The mismatch repair endonuclease MutLα tethers duplex regions of DNA together and relieves DNA torsional tension.

In eukaryotic mismatch repair, MutS homologs recognize mismatches and recruit the MutLα endonuclease which introduces a nick in the newly replicated, error-containing DNA strand. The nick occurs in response to the mismatch, but at a site up to several hundred base pairs away. The MutLα nick promotes mismatch excision by an exonuclease (Exo1) or removal by the strand displacement activity of a DNA polymerase which may work in conjunction with a flap endonuclease. Models have suggested that MutL homolog endonucleases form oligomeric complexes which facilitate and are activated by strand capture mechanisms, although such models have never been explicitly tested. We present evidence that the mismatch repair MutLα endonuclease is activated by DNA-DNA associations and that it can use this property to overcome DNA torsional barriers. Using DNA ligation and pull-down experiments, we determined that the MutLα endonuclease associates two DNA duplexes. Using nuclease assays, we determined that this activity stimulates MutLα's endonuclease function. We also observe that MutLα enhances a topoisomerase without nicking the DNA itself. Our data provide a mechanistic explanation for how MutL proteins interact with DNA during mismatch repair, and how MutL homologs participate in other processes, such as recombination and trinucleotide repeat expansions.

Implementation and Monitoring of a Telemedicine Model in Acromegalic Outpatients in a Low-Income Country During the COVID-19 Pandemic.

Background: Telemedicine is a resource to provide health care to patients social distancing and prevent their exposure to the risk of contamination by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in medical-hospital settings. This study evaluated a virtual model of care in acromegalic patients. Methods: We recruited 78 acromegalic patients, 65% female, median age 63 years. Outpatient management was remodeled to simplify access to care by (1) adoption of virtual meetings; (2) collection of blood samples at home; (3) abolishment of printed prescription and provision of electronic files directly to central pharmacy; and (4) drugs delivered to patients' home. Patients and physicians filled electronic surveys 48 h after each consultation. Results: The patients expressed satisfaction with convenience (91.1%), decreased wait time (85.1%), and saving money (79.2%) compared to face-to-face visits. Most patients felt supported by the medical team (89.1%) and kept the prescriptions updated (84.8%). The physicians reported resolutive appointments in 92.2% of cases, despite longer time to reach the patients and subsequent calls to complement missing information. Satisfaction and patient-provider relationship were maintained during the study, but the choice for virtual appointment for the next appointment fell from 78.7% to 34.8% after 6 months. Coronavirus disease 2019 (COVID-19) was confirmed in 13% of patients, mostly mild and moderate manifestations. Conclusion: Telemedicine is a tool for medical care in underserved populations, feasible even in low-income countries. This study suggests that it is difficult to sustain exclusive remote care for more than 6 months. The method could be adopted interchangeably with in-person consultations in acromegalic patients with stable disease.

Degenerative Severe Aortic Stenosis and Concomitant Coronary Artery Disease: What Is Changing in the Era of the "Transcatheter Revolution"?

PURPOSE OF REVIEW: To summarize epidemiology, pathophysiology, prognostic relevance, and treatment options of coronary artery disease (CAD) when coupled with severe aortic stenosis (SAS). In regard to treatment options, we focused on the most recently adopted therapeutic approaches and on the future perspectives in light of the latest percutaneous and surgical technical improvements in the field of both CAD and SAS management. RECENT FINDINGS: Nowadays, SAS is the most common valve disease requiring intervention, either surgical or percutaneous. On the other side, CAD is one of the leading causes of death in the developed countries. CAD and degenerative SAS share several predisposing factors and are often concurrently found in clinical practice. Despite in the last years the transcatheter aortic valve replacement (TAVR) has been deeply changing the therapeutic approach to SAS, the correct management of patients with concomitant CAD remains controversial due to limited and heterogeneous data in the literature. Coronary revascularization is often performed in patients with concomitant CAD and SAS. Complete surgical approach is still the standard of care according to international guidelines. However, in light of the recent results of TAVR trials, the therapeutic approach is expected to change. To date, percutaneous coronary intervention performed before TAVR is safe and feasible even if the optimal timing for revascularization remains debated. Due to the great complexity of the patients affected by SAS and CAD and until unquestionable truths will come from large randomized trials, the role of the Heart Team in the decision-making process is of primary importance to guarantee the best tailored therapeutic strategy for the single patient.

Ultrasound-guided venipuncture for implantation of cardiac implantable electronic devices: A single-center, retrospective study.

