Rare diseases in the elderly: a new perspective for the specialist in geriatrics

Rare diseases (RD) encompass a broad spectrum of highly heterogeneous illnesses characterized by a prevalence lower than 1: 2000 in general population. Although relatively uncommon, when considered as a whole, these pathologies represent a relevant public health problem. In light of their usual early onset and high severity and mortality, RD have been traditionally regarded as affecting mainly childhood or young adulthood, and considered to be excluded from filed of interest of geriatric specialists. However, more recent epidemiological studies, suggest that demographic changes, sometimes joined with advances in diagnostic and therapeutic strategies, are permitting longer survival of some persons affected by these conditions, thus making RD compatible with geriatric age. Hence, in the next future, specialists in geriatrics will be referred to by an increasing number of elderly subjects with RD seeking medical care. Geriatricians should be aware about the high management complexity of elderly patients with RD, characterized by considerable frailty status, related to both the primary RD and to the ageing-related condition

Hepatocellular Carcinoma: Known and Emerging Risk Factors

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer with a high mortality rate. While chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections represent the leading risk factors worldwide, the spreading of metabolic disorders, such as diabetes, obesity and non-alcoholic fatty liver disease (NAFLD) justifies the increasing attention on their oncogenic mechanisms. This review discusses about the main pathogenic mechanisms implicated in occurrence of HCC in presence of viral and metabolic diseases. Additionally, it points to the importance of clinical surveillance for those patients considered at risk of HCC and highlights the strategical role of serum markers, such as alfa-fetoprotein (αFP) and Protein Induced by Vitamin K Absence or Antagonist II (PIVKA-II), which, in association to a strictly instrumental follow-up, contribute to the early detection of hepatic nodules with a better prognosis for affected patients

Monocyte-to-HDL Ratio (MHR) Predicts Vitamin D Deficiency in Healthy and Metabolic Women: A Cross-Sectional Study in 1048 Subjects

Vitamin D deficiency is often linked with Metabolic Syndrome, both being more frequent with ageing and associated with an increase inflammatory state. Recently, monocytes-to-high density lipoprotein (HDL) ratio (MHR) has emerged as a powerful index to predict systemic inflammation. In this cross-sectional study, we investigated the association between circulating vitamin D level (25-OH vitamin D) and inflammatory status in a population of 1048 adult individuals. Our study reveals an inverse association between 25-OH vitamin D levels and MHR in the overall population. When the population is stratified by gender, waist circumference, and body mass index (BMI), we observed that while in men this relation is strongly significative only in condition of central obesity, in women a lifelong negative correlation exists between circulating 25-OH vitamin D and MHR and it is independent of the metabolic status. These observations underscore the relevance of circulating biomarkers such as MHR in the prediction of systemic inflammatory conditions sustained by vitamin D deficiency also in healthy and young women

The Multidimensional Prognostic Index (MPI) for the prognostic stratification of hospitalized older patients with COVID-19: a prospective multicenter observational cohort study. Objectives, study design and expected outcomes (MPI_COVID-19)

The emergent coronavirus-19 disease (COVID-19) pandemic posed and still poses serious issues in the management of the inpatients and in the resource allocation, in particular for those patients requiring Intensive Care Unit (ICU) management. Epidemiological data clearly suggest that multimorbid older patients have the poorest prognosis. However, it is conceivable that age and number of comorbidities alone do not reflect the real condition and the expected prognosis of the patients affected by COVID-19. A different approach based on comprehensive geriatric assessment (CGA) could help to better identify older patients more at risk of dismal outcomes and who, at some point of their clinical course, will need the ICU admission. The Multidimensional Prognostic Index (MPI) is a well-accepted tool derived from a standard CGA which allows to measure prognosis of older patients in different clinical settings including hospital. Therefore, we designed a multicenter, prospective, observational study to evaluate the role of MPI in predicting risk of ICU admission and in-hospital mortality among 500 COVID-19-positive older subjects admitted to geriatric and internal medicine wards. In addition, risk of re-hospitalization, institutionalization and death after 3 months from discharge will be assessed. The MPI yields a straightforward value from 0 to 1 and might be able to adequately stratify complex, vulnerable COVID-19 patients for best possible decision-making and treatment allocation

Identification of peculiar gene expression profile in peripheral blood mononuclear cells (PBMC) of celiac patients on gluten free diet.

Celiac disease (CD) is a systemic disorder characterized by an immune-mediated reaction to gluten and a wide spectrum of clinical manifestations. Currently, the main treatment of CD is represented by adherence to a gluten-free diet (GFD) which determines the resolution of symptoms, and the normalization of the serology and of the duodenal villous atrophy. In the present study, we aimed to identify changes in gene expression in peripheral blood mononuclear cells (PBMCs) of celiac patients on GFD for at least 2 years, in order to identify novel disease biomarkers and candidate targets for putative therapeutic approaches. Microarray analysis was performed on PBMCs from 17 celiac patients on long-term GFD and 20 healthy controls. We identified 517 annotated genes that were significantly modulated between celiac patients and controls. Significant biological pathways were functionally clustered using the Core Function of Ingenuity System Pathway Analysis (IPA). Intriguingly, despite being on a GFD, celiac patients exhibited a peculiar PBMC profile characterized by an aberrant expression of genes involved in the regulation of immunity, inflammatory response, metabolism, and cell proliferation. Random forest algorithm was then used to validate the prediction ability of core genes as classifiers of the "celiac status". In conclusion, our study identified a characteristic PBMCs signature profile in clinically asymptomatic celiac patient

