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The incidence of “Long COVID” syndrome appears to be increasing, particularly in the geriatric population. At present, there are few data regarding the relationship between long COVID and the risk of re-hospitalization in the oldest old survivors. Patients older than 80 years consecutively hospitalized for COVID-19 in our tertiary care hospital were enrolled and followed after discharge in a 12-month ambulatory program. A comprehensive geriatric assessment (CGA), including functional capabilities and physical and cognitive performances, was performed at 6-month follow-up. Frailty degree was assessed using a 30-item frailty index. The re-hospitalization rate was assessed at 12-month follow-up through a computerized archive and phone interviews. Out of 100 patients discharged after hospitalization for COVID-19 (mean [SD] age 85 [4.0] years), 24 reported serious adverse events requiring re-hospitalization within 12 months. The most frequent causes of re-hospitalization were acute heart failure (HF), pneumonia and bone fracture (15.3% each). By multivariate logistic analysis, after adjustment for potential confounders, history of chronic HF [aOR: 3.00 (CI 95%: 1.10–8.16), p = 0.031] or chronic renal failure [aOR: 3.83 (CI 95%: 1.09–13.43), p = 0.036], the burden of comorbidity [(CIRSc) aOR: 1.95 (CI 95%: 1.28–2.97), p = 0.002] and frailty [aOR: 7.77 (CI 95%: 2.13–28.27), p = 0.002] resulted as independent predictors of re-hospitalization. One-fourth of the oldest old patients previously hospitalized for COVID-19 suffered from adverse events requiring re-hospitalization, two-thirds of them within three months after discharge. Frailty, the burden of comorbidity, history of chronic HF or chronic renal failure, but not COVID-19 disease severity, independently predicted re-hospitalization.

Background. Cytokine dysregulation plays a critical role in COVID-19, and its timely recognition is pivotal for a favourable outcome, typically in the oldest patient. Lung ultrasound (LUS) has been proven to be an easy-to-perform, accurate tool for detecting COVID-19 pneumonia. The current study aimed to evaluate the relationship between inflammatory markers and pulmonary injury assessed by LUS in older patients with COVID-19. Methods. We consecutively evaluated older patients (age ≥ 65 years) hospitalized for COVID-19 pneumonia in our tertiary care hospital. All the patients underwent LUS, physical examination, and blood tests. LUS score for monitoring aeration, based on the number of B-lines for each scanned zone was assessed. Kendall’s Correlation was calculat-ed to verify the relationship between LUS and inflammation markers. A 7.5 mg/dl Hs-CRP cut-off was set to define the “hyper-inflammation” state. Finally, a receiver operating curve (ROC) was evaluated to define a cytokine storm – LUS-defined cut-off. Results. Overall, 65 older patients [mean (SD), 82.0 (6.9) years] were included in the analysis. LUS score was related inversely to PaO2/FiO2 ratio at admission (tau-0.29, p < 0.01) and nadir (tau-0.21, p < 0.01), and positively to Hs-CRP (tau 0.35, p < 0.001). An indexed LUS score higher than 0.8 was highly predictive of cytokine storm (AUROC 0.78, p < 0.001; Sensitivity 86%, Specificity 68%). Conclusions. Lung involvement evaluated by LUS correlates direct-ly with inflammatory markers and inversely with PaO2/ FiO2 ratio. LUS values qualified as an independent predictor of cytokine storm, and a score greater than 0.8 is the most predictive cut-off.

