Citations

Introduction Public reporting of outcomes drives healthcare improvement in many fields, including hematopoietic cell transplantation (HCT), although with possible unintended consequences. The Center for International Blood & Marrow Transplant Research (CIBMTR) publishes an annual Center-Specific Survival Analysis (CSA), which compares HCT centers' observed 1-year overall survival (OS) with their statistically modeled expected 1-year OS, with 95% confidence intervals (CI). Centers with OS within their 95% CI receive a 0 score, indicating as expected outcomes. Those with OS below / above their 95% CI receive a -1 / +1 score, indicating below / above expected OS, respectively. After a -1 report, centers may change their patient selection criteria, causing unintentional systematic exclusion of patient populations who could benefit from HCT. We analyzed how the CSA report influences patient selection practices among centers receiving a -1 score. Methods Centers receiving a -1 report between 2012 and 2016 that had ‘as expected’ survival in the preceding 2 years were classified as newly below expected OS centers (NBCs). The year of their -1 report was used as the index year. Centers with ‘as expected’ OS in the 3 years before and after each index year were identified as control centers, reflecting expected evolution of patient selection in the HCT field. The patient population variables analyzed are shown in Table 1. The difference in patient population characteristics in the 3 years before vs the 3 years after the index years defined the change in patient selection behavior at the NBCs and the controls. A multivariate model adjusting for baseline patient population characteristics and center size was used to compare the change in patient population from before and after the index year in the NBCs and that of the controls. The difference in differences (ΔinΔ) were calculated as ΔNBC - ΔControl. A significance threshold of p<0.01 was used to account for multiple testing. Results After adjusting for overall trends, center size, and baseline patient population characteristics, no differences in patient selection behavior meeting the pre-specified threshold for statistical significance were identified when comparing the NBCs (n=24 centers) with the controls (n=195 centers). In the 3 years following the index years, 4,150 and 25,013 patients were transplanted at NBCs and controls, respectively. The proportion of patients receiving reduced intensity or non-myeloablative conditioning regimens decreased 4.1% in NBCs and increased 5.0% in controls, for a net difference of -9.1% (95% CI: -16.7% to -1.6%, p=0.02). All other patient characteristic proportions changed in the same direction at NBCs and controls, albeit to varying degrees (Table 1). In some high-risk characteristics, (e.g. HCT-CI > 3), a greater increase was seen at NBCs vs controls (ΔinΔ 2.1% 95% CI: -2.8% to 6.9%, p=0.40). In others, (e.g. age 60+ years), a greater increase was seen at controls vs NBCs (ΔinΔ -2.6% 95% CI: -5.9% to 0.7%, p=0.12). To capture a holistic measure of centers' patient population risk, the predicted 1-year survival was compared in the NBCs vs controls using the logistic regression model generated for each year's CSA. The predicted OS increased by 3.08% and 3.30% in the NBCs and controls respectively, with no statistically significant difference (-0.23%, 95% CI: -1.4% to 0.9%, p=0.70, Figure 1). The observed overall survival (adjusted for predicted 1 year OS) also increased in both BECs and controls by 0.9% and 4.5% respectively, without statistically significant difference (-3.6%, 95% CI: -6.7% to -0.7%, p=0.02). Discussion For centers receiving a -1 report, no statistically significant changes were seen in patient population characteristics in the following 3 years when compared to centers with OS was as expected. There was variability in the changes in high-risk patient characteristics at the NBCs relative to the controls, and in some cases more patients with high-risk characteristics were selected at these centers compared to those at controls. The change in predicted overall survival at 1 year, a summary indicator of survival risk, was similar between BECs and control centers. Although the number of patients in centers with below expected OS was small, these findings suggest the public reporting of outcomes in HCT in the US does not unintentionally affect access to HCT for high-risk patients at NBCs.

Use of ultrasound as a diagnostic tool is fast becoming an expectation in clinical practice. With formal outcomes now being included as competencies in many residency programs, earlier exposure to use of ultrasound is being achieved through informal activities embedded within medical school curricula. Using ultrasound to learn anatomy is now standard practice for many courses in the United States. However, very few if any offer formal opportunities to assess student skill and anatomical knowledge at the same time. As part of the Mini Ultrasound Skills Institute (MUSI) in Anatomy, a component of the first year anatomy course, students were expected to complete a team‐based, hands‐on ultrasound skills assessment. Throughout the course, students received both didactic briefing sessions and hands‐on training on ultrasound basics, image interpretation, and scanning techniques. The ultrasound content was presented in parallel to anatomy and radiology curriculum. In the past, ultrasound knowledge was assessed via static images; however, due to the contextual nature of ultrasound interpretation, a live, hands‐on method was devised to assess student learning. At regular intervals during the course, students completed an ultrasound skills assessment. In their dissection teams of four, students completed four tasks: setup the machine, obtained, oriented, and labeled a desired image using a live model. Each student was given a unique role within this exercise. Students were graded on a rubric scale for each of the four components and given an overall team score. At the conclusion of the course, students completed a graded ultrasound objective structural practical examination (OSPE). Rotating through four stations, students completed the four tasks on four different structures. Students rotated through roles within their team as they moved between stations. OSPE grade was incorporated into their final laboratory practical grade. Preliminary data from formative OSPE assessments ‐‐‐‐showed an average score of 72% (±21%) with a minimum of 50%, maximum of 100%. Within the skill specific breakdown, students were very comfortable at labeling obtained images (100%) and had the most challenging time with either selecting the correct probe or setting up the scanner 40% (±51%). Overall, team‐based OSPE is an effective method to promote and evaluate ultrasound skills learned in an anatomy course.

