Metastatic melanoma of the heart: Retrospective cohort study and systematic review of prevalence, clinical characteristics, and outcomes.

BACKGROUND: Cardiac metastasis of melanoma is rare and typically diagnosed post-mortem. Here we perform a retrospective cohort study and systematic review of patients with metastatic melanoma to characterize prevalence, clinical characteristics, and outcomes of cardiac metastasis. METHODS: We reviewed the electronic medical records of all outpatients with metastatic melanoma who underwent evaluation at the University of Michigan in Ann Arbor from January 2009 to January 2022, identifying patients with a clinical or histopathologic diagnosis of cardiac metastasis. We performed a systematic review of the literature to summarize the clinical characteristics and outcomes of patients with melanoma and cardiac metastasis. RESULTS: Overall, 23 of 1254 (1.8%) patients with metastatic melanoma were diagnosed with cardiac metastasis. Cardiac metastasis was reported in the right ventricle (65%), left ventricle (35%), and right atrium (35%). A total of 11 (48%) patients experienced at least one cardiovascular complication after the diagnosis of cardiac metastasis, the most common being arrhythmia (30%), heart failure (22%), and pericardial effusion (17%). Immunotherapy was more commonly used in patients with cardiac metastasis (80% vs 65%; p = 0.005). Mortality at 2-years post-diagnosis was higher for patients with cardiac metastasis compared to those without (59% vs 37%; p = 0.034). Progression of malignancy was the underlying cause of death of all patients. CONCLUSIONS: Cardiac metastasis occurs in <2% of patients with metastatic melanoma, can affect all cardiac structures, and is associated with various cardiovascular complications and high mortality.

Racial and ethnic variation in COVID-19 care, treatment, and outcomes: A retrospective cohort study from the MiCOVID-19 registry.

BACKGROUND: Racial and ethnic disparities in COVID-19 outcomes exist, but whether in-hospital care explains this difference is not known. We sought to determine racial and ethnic differences in demographics, comorbidities, in-hospital treatments, and in-hospital outcomes of patients hospitalized with COVID-19. METHODS AND FINDINGS: This was a cohort study using MiCOVID-19, a multi-center, retrospective, collaborative quality improvement registry, which included data on patients hospitalized with COVID-19 across 38 hospitals in the State of Michigan. 2,639 adult patients with COVID-19 hospitalized at a site participating in the MiCOVID-19 Registry were randomly selected. Outcomes included in-hospital mortality, age at death, intensive care unit admission, and need for invasive mechanical ventilation by race and ethnicity. Baseline comorbidities differed by race and ethnicity. In addition, Black patients had higher lactate dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, creatine phosphokinase, and ferritin levels. Black patients were less likely to receive dexamethasone and remdesivir compared with White patients (4.2% vs 14.3% and 2.2% vs. 11.8%, p < 0.001 for each). Black (18.7%) and White (19.6%) patients experienced greater mortality compared with Asian (13.0%) and Latino (5.9%) patients (p < 0.01). The mean age at death was significantly lower by 8 years for Black patients (69.4 ± 13.3 years) compared with White (77.9 ± 12.6), Asian (77.6 ± 6.6), and Latino patients (77.4 ± 15.5) (p < 0.001). CONCLUSIONS: COVID-19 mortality appears to be driven by both pre-hospitalization clinical and social factors and potentially in-hospital care. Policies aimed at population health and equitable application of evidence-based medical therapy are needed to alleviate the burden of COVID-19.

Race, Ethnicity, and 60-Day Outcomes After Hospitalization With COVID-19.

