Characteristics and outcome of anti-hepatitis D virus positive patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Chronic hepatitis D virus (HDV) often leads to end-stage liver disease and hepatocellular carcinoma (HCC). Comprehensive data pertaining to large populations with HDV and HCC are missing, therefore we sought to assess the characteristics, management, and outcome of these patients, comparing them to patients with hepatitis B virus (HBV) infection. METHODS: We analysed the Italian Liver Cancer database focusing on patients with positivity for HBV surface antigen and anti-HDV antibodies (HBV/HDV, n = 107) and patients with HBV infection alone (n = 588). Clinical and oncological characteristics, treatment, and survival were compared in the two groups. RESULTS: Patients with HBV/HDV had worse liver function [Model for End-stage Liver Disease score: 11 vs. 9, p < .0001; Child-Turcotte-Pugh score: 7 vs. 5, p < .0001] than patients with HBV. HCC was more frequently diagnosed during surveillance (72.9% vs. 52.4%, p = .0002), and the oncological stage was more frequently Milan-in (67.3% vs. 52.7%, p = .005) in patients with HBV/HDV. Liver transplantation was more frequently performed in HBV/HDV than in HBV patients (36.4% vs. 9.5%), while the opposite was observed for resection (8.4% vs. 20.1%, p < .0001), and in a competing risk analysis, HBV/HDV patients had a higher probability of receiving transplantation, independently of liver function and oncological stage. A trend towards longer survival was observed in patients with HBV/HDV (50.4 vs. 44.4 months, p = .106). CONCLUSIONS: In patients with HBV/HDV, HCC is diagnosed more frequently during surveillance, resulting in a less advanced cancer stage in patients with more deranged liver function than HBV alone. Patients with HBV/HDV have a heightened benefit from liver transplantation, positively influencing survival.

Sorafenib and Metronomic Capecitabine in Child-Pugh B patients with advanced HCC: A real-life comparison with best supportive care.

BACKGROUND AND AIMS: The efficacy of systemic therapy for unresectable advanced hepatocellular carcinoma (aHCC) has not been proven in patients with Child-Pugh (C-P) B cirrhosis. Nevertheless, in real-world these patients are treated both with tyrosine kinase inhibitors (TKIs) and with metronomic capecitabine (MC). This study aimed to compare sorafenib and MC outcomes versus best supportive care (BSC) in C-P B patients. METHOD: Between 2008 and 2020, among 774 C-P B patients with aHCC not amenable/responsive to locoregional treatments, 410 underwent sorafenib, 62 MC, and 302 BSC. The propensity score matching method was used to correct the baseline unbalanced prognostic factors. RESULTS: In the unmatched population, median OS was 9.7 months in patients treated with sorafenib, 8.0 with MC, and 3.9 months with BSC. In sorafenib vs. BSC-matched patients (135 couples), median OS was 7.3 (4.9-9.6) vs. 3.9 (2.6-5.2) months (p<0.001). ECOG-Performance Status, tumor size, macrovascular invasion, AFP, treatment-naive, and sorafenib were independent predictors of survival. In MC vs. BSC-matched patients (40 couples), median OS was 9.0 (0.2-17.8) vs.3.0 (2.2-3.8) months (p<0.001). Median OS did not differ (p = 0.283) in sorafenib vs. MC-matched patients (55 couples). CONCLUSION: C-P B patients with aHCC undergoing BSC have poor survival. Both Sorafenib and MC treatment improve their prognosis.

Can We Slow Down Biological Age Progression? Study Protocol for the proBNPage Reduction (PBAR) Randomized, Double-Blind, Placebo-Controlled Trial (Effects of 4 "Anti-Aging" Food Supplements in Healthy Older Adults).

