Galectina-3 Associada a Formas Graves e Mortalidade em Longo Prazo em Pacientes com Doença de Chagas

Background The histopathological characteristics of Chagas disease (ChD) are: presence of myocarditis, destruction of heart fibers, and myocardial fibrosis. Galectin-3 (Gal-3) is a biomarker involved in the mechanism of fibrosis and inflammation that may be useful for risk stratification of individuals with ChD.Objectives We sought to evaluate whether high Gal-3 levels are associated with severe forms of Chagas cardiomyopathy (CC) and whether they are predictive of mortality.Methods We studied anti-T. cruzi positive blood donors (BD): Non-CC-BD (187 BD without CC with normal electrocardiogram [ECG] and left ventricular ejection fraction [LVEF]); CC-Non-Dys-BD (46 BD with CC with abnormal ECG but normal LVEF); and 153 matched serum-negative controls. This cohort was composed of 97 patients with severe CC (CC-Dys). We used Kruskall-Wallis and Spearman’s correlation to test hypothesis of associations, assuming a two-tailed p<0.05 as significant.Results The Gal-3 level was 12.3 ng/mL for Non-CC-BD, 12.0 ng/mL for CC-Non-Dys-BD, 13.8 ng/mL for controls, and 15.4 ng/mL for CC-Dys. LVEF<50 was associated with higher Gal-3 levels (p=0.0001). In our linear regression adjusted model, we found association between Gal-3 levels and echocardiogram parameters in T. cruzi-seropositive subjects. In CC-Dys patients, we found a significant association of higher Gal-3 levels (≥15.3 ng/mL) and subsequent death or heart transplantation in a 5-year follow-up (Hazard ratio – HR 3.11; 95%CI 1.21–8.04; p=0.019).Conclusions In ChD patients, higher Gal-3 levels were significantly associated with severe forms of the disease and more long-term mortality, which means it may be a useful means to identify high-risk patients. (Arq Bras Cardiol. 2021; 116(2):248-256)     

Efficacy and safety of low intensity vitamin K antagonists in Western and East-Asian patients with left-sided mechanical heart valves

Journal of Thrombosis and Thrombolysis - The optimal INR target in patients with mechanical heart valves is unclear. Higher INR targets are often used in Western compared with East Asian countries....     

Technique advance to avoid hepatic venous outflow obstruction in pediatric living‐donor liver transplantation

HVOO represents a serious critical complication of pediatric living‐donor liver transplantation because open surgical repair is virtually impossible. Currently, despite several technical innovations and the introduction of triangulated anastomosis for hepatic vein reconstruction, the reported incidence of HVOO is still considerable. The aim of this study was to propose a new technique for hepatic venous reconstruction that avoids the original orifice of the recipient hepatic veins. Instead, anastomosis is performed in a newly created wide longitudinal orifice in the anterior wall of the recipient inferior vena cava. A total of 210 living related‐donor liver transplantations were performed using two methods for reconstruction of the hepatic vein. Group 1 included 69 patients subjected to direct anastomosis of the orifice of the graft hepatic vein and a wide orifice created in the recipient inferior vena cava by the confluence of the orifices of the right, left, and middle hepatic veins. Group 2 included 141 patients in whom the original orifices of the recipient hepatic veins were closed, the inferior vena cava was widely opened, and a long longitudinal anastomosis was performed using two lines of continuous sutures. Diagnosis of HVOO was suspected based on clinical findings and ultrasound studies and then confirmed by liver biopsy and interventional radiology examinations. Among the 69 recipients in group 1, 16 patients died due to graft problems during the postoperative period and eight of the survivors (15.1%) presented with HVOO. In group 2 (141 patients), 21 patients died, and there were no cases of HVOO. A comparison of the incidence of HVOO between groups revealed a significant difference (p = 0.01). Hepatic venous reconstruction during pediatric living‐donor liver transplantation should be performed using a wide longitudinal incision in the anterior wall of the recipient inferior vena cava because this technique eliminated anastomosis complications.     

