Faculty Bibliography

Neurological complications of COVID-19 are not well described. We report two patients who were diagnosed with COVID-19 after presenting with diplopia and ophthalmoparesis.

Background/UNASSIGNED:The coronavirus disease 2019 pandemic has or threatens to overwhelm health care systems. Many institutions are developing ventilator triage policies. Objective/UNASSIGNED:To characterize the development of ventilator triage policies and compare policy content. Design/UNASSIGNED:Survey and mixed-methods content analysis. Setting/UNASSIGNED:North American hospitals associated with members of the Association of Bioethics Program Directors. Participants/UNASSIGNED:Program directors. Measurements/UNASSIGNED:Characteristics of institutions and policies, including triage criteria and triage committee membership. Results/UNASSIGNED:Sixty-seven program directors responded (response rate, 91.8%); 36 (53.7%) hospitals did not yet have a policy, and 7 (10.4%) hospitals' policies could not be shared. The 29 institutions providing policies were relatively evenly distributed among the 4 U.S. geographic regions (range, 5 to 9 policies per region). Among the 26 unique policies analyzed, 3 (11.3%) were produced by state health departments. The most frequently cited triage criteria were benefit (25 policies [96.2%]), need (14 [53.8%]), age (13 [50.0%]), conservation of resources (10 [38.5%]), and lottery (9 [34.6%]). Twenty-one (80.8%) policies use scoring systems, and 20 of these (95.2%) use a version of the Sequential Organ Failure Assessment score. Among the policies that specify the triage team's composition (23 [88.5%]), all require or recommend a physician member, 20 (87.0%) a nurse, 16 (69.6%) an ethicist, 8 (34.8%) a chaplain, and 8 (34.8%) a respiratory therapist. Thirteen (50.0% of all policies) require or recommend those making triage decisions not be involved in direct patient care, but only 2 (7.7%) require that their decisions be blinded to ethically irrelevant considerations. Limitation/UNASSIGNED:The results may not be generalizable to institutions without academic bioethics programs. Conclusion/UNASSIGNED:Over one half of respondents did not have ventilator triage policies. Policies have substantial heterogeneity, and many omit guidance on fair implementation.

OBJECTIVE:We postulated that cerebral amyloid angiopathy (CAA) is associated with white matter atrophy (WMA) and that WMA can be related to cognitive changes in CAA. METHODS:White matter volume expressed as percent of intracranial volume (pWMV) of prospectively enrolled patients without dementia diagnosed with probable CAA was compared to age-matched healthy controls (HC) and patients with Alzheimer disease (AD). Cognitive scores were also sought to understand the potential effects of WMA on cognitive function. RESULTS:= 0.003, respectively). All associations remained independent in multivariable analyses. Within the CAA cohort, higher pWMV independently correlated with better scores of executive function. CONCLUSIONS:Patients with CAA show WMA when compared to age-matched HC and patients with AD. WMA independently correlates with the number of lobar microbleeds, a marker of CAA severity. Consistent spatial patterns of WMA especially in posterior regions might be related to CAA. The association between WMA and measures of executive function suggests that WMA might represent an important mediator of CAA-related neurologic dysfunction.

Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with relatively low incidence of GVHD. Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haploHCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with AML, ALL, MDS, or CML who underwent PTCy-based haploHCT (2013-2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced intensity (RIC) conditioning and bone marrow (BM) or peripheral blood (PB) graft source. 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2-4 aGVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (p=0.002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (p<0.001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2-4 acute GVHD; however, older donor age (30-49 versus <29 years) was significantly associated with higher rates of grade 2-4 acute GVHD (HR 1.53, 95% CI 1.11-2.12, p=0.01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR 1.70, 95% CI 1.11-2.62, p=0.01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haploHCT.  Our results indicate that in RIC haploHCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.

Pediatric practice increasingly involves providing care for children with medical complexity. Telehealth offers a strategy for providers and health care systems to improve care for these patients and their families. However, lack of awareness related to the unintended negative consequences of telehealth on vulnerable populations--coupled with failure to intentional design best practices for telehealth initiatives--implies that these novel technologies may worsen health disparities in the long run. This article reviews the positive and negative implications of telehealth. In addition, to achieve optimal implementation of telehealth, it discusses 10 considerations to promote optimal care of children using these technologies.

Medical knowledge examinations employing open-ended (constructed response) items can be useful to assess medical students' factual and conceptual understanding. Modern day curricula that emphasize active learning in small groups and other interactive formats lend themselves to an assessment format that prompts students to share conceptual understanding, explain, and elaborate. The open-ended question examination format can provide faculty with insights into learners' abilities to apply information to clinical or scientific problems, and reveal learners' misunderstandings about essential content. To implement formative or summative assessments with open-ended questions in a rigorous manner, educators must design systems for exam creation and scoring. This includes systems for constructing exam blueprints, items and scoring rubrics, and procedures for scoring and standard setting. Information gained through review of students' responses can guide future educational sessions and curricular changes in a cycle of continuous improvement.

