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Objectives To determine the effect of therapeutic anticoagulation, with low molecular weight heparin (LMWH) or unfractionated heparin (UFH, high dose nomogram), compared to standard care in hospitalized patients admitted for COVID-19 with an elevated D-dimer on the composite outcome of intensive care unit (ICU) admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death up to 28 days. Trial design Open-label, parallel, 1:1, phase 3, 2-arm randomized controlled trial Participants The study population includes hospitalized adults admitted for COVID-19 prior to the development of critical illness. Excluded individuals are those where the bleeding risk or risk of transfusion would generally be considered unacceptable, those already therapeutically anticoagulated and those who have already have any component of the primary composite outcome. Participants are recruited from hospital sites in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and the United States of America. The inclusion criteria are: Laboratory confirmed COVID-19 (diagnosis of SARS-CoV-2 via reverse transcriptase polymerase chain reaction as per the World Health Organization protocol or by nucleic acid based isothermal amplification) prior to hospital admission OR within first 5 days (i.e. 120 hours) after hospital admission; Admitted to hospital for COVID-19; One D-dimer value above the upper limit of normal (ULN) (within 5 days (i.e. 120 hours) of hospital admission) AND EITHER: D-Dimer ≥2 times ULN OR D-Dimer above ULN and Oxygen saturation ≤ 93% on room air; > 18 years of age; Informed consent from the patient (or legally authorized substitute decision maker). The exclusion criteria are: pregnancy; hemoglobin platelet count 9/L in the last 72 hours; known fibrinogen known INR >1.8 (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation); patient already prescribed intermediate dosing of LMWH that cannot be changed (determination of what constitutes an intermediate dose is to be at the discretion of the treating clinician taking the local institutional thromboprophylaxis protocol for high risk patients into consideration); patient already prescribed therapeutic anticoagulation at the time of screening [low or high dose nomogram UFH, LMWH, warfarin, direct oral anticoagulant (any dose of dabigatran, apixaban, rivaroxaban, edoxaban)]; patient prescribed dual antiplatelet therapy, when one of the agents cannot be stopped safely; known bleeding within the last 30 days requiring emergency room presentation or hospitalization; known history of a bleeding disorder of an inherited or active acquired bleeding disorder; known history of heparin-induced thrombocytopenia; known allergy to UFH or LMWH; admitted to the intensive care unit at the time of screening; treated with non-invasive positive pressure ventilation or invasive mechanical ventilation at the time of screening; Imminent death according to the judgement of the most responsible physician; enrollment in another clinical trial of antithrombotic therapy involving hospitalized patients. Intervention and comparator Intervention: Therapeutic dose of LMWH (dalteparin, enoxaparin, tinzaparin) or high dose nomogram of UFH. The choice of LMWH versus UFH will be at the clinician’s discretion and dependent on local institutional supply. Comparator: Standard care [thromboprophylactic doses of LMWH (dalteparin, enoxaparin, tinzaparin, fondaparinux)] or UFH. Administration of LMWH, UFH or fondaparinux at thromboprophylactic doses for acutely ill hospitalized medical patients, in the absence of contraindication, is generally considered standard care. Main outcomes The primary composite outcome of ICU admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death at 28 days. Secondary outcomes include (evaluated up to day 28): All-cause death Composite of ICU admission or all-cause death Composite of mechanical ventilation or all-cause death Major bleeding as defined by the ISTH Scientific and Standardization Committee (ISTH-SSC) recommendation; Red blood cell transfusion (>1 unit); Transfusion of platelets, frozen plasma, prothrombin complex concentrate, cryoprecipitate and/or fibrinogen concentrate; Renal replacement therapy; Hospital-free days alive; ICU-free days alive; Ventilator-free days alive; Organ support-free days alive; Venous thromboembolism (defined as symptomatic or incidental, suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); Arterial thromboembolism (defined as suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); Heparin induced thrombocytopenia; Trajectories of COVID-19 disease-related coagulation and inflammatory biomarkers. Randomisation Randomisation will be stratified by site and age (>65 versus ≤65 years) using a 1:1 computer-generated random allocation sequence with variable block sizes. Randomization will occur within the first 5 days (i.e. 120 hours) of participant hospital admission. However, it is recommended that randomization occurs as early as possible after hospital admission. Central randomization using an interactive web response system will ensure allocation concealment. Blinding (masking) No blinding involved. This is an open-label trial. Numbers to be randomised (sample size) 462 patients (231 per group) are needed to detect a 15% risk difference, from 50% in the control group to 35% in the experimental group, with power of 90% at a two-sided alpha of 0.05. Trial Status Protocol Version Number 1.4. Recruitment began on May 11th, 2020. Recruitment is expected to be completed March 2022. Recruitment is ongoing. Trial registration ClinicalTrials.gov Identifier: NCT04362085 Date of Trial Registration: April 24, 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

IMPORTANCE: Early-stage chronic kidney disease (CKD) characterized by microalbuminuria is associated with future cardiovascular events, progression toward end-stage renal disease, and early mortality in patients with type 2 diabetes. OBJECTIVE: To compare the albuminuria-lowering effects of Roux-en-Y gastric bypass (RYGB) surgery vs best medical treatment in patients with early-stage CKD, type 2 diabetes, and obesity. DESIGN, SETTING, AND PARTICIPANTS: For this randomized clinical trial, patients with established type 2 diabetes and microalbuminuria were recruited from a single center from April 1, 2013, through March 31, 2016, with a 5-year follow-up, including prespecified intermediate analysis at 24-month follow-up. INTERVENTION: A total of 100 patients with type 2 diabetes, obesity (body mass indexes of 30 to 35 [calculated as weight in kilograms divided by height in meters squared]), and stage G1 to G3 and A2 to A3 CKD (urinary albumin-creatinine ratio [uACR] >30 mg/g and estimated glomerular filtration rate >30 mL/min) were randomized 1:1 to receive best medical treatment (n = 49) or RYGB (n = 51). MAIN OUTCOMES AND MEASURES: The primary outcome was remission of albuminuria (uACR

