Citations

Abstract Introduction Introduction: Rapid eye movement (REM) sleep behavior disorder (RBD) is strongly associated with progressive phenoconversion to an overt synucleinopathy (e.g., parkinsonism). Neurotrauma [i.e., traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD)], increases the odds of RBD diagnosis by ~2.5-fold and is associated with an increased later diagnosis of Parkinson’s Disease (PD), a service-connected illness in Veterans. Thus, RBD and neurotrauma are both independently associated with parkinsonism; however, it is unclear how neurotrauma influences neurological symptoms and exam findings in patients with RBD. Methods Methods: Participants ≥18 years of age with overnight polysomnogram-confirmed RBD were enrolled between 8/2018 to 4/2021 as part of the North American Prodromal Synucleinopathy (NAPS) Consortium. Standardized assessments for RBD, TBI, and PTSD history, as well as cognitive, motor, sensory and autonomic function were completed. This sub-study applied a cross-sectional, case-control (1:4 ratio) analysis comparing cases (n=24; RBD+TBI+PTSD) to controls (n=96; RBD) matched for age (±2 years), sex, and years of education (±2 years). Results Results: Participants with neurotrauma reported an earlier age of RBD symptom onset and more severe RBD phenotype, more severe anxiety and depression, greater frequency of hypertension, and significantly worse cognitive, motor, and autonomic function compared to participants without neurotrauma. Conclusion Conclusion: This cross-sectional, matched case:control study showed that individuals with comorbid neurotrauma and RBD have significantly worse neurological outcomes related to common features of early parkinsonism. Although confirmatory longitudinal studies are still ongoing, these results may be a sign of further/faster progression of synucleinopathy in those with comorbid neurotrauma and RBD. Support (if any) Support: NIH R34 AG056639, NIH U19 AG071754, VA RRD 1K2 RX002947, Parkinsons Center of Oregon

Abstract Objective To retrospectively identify patients with VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) among male patients with bone marrow vacuolization using a clinically applicable, targeted-screening approach. Methods Bone marrow reports from 1 May 2014 through 18 February 2022 were reviewed for documentation of cytoplasmic vacuolization. Patients with acute leukaemia, lymphoma, metastatic solid tumour, amyloidosis or POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome were excluded, as were those without clinical records available for direct chart review. Cases were rated for suspicion of VEXAS syndrome using a 5-point scale based on the presence of laboratory findings, clinical features and treatment response. Patients with available DNA material and moderate (three patients) or high (four to five patients) suspicion were tested for somatic UBA1 variants associated with VEXAS syndrome. Results A total of 315 reports from 292 unique patients included documentation of vacuolization. Following exclusion criteria, 64 patients underwent direct medical chart review to assess likelihood of VEXAS syndrome, for which 21 patients met moderate to high suspicion. Available DNA was present in eight patients, seven (87.5%) of whom had a pathogenic somatic UBA1 variant consistent with VEXAS syndrome. The distribution of cytoplasmic vacuolization in the bone marrow biopsy reports among patients with VEXAS syndrome were erythroid and myeloid precursors (6/7), erythroid precursors only (1/7) and myeloid precursors only (0/7). Conclusion In this study, the utilization of a clinically applicable targeted-screening approach to test bone marrow specimens (with vacuolization) for the presence of previously undiagnosed VEXAS syndrome resulted in a positive detection rate of 87.5%.

AbstractObjectiveThe goal of the current study is to advance efforts to increase the quality of care for childhood anxiety disorder (CADs) through (1) detailing the content of community‐based treatment sessions, (2) exploring the validity of therapist surveys, (3) examining the influence of setting differences, and (4) testing the effects of a technology‐based training on use of nonexposure strategies.MethodsThirteen therapists were randomly assigned to technology‐based training in the use of exposure therapy or treatment as usual (TAU) for CADs. Therapeutic techniques were coded from 125 community‐based treatment sessions.ResultsConsistent with survey responses community therapists spent the majority of session time reviewing symptoms (34% of session time), implementing nonexposure cognitive behavioral therapy (CBT; 36%), and rarely engaged in exposure (3%). An integrated behavioral health setting was associated with greater endorsement of exposure on survey, p < 0.05, although this difference was not significant in session recordings, p = 0.14. Multilevel models indicated that technology‐based training that has been shown to increase exposure, also decreased use of nonexposure CBT techniques (2% vs. 29%, p < 0.001).ConclusionThe study supports the validity of survey‐based findings that community‐based care for CADs consists of non‐exposure CBT techniques. Efforts should be invested in dissemination of within‐session exposure.