Purpose: The availability of a simple and reliable marker of biological age might allow an acceleration of the research in the field of longevity extension. Previous studies suggest that this marker might be the N-terminal of B-type natriuretic peptide precursor (NT-proBNP), from which proBNPage, a biological age surrogate, can be calculated. Objectives of the study: 1) To fine-tune the method of proBNPage progression assessment and 2) To establish whether 4 "anti-aging" treatments, which provided promising results in previous studies, can modify proBNPage progression. Patients and Methods: This is a double-blind randomized placebo-controlled clinical trial on 120 adults aged 65-80 years, free of cardiovascular diseases. Participants will be randomized into 3 groups: A) Coenzyme Q10 100 mg bid + Selenium 100 mcg; B) Resveratrol 350 mg bid + TA-65 (Astragalus Membranaceus extract) 100U; C) Placebo-1 bid + Placebo-2. They will be followed for 2 years and checked 8 times, to assess both proBNPage progression and treatment safety. Secondary variables (handgrip strength, aerobic capacity at the step test and quality of life) will also be assessed. Primary outcome will be the demonstration of significant changes of proBNPage, compared to baseline, in the 3 groups at 6, 12, 18 and 24 months. Secondary outcome will be the demonstration of similar changes of secondary variables. Statistical analyses will be mainly performed by repeated measures ANOVA (both according to intention to treat and per protocol) and paired t tests. The study was approved by the Ethics Committee Area Vasta Emilia Centro, Emilia-Romagna Region, ID: 64/2022/Sper/AOUBo. Trial registration: ClinicalTrials.gov, NCT05500742. Conclusion: The use of proBNPage as a surrogate of biological age may prove an easy method to select anti-aging treatments worthy of further, more complex assessments.

Predictors of non-transplantable recurrence in hepatocellular carcinoma patients treated with frontline liver resection.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) recurrence is common in patients treated with liver resection (LR). In this study, we aimed to evaluate the incidence and preoperative predictors of non-transplantable recurrence in patients with single HCC ≤5 cm treated with frontline LR. METHODS: From the Italian Liver Cancer (ITA.LI.CA) database, 512 patients receiving frontline LR for single HCC ≤5 cm were retrieved. Incidence and predictors of recurrence beyond Milan criteria (MC) and up-to-seven criteria were compared between patients with HCC <4 and ≥4 cm. RESULTS: During a median follow-up of 4.2 years, the overall recurrence rate was 55.9%. In the ≥4 cm group, a significantly higher proportion of patients recurred beyond MC at first recurrence (28.9% vs. 14.1%; p < 0.001) and overall (44.4% vs. 25.2%; p < 0.001). Similar results were found considering recurrence beyond up-to-seven criteria. Compared to those with larger tumours, patients with HCC <4 cm had a longer recurrence-free survival and overall survival. HCC size ≥4 cm and high alpha-fetoprotein (AFP) level at the time of LR were independent predictors of recurrence beyond MC (and up-to-seven criteria). In the subgroup of patients with available histologic information (n = 354), microvascular invasion and microsatellite lesions were identified as additional independent risk factors for non-transplantable recurrence. CONCLUSIONS: Despite the high recurrence rate, LR for single HCC ≤5 cm offers excellent long-term survival. Non-transplantable recurrence is predicted by HCC size and AFP levels, among pre-operatively available variables. High-risk patients could be considered for frontline LT or listed for transplantation even before recurrence.

Landscape of alcohol-related hepatocellular carcinoma in the last 15 years highlights the need to expand surveillance programs.

