Short-term outpatient follow-up of COVID-19 patients: A multidisciplinary approach.

BACKGROUND: Short-term follow-up of COVID-19 patients reveals pulmonary dysfunction, myocardial damage and severe psychological distress. Little is known of the burden of these sequelae, and there are no clear recommendations for follow-up of COVID-19 patients.In this multi-disciplinary evaluation, cardiopulmonary function and psychological impairment after hospitalization for COVID-19 are mapped. METHODS: We evaluated patients at our outpatient clinic 6 weeks after discharge. Cardiopulmonary function was measured by echocardiography, 24-hours ECG monitoring and pulmonary function testing. Psychological adjustment was measured using questionnaires and semi-structured clinical interviews. A comparison was made between patients admitted to the general ward and Intensive care unit (ICU), and between patients with a high versus low functional status. FINDINGS: Eighty-one patients were included of whom 34 (41%) had been admitted to the ICU. New York Heart Association class II-III was present in 62% of the patients. Left ventricular function was normal in 78% of patients. ICU patients had a lower diffusion capacity (mean difference 12,5% P = 0.01), lower forced expiratory volume in one second and forced vital capacity (mean difference 14.9%; P<0.001; 15.4%; P<0.001; respectively). Risk of depression, anxiety and PTSD were 17%, 5% and 10% respectively and similar for both ICU and non-ICU patients. INTERPRETATION: Overall, most patients suffered from functional limitations. Dyspnea on exertion was most frequently reported, possibly related to decreased DLCOc. This could be caused by pulmonary fibrosis, which should be investigated in long-term follow-up. In addition, mechanical ventilation, deconditioning, or pulmonary embolism may play an important role.

Changes in brain activity after weight loss.

OBJECTIVES: The importance of the regulatory role of the brain in directing glucose homeostasis, energy homeostasis, eating behaviour, weight control and obesity is increasingly recognized. Brain activity in (sub)cortical neuronal networks involved in homeostatic control and hedonic responses is generally increased in persons with obesity. Currently, it is not known if these functional changes can be affected by dieting. The aim of the current study was to investigate whether prolonged fasting and/or weight loss influences neuronal brain activity in obese persons. METHODS: Fourteen participants with obesity were included (two male participants and 12 female participants, body mass index 35.2 ± 1.2 kg m-2). Whole-brain resting-state functional magnetic resonance imaging was performed after an overnight fast, after a prolonged 48-h fast and after an 8-week weight loss intervention. RESULTS: An 8-week weight loss intervention decreased BOLD signal in areas of the brain involved in salience, sensory motor and executive control. BOLD signal in these areas correlated with leptin levels and body mass index. CONCLUSIONS: Weight loss decreased activity in brain areas involved in feeding behaviour and reward processing. These results indicate that these obesity-associated alterations in neuronal activity are related to excessive body weight and might change after weight loss.

Obesity is marked by distinct functional connectivity in brain networks involved in food reward and salience.

We hypothesized that brain circuits involved in reward and salience respond differently to fasting in obese versus lean individuals. We compared functional connectivity networks related to food reward and saliency after an overnight fast (baseline) and after a prolonged fast of 48 h in lean versus obese subjects. We included 13 obese (2 males, 11 females, BMI 35.4 ± 1.2 kg/m(2), age 31 ± 3 years) and 11 lean subjects (2 males, 9 females, BMI 23.2 ± 0.5 kg/m(2), age 28 ± 3 years). Resting-state functional magnetic resonance imaging scans were made after an overnight fast (baseline) and after a prolonged 48 h fast. Functional connectivity of the amygdala, hypothalamus and posterior cingulate cortex (default-mode) networks was assessed using seed-based correlations. At baseline, we found a stronger connectivity between hypothalamus and left insula in the obese subjects. This effect diminished upon the prolonged fast. After prolonged fasting, connectivity of the hypothalamus with the dorsal anterior cingulate cortex (dACC) increased in lean subjects and decreased in obese subjects. Amygdala connectivity with the ventromedial prefrontal cortex was stronger in lean subjects at baseline, which did not change upon the prolonged fast. No differences in posterior cingulate cortex connectivity were observed. In conclusion, obesity is marked by alterations in functional connectivity networks involved in food reward and salience. Prolonged fasting differentially affected hypothalamic connections with the dACC and the insula between obese and lean subjects. Our data support the idea that food reward and nutrient deprivation are differently perceived and/or processed in obesity.

Obesity is associated with an altered autonomic nervous system response to nutrient restriction.

OBJECTIVE: Heart rate variability (HRV) reflects the balance of activities of sympathetic and parasympathetic components of the autonomic nervous system. We compared HRV parameters in response to a prolonged fast in obese versus normal weight humans. In addition, the effect of weight-loss was evaluated in obese individuals. DESIGN: Intervention study. PATIENTS: The study subjects included 14 nondiabetic obese (12 females/2 males, aged 30 ± 3 years, Body Mass Index (BMI) 35·2 ± 1·2 kg/m(2) ) and 12 lean subjects (10 females/2 males, aged 27 ± 3 years, BMI 23·3 ± 0·5 kg/m(2) ). MEASUREMENTS: HRV was examined 75 min after standardized breakfast and after a 48-h fast in 14 nondiabetic obese and 12 lean subjects. The postprandial measurement was repeated in 12 obese subjects after weight-loss. RESULTS: In lean subjects, fasting decreased high-frequency (HF) power by 43% (P < 0·05) and decreased low-frequency (LF) power by 37% (P = 0·1), leaving the LF/HF ratio unchanged (P = 0·7). In the obese group, autonomic nervous system tone shifted to sympathetic dominance as the LF/HF increased from 0·61 to 1·14 (P = 0·03). After an average weight-loss of 13·8 kg in obese subjects, a trend for sympathetic dominance was found; the LF/HF ratio increased by 56% (P = 0·06). CONCLUSION: Our data show that a 48-h fast leaves autonomic nervous system balance unaltered in lean subjects. In contrast, a 48-h fast, as well as weight-loss, induces sympathetic dominance in obese humans.

Effects of low doses of casein hydrolysate on post-challenge glucose and insulin levels.

BACKGROUND: Ingestion of high doses of casein hydrolysate stimulates insulin secretion in healthy subjects and patients with type 2 diabetes. The effects of low doses have not been studied. The aim of this study was to assess the effect of lower doses of a casein hydrolysate on the glucose and insulin responses to an oral glucose tolerance test in patients with type 2 diabetes. METHODS: In this randomized, placebo-controlled, double-blind study, thirteen patients with type 2 diabetes (age: 58±1 years) were studied. Glucose, insulin and C-peptide responses were determined after the oral administration of 0 (control), 6 or 12 g protein hydrolysate in combination with 50 g carbohydrate. RESULTS: Twelve grams of casein hydrolysate, but not 6g, elevated insulin levels and decreased glucose levels post-challenge. These changes over time were not large enough to also affect the total area under the curve of glucose and insulin. C-peptide levels did not change after both treatments. CONCLUSION: Ingestion of six grams of casein hydrolysate did not affect glucose or insulin responses. Intake of 12 g of casein hydrolysate has a small positive effect on post-challenge insulin and glucose levels in patients with type 2 diabetes.