Phase 2, Double-Blind, Placebo-controlled Trial of a c-Jun N-Terminal Kinase Inhibitor in Idiopathic Pulmonary Fibrosis.

Rationale: Idiopathic pulmonary fibrosis is a fatal and progressive disease with limited treatment options. Objectives: To assess the efficacy and safety of CC-90001, an oral inhibitor of c-Jun N-terminal kinase 1, in patients with idiopathic pulmonary fibrosis. Methods: NCT03142191 was a phase 2, randomized (1:1:1), double-blind, placebo-controlled study in which patients received CC-90001 (200 or 400 mg) or placebo once daily for 24 weeks. Background antifibrotic treatment (pirfenidone) was allowed. The primary endpoint was change in percentage of predicted forced vital capacity (ppFVC) from baseline to Week 24; secondary endpoints included safety. Measurements and Main Results: In total, 112 patients received ≥1 dose of study drug. The study was terminated early due to a strategic decision made by the sponsor. Ninety-one patients (81%) completed the study. The least-squares mean changes from baseline in ppFVC at Week 24 were -3.1% (placebo), -2.1% (200 mg), and -1.0% (400 mg); the differences compared with placebo were 1.1% (200 mg; 95% CI: -2.1, 4.3; P=.50) and 2.2% (400 mg; 95% CI: -1.1, 5.4; P=.19). Adverse event frequency was similar in patients in the combined CC-90001 arms versus placebo. The most common adverse events were nausea, diarrhea, and vomiting, which were more frequent in patients in CC-90001 arms versus placebo. Fewer patients in the CC-90001 than in the placebo arm experienced cough and dyspnea. Conclusions: Treatment with CC-90001 over 24 weeks led to numerical improvements in ppFVC in patients with idiopathic pulmonary fibrosis compared to placebo. CC-90001 was generally well tolerated, consistent with previous studies. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT03142191.

[Incidence of pulmonary complications in myocardial revascularization]. / Incidência de complicações pulmonares na cirurgia de revascularização do miocárdio.

BACKGROUND: despite the increasingly careful attempts to reduce perioperative risks, pulmonary complications following surgery are still very common, leading to longer length of hospital stays or death. OBJECTIVE: to describe the incidence of pulmonary complications and identify their association with duration of extracorporeal circulation (ECC), surgery and ischemia, number of bypass grafts performed, location of drains and length of drainage following myocardial revascularization (MRV). METHODS: this contemporaneous cohort consisted of 202 patients undergoing elective myocardial revascularization (MRV) with saphenous vein graft and internal mammary artery graft and ECC, at a referral university cardiology hospital in Southern Brazil, from April 2006 to November 2007. The following outcomes were analyzed: duration of mechanical ventilation; pneumonia onset; atelectasis; pleural effusion; location of drains and time of removal; and length of hospital stay. RESULTS: of the 202 patients, 90 developed some sort of pulmonary complication. The incidence of pleural effusion was 84%, whereas atelectasis was 65%. The following variables were associated with pulmonary complications: duration of ECC (p = 0.003), surgery (p = 0.040) and ischemia (p = 0.001); length of drainage (p = 0.050) and location of pleural drains (p = 0.033); age (p = 0.001); ejection fraction (p = 0.010); diagnosis of asthma (p = 0.047) and preoperative abnormal chest X-ray findings (p = 0.029). CONCLUSION: variables related to the complexity of the surgery and preexisting comorbidities are associated with a high incidence of postoperative pulmonary complications. These data reinforce the importance of having patients undergo perioperative clinical assessment to detect early respiratory complications after MRV.

Intravenous azithromycin plus ceftriaxone followed by oral azithromycin for the treatment of inpatients with community-acquired pneumonia: an open-label, non-comparative multicenter trial.