Background & Aims: Alcohol abuse and metabolic disorders are leading causes of hepatocellular carcinoma (HCC) worldwide. Alcohol-related aetiology is associated with a worse prognosis compared with viral agents, because of the lower percentage of patients diagnosed with HCC under routine surveillance and a higher burden of comorbidity in alcohol abusers. This study aimed to describe the evolving clinical scenario of alcohol-related HCC over 15 years (2006-2020) in Italy. Methods: Data from the Italian Liver Cancer (ITA.LI.CA) registry were used: 1,391 patients were allocated to three groups based on the year of HCC diagnosis (2006-2010; 2011-2015; 2016-2020). Patient characteristics, HCC treatment, and overall survival were compared among groups. Survival predictors were also investigated. Results: Approximately 80% of alcohol-related HCCs were classified as cases of metabolic dysfunction-associated fatty liver disease. Throughout the quinquennia, <50% of HCCs were detected by surveillance programmes. The tumour burden at diagnosis was slightly reduced but not enough to change the distribution of the ITA.LI.CA cancer stages. Intra-arterial and targeted systemic therapies increased across quinquennia. A modest improvement in survival was observed in the last quinquennia, particularly after 12 months of patient observation. Cancer stage, HCC treatment, and presence of oesophageal varices were independent predictors of survival. Conclusions: In the past 15 years, modest improvements have been obtained in outcomes of alcohol-related HCC, attributed mainly to underuse of surveillance programmes and the consequent low amenability to curative treatments. Metabolic dysfunction-associated fatty liver disease is a widespread condition in alcohol abusers, but its presence did not show a pivotal prognostic role once HCC had developed. Instead, the presence of oesophageal varices, an independent poor prognosticator, should be considered in patient management and refining of prognostic systems. Impact and Implications: Alcohol abuse is a leading and growing cause of hepatocellular carcinoma (HCC) worldwide and is associated with a worse prognosis compared with other aetiologies. We assessed the evolutionary landscape of alcohol-related HCC over 15 years in Italy. A high cumulative prevalence (78%) of metabolic dysfunction-associated fatty liver disease, with signs of metabolic dysfunction, was observed in HCC patients with unhealthy excessive alcohol consumption. The alcohol + metabolic dysfunction-associated fatty liver disease condition tended to progressively increase over time. A modest improvement in survival occurred over the study period, likely because of the persistent underuse of surveillance programmes and, consequently, the lack of improvement in the cancer stage at diagnosis and the patients' eligibility for curative treatments. Alongside the known prognostic factors for HCC (cancer stage and treatment), the presence of oesophageal varices was an independent predictor of poor survival, suggesting that this clinical feature should be carefully considered in patient management and should be included in prognostic systems/scores for HCC to improve their performance.

Potential feasibility of atezolizumab-bevacizumab therapy in patients with hepatocellular carcinoma treated with tyrosine-kinase inhibitors.

BACKGROUND: The combination of atezolizumab-bevacizumab has been proven to be superior to sorafenib for the treatment of unresectable hepatocellular carcinoma not amenable to locoregional treatments, becoming the standard of care of systemic therapy. AIM: This study aimed at assessing real-world feasibility of atezolizumab-bevacizumab in patients treated with tyrosine-kinase inhibitors. METHODS: Among 1447 patients treated with tyrosine-kinase inhibitors from January 2010 to December 2020, we assessed the percentage of those potentially eligible to atezolizumab-bevacizumab (according to IMbrave-150 trial criteria), and the overall survival of eligible and non-eligible patients. RESULTS: 422 (29%) patients were qualified for atezolizumab-bevacizumab therapy. The main exclusion causes were Child-Pugh class and Performance Status. Adopting the more permissive inclusion criteria of SHARP trial, 535 patients became eligible. The median overall survival of tyrosine-kinase inhibitors patients was 14.9 months, longer in eligible patients than in their counterpart due to better baseline liver function and oncological features. CONCLUSION: Real-world data indicate that less than one-third of hepatocellular carcinoma patients treated with tyrosine-kinase inhibitors are potentially eligible to atezolizumab-bevacizumab according to the registration trial criteria. These patients have a longer survival than the non-eligible ones. If the selection criteria of atezolizumab-bevacizumab trial are maintained in clinical practice, tyrosine-kinase inhibitors will remain the most used systemic therapy for hepatocellular carcinoma patients.

Characteristics and survival of patients with primary biliary cholangitis and hepatocellular carcinoma.

BACKGROUND: Comprehensive and contemporary data pertaining large populations of patients with Primary Biliary Cholangitis (PBC) and hepatocellular carcinoma (HCC) are missing. AIM: To describe main characteristics and outcome of PBC patients with HCC diagnosed in the new millennium. METHODS: Analysing the Italian Liver Cancer registry we identified 80 PBC patients with HCC diagnosed after the year 2000, and described their clinical characteristics, access to treatment and survival. RESULTS: Median age of patients was 71 years and 50.0% were males. Cirrhosis was present in 86.3% of patients, being well-compensated in 58.0%. Median HCC diameter was smaller in patients under surveillance (2.6 vs 4.0 cm, P = 0.007). Curative treatment, feasible in 50.0% of patients, was associated with improved survival compared to palliative and supportive care (42 vs 33 vs 6 months, P<0.0001). Surveillance was associated with a non-significant improved survival (36 vs 23 months), likely due to similar rate of curative treatment in patients under (51.4%) and outside surveillance (42.6%). CONCLUSIONS: PBC patients with HCC are often elderly males with well-preserved liver function. Feasibility of curative treatment is high and associated with improved prognosis. Description of these patients may help focus surveillance to identify earlier tumours, increase their curability, and improve prognosis.