BACKGROUND: The venous access for the insertion of permanent leads of cardiac implantable electronic devices is often achieved by venous cutdown of the cephalic vein, or by "blind" puncture of the subclavian vein using anatomical landmarks, or by fluoroscopy-assisted methods. METHODS: We have retrospectively analyzed our clinical experience to verify the feasibility, the safety, and efficacy of the adoption of ultrasound-guided puncture/cannulation of the axillary vein for this purpose. RESULTS: Nine hundred eighty-seven leads were placed during 548 consecutive procedures, accessing the axillary vein in the infraclavicular area using real-time ultrasound guidance. Venipuncture was successful in 99.8% of cases. The access time was 11 seconds (range 4-580). We recorded three cases of pneumothorax (0.5%), but no hemothorax and no hemo-mediastinum. The incidence of local hematoma was 2.1% (12 cases). No injury to the brachial plexus or to the phrenic nerve was recorded. In a follow-up of 33 months (range 16-39), we observed no cases of "subclavian crush syndrome" (damage of the leads at the level of the thoracic inlet), and the rate of pocket infection/infective endocarditis was 0.7%. CONCLUSION: In our experience, ultrasound-guided puncture/cannulation of the axillary vein for implantation of permanent leads is feasible, effective, and safe. It might be considered as a first option for this procedure.

Echocardiographic features of post-transcatheter aortic valve implantation thrombosis and endocarditis.

BACKGROUND: Transcatheter heart valve thrombosis (THV-t) and endocarditis (THV-e) are relevant complications after transcatheter aortic valve implantation (TAVI). Transcatheter heart valve (THV) dysfunction definition is mostly based on Doppler (stenosis/regurgitation) without considering leaflets characteristics. PURPOSE: To evaluate the additional diagnostic value of leaflets echocardiographic features over Doppler when prosthetic valve complication is suspected. METHODS: Among 621 post-TAVI patients, 128 cases with probable valve complication were identified. THV-t was finally diagnosed in 13 patients (10%) and THV-e in 8 (6%), while the remaining 107 (84%) had no definitive diagnosis of thrombosis/endocarditis (THV-no). We analyzed at 2 time points (baseline and follow-up) both traditional Doppler parameters and leaflets morpho-functional features. RESULTS: Both Doppler and leaflets parameters showed high sensitivity (sensitivity 92%) and low specificity (ranging from specificity 32% to 74%) in detecting THV-t. Interestingly, the combination of mean aortic pressure gradient ≥20 mm Hg and leaflet thickening significantly improved the specificity of echocardiography for diagnosis of THV thrombosis (specificity 94%). On the other hand, echocardiographic diagnosis of THV endocarditis remained limited by very low sensitivity despite showing high specificity. CONCLUSIONS: The combination of Doppler and leaflets parameters can improve the echocardiographic diagnosis of THV thrombosis in post-TAVI patients with suspicious symptoms, via a significant increase in the overall test specificity. This would potentially allow more rational gatekeeping to more expensive/invasive diagnostic examinations (eg, CT scan) or therapeutic trials (eg, unnecessary anticoagulation).

PFO closure with only fluoroscopic guidance: 7 years real-world single centre experience.

AIMS: To evaluate the safety and the efficacy of fluoroscopy-guided only (Fluo-G) and of echocardiography-guided (Echo-G; trans-esophageal echocardiography-TEE-or intracardiac echocardiography-ICE) percutaneous closure of patent foramen ovale (PFO). METHODS AND RESULTS: Single center retrospective registry enrolling 368 consecutive patients (mean age 50.5 years) who underwent PFO closure between June 2004 and December 2011. Most patients had prior cryptogenic stroke (n = 126; 34.2%), TIA (n = 218; 51.1%); some of these had recurrent neurological events [multiple strokes n = 28 (7.8%); multiple TIAs n = 72 (18.6%)]. All the patients underwent a preprocedure TEE. PFO closure was performed with Echo-G in 187 patients (50.8%) (TEE n = 69, 36.8% and ICE n = 124, 66.3%). In Fluo-G cases, PFO with atrial septal aneurysm (ASA) was significantly less present (P < 0.005) and smaller devices (<25 mm) were implanted more frequently (P < 0.001). Both fluoroscopy and total procedural time were lower in the Fluo-G group (P < 0.0001). No differences were found in terms of successful device deployment (98.3% Fluo-G vs. 98.3% Echo-G) and RtL-shunt at follow-up (11.7% Fluo-G vs. 7.6% Echo-G). The rate of conversion from Fluoro-G to Echo-G procedure was 4.4% (n = 8). At a median follow-up of 4 years, freedom from recurrent embolic events rate was similar between the two groups (Echo-G 94.5 vs. Fluo-G 95.7%). CONCLUSIONS: In our experience Fluoro-G PFO closure was performed mainly in cases of simple anatomy, with similar results in terms of safety and efficacy compared to Echo-G cases. Both fluoroscopy and total procedural times were lower in the Fluo-G cases.

Safety and Efficacy of PCSK9 Inhibitors in Patients with Acute Coronary Syndrome Who Underwent Coronary Artery Bypass Grafts: A Comparative Retrospective Analysis.

Background. The in-hospital reduction in low-density lipoprotein cholesterol (LDL-C) levels following acute coronary syndrome (ACS) is recommended in the current clinical guidelines. However, the efficacy of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors in those patients undergoing coronary artery bypass graft (CABG) has never been demonstrated. Methods. From January 2022 to July 2023, we retrospectively analyzed 74 ACS patients characterized by higher LDL-C levels than guideline targets and who underwent coronary bypass surgery. In the first period (January 2022-January 2023), the patients increased their statin dosage and/or added Ezetimibe (Group STEZE, 43 patients). At a later time (February 2023-July 2023), the patients received not only statins and Ezetimibe but also Evolocumab 140 mg every 2 weeks starting as early as possible (Group STEVO, 31 patients). After one and three months post-discharge, the patients underwent clinical and laboratory controls with an evaluation of the efficacy lipid measurements and every adverse event. Results. The two groups did not differ in terms of preoperative risk factors and Euroscore II (STEVO: 2.14 ± 0.75 vs. STEZE: 2.05 ± 0.6, p = 0.29). Also, there was no difference between the groups in terms of ACS (ST-, Instable angina, or NSTE) and time of symptoms onset regarding total cholesterol, LDL-C, and HDL-C trends from the preprocedural period to 3-month follow-up, but there was a more significant reduction in LDL-C and total cholesterol in the STEVO group (p = 0.01 and p = 0.04, respectively) and no difference in HDL-C rise (p = 0.12). No deaths were reported. In three STEZE group patients, angina recurrence posed the need for percutaneous re-revascularization. No STEVO patients developed significant adverse events. The statistical difference in these serious events, 7% in STEZE vs. 0% in STEVO, was not significant (p = 0.26). Conclusions. Evolocumab initiated "as soon as possible" in ACS patients submitted to CABG with high-intensity statin therapy and Ezetimibe was well tolerated and resulted in a substantial and significant reduction in LDL-C levels at discharge, 1 month, and 3 months. This result is associated with a reduction but without a statistical difference between groups.

How many clues make an evidence? An unusual case of aborted cardiac arrest due to mitral valve prolapse.

There is an increasing awareness on the association between mitral valve prolapse (MVP) and sudden cardiac death. Mitral annular disjunction (MAD) is a phenotypic risk feature that can help in risk stratification. We present a case of a 58-year-old woman who experienced an out-of-hospital cardiac arrest caused by ventricular fibrillation interrupted by a direct current shock. No coronary lesions were documented. Echocardiogram showed myxomatous MVP. Nonsustained ventricular tachycardia have been registered during hospital stay. Interestingly, cardiac magnetic resonance revealed MAD and a late gadolinium enhancement area in inferior wall. Finally, a defibrillator has been implanted. For arrhythmic risk stratification of MVP with MAD, multimodality imaging is the diagnostic tool to find out the disease behind many cardiac arrests of unknown cause.

Classic cardiovascular risk factors improve in very elderly hypopituitary patients treated on standard hormone replacement in long term follow- up.

BACKGROUND: Hypopituitarism in the elderly population is an underdiagnosed condition and may increase comorbidities related to glucose metabolism, dyslipidemia, and cardiovascular risk factors. Optimization of hormone replacement that considers alterations in clearance rates of hormones, interaction with other medications, and evaluation of the risk-benefit ratio of treatment is a big challenge for clinical practice. OBJECTIVES: This study aimed to evaluate classic cardiovascular risk factors in hypopituitary septuagenarians and octagenarians by diagnosis and after long-term hormone replacement. METHODS: This is a retrospective observational study, with patients recruited and selected from a registry in a tertiary medical center. We included patients aged 70-99 years with hypopituitarism, evaluated hormonal and biochemical parameters, and cardiovascular risk scores were calculated by diagnosis and compared after long-term follow-up. All patients gave informed consent. Patient data were compared to a sex and age-matched control group, with long-term geriatric follow-up, without endocrine diseases. RESULTS: Thirty-five patients were included, 16 patients aged 70-75 years (72.61), 12 patients 76-80 years (72.28), 7 patients 81-99 years (89.28). Pituitary macroadenomas were the main cause of hypopituitarism, mean maximal diameter 3.4 cm (2.9-4.3), and invasive craniopharyngiomas. At the moment of diagnosis, most patients were overweight, and abdominal adiposity was observed in 76.9% of women and 36.4% of men, primarily in octagenarians and nonagenarians. Comorbidities were frequent; 85.7% presented hypertension, 37.1% diabetes, 53.1% low HDL, 51.5% hypertriglyceridemia. Most patients presented more than two combined pituitary deficiencies; hypogonadism in 88.6%, central hypothyroidism in 82.9%, GH deficiency in 65.7%, and adrenal insufficiency in 25.7%. Analysis of cardiovascular risk prediction in the total cohort showed that 57.1% of patients presented a reduction in the General Cardiovascular Disease (CVD) Risk Prediction Score and 45.7% in atherosclerotic CVD risk estimated by ACC/AHA 2013 Pooled Cohort Equation, despite being submitted to conventional hormone replacement, during the mean follow-up of 14.5 years. This reduction was not observed in the control group. DISCUSSION AND CONCLUSION: In this study, aged hypopituitary patients presented a reduction in estimated general CVD risk during long-term follow-up, despite replacement with corticosteroids, levothyroxine, or gonadal steroids. Early diagnosis and treatment of hypopituitarism in the elderly remain challenging. Larger studies should be performed to assess the risk-benefit ratio of hormone replacement on the metabolic profile in septuagenarian and octogenarian patients.

Cardiac arrest in type II Kounis syndrome after oral intake of amoxicilline.

BACKGROUND: Kounis syndrome (KS) is defined as the occurrence of an acute coronary syndrome related to allergic or hypersensitivity reaction. KS is currently classified into three variants, based on coronary arteries status. This syndrome is often neglected or misdiagnosed in clinical practice. METHODS AND RESULTS: We described a type II KS case. This acute coronary syndrome (ACS) began with cardiac arrest (an uncommon clinical expression for KS) immediately after oral intake of amoxicilline. Coronary angiography revealed coronary arteries stenoses which were considered unsuitable for revascularization. Optimization of medical therapies was the goal of the management for this patient. Follow-up visits revealed normal echocardiographic findings and no malignant arrhythmias at ECG Holter monitoring. CONCLUSIONS: KS can be a rare case for ACS, sometimes occurring with sudden cardiac arrest. Physicians should pay attention to the history of the patients in order to identify the correct cause of ACSs.

Accuracy and reproducibility of aortic annular measurements obtained from echocardiographic 3D manual and semi-automated software analyses in patients referred for transcatheter aortic valve implantation: implication for prosthesis size selection.

Aims: A 3D transoesophageal echocardiography (3D-TOE) reconstruction tool has recently been introduced. The system automatically configures a geometric model of the aortic root and performs quantitative analysis of these structures. We compared the measurements of the aortic annulus (AA) obtained by semi-automated 3D-TOE quantitative software and manual analysis vs. multislice computed tomography (MSCT) ones. Methods and results: One hundred and seventy-five patients (mean age 81.3 ± 6.3 years, 77 men) who underwent both MSCT and 3D-TOE for annulus assessment before transcatheter aortic valve implantation were analysed. Hypothetical prosthetic valve sizing was evaluated using the 3D manual, semi-automated measurements using manufacturer-recommended CT-based sizing algorithm as gold standard. Good correlation between 3D-TOE methods vs. MSCT measurements was found, but the semi-automated analysis demonstrated slightly better correlations for AA major diameter (r = 0.89), perimeter (r = 0.89), and area (r = 0.85) (all P < 0.0001) than manual one. Both 3D methods underestimated the MSCT measurements, but semi-automated measurements showed narrower limits of agreement and lesser bias than manual measurements for most of AA parameters. On average, 3D-TOE semi-automated major diameter, area, and perimeter underestimated the respective MSCT measurements by 7.4%, 3.5%, and 4.4%, respectively, whereas minor diameter was overestimated by 0.3%. Moderate agreement for valve sizing for both 3D-TOE techniques was found: Kappa agreement 0.5 for both semi-automated and manual analysis. Interobserver and intraobserver agreements for the AA measurements were excellent for both techniques (intraclass correlation coefficients for all parameters >0.80). Conclusion: The 3D-TOE semi-automated analysis of AA is feasible and reliable and can be used in clinical practice as an alternative to MSCT for AA assessment.

Modelo alternativo para o treinamento de técnicas de microssuturas em "patch" de pericárdio bovino / Alternative model for training microsuture techniques in bovine pericardium patches

Introdução: As técnicas microcirúrgicas caracterizam-se pela aplicação de manobras e suturas em estruturas milimétricas com o auxílio de lentes de aumento. São técnicas complexas, utilizadas em diversas especialidades médicas, que demandam grande habilidade e treinamento antes da aplicação em humanos. O objetivo é desenvolver um modelo de baixo custo e alta fidelidade, para o treinamento de técnicas de microcirurgia, utilizando um fragmento de patch de pericárdio bovino. Método: São utilizados para a confecção deste modelo segmentos remanescentes de uma placa de pericárdio bovino, previamente utilizado em reparos vasculares. O material é recortado em duas partes simétricas e suas extremidades fixadas aos campos cirúrgicos, com auxílio de clamps. A borda superior de cada uma das partes é, então, suturada à borda inferior com fio de Prolene 8-0, de maneira que cada uma forme uma estrutura tubular. Posteriormente, as extremidades tubulares livres passam pela dissecção da camada adventícia e são suturadas entre si, mimetizando uma anastomose vascular término-terminal. Resultados: Com o modelo, simulam-se os mesmos inconvenientes/ dificuldades presentes nas suturas vasculares humanas, como a delaminação de camadas, excesso da camada adventícia e risco de sutura inadvertida da parede posterior, provando sua utilidade na aquisição de habilidades microcirúrgicas básicas, sem necessidade de manipulação de tecidos humanos ou animais. A prática neste modelo pode ocorrer dentro do próprio centro cirúrgico e emprega materiais que seriam descartados. Conclusão: A utilização do pericárdio bovino para confecção de suturas milimétricas mimetiza o tecido vascular humano e é um procedimento de baixo custo, que possibilita o treinamento de habilidades microcirúrgicas.

Introduction: Microsurgical techniques are characterized by the application of maneuvers and sutures to millimetric structures with the aid of magnifying lenses. These are complex techniques, used in various medical specialties, which require great skill and training before applying them to humans. The objective is to develop a lowcost and high-fidelity model for training microsurgery techniques using a fragment of bovine pericardium patch. Method: Remaining segments of a bovine pericardium plate, previously used in vascular repairs, are used to create this model. The material is cut into two symmetrical parts, and its ends are fixed to the surgical drapes with the aid of clamps. The upper edge of each part is then sutured to the lower edge with 8-0 Prolene thread so that each one forms a tubular structure. Subsequently, the free tubular ends undergo dissection of the adventitial layer and are sutured together, mimicking an end-to-end vascular anastomosis. Results: With the model, the same inconveniences/ difficulties present in human vascular sutures are simulated, such as delamination of layers, excess of the adventitial layer, and risk of inadvertent suturing of the posterior wall, proving its usefulness in the acquisition of basic microsurgical skills, without need to manipulate human or animal tissues. Practice in this model can take place within the surgical center itself and uses materials that would otherwise be discarded. Conclusion: The use of bovine pericardium to create millimetric sutures mimics human vascular tissue and is a low-cost procedure that allows the training of microsurgical skills.

The exoproteome profiles of three Staphylococcus saprophyticus strains reveal diversity in protein secretion contents.

Staphylococcus saprophyticus is a gram-positive microorganism responsible for urinary tract infections (UTIs). Although some virulence factors are characterized, such as urease, autolysins, adhesins and hemagglutinins, large-scale proteomic studies have not been performed within this species. We performed the characterization of the exoproteome from three S. saprophyticus strains: the reference strain ATCC 15,305, a non-capsular strain 7108 and the 9325 strain containing a thick capsule which were cultured in BHI medium and culture supernatants were analysed by using mass spectrometry approach. We observed a core of 72 secreted proteins. In addition, it was possible to detect diversity in the protein profiles of the exoproteomes. Interestingly, strain 7108 presented no secretion of three antigenic proteins, including the classical SsaA antigen. In addition, the level of antigenic proteins secreted by strain 9325 was higher than in ATCC 15,305. This result was confirmed by Western blot analysis using anti-SsaA polyclonal antibodies, and no production/ secretion of SsaA was detected in strain 7108. Transcriptional data shows that 7108 strain produces transcripts encoding SsaA, suggesting post-transcriptional regulation occurs in this strain. Moreover, when compared with the other strains that were analyzed, it was possible to detect higher levels of proteases secreted by strain 7108 and higher levels of antigenic proteins and transglycosylases secreted by 9325 strain. The results reveal diversity in protein secretion among strains. This research is an important first step towards understanding the variability in S. saprophyticus exoproteome profile and could be significant in explaining differences among strains.

A proteomic dataset of secreted proteins by three Staphylococcus saprophyticus strains.

This article presents a proteomic dataset generated from a comparative analysis of the exoproteome of Staphylococcus saprophyticus, ATCC 15305, 7108 and 9325 strains. The extract of secreted proteins were obtained after incubation of stationary phase cells in BHI medium. All samples were submitted to nano-ESI-UPLC-MSE, and the spectrum obtained was processed and analyzed by ProteinLynx Global Server (PLGS), Uniprot and Pedant databases, for identification, annotation and functional classification of proteins. Fold changes and protein relative abundances were properly reported. This report is related to the research article entitled "The exoproteome profiles of three Staphylococcus saprophyticus strains reveal diversity in protein secretion contents" (Oliveira et al., 2018). The proteomic data generated have been deposited to the ProteomeXchange Consortium, via the PRIDE partner repository, with a project number PXD008643, https://www.ebi.ac.uk/pride/archive/projects/PXD008643.

Realidade epidemiológica da morbimortalidade hospitalar por acidente vascular cerebral no nordeste brasileiro, de 2015 a 2019 / Epidemiological reality of hospital morbimortality due to cerebral vascular accident in northeast brazil, from 2015 to 2019 / Realidad epidemiológica de la morbimortalidad hospitalaria por accidente vascular cerebral en el noreste de brasil, de 2015 a 2019

Com grande impacto social por alta mortalidade e morbidade no Brasil e no Mundo, o AVC continua em destaque dentre as Doenças Crônicas Não transmissíveis. Visando oferecer subsídios técnico-científicos sobre o perfil epidemiológico desta patologia no Nordeste, este artigo consiste em um estudo de corte transversal, quantitativo, epidemiológico, de série temporal, entre os anos de 2015 a 2019, tendo por base os dados disponibilizados na plataforma DATASUS. Evidenciou-se que o ano de 2019 foi o ano com maior número de internações por esta patologia, predominando em homens. No entanto, as mulheres tiveram mais óbitos. A raça mais acometida foi a parda, com mais de 82% das internações e mais de 83% dos óbitos. Os óbitos ocorreram em todas as faixas etárias, predominando nos mais idosos. O Estado com maior quantitativo de óbitos foi a Bahia, também o mais populoso do estudo. O perfil epidemiológico geral, do paciente acometido por AVC na região Nordeste do Brasil no período avaliado, foi, homem, com idade mais avançada (a partir de 60 anos), pardo, permanecendo cerca de 7,8 dias internados. O custo total desse período, com internações por AVC, foi de R$278.874.426.3, certamente, um custo bastante oneroso ao nosso sistema de saúde. As unidades federativas com maior acometimento são também as mais populosas. Percebendo-se que, por se tratar de uma doença prevenível, com graves sequelas e que causam grandes prejuízos pessoais, sociais e econômicos, torna-se relevante que o sistema público de saúde adote rigorosas medidas para sua prevenção.

With a great social impact due to high mortality and morbidity in Brazil and the world, stroke continues to be highlighted among Chronic Non-communicable Diseases. Aiming to offer technical-scientific support on the epidemiological profile of this pathology in the Northeast, this article consists of a cross-sectional, quantitative, epidemiological, time series study, between the years 2015 and 2019, based on data available on the DATASUS platform . It was evident that 2019 was the year with the highest number of hospitalizations for this pathology, predominantly in men. However, women had more deaths. The most affected race was the mixed race, with more than 82% of hospitalizations and more than 83% of deaths. Deaths occurred in all age groups, predominantly among the elderly. The State with the highest number of deaths was Bahia, also the most populous in the study. The general epidemiological profile of the patient affected by stroke in the Northeast region of Brazil during the period evaluated was male, older (60 years and older), mixed race, and remained hospitalized for approximately 7.8 days. The total cost of this period, with hospitalizations for stroke, was R$278,874,426.3, certainly a very costly cost to our health system. The federative units most affected are also the most populous. Realizing that, as it is a preventable disease, with serious consequences and causing great personal, social and economic losses, it is important that the public health system adopts strict measures for its prevention.

