Consensus of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) and the Brazilian Ministry of Health - General management of blood and blood products on the tests necessary for the release of exceptional medicines for sickle cell disease

Abstract To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety.

Consensus of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) and the Brazilian Ministry of Health - General management of blood and blood products on the tests necessary for the release of exceptional medicines for sickle cell disease.

To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety.

Hybrid Cardiac Telerehabilitation After Acute Coronary Syndrome: Self-selection Predictors and Outcomes.

Aims: To evaluate the effectiveness of a hybrid cardiac telerehabilitation (HCTR) program after acute coronary syndrome (ACS) on patient quality of life (QoL) and physical activity indices throughout phases 2-3 and establish predictors for hybrid program self-selection. Methodology: This single-centre longitudinal retrospective study included patients who attended a cardiac rehabilitation program (CRP) between 2018-2021. Patients self-selected between two groups: Group 1 - conventional CRP (CCRP); Group 2 - HCTR. Baseline characteristics were registered. EuroQol-5D (EQ-5D) and International Physical Activity Questionnaire (IPAQ) were applied at three times: T0 - phase 2 onset; T1 - phase 3 onset; T2 - 3 months after T1. Results: 59 patients participated (Group 1 - 27; Group 2 - 32). We found significant between-group differences regarding occupation (p=0.003). Diabetic patients were less likely to self-select into HCTR (OR=0.21; p<0.05). EQ-5D visual analogue scale and IPAQ result significantly improved between T0-T2 only for HCTR (p=0.001; p=0.021). Conclusions: HCTR was superior to CCRP on physical activity indices and QoL of ACS patients.

Novel FERMT3 and PTPRQ Mutations Associated with Leukocyte Adhesion Deficiency-III and Sensorineural Hearing Loss.

Leukocyte adhesion deficiency-III (LAD-III) is a rare genetic disease caused by defective integrin activation in hematopoietic cells due to mutations in the FERMT3 gene. The PTPRQ gene encodes the protein tyrosine phosphatase receptor Q and is essential for the normal maturation and function of hair bundle in the cochlea. Homozygous PTPRQ mutations impair the stereocilia in hair cells which lead to nonsyndromic sensorineural hearing loss (SNHL) with vestibular dysfunction. Here, we report two novel pathogenic homozygous mutations found in two genes, FERMT3 and PTPRQ , in a Brazilian patient with LAD-III and SNHL, which may develop our understanding of the phenotype-genotype correlation and prognosis of patients with these rare diseases.

HR1 Robot: An Assistant for Healthcare Applications.

According to the World Health Organization the percentage of healthcare dependent population, such as elderly and people with disabilities, among others, will increase over the next years. This trend will put a strain on the health and social systems of most countries. The adoption of robots could assist these health systems in responding to this increased demand, particularly in high intensity and repetitive tasks. In a previous work, we compared a Socially Assistive Robot (SAR) with a Virtual Agent (VA) during the execution of a rehabilitation task. The SAR consisted of a humanoid R1 robot, while the Virtual Agent represented its simulated counter-part. In both cases, the agents evaluated the participants' motions and provided verbal feedback. Participants reported higher levels of engagement when training with the SAR. Given that the architecture has been proven to be successful for a rehabilitation task, other sets of repetitive tasks could also take advantage of the platform, such as clinical tests. A commonly performed clinical trial is the Timed Up and Go (TUG), where the patient has to stand up, walk 3 m to a goal line and back, and sit down. To handle this test, we extended the architecture to evaluate lower limbs' motions, follow the participants while continuously interacting with them, and verify that the test is completed successfully. We implemented the scenario in Gazebo, by simulating both participants and the interaction with the robot. A full interactive report is created when the test is over, providing the extracted information to the specialist. We validate the architecture in three different experiments, each with 1,000 trials, using the Gazebo simulation. These experiments evaluate the ability of this architecture to analyse the patient, verify if they are able to complete the TUG test, and the accuracy of the measurements obtained during the test. This work provides the foundations towards more thorough clinical experiments with a large number of participants with a physical platform in the future. The software is publicly available in the assistive-rehab repository and fully documented.