Community-Acquired Pneumonia (CAP) is a major public health problem. In Brazil it has been estimated that 2,000,000 people are affected by CAP every year. Of those, 780,000 are admitted to hospital, and 30,000 have death as the outcome. This is an open-label, non-comparative study with the purpose of evaluating efficacy, safety, and tolerability levels of IV azithromycin (IVA) and IV ceftriaxone (IVC), followed by oral azithromycin (OA) for the treatment of inpatients with mild to severe CAP. Eighty-six patients (mean age 56.6 +/- 19.8) were administered IVA (500 mg/day) and IVC (1g/day) for 2 to 5 days, followed by AO (500 mg/day) to complete a total of 10 days. At the end of treatment (EOT) and after 30 days (End of Study--EOS) the medication was evaluated clinically, microbiologically and for tolerability levels. Out of the total 86-patient population, 62 (72.1%) completed the study. At the end of treatment, 95.2% (CI95: 88.9% - 100%) reported cure or clinical improvement; at the end of the study, that figure was 88.9% (CI95: 74.1% - 91.7%). Out of the 86 patients enrolled in the study, 15 were microbiologically evaluable for bacteriological response. Of those, 6 reported pathogen eradication at the end of therapy (40%), and 8 reported presumed eradication (53.3%). At end of study evaluation, 9 patients showed pathogen eradication (50%), and 7 showed presumed eradication (38.89%). Therefore, negative cultures were obtained from 93.3% of the patients at EOT, and from 88.9% at the end of the study. One patient (6.67% of patient population) reported presumed microbiological resistance. At study end, 2 patients (11.11%) still reported undetermined culture. Uncontrollable vomiting and worsening pneumonia condition were reported by 2.3% of patients. Discussion and Conclusion Treatment based on the administration of IV azithromycin associated to ceftriaxone and followed by oral azithromycin proved to be efficacious and well-tolerated in the treatment of Brazilian inpatients with CAP.

Incidência de complicações pulmonares na cirurgia de revascularização do miocárdio / Incidence of pulmonary complications in myocardial revascularization / Incidencia de complicaciones pulmonares en la cirugía de revascularización del miocardio

FUNDAMENTO: No período do peri-operatório, os cuidados têm sido cada vez mais criteriosos, entretanto, as complicações pulmonares após a abordagem cirúrgica ainda são frequentes, predispondo o paciente a um maior tempo de internação ou ao óbito. OBJETIVO: Descrever a incidência de complicações pulmonares e identificar a sua associação com tempos de circulação extracorpórea (CEC); cirurgia e isquemia; número de enxertos; localização e tempo de drenos após cirurgia de revascularização do miocárdio (CRM). MÉTODOS: Nesta coorte contemporânea, foram estudados 202 pacientes em hospital universitário de referência para cardiologia no sul do Brasil, submetidos à CRM eletiva com ponte safena e artéria mamária interna com CEC, no período de abril/2006 a novembro/2007. Os desfechos considerados foram: tempo de ventilação mecânica; surgimento de pneumonia; atelectasia; derrame pleural; hora da retirada e localização dos drenos; e tempo de internação. RESULTADOS: Observou-se algum tipo de complicação pulmonar em 90 dos 202 pacientes. A frequência de derrame pleural foi de 84 por cento e a de atelectasia foi de 65 por cento. Apresentaram associação com complicações pulmonares os tempos de CEC (p = 0,003), cirúrgico (p = 0,040) e isquemia (p = 0,001); o tempo de permanência de drenos (p = 0,050) e a localização pleural dos drenos (p = 0,033), além de idade (p = 0,001), fração de ejeção (p = 0,010), diagnóstico de asma (p = 0,047) e exame radiológico de tórax pré-operatório anormal (p = 0,029). CONCLUSÃO: Variáveis relacionadas à complexidade do ato cirúrgico e comorbidades pré-existentes estão associadas a uma alta incidência de complicações pulmonares no pós-operatório. Esses dados reforçam a importância da avaliação clínica peri-operatória para detecção precoce de complicação respiratória após CRM.

BACKGROUND: Despite the increasingly careful attempts to reduce perioperative risks, pulmonary complications following surgery are still very common, leading to longer length of hospital stays or death. OBJECTIVE: To describe the incidence of pulmonary complications and identify their association with duration of extracorporeal circulation (ECC), surgery and ischemia, number of bypass grafts performed, location of drains and length of drainage following myocardial revascularization (MRV). METHODS: This contemporaneous cohort consisted of 202 patients undergoing elective myocardial revascularization (MRV) with saphenous vein graft and internal mammary artery graft and ECC, at a referral university cardiology hospital in Southern Brazil, from April 2006 to November 2007. The following outcomes were analyzed: duration of mechanical ventilation; pneumonia onset; atelectasis; pleural effusion; location of drains and time of removal; and length of hospital stay. RESULTS: Of the 202 patients, 90 developed some sort of pulmonary complication. The incidence of pleural effusion was 84 percent, whereas atelectasis was 65 percent. The following variables were associated with pulmonary complications: duration of ECC (p = 0.003), surgery (p = 0.040) and ischemia (p = 0.001); length of drainage (p = 0.050) and location of pleural drains (p = 0.033); age (p = 0.001); ejection fraction (p = 0.010); diagnosis of asthma (p = 0.047) and preoperative abnormal chest X-ray findings (p = 0.029). CONCLUSION: Variables related to the complexity of the surgery and preexisting comorbidities are associated with a high incidence of postoperative pulmonary complications. These data reinforce the importance of having patients undergo perioperative clinical assessment to detect early respiratory complications after MRV.

FUNDAMENTO: En el período del peri-operatorio, los cuidados han sido cada vez más criteriosos, entre tanto, las complicaciones pulmonares después del abordaje quirúrgico aun son frecuentes, predisponiendo al paciente a un mayor tiempo de internación o al óbito. OBJETIVO: Describir la incidencia de complicaciones pulmonares y identificar su asociación con tiempos de circulación extracorporal (CEC); cirugía e isquemia; número de injertos; localización y tiempo de drenajes después de cirugía de revascularización del miocardio (CRM). MÉTODOS: En esta cohorte contemporánea, fueron estudiados 202 pacientes en hospital universitario de referencia para cardiología en el sur del Brasil, sometidos a la CRM electiva con puente safena y arteria mamaria interna con CEC, en el período de abril/2006 a noviembre/2007. Los desenlaces considerados fueron: tiempo de ventilación mecánica; surgimiento de neumonía; atelectasia; derrame pleural; hora de la retirada y localización de los drenajes; y tiempo de internación. RESULTADOS: Se observó algún tipo de complicación pulmonar en 90 de los 202 pacientes. La frecuencia de derrame pleural fue de 84 por ciento y la de atelectasia fue de 65 por ciento. Presentaron asociación con complicaciones pulmonares los tiempos de CEC (p = 0,003), quirúrgico (p = 0,040)e isquemia (p = 0,001); el tiempo de permanencia de drenajes (p = 0,050) y la localización pleural de los drenajes (p = 0,033), además de edad (p = 0,001), fracción de eyección (p = 0,010), diagnóstico de asma (p = 0,047) y examen radiológico de tórax pre-operatorio anormal (p = 0,029). CONCLUSIÓN: Variables relacionadas a la complejidad del acto quirúrgico y comorbilidades pre-existentes están asociadas a una alta incidencia de complicaciones pulmonares en el post-operatorio. Esos datos refuerzan la importancia de la evaluación clínica peri-operatoria para detección precoz de complicación respiratoria después de CRM.

