Smoking: what has been addressed in brazilian journals

O tema tabagismo, em seus vários aspectos, vem recebendo crescente atenção entre os pesquisadores ao longo dos últimos anos, o que tem se refletido em maior e mais sólida produção científica sobre o assunto em periódicos nacionais. Este artigo tem como objetivo comentar os estudos que abordaram o tema tabagismo publicados entre janeiro de 2010 e junho de 2012, nas revistas Arquivos Brasileiros de Cardiologia, Brazilian Journal of Medical and Biological Research, Clinics (São Paulo), Jornal Brasileiro de Pneumologia, Revista da Associação Médica Brasileira e Revista Brasileira de Cirurgia Cardiovascular. No período foram publicados 58 artigos, 52 originais, abordando variados aspectos, como efeitos na saúde, epidemiologia, cessação e estudos experimentais

COVID-19 atypical Parsonage-Turner syndrome: a case report

Background Neurological manifestations of Sars-CoV-2 infection have been described since March 2020 and include both central and peripheral nervous system manifestations. Neurological symptoms, such as headache or persistent loss of smell and taste, have also been documented in COVID-19 long-haulers. Moreover, long lasting fatigue, mild cognitive impairment and sleep disorders appear to be frequent long term neurological manifestations after hospitalization due to COVID-19. Less is known in relation to peripheral nerve injury related to Sars-CoV-2 infection. Case presentation We report the case of a 47-year-old female presenting with a unilateral chest pain radiating to the left arm lasting for more than two months after recovery from Sars-CoV-2 infection. After referral to our post-acute outpatient service for COVID-19 long haulers, she was diagnosed with a unilateral, atypical, pure sensory brachial plexus neuritis potentially related to COVID-19, which occurred during the acute phase of a mild Sars-CoV-2 infection and persisted for months after resolution of the infection. Conclusions We presented a case of atypical Parsonage-Turner syndrome potentially triggered by Sars-CoV-2 infection, with symptoms and repercussion lasting after viral clearance. A direct involvement of the virus remains uncertain, and the physiopathology is unclear. The treatment of COVID-19 and its long-term consequences represents a relatively new challenge for clinicians and health care providers. A multidisciplinary approach to following-up COVID-19 survivors is strongly advised

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

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

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

: The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways

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

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

Insight from an Italian Delphi Consensus on EVAR feasibility outside the instruction for use: the SAFE EVAR Study

BACKGROUND: The SAfety and FEasibility of standard EVAR outside the instruction for use (SAFE-EVAR) Study was designed to define the attitude of Italian vascular surgeons towards the use of standard endovascular repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA) outside the instruction for use (IFU) through a Delphi consensus endorsed by the Italian Society of Vascular and Endovascular Surgery (Societa Italiana di Chirurgia Vascolare ed Endovascolare - SICVE). METHODS: A questionnaire consisting of 26 statements was developed, validated by an 18 -member Advisory Board, and then sent to 600 Italian vascular surgeons. The Delphi process was structured in three subsequent rounds which took place between April and June 2023. In the first two rounds, respondents could indicate one of the following five degrees of agreement: 1) strongly agree; 2) partially agree; 3) neither agree nor disagree; 4) partially disagree; 5) strongly disagree; while in the third round only three different choices were proposed: 1) agree; 2) neither agree nor disagree; 3) disagree. We considered the consensus reached when &gt;70% of respondents agreed on one of the options. After the conclusion of each round, a report describing the percentage distribution of the answers was sent to all the participants. RESULTS: Two -hundred -forty-four (40.6%) Italian Vascular Surgeons agreed to participate the first round of the Delphi Consensus; the second and the third rounds of the Delphi collected 230 responders (94.3% of the first -round responders). Four statements (15.4%) reached a consensus in the first rounds. Among the 22 remaining statements, one more consensus (3.8%) was achieved in the second round. Finally, seven more statements (26.9%) reached a consensus in the simplified last round. Globally, a consensus was reached for almost half of the proposed statements (46.1%). CONCLUSIONS: The relatively low consensus rate obtained in this Delphi seems to confirm the discrepancy between Guideline recommendations and daily clinical practice. The data collected could represent the source for a possible guidelines' revision and the proposal of specific Good Practice Points in all those aspects with only little evidence available

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands