The Evocative Role of Literature in the Search for Truth

Fifty two years ago, in March 1964, a military coup deposed João Goulart, the democratically elected President of Brazil. Two years later, in 1966, the democratically elected President of Argentina was also forced to step down by a military coup. A few years later, Uruguay’s President was the victim of the same scenario. And finally, on 9/11, 1973, Salvador Allende, the democratically elected President of Chile, was deposed by a military coup led by General Augusto Pinochet. President Allende shot himself at the Palace of La Moneda, which had been bombarded by air and attacked by tanks. Four coups in a row... All in the same region. Could it have been a simple coincidence

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

Sunflower seed to swine on growing and finishing phase: digestibility, performance and carcass quality

O uso do grão de girassol (GG) para suínos em crescimento e terminação foi avaliado através de um ensaio de digestibilidade e um experimento de desempenho. Na avaliação zootécnica 48 suínos, com peso médio inicial de 19,78 kg foram tratados com 4 dietas (com 0%, 5%, 10% e 20% de GG) durante 4 períodos (crescimento I e II, terminação e total). Ao abate as carcaças foram eletronicamente tipificadas. A energia digestível e metabolizável do GG foi de 3234 e 3223 kcal/kg, respectivamente. Houve efeito da regressão (p < 0,05) dos níveis do GG no consumo diário de ração (CDR): CDR (crescimento I) = 2066,500 - 20,990X; CDR (crescimento II) = 3098,470 - 36,015X; CDR (terminação) = 4114,030 + 63,420X 6,447X2; CRD (total) = 2859,450 + 9,848X - 2,267X2; GDP (crescimento I) = 831,567 - 6,484X; no ganho diário de peso (GDP): GDP (terminação) = 964,135 + 3,350X - 1,059X2; GDP (total) = 885,029 + 3,794X - 0,587 X2; na conversão alimentar (CA): CA (crescimento II) = 3,356 - 0,025X; CA (total) = 3,265 - 0,014X, na profundidade do músculo na carcaça (PM): PM = 46,215 + 2,218X - 0,099 X2 e no peso da carcaça (PC): PC = 75,303 - 0,464X. Considerando o período total do experimento, a inclusão de 20% de GG favoreceu a CA, embora, para o GDP, os melhores valores foram obtidos para 0 e 5% de inclusão. A inclusão de 20% de GG piorou linearmente o peso da carcaça.   Two experiments (a digestibility and a performance tests) were carried out to evaluate sunflower seed (SS) as swine feeding on growing and finishing phases. To performance evaluation 48 pigs, with 19.78 kg liveweight were allotted to four treatments (diet without SS, 5%, 10% and diet with 20% of SS) and they were evaluated during four periods (growing I and II, finishing and total period). All animals were slaughtered and submitted to an electronic carcass evaluation at the end of the experiment. The digestible and metabolizable energy values of SS were 3234 and 3223 kcal/kg, respectively. There were regression effect (P < 0,05) on performance of the following characteristics for the levels of SS: daily feed intake (DFI): DFI(growing I) = 2066.500 - 20.990X; DFI (growing II) = 3098.470 - 36.015X; DFI (finishing) = 4114.030 + 63.420X - 6.447X2; DFI (total) = 2859.450 + 9.848X - 2.267 X2, daily weight gain (DWG): DWG (growing I) = 831.567 - 6.484X, DWG (finishing) = 964.135 + 3.350X - 1.059 X2, DWG (total) = 885.029 + 3.794X - 0.587 X2; feed gain ratio (FGR): FGR (growing II) = 3.356 - 0.025X; FGR (total) = 3.265 - 0.014X; muscle depth on carcass (MD): MD = 46.215 + 2.218X - 0.099 X2 and carcass weight (CW): CW = 75.303 - 0.464X. From the total period of the experiment, the best results to FGR were observed for rations with 20% of SS, and the best results for DWG were observed for rations with 0 and 5% of SS. Ration with 20% of SS affected negativelly the carcass weight

Combining discovery and targeted proteomics reveals a prognostic signature in oral cancer

Different regions of oral squamous cell carcinoma (OSCC) have particular histopathological and molecular characteristics limiting the standard tumor-node-metastasis prognosis classification. Therefore, defining biological signatures that allow assessing the prognostic outcomes for OSCC patients would be of great clinical significance. Using histopathology-guided discovery proteomics, we analyze neoplastic islands and stroma from the invasive tumor front (ITF) and inner tumor to identify differentially expressed proteins. Potential signature proteins are prioritized and further investigated by immunohistochemistry (IHC) and targeted proteomics. IHC indicates low expression of cystatin-B in neoplastic islands from the ITF as an independent marker for local recurrence. Targeted proteomics analysis of the prioritized proteins in saliva, combined with machine-learning methods, highlights a peptide-based signature as the most powerful predictor to distinguish patients with and without lymph node metastasis. In summary, we identify a robust signature, which may enhance prognostic decisions in OSCC and better guide treatment to reduce tumor recurrence or lymph node metastasis.Peer reviewe

II Brazilian Society of Rheumatology consensus for lupus nephritis diagnosis and treatment

Abstract Objective To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN). Methods Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion. Results All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy. Conclusion This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil

Combining discovery and targeted proteomics reveals a prognostic signature in oral cancer

Abstract Different regions of oral squamous cell carcinoma (OSCC) have particular histopathological and molecular characteristics limiting the standard tumor−node−metastasis prognosis classification. Therefore, defining biological signatures that allow assessing the prognostic outcomes for OSCC patients would be of great clinical significance. Using histopathology-guided discovery proteomics, we analyze neoplastic islands and stroma from the invasive tumor front (ITF) and inner tumor to identify differentially expressed proteins. Potential signature proteins are prioritized and further investigated by immunohistochemistry (IHC) and targeted proteomics. IHC indicates low expression of cystatin-B in neoplastic islands from the ITF as an independent marker for local recurrence. Targeted proteomics analysis of the prioritized proteins in saliva, combined with machine-learning methods, highlights a peptide-based signature as the most powerful predictor to distinguish patients with and without lymph node metastasis. In summary, we identify a robust signature, which may enhance prognostic decisions in OSCC and better guide treatment to reduce tumor recurrence or lymph node metastasis

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