Mechanisms of atherothrombosis in chronic obstructive pulmonary disease

Patients affected by chronic obstructive pulmonary disease (COPD) have an increased risk of atherothrombotic acute events, independent of smoking and other cardiovascular risk factors. As a consequence, myocardial ischemia is a relevant cause of death in these patients. We reviewed studies concerning the potential mechanisms of atherothrombosis in COPD. Bronchial inflammation spreads to the systemic circulation and is known to play a key role in plaque formation and rupture. In fact, C-reactive protein blood levels increase in COPD and provide independent prognostic information. Systemic inflammation is the first cause of the hypercoagulable state commonly observed in COPD. Furthermore, hypoxia is supposed to activate platelets, thus accounting for the increased urinary excretion of platelet-derived thromboxane in COPD. The potential metabolic risk in COPD is still debated, in that recent studies do not support an association between COPD and diabetes mellitus. Finally, oxidative stress contributes to the pathogenesis of COPD and may promote oxidation of low-density-lipoproteins with foam cells formation. Retrospective observations suggest that inhaled corticosteroids may reduce atherothrombotic mortality by attenuating systemic inflammation, but this benefit needs confirmation in ongoing randomized controlled trials. Physicians approaching COPD patients should always be aware of the systemic vascular implications of this disease

Distancing Measures in COVID-19 Pandemic: Loneliness, More than Physical Isolation, Affects Health Status and Psycho-Cognitive Wellbeing in Elderly Patients with Chronic Obstructive Pulmonary Disease.

Since the outbreak of the SARS-CoV-2 pandemic in 2020, many governments have been imposing confinement and physical distancing measures. No data exist on the effects of lockdowns on the health status of patients affected by chronic pathologies, specifically those with Chronic Obstructive Pulmonary Disease (COPD). Our study aims to establish variations across the psychological and cognitive profile of patients during the isolation period in Italy, in a cohort of patients affected by COPD, between February and May 2020. Forty patients with established COPD were comprehensively evaluated by geriatric multidimensional assessment before the spread of the epidemic in Italy, and submitted to a second evaluation during the subsequent lockdown. We assessed functional ability, basic and instrumental Activities of Daily Living (ADL and IADL), cognition and mood status. We compared the scores obtained at baseline against those obtained during the pandemic, and used mean differences for correlation with major clinical and functional indexes. The score differences from MMSE, ADL and IADL were statistically significant. Such differences were correlated to the presence of a caregiver and to the total number of family members living together. Remarkably, the loneliness dimension, more than the restrictions themselves, seemed to represent the major determinant of altered health status and depressed psycho-cognitive profile in our population. Also remarkably, we detected no correlation between the score variation and the respiratory function indexes of disease severity. The isolation measures adopted during the SARS-CoV-2 pandemic have triggered the classic clinical string associated to geriatric isolation, which leads to a deterioration of cognitive functions, independence and frailty levels in a population affected by a chronic degenerative disease, such as COPD. If considered from a multidimensional geriatric point of view, the individual benefit of isolation measures could be small or non-existent

Burnout in cardiac anesthesiologists. results from a national survey in italy

Objective: There is increasing burnout incidence among medical disciplines, and physicians working in emergency settings seem at higher risk. Cardiac anesthesiology is a stressful anesthesiology subspecialty dealing with high-risk patients. The authors hypothesized a high risk of burnout in cardiac anesthesiologists. Design: National survey conducted on burnout Setting: Italian cardiac centers. Participants: Cardiac anesthesiologists. Interventions: The authors administered via email an anonymous questionnaire divided into 3 parts. The first 2 parts evaluated workload and private life. The third part consisted of the Maslach Burnout Inventory test with its 3 constituents: high emotional exhaustion, high depersonalization, and low personal accomplishment. Measurements and Main Results: The authors measured the prevalence and risk of burnout through the Maslach Burnout Inventory questionnaire and analyzed factors influencing burnout. Among 670 contacts from 71 centers, 382 cardiac anesthesiologists completed the survey (57%). The authors found the following mean Maslach Burnout Inventory values: 14.5 ± 9.7 (emotional exhaustion), 9.1 ± 7.1 (depersonalization), and 33.7 ± 8.9 (personal accomplishment). A rate of 34%, 54%, and 66% of respondents scored in “high” or “moderate-high” risk of burnout (emotional exhaustion, depersonalization, and personal accomplishment, respectively). The authors found that, if offered to change subspecialty, 76% of respondents would prefer to remain in cardiac anesthesiology. This preference and parenthood were the only 2 investigated factors with a protective effect against all components of burnout. Significantly lower burnout scores were found in more experienced anesthesiologists. Conclusion: A relatively high incidence of burnout was found in cardiac anesthesiologists, especially regarding high depersonalization and low personal accomplishment. Nonetheless, most of the respondents would choose to remain in cardiac anesthesiology

