Citations

Abstract Video-polysomnography (v-PSG) is essential for diagnosing rapid eye movement (REM) sleep behavior disorder (RBD). Although there are current American Academy of Sleep Medicine standards to diagnose RBD, several aspects need to be addressed to achieve harmonization across sleep centers. Prodromal RBD is a stage in which symptoms and signs of evolving RBD are present, but do not yet meet established diagnostic criteria for RBD. However, the boundary between prodromal and definite RBD is still unclear. As a common effort of the Neurophysiology Working Group of the International RBD Study Group, this manuscript addresses the need for comprehensive and unambiguous v-PSG recommendations to diagnose RBD and identify prodromal RBD. These include: (1) standardized v-PSG technical settings; (2) specific considerations for REM sleep scoring; (3) harmonized methods for scoring REM sleep without atonia; (4) consistent methods to analyze video and audio recorded during v-PSGs and to classify movements and vocalizations; (5) clear v-PSG guidelines to diagnose RBD and identify prodromal RBD. Each section follows a common template: The current recommendations and methods are presented, their limitations are outlined, and new recommendations are described. Finally, future directions are presented. These v-PSG recommendations are intended for both practicing clinicians and researchers. Classification and quantification of motor events, RBD episodes, and vocalizations are however intended for research purposes only. These v-PSG guidelines will allow collection of homogeneous data, providing objective v-PSG measures and making future harmonized multicentric studies and clinical trials possible.

INTRODUCTION: Functional luminal imaging probe (FLIP) panometry can evaluate esophageal motility in response to sustained esophageal distension at the time of sedated endoscopy. This study aimed to describe a classification of esophageal motility using FLIP panometry and evaluate it against high-resolution manometry (HRM) and Chicago Classification v4.0 (CCv4.0). METHODS: Five hundred thirty-nine adult patients who completed FLIP and HRM with a conclusive CCv4.0 diagnosis were included in the primary analysis. Thirty-five asymptomatic volunteers (“controls”) and 148 patients with an inconclusive CCv4.0 diagnosis or systemic sclerosis were also described. Esophagogastric junction (EGJ) opening and the contractile response (CR) to distension (i.e., secondary peristalsis) were evaluated with a 16-cm FLIP during sedated endoscopy and analyzed using a customized software program. HRM was classified according to CCv4.0. RESULTS: In the primary analysis, 156 patients (29%) had normal motility on FLIP panometry, defined by normal EGJ opening and a normal or borderline CR; 95% of these patients had normal motility or ineffective esophageal motility on HRM. Two hundred two patients (37%) had obstruction with weak CR, defined as reduced EGJ opening and absent CR or impaired/disordered CR, on FLIP panometry; 92% of these patients had a disorder of EGJ outflow per CCv4.0. DISCUSSION: Classifying esophageal motility in response to sustained distension with FLIP panometry parallels the swallow-associated motility evaluation provided with HRM and CCv4.0. Thus, FLIP panometry serves as a well-tolerated method that can complement, or in some cases be an alternative to HRM, for evaluating esophageal motility disorders.

Background: The loss of extensor mechanism continuity that occurs with patellar and quadriceps tendon rupture has devastating consequences on patient function. Purpose: To describe a treatment strategy for extensor mechanism disruption and evaluate the outcomes of 3 techniques: primary repair, repair with semitendinosus tendon autograft augmentation, and reconstruction with Achilles tendon allograft. Study Design: Case series; Level of evidence, 4. Methods: The authors reviewed surgeries for extensor mechanism disruption performed by a single surgeon between 1999 and 2019. Patient characteristics, imaging studies, surgical techniques, and outcomes were recorded. Primary ruptures with robust tissue quality were repaired primarily, and first-time ruptures with significant tendinosis or moderate tissue loss were repaired using quadrupled semitendinosus tendon autograft augmentation. Patients with failed previous extensor mechanism repair or reconstruction and poor tissue quality underwent reconstruction with Achilles tendon allograft. The primary outcome was extensor mechanism integrity at a minimum 1-year follow-up, with extensor mechanism lag defined as >5° loss of terminal, active knee extension. Secondary outcomes included postoperative knee range of motion, International Knee Documentation Committee (IKDC) and Tegner activity scores, and the radiographic Caton-Deschamps Index. Results: Included were 22 patellar tendon and 21 quadriceps tendon surgeries (patients: 82.5% male; mean age, 48.1 years; body mass index, 31). Seventeen (39.5%) cases underwent primary tendon repair, 13 (30.2%) had repair using semitendinosus tendon autograft augmentation, and 13 (30.2%) underwent reconstruction using an Achilles tendon allograft. Seventeen (39.5%) cases had at least 1 prior failed extensor mechanism surgery performed at an outside facility. At the last follow-up, 4 (9.3%) cases had an extensor mechanism lag, no cases required additional extensor mechanism surgery, and all cases were able to achieve >90° of knee flexion. Postoperative IKDC scores were significantly improved with all methods of extensor mechanism surgery, and postoperative Tegner activity scores were significantly improved in patients who underwent primary repair and Achilles tendon allograft reconstruction ( P < .05 for all). Conclusion: Primary repair alone, repair using quadrupled semitendinosus tendon autograft augmentation, and reconstruction using Achilles tendon allograft were all effective methods to restore extensor mechanism and knee function with the proper indications. Persistent knee extensor lag was more common in chronic extensor mechanism injuries after failed surgery, although patients still reported significantly improved postoperative functional outcomes.

