Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Avaliação do Uso do Lactobacillus reuteri em Pacientes Portadores da Síndrome de Supercrescimento Bacteriano Diagnosticados por Teste Respiratório / Evaluation of the Use of Lactobacillus reuteri in Patients with Bacterial Overgrowth Syndrome Diagnosed

Objetivo: Avaliar a ação de probiótico constituído pelo Lactobacillus reuteri em pacientes selecionados como portadores da síndrome do supercrescimento bacteriano do intestino delgado (SSCBID), através do teste respiratório da lactulose. Métodos: Foram incluídos 21 pacientes que apresentavam sintomas gastrointestinais inespecíficos, mas sugestivos de SSCBID. Foram selecionados através do questionário específico, para serem submetidos ao teste respiratório para lactulose. Os indivíduos com teste positivo foram convocados para iniciarem tratamento com probiótico composto por 100.000.000 UFC de Lactobacillus reuteri por quatro semanas e posterior reavaliação dos sintomas. Resultados: O resultado do teste respiratório foi positivo em 13 (61,90%) participantes (p=0,0391). A principal queixa foi a dor e/ou desconforto abdominal, com 46,15% (6/13) dos casos. A síndrome do intestino irritável representou o diagnóstico prévio de 30,77% (4/13) dos casos. 9 dos 13 pacientes tratados (69,23%) obtiveram melhora do quadro clínico inicial com o uso do probiótico. Conclusão: As evidências indicam que novos estudos devem ser realizados sobre os probióticos, para que sua aplicação clínica na síndrome do supercrescimento bacteriano seja definida. Neste estudo, o probiótico reduziu a sintomatologia abdominal em pacientes com SSCBID, com impacto na qualidade de vida destes indivíduos.  Palavras chave: supercrescimento bacteriano, teste respiratório, síndrome do intestino irritável, probióticos.   ABSTRACT Objective: To assess the efficacy of probiotic Lactobacillus reuteri made by patients selected as having syndrome of small intestinal bacterial overgrowth (SSCBID) through the lactulose breath test. Methods: We included 21 patients who had nonspecific gastrointestinal symptoms, but suggestive of SSCBID, who were selected through specific questionnaire to be submitted to the breath test lactulose. Individuals with a positive test were called for starting treatment with probiotic composed of Lactobacillus reuteri UFC 100 million for four weeks and subsequent reassessment of symptoms. Results: The results of the breath test was positive in 13 (61.90%) participants (p=0.0391). The main complaint was pain and/or abdominal discomfort, with 46.15% (6/13) of cases. The irritable bowel syndrome represented the previous diagnosis of 30.77% (4/13) of cases. Nine out of the 13 patients (69.23%) had clinical improvement starting with the use of probiotics. Conclusion: Evidence indicates that further studies should be conducted on probiotics, so its clinical application in bacterial overgrowth syndrome is defined. In this study, the probiotic reduced abdominal symptoms in patients with SSCBID, with impact on the quality of life of these individuals.  Keywords: bacterial overgrowth, breath test, irritable bowel syndrome, probiotics

Tumor Estromal Gastrintestinal de Localização Esofágica: Relato de Caso/ Gastrointestinal Stromal Tumor Location Esophageal: Case Report

