Search

Natalia A Wilson,1 James E Tcheng,2 Jove Graham,3 Joseph P Drozda Jr4 1College of Health Solutions, Arizona State University, Phoenix, AZ, USA; 2Department of Medicine, Duke University School of Medicine, Durham, NC, USA; 3Center for Pharmacy Innovation and Outcomes, Geisinger, Danville, PA, USA; 4Mercy Research, Mercy, Chesterfield, MO, USACorrespondence: Natalia A Wilson, College of Health Solutions, Arizona State University, Phoenix, AZ, USA, Email natalia.wilson@asu.eduBackground: The requirement for medical device manufacturers to label their devices with a unique device identifier (UDI) was formalized by the 2013 US Food and Drug Administration Unique Device Identification System Rule. However, parallel regulatory requirement for US health systems to use UDIs, particularly the electronic documentation of UDIs during patient care is lacking. Despite the lack of regulation, some health systems have implemented and are using UDIs. To assess the current state, we studied representative health system UDI implementation experiences, including barriers and the strategies to overcome them, and identified next steps to advance UDI adoption.Methods: Semi-structured interviews were performed with health system personnel involved in UDI implementation in their cardiac catheterization labs or operating rooms. Interviews were transcribed and analyzed using the framework methodology of Ritchie and Spencer. An expert panel evaluated findings and informed barriers, strategies, and next steps.Results: Twenty-four interviews at ten health systems were performed. Identified barriers were internal (lack of organizational support, information technology gaps, clinical resistance) and external (information technology vendor resistance, limitations in manufacturer support, gaps in reference data, lack of an overall UDI system). Identified strategies included relationship building, education, engagement, and communication. Next steps to advance UDI adoption focus on education, research, support, and policy.Conclusions and Implications: Delineation of UDI implementation barriers and strategies provides guidance and support for health systems to adopt the UDI standard and electronically document UDIs during clinical care. Next steps illuminate critical areas for attention to advance UDI adoption and achieve a comprehensive UDI system in health care to strengthen patient care and safety.Keywords: unique device identifier, FDA, implementation barriers, implementation strategies, information technology systems, device manufacturer responsibilities

Natalia A Wilson, 1 James E Tcheng, 2 Jove Graham, 3 Joseph P Drozda Jr 4 1College of Health Solutions, Arizona State University, Phoenix, AZ, USA; 2Duke University School of Medicine and Health System, Durham, NC, USA; 3Center for Pharmacy Innovation and Outcomes, Geisinger, Danville, PA, USA; 4Outcomes Research, Mercy, Chesterfield, MO, USACorrespondence: Natalia A WilsonCollege of Health Solutions, Arizona State University, 500 N. 3rd St., Phoenix, AZ, 85004, USAEmail natalia.wilson@asu.eduBackground: The US Food and Drug Administration’s Unique Device Identification System Rule of 2013 mandated manufacturers to assign unique device identifiers (UDIs) to their medical devices. Most high-risk (Class III), moderate-risk (Class II) and implantable devices now have UDIs. To achieve the necessary next step for a comprehensive UDI-enabled system for patient safety, UDIs must be electronically documented during patient care, a process not routinely done. The purpose of this research was to study the implementation experiences of diverse health systems in order to develop a roadmap for UDI implementation at the point of care.Methods: Semi-structured interviews were conducted with personnel at health systems that had implemented UDI for implantable devices in their cardiac catheterization labs or operating rooms. Interviews were audio-recorded, transcribed, and analyzed using the framework methodology of Ritchie and Spencer. Data interpretation involved development of a conceptual model and detailed recommendations for UDI implementation. An expert panel evaluated and provided input on the roadmap.Results: Twenty-four interviews at ten health systems were conducted by phone. Participants described implementation steps, factors and barriers impacting implementation. Findings populated a UDI implementation roadmap, that includes Foundational Themes, Key Components, Key Steps, UDI Use, and Outcomes.Conclusions and Implications: The UDI implementation roadmap provides a framework for health systems to address the necessary steps and multilevel factors that underpin UDI implementation at the point of care. It is intended to guide and advance routine electronic documentation of UDIs for devices used during clinical care, the critical next step for a comprehensive UDI-enabled system to enhance medical device safety and effectiveness for patients.Keywords: unique device identifiers, implants, implementation framework, UDI-enabled system, implantable devices

AbstractBackground The Covid-19 pandemic has affected patients with end-stage kidney disease (ESKD). Whether dialysis parameters have a prognostic value in ESKD patients with Covid-19 remains unclear.Materials and Methods We retrospectively evaluated clinical characteristics, blood pressure (BP) and dialysis parameters in ESKD patients undergoing maintenance outpatient hemodialysis, with (Covid-ESKD) and without (No-Covid-ESKD) Covid-19, at four Brazilian hemodialysis facilities. The Covid-ESKD (n = 107; 54% females; 60.8 ± 17.7 years) and No-Covid-ESKD (n = 107; 62% females; 58.4 ± 14.6 years) groups were matched by calendar time. The average BP and dialysis parameters were calculated during the pre-infection, acute infection, and post-infection periods. The main outcomes were Covid-19 hospitalization and all-cause mortality.Results Covid-ESKD patients had greater intradialytic and postdialysis systolic BP and lower predialysis weight, postdialysis weight, ultrafiltration rate, and interdialytic weight gain during acute-illness compared to 1-week-before-illness, while these changes were not observed in No-Covid-ESKD patients. After 286 days of follow-up (range, 276–591), there were 18 Covid-19-related hospitalizations and 28 deaths among Covid-ESKD patients. Multivariable logistic regression analysis showed that increases in predialysis systolic BP from 1-week-before-illness to acute-illness (OR, 95%CI = 1.06, 1.02–1.10; p = .004) and Covid-19 vaccination (OR, 95%CI = 0.16, 0.04–0.69; p = .014) were associated with hospitalization in Covid-ESKD patients. Multivariable Cox-regression analysis showed that Covid-19-related hospitalization (HR, 95%CI = 5.17, 2.07–12.96; p