Prevalence and outcomes of thrombotic and hemorrhagic complications in pediatric acute promyelocytic leukemia in a tertiary Brazilian center

Abstract Introduction: Little attention is given to thrombosis associated with pediatric acute promyelocytic leukemia (APL). This study describes the thrombotic and hemorrhagic manifestations of APL in pediatric patients and evaluates their hemostasis, based on coagulation tests. Methods: Inclusion criteria were age 0-18 years and APL diagnosis between April 2005 and November 2017. Patients who had received blood transfusion prior to coagulation tests were excluded. Baseline coagulation tests, hematologic counts, and hemorrhagic/thrombotic manifestations were evaluated. Results: Median age was 10.7 years (1-15 years). The initial coagulation tests revealed a median Hgb of 8.3 g/dL (4.7-12.9 g/dL), median leucocyte count of 10.9 × 109/L (1.1-95.8 × 109/L), median platelet count of 31.8 × 109/L (2.0-109.0 × 109/L), median activated partial thromboplastin time (aPTT) of 31.7 s (23.0-50.4 s), median aPTT ratio of 1.0 (0.78-1.6), median thromboplastin time (PT) of 17.5 s (13.8-27.7 s), median PT activity of 62% (25-95 %), and median fibrinogen of 157.7 mg/dL (60.0-281.0 mg/dL). Three patients (13%) had thrombosis. At diagnosis, 21 patients (91.3%) had bruising, one patient (4.3%) had splenic vein and artery thrombosis and one patient (4.3%) presented without thrombohemorrhagic manifestations. During treatment, two patients (8.6%) had thrombosis. Conclusion: Knowledge of thrombosis in pediatric APL is important to determine its risk factors and the best way to treat and prevent this complication.

Prevalence and outcomes of thrombotic and hemorrhagic complications in pediatric acute promyelocytic leukemia in a tertiary Brazilian center.

INTRODUCTION: Little attention is given to thrombosis associated with pediatric acute promyelocytic leukemia (APL). This study describes the thrombotic and hemorrhagic manifestations of APL in pediatric patients and evaluates their hemostasis, based on coagulation tests. METHODS: Inclusion criteria were age 0-18 years and APL diagnosis between April 2005 and November 2017. Patients who had received blood transfusion prior to coagulation tests were excluded. Baseline coagulation tests, hematologic counts, and hemorrhagic/thrombotic manifestations were evaluated. RESULTS: Median age was 10.7 years (1-15 years). The initial coagulation tests revealed a median Hgb of 8.3 g/dL (4.7-12.9 g/dL), median leucocyte count of 10.9 × 109/L (1.1-95.8 × 109/L), median platelet count of 31.8 × 109/L (2.0-109.0 × 109/L), median activated partial thromboplastin time (aPTT) of 31.7 s (23.0-50.4 s), median aPTT ratio of 1.0 (0.78-1.6), median thromboplastin time (PT) of 17.5 s (13.8-27.7 s), median PT activity of 62% (25-95 %), and median fibrinogen of 157.7 mg/dL (60.0-281.0 mg/dL). Three patients (13%) had thrombosis. At diagnosis, 21 patients (91.3%) had bruising, one patient (4.3%) had splenic vein and artery thrombosis and one patient (4.3%) presented without thrombohemorrhagic manifestations. During treatment, two patients (8.6%) had thrombosis. CONCLUSION: Knowledge of thrombosis in pediatric APL is important to determine its risk factors and the best way to treat and prevent this complication.

Dual antiplatelet therapy in myocardial infarction with non-obstructive coronary artery disease - insights from a nationwide registry.