Autologous stem cell transplantation (ASCT) remains the standard-of-care for transplant-eligible multiple myeloma (MM) patients. Bortezomib with lenalidomide and dexamethasone (VRD) is the most common triplet regimen for newly diagnosed MM in the US. Carfilzomib with lenalidomide and dexamethasone (KRD) has promising efficacy and may supplant VRD. We compared stem cell yields and autograft minimal residual disease (MRD)-negativity after VRD and KRD induction. Deeper responses (very good partial response or better) were more common with KRD. Pre-collection bone marrow cellularity, interval from the end of induction therapy to start of stem cell collection, and method of stem cell obilization were similar for the two cohorts. Days to complete collection was greater with KRD (VRD 1.81 vs. KRD 2.2 days), which more often required ≥3 days of apheresis. Pre-collection viable CD34+ cell content was greater with VRD, as was collection yield (VRD 11.11 × 106 vs. KRD 9.19 × 106). Collection failure (<2 × 106 CD34+ cells/kg) was more frequent with KRD (5.4%) than VRD (0.7%). The differences in stem cell yields between VRD and KRD associate with degree of lenalidomide exposure. Age ≥70 predicted poorer collection for both cohorts. Stem cell autograft purity/MRD-negativity was higher with KRD (81.4%) than VRD (57.1%). For both cohorts, MRD-negativity was attained in a larger fraction of autografts than pre-collection bone marrows. For patients proceeding to ASCT, time to neutrophil/platelet engraftment was comparable. In summary, KRD induces deeper clinical responses and greater autograft purity than VRD without compromising stem cell yield or post-transplant engraftment kinetics.

BACKGROUND AND PURPOSE/OBJECTIVE:Patients with the Coronavirus Disease of 2019 (COVID-19) are at increased risk for thrombotic events and mortality. Various anticoagulation regimens are now being considered for these patients. Anticoagulation is known to increase the risk for adverse bleeding events, of which intracranial hemorrhage (ICH) is one of the most feared. We present a retrospective study of 33 patients positive for COVID-19 with neuroimaging-documented ICH and examine anticoagulation use in this population. METHODS:Patients over the age of 18 with confirmed COVID-19 and radiographic evidence of ICH were included in this study. Evidence of hemorrhage was confirmed and categorized by a fellowship trained neuroradiologist. Electronic health records were analyzed for patient information including demographic data, medical history, hospital course, laboratory values, and medications. RESULTS:We identified 33 COVID-19 positive patients with ICH, mean age 61.6 years (range 37-83 years), 21.2% of whom were female. Parenchymal hemorrhages with mass effect and herniation occurred in 5 (15.2%) patients, with a 100% mortality rate. Of the remaining 28 patients with ICH, 7 (25%) had punctate hemorrhages, 17 (60.7%) had small- moderate size hemorrhages, and 4 (14.3%) had a large single site of hemorrhage without evidence of herniation. Almost all patients received either therapeutic dose anticoagulation (in 22 [66.7%] patients) or prophylactic dose (in 3 [9.1] patients) prior to ICH discovery. CONCLUSIONS:Anticoagulation therapy may be considered in patients with COVID-19 though the risk of ICH should be taken into account when developing a treatment regimen.

Cholangiocarcinoma is a highly lethal biliary epithelial tumor that is rare in the general population but has increased rates in patients with primary sclerosing cholangitis (PSC). It is heterogenous, and management varies by location. No effective prevention exists, and screening is likely only feasible in PSC. Patients often present in an advanced state with jaundice, weight loss, and cholestatic liver enzymes. Diagnosis requires imaging with magnetic resonance cholangiopancreatography, laboratory testing, and endoscopic retrograde cholangiopancreatography. Potentially curative options include resection and liver transplant with neoadjuvant or adjuvant chemoradiation. Chemotherapy, radiation, and locoregional therapy provide some survival benefit in unresectable disease.

Although high-protein diets continue to be popular for weight loss and type 2 diabetes, evidence suggests that worsening renal function may occur in individuals with-and perhaps without-impaired kidney function. High dietary protein intake can cause intraglomerular hypertension, which may result in kidney hyperfiltration, glomerular injury, and proteinuria. It is possible that long-term high protein intake may lead to de novo CKD. The quality of dietary protein may also play a role in kidney health. Compared with protein from plant sources, animal protein has been associated with an increased risk of ESKD in several observational studies, including the Singapore Chinese Health Study. Potential mediators of kidney damage from animal protein include dietary acid load, phosphate content, gut microbiome dysbiosis, and resultant inflammation. In light of such findings, adopting current dietary approaches that include a high proportion of protein for weight reduction or glycemic control should be considered with care in those at high risk for kidney disease. Given the possibility of residual confounding within some observational studies and the conflicting evidence from previous trials, long-term studies including those with large sample sizes are warranted to better ascertain the effects of high protein intake on kidney health.