ABSTRACTIncome from goats highly depends on prolificacy, which is difficult to improve by traditional breeding methods. The study aimed to identify SNP markers for prolificacy, using a case–control genome-wide association study (GWAS) on 111 genotyped Cameroon native goat (CNG) does, based on the 50 K single nucleotide polymorphism (SNP) chip panel. None of the top SNPs reached the significant p-value of 5 × 10−8. The highest p-value was 0.0009. Despite the number of cases being about a quarter of the number of controls, the highest allele frequency of some of the top 20 variants in the cases was indicative of their potential role in the trait. These top variants included the following 15: rs268285661, rs268235169, rs268236449, rs268235135, rs268240394 in Sphingosine-1-phosphate phosphatase 2 (SGPP2) gene, rs268283635 in Solute carrier family 24 member 2 (SLC24A2) gene, rs268251678 in Androgen-induced gene 1 (AIG1) gene, rs268267018, rs268239617, rs268281364, rs268273029, rs268286941, rs268236144, rs268233233 in CEP126 gene and rs268278159, respectively. Our findings indicate that GWAS enable the identification of some loci within genes, with known biological functions and pathways in human being and mice animal model but far-ranging to what was previously hypothesized and tested in goat.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is linked to high mortality, primarily through an intense inflammatory response. Diacerein has emerged as a potential therapy for COVID-19 due to its potential impact in decreasing the inflammasome activation and coronavirus replication. This study aims to explore diacerein’s influence in inhibiting both viral replication and the inflammatory response after SARS-CoV-2 infection.MethodsHuman peripheral blood mononuclear cells (PBMCs) were obtained from healthy volunteers and infected in vitro with SARS-CoV-2. Additionally, we carried out a pilot randomized, double-blind, placebo-controlled study with 14 participants allocated to diacerein (n = 7) or placebo (n = 7) therapies every 12 h for 10 days. The primary endpoint was change in plasma markers of inflammasome activation (NLRP3, caspase-1, and gasdermin-D).ResultsIn vitro protocols have shown that rhein, diacerein’s primary metabolite, decreased IL-1β secretion caused by SARS-CoV-2 infection in human PBMCs (p < 0.05), and suppressed viral replication when administered either before or after the virus incubation (p < 0.05). This later effect was, at least partially, attributed to its inhibitory effect on 3-chymotrypsin-like protease (SARS-CoV-2 3CLpro) and papain-like protease in the SARS-CoV-2 (SARS-CoV-2 PLpro) virus and in the phosphorylation of proteins related cytoskeleton network (p < 0.05). Diacerein-treated COVID-19 patients presented a smaller area under the curve for NLRP3, caspase-1 and GSDM-D measured on days 2, 5, and 10 after hospitalization compared to those receiving a placebo (p < 0.05).ConclusionThe indicated mechanisms of action of diacerein/rhein can reduce viral replication and mitigate the inflammatory response related to SARS-CoV-2. These findings are preliminary and require confirmation in clinical trials.

Abstract The accumulation of advanced glycation end-products (AGEs) elicits morphofunctional kidney impairment. AGEs levels can be noninvasively estimated by skin autofluorescence (SAF). We explored whether high SAF predicts kidney outcomes in type 2 diabetes (T2D) individuals. The study was conducted as a predefined analysis of the Brazilian Diabetes Study, a prospective single-center cohort of T2D adults. Data from 155 individuals followed for up to 1716 days were considered. The incidence of major adverse kidney events (MAKE) was 9.6%. Individuals with above-median SAF had a higher incidence of MAKEs (4.6% vs. 21%; p = 0.002), with an HR of 3.39 [95% CI: 1.06–10.85; p = 0.040] after adjustment by age and gender. The mean adjusted eGFR change was 1.08 units (SE: 1.15; 95%CI: –1.20, 3.37) in the low SAF and –5.19 units [SE: 1.93; 95%CI: –9.10, –1.29] in the high SAF groups (between-subject difference: F: 5.62, p = 0.019). The high-SAF group had a greater prevalence of rapid decliners than the low-SAF group (36.7% vs. 15.8%; p = 0.028). In conclusion, high SAF was related to increased incidence of MAKEs and faster decline in eGFR among T2D subjects. This should be considered by healthcare providers when identifying individuals more prone to diabetes-related kidney complications.

Background 123Iodine‐meta‐iodobenzylguanidine scintigraphy is useful for assessing cardiac autonomic dysfunction and predict outcomes in heart failure (HF). The relationship of cardiac sympathetic function with myocardial remodeling and diffuse fibrosis remains largely unknown. We aimed to evaluate the cardiac sympathetic function of patients with HF and its relation with myocardial remodeling and exercise capacity. Methods and Results Prospectively enrolled patients with HF (New York Heart Association class II–III) were stratified into HF with preserved left ventricular ejection fraction [LVEF] ≥45%) and reduced LVEF. Ventricular morphology/function and myocardial extracellular volume (ECV) fraction were quantified by cardiovascular magnetic resonance, global longitudinal strain by echocardiography, cardiac sympathetic function by heart‐to‐mediastinum ratio from 123iodine‐meta‐iodobenzylguanidine scintigraphy. All participants underwent cardiopulmonary exercise testing. The cohort included 33 patients with HF with preserved LVEF (LVEF, 60±10%; NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide], 248 [interquartile range, 79–574] pg/dL), 28 with HF with reduced LVEF (LVEF, 30±9%; NT‐proBNP, 743 [interquartile range, 250–2054] pg/dL) and 20 controls (LVEF, 65±5%; NT‐proBNP, 40 [interquartile range, 19–50] pg/dL). Delayed (4 hours) 123iodine‐meta‐iodobenzylguanidine heart‐to‐mediastinum ratio was lower in HF with preserved LVEF (1.59±0.25) and HF with reduced LVEF (1.45±0.16) versus controls (1.92±0.24; P

Resumo Fundamento: A terapia de reperfusão precoce é reconhecida como a abordagem mais eficaz para reduzir as taxas de letalidade de casos em pacientes com infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST). Objetivo: Estimar as consequências clínicas e econômicas do atraso da reperfusão em pacientes com IAMCSST. Métodos: O presente estudo de coorte retrospectivo avaliou as taxas de mortalidade e as despesas totais decorrentes do atraso na terapia de reperfusão em 2.622 indivíduos com IAMCSST. Os custos de cuidados hospitalares e perda de produtividade por morte ou incapacidade foram estimados sob a perspectiva do Sistema Único de Saúde indexado em dólares internacionais (Int$) ajustados pela paridade do poder de compra. Foi considerado estatisticamente significativo p < 0,05. Resultados: Cada hora adicional de atraso na terapia de reperfusão foi associada a um aumento de 6,2% (intervalo de confiança de 95%: 0,3% a 11,8%, p = 0,032) no risco de mortalidade hospitalar. As despesas gerais foram 45% maiores entre os indivíduos que receberam tratamento após 9 horas em comparação com aqueles que foram tratados nas primeiras 3 horas, impulsionados principalmente pelos custos hospitalares (p = 0,005). Um modelo de regressão linear multivariada indicou que para cada 3 horas de atraso na trombólise, houve um aumento nos custos hospitalares de Int$ 497 ± 286 (p = 0,003). Conclusões: Os achados do nosso estudo oferecem mais evidências que enfatizam o papel crucial da terapia de reperfusão imediata no salvamento de vidas e na preservação dos recursos de saúde pública. Estes resultados enfatizam a necessidade urgente de implementação de uma rede para gerir casos de IAMCSST.