OBJECTIVE: To examine racial and ethnic disparities in clinical, financial, and mental health outcomes within a diverse sample of hospitalized COVID-19-positive patients in the 60 days postdischarge. DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: A total of 2217 adult patients who were hospitalized with a COVID-19-positive diagnosis as evidenced by test (reverse-transcriptase polymerase chain reaction), a discharge diagnosis of COVID-19 (ICD-10 code U07.1), or strong documented clinical suspicion of COVID-19 but no testing completed or recorded owing to logistical constraints (n=24). METHODS: Patient records were abstracted for the Mi-COVID19 data registry, including the hospital and insurer data of patients discharged from one of 38 participating hospitals in Michigan between March 16, 2020, and July 1, 2020. Registry data also included patient responses to a brief telephone survey on postdischarge employment, mental and emotional health, persistence of COVID-19-related symptoms, and medical follow-up. Descriptive statistics were used to summarize data; analysis of variance and Pearson chi-squared test were used to evaluate racial and ethnic variances among patient outcomes and survey responses. RESULTS: Black patients experienced the lowest physician follow-up postdischarge (n = 65, 60.2%) and the longest delays in returning to work (average 35.5 days). More than half of hospital readmissions within the 60 days following discharge were among nonwhite patients (n = 144, 55%). The majority of postdischarge deaths were among white patients (n = 153, 21.5%), most of whom were discharged on palliative care (n = 103). Less than a quarter of patients discharged back to assisted living, skilled nursing facilities, or subacute rehabilitation facilities remained at those locations in the 60 days following discharge (n = 48). CONCLUSIONS AND IMPLICATIONS: Increased attention to postdischarge care coordination is critical to reducing negative health outcomes following a COVID-19-related hospitalization.

Diagnostic patterns and stress testing trends after implementing high-sensitivity troponin assay.

OBJECTIVES: High-sensitivity troponin T (hsTnT) testing was approved in the United States to better facilitate diagnosis of acute coronary syndrome (ACS). Although hsTnT has been widely studied internationally, the impact of hsTnT on discharge diagnoses and health care utilization within the United States is less known. We sought to evaluate the effects of implementing hsTnT on diagnosis patterns and stress testing utilization. STUDY DESIGN: We performed a retrospective cohort analysis consisting of patients with suspected ACS undergoing either conventional troponin I (n = 14,631) or hsTnT (n = 7237) testing between January 2016 and February 2019. METHODS: Log-binomial regression with interrupted time series modeled diagnosis patterns, and logistic regression with segmented time trends modeled stress testing rates. Observed trends were compared with expected trends using average marginal effect (AME). RESULTS: Rates of acute myocardial infarction-related diagnoses were similar in the post-hsTnT period (AME, -0.6%; P = .065). Post hsTnT introduction, patients were more likely to receive a diagnosis of heart failure (2.1%; P < .001) or atrial fibrillation/flutter (0.9%; P < .001) and less likely to receive a diagnosis of hypertensive heart disease (-10.2%; P < .01) or hypertensive heart disease with chronic kidney disease (-3.7%; P < .001). Likelihood of receiving stress testing increased after hsTnT implementation (2.3%; P < .001). CONCLUSIONS: Variations in discharge diagnosis patterns and increases in stress test utilization were observed following hsTnT implementation. Hospitals can expect similar changes, which may have long-term implications on health care utilization, cost, and hospital reimbursement.

Eliminating Inappropriate Telemetry Monitoring: An Evidence-Based Implementation Guide.

In-hospital continuous electrocardiographic monitoring, commonly referred to as telemetry, has allowed for rapid recognition of life-threatening conditions, including complex arrhythmias and myocardial ischemia. However, inappropriate use can lead to unnecessary downstream testing from "false alarms," which in turn affects clinician efficiency and increases health care costs without benefiting patients. For these reasons, the Society of Hospital Medicine's Choosing Wisely campaign recommended use of a protocol-driven discontinuation of telemetry. The American Heart Association (AHA) developed a set of Practice Standards for the appropriate use of telemetry monitoring in 2004, which they updated in 2017. Unfortunately, the AHA Practice Standards have not been widely adopted-with as many as 43% of monitored patients lacking a recommended indication for monitoring. Thus, we created an overview discussing the safety and efficacy of incorporating the AHA Practice Standards and a review of studies highlighting their successful incorporation within patient care workflow. We conclude by outlining an "implementation blueprint" for health system professionals and administrators seeking to change their institution's culture of telemetry use. As the health care landscape continues to shift, enacting high-value initiatives that improve patient safety and efficiency of care will be critical.

Current Trends in Anticoagulation Bridging for Patients With Chronic Atrial Fibrillation on Warfarin Undergoing Endoscopy.