Fourth case of louse-borne relapsing fever in Young Migrant, Sicily, Italy, December 2015. Mini Review Article

Objectives Currently louse-borne relapsing fever (LBRF) is primarily found in limited endemic foci in Ethiopia, Somalia and Sudan; no case of imported LBRF has been reported in Europe in the 9 years prior to 2015. The aim of our paper is to describe a new case of imported LBRF detected in Sicily, Italy, and to review all cases reported in migrants arrived in Europe in the last 10 years. Study design Mini review of all published cases of louse-borne relapsing fever in Europe in the last 10 years. Methods A computerized search without language restriction was conducted using PubMed combining the terms ‘(louse-borne relapsing fever or LBRF or recurrentis) and (refugee or Europe or migrant)’ without limits. Furthermore, the ‘Ahead-of-Print Articles’ of the top 10 journals (ranked by Impact factor – Web of Science) of Infectious diseases and of Epidemiology were checked. Results Our search identified 26 cases of LBRF between July and October 2015 in migrants recently arrived in Europe: 8 had been described in Italy; 1 in Switzerland; 2 in the Netherlands; 15 in Germany. We describe data regarding the clinical characteristics, diagnostic methods, therapy and outcome of these patients and of the new case. Conclusions LBRF by Borrelia recurrentis should be considered among the clinical hypotheses in migrants presenting with fever, headache, chills, sweating, arthralgia, myalgia, dizziness, nausea and vomiting

Bausteine zur deutschen und italienischen Geschichte. Festschrift zum 70. Geburtstag von Horst Enzensberger

Die Festschrift zum 70. Geburtstag von Horst Enzensberger greift mit ihren Beiträgen die Forschungsgebiete des Jubilars auf. Das Spektrum reicht von der spätantiken Geschichte Italiens bis zur deutschen Mittelalterforschung im 20. Jahrhundert. Die Beiträge geben Einblick in die vielfältigen kulturellen Einflüsse und Überlagerungen auf Sizilien, in die Geschichte religiöser Orden, Praktiken und kirchlicher Strukturen sowie in die kriegerischen Auseinandersetzungen Europas. Besonders hervorgehoben werden dabei die Kontakte zwischen der italienischen Halbinsel und MitteleuropaAll the articles united in this volume on the occasion of Horst Enzensberger’s 70th anniversary refer to his manifold fields of research. The issues range from the late Antiquity in Italy to German medieval studies in the 20th century. The articles provide an insight into varied cultural influences and interactions in Sicily, into the history of religious orders, practices and ecclesiastical structures as well as into Europe’s military conflicts. Particular attention is drawn to the contacts between the Italian peninsula and Central Europ

Dual Relief of T-lymphocyte Proliferation and Effector Function Underlies Response to PD-1 Blockade in Epithelial Malignancies