Abstract Background The escalating prevalence of type 2 diabetes (T2DM) poses an unparalleled economic catastrophe to developing countries. Cardiovascular diseases remain the primary source of costs among individuals with T2DM, incurring expenses for medications, hospitalizations, and surgical interventions. Compelling evidence suggests that the risk of cardiovascular outcomes can be reduced by three classes of glucose-lowering therapies (GLT), including SGLT2i, GLP-1A, and pioglitazone. However, an evidence-based and cost-effective protocol is still unavailable for many countries. The objective of the current study is to compare the effectiveness and cost-effectiveness of GLT in individuals with T2DM in Brazil. Methods We employed Bayesian Networks to calculate the incremental cost-effectiveness ratios (ICER), expressed in international dollars (Int$) per disease-adjusted life years [DALYs] averted. To determine the effectiveness of GLT, we conducted a systematic review with network meta-analysis (NMA) to provide insights for our model. Additionally, we obtained cardiovascular outcome incidence data from two real-world cohorts comprising 851 and 1337 patients in primary and secondary prevention, respectively. Our cost analysis took into account the perspective of the Brazilian public health system, and all values were converted to Int$. Results In the NMA, SGLT2i [HR: 0.81 (95% CI 0.69–0.96)], GLP-1A [HR: 0.79 (95% CI 0.67–0.94)], and pioglitazone [HR: 0.73 (95% CI 0.59–0.91)] demonstrated reduced relative risks of non-fatal cardiovascular events. In the context of primary prevention, pioglitazone yielded 0.2339 DALYs averted, with an ICER of Int$7,082 (95% CI 4,521–10,770) per DALY averted when compared to standard care. SGLT2i and GLP-1A also increased effectiveness, resulting in 0.261 and 0.259 DALYs averted, respectively, but with higher ICERs of Int$12,061 (95% CI: 7,227–18,121) and Int$29,119 (95% CI: 23,811–35,367) per DALY averted. In the secondary prevention scenario, all three classes of treatments were deemed cost-effective at a maximum willingness-to-pay threshold of Int$26,700. Notably, pioglitazone consistently exhibited the highest probability of being cost-effective in both scenarios. Conclusions In Brazil, pioglitazone presented a higher probability of being cost-effective both in primary and secondary prevention, followed by SGLT2i and GLP-1A. Our findings support the use of cost-effectiveness models to build optimized and hierarchical therapeutic strategy in the management of T2DM. Trial registration CRD42020194415.

Background and aims: Cardiomyocyte hypertrophy and interstitial fibrosis are key components of myocardial remodeling in Heart Failure (HF) with preserved (HFpEF) or reduced ejection fraction (HFrEF). MicroRNAs (miRNAs) are non-coding, evolutionarily conserved RNA molecules that may offer novel insights into myocardial remodeling. This study aimed to characterize miRNA expression in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF

Additive manufacturing has evolved from a rapid prototyping technology to a technology with the ability to produce highly complex parts with superior mechanical properties than those obtained conventionally. The processing of metallic powders by means of a laser makes it possible to process any type of alloy and even metal matrix composites. The present work analyzes the tensile and compressive response of 316L stainless steel processed by laser-based powder bed fusion. The resulting microstructure was evaluated by optical microscopy. Regarding the mechanical properties, the yield strength, ultimate tensile strength, percentage of elongation before breakage, compressive strength and microhardness were determined. The results show that the microstructure is constituted by stacked micro molten pools, within which cellular sub-grains are formed due to the high thermal gradient and solidification rate. The compressive strength (1511.88 ± 9.22 MPa) is higher than the tensile strength (634.80 ± 11.62 MPa). This difference is mainly associated with strain hardening and the presence of residual stresses. The initial microhardness was 206.24 ± 11.96 HV; after the compression test, the hardness increased by 23%.

ABSTRACT In individuals with very low high-density lipoprotein (HDL-C) cholesterol, such as Tangier disease, LCAT deficiency, and familial hypoalphalipoproteinemia, there is an increased risk of premature atherosclerosis. However, analyzes based on comparisons of populations with small variations in HDL-C mediated by polygenic alterations do not confirm these findings, suggesting that there is an indirect association or heterogeneity in the pathophysiological mechanisms related to the reduction of HDL-C. Trials that evaluated some of the HDL functions demonstrate a more robust degree of association between the HDL system and atherosclerotic risk, but as they were not designed to modify lipoprotein functionality, there is insufficient data to establish a causal relationship. We currently have randomized clinical trials of therapies that increase HDL-C concentration by various mechanisms, and this HDL-C elevation has not independently demonstrated a reduction in the risk of cardiovascular events. Therefore, this evidence shows that (a) measuring HDL-C as a way of estimating HDL-related atheroprotective system function is insufficient and (b) we still do not know how to increase cardiovascular protection with therapies aimed at modifying HDL metabolism. This leads us to a greater effort to understand the mechanisms of molecular action and cellular interaction of HDL, completely abandoning the traditional view focused on the plasma concentration of HDL-C. In this review, we will detail this new understanding and the new horizon for using the HDL system to mitigate residual atherosclerotic risk.

Sodium glucose cotransporter 2 inhibitors (SGLT2) have been increasingly pursued as a promising target for addressing residual cardiovascular risk. Prior trials demonstrated that SGLT2i not only promotes glucose-lowering, but also improves endothelial dysfunction, adiposity, fluid overload, and insulin sensitivity thus contributing to hemodynamic changes implicated in its cardiorenal benefits. The mechanisms in the effect of SGLT2i on blood pressure and their potential role in preventing cardiovascular events are hereby revised.

Introduction: The African Goat Improvement Network Image Collection Protocol (AGIN-ICP) is an accessible, easy to use, low-cost procedure to collect phenotypic data via digital images. The AGIN-ICP collects images to extract several phenotype measures including health status indicators (anemia status, age, and weight), body measurements, shapes, and coat color and pattern, from digital images taken with standard digital cameras or mobile devices. This strategy is to quickly survey, record, assess, analyze, and store these data for use in a wide variety of production and sampling conditions.Methods: The work was accomplished as part of the multinational African Goat Improvement Network (AGIN) collaborative and is presented here as a case study in the AGIN collaboration model and working directly with community-based breeding programs (CBBP). It was iteratively developed and tested over 3 years, in 12 countries with over 12,000 images taken.Results and discussion: The AGIN-ICP development is described, and field implementation and the quality of the resulting images for use in image analysis and phenotypic data extraction are iteratively assessed. Digital body measures were validated using the PreciseEdge Image Segmentation Algorithm (PE-ISA) and software showing strong manual to digital body measure Pearson correlation coefficients of height, length, and girth measures (0.931, 0.943, 0.893) respectively. It is critical to note that while none of the very detailed tasks in the AGIN-ICP described here is difficult, every single one of them is even easier to accidentally omit, and the impact of such a mistake could render a sample image, a sampling day’s images, or even an entire sampling trip’s images difficult or unusable for extracting digital phenotypes. Coupled with tissue sampling and genomic testing, it may be useful in the effort to identify and conserve important animal genetic resources and in CBBP genetic improvement programs by providing reliably measured phenotypes with modest cost. Potential users include farmers, animal husbandry officials, veterinarians, regional government or other public health officials, researchers, and others. Based on these results, a final AGIN-ICP is presented, optimizing the costs, ease, and speed of field implementation of the collection method without compromising the quality of the image data collection.

The African Goat Improvement Network (AGIN) is a collaborative group of scientists focused on genetic improvement of goats in small holder communities across the African continent. The group emerged from a series of workshops focused on enhancing goat productivity and sustainability. Discussions began in 2011 at the inaugural workshop held in Nairobi, Kenya. The goals of this diverse group were to: improve indigenous goat production in Africa; characterize existing goat populations and to facilitate germplasm preservation where appropriate; and to genomic approaches to better understand adaptation. The long-term goal was to develop cost-effective strategies to apply genomics to improve productivity of small holder farmers without sacrificing adaptation. Genome-wide information on genetic variation enabled genetic diversity studies, facilitated improved germplasm preservation decisions, and provided information necessary to initiate large scale genetic improvement programs. These improvements were partially implemented through a series of community-based breeding programs that engaged and empowered local small farmers, especially women, to promote sustainability of the production system. As with many international collaborative efforts, the AGIN work serves as a platform for human capacity development. This paper chronicles the evolution of the collaborative approach leading to the current AGIN organization and describes how it builds capacity for sustained research and development long after the initial program funds are gone. It is unique in its effectiveness for simultaneous, multi-level capacity building for researchers, students, farmers and communities, and local and regional government officials. The positive impact of AGIN capacity building has been felt by participants from developing, as well as developed country partners.

IntroductionData on patients hospitalized with acute heart failure in Brazil scarce.MethodsWe performed a cross-sectional, retrospective, records-based study using data retrieved from a large public database of heart failure admissions to any hospital from the Brazilian National Public Health System (SUS) (SUS Hospital Information System [SIHSUS] registry) to determine the in-hospital all-cause mortality rate, in-hospital renal replacement therapy rate and its association with outcome.ResultsIn total, 910,128 hospitalizations due to heart failure were identified in the SIHSUS registry between April 2017 and August 2021, of which 106,383 (11.7%) resulted in in-hospital death. Renal replacement therapy (required by 8,179 non-survivors [7.7%] and 11,496 survivors [1.4%, p

Seasonal variation of blood pressure (BP) is a topic in cardiology that has gained more attention throughout the years. Although it is extensively documented that BP increases in seasons coupled with lower temperatures, there are still many gaps in this knowledge field that need to be explored. Notably, seasonal variation of BP phenotypes, such as masked and white coat hypertension, and the impact of air pollution, latitude, and altitude on seasonal variation of BP are still poorly described in the literature, and the levels of the existing evidence are low. Therefore, further investigations on these topics are needed to provide robust evidence that can be used in clinical practice.

Abstract Background Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve endothelial dysfunction and reduce cardiovascular events in individuals with type 2 diabetes (T2D). Proprotein convertase subtilisin/kexin 9 (PCSK9i) inhibitors reduce cardiovascular events in high-risk patients. Whether the addition of PCSK9i to SGLT2i treatment adds benefits is not known. Objectives To assess the PCSK9-i effect on the endothelial function of T2D individuals under treatment with SGLT2-i. Methods Individuals with T2D were randomized in a 1:1 ratio to a 16-week treatment with either empagliflozin (E) or empagliflozin plus evolocumab (EE). The primary endpoint was post-treatment change from baseline in flow-mediated dilation (FMD) at 1-min. Secondary outcomes included changes in plasma levels of nitric oxide metabolites and isoprostane. Results A total of 110 patients were enrolled, the mean age was 58 years, and 71% were men. The median post-treatment change in FMD at 1-min was 2.7% (interquartile range [IQR]: 0.9%) and 0.4% (IQR: 0.9%) in the EE and E groups, respectively (p

Abstract This study aimed at comparing the prevalence of abnormal blood pressure (BP) phenotypes among 241 adolescents referred for hypertension (15.4 ± 1.4 years, 62% males, 40% obese) according to mostly used or available criteria for hypertension [AAP or ESH criteria for high office BP (OBP); Arsakeion or Goiânia schools’ criteria for high home BP monitoring (HBPM)]. High OBP prevalence was greater when defined by AAP compared with ESH criteria (43.5% vs. 24.5%; p

Resumo Fundamento A nefropatia induzida por contraste (NIC) é definida como deterioração da função renal, representada por um aumento da creatinina sérica ≥25% ou ≥0,5 mg/dL até 72 horas após a exposição ao meio de contraste iodado (MCI). A medida preventiva mais eficaz até o momento é a hidratação venosa (HV). Pouco se sabe sobre a eficácia da hidratação oral (HO) ambulatorial. Objetivo Investigar se a HO ambulatorial com água é tão eficaz quanto a HV com solução salina a 0,9% na prevenção de NIC em procedimentos coronarianos eletivos. Métodos Neste estudo observacional retrospectivo, foram analisados prontuários médicos e dados laboratoriais para coletar dados de indivíduos submetidos a procedimentos coronarianos percutâneos com MCI. Os dados coletados entre 2012 e 2015 avaliaram indivíduos que foram submetidos à HV e entre 2016 e 2020 (após a implementação de um protocolo de HO), os indivíduos que foram submetidos à HO em casa antes e depois de procedimentos coronarianos, conforme orientação da equipe de enfermagem. A significância estatística adotada foi de α=0,05. Resultados No total, 116 pacientes foram incluídos neste estudo, 58 no grupo HV e 58 no grupo HO. Observou-se incidência de NIC de 15% (9/58) no grupo que recebeu HV e 12% (7/58) no grupo que recebeu HO (p=0,68). Conclusão O protocolo de HO realizado pelo paciente parece ser tão eficaz quanto o protocolo de HV hospitalar na proteção renal de indivíduos suscetíveis a desenvolver NIC em intervenções coronarianas eletivas. Essas descobertas devem ser testadas em ensaios mais abrangentes.

Abstract There are limited data on the effects of anthracyclines on right ventricular (RV) structure, function, and tissue characteristics. The goal of this study was to investigate the effects of anthracyclines on the RV using cardiac magnetic resonance (CMR). This was a post-hoc analysis of a prospective study of 27 breast cancer (BC) patients (51.8 ± 8.9 years) using CMR prior, and up to 3-times after anthracyclines (240 mg/m2) to measure RV volumes and mass, RV extracellular volume (ECV) and cardiomyocyte mass (CM). Before anthracyclines, LVEF (69.4 ± 3.6%) and RVEF (55.6 ± 9%) were normal. The median follow-up after anthracyclines was 399 days (IQR 310–517). The RVEF reached its nadir (46.3 ± 6.8%) after 9-months (P

Abstract This study investigated the impact of changing abnormal home blood pressure monitoring (HBPM) cutoff from 135/85 to 130/80 mmHg on the prevalence of hypertension phenotypes, considering an abnormal office blood pressure cutoff of 140/90 mmHg. We evaluated 57 768 individuals (26 876 untreated and 30 892 treated with antihypertensive medications) from 719 Brazilian centers who performed HBPM. Changing the HBPM cutoff was associated with increases in masked (from 10% to 22%) and sustained (from 27% to 35%) hypertension, and decreases in white‐coat hypertension (from 16% to 7%) and normotension (from 47% to 36%) among untreated participants, and increases in masked (from 11% to 22%) and sustained (from 29% to 36%) uncontrolled hypertension, and decreases in white‐coat uncontrolled hypertension (from 15% to 8%) and controlled hypertension (from 45% to 34%) among treated participants. In conclusion, adoption of an abnormal HBPM cutoff of 130/80 mmHg markedly increased the prevalence of out‐of‐office hypertension and uncontrolled hypertension phenotypes.