The aim of this single-center, open-label, randomized controlled study was to evaluate which formulation of vitamin D—between cholecalciferol and calcifediol—is most effective in the treatment of hypovitaminosis D in older adults. Demographic characteristics, clinical history, and comprehensive geriatric assessment were recorded at admission. Eligible patients were randomly assigned an equivalent vitamin D supplement, either with cholecalciferol or calcifediol, from the time of hospital admission to three months after discharge. Among the 140 older patients included (mean age 83 ± 6.6 years, 57.8% females), 69 received cholecalciferol and 71 received calcifediol. The mean plasma values of 25-hydroxyvitamin D3 (25OH-vitamin D3) found at the time of enrollment were 16.8 ± 9.9 ng/mL in patients receiving cholecalciferol and 18.8 ± 13.3 ng/mL in those treated with calcifediol (p = 0.31). At the three month follow-up, the mean concentration of 25OH-vitamin D3 was significantly higher in patients treated with calcifediol than in those receiving cholecalciferol (30.7 ± 8.4 vs. 45.4 ± 9.8 ng/mL, respectively; p < 0.001). Supplementation with either cholecalciferol or calcifediol effectively results in reaching the optimal circulating values of 25OH-vitamin D3 in older patients suffering from hypovitaminosis D. However, supplementation with calcifediol led to average circulating values of 25OH-vitamin D3 that were significantly higher (over 50%) than those obtained with cholecalciferol.

Corticosteroids have been widely used for acute respiratory distress syndrome (ARDS), but their role in the early phase of SARS-CoV-2 infection is controversial. Our study aimed to determine the effectiveness of early corticosteroid therapy (ECT) in preventing the progression of disease, reducing the escalation of care and improving clinical outcome in older patients hospitalized for COVID-19 pneumonia. A total of 90 subjects (47.7% women; mean age = 82.3 ± 6.7 years) were enrolled. ECT was administered to 33 out of 90 patients before the hospitalization. At admission, no difference was detected in median SOFA score (2, IQR:2 vs. 2, IQR: 2). We found a significant difference in mean PaO2 /FiO2 ratio during the first week of hospitalization between ECT patients and controls (F = 5.49, p = 0.002) and in mean PaO2 /FiO2 ratio over time (F = 6.94, p < 0.0001). We detected no-significant differences in terms of in-hospital mortality and transfer to ICU between ECT patients and controls (27.1% vs. 22.8%, respectively, p = 0.63). ECT was associated with worse clinical outcomes, showing no benefit in attenuating the progression of the disease or reducing the escalation of care. These findings are crucial given the current pandemic, and further studies are needed to provide additional data on the optimal timing of initiating corticosteroid treatment.

Background: Direct oral anticoagulants (DOACs) pharmacokinetics depends on estimated glomerular filtration rate (eGFR), whose estimation is crucial for optimal risk/benefit balance. Aims: To assess the concordance among different eGFR formulas and the potential impact on DOACs prescription appropriateness and bleeding risk in oldest hospitalized patients. Methods: Post hoc analysis of a single-centre prospective cohort study. eGFR was calculated by creatinine-based (MDRD, CKD-EPICr, BIS1) and creatinine–cystatin-C-based (CKD-EPIComb and BIS2) formulas. Patients were stratified according to eGFR [severely depressed (SD) 15–29; moderately depressed (MD) 30–49; preserved/mildly depressed (PMD): ≥ 50 ml/min/1.73 m2]. Concordance between the different equations was assessed by Cohen’s kappa coefficient. Results: Among AF patients, 841 (59.2% women, mean age 85.9 ± 6.5 years) received DOACs. By CKD-EPICr equation, 135 patients were allocated in the SD, 255 in the MD and 451 in the PMD group. The concordance was excellent only between BIS 2 and CKD-EPIComb and MDRD and CKD-EPICr, while was worse (from good to poor) between the other formulas. Indeed, by adding cystatin-C almost over 1/3 of the patients were reallocated to a worse eGFR class. Bleeding prevalence increased by 2–3% in patients with discordant eGFR between formulas, reallocated to a worse chronic kidney disease (CKD) stage, although without reaching statistical significance. CKD-EPIComb resulted the best predictor of bleeding events (AUROC 0.71, p = 0.03). Discussion: This study highlights the variability in CKD staging according to different eGFR formulas, potentially determining inappropriate DOACs dosing. Although the cystatin-C derived CKDEPIComb equation is the most accurate for stratifying patients, BIS1 may represent a reliable alternative.

