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BackgroundOnce the pandemic ended, SARS-CoV-2 became endemic, with flare-up phases. COVID-19 disease can still have a significant clinical impact, especially in older patients with multimorbidity and frailty.ObjectiveThis study aims at evaluating the main characteristics associated to in-hospital mortality among data routinely collected upon admission to identify older patients at higher risk of death.MethodsThe present study used data from Gerocovid-acute wards, an observational multicenter retrospective-prospective study conducted in geriatric and internal medicine wards in subjects ≥60 years old during the COVID-19 pandemic. Seventy-one routinely collected variables, including demographic data, living arrangements, smoking habits, pre-COVID-19 mobility, chronic diseases, and clinical and laboratory parameters were integrated into a web-based machine learning platform (Just Add Data Bio) to identify factors with the highest prognostic relevance. The use of artificial intelligence allowed us to avoid variable selection bias, to test a large number of models and to perform an internal validation.ResultsThe dataset was split into training and test sets, based on a 70:30 ratio and matching on age, sex, and proportion of events; 3,520 models were set out to train. The three predictive algorithms (optimized for performance, interpretability, or aggressive feature selection) converged on the same model, including 12 variables: pre-COVID-19 mobility, World Health Organization disease severity, age, heart rate, arterial blood gases bicarbonate and oxygen saturation, serum potassium, systolic blood pressure, blood glucose, aspartate aminotransferase, PaO2/FiO2 ratio and derived neutrophil-to-lymphocyte ratio.ConclusionBeyond variables reflecting the severity of COVID-19 disease failure, pre-morbid mobility level was the strongest factor associated with in-hospital mortality reflecting the importance of functional status as a synthetic measure of health in older adults, while the association between derived neutrophil-to-lymphocyte ratio and mortality, confirms the fundamental role played by neutrophils in SARS-CoV-2 disease.

(1) Background: Subclinical hypothyroidism (SHT) is a condition that has been a subject of controversy in the literature due to its association with psychological and psychiatric symptoms as well as autonomic imbalances. To gain a better understanding of the effects of SHT on patients, a research study has been undertaken to investigate the presence of psychological symptoms and autonomic imbalances in a group of individuals diagnosed with SHT. (2) Methods: In this case–control study, 50 patients diagnosed with SHT who accessed the Department of Endocrinology of the University of Pisa were consecutively recruited. Psychological symptoms were measured through the Crown–Crisp Experiential Index (CCEI), whereas autonomic imbalance was described using the Psychophysiological Stress Profile (PSP), with simultaneous recording of the following psychophysiological parameters: Surface Electromyogram (sEMG), Skin Conductance Level (SCL), heart rate (HR), and peripheral temperature (PT). The patients’ values were compared to those of 50 healthy control subjects. (3) Results: The comparison between groups highlighted significant differences in the CCEI and PSP. In particular, patients reported higher rates of psychological symptoms (anxiety, depression, somatic complaints, and hysteria behavior). Significantly higher levels of autonomic arousal were also recorded. More specifically, the sEMG, SCL, HR, and PT values were different between the two groups. (4) Conclusions: The study has confirmed the presence of autonomic hyperarousal in patients diagnosed with subclinical hypothyroidism. This is likely due to the body’s attempt to compensate for a general lack of energy by accelerating the autonomic activity. The findings also underline the significance of a comprehensive assessment approach that takes into account various dimensions such as psychological and psychophysical well-being. Such an approach helps in evaluating the impact of subclinical diseases on overall health and well-being.