INTRODUCTION AND OBJECTIVES: Dual antiplatelet therapy (DAPT) is a mainstay for myocardial infarction (MI) therapy. However, in patients with myocardial infarction with non-obstructive coronary artery disease (MINOCA), clear recommendations are lacking in the literature. This study aims to identify the cases in which DAPT is currently prescribed at discharge for MINOCA. METHODS: The authors analyzed a cohort of patients from a multicenter national registry enrolling patients who suffered their first MI between 2010 and 2017, and underwent coronary angiography revealing absence of stenosis ≥50%. Individual antithrombotic therapy was identified. A logistic regression analysis was applied to search for predictors of DAPT. RESULTS: From a total of 16 237 patients analyzed, 709 (4.4%) were categorized as MINOCA. Mean age was 64±13 years, 46.3% (n=409) were females. 390 (55.0%) of MINOCA patients were discharged on DAPT. Males (OR 1.67, CI 95 [1.05-2.38], p=0.027), active smokers (OR=1.82, CI 95 [1.05-3.16], p=0.033), previous percutaneous intervention (OR 3.18, CI 95 [1.48-6.81], p=0.003), ST elevation MI (OR 2.70, CI 95 [1.59-4.76], p<0.001) and sinus rhythm at admission (OR=3.94, CI 95 [2.07-7.48], p<0.001) were independent predictors of DAPT use. CONCLUSION: In this nationwide registry, DAPT was prescribed at discharge in 55% of MINOCA patients. Beyond sinus rhythm, the variables presented as independent predictors for DAPT use identify subgroups of patients who are classified as more prone to thrombotic events. The issue of how to handle antithrombotic agents in MINOCA patients is a topic open for discussion.

Beta-blockers for post-acute coronary syndrome mid-range ejection fraction: a nationwide retrospective study.

BACKGROUND: Patients with mid-range ejection fraction (40-49%) are in focus due to the newly defined entity of heart failure with mid-range ejection fraction. Acute coronary syndromes are a major aetiology for heart failure with mid-range ejection fraction. We aim to evaluate which therapeutic decisions are associated with inhospital survival benefit in post-acute coronary syndrome patients categorised according to the ejection fraction. METHODS AND RESULTS: The authors analysed a cohort of a multicentre national registry enrolling acute coronary syndrome patients between 2010 and 2016, classified according to their ejection fraction before hospital discharge. Patients with previously known heart failure or with no ejection fraction evaluation were excluded. A total of 9429 patients were included and categorised in three groups: (a) ejection fraction of 50% or greater (n=6113, 65%); (b) ejection fraction of 40-49% (n=1926, 20%); and (c) ejection fraction less than 40% (n=1390, 15%). The primary endpoint was inhospital mortality. To eliminate confounding factors, a multivariate logistic regression analysis was conducted, including acute coronary syndrome type, baseline characteristics, pharmacological treatment, clinical data, laboratory data and coronary anatomy when known. The overall inhospital mortality was 2.8% (n=263): 0.9% (n=53) in group 1, 2.4% (n=37) in group 2 and 11.4% (n=159) in group 3. After multivariate analysis, an invasive strategy had a positive impact in all groups, inhospital beta-blocker administration had a positive impact for groups 2 and 3, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and spironolactone had a positive impact on group 3. CONCLUSION: Post-acute coronary syndrome mid-range ejection fraction patients represent an intermediate risk group in which beta-blocker administration was associated with inhospital survival benefit. An invasive strategy was a survival predictor for all groups, regardless of ejection fraction category.

Ultra-rapid progression of coronary artery disease or undiagnosed unstable plaque? A brief review from a case report. / Progressão ultrarrápida de doença coronária ou placa instável não detetada?

Coronary artery disease rarely manifests itself in the first decades of life, which explains why this population is underrepresented in clinical studies. The mechanisms and natural history of the disease seem to differ between this population and older patients. Recent studies suggest a more rapid disease progression in youth, presenting more unstable atherosclerotic plaques, although this correlation has yet to be proven. In this paper, we present the case of a 41-year-old man who presented with a non-ST elevation myocardial infarction, with percutaneous coronary intervention of the culprit lesion (70-90% lesion at bifurcation of the circumflex artery with the first marginal obtuse artery and a sub-occlusive lesion of the ramus intermedius). There was also a non-significant lesion (estimated at 30%) located in the left anterior descending coronary artery. Ten days after discharge, the patient suffered another non-ST elevation myocardial infarction. The coronary angiography revealed a surprising sub-occlusive lesion of the left anterior descending coronary artery. Regarding this case, the authors reviewed the literature on the pathophysiology of rapidly progressive coronary artery disease and the approach for non-significant lesions in patients with acute coronary syndrome, especially in the younger population.