Transarterial Chemoembolization for Hepatocellular Carcinoma in Clinical Practice: Temporal Trends and Survival Outcomes of an Iterative Treatment.

BACKGROUND: Transarterial chemoembolization (TACE) is one of the most frequently applied treatments for hepatocellular carcinoma (HCC) worldwide. In this study, we aimed at evaluating whether and how TACE application and repetition, as well as the related outcome, have changed over the last three decades in Italy. METHODS: Data of 7,184 patients with HCC were retrieved from the Italian Liver Cancer (ITA.LI.CA) database. Patients were divided according to the period of diagnosis in six cohorts: P1 (1988-1993), P2 (1994-1998), P3 (1999-2004), P4 (2005-2009), P5 (2010-2014), and P6 (2015-2019). All the analyses were repeated in the overall patient population and in Barcelona Clinic Liver Cancer (BCLC) B patients, who are the subgroup of HCC patients originally supposed to receive TACE according to guidelines. TACE was defined as either the first or the main (more effective) treatment. RESULTS: The proportion of patients receiving TACE as first or main therapy declined over time, and less than 50% of BCLC B patients were treated with chemoembolization from P3 onward. Conversely, TACE was widely used even outside the intermediate stage. Survival of TACE-treated patients progressively increased from P1 to P6. Although TACE was performed only once in the majority of patients, there was an increasing proportion of those receiving 2 or ≥3 treatments sessions over time. The overall survival (OS) of patients undergoing repeated treatments was significantly higher compared to those managed with a single TACE (median OS 40.0 vs. 65.0 vs. 71.8 months in 1, 2, and ≥3 TACE groups, respectively; p < 0.0001). However, after a first-line TACE, the adoption of curative therapies provided longer survival than repeating TACE (83.0 vs. 42.0 months; p < 0.0001), which in turn was associated with better outcomes compared to systemic therapies or best supportive care (BSC). CONCLUSIONS: Despite a decline in the percentage of treated patients over time, TACE has still an important role in the management of HCC patients. The survival of TACE-treated patients gradually improved over time, probably due to a better patient selection. Iterative TACE is effective, but an upward shift to curative therapies provides better outcomes while transition to systemic therapies and BSC leads to a worse prognosis.

The association of proBNPage with manifestations of age-related cardiovascular, physical, and psychological impairment in community-dwelling older adults.

NT-proB-type natriuretic peptide (NT-proBNP) serum concentration can be transformed by simple formulas into proBNPage, a surrogate of biological age strongly associated with chronological age, all-cause mortality, and disease count. This cross-sectional study aimed to assess whether proBNPage is also associated with other manifestations of the aging process in comparison with other variables. The study included 1117 noninstitutionalized older adults (73.1 ± 5.6 years, 537 men). Baseline measurements of serum NT-proBNP, erythrocyte sedimentation rate, hemoglobin, lymphocytes, and creatinine, which have previously been shown to be highly associated with both age and all-cause mortality, were performed. These variables were compared between subjects with and without manifestations of cardiovascular impairment (myocardial infarction (MI), stroke, peripheral artery disease (PAD), arterial revascularizations (AR)), physical impairment (long step test duration (LSTD), walking problems, falls, deficit in one or more activities of daily living), and psychological impairment (poor self-rating of health (PSRH), anxiety/depression, Mini Mental State Examination (MMSE) score < 24). ProBNPage (years) was independently associated (OR, 95% CI) with MI (1.08, 1.07-1.10), stroke (1.02, 1.00-1.05), PAD (1.04, 1.01-1.06), AR (1.06, 1.04-1.08), LSTD (1.03, 1.02-1.04), walking problems (1.02, 1.01-1.03), and PSRH (1.02, 1.01-1.02). For 5 of these 7 associations, the relationship was stronger than that of chronological age. In addition, proBNPage was univariately associated with MMSE score < 24, anxiety/depression, and falls. None of the other variables provided comparable performances. Thus, in addition to the known associations with mortality and disease count, proBNPage is also associated with cardiovascular manifestations as well as noncardiovascular manifestations of the aging process.

