Vitamin D deficiency, secondary hyperparathyroidism and respiratory insufficiency in hospitalized patients with COVID-19.

PURPOSE: Hypovitaminosis D has emerged as potential risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the general population with variable effects on the outcome of the coronavirus disease-19 (COVID-19). The aim of this retrospective single-center study was to investigate the impact of hypovitaminosis D and secondary hyperparathyroidism on respiratory outcomes of COVID-19. METHODS: Three-hundred-forty-eight consecutive patients hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano, Milan (Italy) were evaluated for arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, serum 25hydroxy-vitamin D [25(OH)D], parathyroid hormone (PTH) and inflammatory parameters at study entry and need of ventilation during the hospital stay. RESULTS: In the entire population, vitamin D deficiency (i.e., 25(OH)D values < 12 ng/mL) was significantly associated with acute hypoxemic respiratory failure at the study entry [adjusted odds ratio (OR) 2.48, 95% confidence interval 1.29-4.74; P = 0.006], independently of age and sex of subjects, serum calcium and inflammatory parameters. In patients evaluated for serum PTH (97 cases), secondary hyperparathyroidism combined with vitamin D deficiency was significantly associated with acute hypoxemic respiratory failure at study entry (P = 0.001) and need of ventilation during the hospital stay (P = 0.031). CONCLUSION: This study provides evidence that vitamin D deficiency, when associated with secondary hyperparathyroidism, may negatively impact the clinical outcome of SARS-CoV-2-related pneumonia.

Clinical efficacy and predictors of response to dulaglutide in type-2 diabetes.

Aim of this retrospective multicenter observational study was to evaluate the efficacy and safety of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) dulaglutide in a type-2 diabetic real-world population and to determine the factors predicting the response in terms of glycated haemoglobin (HbA1c) and other relevant clinical outcomes. Data for efficacy outcomes, adverse events and drug discontinuation were collected from records of patients with type-2 diabetes treated with once-a-week 1.5 mg of dulaglutide for 12 months in routine clinical practice. Initial analysis included 782 patients and 626 had complete follow-up at 6- and 12-months. There was a significant reduction of HbA1c at 6 months (-1 ± 0.8 %, p < 0.0001), which remained stable at 12-months follow-up (-1 ± 0.9 %, p < 0.0001). The percentage of subjects with HbA1c≤7.0 % increased significantly from 7.2 % at baseline to 52.7 % at 6 months to 55.8 % at 12 months. Predictors of the achievement of HbA1c≤7.0 % were low baseline HbA1c and short duration of diabetes. The reduction of HbA1c was associated with reductions of BMI, waist circumference, fasting plasma glucose and blood pressures. Neither sex nor age had significant effects on any clinical or laboratory outcome. The effects of dulaglutide on HbA1c, BMI and SBP tended to be greater in patients who shifted from dipeptidyl peptidase-IV inhibitors (-0.8 ± 0.8 %) than other GLP-1 RA, even if an improvement of HbA1c reduction (-0.5 %) was also seen in those shifting from other GLP-1 RA. This study confirms that addition of dulaglutide 1.5 mg once a week in real word settings has beneficial effects on both clinical and laboratory outcomes in patients with uncontrolled type-2 diabetes. Dulaglutide has a greater effect on HbA1c in patients with higher baseline values and helps achieve a target HbA1c≤7.0 %, more consistently in patients with lower baseline HbA1c and shorter diabetes duration.

Cognitive and affective disorders in the elderly: a neuroendocrine study.

Both in physiological and pathological brain aging, cognitive and affective disorders usually keep up with significant morphological and metabolic changes of brain areas possibly involved in the control of mood, learning and memory, as well as in the modulation of the hypothalamo-pituitary-adrenal (HPA) axis. The aim of this work was to study the circadian rhythm of serum cortisol and dehydroepiandrosterone (DHEAS) in 25 old demented patients and 10 old unipolar depressed patients, compared with 21 old and 13 young controls. The circadian profile of serum cortisol was clearly flattened in elderly subjects,both healthy and demented, in comparison to young controls, with significantly higher cortisol levels at nighttime. The occurrence of minor depression was associated with a further increase of the cortisol mean levels in old demented subjects, but not in the healthy ones. The trend towards the increase of the nocturnal cortisol levels was also evident in old subjects with major depression. The decline of DHEAS secretory pattern was clearly age related,being additive factors to both dementia and major depression. No significant influence of minor depression on DHEAS secretion was found. The cortisol/DHEAS molar ratio,considered as a good index of the brain steroidal milieu, progressively increased with aging and exhibited a further increase related to the occurrence of senile dementia or minor depressive symptoms. The value of the same ratio was higher in elderly subjects with major depression, than in age-matched healthy controls. In conclusion, the occurrence of major depression or even only of depressive symptoms seems to amplify the changes of the adrenal steroidal secretory pattern, already present in physiological aging.

AIDS-related lipodystrophy/insulin resistance syndrome.

The recent development and clinical use of three different types of highly effective anti-HIV-1 drugs, including nucleotide and non-nucleotide reverse transcriptase inhibitors (NRTIs) and non-peptidic viral protease inhibitors (PIs) and their combinations, termed highly active antiretroviral therapy (HAART), have dramatically reduced the infection-related mortality of AIDS patients in developed countries. However, the prolongation of the life expectancy of HIV-1-infected patients and/or long-term use of the above antiviral agents have generated a score of new problems and complications. Among them is the relatively common AIDS-related lipodystrophy/insulin resistance syndrome, which is associated with severe metabolic disturbances such as carbohydrate intolerance/diabetes mellitus and severe dyslipidemia, which influence the quality of life and threaten the life expectancies of HIV-1-infected patients by increasing the risk of atherosclerotic cardiovascular disease. The etiology of this syndrome appears to be multi-factorial; the classes of anti-viral drugs listed above, hypercytokinemia in AIDS patients, and the HIV-1 infection itself could induce the pathologic changes of this syndrome or increase the vulnerability of patients to the adverse effect of the therapeutic compounds. In this article, we review our current understanding of the pathogenesis of this severe AIDS-associated metabolic disorder.