Frailty is associated with in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands:the COVID-OLD study

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting. OBJECTIVE: The aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands. METHODS: This was a multicentre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality. RESULTS: A total of 1,376 patients were included (median age 78 years (interquartile range 74-84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6-9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 versus 7 days), lower oxygen demand and lower levels of C-reactive protein. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared with patients with CFS 1-3, patients with CFS 4-5 had a two times higher risk (odds ratio (OR) 2.0 (95% confidence interval (CI) 1.3-3.0)) and patients with CFS 6-9 had a three times higher risk of in-hospital mortality (OR 2.8 (95% CI 1.8-4.3)). CONCLUSIONS: The in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms

Imaging of serotonin transporters with [I-123]FP-CIT SPECT in the human hypothalamus

Background: Serotonergic neurons in the rodent hypothalamus are implicated in key neuroendocrine and metabolic functions, including circadian rhythmicity. However, the assessment of the serotonergic system in the human hypothalamus in vivo is difficult as delineation of the hypothalamus is cumbersome with conventional region-of-interest analysis. In the present study, we aimed to develop a method to visualize serotonin transporters (SERT) in the hypothalamus. Additionally, we tested the hypothesis that hypothalamic SERT binding ratios are different between patients with hypothalamic impairment (HI), pituitary insufficiency (PI), and control subjects (C). Methods: SERT availability was determined in 17 subjects (6 HI, 5 PI, and 6 healthy controls), 2 h after injection of I-123-N-omega-fluoropropyl-2 beta-carboxymethoxy-3 beta-(4-iodophenyl) nortropane ([I-123]FP-CIT), using single-photon emission computed tomography (performed on a brain-dedicated system) fused with individual magnetic resonance imaging (MRI) scans of the brain. The hypothalamus (representing specific SERT binding) and cerebellum (representing nonspecific binding) were manually delineated on each MRI to assess [I-123]FP-CIT binding and specific-to-nonspecific binding ratios. Results: In each healthy subject, [I-123]FP-CIT binding was higher in the hypothalamus than in the cerebellum, and the mean hypothalamic binding ratio of SERT was 0.29 +/- 0.23. We found no difference in hypothalamic binding ratios between HI, PI, and control subjects (HI 0.16 +/- 0.24, PI 0.45 +/- 0.39, C 0.29 +/- 0.23, p value 0.281). Conclusions: We were able to demonstrate SERT binding in the human hypothalamus However, we did not find altered hypothalamic SERT binding in patients with hypothalamic impairmen

Determinants of vascular and cardiac baroreflex sensitivity values in a random population sample

The arterial baroreflex regulates blood pressure by modifying heart rate and systemic vascular resistance. Baroreflex sensitivity is expressed as the relation between changes in blood pressure and the resulting changes in reciprocal values of heart rate (cardBRS) and in reciprocal values of vascular resistance (vascBRS). This study investigated determinants of vascBRS and cardBRS and their relationship in a random population sample. Continuous noninvasive arterial pressure was analyzed in 105 adults (43 males) with a median age of 45 (range 18-95) years and body mass index of 24.5 (range 18.1-39.1) kg m⁻². Systolic and diastolic blood pressures were 130 (range 95-205) and 80 (range 47-141) mmHg, and heart rate was 66 (range 42-109) beats min⁻¹. Pulse contour (CO-trek)-determined vascular resistance was 1.37 (range 0.60-7.75) mmHg s ml⁻¹. The results of vascBRS and cardBRS were log-transformed; linear regression analysis revealed that age, resistance⁻¹, systolic and diastolic blood pressures were major determinants of log(vascBRS) explaining 30.5 % of the variance. Determinants of log(cardBRS) were age, body mass index, heart rate, systolic and diastolic blood pressures, explaining 70.4 % of the variance. Thus, some established determinants of cardBRS were not correlated with vascBRS. There was no correlation between log(cardBRS) and log(vascBRS) after correction for age, supporting that vascBRS is an independent description of baroreflex regulation. These findings suggest that vascBRS and cardBRS report different modalities of cardiovascular autonomic functio

Hypothalamic neuropeptide Y (NPY) controls hepatic VLDL-triglyceride secretion in rats via the sympathetic nervous system

