischemic stroke (AIS) are ongoing from multiple international groups. Future development of clinical guidelines depends on meta‐analyses of these trials calling for a degree of homogeneity of elements across the different studies. The aim of this common data element study was to provide an overview of the key features of pertinent large core infarct trials. Methods PubMed and ClinicalTrials.gov databases were screened for published and ongoing clinical trials assessing mechanical thrombectomy in patients with AIS with large core infarct. Nested Knowledge AutoLit living review platform was utilized to categorize primary and secondary outcomes as well as inclusion and exclusion criteria for patient selection in the clinical trials. Results The most reported data element was ASPECTS score, but with varied definitions of what compromises large core. Non‐utility‐weighted modified Rankin Score (mRS) was reported in 6/7 studies as the primary outcome, while the utility‐weighted mRS was the outcome of interest in the TESLA trial, all of them at the 3‐months mark, with only LASTE looking for mRS shift at the 6‐months mark. Secondary outcomes had more variations. Mortality is reported separately only in 4/7 trials, all at the 3‐month mark. Additionally, the TENSION trial reports the frequency of serious adverse events, including mortality, at the 1‐week and 12‐month mark. Conclusions In the published and the ongoing large core trials, there is a large degree of variability in the collected data elements. Differences in definition and timepoints renders reaching a unified standard difficult, which hinders high quality meta‐analyses and cohesive evidence‐driven synthesis.

Background: Ganglion cysts are benign soft-tissue tumors that are most commonly found in the wrist. Within the wrist, 60% to 70% of ganglion cysts occur on the dorsal side and 20% to 30% occur on the volar side 1 . Although ganglia arise from multiple sites over the dorsal wrist, dorsal ganglia most commonly originate at the scapholunate joint 2,3 . Open excision is the standard surgical treatment for dorsal wrist ganglia. This procedure is considered when symptoms such as pain and range-of-motion deficits begin to impact activities of daily living. Description: Open excision of a dorsal wrist ganglion is commonly performed with the patient under general anesthesia or a regional block. The patient is placed in the supine position, and a tourniquet is applied on the affected upper limb. After outlining the periphery of the palpable ganglion, the surgeon makes a transverse or longitudinal incision over the ganglion. The surgeon then begins a deep dissection, dissecting through the subcutaneous tissue and isolating the ganglion while avoiding any rupture, if possible. Once the cyst has been identified, extensor tendons surrounding the cyst are retracted and the cyst and stalk are mobilized. The cyst and stalk are subsequently excised, and the wound is closed 4 . Alternatives: Alternative treatments for dorsal wrist ganglia include nonoperative interventions such as observation, aspiration, controlled rupture, and injection. Operative treatments include arthroscopic and open dorsal wrist ganglion resections. Rationale: Although nonoperative treatment can produce successful outcomes, the various modalities have been associated with recurrence rates ranging from 15% to 90% 4 . As a result, surgical excision remains the gold standard of treatment and is typically indicated when weakness, pain, and limited range of motion interfere with activities of daily living. Among surgical interventions, arthroscopic excision is a minimally invasive procedure that has become more common because of the reduced scarring and faster recovery 5 . However, open excision, which does not involve complex equipment, is regarded as the standard among surgical treatments. Although the rates of recurrence for arthroscopic versus open dorsal ganglion excision are similar, arthroscopic excision is less effective with regard to pain relief 5,6 . This difference in pain relief could potentially be the result of the neurectomy of the posterior interosseous nerve in an open excision. In contrast, an arthroscopic procedure may provide less relief of pain from the posterior interosseous nerve stump attaching to the scarred capsule 5 . Expected Outcomes: Open excision of a dorsal wrist ganglion is a safe, reliable procedure. The recurrence rate after open excision is similar to that after arthroscopic excision and significantly lower recurrence than that after ganglion cyst aspiration 6,7 . Additionally, not all ganglion cysts can be aspirated. In a retrospective study assessing the risk of recurrence after open excision of ganglion cysts in 628 patients, researchers reported a recurrence rate of 4.1% among the 341 who underwent open dorsal ganglion excision. Furthermore, the authors reported male sex and less surgeon experience as significant risk factors for cyst recurrence 8 . In a study assessing outcomes of open dorsal ganglion excision in 125 active-duty military personnel, researchers reported a recurrence rate of 9%. More notably, the researchers found persistent pain at 4 weeks postoperatively in 14% of the participants. The authors recommended that patients whose daily activities require forceful wrist extension, such as athletes and military personnel, should be counseled on the potential functional limitations and residual pain from open dorsal wrist ganglion excision 9 . Important Tips: When conducting an open excision, it is beneficial to identify the stalk of the cyst, allowing the surgeon to excise the complete ganglion complex and prevent recurrence. For large cysts that adhere to the surrounding soft tissue, it is helpful to rupture the ganglion in order to facilitate an easier deep dissection. Excising the scapholunate interosseous ligament could possibly lead to scapholunate dissociation and instability. The posterior interosseous nerve courses past the 4th dorsal compartment and may be resected during the deep dissection.

Background and Aims: The presence of at-risk NASH is associated with an increased risk of cirrhosis and complications. Therefore, noninvasive identification of at-risk NASH with an accurate biomarker is a critical need for pharmacologic therapy. We aim to explore the performance of several magnetic resonance (MR)-based imaging parameters in diagnosing at-risk NASH. Approach and Results: This prospective clinical trial (NCT02565446) includes 104 paired MR examinations and liver biopsies performed in patients with suspected or diagnosed NAFLD. Magnetic resonance elastography-assessed liver stiffness (LS), 6-point Dixon-derived proton density fat fraction (PDFF), and single-point saturation-recovery acquisition-calculated T1 relaxation time were explored. Among all predictors, LS showed the significantly highest accuracy in diagnosing at-risk NASH [AUCLS: 0.89 (0.82, 0.95), AUCPDFF: 0.70 (0.58, 0.81), AUCT1: 0.72 (0.61, 0.82), z-score test z >1.96 for LS vs any of others]. The optimal cutoff value of LS to identify at-risk NASH patients was 3.3 kPa (sensitivity: 79%, specificity: 82%, negative predictive value: 91%), whereas the optimal cutoff value of T1 was 850 ms (sensitivity: 75%, specificity: 63%, and negative predictive value: 87%). PDFF had the highest performance in diagnosing NASH with any fibrosis stage [AUCPDFF: 0.82 (0.72, 0.91), AUCLS: 0.73 (0.63, 0.84), AUCT1: 0.72 (0.61, 0.83), |z| <1.96 for all]. Conclusion: Magnetic resonance elastography-assessed LS alone outperformed PDFF, and T1 in identifying patients with at-risk NASH for therapeutic trials.