Introdução: A cromomicose consiste em infecção causada por fungos demáceos pigmentados: Fonsecaea spp, Cladophialophora, Phialophora e Rhinocladiella. A inoculação de esporos por via transcutânea resulta em infecções cutânea ou subcutânea, sendo raro o envolvimento do sistema nervoso central. Em revisão da literatura observou-se que apenas 4,3% dos casos de cromomicose ocorrem na região cervical ou cefálica (Santos et al., 2021). Objetivo: Em vista da rara ocorrência e manejo terapêutico incerto este estudo visa relatar caso abscesso cerebral por Fonsecaea spp em um paciente transplantado cardíaco com boa evolução após abordagem terapêutica e cirúrgica. Resultados: Caso: Homem, 43 anos, natural de Porteirinha/MG, residente em Campinas desde 1995. Paciente transplantado cardíaco por doença de Chagas em 2017, com inúmeros episódios de rejeição (último em março de 2021), com infecção por CMV de difícil controle tratada por 9 meses, de 2017-2018. Em uso de azatioprina, tacrolimus e prednisona. Em março de 2021 apresentou lesão vegetante em região temporal direita e em membro superior direito. Realizou exérese da lesão cutânea temporal direita que evidenciou processo inflamatório crônico inespecífico com granulomas do tipo corpo estranho envolvendo estruturas arredondadas, compatível com cromomicose. Foi iniciado tratamento com itraconazol. Em 08/10/22 apresentou confusão mental e desorientação no tempo e espaço, sem demais alterações descritas ao exame neurológico. Foi internado e na investigação a tomografia computadorizada de crânio evidenciou processo inflamatório e edema em córtex fronto-parietal; lesão circular medindo 3 × 2 × 2,5cm em seus maiores eixos na substância branca em hemisfério esquerdo, causando desvio de aproximadamente 2cm da linha média. Foi realizada punção diagnóstica com saída de líquido róseo com grumos. Em vista dos resultados inconclusivos, foi realizada nova abordagem neurocirúrgica com biópsia do tecido cerebral que evidenciou hifas demáceas e crescimento em cultura de Fonsecaea sp, sensível a anfotericina B, voriconazol e itraconazol. O paciente iniciou o tratamento com anfotericina B complexo lipídico, posteriormente trocado para vorizonazol, endovenoso e, dois meses após, quando estabilização clínica, via oral. Paciente manteve o tratamento até abril de 2022. TC de controle não demonstrava atividade de doença. Continua em seguimento ambulatorial com terapia imunossupressora com tacrolimus e prednisona.

Abstract We compared the effect of dapagliflozin versus glibenclamide on the ratio of lean-to total mass in patients with type 2 diabetes mellitus, carotid subclinical atherosclerosis, HbA1c 7.0–9.0% and 40–70 years-old. Ninety-eight patients (61% male; mean age 57 ± 7 years) were randomized into dapagliflozin 10 mg/day or glibenclamide 5 mg/day on top of metformin. Body composition was measured by Dual Energy X-Ray at randomization and after 12 weeks of treatment. Glycemic control was equivalent in both groups. Dapagliflozin decreased total body mass (−2741 g [95% CI: −3360 to 1945]; p

Abstract Aims Despite of recent advances in the pharmacological treatment, heart failure (HF) maintains significant morbidity and mortality rates. While serum potassium disorders are common and associated with adverse outcomes, the exact recommended potassium level for patients with HF are not entirely established. We aimed to investigate the prognostic role of potassium levels on a cohort of patients with symptomatic chronic HF. Methods and results Patients with symptomatic chronic HF were identified at the referral to 6 min walking test (6MWT) and were prospectively followed up for cardiovascular events. Clinical and laboratorial data were retrospectively obtained. The primary endpoint was the composite of cardiovascular death, hospitalization due to HF, and heart transplantation. The cohort included 178 patients with HF with the mean age of 51 ± 12.76 years, 39% were female, 85% of non‐ischaemic cardiomyopathy, and 38% had New York Heart Association Class III with a relatively high Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) score (12.91 ± 6.6). The mean left ventricular ejection fraction was 39.98 ± 15.79%, and the mean 6MWT distance was 353 ± 136 m. After a median follow‐up of 516 days, there were 22 major cardiovascular events (4 cardiovascular deaths, 13 HF admissions, and 5 heart transplants). Patients were stratified according to cut‐point level of serum potassium of 4.7 mmol/L to predict combined cardiac events based on receiver operating characteristic analysis. Individuals with higher potassium levels had worse renal function (glomerular filtration rate, K ≤ 4.7: 102.8 ± 32.2 mL/min/1.73 m2 vs. K > 4.7: 85.42 ± 36.2 mL/min/1.73 m2, P = 0.004), higher proportion of New York Heart Association Class III patients (K ≤ 4.7: 28% vs. K > 4.7: 48%, P = 0.0029), and also higher MAGGIC score (K ≤ 4.7: 12.08 ± 5.7 vs. K > 4.7: 14.9 ± 7.9, P = 0.0089), without significant differences on the baseline pharmacological HF treatment. Both potassium levels [hazard ratio (HR) 4.26, 95% confidence interval (CI) 1.59–11.421, P = 0.003] and 6MWT distance (HR 0.99, 95% CI 0.993–0.999, P = 0.01) were independently associated with the primary outcome. After adjustments for MAGGIC score and 6MWT distance, potassium levels > 4.7 mmol/L maintained a significant association with outcomes (HR 3.57, 95% CI 1.305–9.807, P = 0.013). Patients with K > 4.7 mmol/L were more likely to present clinical events during the follow‐up (log rank = 0.005). Adding potassium levels to the model including 6MWT and MAGGIC significantly improved the prediction of events over 2 years (integrated discrimination index 0.105, 95% CI 0.018–0.281, P = 0.012 and net reclassification index 0.447, 95% CI 0.077–0.703, P = 0.028). Conclusions Potassium levels were independently associated with worse outcomes in patients with chronic symptomatic HF, also improving the accuracy model for prognostic prediction when added to MAGGIC score and 6MWT distance. The potassium levels above 4.7 mmol/L might identify those patients at an increased risk of cardiovascular events.

Abstract Background Copy number variations (CNV) are a significant source of variation in the genome and are therefore essential to the understanding of genetic characterization. The aim of this study was to develop a fine-scaled copy number variation map for African goats. We used sequence data from multiple breeds and from multiple African countries. Results A total of 253,553 CNV (244,876 deletions and 8677 duplications) were identified, corresponding to an overall average of 1393 CNV per animal. The mean CNV length was 3.3 kb, with a median of 1.3 kb. There was substantial differentiation between the populations for some CNV, suggestive of the effect of population-specific selective pressures. A total of 6231 global CNV regions (CNVR) were found across all animals, representing 59.2 Mb (2.4%) of the goat genome. About 1.6% of the CNVR were present in all 34 breeds and 28.7% were present in all 5 geographical areas across Africa, where animals had been sampled. The CNVR had genes that were highly enriched in important biological functions, molecular functions, and cellular components including retrograde endocannabinoid signaling, glutamatergic synapse and circadian entrainment. Conclusions This study presents the first fine CNV map of African goat based on WGS data and adds to the growing body of knowledge on the genetic characterization of goats.

Abstract Background Physical activity has been associated with reduced risk of seven types of cancer. It remains unclear, however, whether muscle-strengthening activities also reduce cancer incidence and mortality. Methods PubMed, Embase, Web of Science and Scopus were searched from inception to March 2020. Summary hazard ratio (HR) and 95% confidence intervals (CI) were estimated using random-effects models. Results Twelve studies (11 cohorts; 1 case-control), 6 to 25 years of follow-up, including 1,297,620 participants, 32,196 cases and 31,939 deaths, met inclusion criteria. Muscle-strengthening activities were associated with a 26% lower incidence of kidney cancer (HR for high vs low levels of muscle-strengthening activities: 0.74; 95% CI 0.56 to 0.98; I 2 0%; 2 studies), but not with incidence of other 12 types of cancer. Muscle-strengthening activities were associated with lower total cancer mortality: HRs for high vs low levels of muscle-strengthening activities was 0.87 (95% CI 0.73 to 1.02; I 2 58%; 6 studies); and HR for ≥2 times/week vs

Abstract Background The glucose-lowering independent effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on arterial wall function has not yet been clarified. This study aims to assess whether SGLT2i treatment can attenuate endothelial dysfunction related to type 2 diabetes mellitus (T2D) compared with glucose-lowering equivalent therapy. Methods In a prospective, open-label, single-center, randomized clinical trial, 98 patients with T2DM and carotid intima-media thickness above the 75th percentile were randomized 1:1 to 12 weeks of therapy with dapagliflozin or glibenclamide in addition to metformin in glucose-lowering equivalent regimens. The coprimary endpoints were 1-min flow-mediated dilation (FMD) at rest and 1-min FMD after 15 min of ischemia followed by 15 min of reperfusion time (I/R). Results Ninety-seven patients (61% males, 57 ± 7 years) completed the study. The median HbA1c decreased by − 0.8 (0.7)% and -0.7 (0.95)% following dapagliflozin and glibenclamide, respectively. The first coprimary endpoint, i.e., rest FMD changed by + 3.3(8.2)% and − 1.2(7.5)% for the dapagliflozin and glibenclamide arms, respectively (p = 0.0001). Differences between study arms in the second coprimary endpoint were not significant. Plasma nitrite 1 min after rest FMD was higher for dapagliflozin [308(220) nmol/L] than for glibenclamide (258[110] nmol/L; p = 0.028). The resistive indices at 1 min [0.90 (0.11) vs. 0.93 (0.07); p = 0.03] and 5 min [0.93 (0.07) vs. 0.95 (0.05); p = 0.02] were higher for the glibenclamide group than for the dapagliflozin group. Plasma biomarkers for inflammation and oxidative stress did not differ between the treatments. Conclusions Dapagliflozin improved micro- and macrovascular endothelial function compared to glibenclamide, regardless of glycemic control in patients with T2DM and subclinical carotid atherosclerotic disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs angiotensin-converting enzyme 2 (ACE2) as its receptor for cell entrance, and studies have suggested that upon viral binding, ACE2 catalytic activity could be inhibited; therefore, impacting the regulation of the renin-angiotensin-aldosterone system (RAAS). To date, only few studies have evaluated the impact of SARS-CoV-2 infection on the blood levels of the components of the RAAS. The objective of this study was to determine the blood levels of ACE, ACE2, angiotensin-II, angiotensin (1–7), and angiotensin (1–9) at hospital admission and discharge in a group of patients presenting with severe or critical evolution of coronavirus disease 2019 (COVID-19). We showed that ACE, ACE2, angiotensin (1–7), and angiotensin (1–9) were similar in patients with critical and severe COVID-19. However, at admission, angiotensin-II levels were significantly higher in patients presenting as critical, compared to patients presenting with severe COVID-19. We conclude that blood levels of angiotensin-II are increased in hospitalized patients with COVID-19 presenting the critical outcome of the disease. We propose that early measurement of Ang-II could be a useful biomarker for identifying patients at higher risk for extremely severe progression of the disease.

BackgroundChronic Chagas cardiomyopathy (CCC) constitutes the most life-threatening consequence of the Trypanosoma cruzi infection. Our goal was to test in CCC the associations of the myocardial tissue phenotype with cardiac dysfunction, and heart failure (HF) severity, using cardiac magnetic resonance (CMR).MethodsWe performed a prospective observational cohort of patients with consecutive CCC with a CMR protocol, including ventricular function, myocardial T1, and late gadolinium enhancement (LGE). Extracellular volume (ECV), and intracellular water lifetime, τic, a measure of cardiomyocyte diameter, were compared to CCC disease progression, including Rassi score and New York Heart Association (NYHA) class. An exploratory prognostic analysis was performed to investigate the association of both ECV and τic with CV death.ResultsA total of 37 patients with intermediate-to-high-risk CCC were enrolled (Chagas Rassi score ≥7, mean left ventricle (LV) ejection fraction (EF) 32 ± 16%). Myocardial ECV (0.40 ± 0.07) was correlated with Rassi score (r = 0.43; P = 0.009), higher NYHA class, and LV EF (r = −0.51; P = 0.0015). τic decreased linearly with NYHA class (P = 0.007 for non-parametric test of linear trend) and showed a positive association with LV EF (r = 0.47; P = 0.004). Over a median follow-up of 734 days (range: 6–2,943 days), CV death or cardiac transplantation occurred in 10 patients. The Rassi score (heart rate [HR] = 1.3; 95% CI = [1.0, 1.8]; P = 0.028) and ECV (HR = 3.4 for 0.1 change, 95% CI = [1.1, 11.0], P = 0.039) were simultaneously associated with CV death.ConclusionIn patients with intermediate-to-high-risk CCC, an expanded ECV and regression of cardiomyocyte diameter were associated with worsening systolic function and HF severity, respectively. The exploratory analysis indicates that ECV may have a prognostic value to identify patients with CCC at a higher risk for cardiovascular events.

ObjectiveLeft ventricular hypertrophy (LVH) is a common complication of hypertension and microRNAs (miRNAs) are considered to play an important role in cardiac hypertrophy development. This study evaluated the relationship between circulating miRNAs and LVH in hypertensive patients.MethodsTwo cohorts [exploratory (n = 42) and validation (n = 297)] of hypertensive patients were evaluated by clinical, laboratory and echocardiography analysis. The serum expression of 754 miRNAs in the exploratory cohort and 6 miRNAs in the validation cohort was evaluated by the TaqMan OpenArray® system and quantitative polymerase chain reaction, respectively.ResultsAmong the 754 analyzed miRNAs, ten miRNAs (miR-30a-5p, miR-let7c, miR-92a, miR-451, miR-145-5p, miR-185, miR-338, miR-296, miR-375, and miR-10) had differential expression between individuals with and without LVH in the exploratory cohort. Results of multivariable regression analysis adjusted for confounding variables showed that three miRNAs (miR-145-5p, miR-451, and miR-let7c) were independently associated with LVH and left ventricular mass index in the validation cohort. Functional enrichment analysis demonstrated that these three miRNAs can regulate various genes and pathways related to cardiac remodeling. Furthermore, in vitro experiments using cardiac myocytes demonstrated that miR-145-5p mimic transfection up-regulated the expression of brain and atrial natriuretic peptide genes, which are markers of cardiac hypertrophy, while anti-miR-145-5p transfection abrogated the expression of these genes in response to norepinephrine stimulus.ConclusionsOur data demonstrated that circulating levels of several miRNAs, in particular miR-145-5p, miR-451, and let7c, were associated with LVH in hypertensive patients, indicating that these miRNAS may be potential circulating biomarkers or involved in hypertension-induced LV remodeling.

Diamond has attracted great interest as an appealing material for various applications ranging from classical to quantum optics. To date, Raman lasers, single photon sources, quantum sensing and quantum communication have been demonstrated with integrated diamond devices. However, studies of the nonlinear optical properties of diamond have been limited, especially at the nanoscale. Here, a metasurface consisting of plasmonic nanogap cavities is used to enhance both χ(2) and χ(3) nonlinear optical processes in a wedge-shaped diamond slab with a thickness down to 12 nm. Multiple nonlinear processes were enhanced simultaneously due to the relaxation of phase-matching conditions in subwavelength plasmonic structures by matching two excitation wavelengths with the fundamental and second-order modes of the nanogap cavities. Specifically, third-harmonic generation (THG) and second-harmonic generation (SHG) are both enhanced 1.6 × 107-fold, while four-wave mixing is enhanced 3.0 × 105-fold compared to diamond without the metasurface. Even though diamond lacks a bulk χ(2) due to centrosymmetry, the observed SHG arises from the surface χ(2) of the diamond slab and is enhanced by the metasurface elements. The efficient, deeply subwavelength diamond frequency converter demonstrated in this work suggests an approach for conversion of color center emission to telecom wavelengths directly in diamond.

