Examination of Early CNS Symptoms and Severe Coronavirus Disease 2019: A Multicenter Observational Case Series.

To determine if early CNS symptoms are associated with severe coronavirus disease 2019. DESIGN: A retrospective, observational case series study design. SETTING: Electronic health records were reviewed for patients from five healthcare systems across the state of Florida, United States. PATIENTS: A clinical sample (n = 36,615) of patients with confirmed diagnosis of coronavirus disease 2019 were included. Twelve percent (n = 4,417) of the sample developed severe coronavirus disease 2019, defined as requiring critical care, mechanical ventilation, or diagnosis of acute respiratory distress syndrome, sepsis, or severe inflammatory response syndrome. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We reviewed the electronic health record for diagnosis of early CNS symptoms (encephalopathy, headache, ageusia, anosmia, dizziness, acute cerebrovascular disease) between 14 days before the diagnosis of coronavirus disease 2019 and 8 days after the diagnosis of coronavirus disease 2019, or before the date of severe coronavirus disease 2019 diagnosis, whichever came first. Hierarchal logistic regression models were used to examine the odds of developing severe coronavirus disease 2019 based on diagnosis of early CNS symptoms. Severe coronavirus disease 2019 patients were significantly more likely to have early CNS symptoms (32.8%) compared with nonsevere patients (6.11%; χ2[1] = 3,266.08, p < 0.0001, φ = 0.29). After adjusting for demographic variables and pertinent comorbidities, early CNS symptoms were significantly associated with severe coronavirus disease 2019 (odds ratio = 3.21). Diagnosis of encephalopathy (odds ratio = 14.38) was associated with greater odds of severe coronavirus disease 2019; whereas diagnosis of anosmia (odds ratio = 0.45), ageusia (odds ratio = 0.46), and headache (odds ratio = 0.63) were associated with reduced odds of severe coronavirus disease 2019. CONCLUSIONS: Early CNS symptoms, and specifically encephalopathy, are differentially associated with risk of severe coronavirus disease 2019 and may serve as an early marker for differences in clinical disease course. Therapies for early coronavirus disease 2019 are scarce, and further identification of subgroups at risk may help to advance understanding of the severity trajectories and enable focused treatment.

Ventricular Assist Device Implantation and Bariatric Surgery: A Route to Transplantation in Morbidly Obese Patients with End-Stage Heart Failure.

We reviewed our experience of morbidly obese patients with end-stage heart failure that underwent left ventricular assist device (LVAD) implantation. From January 1, 2008 to January 1, 2018, 240 adult LVADs were implanted at our center. We reviewed the cases of patients presenting with end-stage heart failure and morbid obesity (preoperative body mass index [BMI] ≥ 35 kg/m2) who underwent LVAD-alone, and compared that to a group that underwent LVAD and bariatric surgery (laparoscopic sleeve gastrectomy [LSG]) as a means for weight reduction. Demographic characteristics, perioperative details, BMI, and status of transplant candidacy were recorded. Statistical analysis was performed (SPSS version 25) with χ2 analysis, Kaplan-Meier survival analysis, regression analysis, and Student's t-test. Twenty-nine patients met criteria and underwent LVAD implantation. Fifteen patients underwent LVAD-alone. Fourteen patients underwent LVAD + LSG. Both groups showed good survival outcomes, LVAD-alone (88.9 ± 5.9 months) versus LVAD +LSG (96.1 ± 12.4 months) but were not significantly different. However, we did note that more patients in the LVAD + LSG group were bridged to heart transplantation (p < 0.001). LVAD-alone and/or LVAD + LSG are both technically feasible and effective treatment options for the long-term survival of morbidly obese patients with end-stage heart failure. Combining LVAD + LSG can help bridge patients to heart transplantation.

Female C57BL/6J mice lacking the circadian clock protein PER1 are protected from nondipping hypertension.

The circadian clock is integral to the maintenance of daily rhythms of many physiological outputs, including blood pressure. Our laboratory has previously demonstrated the importance of the clock protein period 1 (PER1) in blood pressure regulation in male mice. Briefly, a high-salt diet (HS; 4% NaCl) plus injection with the long-acting mineralocorticoid deoxycorticosterone pivalate (DOCP) resulted in nondipping hypertension [<10% difference between night and day blood pressure (BP) in Per1-knockout (KO) mice but not in wild-type (WT) mice]. To date, there have been no studies that have examined the effect of a core circadian gene KO on BP rhythms in female mice. The goal of the present study was to determine whether female Per1-KO mice develop nondipping hypertension in response to HS/DOCP treatment. For the first time, we demonstrate that loss of the circadian clock protein PER1 in female mice does not significantly change mean arterial pressure (MAP) or the BP rhythm relative to female C57BL/6 WT control mice. Both WT and Per1-KO female mice experienced a significant increase in MAP in response to HS/DOCP. Importantly, however, both genotypes maintained a >10% dip in BP on HS/DOCP. This effect is distinct from the nondipping hypertension seen in male Per1-KO mice, demonstrating that the female sex appears to be protective against PER1-mediated nondipping hypertension in response to HS/DOCP. Together, these data suggest that PER1 acts in a sex-dependent manner in the regulation of cardiovascular rhythms.

Renal Na-handling defect associated with PER1-dependent nondipping hypertension in male mice.

Many physiological functions have a circadian rhythm, including blood pressure (BP). BP is highest during the active phase, whereas during the rest period, BP dips 10-20%. Patients that do not experience this dip at night are termed "nondippers." Nondipping hypertension is associated with increased risk of cardiovascular disease. The mechanisms underlying nondipping hypertension are not understood. Without the circadian clock gene Per1, C57BL/6J mice develop nondipping hypertension on a high-salt diet plus mineralocorticoid treatment (HS/DOCP). Our laboratory has shown that PER1 regulates expression of several genes related to sodium (Na) transport in the kidney, including epithelial Na channel (ENaC) and Na chloride cotransporter (NCC). Urinary Na excretion also demonstrates a circadian pattern with a peak during active periods. We hypothesized that PER1 contributes to circadian regulation of BP via a renal Na-handling-dependent mechanism. Na-handling genes from the distal nephron were inappropriately regulated in KO mice on HS/DOCP. Additionally, the night/day ratio of Na urinary excretion by Per1 KO mice is decreased compared with WT (4 × vs. 7×, P < 0.001, n = 6 per group). Distal nephron-specific Per1 KO mice also show an inappropriate increase in expression of Na transporter genes αENaC and NCC. These results support the hypothesis that PER1 mediates control of circadian BP rhythms via the regulation of distal nephron Na transport genes. These findings have implications for the understanding of the etiology of nondipping hypertension and the subsequent development of novel therapies for this dangerous pathophysiological condition.