Myocardial infarction with nonobstructive coronary arteries: a single-center retrospective study.

BACKGROUND: Myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is a heterogeneous entity often overlooked in contemporary medicine. We aim to determine MINOCA differential characteristics, the main etiologies, and prognostic outcomes. PATIENTS AND METHODS: We carried out a retrospective longitudinal analysis including 1047 patients with MI, from 1 January 2011 to 1 January 2016, subjected to coronary angiography and classified according to the presence [MI and obstructive coronary artery disease (MICAD)] or absence (MINOCA) of any coronary stenosis of at least 50%. Studied data included clinical, demographic, laboratorial, and angiographic features. The median follow-up duration was 35 (interquartile range: 25) months. Mortality was the primary endpoint. To identify MINOCA underlying etiologies, only the final diagnosis obtained according to the European Society of Cardiology proposed algorithm was accepted. To determine MINOCA predictors, multivariate analysis with logistic regression was carried out. RESULTS: The mean age of the patients was 66.3±13.4 years; 319 (30.5%) patients were women. The MINOCA group included 114 (10.8%) patients. The underlying final diagnosis in the MINOCA group was obtained in 78 (68.4%) patients. The total mortality rate was 8.8% (n=10) in the MINOCA group versus 17.7% (n=165) in the MICAD group, P=0.018. After multivariate analysis, age [odds ratio (OR)=1.05, 95% confidence interval (CI): 1.03-1.07, P<0.001], female sex (OR=3.91, 95% CI: 2.53-6.06, P<0.001), no previous tobacco use (OR=3.41, 95% CI: 1.68-3.90, P=0.001), atrial fibrillation (OR=3.62, 95% CI: 1.56-8.40, P=0.003), no previous AMI (OR=6.85, 95% CI: 1.65-28.5, P=0.008), and non-ST-segment elevation myocardial infarction diagnosis (OR=5.36, 95% CI: 2.62-10.96, P<0.001) remained independent predictors of MINOCA. CONCLUSION: MINOCA represents a challenging group of heterogeneous patients whose clinical characteristics contrast with classical cardiovascular risk factors. Despite lower mortality than MICAD, the commonly attributed low-risk classification for MINOCA may be erroneous.

A rare late finding in corrected tetralogy of Fallot: a case report.

INTRODUCTION: Isolated pulmonary valve endocarditis is a rare phenomenon. Pulmonary prosthesis endocarditis is even more unusual, with only about 50 descriptions in worldwide literature, and its diagnosis and treatment is a challenge. Due to the increasing number of surgically corrected tetralogy of Fallot (TOF) patients, that often include pulmonary valve implantation, this clinical scenario is likely to become more frequent. CASE PRESENTATION: We describe a 37-year-old man with a previously implanted biologic pulmonary prosthesis after a TOF correction that presented to the emergency department with new-onset fever, orthopnoea, and lower limb oedema. Blood cultures were positive for Streptococcus mitis. Transthoracic echocardiography showed a large mobile mass in the right ventricular outflow tract, apparently originating from the pulmonary prosthesis. Transoesophageal echocardiography (TOE) showed the presence of multiple mobile structures arising from the arterial surface of the prosthesis, extending into the right pulmonary artery and causing right ventricular obstruction. Antibiogram guided treatment was administered and surgery was performed, removing a 9 cm vegetation and replacing the valve. Patient recovered well and was discharged 35 days after. DISCUSSION: In right-sided endocarditis, surgery indications and its timing are much less clear than in left-sided infections, but current literature describes it as associated with a significant morbidity, mortality, and high likelihood of requiring surgery. Large vegetations and clinical signs of haemodynamic impact should prompt consideration of early surgical intervention. The combination of transthoracic and TOE allowed a correct diagnosis and a timely treatment.

