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

Prediction of metastatic axillary lymph node in patients with breast cancer in early stages according to the immunohistochemical subtype, age and tumor size

INTRODUÇÃO: O aprimoramento dos métodos de rastreamento e a conscientização da população geral contribuíram para o diagnóstico cada vez mais precoce do câncer de mama e proporcionou, juntamente com o avanço na terapêutica, altas taxas de sobrevida. O estado do acometimento axilar por metástase é um dos principais fatores prognósticos em pacientes com câncer de mama, particularmente naquelas com diagnóstico em estádio inicial. Na última década, esforços científicos foram direcionados para simplificar a amostragem dos linfonodos axilares, diminuindo a morbidade, mas respeitando os princípios oncológicos. Nesse sentindo, a biópsia do linfonodo sentinela foi considerada o avanço mais importante. Ao se obter um método preditor do estado axilar, que apresente os benefícios da abordagem padrão dissecção axilar e biópsia de linfonodo sentinela porém sem seus efeitos colaterais e que seja facilmente reproduzível, realizaremos um grande avanço na avaliação e terapêutica do câncer de mama inicial. MÉTODOS: Foi realizado estudo transversal retrospectivo com base nos prontuários de pacientes com câncer de mama invasivo, não metastático, com qualquer idade, atendidas entre 1999 e 2007 no Setor de Mastologia da Disciplina de Ginecologia do Departamento de Obstetrícia e Ginecologia da Faculdade de Medicina da Universidade de São Paulo e Clínica Professor José Aristodemo Pinotti, cujo estudo histopatológico e imunoistoquímico foi supervisionado por um único médico patologista. Realizamos uma subdivisão imunoistoquímica dos tumores, sendo considerado luminal A os tumores com receptores hormonais positivos e HER 2 negativo; luminal B os com receptores hormonais positivos e HER 2 positivo; HER 2 as pacientes com receptores hormonais negativos e HER 2 positivo e triplo negativo aquelas com receptores hormonais e HER 2 negativos. Correlacionamos esses subtipos com as variáveis clínicas idade e tamanho tumoral para predizer a probabilidade de acometimento linfonodal axilar. RESULTADOS: Duzentos e trinta e nove casos foram analisados. No subtipo luminal A, a possibilidade de metástase foi maior quanto menor a idade da paciente e maior o tamanho do tumor. Essa foi a única associação que apresentou diferença estatisticamente significante. As pacientes que possuíam tumores triplo negativo tiveram, aproximadamente, 90% menos chance de metástase linfonodal que as pacientes com tumor luminal A. CONCLUSÕES: As pacientes com tumor luminal A apresentaram, significativamente, maior probabilidade de metástase linfonodal axilar. As pacientes com de tumores triplo negativo, com idade superior a 55 anos ou tumores menores que 2 cm, revelaram menor probabilidade de metástase axilarINTRODUTION: The improvement of screening methods and awareness of general population contributed to the increasingly early diagnosis of breast cancer and provided, together with advances in therapy, high survival rates. The status of axillary involvement is a major prognostic factor in patients with breast cancer, particularly those with early stage. In the last decade, research efforts were directed to simplify the sampling of axillary lymph nodes, decreasing the morbidity, but respecting the oncological principles. In this sense, the sentinel lymph node biopsy was considered the most important advance. If we obtain a method to predict the axillary status, with the benefits of the standard approach - axillary dissection and sentinel lymph node biopsy - without its side effects and easily reproducible, we will hold a major advance in the assessment and treatment of early breast cancer. METHODS: We conducted a retrospective cross-sectional study based on records of patients with invasive breast cancer, non metastatic, with any age, treated between 1999 and 2007 in the breast cancer Sector of the Gynecology Discilpine of the Department of Obstetrics and Gynecology, Faculty of Medicine, University of São Paulo and Private Clinic of Professor José Aristodemo Pinotti, whose histopathological studies were supervised by a single pathologist. We performed an immunohistochemical subdivision of the tumors, and considered luminal A tumors with positive hormonal receptors and negative HER 2, luminal B with positive hormonal receptors and positive HER 2, HER 2 patients with negative hormonal receptors and positive HER 2 and the triple-negative those with negative hormonal receptors and HER 2. Those subtypes were correlated with the clinical variables age and tumor size in predicting the likelihood of axillary lymph node involvement. RESULTS: Two hundred and nine cases were analyzed. In the luminal A, the possibility of axillary metastasis was higher in the younger patients and larger tumors. That was the only combination that showed statistically significant difference. The patients who had triplenegative tumors had approximately 90% less chance of lymph node metastasis than patients with tumors luminal A. CONCLUSIONS: The patients with luminal A tumors showed a significantly association with greater likelihood of axillary lymph node metastasis. The patients with triple negative tumors, age over 55 years or tumors smaller than 2 cm showed a lower likelihood of axillary lymph node metastasi

Analysis of the concordance rates between core needle biopsy and surgical excision in patients with breast cancer

OBJECTIVE: To evaluate whether immunohistochemical marker studies performed on core needle biopsy (CNB) specimens accurately reflect the marker status of the tumor obtained from final surgical specimen. METHODS: This was a retrospective study that used the database of the Division of Mastology of the Hospital das Clínicas, São Paulo, Brazil. Sixty-nine patients submitted to ultrasound-guided CNB diagnosed with breast cancer were retrospectively analyzed. Immunohistochemistry (IHC) on core biopsy specimens was compared to that of excisional biopsy regarding estrogen receptor (ER), progesterone receptor (PR), human epidermal gowth factor receptor 2 gene (HER2), p53, and Ki67. The analysis of the concordance between CNB and surgical biopsy was performed using the kappa (k) coefficient (95% CI). RESULTS: A perfect concordance between the labeling in the surgical specimens and the preoperative biopsies in p53 (k = 1.0; 95% CI: 0.76-1.0) was identified. There was an almost perfect concordance for ER (k = 0.89; 95% CI: 0.65-1.0) and a substantial concordance for PR (k = 0.70; 95% CI: 0.46-0.93). HER2 (k = 0.61; 95% CI: 0.38-0.84) and Ki-67 (k = 0.74; 95% CI: 0.58-0.98) obtained a substantial concordance this analysis. CONCLUSION: The results of this study indicate that the immunohistochemical analysis of ER, PR, Ki-67, and p53 from core biopsy specimens provided results that accurately reflect the marker status of the tumor. The concordance rate of HER2 was less consistent; although it produced substantial concordance, values were very close to moderate concordance

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