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.

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.

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.

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.

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.

Changes of liver enzymes and bilirubin during ischemic stroke: mechanisms and possible significance.

BACKGROUND: Small changes of bilirubin and liver enzymes are often detected during the acute phase of stroke, but their origin and significance are still poorly understood. METHODS: On days 0, 3, 7, and 14 after admission, 180 patients with ischemic stroke underwent serial determinations of bilirubin, GOT, GPT, γGT, alkaline phosphatase, C-reactive protein (CRP) and complete blood count. On days 0 and 7 common bile duct diameter was measured by ultrasound, and on day 3 cerebral infarct volume (IV) was calculated from CT scan slices. RESULTS: During the first week GOT, GPT, γGT (P < 0.001) and CRP (P = 0.03) increased with subsequent plateau, while significant decrements (P < 0.001) concerned unconjugated bilirubin, erythrocytes and haemoglobin. Alkaline phosphatase, direct bilirubin and common bile duct diameter remained stable. IV correlated with CRP, leukocytes, GOT, γGT (r > 0.3, P < 0.001 for all) and direct bilirubin (r = 0.23, P = 0.008). In multivariate analysis only CRP and GOT remained independently associated with IV (P < =0.001). The correlation of IV with GOT increased progressively from admission to day 14. GOT independently correlated with GPT which, in turn, correlated with γGT. γGT was also highly correlated with leukocytes. Unconjugated bilirubin correlated with haemoglobin, which was inversely correlated with CRP. CONCLUSIONS: The changes of bilirubin and liver enzymes during ischemic stroke reflect two phenomena, which are both related to IV: 1) inflammation, with consequent increment of CRP, leukocytes and γGT, and decrease of haemoglobin and unconjugated bilirubin and 2) an unknown signal, independent from inflammation, leading to increasing GOT and GPT levels.

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.

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.

Metabolic syndrome and all-cause mortality in older men and women.

BACKGROUND: Prevalence of metabolic syndrome (MetS) increases with age, but its association with all-cause mortality in older persons remains uncertain. This study investigated the association of all-cause mortality with MetS and its individual components in older men and women. METHODS: A total of 917 men and 1043 women aged 65 years and older from two Italian population-based cohorts were included in the study. MetS was defined according to four different definitions: National Cholesterol Education Program (NCEP), NCEP revised according to the American Heart Association and National Heart Lung Blood Institute (NCEP-R), International Diabetes Organization (IDF) and Joint Interim Statement (JIS). All of these definitions include abdominal obesity, hyperglycaemia, hypertriglyceridaemia, low high-density lipoprotein cholesterol and hypertension. Hazard Ratios (HR) and their corresponding 95% confidence interval (95%CI) estimated from multivariable-adjusted Cox regression models were used to investigate the associations of all-cause mortality with baseline MetS status and individual MetS components. RESULTS: After 6·5 ± 1·8 years of follow-up, there were 179 deaths among women and 193 among men. Mortality risk was increased in women with MetS by any definition, regardless of individual components, but limited to age 70-79 years (NCEP, HR = 2·02, 95%CI, 1·16-3·53; NCEP-R, HR = 2·51, 95%CI, 1·45-4·34; IDF, HR = 2·16, 95%CI, 1·26-3·72; JIS, HR = 2·16, 95%CI, 1·26-3·72). Mortality risk of men was associated with hypertriglyceridaemia below age 70 years (HR = 2·50, 95%CI, 1·19-5·25), but unrelated to MetS status. CONCLUSIONS: Metabolic Syndrome is associated with all-cause mortality in older women but not in men. The association, however, is limited to a narrow age range.

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.

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.

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.

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.

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.

Chronic endurance exercise training prevents aging-related cognitive decline in healthy older adults: a randomized controlled trial.

OBJECTIVE: To evaluate the effects of endurance exercise training (EET) on the cognitive status of healthy community-dwelling older adults. METHODS: A randomized controlled trial was conducted involving community-dwelling older adults from the town of Pianoro (northern Italy). We randomized 120 healthy subjects aged 65-74 years, both genders, to treatment (N = 60) and control (N = 60) groups. The treatment consisted of 12 months of supervised EET in a community gym, 3 h a week. All participants were assessed both at baseline and after 12 months on an intention-to-treat analysis. Cognitive status was assessed by one single test (Mini Mental State Examination, MMSE). Anthropometric indexes, routine laboratory measurements and C-reactive protein (CRP) were also assessed. RESULTS: The control group showed a significant decrease in MMSE score (mean difference -1.21, 95% CI -1.83/-0.60, p = 0.0002), which differed significantly (p = 0.02) from the treatment group scores (-0.21, 95% CI -0.79/0.37, p = 0.47). The odds ratio for the treated older adults to have a stable cognitive status after 1 year, as compared to the control group, was 2.74 (95% CI 1.16/6.48) after adjustment for age, gender, educational level and several other possible confounders. Blood pressure, body mass index, waist circumference and serum cholesterol did not differ significantly between the two groups, while CRP decreased only in the treatment group. CONCLUSIONS: A 12-month EET intervention may reduce the progression of age-related cognitive decline in healthy older adults.

Mean platelet volume (MPV) increase during acute non-lacunar ischemic strokes.

