Red Blood Cell Abnormalities as the Mirror of SARS-CoV-2 Disease Severity: A Pilot Study.

PURPOSE: Unraveling the pathophysiology of COVID-19 disease is of crucial importance for designing treatment. The purpose of this study is to investigate the effects of the disease on erythrocytes (RBCs) and to correlate the findings with disease severity. MATERIALS AND METHODS: Hospitalized patients (n = 36) with COVID-19 and control group of healthy volunteers (n = 18) were included in the study. Demographic data, clinical, laboratory and chest Computed Tomography (CT) findings at time of admission were recorded. Laboratory measurements included: Hemoglobin (H b), indirect billirubin, LDH, D-Dimers, and plasma free hemoglobin (plasma free-Hb). On RBCs were performed: osmotic fragility (MCF), Free-Hb after mechanical stress (Free-Hb-MECH), intracellular RBC concentration of calcium ions (iCa2+), intracellular ROS (iROS), G6PD, intracellular active caspase-3 (RBC-caspase-3), IgG immunoglobulins (RBC-IgGs), which are bound on RBCs' senescent neo-antigen proteins and RBC surface phosphatidylserine (RBC-PS). RESULTS: The percentage of males was 50 and 66% and the mean age was 65.16 ± 14.24 and 66.33 ± 13.48 years among patients and controls respectively (mean ± SD, p = 0.78). Upon admission patients' PO2/FiO2 ratio was 305.92 ± 76.75 and distribution of infiltration extend on chest CT was: 0-25% (N = 19), 25-50%: (N = 7), and 50-75% (N = 9). Elevated hemolysis markers (LDH and plasma free-Hb) were observed in patients compared to the control group. Patients' RBCs were more sensitive to mechanical stress, and exhibited significantly elevated apoptotic markers (iCa2+, RBC-PS). Plasma free Hb levels correlated with the extend of pulmonary infiltrates on chest CT in COVID-19 patients. Surprisingly, patients' RBC-iROS were decreased, a finding possibly related with the increased G6PDH levels in this group, suggesting a possible compensatory mechanism against the virus. This compensatory mechanism seemed to be attenuated as pulmonary infiltrates on chest CT deteriorated. Furthermore, RBC-IgGs correlated with the severity of pulmonary CT imaging features as well as the abnormality of lung function, which are both associated with increased disease severity. Lastly, patients' D-Dimers correlated with RBC surface phosphatidylserine, implying a possible contribution of the red blood cells in the thrombotic diathesis associated with the SARS-CoV-2 disease. CONCLUSION: This pilot study suggests that SARS-CoV-2 infection has an effect on red blood cells and there seems to be an association between RBC markers and disease severity in these patients.

Ectopic adrenocorticotrophic hormone syndrome (EAS) with phaeochromocytoma: a challenging endocrine case with a happy ending.

Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is rarely caused by a phaeochromocytoma. We report a case of a 51-year-old woman with an 8-year history of severe constipation who underwent extensive investigations including gastroscopy, colonoscopy, ultrasonography, colonic transit studies and isotope defeacography, which did not reveal any pathology other than slow colonic transit time. The unifying diagnosis of ectopic ACTH and phaeochromocytoma was made after the case was initially investigated for an adrenal incidentaloma. Multiple challenges had to be overcome prior to surgery for the functioning adrenal adenoma including management of refractory hypokalaemia, poor nutritional status, persistent hyperglycaemia, labile blood pressure and florid hypercortisolaemia driving the metabolic derangements. She underwent an uneventful left-sided adrenalectomy and required no medication thereafter with normal blood pressure, blood glucose and serum potassium and resolution of constipation and abdominal symptoms. In conclusion, patients with EAS related to phaeochromocytoma are rare and present with distinctive diagnostic and management challenges but if diagnosed successfully and managed intensively, they are curable.

Combination therapy with GLP-1 analogues and SGLT-2 inhibitors in the management of diabesity: the real world experience.

Diabesity-obesity resulting in diabetes-is a major health problem globally because of the obesity epidemic. Several anti-diabetic medications cause weight gain and may worsen obesity, and possibly diabeisty. Two recent small retrospective cohort studies showed weight loss and diabetes improvement with combination of glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose co-transporter type-2 (SGLT-2) inhibitors in obese subjects. We assessed the effect of combination therapy with GLP-1 agonists and SGLT-2 inhibitors in the management of diabesity in a retrospective study at the Wolverhampton Diabetes Centre. Out of 79 patients on this combination regimen with other anti-diabetic medications, 37 cases who had follow up at 3-6 months were studied. Mean age and duration of follow up were 57.4 (+/-7.8) and 139 (+/-32.6) days, respectively. Twenty-two patients (59.5 %) were Asians. Statistically significant improvements in clinical parameters such as body weight reduction (3.07 kg), glycated haemoglobin (HbA1c) reduction (1.05 %), lower BMI (-1.13 kg/M2) and insulin dose reduction (6.8 units) were observed (p < 0.05 for all) in patients on combination regimen. Linear regression analysis showed that baseline HbA1c and baseline insulin dose were independent predictors of HbA1c reduction and insulin dose reduction, respectively. Our results suggest that combination therapy with GLP-1 agonists and SGLT-2 inhibitors is a promising option for patients with diabesity.

Effects of gender and age on hypothalamic-pituitary-adrenal reactivity after pharmacological challenge with low-dose 1-µg ACTH test: a prospective study in healthy adults.

OBJECTIVE: Τhe aim of this study was to observe cortisol responses to a pharmacological challenge with 1 µg ACTH as a function of age and gender. PATIENTS: Twenty-one young (13 women and 8 men; mean age: 43∙48 ± 10∙52 years) and forty elderly (20 women and 20 men; mean age: 79 ± 6∙76 years) volunteers without overt acute or chronic disease participated in this study. MEASUREMENTS: Basal serum cortisol levels were measured, and cortisol values were obtained at 30 and 60 min after administration of 1 µg ACTH. Free thyroxine, triiodothyronine, thyrotrophin, prolactin, dehydroepiandrosterone sulphate (DHEAS), insulin-like growth factor-1, follicle stimulating hormone, luteinizing hormone, oestradiol levels in women and total testosterone levels in men were also measured at baseline. RESULTS: No differences were observed between the groups of older and younger individuals in baseline plasma cortisol levels and mean cortisol responses at 30 and 60 min postchallenge. In the elderly subjects, statistically lower cortisol responses were observed in men at 30 and 60 min after 1-µg ACTH challenge (540∙17 ± 112∙28 vs 670∙11 ± 146∙49 nmol/l in women, P = 0∙003 at 30 min, and 482∙24 ± 108∙14 vs 568∙04 ± 135∙73 nmol/l in women, P = 0∙03 at 60 min). Furthermore, significant lower values in PRL, IGF-1, DHEAS and T3 were detected in older subjects when compared to the younger age group. Interestingly, a higher incidence of individuals who did not achieve normal responses to 1-µg ACTH test (>497 nmol/l) was noted in the group of elderly male subjects. CONCLUSION: This study documents a marked gender effect in the elderly, in the cortisol response levels to 1-µg ACTH stimulation. Elderly men demonstrate a decreased responsiveness compared to women in the same age range.