A Comparative Proteomic Analysis of Praziquantel-Susceptible and Praziquantel-Resistant Schistosoma mansoni Reveals Distinct Response Between Male and Female Animals

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Can we rely on iFR for avoiding FFR? Conclusions of a 5-year experience

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017Background: Recently, the instantaneous wave free ratio (iFR), has been proposed an alternative or complementary method to fractional flow reserve (FFR). This new method does not require the use of adenosine and may expedite the speed of functional assessment. The iFR “hybrid strategy” relies on values 0,93 as definitive results which would not require the use of FFR. However, this strategy is much less consensual than FFR alone. Purpose: We aimed to assess the concordance of FFR and iFR results using the principle of the “hybrid strategy”, based on the 5-year experience of a single center. We also aimed to analyse the effect of iFR in the operator's decision to proceed to FFR, and its impact on procedure duration and radiation time/dosage. Methods: Single-center registry of all patients undergoing functional coronary lesion assessment during 5 years. FFR was used as a gold standard (with a cut-off point for intervention ≤0,80) for assessing the diagnostic accuracy of iFR in every patient who underwent measurements with both techniques. For analysis purposes, an iFR value 0,93 was considered negative (i.e. defer intervention). Values in between were deemed inconclusive. For statistical analysis we used the T student and Chi-Square tests. Results: Functional testing was undertaken in 326 patients (67±11 years, 65,6% male), encompassing 402 lesions. 154 lesions underwent assessment with both techniques, 222 by FFR only and 26 cases iFR only. The average iFR was 0,9±0,1. 60 lesions had an iFR >0,93 and 21 an iFR <0,86. An iFR value between 0,86 and 0,93 was strongly associated with the decision to proceed to FFR (χ2=30,1; p0,93 (71,4% vs 68%; p=0,792). In these cases, there was a statistically significant concordance of 87% between the iFR and FFR results (χ2=22,43; p<0,001). Notwithstanding, there were 4 out of 13 cases (30,7%) of positive iFR with negative FFR and 3 out of 42 (7,1%) cases of negative iFR and positive FFR. This difference was statistically significant (p=0,026). Regarding procedural time, radiation time and radiation dose, there were no statistically significant differences between patients who only underwent iFR, FFR only, or both techniques. Conclusions: The iFR results were inconclusive (i.e. between 0,86 and 0,93) in most cases. There was a high degree of concordance between the iFR and FFR values. However, a significant proportion of patients, particularly in cases of positive iFR (<0,86), were classified as negative by FFR. The use of iFR had no impact on procedural time, radiation time and radiation dose.info:eu-repo/semantics/publishedVersio

Prognostic value of NT-proBNP, adrenomedullin, copeptin and proenkephalin in patients with pulmonary hypertension

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017.Introduction: Pulmonary hypertension (PH) comprises a group of progressive diseases characterized by an increase in pulmonary vascular resistance, leading to right ventricular dysfunction. Risk stratification is essential for prognostic evaluation and therapeutic decision, making the determination of new biomarkers important. Purpose: To assess the prognostic value of new biomarkers in the prognostic evaluation of patients with PH. Methods: Prospective cohort study of patients (pts) with PH confirmed by hemodynamic evaluation. Pts underwent clinical and laboratory evaluations at baseline and every 3 months. Follow-up lasted for 18 months. NTproBNP and the new biomarkers (adrenomedullin, copeptin and proenkephalin) were measured. The Mann-Whitney test, Kaplan-Meier survival analysis and Cox regression were used for statistical analysis. Results: Fifty one pts (75% males, mean age: 54±15 years) belonging to all groups of the WHO PH classification were included. At inclusion, all pts were in WHO functional class II or III. During the study period, 17 pts (33%) died. Baseline NTproBNP values were significantly higher in the non-survivors group (1327; 1061–2703pg/ml vs. 353.5; 190–1661pg/ml; p=0.022). The same did not occur for adrenomedullin, copeptin and proenkephalin baseline levels. The maximum NTproBNP, adrenomedullin and copeptin levels recorded during the follow-up period were significantly higher in the non-survivors group [2347.5 (1667–5073.25) pg/ml vs. 642.5 (208.25–4109.5) pg/ml, p=0.007; 53.6 (38.8- 94.2) pg/ml vs. 33.4 (27–48.8) pg/ml, p=0.0075; 20.69 (13.18–35.69) pmol/L vs. 9.97 (6.18–14.74) pmol/L, p=0.022, respectively]. This did not occur for the maximum proenkephalin level. The NT-proBNP level at admission and adremedullin level at 3 months were independent predictors of mortality (HR 2.78, CI95 1.23–6.30, p=0.01; HR 4.36, CI95 1.17–16.2, p=0.03).Conclusion: The maximum level of NTproBNP, adrenomedullin and copeptin during the follow up were associated with higher mortality in pts with PH. NTproBNP level proved to be an independent predictor of mortality in those patients. These results suggest the prognostic importance of these biomarkers in the approach of pts with PH.info:eu-repo/semantics/publishedVersio

Association between Metabolic Disorders and Cholangiocarcinoma: Impact of a Postulated Risk Factor with Rising Incidence