Abstract Aim Relationships of pulmonary artery systolic pressure (PASP) and right ventricular (RV) dysfunction with exercise capacity are understudied. To assess the relationship of PASP and RV function with functional capacity and ventilatory efficiency in heart failure (HF) with a wide range of left ventricular ejection fraction (LVEF). Methods and results Five hundred thirty‐two consecutive HF patients referred for cardiopulmonary exercise testing [percent predicted peak VO2 (ppVO2), VE/VCO2 slope] and echocardiography [LVEF, PASP, and RV fractional area change (RVFAC)] were studied. Associations of PASP and RVFAC with ppVO2 and VE/VCO2 slope were assessed by multivariable linear regression and restricted cubic splines. Associations with composite of death, heart transplant, and LV assist device (median 3.9 year follow‐up) was assessed using multivariable Cox proportional hazard models. Mean age was 56 ± 14 years and mean LVEF was 35 ± 15%. Mean PASP was 34 ± 12 mmHg, RVFAC was 41 ± 13%, ppVO2 was 60 ± 21%, and VE/VCO2 slope was 35 ± 12. After adjusting for demographics, co‐morbidities, LVEF, mitral regurgitation severity, and left atrial volume index, higher PASP was associated with worse ppVO2 (P = 0.004) and was more robust in patients with LVEF ≥45% vs.

Magnetic nanoparticles (MNps) have become powerful tools for multiple biomedical applications such as hyperthermia drivers, magnetic resonance imaging (MRI) vectors, as well as drug-delivery systems. However, their toxic effects on human health have not yet been fully elucidated, especially in view of their great diversity of surface modifications and functionalizations. Citrate-coating of MNps often results in increased hydrophilicity, which may positively impact their performance as drug-delivery systems. Nonetheless, the consequences on the intrinsic toxicity of such MNps are unpredictable. Herein, novel magnetite (Fe3O4) nanoparticles covered with citrate were synthesized and their potential intrinsic acute toxic effects were investigated using in vitro and in vivo models. The proposed synthetic pathway turned out to be simple, quick, inexpensive, and reproducible. Concerning toxicity risk assessment, these citrate-coated iron oxide nanoparticles (IONps) did not affect the in vitro viability of different cell lines (HaCaT and HepG2). Moreover, the in vivo acute dose assay (OECD test guideline #425) showed no alterations in clinical parameters, relevant biochemical variables, or morphological aspects of vital organs (such as brain, liver, lung and kidney). Iron concentrations were slightly increased in the liver, as shown by Graphite Furnace Atomic Absorption Spectrometry and Perls Prussian Blue Staining assays, but this finding was considered non-adverse, given the absence of accompanying functional/clinical repercussions. In conclusion, this study reports on the development of a simple, fast and reproducible method to obtain citrate-coated IONps with promising safety features, which may be used as a drug nanodelivery system in the short run. (263 words).

ObjectiveThis study compared clinical, echocardiographic, and prognostic characteristics among patients with aortic dissection (AD) with (HypHist) and without (No-HypHist) hypertension history and evaluated the association of blood pressure (BP) at presentation with 1-year mortality, left ventricular (LV) remodeling and renal dysfunction.MethodsWe investigated clinical and echocardiographic characteristics and 1-year mortality among 367 patients with AD (81% HypHist, 66% Type-A) from three Brazilian centers.ResultsPatients with No-HypHist were more likely to have Marfan syndrome, bicuspid aortic valve, to undergo surgical therapy, were less likely to have LV hypertrophy and concentricity, and had similar mortality compared with HypHist patients. Adjusted restricted cubic spline analysis showed that systolic BP (SBP) and diastolic BP (DBP) at presentation had a J-curve association with mortality among patients with No-HypHist, but did not associate with death among patients with HypHist (p for interaction = 0.001 for SBP and = 0.022 for DBP). Conversely, the association between SBP at presentation and mortality was influenced by previous use of antihypertensive medications in the HypHist group (p for interaction = 0.002). Results of multivariable logistic regression analysis comprising the whole sample showed direct associations of SBP and DBP at presentation with LV hypertrophy (p = 0.009) and LV concentricity (p = 0.015), respectively, and an inverse association between pulse pressure at presentation and estimated glomerular filtration rate (eGFR)

Endocardite Infecciosa (EI) é uma condição clínica que requer rápido diagnóstico e abordagem terapêutica precoce, oportuna e apropriada, sendo que o diagnóstico microbiológico frequentemente se fundamenta nas técnicas de hemoculturas. No entanto, nas EI com hemoculturas negativas, outras estratégias para o diagnóstico laboratorial devem ser consideradas visando a detecção de patógenos de difícil crescimento em meios de cultura, incluindo-se Bartonella e Coxiella. M.F.P, masculino, 45 anos, com antecedente de hipertensão arterial sistêmica, obesidade, etilismo e tabagismo, transferido de outro serviço para investigação de perda de força em membro superior direito e afasia. À admissão, devido a sopro diastólico aórtico à ausculta cardíaca e tomografia computadorizada de crânio com presença de isquemia frontal à esquerda, foi submetido a ecocardiograma transtorácico (ECO-TT), que evidenciou vegetação em valva aórtica medindo 10 × 15mm. Apresentou 6 amostras de hemoculturas negativas durante tempo de internação. Iniciado tratamento para EI com ampicilina-sulbactam + gentamicina. Submetido a ecocardiograma transesofágico que confirmou a presença de vegetação. ECO-TT de controle realizado em D15 de tratamento evidenciou aumento da vegetação (20 × 14mm). Submetido à cirurgia em D 15 de internação e D20 de antibioticoterapia para troca de valva por prótese metálica. Solicitada interconsulta (IC) à Infectologia para discussão do tempo de antibioticoterapia. Frente aos históricos de hemoculturas negativas (iniciais e sequenciais), deterioração clínica e ecocardiográfica em vigência de antibioticoterapia e cultura negativa da válvula cardíaca retirada, recomendada ampliação da investigação etiológica para patógenos de difícil crescimento em cultura, dentre eles Coxiella burnetii, para a qual sorologia por Imunofluorescência indireta se mostrou reagente em amostras pareadas com títulos elevados (1600), resultados (≥ 800) considerados confirmatórios para infecção pela C. burnetii. Recomendada adequação do esquema com doxiciclina associada à hidroxicloroquina. Paciente recebeu alta hospitalar para seguimento ambulatorial conjunto entre as especialidades. O presente relato reforça a importância da IC precoce com Infectologia e que, diante de casos de EI com hemocultura negativa, além da suspeita qualificada há a necessidade de investigação laboratorial apropriada e sistemática para detecção de patógenos de difícil crescimento em meios de cultura convencionais.

