Citations

Abstract Purpose While COVID-19 vaccine emergency use authorization (EUA) deemed the vaccines to be effective and safe for public use, the phase 3 trials leading to EUA predominantly excluded patients with immunocompromising conditions. Immunocompromised patients make up a significant proportion of the population, and in light of recent mass vaccination efforts, we aim to review current evidence and recommendations of COVID-19 vaccines in 4 patient populations with immunocompromising disorders or conditions: human immunodeficiency virus (HIV) infection, solid organ transplantation, rheumatoid arthritis, and inflammatory bowel disease. Summary Given the evolving data on the safety and efficacy of the approved COVID-19 vaccines in the immunocompromised population, it is vital that pharmacists and other immunizing providers understand the current data and recommendations and provide the public with accurate information. To date, the only immunocompromised subgroup included in phase 3 COVID-19 vaccine trials have been those with HIV infection. However, recent retrospective trials have provided reassuring data on the safety of the COVID-19 vaccine in immunocompromised patients, and the interim analysis of the Moderna phase 3 trial produced promising data on efficacy in HIV-infected patients. Presently, the US Centers for Disease Control and Prevention, British Society for Immunology, and various other governmental and professional societies and organizations endorse COVID-19 vaccination in the immunocompromised population. Conclusion While additional data is needed to determine the effects of immunocompromising medical conditions and immunosuppressing medications on the efficacy of the vaccine, the benefits of vaccination is anticipated to outweigh theoretical risks. Thus, COVID-19 vaccination is recommended for immunocompromised patients at this time, and providers should make efforts to decrease vaccine hesitancy in this population through education and reassurance.

The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer or uterine sarcoma. These NCCN Guidelines Insights focus on the recent addition of molecular profiling information to aid in accurate diagnosis, classification, and treatment of uterine sarcomas.

Abstract Lineage-ambiguous leukemias are high-risk malignancies of poorly understood genetic basis. Here, we describe a distinct subgroup of acute leukemia with expression of myeloid, T lymphoid, and stem cell markers driven by aberrant allele-specific deregulation of BCL11B, a master transcription factor responsible for thymic T-lineage commitment and specification. Mechanistically, this deregulation was driven by chromosomal rearrangements that juxtapose BCL11B to superenhancers active in hematopoietic progenitors, or focal amplifications that generate a superenhancer from a noncoding element distal to BCL11B. Chromatin conformation analyses demonstrated long-range interactions of rearranged enhancers with the expressed BCL11B allele and association of BCL11B with activated hematopoietic progenitor cell cis-regulatory elements, suggesting BCL11B is aberrantly co-opted into a gene regulatory network that drives transformation by maintaining a progenitor state. These data support a role for ectopic BCL11B expression in primitive hematopoietic cells mediated by enhancer hijacking as an oncogenic driver of human lineage-ambiguous leukemia. Significance: Lineage-ambiguous leukemias pose significant diagnostic and therapeutic challenges due to a poorly understood molecular and cellular basis. We identify oncogenic deregulation of BCL11B driven by diverse structural alterations, including de novo superenhancer generation, as the driving feature of a subset of lineage-ambiguous leukemias that transcend current diagnostic boundaries. This article is highlighted in the In This Issue feature, p. 2659

AbstractIntroductionRepresentation of Mexican Americans in Alzheimer's disease (AD) clinical research has been extremely poor.MethodsData were examined from the ongoing community‐based, multi‐ethnic Health & Aging Brain among Latino Elders (HABLE) study. Participants underwent functional exams, clinical labs, neuropsychological testing, and 3T magnetic resonance imaging of the brain. Fasting proteomic markers were examined for predicting mild cognitive impairment (MCI) and AD using support vector machine models.ResultsData were examined from n = 1649 participants (Mexican American n = 866; non‐Hispanic White n = 783). Proteomic profiles were highly accurate in detecting MCI (area under the curve [AUC] = 0.91) and dementia (AUC = 0.95). The proteomic profiles varied significantly between ethnic groups and disease state. Negative predictive value was excellent for ruling out MCI and dementia across ethnic groups.DiscussionA blood‐based screening tool can serve as a method for increasing access to state‐of‐the‐art AD clinical research by bridging between community‐based and clinic‐based settings.

AbstractCSNK2B has recently been implicated as a disease gene for neurodevelopmental disability (NDD) and epilepsy. Information about developmental outcomes has been limited by the young age and short follow‐up for many of the previously reported cases, and further delineation of the spectrum of associated phenotypes is needed. We present 25 new patients with variants in CSNK2B and refine the associated NDD and epilepsy phenotypes. CSNK2B variants were identified by research or clinical exome sequencing, and investigators from different centers were connected via GeneMatcher. Most individuals had developmental delay and generalized epilepsy with onset in the first 2 years. However, we found a broad spectrum of phenotypic severity, ranging from early normal development with pharmacoresponsive seizures to profound intellectual disability with intractable epilepsy and recurrent refractory status epilepticus. These findings suggest that CSNK2B should be considered in the diagnostic evaluation of patients with a broad range of NDD with treatable or intractable seizures.

ABSTRACT The extracellular matrix glycoprotein, fibronectin, is a potent promoter of peripheral neurite outgrowth. Interactions of peripheral neurons with fibronectin have been shown to be primarily mediated by the β1 class of integrin heterodimers. In the present study, we have examined the expression and regulation of fibronectin and its integrin receptor, α5 β1, in developing and regenerating chick peripheral nerve. We show that fibronectin and α5β1 α5β1 are expressed at comparatively high levels in developing nerve with α5β1 expression on axons and non-neuronal cells. With nerve maturation, both proteins are less prominently expressed and the cellular pattern of α5β1,expression becomes more restricted. Following lesion of mature nerve, both fibronectin and α5β1, are strongly induced with prominent expression of α5β1, on regenerating neurites and Schwann cells. The elevation in fibronectin levels in the regenerating nerve is highest in the vicinity of the lesion, an area undergoing extensive cellular remodeling including Schwann cell migration and growth cone extension. Our results suggest that fibronectin and its receptor, α5β1, may mediate functionally important interactions in the development and regeneration of peripheral nerve.