A Systemic and Severe Infection via Cytomegalovirus and Other Herpesviruses in a Young Apparently Immunocompetent Patient: A Case Report

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Analysis of hepatic stiffness after viral eradication in a population with chronic hepatitis C treated with DAAs

Introduction and objectives: Despite chronic hepatitis C (CHC) is still a global burden as the high morbidity and mortality, the recently approved direct-acting antivirals (DAAs) permit a very high rate of sustained virologic response (SVR) in these patients. The clinical improvement due to viral eradication is being documented, however it is not clear why a subset of patients does not benefit in terms of fibrosis regression or hepatocellular carcinoma (HCC) development. Aim of the study was to assess the hepatic stiffness regression at SVR24 and detect factors impacting stiffness course. Patients and methods: Hepatic stiffness assessed by acoustic radiation force impulse (ARFI) and anthropometric- and biochemical parameters were retrospectively collected by 166 CHC patients treated with DAAs, form baseline and SVR24. Results: Viral eradication significantly improved overall hepatic stiffness and other related hepatitis hallmarks such as ALT, AST, γGT, platelets count, AST to Platelets ratio Index (APRI), total- and LDL cholesterol. The multiple regression analysis showed that patients with baseline glucose > 110mg/dl presented a stiffness regression significantly lower when compared to low glucose patients (<110mg/dl), moreover baseline HbA1c strongly correlated with DeltaStiffness. 7 patients (4.2%) developed HCC and importantly, presented hyperglycaemia and no stiffness regression nor platelets count recover. Conclusions: Although viral eradication with DAAs entails overall benefits, glycaemic decompensation negatively affects fibrosis regression and probably facilitates HCC development

Frailty trajectories in community-dwelling older adults during COVID-19 pandemic: The PRESTIGE study

Background Frailty has been recognized as potential surrogate of biological age and relevant risk factor for COVID-19 severity. Thus, it is important to explore the frailty trajectories during COVID-19 pandemic and understand how COVID-19 directly and indirectly impacts on frailty condition. Methods We enrolled 217 community-dwelling older adults with available information on frailty condition as assessed by multidimensional frailty model both at baseline and at one-year follow-up using Multidimensional Prognostic Index (MPI) tools. Pre-frail/frail subjects were identified at baseline as those with MPI score >0.33 (MPI grades 2-3). Frailty worsening was defined by MPI difference between 12 months follow-up and baseline >= 0.1. Multivariable logistic regression was modelled to identify predictors of worsening of frailty condition. Results Frailer subjects at baseline (MPI grades 2-3 = 48.4%) were older, more frequently female and had higher rates of hospitalization and Sars-CoV-2 infection compared to robust ones (MPI grade 1). Having MPI grades 2-3 at baseline was associated with higher risk of further worsening of frailty condition (adjusted odd ratio (aOR): 13.60, 95% confidence interval (CI): 4.01-46.09), independently by age, gender and Sars-CoV-2 infection. Specifically, frail subjects without COVID-19 (aOR: 14.84, 95% CI: 4.26-51.74) as well as those with COVID-19 (aOR: 12.77, 95% CI: 2.66-61.40, p = 0.001) had significantly higher risk of worsening of frailty condition. Conclusions Effects of COVID-19 pandemic among community-dwelling frailer individuals are far beyond the mere infection and disease, determining a significant deterioration of frailty status both in infected and non-infected subjects

1H-NMR metabolomics reveals a multitarget action of Crithmum maritimum ethyl acetate extract in inhibiting hepatocellular carcinoma cell growth

Hepatocellular carcinoma (HCC) is nowadays the sixth cause of tumour-related deceases worldwide, estimated to become the third in Western countries by 2030. New drugs for HCC treatment still have many adverse effects. Several lines of evidence indicate that plant metabolites offer concrete opportunities for developing new therapeutic strategies for many diseases, including cancer. We previously reported that ethyl acetate extract of a spontaneous edible plant harvested in Apulia, Crithmum maritimum, significantly inhibited cell growth in HCC cells. By 1H-NMR spectroscopy, here we show that Crithmum maritimum ethyl acetate extract counteracts the Warburg effect, by reducing intracellular lactate, inhibits protein anabolism, by decreasing amino acid level, and affects membrane biosynthesis by lowering choline and phosphocholine. Also, we observed an effect on lipid homeostasis, with a reduction in triglycerides, cholesterol, monounsaturated fatty acids (MUFA), and diunsaturated fatty acids (DUFA), and an increase in polyunsaturated fatty acids (PUFA). Taken together, these data demonstrate that Crithmum maritimum-induced cytostasis is exerted through a multi-effect action, targeting key metabolic processes in HCC cells. Overall, our findings highlight the role of Crithmum maritimum as a promising tool for the prevention and the improvement of the therapeutic options for HCC and other types of tumours

Differential inhibition of the TGF-b signaling pathway in HCC cells using the small molecule inhibitor LY2157299 and the D10 monoclonal antibody against TGF-β receptor Type II

We investigated blocking the TGF-b signaling pathway in HCC using two small molecule inhibitors (LY2157299, LY2109761) and a neutralizing humanized antibody (D10) against TGF-bRII. LY2157299 and LY2109761 inhibited HCC cell migration on Laminin-5, Fibronectin, Vitronectin, Fibrinogen and Collagen-I and de novo phosphorylation of pSMAD2. LY2157299 inhibited HCC migration and cell growth independently of the expression levels of TGF-bRII. In contrast to LY2157299, D10 showed a reduction in pSMAD2 only after a short exposure. This study supports the use of LY2157299 in clinical trials, and presents new insights into TGF-b receptor cycling in cancer cells