Introduction and objectives: The incidence of cholangiocarcinoma (CCA) has been increasing globally. Although a concomitant increase in the incidence of metabolic disorders might suggest a causal relationship, the data are scarce. We aimed to describe the prevalence of metabolic disorders in patients with CCA and report the clinical features and outcomes. Patients and Methods: Retrospective study including patients with CCA. Patients were divided into: (1) past history of diabetes or/and overweight/obesity (“metabolic disorder group”) and (2) without any of these features (“non-metabolic-disorder group”). A Cox regression model was used to determine the prognostic factors. Results: 122 patients were included. In total, 36 (29.5%) had overweight/obesity, 24 (19.7%) had diabetes, and 8 (6.6%) had both. A total of 29 (23.8%) patients had resectable disease and received upfront surgery. A total of 104 (85.2%) received chemotherapy for advanced/recurrent disease. The overall survival of the cohort was 14.3 months (95% CI: 10.1–17.3). ECOG-PS 0 (p < 0.0001), resectable disease (p = 0.018) and absence of vascular invasion (p = 0.048) were independently associated with better prognosis. The “metabolic disorder group” (n = 52) had a median survival of 15.5 months (95% CI 10.9–33.9) vs. 11.5 months (95% CI 8.4–16.5) in the “non-metabolic-disorder group” (n = 70) (HR: 1.10; 95% CI 0.62–1.94). Patients with resectable disease in the “metabolic group” had longer survival than patients in the “non-metabolic group” (43.4 months (95% CI 33.9-NR) vs. 21.8 months (95% CI 8.6–26.9); HR = 0.12, 95% CI 0.03–0.59). Conclusion: Metabolic disorders are frequent among CCA patients. Underlying metabolic comorbidities may be associated with prognosis in resectable CCA. There is a need to explore the mechanism that drives CCA carcinogenesis in a metabolic background

Hepatocellular carcinoma (HCC) in patients with Non-Alcoholic Fatty Liver Disease (NAFLD): screening, treatment and survival analysis in a Brazilian series

Objective: The aim of the present study was to evaluate the clinical features, Hepatocellular Carcinoma (HCC) screening, treatment modalities, and Overall Survival (OS) in a series of Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma (NAFLD-HCC) Brazilian patients. Methods: This was a cross-sectional study at the Instituto do Cancer do Estado de São Paulo, at the Faculdade de Medicina da Universidade de São Paulo with the approval of the local research ethics committee. NAFLD patients with HCC diagnosed, from May&nbsp;2010 to May&nbsp;2019, were included. Results: A total of&nbsp;131&nbsp;patients were included. Risk factors for NAFLD were present in&nbsp;94.7% of the patients. Only&nbsp;29% of patients were in the HCC screening program before diagnosis. HCC treatment was performed in&nbsp;84.7% of patients. Cumulative survival at the end of the first year was&nbsp;72%, second-year&nbsp;52%, and fifth-year&nbsp;32%. HCC screening before diagnosis was not significantly associated with higher cumulative survival. The independent factors associated with shorter general survival were BCLC C-D, p &lt; 0.001, and the size of the largest nodule&nbsp;&gt; 42&nbsp;mm, p&nbsp;=&nbsp;0.039. Conclusions: Although the efficacy of screening in our population regarding overall survival was hampered due to the sample size (29%&nbsp;had screening), BCLC stages&nbsp;C‒D and the size of the largest nodule larger than&nbsp;42&nbsp;mm were identified as independent factors of worse prognosis

Anesthesiology Consensus in the Management of the Airway

Os consensos na gestão clínica da via aérea em anestesiologia pretendem disponibilizar informação, baseada na evidência atual ou, na falta desta, na opinião de peritos, no que respeita à abordagem da via aérea difícil previsível ou não previsível. Reforçamos a importância da avaliação da via aérea e da identificação de potenciais problemas que possam condicionar dificuldade na sua abordagem e a adoção de uma estratégia segura que permita identificar e responder em crescendo de intervenção às dificuldades encontradas. Na impossibilidade de intubação traqueal (não intubo) otimizada e limitada a 4 tentativas, da impossibilidade de ventilar e oxigenar (não oxigeno) após 2 tentativas de usar um dispositivo supraglótico ou de uso de máscara facial inicialmente adequada é importante realizar, em tempo útil, uma cricotirotomia para assegurar oxigenação. As situações clínicas de exceção só com planos simples, conhecidos por todos e regularmente treinados e adaptados à nossa atividade clinica podem assegurar melhores “outcomes”. O registo destes eventos e a informação ao nosso doente da dificuldade encontrada e modo como foi resolvido o problema é essencial e constitui ainda um desafio a alargar a uma base nacional.info:eu-repo/semantics/publishedVersio