Objective: Chloroquine (CQ) and hydroxychloroquine (HCQ) were used as off-label treatments for SARS-CoV-2 infection during the first pandemic waves. The urgency of combatting COVID-19 led to the dissemination of medical recommendations with a scarce awareness of possible drug–drug interactions. This issue primarily concerned people already taking multiple medications, such as older individuals. We estimated the prevalence of drug interactions with CQ or HCQ in COVID-19 inpatients during the first pandemic waves and their possible association with hospitalization-related outcomes. Methods: This study considers 487 patients aged ≥60, hospitalized for COVID-19 from March to December 2020, and treated with CQ or HCQ. Data on acute and chronic therapies and hospitalization length and outcomes were derived from medical records. The presence of drugs potentially interacting with CQ and HCQ was identified based on published literature and drug databases. Results: In our sample (mean age 77.1 years, 47.8% females), 255 (52.4%) patients presented with one drug interaction with CQ or HCQ, and 114 (23.4%) had more than two interactions. The most frequent drugs potentially interacting with CQ or HCQ were lopinavir/ritonavir (50.4%), azithromycin (47.2%), tocilizumab (15.4%), levofloxacin (8.7%), clarithromycin (6.0%), amlodipine (3.3%), and trazodone (2.4%). No substantial differences in the duration and outcomes of the hospitalization emerged as a function of the presence of drug–drug interactions. Conclusions: Many older patients prescribed with CQ or HCQ, which have lately proved ineffective against COVID-19, were exposed to the risk of drug–drug interaction. This underlines that medical recommendations should undergo careful peer review before being widely disseminated, even in emergencies like a pandemic.

BackgroundNumerous individual and organizational factors can influence the spread of SARS-CoV-2 infection in Long Term Care Facilities (LTCFs). A range of outbreak control measures are still implemented in most facilities involving administrations, staff, residents and their families. This study aims to evaluate which measure could influence the transmission of SARS-CoV-2 infection among residents during the period March 2021-June 2022.MethodsWe enrolled 3,272 residents aged ≥60 years. The outbreak control measures adopted to prevent or manage the infection included entry regulations, contact-regulating procedures, and virological surveillance of residents and staff. The association between LTCFs' and participants' characteristics with new cases of COVID-19 infections was analyzed using multilevel logistic regression models.ResultsIn 33.8% of the facilities 261 cases of SARS-CoV-2 infection were reported. Among participant characteristics, gender and age were not associated with SARS-CoV-2 infection, while having received the vaccine booster dose was protective against infection [Odds Ratio (OR) = 0.34, 95% Confidence Interval (CI) 0.12–0.99, p = 0.048]. In addition, the implementation of protected areas for family visits was associated with a significant reduction of the probability of infections (OR = 0.18, 95% CI 0.03–0.98, p = 0.047). Overall, about 66% of the variability in the probability of SARS-CoV-2 infection during the observational period may be due to facility structure characteristics and 34% to the participant characteristics.ConclusionsThese data showed that vaccination booster doses and family visit restriction-control are still needed to make the LTCFs safer against SARS-CoV-2 infection.

Sarcopenia is an age-related clinical complaint characterized by the progressive deterioration of skeletal muscle mass and strength over time. Type 2 diabetes (T2D) is associated with faster and more relevant skeletal muscle impairment. Both conditions influence each other, leading to negative consequences on glycemic control, cardiovascular risk, general health status, risk of falls, frailty, overall quality of life, and mortality. PubMed/Medline, Scopus, Web of Science, and Google Scholar were searched for research articles, scientific reports, observational studies, clinical trials, narrative and systematic reviews, and meta-analyses to review the evidence on the pathophysiology of di-abetes-induced sarcopenia, its relevance in terms of glucose control and diabetes-related outcomes, and diagnostic and therapeutic challenges. The review comprehensively addresses key elements for the clinical definition and diagnostic criteria of sarcopenia, the pathophysiological correlation be-tween T2D, sarcopenia, and related outcomes, a critical review of the role of antihyperglycemic treatment on skeletal muscle health, and perspectives on the role of specific treatment targeting myokine signaling pathways involved in glucose control and the regulation of skeletal muscle metabolism and trophism. Prompt diagnosis and adequate management, including lifestyle inter-vention, health diet programs, micronutrient supplementation, physical exercise, and pharmaco-logical treatment, are needed to prevent or delay skeletal muscle deterioration in T2D.