Abstract Background Routine childhood immunization against varicella-zoster virus has led to a dramatic reduction in the incidence of primary varicella. However, there are rare, yet significant cases reported of reactivated Oka-strain varicella, primarily in immunocompromised hosts.Case Presentation A 16-year-old female with Hodgkin’s lymphoma developed a tender vesicular rash shortly after completing chemotherapy. Swabs obtained from the vesicles were positive for varicella-zoster virus. By the time of hospitalization, the patient developed a disseminated rash involving multiple dermatomes. Subsequent polymerase chain reaction confirmed Oka vaccine-strain varicella-zoster virus. The patient had previously received a primary series against varicella in 2008 and 2012, 11 years before her diagnosis of Hodgkin’s lymphoma. The patient was treated with parenteral acyclovir upon hospitalization and was monitored clinically for cutaneous disease progression as well as sequelae. After 8 days of inpatient treatment, her rash had stopped spreading with no new lesions. All earlier lesions had crusted over. No serious sequelae of disease such as pneumonitis, hepatitis, encephalitis, or meningitis occurred, and she made a complete recovery.Conclusions There are individual and community-wide benefits to childhood immunization against varicella. This case highlights an unusual presentation of disseminated vaccine-strain varicella-zoster virus in an adolescent with secondary immunodeficiency 11 years after completing primary immunization. In addition, this case informs pediatricians of complications that can arise in immunized subjects if they become immunosuppressed years later. Providers should be cognizant of potential vaccine virus reactivation in their differential. Considerations for work-up and management should include infection control and viral resistance in refractory cases.

Introduction: Genome-wide association studies (GWAS) have discovered >300 associations for CAD. Few loci are functionally characterized and may represent new mechanisms of disease. Hypothesis: Can an unbiased transcriptional screen for the >2000 candidate GWAS genes in endothelial cells (ECs) identify causal genes and disease-relevant pathways at CAD GWAS loci. Methods: We applied CRISPRi-Perturb-seq to knock down expression of genes within 500 Kb of coronary artery disease GWAS loci (2,300 genes in total) and measure their transcriptomic effects using single-cell RNA-seq. Validation of candidate causal genes was conducted in primary human ECs and zebrafish. Results: We identified 50 programs of co-expressed genes, which represent core cellular pathways (i.e. ribosome biogenesis) and 13 EC-specific pathways such as flow response and angiogenesis. The EC-specific programs show the greatest contribution to CAD heritability. 5 EC-specific programs have the greatest number of GWAS candidate genes. We find that 43 of 306 CAD GWAS signals converge onto these 5 gene programs, and all are regulated by genes in the cerebral cavernous malformations (CCM) pathway—which coordinates KLF2/4 transcriptional responses in endothelial cells, but has not been linked to CAD risk. The strongest regulator of these programs is TLNRD1 , which we show is a new CAD gene and novel regulator of the CCM pathway. TLNRD1 loss-of-function alters actin organization and barrier function in endothelial cells in vitro , and heart development in zebrafish in vivo . Conclusions: High-throughput functional analysis of 2,300 genes proximal to CAD GWAS loci prioritized pathways—such as angiogenesis and EC migration—that are regulated by multiple risk SNPs. Our study identifies new genes that likely influence risk for CAD, identifies convergence of CAD genes into certain pathways in endothelial cells, and prioritizes study of genes in the CCM-signaling pathway for contribution to CAD risk.

Background and Aims: Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (×ULN) after 12-month UDCA. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains. Approach and Results: We performed a retrospective cohort study of 1047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation, or death was assessed using adjusted restricted mean survival time (RMST) analysis. The overall incidence rate of events was 17.0 (95% CI: 13.7–21.1) per 1000 out of 4763.2 patient-years. On the whole population, normal serum ALP values (but not normal gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST); or total bilirubin < 0.6 ×ULN) were associated with a significant absolute complication-free survival gain at 10 years (mean 7.6 months, 95% CI: 2.7 - 12.6 mo.; p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10 kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95% CI: 45.7–59.9, p < 0.001) when these 2 conditions were met. Conclusions: PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 ×ULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients.

Background: Electronic massagers have gained popularity for their non-invasive and cost-effective approach to healthcare. However, existing electronic massagers require manual manipulation, leading to inconsistency. Objective: To investigate the feasibility and acceptability of the Electronic Massager—Expert Manipulative Massage Automation (EMMA) among the American population. Methods: A single-arm pilot study was conducted at Mayo Clinic Rochester campus. Participants received massage therapy with the EMMA treatment model and completed a demographics and Satisfaction Survey Questionnaire. Data were collected using REDCap, and statistical analysis was performed. Results: Twenty healthy volunteers (13 women, 7 men; median age, 47 years) participated and completed the intervention within 2 weeks. No adverse events were reported. Overall, the acceptability and satisfaction of massage utilizing EMMA were high, with all participants finding the study worthwhile, willing to participate again, and willing to recommend the study to others. Regarding the overall experience, 65.0% reported a better-than-expected experience. Responses to open-ended post-treatment questions showed that most participants enjoyed the warmth (35%), pressure (25%), and relaxation (20%) provided by EMMA, with the majority suggesting no changes or improvements were needed. However, some participants expressed a desire for an expanded massage area (20%). Conclusions: This study suggests that the EMMA massager has high acceptability and satisfaction among healthy volunteers, thus demonstrating its feasibility. However, further research is needed to optimize EMMA and assess its clinical effectiveness.