Clinical Role of Lung Ultrasound for the Diagnosis and Prognosis of Coronavirus Disease Pneumonia in Elderly Patients: A Pivotal Study.

BACKGROUND: Lung ultrasound (LUS) showed a promising role in the diagnosis and monitoring of patients hospitalized for novel coronavirus disease (COVID-19). However, no data are available on its role in elderly patients. AIMS: The aim of this study was to evaluate the diagnostic and prognostic role of LUS in elderly patients hospitalized for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pneumonia. METHODS: Consecutive elderly patients (age >65 years) hospitalized for COVID-19 were enrolled. Demographics, laboratory, comorbidity, and the clinical features of the patients were collected. All patients underwent LUS on admission to the ward. LUS characteristics have been analyzed. Uni- and multivariate analyses to evaluate predictors for in-hospital death were performed. RESULTS: Thirty-seven hospitalized elderly patients (19 men) with a diagnosis of SARS-CoV-2 infection were consecutively enrolled. The median age was 82 years (interquartile range 74.5-93.5). Ultrasound alterations were found in all patients enrolled; inhomogeneous interstitial syndrome with spared areas (91.9%) and pleural alterations (100%) were the most frequent findings. At univariate analysis, LUS score (hazard ratio [HR] 1.168, 95% CI 1.049-1.301) and pleural effusions (HR 3.995, 95% CI 1.056-15.110) were associated with in-hospital death. At multivariate analysis, only LUS score (HR 1.168, 95% CI 1.049-1.301) was independelty associated with in-hospital death. The LUS score's best cutoff for distinguishing patients experiencing in-hospital death was 17 (at multivariate analysis LUS score ≥17, HR 4.827, 95% CI 1.452-16.040). In-hospital death was significantly different according to the LUS score cutoff of 17 (p = 0.0046). CONCLUSION: LUS could play a role in the diagnosis and prognosis in elderly patients hospitalized for SARS-CoV-2 infection.

N-terminal pro B-type natriuretic peptide (NT-proBNP): a possible surrogate of biological age in the elderly people.

NT-proB-type natriuretic peptide (NT-proBNP) increases with age and is associated with all-cause mortality. With this study, we assessed its possible utilization as a marker of biological age in comparison with other variables. The study included 1079 non-institutionalized elderly subjects (mean age 72.8 ± 5.5 years, 561 women). Baseline measurements were performed of serum NT-proBNP and of some laboratory variables previously utilized to estimate biological age (creatinine, albumin, C-reactive protein, cholesterol, blood glucose, leukocytes, lymphocytes, hemoglobin, mean cell volume). During 7 years of follow-up, 114 all-cause deaths occurred. The logarithm of NT-proBNP was the most age-related parameter (r = 0.35, P < 0.0001). Its relationship with mortality, according to Cox regression and ROC curve (AUC = 0.707, 95% CI 0.654-0.759), was stronger than that of all other variables, including age. In multivariate analysis, only NT-proBNP and age remained independently associated with mortality. The regression lines between age and NT-proBNP (pg/ml) allowed a separate estimation of biological age ("proBNPage") for men (= [log(NT-proBNP) + 1.2068]/0.0827) and for women (= [log(NT-proBNP) - 1.5258]/0.0478). The hazard ratio of all-cause mortality for the fifth quintile of proBNP age (≥ 85 years) compared with the first quintile (< 61 years) was 7.9 (95% CI 3.6-17.5). Similarly, the difference between pro-BNPage and chronological age was associated with a hazard ratio of 3.5 in the fifth quintile (95% CI 1.9-6.4) and was associated with disease count (P for trend = 0.0002). In conclusion, NT-proBNP was the best indicator of biological age, which can be estimated by simple formulas and might be used for prognostic purposes or as a surrogate end point in epidemiological and intervention studies.

