CNS Demyelinating Attacks Requiring Ventilatory Support With Myelin Oligodendrocyte Glycoprotein or Aquaporin-4 Antibodies.

BACKGROUND AND OBJECTIVE: Severe attacks of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorder (MOGAD) and aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) may require ventilatory support, but data on episodes are limited, particularly for MOGAD. We sought to compare the frequency, characteristics, and outcomes of MOGAD and AQP4-NMOSD attacks requiring ventilatory support. METHODS: This retrospective descriptive study identified Mayo Clinic patients (January 1, 1996-December 1, 2020) with MOGAD or AQP4-NMOSD and an attack requiring noninvasive or invasive ventilation at Mayo Clinic or an outside facility by searching for relevant terms in their electronic medical record. Inclusion criteria were (1) attack-related requirement for noninvasive (bilevel positive airway pressure or continuous positive airway pressure) or invasive respiratory support (mechanical ventilation); (2) MOG or AQP4 antibody positivity with fulfillment of MOGAD and AQP4-NMOSD clinical diagnostic criteria, respectively; and (3) sufficient clinical details. We collected data on demographics, comorbid conditions, indication for and duration of respiratory support, MRI findings, treatments, and outcomes. The races of those with attacks requiring respiratory support were compared to those without such attacks in MOGAD and AQP4-NMOSD. RESULTS: Attacks requiring ventilatory support were similarly rare in patients with MOGAD (8 of 279, 2.9%) and AQP4-NMOSD (11 of 503 [2.2%]) (p = 0.63). The age at attack (median years [range]) (MOGAD 31.5 [5-47] vs AQP4-NMOSD 43 [14-65]; p = 0.01) and percentage of female sex (MOGAD 3 of 8 [38%] vs AQP4-NMOSD 10 of 11 [91%]; p = 0.04) differed. The reasons for ventilation differed between MOGAD (inability to protect airway from seizure, encephalitis or encephalomyelitis with attacks of acute disseminated encephalomyelitis 5 [62.5%] or unilateral cortical encephalitis 3 [37.5%]) and AQP4-NMOSD (inability to protect airway from cervical myelitis 9 [82%], rhombencephalitis 1 [9%], or combinations of both 1 [9%]). Median ventilation duration for MOGAD was 2 days (range 1-7 days) vs 19 days (range 6-330 days) for AQP4-NMOSD (p = 0.01). All patients with MOGAD recovered, but 2 of 11 (18%) patients with AQP4-NMOSD died of the attack. For AQP4-NMOSD, Black race was overrepresented for attacks requiring ventilatory support vs those without these episodes (5 of 11 [45%] vs 88 of 457 [19%]; p = 0.045). DISCUSSION: Ventilatory support is rarely required for MOGAD and AQP4-NMOSD attacks, and the indications differ. Compared to MOGAD, these attacks in AQP4-NMOSD may have higher morbidity and mortality, and those of Black race were more predisposed, which we suspect may relate to socially mediated health inequality.

Promoting Well-being Among Neurology Residents: A Data-Driven Approach.

OBJECTIVE: To assess whether the creation of a formal structure to measure and promote wellness among neurology residents would facilitate the development of interventions associated with measurable improvements. METHODS: In 2018 we founded the Resident Wellness Committee for the Department of Neurology at our institution. The Resident Wellness Committee was led by resident and staff neurologist co-chairs and had as its vision to promote well-being through initiatives centered in work-life integration, emotional and physical well-being, and social engagement. Web-based surveys assessing various aspects of well-being were administered at baseline and 1 year after launch, comprising the period June 21, 2018, through June 30, 2019. RESULTS: Response rates were high at baseline (21 of 34; 62%) and follow-up (25 of 33; 76%). Interventions pursued in the interim included education on handling unexpected absences, adjustments to holiday schedule policies, infrastructure for nutrition and respite, and a team-based department fitness challenge, among others. Overall, at both timepoints more than 80% (18 of 21; 21 of 25) of respondents endorsed at least mild burnout symptoms, although clinical workload, independence, and education were overwhelmingly viewed positively throughout. Notable improvements at follow-up included greater comfort with adjusting schedules at times of need, increased camaraderie within the program, and a smaller proportion of respondents endorsing substantial burnout symptoms. CONCLUSION: Through deliberate and sustained efforts backed by data, our work demonstrates that concrete changes can be successfully pursued to promote well-being among neurology residents. Given that Neurology has one of the highest burnout rates among medical specialties, our approach may serve as a model for other programs to replicate.

Relevance of the C-5 position to schweinfurthin induced cytotoxicity.

The schweinfurthins are an intriguing group of anti-proliferative agents that display low nanomolar activities against several cell types, including the human-derived glioblastoma cell line SF-295, but have little impact on other cell lines even at micromolar concentrations. This activity has inspired the synthesis of seven of the natural schweinfurthins, all with the correct absolute stereochemistry, and a variety of analogues designed to probe different facets of the pharmacophore. Reported herein is the synthesis of several new schweinfurthin analogues varied at the C-5 position along with data on their biological activity in the NCI 60 cell-line assay.