Background: Various models have been proposed to predict frailty, including those based on clinical criteria and phenotypes. However, a simple biomarker associated with frailty has been not yet identified. The aim of this study is to evaluate the relationship between free triiodothyronine (fT3)/free thyroxine (fT4) ratio value and the degree of frailty among three different cohorts of older individuals: (1) acutely ill hospitalized patients, (2) nursing-home (NH) residents, and (3) home-dwelling centenarians.Methods: We performed a secondary analysis of de-identified patient-level data from two prospective observational studies on acutely hospitalized older patients (Geriatric Acute Unit [GAU]), and home-dwelling centenarians (CENT), and a retrospective-prospective observational study on older NH residents. Demographic characteristics, along with a 30-items Frailty Index (FI) and serum thyrotropin, fT3 and fT4 measurements were obtained.Results: Six hundred fifteen individuals (aged 86.4 +/- 8.9 years; 55.1% females) were included in the study, including 298 (48.5%) GAU, 250 (40.6%) NH, and 67 (10.9%) CENT. A significant inverse relationship between fT3/fT4 ratio and FI values was observed (rho(s) = -0.17 [confidence interval; CI: -0.092 to 0.252], p < 0.001), and this was confirmed by logistic multivariate analysis (beta = -0.44, odds ratio [OR]: 0.64 [CI: 0.47-0.87], p < 0.001) (after adjustment for age, sex, and cohorts). Moreover, a progressively decreased mortality risk was associated with rising fT3/fT4 ratio (OR 0.60 [CI: 0.44-0.80] beta = -0.51, p < 0.001].Conclusions: The fT3/fT4 ratio value was inversely correlated with frailty degree and mortality risk in a large cohort of older individuals, including centenarians, regardless of their sex and clinical condition. fT3/fT4 ratio value could represent an easily measured independent biochemical marker of frailty degree in older people.

Dementia affects about 47 million people worldwide, number expected to exponentially increase within 30 years. Alzheimer’s disease (AD) is the most common dementia type, accounting on its own for almost 70% of all dementia cases. Behavioral and psychological symptoms (BPSD) frequently occur during the disease progression; to treat agitation, aggressiveness, delusions and hallucinations, the use of antipsychotic drugs should be limited, due to their safety issues. In this literature review regarding the use of antipsychotics for treating BPSD in dementia, the advantages and limitation of antipsychotic drugs have been evaluated. The available medications for the management of behavioral and psychological symptoms are the antipsychotics, classed into typical and atypical, depending on their action on dopamine and serotonin receptors. First generation, or typical, antipsychotics exhibit lack of tolerability and display a broad range of side effects such as sedation, anticholinergic effects and extrapyramidal symptoms. Atypical, or second generation, antipsychotics bind more selectively to dopamine receptors and simultaneously block serotonin receptors, resulting in higher tolerability. High attention should be paid to the management of therapy interruption or switch between antipsychotics, to limit the possible rebound effect. Several switching strategies may be adopted, and clinicians should “tailor” therapies, accounting for patients’ symptoms, comorbidities, polytherapies and frailty.

Clinical and prognostic differences between symptomatic and asymptomatic older patients with COVID-19 are of great interest since frail patients often show atypical presentation of illness. Lung Ultrasound (LUS) has been proven to be a reliable tool for detecting early-phase COVID-19 pneumonic alterations. The current prospective bicentric study aimed to compare LUS score and 3-month overall mortality between asymptomatic and symptomatic older patients with COVID-19, according to frailty status. Patients were stratified according to LUS score tertiles and Clinical Frailty Scale categories. Survival rate was assessed by telephone interviews 3 months after discharge. 64 symptomatic (24 women, aged 80.0 ± 10.8 years) and 46 asymptomatic (31 women, aged 84.3 ± 8.8 years) were consecutively enrolled. LUS score resulted an independent predictor of 3-month mortality [OR 2.27 (CI95% 1.09–4.8), p = 0.03], and the highest mortality rate was observed in symptomatic and asymptomatic pre-frail and frail patients (70.6% and 66.7%, respectively) with greater LUS abnormalities (3rd tertile). In conclusion, LUS identified an acute interstitial lung involvement in most of the older asymptomatic patients. Mortality rate progressively increased according to clinical frailty and LUS score degree, resulting a reliable prognostic tool in both symptomatic and asymptomatic patients.

