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

Análise das expressões imunoistoquímicas da p53, bcl-2 e Ki-67 no adenocarcinoma colorretal e suas correlações com os fatores prognósticos

CONTEXT: Search of tumors markers that allow treatment with higher survival rates, and indicate the response to treatment and recurrence of cancer OBJECTIVE: To analyze the immunoexpression of the proteins p53, bcl-2 and Ki-67 in colorectal adenocarcinoma and correlate them with the clinical-pathological prognostic factors. METHOD: Tissue microarray paraffin blocks were made from colorectal adenocarcinoma tissue resected from 82 patients who had undergone surgery but not chemotherapy or radiotherapy, at Hospital São Paulo, São Paulo, SP, Brazil, between 2002 and 2005. Thin sections (4 µm) were subjected to immunohistochemical reactions, and immunoexpression staining scores were obtained. The scores were correlated with the degree of cell differentiation, staging, disease-free interval, recurrence, survival and specific mortality. The study variables were analyzed using the chi-square and Kaplan-Meier tests to investigate associations with the markers. The significance of the differences between the curves of the disease-free interval and survival was analyzed using the Logrank and Wilcoxon tests. RESULTS: The immunohistochemical expression of p53 was positive in 70 tumors (85.4%) and negative in 12 (14.6%). The expression of bcl-2 was positive in 26 (31.7%) and negative in 56 (68.3%). The expression of Ki-67 was positive in 62 (75.6%) and negative in 20 (24.4%). There was no statistically significant correlation between the expressions of these markers separately or in conjunction, in relation to the degree of cell differentiation, staging, disease-free interval, survival and specific mortality. In relation to recurrence, there was a statistically significant correlation with positive expression of Ki-67 (P = 0.035). CONCLUSION: The immunohistochemical expression of Ki-67 in colorectal cancer is associated with recurrence of this disease.CONTEXTO: Pesquisa de marcadores tumorais que permitam tratamento com maiores índices de sobrevida, além de indicarem a resposta ao tratamento e a recurrência da neoplasia. OBJETIVO: Analisar as expressões imunoistoquímicas das proteínas p53, bcl-2 e Ki-67 no adenocarcinoma colorretal, correlacionando-as com os fatores prognósticos clínico-patológicos. MÉTODO: Foram confeccionados blocos de parafina de TMA com tecido de adenocarcinoma colorretal ressecados cirurgicamente em 82 pacientes no Hospital São Paulo da Universidade Federal der São Paulo, São Paulo, SP, de 2002 a 2005, não submetidos a radio ou quimioterapia. Cortes de 4 µm foram submetidos a reação imunoistoquímica e obtidos escores de intensidade das imunoexpressões, que foram correlacionados com o grau de diferenciação celular, estádio, tempo livre de doença, recidiva, sobrevida e mortalidade específica. As variáveis do estudo foram analisadas pelos testes do qui ao quadrado e de Kaplan-Meier para verificar as associações com os marcadores. A significância das diferenças entre as curvas do tempo livre de doença e da sobrevida foi analisada pelos testes de Logrank e Wilcoxon. RESULTADOS: A expressão imunoistoquímica da p53 foi positiva em 70 tumores (85,4%) e negativa em 12 (14,6%). A bcl-2 foi positiva em 26 tumores (31,7%) e negativa em 56 (68,3%). A expressão imunoistoquímica da Ki-67 foi positiva em 62 tumores (75,6%), sendo em 20 (24,4%) negativa. Não houve correlação estatisticamente significante entre as expressões imunoistoquímicas dos marcadores analisadas separadamente ou em conjunto, envolvendo o grau de diferenciação celular, estádio, tempo livre de doença, sobrevida e mortalidade específica. Com relação à recidiva, observou-se correlação estatisticamente significante com a expressão imunoistoquímica positiva da Ki-67 (P = 0,035). CONCLUSÃO: A expressão imunoistoquímica positiva da Ki-67 no câncer colorretal está relacionada com a incidência de recidiva da doença.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Postgraduate Program on Surgical GastroenterologyFederal University of Alagoas School of Medicine Discipline of ColoproctologyUFAL FM Department of SurgeryState University of Health Sciences of Alagoas Department of PathologyUNIFESP-EPM Discipline of Surgical GastroenterologyUNIFESP, EPM, Postgraduate Program on Surgical GastroenterologyUNIFESP, EPM Discipline of Surgical GastroenterologySciEL