Gerbode defect and multivalvular dysfunction: Complex complications in adult congenital heart disease.

We report a clinical case of a 40-year-old male with surgically corrected congenital heart disease (CHD) 10 years earlier: closure of ostium primum, mitral annuloplasty, and aortic valve and root surgery. The patient was admitted with acute heart failure. Transesophageal echocardiography (TEE) revealed a dysmorphic and severely incompetent aortic valve, a partial tear of the mitral valve cleft repair and annuloplasty ring dehiscence. A true left ventricular-to-right atrial shunt confirmed a direct Gerbode defect. The authors aim to discuss the diagnostic challenge of adult CHD, namely the key role of TEE on septal defects and valve regurgitations description.

Importance of Manchester Triage in acute myocardial infarction: impact on prognosis.

BACKGROUND: Fast and effective diagnosis of patients with acute myocardial infarction (AMI) in the Emergency Department (ED) is needed. Manchester Triage (MT) is based on identification of the patient's main complaint, establishing, through decision flowcharts, a target-time for first observation. This study aimed to evaluate the impact of MT on short-term mortality in AMI and detect potential improvements, and to analyse high-risk groups: diabetic patients, women and older patients. METHODS: 332 consecutive patients (69.0+13.6 years mean age; 34.9% women) with final diagnosis of AMI were assessed in the ED using MT. Data were analysed according to demographics and risk groups, as well as several AMI parameters, admission duration and intrahospital mortality (IHM). Independent predictors of mortality were determined. RESULTS: 82.8% of patients met the ideal goal of ≤10 min target-time for a first observation (ITTFO). This was higher (95%) in typical presentations ('chest pain'), versus 52% in other flowcharts; p<0.01. Patients ≥70 years old were less frequently screened with ITTFO ≤10 min (76.2% vs 90.0% in those under 70; p=0.001) or the 'chest pain' flowchart (66.9% vs 77.5%; p=0.031). IHM was 13.3%. Triage with ≤10 min ITTFO and the 'chest pain' algorithm seems to predict a lower mortality (0.33 OR; 95% CI 0.17 to 0.63; p=0.0005 and 0.49 OR; 95% CI 0.24 to 1.03; p=0.056). CONCLUSION: MT proved to be an effective system. Patients with typical AMI presentation, ST elevation myocardial infarction and less than 70 years old are protected by MT, with lower ITTFO and better short-term survival.

Viral myocarditis--new advances.

The role of viruses in cardiovascular disease has been increasingly recognized in recent years. They are now thought to be the main agent in acute myocarditis and inflammatory cardiomyopathy in the western world. We describe new perspectives on the part viral agents play in heart disease, from molecular mechanisms to recently available diagnostic and therapeutic options. We present a case of post-viral dilated cardiomyopathy in a 29-year-old woman in order to illustrate the severe damage that a viral infection can cause and the different therapeutic options that may be available in the near future.

A rare histiocytosis with severe cardiac involvement: Erdheim-Chester disease.

The term histiocytosis covers various disorders that lead to primary proliferation, infiltration and accumulation of cells of the mononuclear-phagocytic system within the affected tissues. Its pathophysiology is still unclear and the clinical course variable, which explains the lack of specific treatment and the need for a high level of suspicion to arrive at the diagnosis. The authors present the case of a patient with a complex cardiological clinical history, recently referred for surgical treatment of severe mitral insufficiency. Severe thickening of both atrial walls made it impossible to proceed with the intervention. After a complex etiological evaluation, a diagnosis of Erdheim-Chester disease was made. This is a rare, non-Langerhans cell histiocytosis and, to our knowledge, this represents the first case reported in Portugal. The authors also review the literature, particularly of the few cases with cardiac involvement.