Con gran impacto social debido a la alta mortalidad y morbilidad en Brasil y el mundo, el accidente cerebrovascular sigue destacándose entre las Enfermedades Crónicas No Transmisibles. Con el objetivo de ofrecer soporte técnico-científico sobre el perfil epidemiológico de esta patología en el Nordeste, este artículo consiste en un estudio transversal, cuantitativo, epidemiológico, de series temporales, entre los años 2015 y 2019, con base en datos disponibles en la plataforma DATASUS. . Se evidenció que 2019 fue el año con mayor número de hospitalizaciones por esta patología, predominantemente en hombres. Sin embargo, las mujeres tuvieron más muertes. La raza más afectada fue la mestiza, con más del 82% de las hospitalizaciones y más del 83% de las muertes. Las muertes se produjeron en todos los grupos de edad, predominantemente entre los ancianos. El estado con mayor número de muertes fue Bahía, también el más poblado del estudio. El perfil epidemiológico general del paciente afectado por accidente cerebrovascular en la región Nordeste de Brasil durante el período evaluado fue masculino, mayor (60 años y más), mestizo y permaneció hospitalizado durante aproximadamente 7,8 días. El costo total de este período, con las hospitalizaciones por accidente cerebrovascular, fue de R$ 278.874.426,3, ciertamente un costo muy costoso para nuestro sistema de salud. Las unidades federativas más afectadas son también las más pobladas. Al ser conscientes de que, al tratarse de una enfermedad prevenible, de graves consecuencias y que provoca grandes pérdidas personales, sociales y económicas, es importante que el sistema público de salud adopte medidas estrictas para su prevención. PALABRAS CLAVE: Accidente Cerebrovascular; Epidemiología; Salud Pública.

Type C botulism in dogs from rural properties located in Goiânia, Brazil

Botulism is a disease usually fatal, caused by the ingestion of neurotoxins produced by Clostridium botulinum. In dogs, intoxication is caused by the ingestion of botulinum toxin type C, and animals often recover spontaneously. The present study describes the occurrence of type C botulism in two dogs domiciled on neighboring rural properties in the municipality of Goiânia, state of Goiás, Brazil, probably associated with ingestion of decomposing bovine carcass. Upon clinical evaluation, the dogs were alert in the lateral decubitus position with ascending flaccid paralysis, absence of eyelid reflexes, and reduced muscle tone. Due to their worsening clinical symptoms, the animals died within 12 h and 3 days after supportive treatment. Botulinum toxin type C was identified, in the serum and feces of both dogs, by seroneutralization in mice with homologous monovalent antitoxin. The results of the high-throughput gene sequencing showed that the abundance of C. botulinum in the fecal microbiota of one of the affected dogs was low (0.53%). In this way, the present study highlights the need of sanitary practices related to the appropriate collection and disposal of bovine carcasses in rural areas since they represent a risk factor for the occurrence of botulism in dogs domiciled on rural properties.

Mechanical dyssynchrony and deformation imaging in patients with functional mitral regurgitation.

Chronic functional mitral regurgitation (FMR) is a frequent finding of ischemic heart disease and dilated cardiomyopathy (DCM), associated with unfavourable prognosis. Several pathophysiologic mechanisms are involved in FMR, such as annular dilatation and dysfunction, left ventricle (LV) remodeling, dysfunction and dyssynchrony, papillary muscles displacement and dyssynchrony. The best therapeutic choice for FMR is still debated. When optimal medical treatment has already been set, a further option for cardiac resynchronization therapy (CRT) and/or surgical correction should be considered. CRT is able to contrast most of the pathophysiologic determinants of FMR by minimizing LV dyssynchrony through different mechanisms: Increasing closing forces, reducing tethering forces, reshaping annular geometry and function, correcting diastolic MR. Deformation imaging in terms of two-dimensional speckle tracking has been validated for LV dyssynchrony assessment. Radial speckle tracking and three-dimensional strain analysis appear to be the best methods to quantify intraventricular delay and to predict CRT-responders. Speckle-tracking echocardiography in patients with mitral valve regurgitation has been usually proposed for the assessment of LV and left atrial function. However it has also revealed a fundamental role of intraventricular dyssynchrony in determining FMR especially in DCM, rather than in ischemic cardiomyopathy in which MR severity seems to be more related to mitral valve deformation indexes. Furthermore speckle tracking allows the assessment of papillary muscle dyssynchrony. Therefore this technique can help to identify optimal candidates to CRT that will probably demonstrate a reduction in FMR degree and thus will experience a better outcome.

Impact and evolution of right ventricular dysfunction after successful MitraClip implantation in patients with functional mitral regurgitation.