Background Hereditary and acquired thrombophilia are risk factors for venous thromboembolism (VTE). Whether testing helps guide management decisions is controversial. Objective These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about thrombophilia testing. Methods ASH formed a multidisciplinary guideline panel covering clinical and methodological expertise and minimizing bias from conflicts of interest. The McMaster University GRADE Centre provided logistical support, performed systematic reviews, and created evidence profiles and evidence-to-decision tables. The Grading of Recommendations Assessment, Development, and Evaluation approach (GRADE) was used. Recommendations were subject to public comment. Results The panel agreed on 23 recommendations regarding thrombophilia testing and associated management. Nearly all recommendations are based on very low certainty in the evidence due to modeling assumptions. Conclusions The panel issued a strong recommendation against testing the general population before starting combined oral contraceptives (COCs) and conditional recommendations for thrombophilia testing in the following scenarios: (a) patients with VTE associated with nonsurgical major transient or hormonal risk factors; (b) patients with cerebral or splanchnic venous thrombosis, in settings where anticoagulation would otherwise be discontinued; (c) individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance to avoid COCs/hormone replacement therapy; (d) pregnant women with a family history of high-risk thrombophilia types; and (e) patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE. For all other questions, the panel provided conditional recommendations against testing for thrombophilia.

Abstract In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)—a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ("double hit"). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, doxorubicin, vincristine, and etoposide, with rituximab and prednisone (DA-EPOCH-R; 43%); rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 33%); or other intensive chemotherapy programs. We found no significant differences in the rates of complete response (CR), progression-free survival (PFS), or overall survival (OS) between these chemotherapy regimens. CR was attained by 69% of patients. PFS at 2 years was 55.2% and OS was 68.1%. In a multivariable model, the main prognostic factors for PFS and OS were poor performance status, lactate dehydrogenase &gt;3 × upper limit of normal, and a dual-expressor immunophenotype. Age &gt;60 years or presence of MYC rearrangement were not prognostic, but patients with TP53 alterations had a dismal PFS. Presence of MYC rearrangement was not predictive of better PFS in patients treated with DA-EPOCH-R vs R-CHOP. Improvements in the diagnostic criteria and therapeutic approaches beyond dose-intense chemotherapy are needed to overcome the unfavorable prognosis of patients with HGBL-NOS.

OBJECTIVES: To investigate whether a novel acute care multipatient viewer (AMP), created with an understanding of clinician information and process requirements, could reduce time to clinical decision-making among clinicians caring for populations of acutely ill patients compared with a widely used commercial electronic medical record (EMR). DESIGN: Single center randomized crossover study. SETTING: Quaternary care academic hospital. SUBJECTS: Attending and in-training critical care physicians, and advanced practice providers. INTERVENTIONS: AMP. MEASUREMENTS AND MAIN RESULTS: We compared ICU clinician performance in structured clinical task completion using two electronic environments—the standard commercial EMR (Epic) versus the novel AMP in addition to Epic. Twenty subjects (10 pairs of clinicians) participated in the study. During the study session, each participant completed the tasks on two ICUs (7–10 beds each) and eight individual patients. The adjusted time for assessment of the entire ICU and the adjusted total time to task completion were significantly lower using AMP versus standard commercial EMR (–6.11; 95% CI, –7.91 to –4.30 min and –5.38; 95% CI, –7.56 to –3.20 min, respectively; p < 0.001). The adjusted time for assessment of individual patients was similar using both the EMR and AMP (0.73; 95% CI, –0.09 to 1.54 min; p = 0.078). AMP was associated with a significantly lower adjusted task load (National Aeronautics and Space Administration-Task Load Index) among clinicians performing the task versus the standard EMR (22.6; 95% CI, –32.7 to –12.4 points; p < 0.001). There was no statistically significant difference in adjusted total errors when comparing the two environments (0.68; 95% CI, 0.36–1.30; p = 0.078). CONCLUSIONS: When compared with the standard EMR, AMP significantly reduced time to assessment of an entire ICU, total time to clinical task completion, and clinician task load. Additional research is needed to assess the clinicians’ performance while using AMP in the live ICU setting.