Cognitive Function and Atrial Fibrillation: From the Strength of Relationship to the Dark Side of Prevention. Is There a Contribution from Sinus Rhythm Restoration and Maintenance?

Atrial fibrillation (AF) is the most common chronic cardiac arrhythmia with an increasing prevalence over time mainly because of population aging. It is well established that the presence of AF increases the risk of stroke, heart failure, sudden death, and cardiovascular morbidity. In the last two decades several reports have shown an association between AF and cognitive function, ranging from impairment to dementia. Ischemic stroke linked to AF is a well-known risk factor and predictor of cognitive decline. In this clinical scenario, the risk of stroke might be reduced by oral anticoagulation. However, recent data suggest that AF may be a predictor of cognitive impairment and dementia also in the absence of stroke. Cerebral hypoperfusion, reduced brain volume, microbleeds, white matter hyperintensity, neuroinflammation, and genetic factors have been considered as potential mechanisms involved in the pathogenesis of AF-related cognitive dysfunction. However, a cause-effect relationship remains still controversial. Consequently, no therapeutic strategies are available to prevent AF-related cognitive decline in stroke-free patients. This review will analyze the potential mechanisms leading to cognitive dysfunction in AF patients and examine the available data on the impact of a sinus rhythm restoration and maintenance strategy in reducing the risk of cognitive decline

Cystic lymphoepithelial lesions of the parotid gland in HIV-1 infection

The benign cystic lymphoepithelial lesion (BLL) of the parotid gland is a rare disorder affecting HIV-1-infected patients. Here we describe the clinical and histopathological features of 10 cases of BLL, who presented to our observation between November 1992 and December 1996, before the combination antiretroviral therapy was introduced

The benign cystic lymphoepithelial lesion (BLL) of the parotid gland is a viral reservoir in HIV-1 infected patients

he presence of HIV-1 in cystic fluid aspirates from six cases of benign cystic lymphoepithelial lesion (BLL) of the parotid gland, a rare disorder affecting HIV-1-infected patients, has been investigated. HIV-1 p24 protein was present at a concentration ranging from 3 to 15 ng/ml, while it was undetectable in the peripheral blood of the same patients, The number of RNA copies of HIV-1 in the cystic fluids was high, ranging from 0.5 x 10(7) to 7.2 x 10(7) RNA copies/ml. BLL cystic fluid aspirates, despite the high level of HIV-1 RNA, were found to contain only a few infectious virions, The low infectivity correlated with the infrequent detection by electron microscopy of complete HIV-1 particles. The pathogenic mechanism leading to virus accumulation in the cystic fluid was studied by immunohistochemistry of tissue sections. p24 protein was associated with DRC-1(+)/S-100(+) follicular dendritic reticulum cells, which were also present within the cystic cavities, Our findings are consistent with the possibility that the large amounts of virus present in the fluid derive from continuous shedding of HIV-1-infected cells from the surrounding lymphoid tissue

Regional HIV Surveillance in Italy: a starting point for the future national system

BACKGROUND: the Italian National HIV Surveillance, instituted by the Ministerial Decree of March 31st, 2008, is based on 21 regional surveillance systems and adopts an essential data collection form with a definite data flow. The unification of HIV and AIDS surveillance systems and the implementation of an identical data collection form are priorities of the Italian National HIV/AIDS Action Plan 2017 (PNAIDS). OBJECTIVES: to describe the 21 regional HIV surveillance systems and to verify the feasibility of their unification. METHODS: in March 2017, a questionnaire containing 13 questions was sent to all the regional representatives of the 21 surveillance systems. The main questions were about timeliness, data flow, and quality of the system. The quality was measured through a subjective evaluation expressed by the regional referent through scores from 1 (minimum) to 10 (maximum) regarding four indicators (regional coverage, timeliness, correctness, and completeness of the data). RESULTS: more than half of the regional systems use a computerized data collection method. Some of these regions have not completely adapted to the data collection form contained in the Decree and other regions declare a undernotification of the system. The majority of the regions record a slight notification delay by the reporting centres. Some regions report gaps in the completeness of the data received by the reporting centres. CONCLUSIONS: the main strengths of the HIV surveillance system are computerization of the systems and slightly reporting delay. Regarding the quality of the regional systems and its data, the study reports a good self-evaluation. This study also showed useful indications to improve the national HIV surveillance system, such as the unification of HIV surveillance with the AIDS surveillance and the implementation of a unique national system, as suggested by guidelines of the PNAIDS 2017

Diritto e nuove tecnologie. Tra comparazione e interdisciplinarità.

Il fascicolo raccoglie gli atti del Seminario di diritto comparato dell’Associazione “Gruppo di Pisa” del 26 marzo 2021 su “Diritto e nuove tecnologie tra comparazione e interdisciplinarità” – Università degli Studi di Milano

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P<0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)

Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial (Journal of Translational Medicine, (2020), 18, 1, (405), 10.1186/s12967-020-02573-9)

Following publication of the original article [1] the authors identified that the collaborators of the TOCIVID-19 investigators, Italy were only available in the supplementary file. The original article has been updated so that the collaborators are correctly acknowledged. For clarity, all collaborators are listed in this correction article