Outcomes in the emergency endovascular repair of blunt thoracic aortic injuries

Abstract Thoracic aorta blunt injury (BAI) is a highly lethal lesion. A large number of victims die before obtaining emergency care. Thoracic endovascular aneurysm repair (TEVAR) is a less invasive method compared with open surgery and may change protocols for BAI treatment. This retrospective study was developed to evaluate the potential issues about thoracic endografting in the management of these patients. Twenty-seven patients with a BAI underwent aortic stent grafting. Intervention was preceded by the treatment of more urgent associated lesions in nine cases. In-hospital mortality was 7.4%. No paraplegia or ischemic complications developed because of the coverage of the left subclavian artery. In one case (3.2%), a type I endoleak was detected, proximal endograft infolding in two cases (7.4%) and endograft distal migration in further two cases were detected during follow-up (6-110 months). Thoracic endovascular aneurysm repair of BAI showed encouraging results in terms of perioperative mortality and morbidity. Concerns still remain about the potential mid- and long-term complications in younger patients

Control of mucocutaneous leishmaniasis, a neglected disease: results of a control programme in Satipo Province, Peru.

Mucocutaneous leishmaniasis (MCL) is an important health problem in many rural areas of Latin America, but there are few data on the results of programmatic approaches to control the disease. We report the results of a control programme in San Martin de Pangoa District, which reports one of the highest prevalences of MCL in Peru. For 2 years (2001--2002), the technicians at the health post were trained in patient case management, received medical support and were supplied with antimonials. An evaluation after 2 years showed the following main achievements: better diagnosis of patients, who were confirmed by microscopy in 34% (82/240) of the cases in 2001 and 60% of the cases (153/254) in 2002; improved follow-up during treatment: 237 of 263 (90%) patients who initiated an antimonial therapy ended the full treatment course; improved follow-up after treatment: 143 of 237 (60%) patients who ended their full treatment were correctly monitored during the required period of 6 (cutaneous cases) or 12 (mucosal cases) months after the end of treatment. These achievements were largely due to the human and logistical resources made available, the constant availability of medications and the close collaboration between the Ministry of Health, a national research institute and an international non-governmental organization. At the end of this period, the health authorities decided to register a generic brand of sodium stibogluconate, which is now in use. This should allow the treatment of a significant number of additional patients, while saving money to invest in other facets of the case management

Pre-existing T cell-mediated cross-reactivity to SARS-CoV-2 cannot solely be explained by prior exposure to endemic human coronaviruses

T-cell-mediated immunity to SARS-CoV-2-derived peptides in individuals unexposed to SARS-CoV-2 has been previously reported. This pre-existing immunity was suggested to largely derive from prior exposure to ‘common cold’ endemic human coronaviruses (HCoVs). To test this, we characterised the sequence homology of SARS-CoV-2-derived T-cell epitopes reported in the literature across the full proteome of the Coronaviridae family. 54.8% of these epitopes had no homology to any of the HCoVs. Further, the proportion of SARS-CoV-2-derived epitopes with any level of sequence homology to the proteins encoded by any of the coronaviruses tested is well-predicted by their alignment-free phylogenetic distance to SARS-CoV-2 (Pearson's r = −0.958). No coronavirus in our dataset showed a significant excess of T-cell epitope homology relative to the proportion of expected random matches, given their genetic similarity to SARS-CoV-2. Our findings suggest that prior exposure to human or animal-associated coronaviruses cannot completely explain the T-cell repertoire in unexposed individuals that recognise SARS-CoV-2 cross-reactive epitopes

Efficacy of SSRIs on cognition of Alzheimer's disease patients treated with cholinesterase inhibitors.

Background: This study examines the joint effect on cognition of selective serotonin re-uptake inhibitors (SSRIs) and cholinesterase inhibitors (AChEIs) in depressed patients affected by Alzheimer’s disease (AD) living at home. Methods: The study was conducted in two different outpatient neurological clinics. 338 patients with probable ADwere treated with ChEis (donepezil, rivastigmine and galantamine) as per the clinician’s judgment and were observed for nine months. At study entry, participants underwent a multidimensional assessment evaluating cognitive, functional and psychobehavioral domains. All patients were evaluated at baseline, after one (T1), three (T2) and nine months (T3). Patients were grouped in three different categories (patients not depressed and not treated with SSRIs, patients depressed and treated with SSRIs, and patients depressed but not treated with SSRIs). Results: At baseline 182 were diagnosed as not depressed and not treated with SSRIs, 66 as depressed and treated with SSRIs, and 90 as depressed but not treated with SSRIs. The mean change in MMSE score from baseline to nine months showed that depressed patients not treated worsened in comparison with those not depressed and not treated with SSRIs (mean change −0.8±2.3 vs 0.04±2.9; p = 0.02) and patients depressed and treated with SSRI (mean change −0.8±2.3 vs 0.1±2.5; p = 0.03). Conclusions: In AD patients treated with AChEIs, SSRIs may exert some degree of protection against the negative effects of depression on cognition