Atrial Fibrillation: The Role of Atrial Defibrillation

Dual defibrillator implantation represents an emerging option to treat patients with drug refractory atrial fibrillation. Atrial antitachycardia pacing and cardioversion have been demonstrated to be highly effective in treating spontaneous tachyarrhythmias and may reduce atrial fibrillation burden by preventing atrial remodeling. Device implantation has been associated to improved quality of life and reduced hospitalization rate. Patient selection and tailored device programming are critical as regard to clinical outcome. Individual psychological profile analysis as well as underlying heart disease and atrial fibrillation clinical patterns represent the main drivers for the right strategy. Controlled studies are needed in order to define the subset of patients who can benefit more from device implantation.     

Weekly docetaxel versus CMF as adjuvant chemotherapy for elderly breast cancer patients: safety data from the multicentre phase 3 randomised ELDA trial

Within an ongoing multicentre phase 3 randomised trial (ELDA, cancertrials.gov ID: NCT00331097), early breast cancer patients, 65-79 years old, with average to high risk of recurrence, are randomly assigned to receive CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, fluorouracil 600 mg/m2, days 1-8) or docetaxel (35 mg/m2 days 1-8-15), every 4 weeks. Here we report an unplanned safety analysis prompted by an amendment introducing creatinine clearance as a tool to adjust methotrexate dose. Before such change, 101 patients with a median age of 70 were randomly assigned CMF (53 patients) or docetaxel (48 patients). At least one grades 3-4 toxic event of any type was reported in 40 (75.5%) and 19 (39.6%) patients with CMF and docetaxel, respectively (p=0.0002). Grades 3-4 hematological events were observed in 37 (69.8%) vs. 4 (8.3%) cases (p<0.0001) and grades 3-4 non-hematological toxicity in 12 (22.6%) vs. 15 (31.2%) patients (p=0.11), with CMF and docetaxel, respectively. A higher incidence of anemia, neutropenia, thrombocytopenia and febrile neutropenia was reported with CMF. Constipation, mucositis, nausea and vomiting were more common with CMF; diarrhoea, abdominal pain, dysgeusia, neuropathy and liver toxicity were more frequent with docetaxel. No significant interaction was found between the occurrence of severe toxicity and baseline variables, including creatinine clearance and geriatric activity scales. In conclusion, weekly docetaxel appears to be less toxic than CMF in terms of hematological toxicity.     

Multicentre phase III trial on fludarabine, cytarabine (Ara-C), and idarubicin versus idarubicin, Ara-C and etoposide for induction treatment of younger, newly diagnosed acute myeloid leukaemia patients

Fludarabine plus cytarabine (Ara-C) and idarubicin (FLAI) is an effective and well-tolerated induction regimen for the treatment of acute myeloid leukaemia (AML). This phase III trial compared the efficacy and toxicity of FLAI versus idarubicin plus Ara-C and etoposide (ICE) in 112 newly diagnosed AML patients <60 years. Fifty-seven patients received FLAI, as the first induction-remission course, and 55 patients received ICE. Post-induction treatment consisted of high-dose Ara-C (HDAC). After HDAC, patients in complete remission (CR) received a second consolidation course (mitoxantrone, etoposide, Ara-C) and autologous stem cell transplantation (auto-SCT) or allogeneic (allo)-SCT, according to the age, disease risk and donor availability. After a single induction course, CR rate was 74% in the FLAI arm and 51% in the ICE arm (P = 0.01), while death during induction was 2% and 9% respectively. Both haematological (P = 0.002) and non-haematological (P = 0.0001) toxicities, especially gastrointestinal (i.e. nausea, vomiting, mucositis and diarrhoea), were significantly lower in FLAI arm. In both arms, relapses were more frequent in patients who were not submitted to allo-SCT. After a median follow-up of 17 months, 30% and 38% of the patients are in continuous CR in FLAI and ICE arm respectively. Our prospective randomised study confirmed the anti-leukaemic effect and the low toxic profile of FLAI as induction treatment for newly diagnosed AML patients.