Bergamo province was badly hit by the coronavirus disease 2019 (COVID-19) epidemic. We organised a public-funded, multidisciplinary follow-up programme for COVID-19 patients discharged from the emergency department or from the inpatient wards of ‘Papa Giovanni XXIII’ Hospital, the largest public hospital in the area. As of 31 July, the first 767 patients had completed the first post-discharge multidisciplinary assessment. Patients entered our programme at a median time of 81 days after discharge. Among them, 51.4% still complained of symptoms, most commonly fatigue and exertional dyspnoea, and 30.5% were still experiencing post-traumatic psychological consequences. Impaired lung diffusion was found in 19%. Seventeen per cent had D-dimer values two times above the threshold for diagnosis of pulmonary embolism (two unexpected and clinically silent pulmonary thrombosis were discovered by investigating striking D-dimer elevation). Survivors of COVID-19 exhibit a complex array of symptoms, whose common underlying pathology, if any, has still to be elucidated: a multidisciplinary approach is fundamental, to address the different problems and to look for effective solutions.

Purpose To perform a systematic review on published cases of subacute thyroiditis (SAT) secondary to SARS-CoV-2 vaccination, to highlight main features and increase the awareness of this condition. Methods Original reports of SAT developed after SARS-CoV-2 vaccination (mRNA, viral vector, or inactivated virus vaccines) were retrieved from a search of electronic databases. Individual patient data on demographics, medical history, type of vaccine, workup and therapies were collected. Wilcoxon rank-sum, Kruskal–Wallis and chi-squared tests were employed for comparisons. Results 30 articles including 48 reports were retrieved, 3 additional cases evaluated by the Authors were described and included for analysis. Of the 51 patients, 38 (74.5%) were women, median age was 39.5 years (IQR 34–47). Patients developed SAT after a median of 10 days (IQR 4–14) after the vaccine shot. Baseline thyroid exams revealed thyrotoxicosis in 88.2% of patients, decreasing at 31.6% at follow-up. Corticosteroids were used in 56.4% of treated patients. Patients undergoing non-mRNA vaccines were most frequently Asian (p = 0.019) and reported more frequently weight loss (p = 0.021). All patients with a previous diagnosis of thyroid disease belonged to the mRNA vaccine group. Conclusion SARS-CoV-2 vaccine-associated SAT is a novel entity that should be acknowledged by physicians. Previous history of thyroid disease may predispose to develop SAT after mRNA vaccines, but further studies and larger cohorts are needed to verify this suggestion. SARS-CoV-2 vaccine-associated SAT is usually of mild/moderate severity and could be easily treated in most cases, thus it should not raise any concern regarding the need to be vaccinated.

We confirm that in patients with AGHD, rhGH therapy is associated with a small, although significant, decrement of fT4 in the first 6 months of replacement therapy. However, the incidence of hypothyroidism is low. Monitoring of thyroid function during rhGH therapy is advisable, particularly in the first year of therapy when the largest decrease in fT4 occurs.

Sodium-glucose cotransporters inhibitors (SGLT2-i) and GLP-1 receptor agonists (GLP1-RA) are glucose-lowering drugs that are proved to reduce the cardiovascular (CV) risk in type 2 diabetes mellitus (T2DM). In this process, the renin-angiotensin-aldosterone system (RAAS) is assumed to play a role. The inhibition of SGLT2 improves hyperglycemia hampering urinary reabsorption of glucose and inducing glycosuria. This “hybrid” diuretic effect, which couples natriuresis with osmotic diuresis, potentially leads to systemic RAAS activation. However, the association between SGLT2-i and systemic RAAS activation is not straightforward. Available data indicate that SGLT2-i cause plasma renin activity (PRA) increase in the early phase of treatment, while PRA and aldosterone levels remain unchanged in chronic treated patients. Furthermore, emerging studies provide evidence that SGLT2-i might have an interfering effect on aldosterone/renin ratio (ARR) in patients with T2DM, due to their diuretic and sympathoinhibition effects. The cardio- and reno-protective effects of GLP-1-RA are at least in part related to the interaction with RAAS. In particular, GLP1-RA counteract the action of angiotensin II (ANG II) inhibiting its synthesis, increasing the inactivation of its circulating form and contrasting its action on target tissue like glomerular endothelial cells and cardiomyocytes. Furthermore, GLP1-RA stimulate natriuresis inhibiting Na+/H+ exchanger NHE-3, which is conversely activated by ANG II. Moreover, GLP1 infusion acutely reduces circulating aldosterone, but this effect does not seem to be chronically maintained in patients treated with GLP1-RA. In conclusion, both SGLT2-i and GLP1-RA seem to have several effects on RAAS, though additional studies are needed to clarify this relationship.

Summary:Purpose: To assess the influence of aging on the steady-state pharmacokinetics of carbamazepine (CBZ) in a large population of patients evaluated in a therapeutic drug monitoring (TDM) setting.Methods: The database of a large TDM service was used to identify retrospectively steady-state serum CBZ concentrations in 157 elderly patients with epilepsy (65 years and older) treated with CBZ alone or in combination with phenobarbital (PB). CBZ apparent oral clearance (CL/F) values were calculated and compared with those determined in an equal number of controls aged 20 to 50 years, and matched for gender, body weight, and comedication.Results: Compared with corresponding controls, mean CBZ CL/F values were 23% and 24% lower, respectively, in the groups of elderly patients receiving monotherapy (57.1 ± 20.6 vs. 74.6 ± 28.3 ml/h/kg; p < 0.0001) and PB comedication (74.7 ± 25.5 vs. 98.7 ± 34.9 ml/h/kg; p < 0.01). Within each age group, patients comedicated with PB showed significantly higher CBZ CL/F values than those on monotherapy. A negative correlation between CL/F and age was found both within the monotherapy and the PB comedicated groups. In addition, CL/F values showed a positive relation with the administered daily dosage, which persisted within subgroups homogeneous for age and comedication. The independent influence of age, CBZ dosage, and comedication on CBZ CL/F was confirmed by multiple regression analysis.Conclusions: CBZ CL/F is decreased in an age-dependent manner in elderly patients compared with younger subjects, presumably because a reduction in the rate of CYP3A4-mediated drug metabolism. Elderly patients retain their sensitivity to dose-dependent autoinduction and to heteroinduction by enzyme-inducing AEDs, but their metabolic rates remain considerably below those observed in matched controls. As a result of this, patients in old age will require lower CBZ dosages to achieve serum concentrations comparable with those found in nonelderly adults.