209 research outputs found
Current guidelines for the management of non-alcoholic fatty liver disease: A systematic review with comparative analysis
The current epidemic of non-alcoholic fatty liver disease (NAFLD) is reshaping the field of hepatology all around the world. The widespread diffusion of metabolic risk factors such as obesity, type2-diabetes mellitus, and dyslipidemia has led to a worldwide diffusion of NAFLD. In parallel to the increased availability of effective anti-viral agents, NAFLD is rapidly becoming the most common cause of chronic liver disease in Western Countries, and a similar trend is expected in Eastern Countries in the next years. This epidemic and its consequences have prompted experts from all over the word in identifying effective strategies for the diagnosis, management, and treatment of NAFLD. Different scientific societies from Europe, America, and Asia-Pacific regions have proposed guidelines based on the most recent evidence about NAFLD. These guidelines are consistent with the key elements in the management of NAFLD, but still, show significant difference about some critical points. We reviewed the current literature in English language to identify the most recent scientific guidelines about NAFLD with the aim to find and critically analyse the main differences. We distinguished guidelines from 5 different scientific societies whose reputation is worldwide recognised and who are representative of the clinical practice in different geographical regions. Differences were noted in: the definition of NAFLD, the opportunity of NAFLD screening in high-risk patients, the noninvasive test proposed for the diagnosis of NAFLD and the identification of NAFLD patients with advanced fibrosis, in the follow-up protocols and, finally, in the treatment strategy (especially in the proposed pharmacological management). These difference have been discussed in the light of the possible evolution of the scenario of NAFLD in the next years
A Fatal Case of Pseudomonas aeruginosa Community-Acquired Pneumonia in an Immunocompetent Patient: Clinical and Molecular Characterization and Literature Review
Rare cases of Pseudomonas aeruginosa community-acquired pneumonia (PA-CAP) were
reported in non-immunocompromised patients. We describe a case of Pseudomonas aeruginosa
(PA) necrotizing cavitary CAP with a fatal outcome in a 53-year-old man previously infected with
SARS-CoV-2, who was admitted for dyspnea, fever, cough, hemoptysis, acute respiratory failure
and a right upper lobe opacification. Six hours after admission, despite effective antibiotic therapy,
he experienced multi-organ failure and died. Autopsy confirmed necrotizing pneumonia with
alveolar hemorrhage. Blood and bronchoalveolar lavage cultures were positive for PA serotype
O:9 belonging to ST1184. The strain shares the same virulence factor profile with reference genome
PA01. With the aim to better investigate the clinical and molecular characteristics of PA-CAP, we
considered the literature of the last 13 years concerning this topic. The prevalence of hospitalized
PA-CAP is about 4% and has a mortality rate of 33–66%. Smoking, alcohol abuse and contaminated
fluid exposure were the recognized risk factors; most cases presented the same symptoms described
above and needed intensive care. Co-infection of PA-influenza A is described, which is possibly
caused by influenza-inducing respiratory epithelial cell dysfunction: the same pathophysiological
mechanism could be assumed with SARS-CoV-2 infection. Considering the high rate of fatal
outcomes, additional studies are needed to identify sources of infections and new risk factors, along
with genetic and immunological features. Current CAP guidelines should be revised in light of
these results
Depressive Symptoms during Pregnancy. Prevalence and Correlates with Affective Temperaments and Psychosocial Factors
Pregnancy is a unique experience in women's life, requiring a great ability of adaptation and self-reorganization; vulnerable women may be at increased risk of developing depressive symptoms. This study aimed to examine the incidence of depressive symptomatology during pregnancy and to evaluate the role of affective temperament traits and psychosocial risk factors in predicting them. We recruited 193 pregnant women, collected data regarding sociodemographic, family and personal clinical variables, social support and stressful life events and administered the Mood Disorder Questionnaire (MDQ), the Patient Health Questionnaire-9 (PHQ-9), and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A). In our sample, prevalence of depressive symptomatology was 41.45% and prevalence of depression was 9.85% (6.75% mild and 3.10% moderate depression). We have chosen a cutoff >4 on PHQ-9 to identify mild depressive symptoms which may predict subsequent depression. Statistically significant differences between the two groups were found in the following factors: gestational age, occupation, partner, medical conditions, psychiatric disorders, family psychiatric history, stressful life events, and TEMPS-A mean scores. In our sample mean scores on all affective temperaments but the hyperthymic, were significantly lower in the control group. Only depressive and hyperthymic temperaments were found to be, respectively, risk and protective factors for depressive symptomatology. The current study confirms the high prevalence and complex aetiology of depressive symptomatology during pregnancy and suggests that affective temperament assessment seems to be a useful adjunctive instrument to predict depressive symptomatology during pregnancy and postpartum
Lifestyles and socio-cultural factors among children aged 6-8 years from five Italian towns: The MAPEC-LIFE study cohort
Background: Lifestyles profoundly determine the quality of an individual’s health and life since his childhood.