Effectiveness of expressive writing protocol in palliative care healthworkers: A quantitative study

Background and aim of the work: Palliative Care professionals are exposed to intense emotional envi-ronment. This puts them at risk for Compassion Fatigue and Burnout. The protective factors that can counter their onset are Compassion Satisfaction, Organizational Commitment and Resilience. Expressive Writing is a valid tool for adapting to traumatic events and enhancing psychological well-being. Aim of this study is to evaluate the effect of the Expressive Writing in Palliative Care professionals on Compassion Satisfaction, Organizational Commitment, Resilience, Compassion Fatigue and perceived distress. Methods: Prospective experimental study with experimental/control groups and pre/post measurements. 50 Palliative Care professionals were recruited in Northern and Central Italy. Participants filled: Organizational Commitment Questionnaire; ProQol-revision III; Resilience Scale for Adults; Impact of Event-Scale Revised; Emotion Thermometer; ad hoc questionnaire for the evaluation of protocol usefulness. Results: Wilcoxon test demon-strated change in Continuative Commitment (Z =-3.357, p = .001), anger (Z =-2.214, p = .027), sleep (Z =-2.268, p = .023), help (Z =-2.184, p = .029), intrusiveness (Z =-2.469, p = .014), hyperarousal (Z =-2.717, p = .007), and total IES (Z =-2.456, p =, 014). Mann Whitney test showed a significantly lower score on post-test Intrusiveness in the experimental group (U = 202, p = .038). Conclusions: The Expressive Writing intervention was effective in improving organizational and emotional variables. Expressive Writing supports healthcare professionals in relieving the burden of traumatic episodes, ordering associated thoughts and emo-tions, and implementing a process of deep comprehension

Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase

Reverse transcriptase (RT) from the human immunodeficiency virus continues to be an attractive drug target for antiretroviral therapy. June 2022 will commemorate the 30th anniversary of the first Human Immunodeficiency Virus (HIV) RT crystal structure complex that was solved with non-nucleoside reverse transcriptase inhibitor nevirapine. The release of this structure opened opportunities for designing many families of non-nucleoside reverse transcriptase inhibitors (NNRTIs). In paying tribute to the first RT-nevirapine structure, we have developed several compound classes targeting the non-nucleoside inhibitor binding pocket of HIV RT. Extensive analysis of crystal structures of RT in complex with the compounds informed iterations of structure-based drug design. Structures of seven additional complexes were determined and analyzed to summarize key interactions with residues in the non-nucleoside inhibitor binding pocket (NNIBP) of RT. Additional insights comparing structures with antiviral data and results from molecular dynamics simulations elucidate key interactions and dynamics between the nucleotide and non-nucleoside binding sites.Fil: Frey, Kathleen M.. University of Yale; Estados UnidosFil: Bertoletti, Nicole. University of Yale; Estados UnidosFil: Chan, Albert H.. University of Yale; Estados UnidosFil: Ippolito, Joseph A.. University of Yale; Estados UnidosFil: Bollini, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina. University of Yale; Estados UnidosFil: Spasov, Krasimir A.. University of Yale; Estados UnidosFil: Jorgensen, William L.. University of Yale; Estados UnidosFil: Anderson, Karen S.. University of Yale; Estados Unido

Consistency of safety and efficacy of new oral anticoagulants across subgroups of patients with atrial fibrillation.

AIMS: The well-known limitations of vitamin K antagonists (VKA) led to development of new oral anticoagulants (NOAC) in non-valvular atrial fibrillation (NVAF). The aim of this meta-analysis was to determine the consistency of treatment effects of NOAC irrespective of age, comorbidities, or prior VKA exposure. METHODS AND RESULTS: All randomized, controlled phase III trials comparing NOAC to VKA up to October 2012 were eligible provided their results (stroke/systemic embolism (SSE) and major bleeding (MB)) were reported according to age (≤ or >75 years), renal function, CHADS2 score, presence of diabetes mellitus or heart failure, prior VKA use or previous cerebrovascular events. Interactions were considered significant at p <0.05. Three studies (50,578 patients) were included, respectively evaluating apixaban, rivaroxaban, and dabigatran versus warfarin. A trend towards interaction with heart failure (p = 0.08) was observed with respect to SSE reduction, this being greater in patients not presenting heart failure (RR = 0.76 [0.67-0.86]) than in those with heart failure (RR = 0.90 [0.78-1.04]); Significant interaction (p = 0.01) with CHADS2 score was observed, NOAC achieving a greater reduction in bleeding risk in patients with a score of 0-1 (RR 0.67 CI 0.57-0.79) than in those with a score ≥2 (RR 0.85 CI 0.74-0.98). Comparison of MB in patients with (RR 0.97 CI 0.79-1.18) and without (RR 0.76 CI 0.65-0.88) diabetes mellitus showed a similar trend (p = 0.06). No other interactions were found. All subgroups derived benefit from NOA in terms of SSE or MB reduction. CONCLUSIONS: NOAC appeared to be more effective and safer than VKA in reducing SSE or MB irrespective of patient comorbidities. Thromboembolism risk, evaluated by CHADS2 score and, to a lesser extent, diabetes mellitus modified the treatment effects of NOAC without complete loss of benefit with respect to MB reduction