AbstractIntroductionLiver transplant anesthesiology is an evolving and expanding subspecialty, and programs have, in the past, exhibited significant variations of practice at transplant centers across the United States. In order to explore current practice patterns, the Quality & Standards Committee from the Society for the Advancement of Transplant Anesthesia (SATA) undertook a survey of liver transplant anesthesiology program directors.MethodsProgram directors were invited to participate in an online questionnaire. A total of 110 program directors were identified from the 2018 Scientific Registry of Transplant Recipients (SRTR) database. Replies were received from 65 programs (response rate of 59%).ResultsOur results indicate an increase in transplant anesthesia fellowship training and advanced training in transesophageal echocardiography (TEE). We also find that the use of intraoperative TEE and viscoelastic testing is more common. However, there has been a reduction in the use of veno‐venous bypass, routine placement of pulmonary artery catheters and the intraoperative use of anti‐fibrinolytics when compared to prior surveys.ConclusionThe results show considerable heterogeneity in practice patterns across the country that continues to evolve. However, there appears to be a movement towards the adoption of specific structural and clinical practices.

Background: Meniscal tears are common in active patients, but treatment trends and surgical outcomes in young patients with lateral meniscal tears are lacking. Purpose: To evaluate treatment trends, outcomes, and failure rates in young patients with lateral meniscal tears. Study Design: Cohort study; Level of evidence, 3. Methods: Patients aged ≤25 years treated surgically for isolated lateral meniscal tears from 2001 to 2017 were identified. Treatment trends were compared over time. International Knee Documentation Committee (IKDC) scores and failure rates were compared by treatment modality (meniscectomy vs meniscal repair). Failure was defined as reoperation, symptomatic osteoarthritis, or a severely abnormal IKDC score. Univariate regression analyses were performed to predict failure and IKDC scores based on treatment, type and location of tear, or extent of meniscectomy. Results: Included were 217 patients (226 knees) with a mean age of 17.4 years (range, 7-25 years); of these patients, 144 knees (64%) were treated with meniscectomy and 82 knees (36%) with meniscal repair. Treatment with repair increased over time compared with meniscectomy ( P < .001). At a minimum 2-year follow-up (mean, 6.1 ± 3.9 years), 107 patients (110 knees) had IKDC scores, and analysis indicated that although scores in both groups improved from pre- to postoperatively (repair: from 69.5 ± 13.3 to 97.4 ± 4.3; meniscectomy: from 75.7 ± 9.0 to 97.3 ± 3.9; P < .001 for both), improvement in IKDC score was greater after repair (27.9 ± 13.9) versus meniscectomy (21.6 ± 9.4) ( P = .005). Included in the failure analysis were 184 patients (192 knees) at a mean follow-up of 8.4 ± 4.4 years. The rates of reoperation, symptomatic osteoarthritis, and failure were not significantly different between the meniscectomy and repair groups. Conclusion: An increase was seen in the rate of isolated lateral meniscal tear repair in young patients. IKDC score improvement was greater after repair than meniscectomy, although postoperative IKDC scores were similar. Symptomatic arthritis, reoperation, and failure rates were similar between groups; however, there was a trend for increased arthritis symptoms in patients treated with meniscectomy, especially total meniscectomy. Treatment modality, type and location of tear, and amount of meniscus removed were not predictive of final IKDC scores or failure.