Abstract Background In older and multimorbid patients, chronic conditions may affect the prognostic validity of computed tomography (CT) findings in COVID-19. This study aims at assessing to which extent CT findings have prognostic implications in COVID-19 older patients. Methods Hospitalized COVID-19 patients aged 60 years or more enrolled in the multicenter, observational and longitudinal GeroCovid study who underwent chest CT were included. Patients were stratified by tertiles of age and pneumonia severity to compare CT findings. Hierarchical clustering based on CT findings was performed to identify CT-related classificatory constructs, if any. The hazard ratio (HR) of mortality was calculated for individual CT findings and for clusters, after adjusting for potential confounders. Results 380 hospitalized COVID-19 patients, with a mean age of 78 (SD:9) years, underwent chest CT scan. Ground glass opacity (GGO), consolidation, and pleural effusion were the three most common CT findings, with GGO prevalence decreasing from younger to older patients and pleural effusion increasing. More severe the pneumonia more prevalent were GGO, consolidation and pleural effusion. HR of mortality was 1.94 (95%CI 1.24–3.06) for pleural effusion and 13 (95%CI 6.41–27) for cluster with a low prevalence of GGO and a high prevalence of pleural effusion (“LH”), respectively. Out of the three CT based clusters, “LH” was the only independent predictor in the multivariable model. Conclusions Pleural effusion qualifies as a distinctive prognostic marker in older COVID-19 patients. Research is needed to verify whether pleural effusion reflects COVID-19 severity or a coexisting chronic condition making the patient at special risk of death. Trial registration ClinicalTrials.gov: NCT04379440

Abstract Acute left colonic diverticulitis (ALCD) in the elderly presents with unique epidemiological features when compared with younger patients. The clinical presentation is more nuanced in the elderly population, having higher in-hospital and postoperative mortality. Furthermore, geriatric comorbidities are a risk factor for complicated diverticulitis. Finally, elderly patients have a lower risk of recurrent episodes and, in case of recurrence, a lower probability of requiring urgent surgery than younger patients. The aim of the present work is to study age-related factors that may support a unique approach to the diagnosis and treatment of this problem in the elderly when compared with the WSES guidelines for the management of acute left-sided colonic diverticulitis. During the 1° Pisa Workshop of Acute Care & Trauma Surgery held in Pisa (Italy) in September 2019, with the collaboration of the World Society of Emergency Surgery (WSES), the Italian Society of Geriatric Surgery (SICG), the Italian Hospital Surgeons Association (ACOI), the Italian Emergency Surgery and Trauma Association (SICUT), the Academy of Emergency Medicine and Care (AcEMC) and the Italian Society of Surgical Pathophysiology (SIFIPAC), three panel members presented a number of statements developed for each of the four themes regarding the diagnosis and management of ALCD in older patients, formulated according to the GRADE approach, at a Consensus Conference where a panel of experts participated. The statements were subsequently debated, revised, and finally approved by the Consensus Conference attendees. The current paper is a summary report of the definitive guidelines statements on each of the following topics: diagnosis, management, surgical technique and antibiotic therapy.

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.

Abstract 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.

Abstract High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO2. Changes of hsTnT, D-dimer and CRP were related; but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals.

Abstract 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.