Escaping High Viral Load Exhaustion: CD8 Cells with Altered Tetramer Binding in Chronic Hepatitis B Virus Infection

Deletion, anergy, and a spectrum of functional impairments can affect virus-specific CD8 cells in chronic viral infections. Here we characterize a low frequency population of CD8 cells present in chronic hepatitis B virus (HBV) infection which survive in the face of a high quantity of viral antigen. Although they do not appear to exert immunological pressure in vivo, these CD8 cells are not classically “tolerant” since they proliferate, lyse, and produce antiviral cytokines in vitro. They are characterized by altered HLA/peptide tetramer reactivity, which is not explained by TCR down-regulation or reduced functional avidity and which can be reversed with repetitive stimulation. CD8 cells with altered tetramer binding appear to have a specificity restricted to envelope antigen and not to other HBV antigens, suggesting that mechanisms of CD8 cell dysfunction are differentially regulated according to the antigenic form and presentation of individual viral antigens

The rationale, design, and methods of a randomized, controlled trial to evaluate the efficacy and safety of an active strategy for the diagnosis and treatment of acute pulmonary embolism during exacerbations of chronic obstructive pulmonary disease

Introduction: Some previous studies have suggested a high prevalence of pulmonary embolism (PE) during exacerbations of chronic obstructive pulmonary disease (ECOPD). The SLICE trial aims to assess the efficacy and safety of an active strategy for the diagnosis and treatment of PE (vs usual care) in patients hospitalized because of ECOPD. Methods: SLICE is a phase III, prospective, international, multicenter, randomized, open-label, and parallel-group trial. A total of 746 patients hospitalized because of ECOPD will be randomized in a 1:1 fashion to receive either an active strategy for the diagnosis and anticoagulant treatment of PE or usual care (ie, standard care without any diagnostic test for diagnosing PE). The primary outcome is a composite of all-cause death, non-fatal (recurrent) venous thromboembolism (VTE), or readmission for ECOPD within 90 days after enrollment. Secondary outcomes are (a) death from any cause within 90 days after enrollment, (b) non-fatal (recurrent) VTE within 90 days after enrollment, (c) readmission within 90 days after enrollment, and (d) length of hospital stay. Results: Enrollment started in September 2014 and is expected to proceed until 2020. Median age of the first 443 patients was 71 years (interquartile range, 64-78), and 26% were female. Conclusions: This multicenter trial will determine the value of detecting PEs in patients with ECOPD. This has implications for COPD patient morbidity and mortality

Contribution of Herpesvirus Specific CD8 T Cells to Anti-Viral T Cell Response in Humans

Herpesviruses infect most humans. Their infections can be associated with pathological conditions and significant changes in T cell repertoire but evidences of symbiotic effects of herpesvirus latency have never been demonstrated. We tested the hypothesis that HCMV and EBV-specific CD8 T cells contribute to the heterologous anti-viral immune response. Volume of activated/proliferating virus-specific and total CD8 T cells was evaluated in 50 patients with acute viral infections: 20 with HBV, 12 with Dengue, 12 with Influenza, 3 with Adenovirus infection and 3 with fevers of unknown etiology. Virus-specific (EBV, HCMV, Influenza) pentamer+ and total CD8 T cells were analyzed for activation (CD38/HLA-DR), proliferation (Ki-67/Bcl-2low) and cytokine production. We observed that all acute viral infections trigger an expansion of activated/proliferating CD8 T cells, which differs in size depending on the infection but is invariably inflated by CD8 T cells specific for persistent herpesviruses (HCMV/EBV). CD8 T cells specific for other non-related non persistent viral infection (i.e. Influenza) were not activated. IL-15, which is produced during acute viral infections, is the likely contributing mechanism driving the selective activation of herpesvirus specific CD8 T cells. In addition we were able to show that herpesvirus specific CD8 T cells displayed an increased ability to produce the anti-viral cytokine interferon-γ during the acute phase of heterologous viral infection. Taken together, these data demonstrated that activated herpesvirus specific CD8 T cells inflate the activated/proliferating CD8 T cells population present during acute viral infections in human and can contribute to the heterologous anti-viral T cell response