Intravenous azithromycin plus ceftriaxone followed by oral azithromycin for the treatment of inpatients with community-acquired pneumonia: an open-label, non-comparative multicenter trial

Community-Acquired Pneumonia (CAP) is a major public health problem. In Brazil it has been estimated that 2,000,000 people are affected by CAP every year. Of those, 780,000 are admitted to hospital, and 30,000 have death as the outcome. This is an open-label, non-comparative study with the purpose of evaluating efficacy, safety, and tolerability levels of IV azithromycin (IVA) and IV ceftriaxone (IVC), followed by oral azithromycin (OA) for the treatment of inpatients with mild to severe CAP. Eighty-six patients (mean age 56.6 ± 19.8) were administered IVA (500mg/day) and IVC (1g/day) for 2 to 5 days, followed by AO (500mg/day) to complete a total of 10 days. At the end of treatment (EOT) and after 30 days (End of Study - EOS) the medication was evaluated clinically, microbiologically and for tolerability levels. Out of the total 86-patient population, 62 (72.1 percent) completed the study. At the end of treatment, 95.2 percent (CI95: 88.9 percent - 100 percent) reported cure or clinical improvement; at the end of the study, that figure was 88.9 percent (CI95: 74.1 percent - 91.7 percent). Out of the 86 patients enrolled in the study, 15 were microbiologically evaluable for bacteriological response. Of those, 6 reported pathogen eradication at the end of therapy (40 percent), and 8 reported presumed eradication (53.3 percent). At end of study evaluation, 9 patients showed pathogen eradication (50 percent), and 7 showed presumed eradication (38.89 percent). Therefore, negative cultures were obtained from 93.3 percent of the patients at EOT, and from 88.9 percent at the end of the study. One patient (6.67 percent of patient population) reported presumed microbiological resistance. At study end, 2 patients (11.11 percent) still reported undetermined culture. Uncontrollable vomiting and worsening pneumonia condition were reported by 2.3 percent of patients. Discussion and Conclusion Treatment based on the administration of IV azithromycin...

Pneumonias tratadas em hospital: estudo de 170 pacientes / Pneumonia treated in a hospital: a study of 170 patients

Apresentam-se 170 casos de pacientes com quadro clínico e radiológico compatível com pneumonia, os quais foram tratados em hospital no período entre julho de 1985 e dezembro de 1988. Havia 116(68%) homens e 54 (32%) mulheres, com idade média de 50,2 anos. No momento da internaçäo, 49 (29%) pacientes já estavam usando algum antibiótico (especialmente penicilina. As manifestaçöes clínicas mais freqüentes foram tosse (97%), expectoraçäo (87%), febre (76%), dispnéia (52%) e dor torácica (51%). O achado radiológico mais comum foi a presença de consolidaçäo pulmonar (90%). O pneumococo foi a bactéria mais vezes encontrada no exame bacterioscópico do escarro. A conclusäo diagnóstica foi de pneumonia bacteriana em 140 (82%) pacientes, pneumonia para agente filtrável em 16 (9%), por legionella em 8(5%), por bacilo tuberculoso em 5(3%) e pneumonia actínica em 1 paciente. O antibiótico mais usado durante a hospitalizaçäo foi ampicilina, seguindo-se penicilina e eritromicina. O tempo médio de internaçäo foi de 13,2 dias. Ocorreram 7 óbitos (4,1%)

Pneumonia tuberculosa: estudo de 17 casos e revisao de literatura / Tuberculosis pneumonia: 17 case reports and review

Os autores apresentam 17 casos de pneumonia tuberculosa por fistula ganglio-bronquica e revisao de literatura, com especial enfase as manifestacoes clinicas e ao diagnostico. Salientam semelhancas na apresentacao clinica e radiologica com a pneumonia pneumococica, bem como aspectos uteis ao diagnostico diferencial. As manifestacoes clinicas mais frequentes foram tosse, escarro purulento, febre, dor toracica, anorexia e emagrecimento. Ao radiograma de torax a achado mais frequente foi o de consolidacao alveolo-ductal. O diagnostico foi efetuado atraves da baciloscopia do escarro em 13 (76 por cento ) casos e de amostra colhida por fibrobroncoscopia nos outros 4 (24 por cento ). A hipotese diagnostica inicial de pneumonia bacteriana foi feita em 88 por cento destes casos, o que chama a atencao para a baixa suspeicao desta forma de manifestacao de tuberculose no diagnostico diferencial das pneumonias