BackgroundHypovitaminosis D has been suggested to play a possible role in coronavirus disease 2019 (COVID-19) infection.MethodsThe aim of this study is to analyze the relationship between vitamin D status and a biochemical panel of inflammatory markers in a cohort of patients with COVID-19. A secondary endpoint was to evaluate the correlation between 25OHD levels and the severity of the disease. Ninety-three consecutive patients with COVID-19-related pneumonia were evaluated from March to May 2020 in two hospital units in Pisa, in whom biochemical inflammatory markers, 25OHD levels, P/F ratio at nadir during hospitalization, and complete clinical data were available.ResultsSixty-five percent of patients presented hypovitaminosis D (25OHD ≤ 20 ng/ml) and showed significantly higher IL-6 [20.8 (10.9–45.6) vs. 12.9 (8.7–21.1) pg/ml, p = 0.02], CRP [10.7 (4.2–19.2) vs. 5.9 (1.6–8.1) mg/dl, p = 0.003], TNF-α [8.9 (6.0–14.8) vs. 4.4 (1.5–10.6) pg/ml, p = 0.01], D-dimer [0.53 (0.25–0.72) vs. 0.22 (0.17–0.35) mg/l, p = 0.002], and IL-10 [3.7 (1.8–6.9) vs. 2.3 (0.5–5.8) pg/ml, p = 0.03]. A significant inverse correlation was found between 25OHD and all these markers, even adjusted for age and sex. Hypovitaminosis D was prevalent in patients with severe ARDS, compared with the other groups (75% vs. 68% vs. 55%, p < 0.001), and 25OHD levels were lower in non-survivor patients.ConclusionsThe relationship between 25OHD levels and inflammatory markers suggests that vitamin D status needs to be taken into account in the management of these patients. If vitamin D is a marker of poor prognosis or a possible risk factor with beneficial effects from supplementation, this still needs to be elucidated.

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.

BackgroundPrevious studies have shown increased risk of fracture in older patients with poor or strict glycemic control (glycated hemoglobin, HbA1c, ≥ 8% or < 6-7% respectively); however, these reports did not investigate the oldest-old population. Comprehensive geriatric assessment (CGA) and a patient-centered approach have been proven to improve the quality of care in the management of Type 2 Diabetes Mellitus (T2DM) in the older patients, but data regarding T2DM in patients with fragility fractures are still lacking.AimTo investigate the prognostic role of HbA1c and frailty level in older diabetic patients admitted for hip fracture.MethodsProspective observational cohort study conducted on diabetic geriatric patients consecutively hospitalized for hip fracture in the orthogeriatric unit of a tertiary care hospital. Preoperative comprehensive geriatric assessment (CGA) was performed. Using the Clinical Frailty Scale (CFS), diabetic patients were categorized in robust (CFS < 5) and frail (CFS ≥ 5), and further stratified according to HbA1c values [Tertile 1 (T1) HbA1c < 48 mmol/mol, Tertile 2 (T2) 48-58 mmol/mol and Tertile 3 (T3) > 58 mmol/mol). Comparisons between continuous variables were performed with analysis of non-parametric test for independent samples, while relationships between categorical variables were assessed by chi-square test. Using logistic multivariate regression, we evaluated the determinants of 1-year all-cause mortality in diabetic older patients with hip fracture.ResultsAmong the 1319 older patients (mean age 82.8 ± 7.5 years, 75.9% females) hospitalized for hip fracture, 204 (15.5%) had a previous diagnosis of T2DM. T2DM patients showed an increased proportion of multiple concurrent fractures occurred during the accidental fall or syncope (12.7% vs 11.2%, p=0.02). One-year mortality after hip fracture surgery was significantly higher in T2DM as compared to not diabetic patients (21.2% vs 12.5%, p