Item does not contain fulltextExcessive secretion of triglyceride-rich very low-density lipoproteins (VLDL-TG) contributes to diabetic dyslipidemia. Earlier studies have indicated a possible role for the hypothalamus and autonomic nervous system in the regulation of VLDL-TG. In the current study, we investigated whether the autonomic nervous system and hypothalamic neuropeptide Y (NPY) release during fasting regulates hepatic VLDL-TG secretion. We report that, in fasted rats, an intact hypothalamic arcuate nucleus and hepatic sympathetic innervation are necessary to maintain VLDL-TG secretion. Furthermore, the hepatic sympathetic innervation is necessary to mediate the stimulatory effect of intracerebroventricular administration of NPY on VLDL-TG secretion. Since the intracerebroventricular administration of NPY increases VLDL-TG secretion by the liver without affecting lipolysis, its effect on lipid metabolism appears to be selective to the liver. Together, our findings indicate that the increased release of NPY during fasting stimulates the sympathetic nervous system to maintain VLDL-TG secretion at a postprandial level

A history of cranial radiotherapy is associated with a higher visceral to subcutaneous fat ratio in men with pituitary insufficiency

Item does not contain fulltextOBJECTIVE: Endocrine deficiencies, like GH and estrogen deficiencies, are likely candidates to explain increased visceral to subcutaneous fat ratio in patients with pituitary insufficiency. However, recent reports pointed to cranial radiotherapy (CRT) as an additional determinant of an unfavorable fat distribution. Therefore, we determined the effect of CRT on abdominal fat distribution in men with treated pituitary insufficiency. DESIGN: Cross-sectional study. METHODS: Thirty-five consecutive male subjects (16 men with and 19 men without CRT aged 62+/-12 and 56+/-14 years respectively, P=0.175) visiting our Endocrine Outpatient Clinic for pituitary insufficiency were invited to participate in this study. A standardized single-slice abdominal CT scan at the level of fourth lumbar vertebra was performed to determine visceral fat area, subcutaneous fat area, and visceral to subcutaneous fat ratio. In addition, we assessed body mass index, total fat percentage with bioelectrical impedance analysis, resting energy expenditure with indirect calorimetry, calorie intake using a diary, and serum hormone concentrations. RESULTS: Subjects with CRT had a smaller subcutaneous fat area (225.1 (71.1-480.7) vs 269.0 (133.2-59.9) cm(2), P=0.022) and a higher visceral to subcutaneous fat ratio (0.79 (0.39-1.55) vs 0.63 (0.23-0.88), P=0.001) than subjects without CRT. Both the groups were comparable for body mass index, waist-hip ratio, resting energy expenditure, and calorie intake. Importantly, serum hormone concentrations were similar. CONCLUSION: In men treated for pituitary insufficiency, previous CRT is associated with a higher visceral to subcutaneous fat ratio

Thyroid hormone transporters and deiodinases in the developing human hypothalamus

Item does not contain fulltextOBJECTIVE: Thyroid hormone (TH) signaling in brain cells is dependent on transport of TH across the plasma membrane followed by intracellular deiodination and binding to the nuclear TH receptors. The aim of this study is to investigate the expression of the specific TH transporters monocarboxylate transporter 8 (MCT8 (SLC16A2)), MCT10, organic anion transporting polypeptide 1C1 (OATP1C1 (SLCO1C1)), and the types 2 and 3 deiodinases (D2 and D3) in the developing human hypothalamus. DESIGN: Fifteen postmortem brain samples of fetuses and young children ranging between 17 weeks of gestation and 29 months of postnatal age including one child (28 months) with central congenital hypothyroidism were studied. METHODS: Sections of the different hypothalami were stained with polyclonal rabbit antisera against MCT8, MCT10, OATP1C1, D2, and D3. RESULTS: We found MCT8 and D3 but not D2 protein expression to be present in our earliest sample of 17 weeks of gestation, indicating triiodothyronine degradation, but not production at this time of development. At term, expression of TH transporters and D2 decreased and D3 expression increased, suggesting decreased TH signaling just before birth. The child with central congenital hypothyroidism showed higher MCT8 and D2 expression compared with the other children of similar age. CONCLUSIONS: This study reports the developmental timing of expression of components crucial for central TH signaling in the human hypothalamus. In general, during fetal hypothalamic development, the coordinated expression of D2 and D3 in combination with the different TH transporters suggests that proper TH concentrations are regulated to prevent untimely maturation of brain cells