A novel case of human visceral leishmaniasis from the urban area of the city of Rio de Janeiro: autochthonous or imported from Spain ?

Universidade Federal do Estado do Rio de Janeiro. Centro de Ciências Biológicas e da Saúde. Hospital Universitário Gaffrée e Guinle, 10ª Enfermaria. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Centro de Ciências Biológicas e da Saúde. Hospital Universitário Gaffrée e Guinle, 10ª Enfermaria. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Centro de Ciências Biológicas e da Saúde. Hospital Universitário Gaffrée e Guinle, 10ª Enfermaria. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Centro de Ciências Biológicas e da Saúde. Hospital Universitário Gaffrée e Guinle, 10ª Enfermaria. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Centro de Ciências Biológicas e da Saúde. Hospital Universitário Gaffrée e Guinle, 10ª Enfermaria. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Centro de Ciências Biológicas e da Saúde. Hospital Universitário Gaffrée e Guinle, 10ª Enfermaria. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Centro de Ciências Biológicas e da Saúde. Hospital Universitário Gaffrée e Guinle, 10ª Enfermaria. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Centro de Ciências Biológicas e da Saúde. Hospital Universitário Gaffrée e Guinle, 10ª Enfermaria. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Centro de Ciências Biológicas e da Saúde. Hospital Universitário Gaffrée e Guinle, 10ª Enfermaria. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Centro de Ciências Biológicas e da Saúde. Hospital Universitário Gaffrée e Guinle. Serviço de Anatomia Patológica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses. Rio de Janeiro, RJ, Brasil

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Somatotrophic and corticotrophic function outcome after transesphenoidal surgery in patients with sellar tumors and pre-operative endocrine deficits Evolução das funções somatotrófica e corticotrófica após cirurgia transesfenoidal em pacientes com tumores selares e deficits endócrinos pré-operatórios

Sixteen patients with sellar tumors that were treated surgically and who had pre-operative somatotrophic and corticotrophic function deficits were submitted to pre- and early post-operative insulin tolerance tests (ITTs). Seven patients had non-functioning adenomas, 5 had prolactinomas, 3 had craniopharyngioma and 1 had cordoma of the clivus. All patients had macro-tumors and none received radiotherapy within the studied period. Seven patients had GH, 4 had Cortisol and 5 had both GH/cortisol function pre-operative deficit. Five patients with isolated GH, 4 with isolated Cortisol and 3 with both GH/cortisol deficiencies showed a postoperative functional recovery. New Cortisol secretion deficits were observed in 2 patients postoperatively and both required long-term steroid replacement. These data suggest that preoperative endocrine deficits may be reversible after surgical decompression of the sellar region and that new endocrine deficits are rarely seen after surgery. All such patients should be tested postoperatively from an endocrinological point of view to reevaluate the need for replacement therapies.Dezesseis pacientes com tumores da região selar que foram tratados cirurgicamente e que possuíam deficits funcionais dos eixos somatotrófico ou corticotrófico foram submetidos a teste de tolerância à insulina pré- e pós-operatoriamente. Sete pacientes possuíam adenomas não-funcionantes, 5 possuíam prolactinomas, 3 craniofaringiomas e 1 possuía cordoma de clivus. Todos os pacientes possuíam macrotumores e nenhum deles foi submetido a radioterapia durante o período do estudo. Sete pacientes possuíam deficiência isolada do setor somatotrófico, 4 isolada do setor corticotrófico e 5 possuíam deficiência de ambos os setores. Cinco pacientes com deficiência isolada do setor somatotrófico, 4 com deficit isolado do setor corticotrófico e 3 com deficiência nos dois setores obtiveram melhora funcional pós-operatoriamente. Novos deficits do setor corticotrófico ocorreram em 2 pacientes, que necessitaram reposição de esteróides por longo prazo. Estes dados sugerem que deficits endócrinos pré-operatórios podem ser revertidos pela descompressão cirúrgica da região selar e que novos deficits causados pela cirurgia são raros. Estes pacientes devem ser retestados pós-operatoriamente do ponto de vista endócrino para se determinar a necessidade de terapia de reposição hormonal