Prognostic value of non-alcoholic fatty liver disease in the elderly patients.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of metabolic syndrome, a risk factor for mortality and cardiovascular morbidity, but we ignore the role of steatosis per se in survival, and there is very little information about this condition in the geriatric patient. AIMS: With the present study, we investigated the independent prognostic value of NAFLD on overall mortality in the elderly. METHODS: Within the Pianoro Project, involving people ≥ 65 years, anamnestic, clinical and laboratoristic data related to NAFLD, insulin resistance, diabetes/hyperglycemia, hypertension, obesity and dyslipidemia were collected in 804 subjects (403 male, 401 female). These subjects were followed up for mortality for a median time of 12.6 years. A multivariate analysis was performed to evaluate the prognostic value of the covariates. RESULTS: At Kaplan-Meier estimator the presence of NAFLD seems to be associated to a lower mortality, and survival tends to increase with the increasing of steatosis grade. Cox's analysis found that survival is increased for subjects having hypercholesterolemia (RR = 0.565), NAFLD (RR = 0.777), hypertension (RR = 0.711) and in female (RR = 0.741), while it is decreased for the older subjects (RR = 3.046), in patients with hypertriglyceridemia (RR = 1.699) and for diabetics (RR = 1.797). The variables BMI and HDL-cholesterol have no role. CONCLUSION: The data obtained in our study show that NAFLD is not associated to overall mortality in the elderly population.

Predictors of cognitive impairment assessed by Mini Mental State Examination in community-dwelling older adults: relevance of the step test.

BACKGROUND: Several predictors of cognitive impairment assessed by Mini Mental State Examination (MMSE) have previously been identified. However, which predictors are the most relevant and what is their effect on MMSE categories remains unclear. METHODS: Cross-sectional and longitudinal study using data from 1116 older adults (72.6 ±â€¯5.6 years, 579 female), 350 of whom were followed for 7 years. At baseline, the following variables were collected: personal data, marital status, occupation, anthropometric measures, risk factors, previous cardiovascular events, self-rated health and physical activity during the last week. Furthermore, routine laboratory tests, abdominal echography and a step test (with measurement of the time needed to ascend and descend two steps 20 times) were performed. The associations of these variables with cross-sectional cognitive deficit (MMSE < 24) and longitudinal cognitive decline (decrease of MMSE score over 7 years of follow-up) were investigated using logistic regression models. RESULTS: Cross-sectional cognitive deficit was independently associated with school education ≤ 5 years, prolonged step test duration, having been blue collar or housewife (P ≤ 0.0001 for all) and, with lower significance, with advanced age, previous stroke and poor recent physical activity (P < 0.05). Longitudinal cognitive decline was mainly associated with step test duration (P = 0.0001) and diastolic blood pressure (P = 0.0002). The MMSE categories mostly associated with step test duration were orientation, attention, calculation and language, while memory appeared to be poorly or not affected. CONCLUSIONS: In our cohort of older adults, step test duration was the most relevant predictor of cognitive impairment.

Inverse Association Between Neck Pain and All-Cause Mortality in Community-Dwelling Older Adults.

Objective: In a previous study, we found an apparent protective effect of neck pain on all-cause mortality in subjects older than age 85 years. The present longitudinal investigation was performed to verify this unexpected finding in a larger sample and to establish its significance. Design: Population follow-up study. Setting: Three towns of Northern Italy. Subjects: We examined 5,253 community-dwelling residents age 65-102 years (55% female). Methods: Through a postal questionnaire, baseline information was obtained concerning cardiovascular risk factors, self-rated health, physical activity, cardiovascular events, medical therapy, and presence of pain in the main joints. Seven-year all-cause mortality was the end point. Results: During follow-up, 1,250 people died. After adjustment for age, sex, anti-inflammatory drugs, physical activity, and main risk factors, neck pain was inversely associated with mortality (hazard ratio = 0.74, 95% confidence interval = 0.64-0.86, P < 0.001). This association was present, with high significance, in each of the eight following subgroups: men, women, age 65-74 years, age 75-84 years, age ≥85 years and residents of each of the three towns. The subjects without neck pain (N = 3,158) were older, more often men, less often hypercholesterolemic, less physically active, and had more frequently had a stroke than the subjects with neck pain (N = 2,095). There were no differences in the causes of death between subjects with or without neck pain. Conclusion: This study has confirmed the existence of an independent inverse association between neck pain and mortality in the elderly, suggesting that reduced sensitivity to neck pain may be a new marker of frailty.

Usefulness of the MrWALLETS Scoring System to Predict First Diagnosed Atrial Fibrillation in Patients With Ischemic Stroke.

