Different glomerular filtration rate estimating formula for prescribing DOACs in oldest patients: appropriate dosage and bleeding risk. Post hoc analysis of a prospective cohort.

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.

SPR-Based Detection of ASF Virus in Cells.

African swine fever (ASF) is one of the most dangerous hemorrhagic infectious diseases that affect domestic and wild pigs. Currently, neither a vaccine nor effective treatments are available for this disease. As regards the degree of virulence, ASFV strains can be divided into high, moderate, or low virulence. The main detection methods are based on the use of the polymerase chain reaction (PCR). In order to prevent an uncontrolled spread of ASF, new on-site techniques that can enable the identification of an early-stage disease are needed. We have developed a specific immunological SPR-based assay for ASFV antigen detection directly in liquid samples. The developed assay allows us to detect the presence of ASFV at the dose of 103 HAD50/mL.

The Porcine Odorant-Binding Protein as a Probe for an Impedenziometric-Based Detection of Benzene in the Environment.

Odorant-binding proteins (OBPs) are a group of small and soluble proteins present in both vertebrates and insects. They have a high level of structural stability and bind to a large spectrum of odorant molecules. In the environmental field, benzene is the most dangerous compound among the class of pollutants named BTEX (benzene, toluene, ethylbenzene, and xylene). It has several effects on human health and, consequently, it appears to be important to monitor its presence in the environment. Commonly, its detection requires the use of very sophisticated and time-consuming analytical techniques (GC-MS, etc.) as well as the presence of specialized personnel. Here, we present the application of an odorant-binding protein (pOBP) isolated from pigs as a molecular recognition element (MRE) for a low-energy impedenziometric biosensor for outdoor and real-time benzene detection. The obtained results show that the biosensor can detect the presence of 64 pM (5 µg/m3) benzene, the limit value of exposure for human health set by the European Directive 2008/50/EC.

Emergent Biosensing Technologies Based on Fluorescence Spectroscopy and Surface Plasmon Resonance.

The purpose of this work is to provide an exhaustive overview of the emerging biosensor technologies for the detection of analytes of interest for food, environment, security, and health. Over the years, biosensors have acquired increasing importance in a wide range of applications due to synergistic studies of various scientific disciplines, determining their great commercial potential and revealing how nanotechnology and biotechnology can be strictly connected. In the present scenario, biosensors have increased their detection limit and sensitivity unthinkable until a few years ago. The most widely used biosensors are optical-based devices such as surface plasmon resonance (SPR)-based biosensors and fluorescence-based biosensors. Here, we will review them by highlighting how the progress in their design and development could impact our daily life.

Spontaneous muscle hematoma in older patients with COVID-19: two case reports and literature review.

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.

Determinants of 1-Year Adverse Event Requiring Re-Hospitalization in COVID-19 Oldest Old Survivors.

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.

An Impedimetric Biosensor for Detection of Volatile Organic Compounds in Food.

The demand for a wide choice of food that is safe and palatable increases every day. Consumers do not accept off-flavors that have atypical odors resulting from internal deterioration or contamination by substances alien to the food. Odor response depends on the volatile organic compounds (VOCs), and their detection can provide information about food quality. Gas chromatography/mass spectrometry is the most powerful method available for the detection of VOC. However, it is laborious, costly, and requires the presence of a trained operator. To develop a faster analytic tool, we designed a non-Faradaic impedimetric biosensor for monitoring the presence of VOCs involved in food spoilage. The biosensor is based on the use of the pig odorant-binding protein (pOBP) as the molecular recognition element. We evaluated the affinity of pOBP for three different volatile organic compounds (1-octen-3-ol, trans-2-hexen-1-ol, and hexanal) related to food spoilage. We developed an electrochemical biosensor conducting impedimetric measurements in liquid and air samples. The impedance changes allowed us to detect each VOC sample at a minimum concentration of 0.1 µM.

An Impedance-Based Immunosensor for the Detection of Ovalbumin in White Wine.

Food allergies are an exceptional response of the immune system caused by the ingestion of specific foods. The main foods responsible for allergic reactions are milk, eggs, seafood, soy, peanuts, tree nuts, wheat, and their derived products. Chicken egg ovalbumin (OVA), a common allergen molecule, is often used for the clarification process of wine. Traces of OVA remain in the wine during the fining process, and they can cause significant allergic reactions in sensitive consumers. Consequently, the European Food Safety Authority (EFSA) and the American Food and Drug Administration (FDA) have shown the risks for allergic people to assume allergenic foods and food ingredients, including eggs. Commonly, OVA detection requires sophisticated and time-consuming analytical techniques. Intending to develop a faster assay, we designed a proof-of-concept non-Faradaic impedimetric immunosensor for monitoring the presence of OVA in wine. Polyclonal antibodies anti-OVA were covalently immobilised onto an 11-mercaptoundecanoic-acid (11-MUA)-modified gold surface. The developed immunosensor was able to detect OVA in diluted white wine without the need for an external probe or any pre-treatment step with a sensitivity of 0.20 µg/mL, complying with the limit established by the resolution OIV/COMEX 502-2012 for the quantification of allergens in wine.