Although understanding of T-cell exhaustion is widely based on mouse models, its analysis in patients with cancer could provide clues indicating tumor sensitivity to immune checkpoint blockade (ICB). Data suggest a role for costimulatory pathways, particularly CD28, in exhausted T-cell responsiveness to PD-1/PD-L1 blockade. Here, we used single-cell transcriptomic, phenotypic, and functional approaches to dissect the relation between CD8+ T-cell exhaustion, CD28 costimulation, and tumor specificity in head and neck, cervical, and ovarian cancers. We found that memory tumor–specific CD8+ T cells, but not bystander cells, sequentially express immune checkpoints once they infiltrate tumors, leading, in situ, to a functionally exhausted population. Exhausted T cells were nonetheless endowed with effector and tumor residency potential but exhibited loss of the costimulatory receptor CD28 in comparison with their circulating memory counterparts. Accordingly, PD-1 inhibition improved proliferation of circulating tumor–specific CD8+ T cells and reversed functional exhaustion of specific T cells at tumor sites. In agreement with their tumor specificity, high infiltration of tumors by exhausted cells was predictive of response to therapy and survival in ICB-treated patients with head and neck cancer. Our results showed that PD-1 blockade–mediated proliferation/reinvigoration of circulating memory T cells and local reversion of exhaustion occur concurrently to control tumors

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Human TH17 and regulatory T cells : shared developmental mechanisms and relationship with the intestinal microbiota

Deux populations de lymphocytes T CD4 régulateurs (Treg), les naturels (nTreg) et induits (iTreg), assurent la tolérance au soi et aux microorganismes commensaux et le contrôle des réponses immunitaires exagérées. Au cours de ma thèse j’ai investigué les mécanismes qui permettraient de cibler de façon différentielle une des populations Treg ainsi que le rôle du microbiote intestinal dans l’ontogénie des iTreg. Les iTreg ont des liens avec la population de lymphocytes T CD4 proinflammatoires TH17. Cela m’a amenée à examiner l’expression du gène IL4I1 codant pour une Lphénylalanine oxydase qui inhibe la prolifération des lymphocytes T et exprimé dans les TH17. J’ai montré que parmi les Treg l’IL4I1 était exprimé préférentiellement dans les iTreg et qu’en conditions inflammatoires son expression augmentait et accompagnait la conversion des Treg en TH17. Le profil différentiel d’expression de l’IL4I1 pourrait fournir une base pour le ciblage spécifique des iTreg.Alors que les nTreg se développent dans le thymus, des modèles murins indiquent que le microbiote intestinal joue un rôle important dans l’ontogénie des iTreg et des TH17. Afin d’étudier l’influence du microbiote intestinal sur le développement des iTreg et des TH17 chez l’homme, je me suis intéressée aux bactéries filamenteuses segmentées (SFB) qui jouent un rôle important dans le développement de l’immunité intestinale chez la souris. Nous avons mis en évidence des réponses T CD4 spécifiques de SFB dont une fraction exprimait les facteurs de transcription et les cytokines caractéristiques des Treg et des TH17. De plus, nos données suggèrent que ces réponses pourraient jouer un rôle dans la polyarthrite rhumatoïde.Two populations of regulatory CD4 T cells (Treg), natural Treg (nTreg) and induced Treg (iTreg), ensure tolerance to self and to commensal microorganisms as well as control of exaggerated immune responses. During my PhD research, I investigated mechanisms that could allow for the differential targeting of these Treg populations as well as the role of intestinal microbiota in iTreg ontogeny. iTreg have close ties to TH17, a population of pro-inflammatory CD4 T cells. This led me to examine the expression of the IL4I1 gene, which encodes an L-phenylalanine oxidase able to inhibit T cell proliferation and that is expressed in TH17 cells. We showed that among Treg IL4I1 was preferentially expressed in iTreg and that in inflammatory conditions its expression was enhanced and accompanied Treg conversion into TH17. The differential expression profile of IL4I1 could provide opportunities for the specific targeting of the iTreg population. Whereas nTreg develop in the thymus, data obtained in mouse models indicate that the intestinal microbiota plays a prominent role in the ontogeny of iTreg as well as in the development of TH17. In order to address the influence of the gut microbiota on the development of human iTreg and TH17, I focused on segmented filamentous bacteria (SFB) that play a central role in the development of intestinal immunity in mice. We detected SFB specific CD4 T cell responses in healthy individuals and a fraction of cells expressed Treg and TH17 signature transcription factors and cytokines. In addition, our data suggest that these responses could play a role in rheumatoid arthritis