Abstract Background Endothelial dysfunction (ED) is a hallmark in type 2 diabetes mellitus (T2DM) that favor both atherogenesis and ischemia and reperfusion injury (IRI). Sodium-glucose-2 co-transporter inhibitors (SGLT2i) may hypothetically improve microvascular and macrovascular functions via a broad spectrum of mechanisms, being superior to traditional antidiabetic therapy such as sulfonylurea, even in subjects under equivalent glycemic control. Hence, the present clinical trial was designed to compare the effect of these two treatments on markers of arterial wall function and inflammation in T2DM patients as well as on the potential mediating parameters. Method and results ADDENDA-BHS2 is a prospective, single-center, active‐controlled, open, randomized trial. Ninety-eight participants (40–70 years old) with HbA1c 7–9% were randomized (1:1, stratified by gender, BMI and HbA1c levels) to either dapagliflozin 10 mg/day or glibenclamide 5 mg/day on top of metformin. The primary endpoint was the change of flow-mediated dilation (FMD) after a 12-week period of treatment evaluated at rest and after IRI between dapagliflozin and glibenclamide arms. Secondary outcomes were defined as the difference between treatments regarding: plasma nitric oxide (NO) change after FMD, plasma isoprostane, plasma levels of vascular inflammatory markers and systemic inflammatory markers, plasma levels of adipokines, anthropometric measures, glucose control parameters, office and ambulatory BP control. Safety endpoints were defined as systolic and diastolic function assessed by echocardiography and retinopathy change. Serious adverse events were recorded. The study protocol was approved by the Independent Scientific Advisory Committee. Conclusion The ADDENDA-BHS2 trial is an investigator-initiated clinical trial comparing the effect of dapagliflozin versus glibenclamide on several aspects of vascular function in high cardiovascular risk T2DM patients. Besides, a large clinical and biochemical phenotype assessment will be obtained for exploring potential mediations and associations. Trial registration Clinical trial registration: NCT 02919345 (September, 2016)

Abstract Background Myocardial infarction (MI) elicits an intense acute inflammatory response that is essential for cardiac repair. However, an excessive inflammatory response also favors myocardial apoptosis, cardiac remodeling, and cardiovascular mortality. Omega-3 polyunsaturated fatty acids (ω-3) bear anti-inflammatory effects, which may mitigate the inflammatory response during MI. This study investigated whether ω-3 intake is associated with attenuation of the MI-related inflammatory response and cardiac remodeling. Methods ST-elevation MI (STEMI) patients (n = 421) underwent clinical, biochemical, nutritional, 3D echocardiogram, Cardiac Magnetic Resonance imaging (CMRi) at 30 days and 3D echocardiogram imaging at six months after the MI. Blood tests were performed at day one (D1) and day five (D5) of hospitalization. Changes in inflammatory markers (ΔD5-D1) were calculated. A validated food frequency questionnaire estimated the nutritional consumption and ω-3 intake in the last 3 months before admission. Results The intake of ω-3 below the median (

Background This study compared left ventricular (LV) characteristics between patients with type‐A and type‐B aortic dissection (AD) and evaluated the ability of LV remodeling phenotypes (hypertrophy, concentricity, or geometric patterns) to predict mortality in both AD types. Methods and Results We evaluated 236 patients with type A and 120 patients with type B who had echocardiograms within 60 days before or after AD diagnosis (median [25th, 75th percentiles] time difference between echocardiogram and AD diagnosis=1 [0, 6] days) from 3 centers. Patients were stratified according to LV phenotypes, and early (90‐day) and late (1‐year) mortality after AD diagnosis were assessed. In adjusted logistic regression analysis, patients with type A had higher and lower odds of concentric and eccentric hypertrophy (odds ratio [OR], 2.56; 95% CI, 1.50–4.36; P

Coronavirus disease 2019 (COVID-19) is caused by the SARS-CoV-2 virus, responsible for an atypical pneumonia that can progress to acute lung injury. MicroRNAs are small non-coding RNAs that control specific genes and pathways. This study evaluated the association between circulating miRNAs and lung injury associated with COVID-19. Methods: We evaluated lung injury by computed tomography at hospital admission and discharge and the serum expression of 754 miRNAs using the TaqMan OpenArray after hospital discharge in 27 patients with COVID-19. In addition, miR-150-3p was validated by qRT-PCR on serum samples collected at admission and after hospital discharge. Results: OpenArray analysis revealed that seven miRNAs were differentially expressed between groups of patients without radiological lung improvement compared to those with lung improvement at hospital discharge, with three miRNAs being upregulated (miR-548c-3p, miR-212-3p, and miR-548a-3p) and four downregulated (miR-191-5p, miR-151a-3p, miR-92a-3p, and miR-150-3p). Bioinformatics analysis revealed that five of these miRNAs had binding sites in the SARS-CoV-2 genome. Validation of miR-150-3p by qRT-PCR confirmed the OpenArray results. Conclusions: The present study shows the potential association between the serum expression of seven miRNAs and lung injury in patients with COVID-19. Furthermore, increased expression of miR-150 was associated with pulmonary improvement at hospital discharge.

This study developed a theoretical model for the determination of the Coke Anisotropy Quotient (CAQ) of semi-coke from the properties of its precursor coal. This is an useful parameter to define the resistance and reactivity of semi-coke in the blast furnace. For 36 semi-coke samples, a textural analysis was performed alongside a fluidity test to determine the real CAQ. The main textures observed were: isotropic and circular for high volatile bituminous coals (HVB); lenticular and fine ribbons for the medium volatile bituminous coals (MVB); and medium and thick ribbons for the low volatile bituminous coals (LVB). The CAQ varied in a range from 1 to 11. A principal component analysis (PCA) and multiple regression allowed to discriminated the importance of certain coal properties, in determining the CAQ to be recognized and to estimate parameters of the mathematical model. The statistical analysis suggested that CAQ can be best predicted from the fluidity, volatile matter, and Ro of the parent coals. The veracity of this model result was then tested using a second dataset from Poland. This work optimizes the usefulness of standard datasets in the prediction of CAQ's offering a means of quality control that could be implemented in Colombian coke production.

Background: Patients with type 2 diabetes mellitus (T2DM) remain at increased cardiovascular residual risk and endothelial dysfunction, even after optimizing metabolic control and treatment by sodium-glucose-2 transporter inhibitors (SGLT2-is). The present study was based on the hypothesis that proprotein convertase subtilisin/kexin 9 inhibitor (PCSK9i) therapy may mitigate endothelial dysfunction in T2DM patients who are on regular treatment by SGLT2-i. Methods: The EXCEED-BHS3 is a prospective, single-center, investigator-blinded, open-label, randomized clinical trial. Participants ( n = 110) will be randomized (1:1) to either empagliflozin 25 mg/day alone or empagliflozin 25 mg/day plus evolocumab 140 mg every 2 weeks in addition to optimal medical care. The primary endpoint was defined as the change in the 1-min flow-mediated dilation (FMD) after 16 weeks of treatment. The secondary endpoint is the FMD change after ischemia/reperfusion injury protocol (reserve FMD) after 16 weeks of treatment. Exploratory outcomes comprise the change in FMD and reserve FMD after 8 weeks of treatment and the change after 16 weeks of treatment in the following parameters: plasma levels of nitric oxide, vascular cell adhesion molecule-1 and isoprostane, high-density lipoprotein (HDL) and low-density lipoprotein subfractions profile, HDL function, blood pressure, body mass index, waist circumference and adipokines. Conclusion: This will be the first study to evaluate the add-on effect of PCSK9i on endothelial function of T2DM patients under regular use of empagliflozin. Trial registration: ClinicalTrials.gov identifier: NCT03932721