Some cryptogenic strokes are caused by undetected paroxysmal atrial fibrillation (AF) and could benefit from oral anticoagulation. In this study, we searched for echocardiographic parameters associated with first diagnosed AF, to form a scoring system for the identification of patients with AF. We examined 571 patients with ischemic stroke (72.7 ± 13.5 years, 50.6% women), subdivided into 4 groups: documented cause without AF, first diagnosed AF, known paroxysmal AF, and permanent AF. All patients underwent transthoracic echocardiography, brain computed tomography scan, carotid/vertebral ultrasound, and continuous electrocardiographic monitoring. Eight factors independently characterized first diagnosed AF and formed the "MrWALLETS" score: mitral regurgitation, mild-to-moderate (+1), white matter lesions (-1), age ≥75 years (+1), left atrium ≥4 cm (+1), cerebral lesion diameter ≥4 cm (+1), left ventricular end-diastolic volume <65 ml (+1), tricuspid regurgitation ≥moderate (+1), carotid stenosis ≥50% (-1). In the patients with ≥3 points, positive predictive value was 80%, specificity 97.5%, and sensitivity 57.1%. In the patients with ≥2 points sensitivity rose to 85.7%, but positive predictive value was 47.1%. The area under the receiver-operating characteristic curve was 0.89 (95% CI 0.83 to 0.95). There were important differences among AF groups, which therefore could not be merged. In conclusion, 4 echocardiographic parameters, 3 additional instrumental parameters, and age allow the identification of stroke patients with first diagnosed AF with high positive predictive value.

Physical Activity and Other Determinants of Survival in the Oldest Adults.

OBJECTIVES: To determine the role of physical activity as a possible survival determinant in the oldest adults. DESIGN: Prospective, longitudinal, population-based cohort. SETTING: The Pianoro Study of community-dwelling older adults in three towns in northern Italy. PARTICIPANTS: Noninstitutionalized individuals aged 85 and older (n = 500; mean age 89.6 ± 3.1, 65% female). MEASUREMENTS: Participants provided information on marital status, educational level, previous work activity, cardiovascular risk factors, previous cardiovascular events, self-rated health, joint pain, and functional status. Physical activity was quantified using the Physical Activity Scale for the Elderly. Seven-year mortality was known for all subjects. RESULTS: During the 7 years of follow-up, 365 subjects died. According to Cox proportional hazards regression, the following factors were found to be independently associated with mortality: PASE score (hazard ratio (HR) = 0.987, 95% confidence interval (CI) = 0.981-0.993, P < .001), male sex (HR = 1.642, 95% CI = 1.411-2.068, P < .001), age in years (HR = 1.077, 95% CI = 1.040-1.116, P < .001), previous stroke (HR = 1.908, 95% CI = 1.362-2.673, P < .001), poor self care (HR = 1.662, 95% CI = 1.231-2.246, P < .001), neck pain (HR = 0.649, 95% CI = 0.497-0.849, P = .002), self rated health (HR = 0.991, 95% CI = 0.985-0.997, P = .002). CONCLUSION: In the oldest adults, accurate quantification of physical activity may provide important prognostic information. The predictive value of cardiovascular risk factors, except age, male sex, and prior stroke, was confirmed to be negligible. An unexpected inverse association between neck pain and mortality may require further investigation.

A Case of Acute Liver Failure during Ritonavir-Boosted Paritaprevir, Ombitasvir and Dasabuvir Therapy in a Patient with HCV Genotype 1b Cirrhosis.

BACKGROUND: Ritonavir-boosted Paritaprevir, Ombitasvir and Dasabuvir plus Ribavirin is one of the current recommended therapies for HCV genotype 1b monoinfected patients in compensated (Child-Pugh A) cirrhosis. Whether it is known that the worsening of liver function is a rare but possible complication of Ritonavir-boosted Paritaprevir, Ombitasvir and Dasabuvir therapy, to our knowledge no description of treatment-related acute liver failure is available in the literature. CASE PRESENTATION: An 84-year-old Caucasian man with chronic compensated HCV genotype 1b cirrhosis received Ritonavir-boosted Paritaprevir, Ombitasvir and Dasabuvir plus Ribavirin therapy. After 13 days he developed grade 4 hyperbilirubinaemia and ascites. Even though treatment was promptly stopped, patient's clinical condition worsened, and he underwent hospitalization, several paracentheses, and developed sub-acute kidney injury. The bilirubinemia returned under three times the upper normal limit only after five months. Notably, he achieved sustained virological response despite the very short duration of therapy. CONCLUSION: Hepatic decompensation and acute liver failure are rare but severe complications of Ritonavir-boosted Paritaprevir, Ombitasvir and Dasabuvir plus Ribavirin therapy in patients with compensated cirrhosis. Close monitoring for signs or symptoms of worsening of liver disease is mandatory, and further research for stratifying risk factors are required.

