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The Neurohospitalist Core Competencies comprise a set of competency-based learning objectives that encapsulate the knowledge, skills, and attitudes of neurohospitalitists who specialize in the care of hospitalized patients with neurologic conditions. These competencies serve to characterize the rapidly expanding field of neurohospitalist medicine. The 27 chapters are divided into 3 sections entitled: neurological conditions, clinical interventions and interpretation of ancillary studies, and neurohospitalist role in the healthcare system. Each individual learning objective in the chapters describes a specific concept with an action verb to illustrate the behavior that the neurohospitalist exhibits. The individual neurohospitalist may not exhibit mastery in each of the topics included as individual practices vary in scope and practice pattern. A few examples of how the complete set of competencies may be used include in the creation of curricula for neurohospitalist fellowships, to assist in defining the scope of practice of neurohospitalists for administrative leaders of hospitals and departments, and in influencing the direction of further research and quality improvement in the field.

Abstract Background Malignant peripheral nerve sheath tumors (MPNSTs) can arise from atypical neurofibromas (ANF). Loss of the polycomb repressor complex 2 (PRC2) is a common event. Previous studies on PRC2-regulated genes in MPNST used genetic add-back experiments in highly aneuploid MPNST cell lines which may miss PRC2-regulated genes in NF1-mutant ANF-like precursor cells. A set of PRC2-regulated genes in human Schwann cells (SCs) has not been defined. We hypothesized that PRC2 loss has direct and indirect effects on gene expression resulting in MPNST, so we sought to identify PRC2-regulated genes in immortalized human Schwann cells (iHSCs). Methods We engineered NF1-deficient iHSCs with loss of function SUZ12 or EED mutations. RNA sequencing revealed 1327 differentially expressed genes to define PRC2-regulated genes. To investigate MPNST pathogenesis, we compared genes in iHSCs to consistent gene expression differences between ANF and MPNSTs. Chromatin immunoprecipitation sequencing was used to further define targets. Methylome and proteomic analyses were performed to further identify enriched pathways. Results We identified potential PRC2-regulated drivers of MPNST progression. Pathway analysis indicates many upregulated cancer-related pathways. We found transcriptional evidence for activated Notch and Sonic Hedgehog (SHH) signaling in PRC2-deficient iHSCs. Functional studies confirm that Notch signaling is active in MPNST cell lines, patient-derived xenografts, and transient cell models of PRC2 deficiency. A combination of MEK and γ-secretase inhibition shows synergy in MPNST cell lines. Conclusions We identified PRC2-regulated genes and potential drivers of MPNSTs. Our findings support the Notch pathway as a druggable target in MPNSTs. Our identification of PRC2-regulated genes and pathways could result in more novel therapeutic approaches.

Background/Aims: The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE ® ) was developed to capture symptomatic adverse events from the patient perspective. We aim to describe statistical properties of PRO-CTCAE items and summary scores and to provide evidence for recommendations regarding PRO-CTCAE administration and reporting. Methods: Using data from the PRO-CTCAE validation study (NCT02158637), prevalence, means, and standard deviations of PRO-CTCAE items, composite scores, and mean and maximum scores across attributes (frequency, severity, and/or interference) of symptomatic adverse events were calculated. For each adverse event, correlations and agreement between attributes, correlations between attributes and composite scores, and correlations between composite, mean, and maximum scores were estimated. Results: PRO-CTCAE items were completed by 899 patients with various cancer types. Most patients reported experiencing one or more adverse events, with the most prevalent being fatigue (87.7%), sad/unhappy feelings (66.0%), anxiety (63.6%), pain (63.2%), insomnia (61.8%), and dry mouth (60.0%). Attributes were moderately to strongly correlated within an adverse event ( r = 0.53 to 0.77, all p < 0.001) but not fully concordant (κ weighted = 0.26 to 0.60, all p < 0.001), with interference demonstrating lowest mean scores and prevalence among attributes of the same adverse event. Attributes were moderately to strongly correlated with composite scores ( r = 0.67 to 0.97, all p < 0.001). Composite scores were moderately to strongly correlated with mean and maximum scores for the same adverse event ( r = 0.69 to 0.94, all p < 0.001). Correlations between composite scores of different adverse events varied widely ( r = 0.04 to 0.68) but were moderate to strong for conceptually related adverse events. Conclusions: Results provide evidence for PRO-CTCAE administration and reporting recommendations that the full complement of attributes be administered for each adverse event, and that attributes as well as summary scores be reported.

