Premature ventricular contraction variability in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

INTRODUCTION: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy, characterized by right ventricular dysfunction and ventricular arrhythmias. Premature ventricular contractions (PVCs) are an important measure in determining disease severity and constitute a minor criterion in the 2010 Task Force Criteria for the diagnosis of ARVD/C. Little information is available regarding the variability in PVCs. METHODS AND RESULTS: Patients (n = 40) from the Johns Hopkins ARVD/C registry, meeting diagnostic criteria were included. Single lead continuous 12-lead electrocardiogram (ECG) monitors (Zio® Patches) were applied to monitor PVC counts. Detailed demographic, phenotypic, and structural information were obtained from registry data. ECG monitors were worn for a mean period of 159.3 hours (±39.3). Average 24-hour PVC count in this population was 1,090.5 (interquartile range = 1,711). One-way analysis of variance demonstrated statistically significant interday variance in mean hourly PVC counts in 76% of ARVD/C-positive subjects (28/37, 3 cases excluded due to insufficient data). Eleven individuals (27.5%) had maximum 24-hour PVC counts of >500 with a corresponding minimum 24-hour PVC count of <500. The average 24-hour PVC count for each patient was derived for each day recorded. The 24-hour PVC count placed 89.6% of counts (223/249) on the correct side of the 500-PVC count. CONCLUSION: Statistically significant variation between 24-hour PVC counts is present in the ARVD/C population. However, 24-hour ECG monitoring was sufficient to identify 89.6% of 24-hour periods to the correct grouping based on 2010 Task Force Criteria.

CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer.

Patients with cancer have high mortality from coronavirus disease 2019 (COVID-19), and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 patients with cancer who were hospitalized for COVID-19, patients with hematologic cancer had higher mortality relative to patients with solid cancer. In two additional cohorts, flow cytometric and serologic analyses demonstrated that patients with solid cancer and patients without cancer had a similar immune phenotype during acute COVID-19, whereas patients with hematologic cancer had impairment of B cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses. Despite the impaired humoral immunity and high mortality in patients with hematologic cancer who also have COVID-19, those with a greater number of CD8 T cells had improved survival, including those treated with anti-CD20 therapy. Furthermore, 77% of patients with hematologic cancer had detectable SARS-CoV-2-specific T cell responses. Thus, CD8 T cells might influence recovery from COVID-19 when humoral immunity is deficient. These observations suggest that CD8 T cell responses to vaccination might provide protection in patients with hematologic cancer even in the setting of limited humoral responses.

CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer.

Cancer patients have increased morbidity and mortality from Coronavirus Disease 2019 (COVID-19), but the underlying immune mechanisms are unknown. In a cohort of 100 cancer patients hospitalized for COVID-19 at the University of Pennsylvania Health System, we found that patients with hematologic cancers had a significantly higher mortality relative to patients with solid cancers after accounting for confounders including ECOG performance status and active cancer status. We performed flow cytometric and serologic analyses of 106 cancer patients and 113 non-cancer controls from two additional cohorts at Penn and Memorial Sloan Kettering Cancer Center. Patients with solid cancers exhibited an immune phenotype similar to non-cancer patients during acute COVID-19 whereas patients with hematologic cancers had significant impairment of B cells and SARS-CoV-2-specific antibody responses. High dimensional analysis of flow cytometric data revealed 5 distinct immune phenotypes. An immune phenotype characterized by CD8 T cell depletion was associated with a high viral load and the highest mortality of 71%, among all cancer patients. In contrast, despite impaired B cell responses, patients with hematologic cancers and preserved CD8 T cells had a lower viral load and mortality. These data highlight the importance of CD8 T cells in acute COVID-19, particularly in the setting of impaired humoral immunity. Further, depletion of B cells with anti-CD20 therapy resulted in almost complete abrogation of SARS-CoV-2-specific IgG and IgM antibodies, but was not associated with increased mortality compared to other hematologic cancers, when adequate CD8 T cells were present. Finally, higher CD8 T cell counts were associated with improved overall survival in patients with hematologic cancers. Thus, CD8 T cells likely compensate for deficient humoral immunity and influence clinical recovery of COVID-19. These observations have important implications for cancer and COVID-19-directed treatments, immunosuppressive therapies, and for understanding the role of B and T cells in acute COVID-19.

Symptomatic relapse and long-term sequelae of COVID-19 in a previously healthy 30-year-old man.

Much has been reported on the clinical course of severe COVID-19, but less is known about the natural history and sequalae of mildly symptomatic cases and the prospects of reinfection or recurrence of symptoms. We report a case of a patient with mildly symptomatic PCR-confirmed COVID-19 who, after being symptom-free for 2 weeks, redeveloped symptoms and was found to be PCR-positive again >4 weeks from original testing. Surprisingly, IgG and IgM antibody testing was negative 2 months after reinfection. Although no negative testing was performed between the two symptomatic bouts, this case raises the possibility of reinfection after controlling the virus and highlights the long period with which a patient can shed virus and experience symptoms after initial infection. Characterising variations in clinical symptoms and length of viral shedding after improvement is essential for informing recommendations on patients safely resuming contact with others.

Opportunity Costs of Receiving Palliative Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma.

PURPOSE: The median overall survival (OS) for metastatic pancreatic ductal adenocarcinoma (mPDAC) is < 1 year. Factors that contribute to quality of life during treatment are critical to quantify. One factor-time spent obtaining clinical services-is understudied. We quantified total outpatient time among patients with mPDAC receiving palliative systemic chemotherapy. METHODS: We conducted a retrospective analysis using four patient-level time measures calculated from the medical record of patients with mPDAC receiving 5-fluorouracil infusion, leucovorin, oxaliplatin, and irinotecan; gemcitabine/nab-paclitaxel; or gemcitabine within the University of Pennsylvania Health System between January 1, 2011 and January 15, 2019. These included the total number of health care encounter days (any day with at least one visit) and total visit time. Total visit time represented the time spent receiving care (care time) plus time spent commuting and waiting for care (noncare time). We performed descriptive statistics on these outpatient time metrics and compared the number of encounter days to OS. RESULTS: A total of 362 patients were identified (median age, 65 years; 52% male; 78% white; 62% received gemcitabine plus nab-paclitaxel). Median OS was 230.5 days (7.6 months), with 79% of patients deceased at the end of follow-up. On average, patients had 22 health care encounter days, accounting for 10% of their total days survived. Median visit time was 4.6 hours, of which 2.5 hours was spent commuting or waiting for care. CONCLUSION: On average, patients receiving palliative chemotherapy for mPDAC spend 10% of survival time on outpatient health care. More than half of this time is spent commuting and waiting for care. These findings provide an important snapshot of the patient experience during ambulatory care, and efforts to enhance efficiency of care delivery may be warranted.