For warfarin-treated patients with atrial fibrillation (AF) at low thromboembolic risk, recent studies have shown harm associated with periprocedural bridging using low-molecular-weight heparin. Clinician surveys have indicated a preference toward excessive bridging, especially among noncardiologists; however, little is known about actual practice patterns in these patients. We performed a retrospective evaluation of bridging in the setting of gastrointestinal endoscopy. We identified 938 patients with AF on warfarin who underwent esophagogastroduodenoscopy or colonoscopy between 2012 and 2016 at a tertiary health center. Urgent, inpatient, or advanced endoscopic procedures were excluded. Clinical variables were abstracted using a predefined data dictionary. Values were expressed as means and compared using a t test or a chi-squared test as appropriate. Three hundred seventy-four patients met criteria for analysis. Twenty-five percent of these patients received bridging therapy, including 11% of patients with CHADS2 scores of 0 to 2 without valvular AF or previous venous thromboembolism. Of the clinical variables assessed, CHADS2, CHA2DS2-VASc, and a history of stroke were the strongest predictors of bridging. Cardiologists were also significantly less likely to prescribe bridging than noncardiology providers (18% vs 30%, p = 0.011); this effect was significant when controlling for CHADS2, CHA2DS2-VASc, or stroke history. In conclusion, patients with AF on warfarin receive excessive low-molecular-weight heparin bridging in the setting of endoscopy; the lower rates of bridging observed among cardiologists suggests a need for their increased involvement in this decision making.

Partnership for Diversity: A Multidisciplinary Approach to Nurturing Cultural Competence at an Emerging Medical School.

Fostering cultural competence in higher education institutions is essential, particularly in training future health care workers to care for diverse populations. The opportunity to explore techniques to address diversity and cultural competence at a new medical school was undertaken by a multidisciplinary team of librarians, faculty, staff, and medical students. From 2011 to 2015, the team sponsored a voluntary programming series to promote cultural competence and raise awareness of health care disparities for the medical school. Thirteen events were hosted with 562 participants across all. This approach to diversity proved effective and could be adapted in any higher education setting.

Radiographically Occult Latent Radiogenic Osteosarcoma Uncovered on Tc-99m Methylene-diphosphonate Bone Scintigraphy.

We present a case of a 70-year-old male who was referred for a technetium-99m methylene-diphosphonate bone scan for mild left hip pain and an elevated alkaline phosphatase level of 770 units/L. No additional information was provided and the patient's history was limited due to a language barrier. We were able to ascertain that the patient had a remote history of prostate cancer, which had been treated with radiation. Originally, we felt the bone scan was compatible with Paget's disease; however, further work-up revealed the presence of osteosarcoma, which was potentially radiation-induced.

Molecular mechanism of selectivity among G protein-coupled receptor kinase 2 inhibitors.

G protein-coupled receptors (GPCRs) are key regulators of cell physiology and control processes ranging from glucose homeostasis to contractility of the heart. A major mechanism for the desensitization of activated GPCRs is their phosphorylation by GPCR kinases (GRKs). Overexpression of GRK2 is strongly linked to heart failure, and GRK2 has long been considered a pharmaceutical target for the treatment of cardiovascular disease. Several lead compounds developed by Takeda Pharmaceuticals show high selectivity for GRK2 and therapeutic potential for the treatment of heart failure. To understand how these drugs achieve their selectivity, we determined crystal structures of the bovine GRK2-Gßγ complex in the presence of two of these inhibitors. Comparison with the apoGRK2-Gßγ structure demonstrates that the compounds bind in the kinase active site in a manner similar to that of the AGC kinase inhibitor balanol. Both balanol and the Takeda compounds induce a slight closure of the kinase domain, the degree of which correlates with the potencies of the inhibitors. Based on our crystal structures and homology modeling, we identified five amino acids surrounding the inhibitor binding site that we hypothesized could contribute to inhibitor selectivity. However, our results indicate that these residues are not major determinants of selectivity among GRK subfamilies. Rather, selectivity is achieved by the stabilization of a unique inactive conformation of the GRK2 kinase domain.