Abstract SRD5A3-CDG is a congenital disorder of glycosylation (CDG) resulting from pathogenic variants in SRD5A3 and follows an autosomal recessive inheritance pattern. The enzyme encoded by SRD5A3, polyprenal reductase, plays a crucial role in synthesizing lipid precursors essential for N-linked glycosylation. Despite insights from functional studies into its enzymatic function, there remains a gap in understanding global changes in patient cells. We sought to identify N-glycoproteomic and proteomic signatures specific to SRD5A3-CDG, potentially aiding in biomarker discovery and advancing our understanding of disease mechanisms. Using tandem mass tag (TMT)-based relative quantitation, we analyzed fibroblasts derived from five patients along with control fibroblasts. N-glycoproteomics analysis by liquid chromatography–tandem mass spectrometry (LC–MS/MS) identified 3,047 glycopeptides with 544 unique N-glycosylation sites from 276 glycoproteins. Of these, 418 glycopeptides showed statistically significant changes with 379 glycopeptides decreased (P &lt; 0.05) in SRD5A3-CDG patient-derived samples. These included high mannose, complex and hybrid glycan-bearing glycopeptides. High mannose glycopeptides from protocadherin Fat 4 and integrin alpha-11 and complex glycopeptides from CD55 were among the most significantly decreased glycopeptides. Proteomics analysis led to the identification of 5,933 proteins, of which 873 proteins showed statistically significant changes. Decreased proteins included cell surface glycoproteins, various mitochondrial protein populations and proteins involved in the N-glycosylation pathway. Lysosomal proteins such as N-acetylglucosamine-6-sulfatase and procathepsin-L also showed reduced levels of phosphorylated mannose-containing glycopeptides. Our findings point to disruptions in glycosylation pathways as well as energy metabolism and lysosomal functions in SRD5A3-CDG, providing clues to improved understanding and management of patients with this disorder.

ABSTRACTIntroductionLung transplantation has become increasingly utilized in patients with COVID‐19. While several single‐center and UNOS database studies have been published on lung transplants (LTs) for end‐stage lung disease (ESLD) from Coronavirus disease 2019 (COVID‐19), there is a lack of multi‐center and international data.MethodsThis is a multicenter analysis from 11 high‐volume lung transplant centers in the United States and Europe. Data were collected through the Multi‐Institutional ECLS Registry and stratified by ESLD due to COVID‐19 versus other etiologies. Demographics and clinical variables were compared using Chi‐square test and Fisher's exact test. Survival was assessed by Kaplan‐Meier curves and compared by log‐rank test with propensity score matching.ResultsOf 1606 lung transplant recipients, 46 (2.9%) were transplanted for ESLD from COVID‐19 compared to 1560 (97.1%) without a history of COVID‐19. Among COVID‐19 patients, 30 (65.2%) had COVID‐19‐associated ARDS and 16 (34.8%) had post‐COVID‐19 fibrosis. COVID‐19 patients had higher lung allocation scores (78.0 vs. 44.4, p < 0.0001), had severely limited functional status (37.0% vs. 2.9%, p < 0.0001), had higher preoperative ECMO usage (65.2% vs. 5.4%, p < 0.0001), and spent less time on the waitlist (32 vs. 137 days, p < 0.0001). A 30‐day survival was comparable between COVID‐19 and non‐COVID‐19 patients before (100% vs. 98.7%, p = 0.39) and after propensity matching (p = 0.15).ConclusionsPatients who received LTs due to COVID‐19 had short‐term survival comparable to that of patients without COVID‐19. Our findings support the idea that lung transplantation should be considered for select patients with ESLD due to COVID‐19.

Abstract: Extracorporeal membrane oxygenation (ECMO) is a mechanical support treatment modality used in patients with refractory cardiac and/or pulmonary failure. Bleeding and thrombotic complications associated with ECMO are inherent concerns that require careful management. Anticoagulation optimization may help mitigate these risks by providing more adequate therapeutic anticoagulation and lessen the bleed risk. Heparin, the most used anticoagulant, carries concerns for heparin-induced thrombocytopenia and possible resistance given its dependence on cofactors and circulating proteins to exert its pharmacologic effect. In contrast, bivalirudin, a direct thrombin inhibitor, exerts its effect independent of cofactors or plasma proteins, and possesses thrombin-binding and metabolism features that may confer advantages in ECMO management. This review of the evidence for bivalirudin utilization in ECMO suggests favorable outcomes in circuit-related thrombosis, bleeding, and dosing reliability. In addition, blood product utilization, circuit interventions, and success in ECMO decannulation and survival were positive findings associated with bivalirudin that merit consideration. Common questions and concerns relative to bivalirudin utilization, including laboratory monitoring, utilization in low-flow states, dosing considerations in renal replacement therapy, reversibility, and cost are also discussed in this review. Moreover, this review suggests that bivalirudin utilization presents the opportunity for ECMO management simplification.