Many diseases in adulthood are avoidable if health-risk behaviors are identified and improved at an early stage of
life. The aim of the present research was to characterize a cohort of children aged 6–8 years selected in order to
perform an epidemiological molecular study (the MAPEC_LIFE study), investigate lifestyles of the children that
could have effect on their health status, and assess possible association between lifestyles and socio-cultural factors.
Methods: A questionnaire composed of 148 questions was administered in two different seasons to parents of
children attending 18 primary schools in five Italian cities (Torino, Brescia, Pisa, Perugia and Lecce) to obtain
information regarding the criteria for exclusion from the study, demographic, anthropometric and health
information on the children, as well as some aspects on their lifestyles and parental characteristics. The results
were analyzed in order to assess the frequency of specific conditions among the different seasons and cities and
the association between lifestyles and socio-economic factors.
Results: The final cohort was composed of 1,164 children (50.9 boys, 95.4% born in Italy). Frequency of some
factors appeared different in terms of the survey season (physical activity in the open air, the ways of cooking
certain foods) and among the various cities (parents’ level of education and rate of employment, sport, traffic
near the home, type of heating, exposure to passive smoking, ways of cooking certain foods). Exposure to
passive smoking and cooking fumes, obesity, residence in areas with heavy traffic, frequency of outdoor play and
consumption of barbecued and fried foods were higher among children living in families with low educational
and/or occupational level while children doing sports and consuming toasted bread were more frequent in families
with high socio-economic level.
Conclusions: The socio-economic level seems to affect the lifestyles of children enrolled in the study including
those that could cause health effects. Many factors are linked to the geographical area and may depend on
environmental, cultural and social aspects of the city of residence
Long-term and real-world safety and efficacy of retroviral gene therapy for adenosine deaminase deficiency
Adenosine deaminase (ADA) deficiency leads to severe combined immunodeficiency (SCID). Previous clinical trials showed that autologous CD34+ cell gene therapy (GT) following busulfan reduced-intensity conditioning is a promising therapeutic approach for ADA-SCID, but long-term data are warranted. Here we report an analysis on long-term safety and efficacy data of 43 patients with ADA-SCID who received retroviral ex vivo bone marrow-derived hematopoietic stem cell GT. Twenty-two individuals (median follow-up 15.4 years) were treated in the context of clinical development or named patient program. Nineteen patients were treated post-marketing authorization (median follow-up 3.2 years), and two additional patients received mobilized peripheral blood CD34+ cell GT. At data cutoff, all 43 patients were alive, with a median follow-up of 5.0 years (interquartile range 2.4-15.4) and 2 years intervention-free survival (no need for long-term enzyme replacement therapy or allogeneic hematopoietic stem cell transplantation) of 88% (95% confidence interval 78.7-98.4%). Most adverse events/reactions were related to disease background, busulfan conditioning or immune reconstitution; the safety profile of the real world experience was in line with premarketing cohort. One patient from the named patient program developed a T cell leukemia related to treatment 4.7 years after GT and is currently in remission. Long-term persistence of multilineage gene-corrected cells, metabolic detoxification, immune reconstitution and decreased infection rates were observed. Estimated mixed-effects models showed that higher dose of CD34+ cells infused and younger age at GT affected positively the plateau of CD3+ transduced cells, lymphocytes and CD4+ CD45RA+ naive T cells, whereas the cell dose positively influenced the final plateau of CD15+ transduced cells. These long-term data suggest that the risk-benefit of GT in ADA remains favorable and warrant for continuing long-term safety monitoring. Clinical trial registration: NCT00598481 , NCT034786
Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19
Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage
Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes
Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19
Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features
The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores (IPGSph1 and IPGSph2). By applying a logistic regression with both IPGS, (IPGSph2 (or indifferently IPGSph1) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%
Bibliotecas escolares en Italia: una hipĂłtesis de investigaciĂłn sobre el patrimonio histĂłrico-educativo
La biblioteca escolar en Italia se define, de acuerdo con las directrices elaboradas por IFLA (FederaciĂłn Internacional de Asociaciones e Instituciones Bibliotecarias), como un entorno educativo donde se fomenta la práctica de la lectura en todas sus formas, incluso si la nociĂłn de una “biblioteca escolar” sugiere una lectura orientada a un propĂłsito. Motivado por el concepto de “patrimonio histĂłrico-educativo”, que distingue la esencia misma del SIPSE, se realizĂł un censo del patrimonio bibliográfico existente en las bibliotecas escolares de todos los niveles en toda Italia, a partir de colecciones locales especĂficas y significativas. La contribuciĂłn tiene como objetivo presentar el trabajo realizado y los resultados obtenidos hasta el momento
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