Objectives: The spread of COVID-19 has undeniably unsettled the social, psychological and emotional life of the entire world population. Particular attention should be paid to older adults with dementia, given their vulnerability to emotional stressors. The aim of this retrospective study is to evaluate the impact of the first wave quarantine related to Covid-19 on psychological and affective well-being of older adults with mild/major neurocognitive disorders and of their caregivers.Methods: Data on participants' assessment before the quarantine (PREQ) were retrospectively collected. Patients with Mild Cognitive Impairment (MCI) or dementia were recruited from different Centers for Cognitive Decline and Dementia in Italy. During the quarantine, psychological and affective well-being were evaluated by phone through the administrations of scales measuring anxiety and depression (DASS), perceived stress (PSS), coping strategies (COPE) and the caregivers' burden (CBI). The scales' results were compared across participants' PREQ cognitive level (Mini Mental State Examination, MMSE ≥25, 23–24, and ≤ 22) with multiple linear regression models.Results: The sample included 168 patients (64% women) with a mean age of 79 ± 7 years. After adjusting for potential confounders, more severe cognitive impairment was independently associated with higher DASS and PSS score, and poorer coping strategies (p < 0.05). Cognitive functioning was also inversely associated with CBI.Conclusions: The impact of the quarantine on the psycho-affective well-being of individuals with MCI and dementia and on caregivers' burden varies according to the PREQ cognitive functioning with more severely impaired patients having worse outcomes.

Background: Long-term care facility (LTCF) residents often present asymptomatic or paucisymptomatic features of SARS-CoV-2 infection. We aimed at investigating signs/symptoms, including their clustering on SARS-CoV-2 infection and mortality rates associated with SARS-CoV-2 infection in LTCF residents. Methods: This is a cohort study of 586 aged ≥ 60 year-old residents at risk of or affected with COVID-19 enrolled in the GeroCovid LTCF network. COVID-19 signs/symptom clusters were identified using cluster analysis. Cluster analyses associated with SARS-CoV-2 infection and mortality were evaluated using logistic regression and Cox proportional hazard models. Results: Cluster 1 symptoms (delirium, fever, low-grade fever, diarrhea, anorexia, cough, increased respiratory rate, sudden deterioration in health conditions, dyspnea, oxygen saturation, and weakness) affected 39.6% of residents and were associated with PCR swab positivity (OR = 7.21, 95%CI 4.78–10.80; p < 0.001). Cluster 1 symptoms were present in deceased COVID-19 residents. Cluster 2 (increased blood pressure, sphincter incontinence) and cluster 3 (new-onset cognitive impairment) affected 20% and 19.8% of residents, respectively. Cluster 3 symptoms were associated with increased mortality (HR = 5.41, 95%CI 1.56–18.8; p = 0.008), while those of Cluster 2 were not associated with mortality (HR = 0.82, 95%CI 0.26–2.56; p = 730). Conclusions: Our study highlights that delirium, fever, and low-grade fever, alone or in clusters should be considered in identifying and predicting the prognosis of SARS-CoV-2 infection in older LTCF patients.

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.

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.

According to the World Alzheimer’s report, dementia was estimated to affect 50 million worldwide in 2018, number expected to increase to more than 150 million within 30 years. Alzheimer’s disease is the most common type of dementia, accounting on its own for 2/3 of all dementia cases. The initial signs and symptoms of Alzheimer’s disease relate to progressive cognitive decline, inexorably progressing until the loss of independence. Neuropsychiatric and behavioral symptoms may occur during the progression of the disease; around 20% of patients without any behavioral symptoms at the diagnosis will experience some of them within 2 years. Consequences are early institutionalization, lower quality of life, of both patients and carers, and more severe cognitive impairment. Treatment options for behavioral symptoms include pharmacological and non-pharmacological approaches. The latter are usually preferred, since antipsychotic therapy is not free from several, and often serious, adverse events. However, behavioral symptoms are not always controllable with non-pharmacological intervention. The psychotropic class of medication more frequently prescribed for behavioral symptoms are atypical antipsychotics; among them, risperidone is the only one licensed for the treatment of aggression, in Europe but not in the USA. On that regard, the use of antipsychotic drugs should be limited, due to the increased risk of mortality, stroke, hallucination, and higher risk of relapse after discontinuation. Some new agents are under evaluation, such as pimavanserin and lumateperone. In this review, we are evaluating the current available pharmacological options to treat behavioral symptoms as well as the forthcoming new agents.