A Randomized, Open-Label Study to Assess Efficacy of Weekly Assumption of Cholecalciferol versus Calcifediol in Older Patients with Hypovitaminosis D.

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.

Determinants of Cause-Specific Mortality and Loss of Independence in Older Patients following Hospitalization for COVID-19: The GeroCovid Outcomes Study.

Hospitalization for acute SARS-CoV-2 infection confers an almost five-fold higher risk of post-discharge, all-cause mortality compared to controls from the general population. A negative impact on the functional autonomy of older patients, especially in cases of severe disease and prolonged hospitalization, has been recently described. However, little is known about the determinants of cause-specific mortality and loss of independence (LOI) in the activities of daily living (ADL) following COVID-19 hospitalization. Thus, the current prospective, multicenter study is aimed at identifying the determinants of post-discharge cause-specific mortality and the loss of autonomy in at least one ADL function. Older patients hospitalized for a SARS-CoV-2 infection were consecutively enrolled in an e-Registry from 1 March 2020, until 31 December 2020. After at least six months from discharge, patients were extensively re-evaluated according to a common protocol at the outpatient clinic of eight tertiary care Italian hospitals. Of 193 patients [109 (56.4%) men, mean age 79.9 ± 9.1 years], 43 (22.3%) died during follow-up. The most common causes of death were cardiovascular diseases (46.0%), respiratory failure (26.5%), and gastrointestinal and genitourinary diseases (8.8% each). Pre-morbid ADLs qualified as an independent mortality risk factor [adjusted HR 0.77 (95%CI: 0.63-0.95)]. Of 132 patients, 28 (21.2%) lost their independence in at least one ADL. The adjusted risk of LOI declined with a lower frailty degree [aOR 0.03 (95%CI: 0.01-0.32)]. In conclusion, at long-term follow-up after hospitalization for acute SARS-CoV-2 infection, more than 40% of older patients died or experienced a loss of functional independence compared to their pre-morbid condition. Given its high prevalence, the loss of functional independence after hospitalization for COVID-19 could be reasonably included among the features of the "Long COVID-19 syndrome" of older patients.

Pitfalls of Early Systemic Corticosteroids Home Therapy in Older Patients with COVID-19 Pneumonia.

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.

Long-term effectiveness and safety of anticoagulation therapy in oldest old, frail people with atrial fibrillation.

BACKGROUND: Atrial Fibrillation (AF) represents a major cause of mortality and morbidity in older people; however, oldest-old frail patients are usually excluded from clinical trials. Aim of the study is to evaluate the impact of oral anticoagulation (OAC) therapy on long-term overall survival and clinically relevant bleedings in a large cohort of hospitalised frail, oldest-old patients with AF. PATIENTS AND METHODS: Prospective, observational, cohort study, evaluating patients consecutively hospitalized for acute illnesses in our Geriatrics Unit (January 2013-July 2017). Participants were divided in two groups, AF and sinus rhythm (SR). Besides recording demographic characteristics and clinical history, comprehensive geriatric assessment (CGA) was obtained. RESULTS: AF patients [1808/5093 (35.5%), 58.5% women] were older, with higher burden of comorbidity than those with SR. At discharge, HAS-BLED [OR 0.77 (95%CI 0.67-0.90), cognitive impairment [OR 0.92 (95%CI 0.90-0.95)], malnutrition [OR 0.74 (95%CI 0.57-0.97)] and CHA2DS2VASc [OR 1.33 (95%CI 1.20-1.47)] emerged as significant independent predictors of anticoagulant prescription. AF patients showed significantly reduced overall survival (OS) than those with SR (11.4 vs 19.4 months, p<.001). However, anticoagulated AF patients (75.2%) had three-times longer OS than those not anticoagulated (15.0 vs 5.6 months, p<.001), comparable to SR patients after adjustment for potential confounders [HR 1.04 (95%CI 0.99-1.10)]. ED readmittance risk for clinically relevant bleeding did not differ between AF patients receiving or not anticoagulation [HR 1.04 (95%CI 0.76-1.14)] CONCLUSION: anticoagulation therapy was associated with significant increase of long-term OS without increased risk of clinically relevant bleeding. CGA resulted an useful tool in OAC therapy decision-making.

Usefulness of lung ultrasound for selecting asymptomatic older patients with COVID 19 pneumonia.

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.

Prognostic Value of Glycated Hemoglobin in Frail Older Diabetic Patients With Hip Fracture.

Background: Previous 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. Aim: To investigate the prognostic role of HbA1c and frailty level in older diabetic patients admitted for hip fracture. Methods: Prospective 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. Results: Among 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<0.001). No significant difference in mortality was found across HbA1c tertiles; however, frail diabetic patients in the second and third HbA1c tertiles showed higher mortality risk compared to the robust counterparts (26.9% vs 5%, p=0.001 for T2 and 43.5% vs 13.3%, p=<0.05 for T3), while no difference was observed among those in T1. Conclusions: Frail patients with HbA1c ≥ 48 mmol/L showed an increased mortality risk as compared to robust counterparts. CFS represents an important tool to select diabetic subjects with higher likelihood of adverse outcome.

Overt and Subclinical Hypothyroidism in the Elderly: When to Treat?

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.