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

Measurement of the charge ratio of atmospheric muons with the CMS detector

We present a measurement of the ratio of positive to negative muon fluxes from cosmic ray interactions in the atmosphere, using data collected by the CMS detector both at ground level and in the underground experimental cavern at the CERN LHC. Muons were detected in the momentum range from 5 GeV/ c to 1 TeV/ c . The surface flux ratio is measured to be 1.2766±0.0032(stat.)±0.0032(syst.) , independent of the muon momentum, below 100 GeV/ c . This is the most precise measurement to date. At higher momenta the data are consistent with an increase of the charge ratio, in agreement with cosmic ray shower models and compatible with previous measurements by deep-underground experiments.We present a measurement of the ratio of positive to negative muon fluxes from cosmic ray interactions in the atmosphere, using data collected by the CMS detector both at ground level and in the underground experimental cavern at the CERN LHC. Muons were detected in the momentum range from 5 GeV/c to 1 TeV/c. The surface flux ratio is measured to be 1.2766 \pm 0.0032(stat.) \pm 0.0032 (syst.), independent of the muon momentum, below 100 GeV/c. This is the most precise measurement to date. At higher momenta the data are consistent with an increase of the charge ratio, in agreement with cosmic ray shower models and compatible with previous measurements by deep-underground experiments

Transverse-momentum and pseudorapidity distributions of charged hadrons in pppp collisions at s\sqrt{s} = 7 TeV

Charged-hadron transverse-momentum and pseudorapidity distributions in proton-proton collisions at $\sqrt{s} = 7$~TeV are measured with the inner tracking system of the CMS detector at the LHC. The charged-hadron yield is obtained by counting the number of reconstructed hits, hit-pairs, and fully reconstructed charged-particle tracks. The combination of the three methods gives a charged-particle multiplicity per unit of pseudorapidity \dnchdeta|_{|\eta| < 0.5} = 5.78\pm 0.01\stat\pm 0.23\syst for non-single-diffractive events, higher than predicted by commonly used models. The relative increase in charged-particle multiplicity from $\sqrt{s} = 0.9$ to 7~TeV is 66.1\%\pm 1.0\%\stat\pm 4.2\%\syst. The mean transverse momentum is measured to be 0.545\pm 0.005\stat\pm 0.015\syst\GeVc. The results are compared with similar measurements at lower energies.Charged-hadron transverse-momentum and pseudorapidity distributions in proton-proton collisions at sqrt(s) = 7 TeV are measured with the inner tracking system of the CMS detector at the LHC. The charged-hadron yield is obtained by counting the number of reconstructed hits, hit-pairs, and fully reconstructed charged-particle tracks. The combination of the three methods gives a charged-particle multiplicity per unit of pseudorapidity, dN(charged)/d(eta), for |eta| < 0.5, of 5.78 +/- 0.01 (stat) +/- 0.23 (syst) for non-single-diffractive events, higher than predicted by commonly used models. The relative increase in charged-particle multiplicity from sqrt(s) = 0.9 to 7 TeV is 66.1% +/- 1.0% (stat) +/- 4.2% (syst). The mean transverse momentum is measured to be 0.545 +/- 0.005 (stat) +/- 0.015 (syst) GeV/c. The results are compared with similar measurements at lower energies

Prompt and non-prompt J/ψ\psi production in pp collisions at s\sqrt{s} = 7 TeV

The production of J/psi mesons is studied in pp collisions at sqrt(s)=7 TeV with the CMS experiment at the LHC. The measurement is based on a dimuon sample corresponding to an integrated luminosity of 314 inverse nanobarns. The J/psi differential cross section is determined, as a function of the J/psi transverse momentum, in three rapidity ranges. A fit to the decay length distribution is used to separate the prompt from the non-prompt (b hadron to J/psi) component. Integrated over J/psi transverse momentum from 6.5 to 30 GeV/c and over rapidity in the range |y| < 2.4, the measured cross sections, times the dimuon decay branching fraction, are 70.9 \pm 2.1 (stat.) \pm 3.0 (syst.) \pm 7.8(luminosity) nb for prompt J/psi mesons assuming unpolarized production and 26.0 \pm 1.4 (stat.) \pm 1.6 (syst.) \pm 2.9 (luminosity) nb for J/psi mesons from b-hadron decays.The production of J/psi mesons is studied in pp collisions at sqrt(s)=7 TeV with the CMS experiment at the LHC. The measurement is based on a dimuon sample corresponding to an integrated luminosity of 314 inverse nanobarns. The J/psi differential cross section is determined, as a function of the J/psi transverse momentum, in three rapidity ranges. A fit to the decay length distribution is used to separate the prompt from the non-prompt (b hadron to J/psi) component. Integrated over J/psi transverse momentum from 6.5 to 30 GeV/c and over rapidity in the range |y| < 2.4, the measured cross sections, times the dimuon decay branching fraction, are 70.9 \pm 2.1 (stat.) \pm 3.0 (syst.) \pm 7.8(luminosity) nb for prompt J/psi mesons assuming unpolarized production and 26.0 \pm 1.4 (stat.) \pm 1.6 (syst.) \pm 2.9 (luminosity) nb for J/psi mesons from b-hadron decays