Obtenção e avaliação da atividade antioxidante de farinha de cascas de uvas Niágara / Collection and evaluation of antioxidant activity of flours from the Niagara grape

Neste trabalho determinou-se a atividade antioxidante dos extratos preparados a partir das farinhas de cascas de uva Niágara (Vitis Labrusca L.), da família Vitaceae, através da redução do 1,1 – difenil – 2 – picrilhidrazil – DPPH. Para o preparo das farinhas, a secagem das cascas foi feita em estufa convencional, em estufa com circulação forçada de ar, em balança de infravermelho e em forno de microondas. Para a obtenção das farinhas de cascas de uva foram usadas diferentes temperaturas/potências, com posteiror moagem. Paralelamente determinou-se o poder antioxidante de uma série de soluções de ácido ascórbico padrão referencial. Observou-se que, dependendo das condições de secagem, o poder antioxidante da farinha obtida foi equivalente ao de uma quantidade diferente de ácido ascórbico, os valores encontrados foram: zero (para 60ºC em estufa normal ou em estufa com circulação forçada); 6,02. 10 – 6M (estufa normal a 90 ºC); 3,261.10 – 5 M (para estufa com circulação forçada a 40ºC); 6,354.10 – 5 M (estufa com circulação forçada a 90ºC); 5,350.10 - 5 M (balança de infravermelho); 8,383.10 – 5 M (forno microondas, potência alta) e 9,455.10 – 5 M de ácido ascórbico (forno microondas, potência média-baixa).

Long-term clinical impact of coronary-collateral vessels after acute myocardial infarction.

BACKGROUND: The positive impact of coronary collateral vessels in the acute phase of myocardial infarction (AMI) is already well established. However, their impact on longterm clinical outcome of these patients is still unclear. AIM: To study the impact of the presence of well established coronary collateral vessels on long-term clinical outcome of post-AMI patients. POPULATION AND METHODS: We analyzed the clinical evolution (mean follow-up time of 15.66.8 months) of 70 patients who underwent coronary angiography shortly after AMI. According to the angiogram, the patients were divided into 2 groups: those with well developed coronary collateral vessels (n = 35) and those who did not show developed collateral circulation (n = 35). RESULTS: Both groups had similar baseline characteristics (regarding demography, coronary artery disease risk factors and predischarge evolution). The group with collaterals had more severe coronary disease compared with the group without collaterals (2.31 +/- 0.61 vs. 1.57 +/- 0.7; p = 0.00001). Moreover, this group more frequently showed significant lesions on the left anterior descending artery (83% vs. 74%; p = NS), left circumflex (71% vs. 43%; p = 0.02) and right coronary arteries (74% vs. 40%; p = 0.003). Primary percutaneous coronary intervention was more often performed in patients without coronary collateral vessels (58% vs. 30%; p = 0.02). Left ventricular function was similar in both groups. During follow-up, both groups underwent similar levels of revascularization by percutaneous coronary intervention and/or coronary artery bypass graft (70% vs. 76%; p = NS). Despite these characteristics, the group with collaterals showed a significantly better clinical outcome, with fewer events (combined endpoint of unstable angina, non-fatal AMI, heart failure and death) after hospital discharge (40% vs. 69%; p = 0.02) and a lower CCS functional class at the end of follow-up (1.26 +/- 0.63 vs. 1.730.71; p = 0.03). CONCLUSION: After acute myocardial infarction, the presence of collateral vessels is associated with a better long-term clinical outcome.

Percutaneous embolization of a congenital aortocaval fistula--clinical case.

Congenital aortocaval fistulae are a rare cause of left-to-right shunt. In this clinical case, an 8-year-old child was referred by the family doctor for pediatric cardiology consultation after detection of a chest murmur. Cardiac auscultation revealed a continuous murmur, best heard on the left sternal edge and back. During the study, cardiac angiography showed a large collateral vessel in the middle third of the thoracic aorta with a complex and sinuous route that ended at the superior vena cava. Percutaneous embolization was performed using a coil. Due to the large size of the collateral a total of three coils were necessary for complete occlusion. No complications were recorded and six-month follow-up confirmed absence of shunt. Compared to the surgical option, this procedure is less invasive and apparently with less risk to the patient.