Distribution of hepatitis B virus subgenotype F2a in São Paulo, Brazil

Abstract\ud \ud \ud \ud Background\ud HBV genotype F is primarily found in indigenous populations from South America and is classified in four subgenotypes (F1 to F4). Subgenotype F2a is the most common in Brazil among genotype F cases. The aim of this study was to characterize HBV genotype F2a circulating in 16 patients from São Paulo, Brazil. Samples were collected between 2006 and 2012 and sent to Hospital Israelita Albert Einstein. A fragment of 1306 bp partially comprising HBsAg and DNA polymerase coding regions was amplified and sequenced. Viral sequences were genotyped by phylogenetic analysis using reference sequences from GenBank (n=198), including 80 classified as subgenotype F2a. Bayesian Markov chain Monte Carlo simulation implemented in BEAST v.1.5.4 was applied to obtain the best possible estimates using the model of nucleotide substitutions GTR+G+I.\ud \ud \ud \ud Findings\ud It were identified three groups of sequences of subgenotype F2a: 1) 10 sequences from São Paulo state; 2) 3 sequences from Rio de Janeiro and one from São Paulo states; 3) 8 sequences from the West Amazon Basin.\ud \ud \ud \ud Conclusions\ud These results showing for the first time the distribution of F2a subgenotype in Brazil. The spreading and the dynamic of subgenotype F2a in Brazil requires the study of a higher number of samples from different regions as it is unfold in almost all Brazilian populations studied so far. We cannot infer with certainty the origin of these different groups due to the lack of available sequences. Nevertheless, our data suggest that the common origin of these groups probably occurred a long time ago.This work has been supported by CNPq and by Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP 2011/50562-0 and 2008/50461-6, HCFMUSP, FFM, Alves de Queiroz Family Fund for Research and IIRS-SBIBAE. These supported institutions provided the found to development the DNA amplification, sequencing and phylogenetic analysis

Distribution of hepatitis B virus subgenotype F2a in São Paulo, Brazil

Abstract\ud \ud \ud \ud Background\ud HBV genotype F is primarily found in indigenous populations from South America and is classified in four subgenotypes (F1 to F4). Subgenotype F2a is the most common in Brazil among genotype F cases. The aim of this study was to characterize HBV genotype F2a circulating in 16 patients from São Paulo, Brazil. Samples were collected between 2006 and 2012 and sent to Hospital Israelita Albert Einstein. A fragment of 1306 bp partially comprising HBsAg and DNA polymerase coding regions was amplified and sequenced. Viral sequences were genotyped by phylogenetic analysis using reference sequences from GenBank (n=198), including 80 classified as subgenotype F2a. Bayesian Markov chain Monte Carlo simulation implemented in BEAST v.1.5.4 was applied to obtain the best possible estimates using the model of nucleotide substitutions GTR+G+I.\ud \ud \ud \ud Findings\ud It were identified three groups of sequences of subgenotype F2a: 1) 10 sequences from São Paulo state; 2) 3 sequences from Rio de Janeiro and one from São Paulo states; 3) 8 sequences from the West Amazon Basin.\ud \ud \ud \ud Conclusions\ud These results showing for the first time the distribution of F2a subgenotype in Brazil. The spreading and the dynamic of subgenotype F2a in Brazil requires the study of a higher number of samples from different regions as it is unfold in almost all Brazilian populations studied so far. We cannot infer with certainty the origin of these different groups due to the lack of available sequences. Nevertheless, our data suggest that the common origin of these groups probably occurred a long time ago.This work has been supported by CNPq and by Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP 2011/50562-0 and 2008/50461-6, HCFMUSP, FFM, Alves de Queiroz Family Fund for Research and IIRS-SBIBAE. These supported institutions provided the found to development the DNA amplification, sequencing and phylogenetic analysis

Photobiomodulation reduces the cytokine storm syndrome associated with Covid-19 in the zebrafish model

Although the exact mechanism of the pathogenesis of COVID-19 is not fully understood, oxidative stress and the release of pro-inflammatory cytokines have been highlighted as playing a vital role in the pathogenesis of the disease. In this sense, alternative treatments are needed to reduce the inflammation caused by COVID-19. Therefore, this study aimed to investigate the potential effect of red PBM as an attractive therapy to downregulate the cytokine storm caused by COVID-19 from a zebrafish model. RT-PCR analyses and protein-protein interaction prediction among SARS-CoV-2 and Danio rerio proteins showed that rSpike was responsible for generating systemic inflammatory processes with significantly increased pro-inflammatory (il1b, il6, tnfa, and nfkbiab), oxidative stress (romo1) and energy metabolism (slc2a1a, coa1) mRNA markers, with a pattern like those observed in COVID-19 cases in humans. On the other hand, PBM treatment decreased the mRNA levels of these pro-inflammatory and oxidative stress markers compared with rSpike in various tissues, promoting an anti-inflammatory response. Conversely, PBM promotes cellular and tissue repair of injured tissues and significantly increases the survival rate of rSpike-inoculated individuals. Additionally, metabolomics analysis showed that the most impacted metabolic pathways between PBM and the rSpike-treated groups were related to steroid metabolism, immune system, and lipids metabolism. Together, our findings suggest that the inflammatory process is an incisive feature of COVID-19, and red PBM can be used as a novel therapeutic agent for COVID-19 by regulating the inflammatory response. Nevertheless, the need for more clinical trials remains, and there is a significant gap to overcome before clinical trials.publishedVersio