The increasing number of bariatric/metabolic operations as important alternatives for the treatment of obesity and type 2 diabetes brought several concerns about the intensive care of patients undergoing those procedures. Intensive Care Unit admission criteria are needed in order to better allocate resources and avoid unnecessary interventions. Furthermore, well-established protocols, helpful in many clinical situations, are not directly applicable to obese patients. Indeed, difficult airway management, mechanical ventilation, fluid therapy protocols, prophylaxis, and treatment of venous thromboembolic events have unique aspects that should be taken into consideration. Finally, new data related to planning nutrition therapy of the critically obese have been highlighted and deserve consideration. In this review, we provide an outline of recent studies related to those important aspects of the care of the bariatric/metabolic patients in critical conditions.

To evaluate the impact of a multifaceted nutritional educational intervention on the quality of nutritional therapy and clinical outcomes in critically ill patients.We conducted a prospective, non-blinded study with a non-contemporaneous control group at a 16-bed intensive care unit (ICU) at the Hospital das Clinicas, Department of Gastroenterology, University of Sao Paulo Medical School in Sao Paulo, Brazil. There were three phases. Phase 1: the quality of NT was evaluated in 50 newly admitted intensive care unit patients in a pre-educational program (Pre-EP). Phase 2: nutritional protocols were created and an education program was implemented. Phase 3: another 50 patients were enrolled and observed in a post-educational program (Post-EP) using phase 1 methodology. Nutritional Therapy practice was evaluated through nutritional assessments, adequacy of energy requirements, duration of fasting, and use of early enteral nutrition. Intensive care unit length of stay and hospital length of stay were measured as primary end-points.The pre-educational program and post-educational program groups did not differ in age, APACHE II score, gender, or nutritional assessment. The mean ± SD duration of fasting decreased (Pre-EP 3.8 ± 3.1 days vs. Post-EP: 2.2 ± 2.6 days; p = 0.002), the adequacy of nutritional therapy improved (Pre-EP 74.2% ± 33.3% vs. Post-EP 96.2% ± 23.8%; p0.001), and enteral nutrition was initiated earlier than 48 h more commonly (Pre-EP 24% vs. Post-E 60%; p = 0.001). Median intensive care unit length of stay decreased (Pre-EP: 18.5 days vs. Post-EP: 9.5 days; p0.001) although hospital length of stay did not.Implementing a multifaceted nutritional educational intervention could improve the quality of nutritional therapy and may decrease intensive care unit length of stay in critically ill patients.

In their excellent review De Vlieger et al. (1) confirmed the steady decrease of nonforensic autopsies, a well-documented phenomenon in Europe, United States(2), and Latin America, including Brazil (figure).However, the causes usually attributed to explain this phenomenon, from my point-of-view, are not causes, but consequences of a change occurring on the concept of disease. The concept of disease should be considered what truly rules the art and science of medicine, giving directions to procedures as well as yielding pathways to research. Hofmann (3) argues that the contemporary concept of disease is technologically constituted. That means, "technology provides the physiological, biochemical, and morphological entities that are applied in defining diseases." I believe the decline of clinical autopsy is the result of a rearrange of conceptual frameworks working on the contemporary medical rationality (4). Trying "to convince" intensive care doctors about the value of autopsies based only on its value per se won't work (5). The autopsies must aggregate value to the procedure itself: new techniques, new insights, as pointed by the authors. In fact, a new status in medical rationality is needed, otherwise the decline will continue.

OBJECTIVES: We designed a cohort study to describe characteristics and outcomes of patients with coronavirus disease (COVID-19) admitted to the intensive care unit (ICU) in the largest public hospital in Sao Paulo, Brazil, as Latin America becomes the epicenter of the pandemic. METHODS: This is the protocol for a study being conducted at an academic hospital in Brazil with 300 adult ICU beds dedicated to COVID-19 patients. We will include adult patients admitted to the ICU with suspected or confirmed COVID-19 during the study period. The main outcome is ICU survival at 28 days. Data will be collected prospectively and retrospectively by trained investigators from the hospital’s electronic medical records, using an electronic data capture tool. We will collect data on demographics, comorbidities, severity of disease, and laboratorial test results at admission. Information on the need for advanced life support and ventilator parameters will be collected during ICU stay. Patients will be followed up for 28 days in the ICU and 60 days in the hospital. We will plot Kaplan-Meier curves to estimate ICU and hospital survival and perform survival analysis using the Cox proportional hazards model to identify the main risk factors for mortality. ClinicalTrials.gov: NCT04378582. RESULTS: We expect to include a large sample of patients with COVID-19 admitted to the ICU and to be able to provide data on admission characteristics, use of advanced life support, ICU survival at 28 days, and hospital survival at 60 days. CONCLUSIONS: This study will provide epidemiological data about critically ill patients with COVID-19 in Brazil, which could inform health policy and resource allocation in low- and middle-income countries.