Hypothyroidism is characterized by increased thyrotropin (TSH) levels and reduced free thyroid hormone fractions while, subclinical hypothyroidism (sHT) by elevated serum TSH in the face of normal thyroid hormones. The high frequency of hypothyroidism among the general population in Western Countries made levothyroxine (LT4) one of the 10 most prescribed drugs. However, circulating TSH has been demonstrated to increase with aging, regardless the existence of an actual thyroid disease. Thus, when confronting an increase in circulating TSH levels in the elderly, especially in the oldest old, it is important to carry an appropriate diagnostic path, comprehensive of clinical picture as well as laboratory and imaging techniques. In the current review, we summarize the recommendations for a correct diagnostic workup and therapeutic approach to older people with elevated TSH value, with special attention to the presence of frailty, comorbidities, and poly-therapy. The treatment of choice for hypothyroid patients is hormone replacement with LT4 but, it is important to consider multiple factors before commencing the therapy, from the age dependent TSH increase to the presence of an actual thyroid disease and comorbidities. When treatment is necessary, a tailored therapy should be chosen, considering poly-pharmacy and frailty. A careful follow-up and treatment re-assessment should be always considered to avoid the risk of over-treatment. It is important to stress the need of educating the patient for a correct administration of LT4, particularly when poly-therapy is in place, and the importance of a tailored therapeutic approach and follow-up, to avoid overtreatment.

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.

Endocrine disruptor compounds are exogenous agents able to interfere with a gland function, exerting their action across different functional passages, from the synthesis to the metabolism and binding to receptors of the hormone produced. Several issues, such as different levels and time of exposure and different action across different ages as well as gender, make the study of endocrine disruptors still a challenge. The thyroid is very sensitive to the action of disruptors, and considering the importance of a correct thyroid function for physical and cognitive functioning, addressing this topic should be considered a priority. In this review, we examined the most recent studies, many of them concentrating on maternal and child exposure, conducted to assess the impact of industrial chemicals which showed an influence on thyroid function. So far, the number of studies conducted on that topic is not sufficient to provide solid conclusions and lead to homogeneous guidelines. The lack of uniformity is certainly due to differences in areas and populations examined, the different conditions of exposures and the remarkable inter-subject variability. Nonetheless, the European Commission for Health and Food Safety is implementing recommendations to ensure that substances identified as endocrine disruptors will be withdrawn from the market.

Francesco Manfredonia1, Livia Pasquali1, Angela Dardano2, Alfonso Iudice1, Luigi Murri1, Fabio Monzani21Department of Neuroscience and 2Department of Internal Medicine, University of Pisa, Pisa, ItalyAbstract: Interferon (INF) β 1a 22 or 44 µg (Rebif®) administered s.c. 3 times a week (t.i.w) is a well established immunomodulating treatment for relapsing remitting multiple sclerosis (RRMS). This review focuses on its mechanisms of action, evidence of efficacy, safety, and tolerability. Several pharmacodynamic properties explain the immunomodulatory actions of INF β 1a 22 or 44 µg s.c. t.i.w. Pivotal trials and post-marketing studies proved that the drug is effective in reducing disease activity and likely in slowing disease progression. Head-to-head comparative studies with other marketed INFs β in RRMS suggested a better therapeutic response associated with higher doses and frequency of administration of Rebif®. Additional evidence indicated a beneficial effect of INF β 1a in patients with clinically isolated syndromes (CIS) suggestive of MS, as treatment reduced time to conversion to clinically definite (CD) disease. Further, although the drug did not prove to slow time to progression there were benefits on relapse- and MRI-related secondary outcome measures in secondary progressive (SP) MS. Pivotal trials, their cross-over extensions, and post-marketing studies consistently showed that INF β 1a 22 or 44 µg s.c. t.i.w. is safe and well tolerated, as adverse drug reactions are usually mild and manageable.Keywords: interferon β 1a, multiple sclerosis, review, clinical trials, post-marketing studies