This Practice Advisory presents a comprehensive and evidence-based set of position statements and recommendations for the use of contrast media in interventional pain procedures. The advisory was established by an international panel of experts under the auspices of 11 multinational and multispecialty organizations based on a comprehensive review of the literature up to December 31, 2019. The advisory discusses the risks of using gadolinium-based contrast agents. These include nephrogenic systemic fibrosis, gadolinium brain deposition/retention, and encephalopathy and death after an unintentional intrathecal gadolinium injection. The advisory provides recommendations on the selection of a specific gadolinium-based contrast agent in patients with renal insufficiency, those who had multiple gadolinium-enhanced magnetic resonance imaging examinations, and in cases of paraspinal injections. Additionally, recommendations are made for patients who have a history of mild, moderate, or severe hypersensitivity reactions to contrast medium.

AbstractBackgroundObservational analyses comparing coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI) among elderly or frail patients are likely biased by treatment selection. PCI is typically chosen for frail patients, while CABG is more common for patients with good recovery potential.HypothesisWe hypothesized that skilled nursing facility (SNF) use after revascularization is a measure of relative frailty associated with outcomes following coronary revascularization.MethodsWe used a 20 percent sample of Medicare beneficiaries aged 65 years or older who received inpatient PCI or CABG between 2007–2014. Key explanatory variables were the revascularization strategy and SNF use after revascularization. We used Cox regression to evaluate death and repeat revascularization within one year and logistic regression to evaluate SNF use and 30‐day readmissions/death.ResultsCABG patients were 25.1 percentage points [95% confidence interval: 24.7, 25.5] more likely to use SNF following revascularization than inpatient PCI patients. SNF use was associated with a higher death rate (hazard ratio (HR): 3.19 [3.02, 3.37]) and a 16.2 percentage point (15.5, 16.9) increase in 30‐day readmissions/death. Among patients with SNF use, CABG was associated with a decrease in 30‐day readmissions/death compared to PCI.ConclusionsWhile CABG was associated with higher rates of SNF use and 30‐day readmission/death overall, CABG was associated with significantly lower rates of 30‐day readmissions/death among patients with SNF use. The findings suggest that caution is needed in treatment selection for patients at high‐risk for SNF use and that selection of inpatient PCI over CABG may be associated with frailty and worse outcomes for some patients.

Introduction Acute sore throat is a common complaint traditionally completed with an in-person visit. However, non-face-to-face telemedicine visits offer greater access at reduced cost. We evaluated patient/caregiver asynchronous text-based electronic visits (eVisits) for acute sore throat and whether there was concordance for individual components and total McIsaac score compared to a clinician’s assessment. eVisits were completed by patients and/or their caregivers via a secure patient portal. Methods In this retrospective study, we manually reviewed charts between February 2017 and July 2019 of patients who had an eVisit, in-person visit and group A streptococcal (GAS) test performed on the same day for an acute sore throat. We calculated a McIsaac score for eVisits and in-person visits, and compared each component and total score using Cohen’s kappa agreement statistic. Results There were 320 instances of patients who had an eVisit, in-person visit and GAS testing done on the same day. Approximately a third of eVisits were missing at least one McIsaac component, with the physical examination elements missing most commonly. Individual score congruence was moderate for cough (0.41), fair for fever (0.34) and slight for tonsillar swelling/exudate and lymphadenopathy (0.17 and 0.08, respectively), with total congruence being slight to fair (0.09–0.37). A McIsaac score of ≤1 showed moderate agreement (0.44). Visits with complete individual score components demonstrated improved congruence: substantial for cough (0.64), moderate for fever (0.57), fair for tonsillar swelling (0.3) and slight for lymphadenopathy (0.13). Discussion Overall agreement for individual score components was better for symptoms than it was for examination components, and was improved when data were complete. A McIsaac score of 1 or 0 had moderate agreement and thus could reasonably be safely used to exclude patients from GAS testing.

Variables in cardiology fellowship applications have not been objectively analyzed against applicants' subsequent clinical performance. We investigated possible correlations in a retrospective cohort study of 65 cardiology fellows at the Mayo Clinic (Rochester, Minn) who began 2 years of clinical training from July 2007 through July 2013. Application variables included the strength of comparative statements in recommendation letters and the authors' academic ranks, membership status in the Alpha Omega Alpha Honor Medical Society, awards earned, volunteer activities, United States Medical Licensing Examination (USMLE) scores, advanced degrees, publications, and completion of a residency program ranked in the top 6 in the United States. The outcome was clinical performance as measured by a mean of faculty evaluation scores during clinical training. The overall mean evaluation score was 4.07 ± 0.18 (scale, 1–5). After multivariable analysis, evaluation scores were associated with Alpha Omega Alpha designation (β=0.13; 95% CI, 0.01–0.25; P=0.03), residency program reputation (β=0.13; 95% CI, 0.05–0.21; P=0.004), and strength of comparative statements in recommendation letters (β=0.08; 95% CI, 0.01–0.15; P=0.02), particularly in letters from residency program directors (β=0.05; 95% CI, 0.01–0.08; P=0.009). Objective factors to consider in the cardiology fellowship application include Alpha Omega Alpha membership, residency program reputation, and comparative statements from residency program directors.