Prognostic significance of carotid and vertebral ultrasound in ischemic stroke patients.

OBJECTIVES: The ultrasound investigation of carotid and vertebral arteries is routinely performed in stroke patients to determine the etiopathogenetic classification and possible need of revascularization. However, the medium and long-term prognostic implications of carotid and vertebral ultrasound in ischemic stroke patients are not yet known. METHODS: This study included 309 ischemic stroke patients (mean age 76.3; 160 men). They all had undergone carotid and vertebral ultrasound (carotid stenoses were measured according to the European Carotid Surgery Trial [ECST] method). After a median interval of 9.4 months, a telephone follow-up was performed to determine their outcome. Dependency or death (modified Rankin scale-mRS >2) and all cause mortality were the study end-points. RESULTS: At follow-up, 158 patients had a mRS >2. In multivariate analysis, of 13 variables univariately predictive of dependency or death, only National Institutes of Health Stroke Scale (NIHSS) score (P < 0.0001), age (P < 0.0001) and ipsi- or contralateral carotid stenosis ≥60% (O.R. 3.5, 95% C.I. 1.5-8.6, P = 0.006) remained associated with a mRS >2. Sixty-nine patients had died. In a Cox proportional hazards regression, of 10 variables univariately predictive of mortality, only NIHSS score (P < 0.0001), age (P = 0.003), total anterior circulation syndrome (P = 0.004), vertebral Doppler abnormalities (O.R. 2.2, 95% C.I. 1.3-3.6, P = 0.006), male sex (P = 0.02), and hypercholesterolemia (P = 0.04, inverse relationship) remained associated with mortality. CONCLUSIONS: In stroke patients, carotid stenoses ≥60%, ipsi- or contralateral to cerebral lesions, were associated with an increased medium and long-term probability of dependency or death, and abnormalities of vertebrobasilar flow were a significant indicator of death risk, independent of stroke severity and age.

No Direct Survival Effect of Light to Moderate Alcohol Drinking in Community-Dwelling Older Adults.

OBJECTIVES: To assess the relationship between light to moderate alcohol consumption and mortality, particularly accounting for baseline health status and physical activity. DESIGN: Prospective, longitudinal, population-based study. SETTING: The Pianoro Study, which consisted of community-dwelling older adults in three towns in northern Italy. PARTICIPANTS: Noninstitutionalized individuals of both sexes aged 65 and older (N = 5,256; 2,318 abstainers, 2,309 light to moderate drinkers (≤2 alcoholic units/d)). MEASUREMENTS: Baseline information about demographic characteristics, lifestyle factors, physical activity (Physical Activity Scale for the Elderly (PASE)), perceived health status (visual analog scale (VAS)), dependency level, risk factors, and previous cardiovascular events was obtained using a structured questionnaire. Follow-up information was obtained 6 years later from 2,752 survivors, and mortality information was obtained from death certificates. RESULTS: Male sex, being physically active, and good health status were independently associated with light to moderate drinking (P < .001). An apparent protective effect of light to moderate drinking on mortality was evident in the unadjusted analysis and after adjusting for age, sex, risk factors, and cardiovascular events (adjusted hazard ratio (aHR) = 0.77, 95% confidence interval (CI) = 0.68-0.88, P < .001), but after also adjusting for PASE and VAS, the relationship was no longer significant (aHR = 0.92, 95% CI = 0.80-1.05, P = .19). Follow-up physical activity was associated with baseline alcohol consumption; baseline physical activity did not predict alcohol consumption during follow-up. CONCLUSION: After accounting for health status and physical activity, light to moderate alcohol drinking had no direct protective effect on mortality.