Abstract The congenital heart care community faces a myriad of public health issues that act as barriers toward optimum patient outcomes. In this article, we attempt to define advocacy and policy initiatives meant to spotlight and potentially address these challenges. Issues are organized into the following 3 key facets of our community: patient population, health care delivery, and workforce. We discuss the social determinants of health and health care disparities that affect patients in the community that require the attention of policy makers. Furthermore, we highlight the many needs of the growing adults with congenital heart disease and those with comorbidities, highlighting concerns regarding the inequities in access to cardiac care and the need for multidisciplinary care. We also recognize the problems of transparency in outcomes reporting and the promising application of telehealth. Finally, we highlight the training of providers, measures of productivity, diversity in the workforce, and the importance of patient–family centered organizations in advocating for patients. Although all of these issues remain relevant to many subspecialties in medicine, this article attempts to illustrate the unique needs of this population and highlight ways in which to work together to address important opportunities for change in the cardiac care community and beyond. This article provides a framework for policy and advocacy efforts for the next decade.

RNA polymerase II (Pol II)-dependent transcription in stimulus-inducible genes requires topoisomerase IIβ (TOP2B)-mediated DNA strand break and the activation of DNA damage response signalling in humans. Here, we report a novel function of the breast cancer 1 (BRCA1)-BRCA1-associated ring domain 1 (BARD1) complex in this process. We found that BRCA1 is phosphorylated at S1524 by the kinases ataxia-telangiectasia mutated and ATR during gene activation, and that this event is important for productive transcription. Our biochemical and genomic analyses showed that the BRCA1-BARD1 complex interacts with TOP2B in the EGR1 transcription start site and in a large number of protein-coding genes. Intriguingly, the BRCA1-BARD1 complex ubiquitinates TOP2B, which stabilizes TOP2B binding to DNA while BRCA1 phosphorylation at S1524 controls the TOP2B ubiquitination by the complex. Together, these findings suggest the novel function of the BRCA1-BARD1 complex in the regulation of TOP2B and Pol II-mediated gene expression.

Abstract Therapeutic advances for glioblastoma have been minimal over the past 2 decades. In light of the multitude of recent phase III trials that have failed to meet their primary endpoints following promising preclinical and early-phase programs, a Society for Neuro-Oncology Think Tank was held in November 2020 to prioritize areas for improvement in the conduct of glioblastoma clinical trials. Here, we review the literature, identify challenges related to clinical trial eligibility criteria and trial design in glioblastoma, and provide recommendations from the Think Tank. In addition, we provide a data-driven context with which to frame this discussion by analyzing key study design features of adult glioblastoma clinical trials listed on ClinicalTrials.gov as “recruiting” or “not yet recruiting” as of February 2021.

Abstract Richter syndrome (RS) represents a transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) to aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), which is associated with a dismal prognosis. Patients with DLBCL-RS have poor outcomes with DLBCL-directed therapy; thus, consolidation with hematopoietic cell transplantation (HCT) has been used, with durable remissions observed. Studies reporting HCT outcomes in patients with DLBCL-RS have been small, have not evaluated the prognostic impact of cytogenetic risk factors, and were conducted prior to the era of novel targeted therapy of CLL/SLL. We performed a Center for International Blood and Transplant Research registry study evaluating outcomes after autologous HCT (auto-HCT; n = 53) and allogeneic HCT (allo-HCT; n = 118) in patients with DLBCL-RS treated in the modern era. More auto-HCT recipients were in complete response (CR) at HCT relative to allo-HCT recipients (66% vs 34%), whereas a higher proportion of allo-HCT recipients had 17p deletion (33% vs 7%) and had previously received novel agents (39% vs 10%). In the auto-HCT cohort, the 3-year relapse incidence, progression-free survival (PFS), and overall survival (OS) were 37%, 48%, and 57%, respectively. Among allo-HCT recipients, the 3-year relapse incidence, PFS, and OS were 30%, 43%, and 52%, respectively. In the allo-HCT cohort, deeper response at HCT was associated with outcomes (3-year PFS/OS, 66%/77% CR vs 43%/57% partial response vs 5%/15% resistant; P &lt; .0001 for both), whereas cytogenetic abnormalities and prior novel therapy did not impact outcomes. In our study, HCT resulted in durable remissions in therapy-sensitive patients with DLBCL-RS treated in the era of targeted CLL/SLL therapy, including patients with high-risk features.