INTRODUCTION: Mean platelet volume (MPV) has been associated with the prognosis in stroke patients. However, its spontaneous variability during the acute phase of the disease is unknown. Materials and Methods - One hundred and thirty-seven patients with ischemic stroke, aged 75.4+/-11.0 (SD) years, were classified according to several criteria: National Institutes of Health Stroke Scale (NIHSS) score, maximum lesion diameter on CT scan, Oxfordshire Community Stroke Projects (OCSP) and Trial of ORG 10172 in Acute Stroke Treatment (TOAST) categories. Platelet parameters were determined 1.2 days after the onset of symptoms, and after 3.0 further days. RESULTS: The initial MPV was higher in non-lacunar than lacunar strokes (8.30+/-1.10 vs. 7.95+/-0.79 fl, P=0.04), and correlated with the sampling delay with respect to the onset of symptoms, especially in the strokes with lesions >=4 cm (r=0.39, P=0.009), NIHSS >=11 (r=0.35, P=0.02) and of cardioembolic origin (r=0.35, P=0.01). Subsequently a late MPV increment was observed in the remaining categories: from 8.20 to 8.38 fl (P=0.02) in the strokes with lesions <4 cm, from 8.11 to 8.31 fl (P=0.01) in the presence of an NIHSS<11 and from 8.20 to 8.61 fl (P=0.03) when the occlusion of a large artery was involved. CONCLUSIONS: Platelet volume is not stable during the acute phase in non-lacunar ischemic strokes, as it increases early in the most severe forms, and later in the remaining subtypes. The release of large and more reactive platelets may contribute to the thrombophilic state associated with ischemic events.

Spleen enlargement on follow-up evaluation: a noninvasive predictor of complications of portal hypertension in cirrhosis.

BACKGROUND & AIMS: Splenomegaly is observed in most but not all patients with cirrhosis, and has been detected more often in patients showing complications of portal hypertension. We aimed to test the hypotheses that spleen enlarges over time in cirrhosis, and that a progressive enlargement may be associated with portal hypertension-related events. METHODS: A total of 127 cirrhotic patients (Child-Pugh, 6.7 +/- 1.7; range, 5-11), observed at our center and followed-up clinically, endoscopically, and with periodic abdominal ultrasound for at least 1 year, were included. Spleen diameter was recorded at each ultrasound examination. The change of spleen diameter over time was calculated. The occurrence of clinical complications of cirrhosis on follow-up evaluation was recorded. RESULTS: At inclusion, spleen diameter was 14.9 +/- 3.1 cm; 83% of the patients had splenomegaly. Spleen was larger in patients with decompensated disease (n = 39) versus patients with compensated disease (n = 88) (16.1 +/- 3.5 vs 14.5 +/- 2.7; P = .012). The mean follow-up period was 53 +/- 37 months. Spleen progressively enlarged over time (analysis of variance, P < .0001). A total of 46.4% of patients showed a spleen enlargement of 1 cm or more at 1 year. Over 5 years of follow-up evaluation patients showing spleen enlargement showed a higher actuarial probability of esophageal varices formation (84.6% vs 16.6%; P = .001) and growth (63.3% vs 20.6%; P = .001). Among patients with compensated cirrhosis at inclusion, those showing a spleen enlargement had a higher actuarial probability of developing the first clinical decompensation of cirrhosis (51.1% vs 19.5%, P = .002). CONCLUSIONS: Spleen enlargement at follow-up evaluation outlines a subgroup of cirrhotic patients at higher risk of complications of portal hypertension. Noninvasive monitoring of spleen diameter allows a prognostic stratification of cirrhotic patients.

Determinants of mean platelet volume (MPV) in an elderly population: relevance of body fat, blood glucose and ischaemic electrocardiographic changes.

Mean platelet volume (MPV) is increased in patients with coronary heart disease or at risk for stroke. However, MPV determinants have never been assessed in a population study. The present investigation is a cross-sectional study involving 366 non-selected subjects (both sexes, mean age 72.9 +/- 5.5 [1 SD] years). The main cardiovascular risk factors, several indexes of adiposity (including percent body fat as estimated by skinfold measurement, and ultrasound detection of hepatic steatosis and thickness of abdominal subcutaneous and visceral fat) and ischaemic electrocardiographic (ECG) changes were assessed in all subjects. Platelet parameters were determined by a Bayer ADVIA 120 counter. In addition to being associated directly with platelet distribution width (PDW) and inversely with platelet count (p < 0.0001 for both), MPV values were associated with subcutaneous abdominal fat (p = 0.02), fasting blood glucose (p = 0.002) and the prevalence of ischaemic ECG changes (p = 0.004), and tended to be higher in the subjects with a greater prevalence of hepatic steatosis (p = 0.07) and higher Homeostasis Model Assessment (HOMA) index (p = 0.09). In multiple logistic regression, of the non-platelet parameters only percent body fat (p = 0.006), ischaemic ECG changes (p = 0.01) and blood glucose (p = 0.03) remained independently associated with an MPV < or =8.4 fl (high tertile). The relative risk (odds ratio) of having ischaemic ECG changes for the subjects with MPV < or =8.4 fl was 4.2 (95% confidence interval: 2.5-7.1; p = 0.006) with respect to the subjects with lower MPV values. Blood glucose, percent body fat and ischaemic ECG changes were the main MPV determinants in our elderly population.