ABSTRACT Some negative-sense RNA viruses, including measles virus (MeV), share the characteristic that during their infection cycle, cytoplasmic inclusion bodies (IBs) are formed where components of the viral replication machinery are concentrated. As a foci of viral replication, how IBs act to enhance the efficiency of infection by affecting virus-host interactions remains an important topic of investigation. We previously established that upon MeV infection, the epigenetic host protein, WD repeat-containing protein 5 (WDR5), translocates to cytoplasmic viral IBs and facilitates MeV replication. We now show that WDR5 is recruited to IBs by forming a complex with IB-associated MeV phosphoprotein via a conserved binding motif located on the surface of WDR5. Furthermore, we provide evidence that WDR5 promotes viral replication by suppressing a major innate immune response pathway, the double-stranded RNA-mediated activation of protein kinase R and integrated stress response. IMPORTANCE MeV is a pathogen that remains a global concern, with an estimated 9 million measles cases and 128,000 measles deaths in 2022 according to the World Health Organization. A large population of the world still has inadequate access to the effective vaccine against the exceptionally transmissible MeV. Measles disease is characterized by a high morbidity in children and in immunocompromised individuals. An important area of research for negative-sense RNA viruses, including MeV, is the characterization of the complex interactome between virus and host occurring at cytoplasmic IBs where viral replication occurs. Despite the progress made in understanding IB structures, little is known regarding the virus-host interactions within IBs and the role of these interactions in promoting viral replication and antagonizing host innate immunity. Herein we provide evidence suggesting a model by which MeV IBs utilize the host protein WDR5 to suppress the protein kinase R-integrated stress response pathway.

Abstract Introduction/ Background Holmium laser enucleation of the prostate (HoLEP) is an increasingly popular size-independent technique of treating male voiding dysfunction due to benign prostatic hypertrophy. Some patients after HoLEP may develop clinically significant prostate cancer and opt for definitive treatment with external beam radiation therapy (EBRT). Little is known about the safety of EBRT after HoLEP and how it may functionally impact voiding after HoLEP has altered the anatomy of the prostate. Our study aimed to assess patient-reported voiding outcomes following EBRT after HoLEP with a focus on incontinence related patient outcomes. Methods/ Materials This study was conducted with approval from our hospital’s institutional review board. Patients that underwent HoLEP followed by EBRT were identified and data was collected in a retrospective nature from a single surgeon HoLEP cohort over the past 4 years (2019–2023). Patient demographics, disease and radiation therapy characteristics, radiation therapy, and baseline voiding symptoms were recorded. Current functional voiding outcomes were also collected via phone-call or portal communication in a cross-sectional manner with questions pertaining to type of incontinence, IPSS quality of life score, and administration of the Michigan Incontinence Symptom Index (M-ISI). Adverse events encountered during follow-up were recorded. Results 24 patients were identified who received RT for prostate cancer after HoLEP with an average age of 73.6 (+/- 5.3). One third of patients reported no incontinence whatsoever after radiation and of those who experienced incontinence, the majority felt that it was not worsened after radiation. Median IPSS QoL score following radiation was 1 (range 0–6), median M-ISI Severity Score was 4 out of a maximum of 32, and median M-ISI Bother Score was 0 out of a maximum of 8. One patient developed a bladder neck contracture (BNC) approximately 1 year following his radiation therapy (approximately 18 months after HoLEP) causing bothersome incontinence and LUTS. Conclusions In our cohort most patients who received RT after HoLEP reported a high urinary-symptom related quality of life and a low rate of urinary incontinence. One patient who received SBRT suffered a BNC which is a known adverse event with RT but given our small sample size it remains unclear if the risk is higher in patients receiving RT after HoLEP. Larger studies should focus on examining the rate of bladder neck contracture in patients receiving RT after HoLEP, particularly focusing on whether the degree of dose fractionation may impact their development.

OBJECTIVE Determine if a longitudinal point-of-care ultrasonography (POCUS) elective for medical students is effective in improving POCUS knowledge. METHODS We share the format of our longitudinal POCUS elective for medical students. To evaluate the efficacy of our longitudinal elective, we compare the difference between pre-elective and post-elective scores on a POCUS test using a paired t-test with threshold of statistical significance of p ≤ .05. We also share the results of a post-elective survey evaluating the effectiveness and quality of the longitudinal POCUS elective. RESULTS Pretest mean score was 56.3% (σ = 13.6), while posttest mean score was 73.3% (σ = 9.4), with an average score improvement of 17.0% (95% CI 9.9-24.0%, p < .0001). All students strongly or moderately agreed that they would recommend the elective to future medical students, that they were more confident with their POCUS skills after completing the elective, that the time commitment of the elective was appropriate, and that they felt they had the time to fit the elective into their schedule as a medical school student. Most students (56.7%) strongly or moderately agreed that the knowledge gained from the POCUS elective had helped them in their clinical rotations. CONCLUSIONS Our longitudinal POCUS curriculum subjectively and objectively improves medical students’ POCUS knowledge while remaining accessible to students. We share our unique longitudinal POCUS elective curriculum, the format of which and its benefits are transferable to other medical schools. Through this, we hope to provide others with ideas on how they may implement a longitudinal POCUS elective.