BACKGROUND: Right ventricular dysfunction (RVdysf) is a predictor of poor outcome in patients with heart failure and valvular disease. The aim of this study was to evaluate the evolution and the impact of RVdysf in patients with moderate-severe functional mitral regurgitation (FMR) successfully treated with MitraClip. METHODS AND RESULTS: From October 2008 to July 2014, 60 consecutive high surgical risk FMR patients were evaluated and stratified into two groups: RVdysf group (TAPSE < 16 mm and/or S'TDI < 10 cm/s, 21 patients) and No-RVdysf group (38 patients). The overall mean age of patients was 73 ± 8 (83% male). Ischemic FMR etiology was present in 67%. Mean LVEF was 30 ± 10%. Overall mean time follow-up was 565 ± 310 days. The only significant difference between the two groups was a greater prevalence of stroke, ICD and use of aldosterone antagonist in RVdysf group. Acute procedural success was achieved in 90% of patients. At 6-month echo-matched analysis significant RV function improvement was observed in patients with baseline RVdysf (TAPSE 15 ± 3.0 vs. 19 ± 4.5, p = 0.007; S'TDI 7 ± 1.2 vs. 11 ± 2.8, p < 0.0001; baseline vs. 6-month, respectively). The mean improvement in the 6-min walking test was significant in both groups (120 and 143 m, RVdysf and No-RVdysf groups, respectively). At Kaplan-Meier analysis, the presence of RVdysf did not affect the outcome in terms of freedom from composite efficacy endpoint. CONCLUSIONS: This study shows that successful MitraClip implantation in patients with FMR and concomitant right ventricular dysfunction yields significant improvement of RV function at mid-term follow-up. Further data on larger population will be required to confirm our observations.

Successful implantation of a second-generation aortic valve in severe aortic regurgitation secondary to a traumatic cusp lesion.

A 67-year-old man with a dilated cardiomyopathy and severe aortic regurgitation (AR) secondary to a traumatic cusp lesion was referred to our institution because of progressive worsening of dyspnea. After formal discussion in the heart team, the patient was scheduled for TAVI (transcatheter aortic valve implantation). The pre procedural computed tomography scan revealed a minimum amount of calcium on the aortic valve and low position of coronary ostia. The TAVI procedure was performed with the implantation of a fully retrievable and repositionable aortic valve prosthesis (Direct Flow 29 mm, Direct Flow Medical, Santa Rosa, California) with an excellent result and no paravalvular leak. The TAVI devices designed for the treatment of calcific aortic stenosis have numerous limitations for the treatment of pure AR such as the risk of residual AR, the lack of repositionability and retrievability, and the need for valve- in-valve implantation. We believe that treatment of selected cases of pure AR with the Direct Flow valve is feasible and takes advantage of the retrievability of the prosthesis.

Role of plaque calcification regulators osteoprotegerin and matrix Gla-proteins in stable angina and acute myocardial infarction.

AIM: To assess serum levels of the plaque calcification regulators osteoprotegerin (OPG) and Matrix Gla-proteins (MGP) in individuals with stable angina and acute myocardial infarction submitted to coronary angiography and their relation to coronary artery disease burden. METHODS: The study included 40 individuals affected by ST-elevation myocardial infarction (STEMI) and 40 individuals with stable angina who all underwent coronary angiography, with evaluation of the extent of coronary artery disease by Syntax Score calculation and measurement of serum OPG and MGP levels. Osteoporosis was excluded by femoral and vertebral computerized bone mineralometry. RESULTS: Serum OPG and MGP levels were respectively 3.87 ±â€Š1.07 pmol/l and 6.80 ±â€Š2.43 nmol/l in the stable angina group, 7.57 ±â€Š1.5 pmol/l and 7.18 ±â€Š1.93 nmol/l in the STEMI group (P < 0.01 and P = 0.33, respectively). Pearson correlation coefficient for OPG and Syntax Score, MGP and Syntax score was respectively 0.79 (P < 0.01) and 0.18 (P = 0.22) in the stable angina group, -0.03 (P = 0.43) and 0.10 (P = 0.5) in the STEMI group.Serum OPG and MGP levels were respectively 5.52 ±â€Š1.02 pmol/l and 7.56 ±â€Š1.42 nmol/l in diabetics, 4.3 ±â€Š0.8 pmol/l and 6.52 ±â€Š1.14 nmol/l in nondiabetics (P < 0.05; P < 0.05). CONCLUSION: OPG, in a relatively small group of patients with stable angina, correlates proportionally with the extent of coronary artery disease (CAD), as evaluated by the Syntax Score. Higher serum OPG levels can be observed in individuals with STEMI regardless of CAD burden. As for MGP, a potential role as marker of plaque calcification remains unproven.