Objective. Dabigatran, a direct inhibitor of thrombin, represents an effective alternative to warfarin. Despite the good tolerance and predictable pharmacokinetic profile, dabigatran may be associated to adverse reactions, including gastrointestinal disorders. Here we report on a case of hepatotoxicity along with an extensive revision of the available literature on dabigatran induced liver injury Methods & results. An 84 years old man attended the Emergency Department after experiencing fatigue for a few days. He suffered from atrial fibrillation and had been initiated on dabigatran (110 mg bid) in the last four weeks. Clinical examination revealed tachycardia, scleral icterus in the absence of signs of chronic hepatic disease. Blood chemistry showed altered liver function tests: AST 809 IU/L, ALT 1629 IU/L, total bilirubin 2.42 mg/dL, gGT 381 IU/L, ALP 388 IU/L, LDH 552 IU/L. Screening laboratory investigations for infectious, autoimmune or metabolic hepatotoxic pathology were unremarkable. The abdominal ultrasound examination excluded vascular causes, revealing non-homogeneous echo-structure consistent with mild hepatic steatosis. At admission to our Geriatric ward dabigatran was discontinued and fondaparinux was introduced. Resolution of the hepatitis and normalization of blood chemistry was observed within two weeks. Few cases are described regarding hepatotoxicity likely caused by the recent onset of treatment with dabigatran. Conclusions. DOACs associated hepatotoxicity is rare but potentially harmful and should be kept in mind, especially in comorbid patients with unexplained liver injury. The mechanism of liver injury during dabigatran therapy is unknown and, not related to cytochrome P450 enzymes since the drug does not affect CYP450 activity.

Background: In late December 2019, a cluster of pneumonia cases due to a novel betacoronavirus, SARS-CoV-2 was reported in China. The so-called COVID 19 is responsible not only for respiratory symptoms, from mild up to pneumonia and even acute respiratory distress syndrome, but also for extrapulmonary involvement. Cases presentation: Here we present two cases of spontaneous muscle hematoma in patients with SARS-CoV-2 infection, both on therapeutic LMWH for atrial fibrillation: the first one was an 86-year-old Caucasian female with a history of hypertensive cardiomyopathy and the second one was an 81-year-old Caucasian male with a history of hypertension, diabetes and ischemic heart disease. Blood tests revealed a considerable drop of hemoglobin and alterations of coagulation system. In both cases, embolization of femoral artery was performed. A few other cases of bleeding manifestations are reported in literature, while a lot has been published about the hypercoagulability related to COVID-19. Conclusions: Our reports and literature review highlight the need of active surveillance for possible hemorrhagic complications in patients with SARS-CoV-2 infection.

Type two diabetes mellitus (T2DM) represents a chronic condition with increasing prevalence worldwide among the older population. The T2DM condition increases the risk of micro and macrovascular complications as well as the risk of geriatric syndromes such as falls, fractures and cognitive impairment. The management of T2DM in the older population represents a challenge for the clinician, and a Comprehensive Geriatric Assessment should always be prioritized, in order to tailor the glycated hemoglobin target according to functional and cognitive status comorbidities, life expectancy and type of therapy. According to the most recent guidelines, older adults with T2DM should be categorized into three groups: healthy patients with good functional status, patients with complications and reduced functionality and patients at the end of life; for each group the target for glycemic control is different, also according to the type of treatment drug. The therapeutic approach should always begin with lifestyle changes; after that, several lines of therapy are available, with different mechanisms of action and potential effects other than glucose level reduction. Particular interest is growing in sodium-glucose cotransporter-2 inhibitors, due to their effect on the cardiovascular system. In this review, we evaluate the therapeutic options available for the treatment of older diabetic patients, to ensure a correct treatment approach.