Introdução: Os tumores estromais gastrintestinais (GIST) são considerados as neoplasias mesenquimatosas mais comuns do trato gastrintestinal (TGI). São derivados das células intersticiais de Cajal, localizadas ao nível do plexo mioentérico e responsáveis pela motilidade gastrintestinal. Podem se originar em qualquer região do TGI, sendo apenas 5% provenientes do esôfago. Casuística: Foi relatado um caso de GIST de localização esofágica em um paciente que iniciou quadro de disfagia para alimentos sólidos e odinofagia, de caráter intermitente, acompanhado de náuseas e vômitos. Foram realizadas Seriografia contrastada de esôfago, Endoscopia Digestiva Alta, Tomografia Computadorizada de Abdome, o resultado histopatológico da biópsia da lesão foi inconclusivo e o diagnóstico foi confirmado pela imunohistoquímica que expressou CD117 (KIT) pelas células neoplásicas. O serviço de oncologia de referência orientou a realização de cirurgia para ressecção tumoral, porém o paciente optou pela utilização do Mesilato de Imatinib (MI), tendo apresentado melhora progressiva do quadro clínico inicial. Discussão: O tratamento padrão para pacientes com GIST não metastático é a ressecção completa da lesão, pois oferece a maior chance de cura. Entretanto, o paciente optou somente pelo tratamento com o MI. Conclusão: Concluímos que o GIST deve ser considerado nas lesões exofíticas esofágicas e que o tratamento somente com o MI pode ser considerado, mesmo sabendo que o tratamento preconizado nestes casos é a ressecção cirúrgica, associada ao MI como terapia adjuvante, com melhora da sobrevida.  Palavras-chave: tumor estromal gastrintestinal, dor abdominal, imunohistoquímica. Introduction: The gastrointestinal stromal tumor (GIST)  considered the most common mesenchymal neoplasm of the gastrointestinal tract (GIT). It is derived from interstitial cells of Cajal, located at the myenteric plexus and responsible for gastrointestinal motility. It can originate anywhere in the GI tract, and only 5% come from the esophagus. Casuistry: We present a case of esophageal GIST location in a patient whose dysphagia for solid food and an intermitent character odynophagia, accompanied by nausea and vomiting. Were performed serioscopy contrasted esophagus, Upper endoscopy, CT scan of abdomen, the histopathological analysis of biopsy was inconclusive and the diagnosis was confirmed by immunohistochemistry that expressed CD117 (KIT) by neoplastic cells. The oncology service reference directed the completion of surgery for tumor resection, but the patient opted for the use of Imatinib mesylate (IM), having presented progressive improvement of clinical picture Discussion: The standard treatment for patients with non-metastatic GIST is complete resection of the lesion, as it offers the greatest chance for cure. However, the patient decided only by treatment with MI. Conclusion: We conclude that GIST should be considered in exophytic esophageal and that treatment only with MI may be considered, even though the recommended treatment in these cases is surgical resection, associated with MI as adjunctive therapy with improved survival. Keywords: gastrointestinal stromal tumor, abdominal pain, immunohistochemistry

Azathioprine toxicity in Crohn's disease: incidence, approach and course

OBJECTIVE: Azathioprine (AZA) is frequently used in Crohn's disease (CD) therapy. This paper aimed to evaluate the frequency, evolution and management of AZA side effects in CD patients. METHODS: One hundred and six CD patients under AZA therapy were evaluated prospectively from January 2002 to December 2006. Clinical and demographic data were recorded, together with a monthly laboratory control of hematological or other adverse reactions by means of clinical evaluation. Comparison was carried out between groups with and without side effects. RESULTS: At least one adverse reaction was found in 56 (52.7%) of the patients studied and required a transient drug reduction; 18 (17%) had to definitely stop use of AZA, often because of hypersensitivity reactions. Nausea, vomit, although slight, occurred in 29 (27.4%). The black race and those with co-morbidities had more gastric intolerance than Caucasians and those without other associated disease (p=0.04). Leucopoenia was the more frequent side effect observed, occurring in 36 (34%). The period of AZA use was longer for patients with leucopoenia than for those without (p=0.001), while the mean dose of AZA was lower for those with leucopoenia when compared to non-leucopoenics (p=0.005). No serious infections, malignancy or death was noticed as a consequence of AZA use. CONCLUSION: In this study use of AZA in therapy for Crohn's disease disclosed that the drug is satisfactorily safe as long as periodical clinical and laboratory supervision is carried out during treatment.OBJETIVO: A azatioprina (AZA) tem sido usada freqüentemente no tratamento da doença de Crohn (DC). O objetivo do presente estudo foi avaliar a freqüência, evolução e abordagem dos efeitos adversos da AZA no tratamento de pacientes com DC. MÉTODOS: Foram incluídos prospectivamente 106 pacientes portadores de DC em uso de AZA, de janeiro de 2002 a dezembro de 2006. Registraram-se dados clínicos e demográficos, com controle laboratorial mensal dos efeitos hematológicos e supervisão de reações adversas por meio de avaliação clínica. Realizou-se comparação entre os grupos com e sem efeitos adversos. RESULTADOS: Cinqüenta e seis (52,7%) dos pacientes estudados apresentaram pelo menos um efeito adverso, requerendo redução transitória da dose da droga; 18 (17%) necessitaram suspender definitivamente o uso de AZA, geralmente devido a reações de hipersensibilidade. Náuseas e vômitos, freqüentemente leves, ocorreram em 29 (27,4%); a raça negra e aqueles com comorbidades apresentaram mais intolerância gástrica do que os brancos e aqueles sem outras doenças associadas (p=0,04). Leucopenia foi o efeito adverso mais freqüente, ocorrendo em 36 (34%). O tempo de uso de AZA foi maior em pacientes com leucopenia do que nos não leucopênicos (p=0,001), enquanto a dose média de AZA foi menor naqueles com leucopenia comparados aos não leucopênicos (p=0,005). Não houve infecções graves, neoplasias ou óbitos durante o tratamento com AZA. CONCLUSÃO: A AZA mostrou ser uma droga relativamente segura no tratamento da DC, desde que seja mantida supervisão clínica e laboratorial periódica durante todo o tratamento

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.13Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt