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Practical use of risk predictive tools and the assessment of their impact on outcome reduction is still a challenge. This pragmatic study of quality improvement (QI) describes the preoperative adoption of a customised postoperative death probability model (SAMPE model) and the evaluation of the impact of a Postoperative Anaesthetic Care Unit (PACU) pathway on the clinical deterioration of high-risk surgical patients. A prospective cohort of 2,533 surgical patients compared with 2,820 historical controls after the adoption of a quality improvement (QI) intervention. We carried out quick postoperative high-risk pathways at PACU when the probability of postoperative death exceeded 5%. As outcome measures, we used the number of rapid response team (RRT) calls within 7 and 30 postoperative days, in-hospital mortality, and non-planned Intensive Care Unit (ICU) admission. Not only did the QI succeed in the implementation of a customised risk stratification model, but it also diminished the postoperative deterioration evaluated by RRT calls on very high-risk patients within 30 postoperative days (from 23% before to 14% after the intervention, p = 0.05). We achieved no survival benefits or reduction of non-planned ICU. The small group of high-risk patients (13% of the total) accounted for the highest proportion of RRT calls and postoperative death. Employing a risk predictive tool to guide immediate postoperative care may influence postoperative deterioration. It encouraged the design of pragmatic trials focused on feasible, low-technology, and long-term interventions that can be adapted to diverse health systems, especially those that demand more accurate decision making and ask for full engagement in the control of postoperative morbi-mortality.

The treat-to-target strategy (T2T) was associated with better outcomes in psoriatic arthritis (PsA) compared to standard care in clinical trials. This study aimed to analyze factors precluding treatment optimization in a T2T strategy conducted in a real-world cohort of PsA patients. A retrospective cross-sectional study nested in a cohort was conducted. Medical records of patients ≥ 18 years old, fulfilling CASPAR criteria and with at least one visit in the PsA clinic, were reviewed. Demographic data, current medication, and minimal disease activity (MDA) criteria were recorded. Reasons for the non-escalation of therapy in patients who were not classified as MDA were reported as absolute and relative frequencies. In the 8-month period, 131 visits (corresponding to 74 patients) were conducted. The MDA criteria were available in 113 visits (86.3%) and patients were classified as MDA in 31.0% of the visits (N = 35/113). Although in 69.0% of the visits patients were not in MDA, (N = 78/113), therapy was adjusted in only 42.3% (N = 33/78). Reasons precluding treatment escalation in non-MDA subjects were physician’s impression of remission (57.7%, N = 26), non-adherence to previous prescription (17.8%, N = 8), restricted access to drugs (17.8%, N = 8), adverse events (11.1%, N = 5), poor understanding of medication instructions (6.7%, N = 3), patient’s refusal to escalate therapy (4.4%, N = 2), and recent change in therapy (2.2%, N = 1). Discordance between the physician’s clinical evaluation and the MDA criteria, non-adherence to prescription, and poor access to drugs were the main factors precluding escalation of therapy in a T2T strategy in a real-world PsA cohort.

Practical use of risk predictive tools and the assessment of their impact on outcome reduction is still a challenge. This pragmatic study of quality improvement (QI) describes the preoperative adoption of a customised postoperative death probability model (SAMPE model) and the evaluation of the impact of a Postoperative Anaesthetic Care Unit (PACU) pathway on the clinical deterioration of high-risk surgical patients. A prospective cohort of 2,533 surgical patients compared with 2,820 historical controls after the adoption of a quality improvement (QI) intervention. We carried out quick postoperative high-risk pathways at PACU when the probability of postoperative death exceeded 5%. As outcome measures, we used the number of rapid response team (RRT) calls within 7 and 30 postoperative days, in-hospital mortality, and non-planned Intensive Care Unit (ICU) admission. Not only did the QI succeed in the implementation of a customised risk stratification model, but it also diminished the postoperative deterioration evaluated by RRT calls on very high-risk patients within 30 postoperative days (from 23% before to 14% after the intervention, p = 0.05). We achieved no survival benefits or reduction of non-planned ICU. The small group of high-risk patients (13% of the total) accounted for the highest proportion of RRT calls and postoperative death. Employing a risk predictive tool to guide immediate postoperative care may influence postoperative deterioration. It encouraged the design of pragmatic trials focused on feasible, low-technology, and long-term interventions that can be adapted to diverse health systems, especially those that demand more accurate decision making and ask for full engagement in the control of postoperative morbi-mortality.

BackgroundPractical use of risk predictive tools and the assessment of their impact on outcome reduction is still a challenge. This pragmatic study of quality improvement (QI) describes the preoperative adoption of a customised postoperative death probability model (SAMPE model) and the evaluation of the impact of a Postoperative Anaesthetic Care Unit (PACU) pathway on the clinical deterioration of high-risk surgical patients.MethodsA prospective cohort of 2,533 surgical patients compared with 2,820 historical controls after the adoption of a quality improvement (QI) intervention. We carried out quick postoperative high-risk pathways at PACU when the probability of postoperative death exceeded 5%. As outcome measures, we used the number of rapid response team (RRT) calls within 7 and 30 postoperative days, in-hospital mortality, and non-planned Intensive Care Unit (ICU) admission.ResultsNot only did the QI succeed in the implementation of a customised risk stratification model, but it also diminished the postoperative deterioration evaluated by RRT calls on very high-risk patients within 30 postoperative days (from 23% before to 14% after the intervention, p = 0.05). We achieved no survival benefits or reduction of non-planned ICU. The small group of high-risk patients (13% of the total) accounted for the highest proportion of RRT calls and postoperative death.ConclusionEmploying a risk predictive tool to guide immediate postoperative care may influence postoperative deterioration. It encouraged the design of pragmatic trials focused on feasible, low-technology, and long-term interventions that can be adapted to diverse health systems, especially those that demand more accurate decision making and ask for full engagement in the control of postoperative morbi-mortality.

COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3–0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59–1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61–8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation. Coalition COVID-19 Brazil, Bayer SA.

After orthotopic heart transplantation (OHT), the allograft undergoes characteristic alterations in myocardial structure, including hypertrophy, increased ventricular stiffness, ischemia, and inflammation, all of which may decrease overall graft survival. Methods to quantify these phenotypes may clarify the pathophysiology of progressive graft dysfunction post-OHT. We performed cardiac magnetic resonance (CMR) with T1 mapping in 26 OHT recipients (mean age 47 ± 7 years, 30 % female, median follow-up post-OHT 6 months) and 30 age-matched healthy volunteers (mean age 50.5 ± 15 years; LVEF 63.5 ± 7 %). OHT recipients had a normal left ventricular ejection fraction (LVEF 65.3 ± 11 %) with higher LV mass relative to age-matched healthy volunteers (114 ± 27 vs. 85.8 ± 18 g; p < 0.001). There was no late gadolinium enhancement in either group. Both myocardial extracellular volume fraction (ECV) and intracellular lifetime of water (τic), a measure of cardiomyocyte hypertrophy, were higher in patients post-OHT (ECV: 0.39 ± 0.06 vs. 0.28 ± 0.03, p < 0.0001; τic: 0.12 ± 0.08 vs. 0.08 ± 0.03, p < 0.001). ECV was associated with LV mass (r = 0.74, p < 0.001). In follow-up, OHT recipients with normal biopsies by pathology (ISHLT grade 0R) in the first year post-OHT exhibited a lower ECV relative to patients with any rejection ≥2R (0.35 ± 0.02 for 0R vs. 0.45 ± 0, p < 0.001). Higher ECV but not LVEF was significantly associated with a reduced rejection-free survival. After OHT, markers of tissue remodeling by CMR (ECV and τic) are elevated and associated with myocardial hypertrophy. Interstitial myocardial remodeling (by ECV) is associated with cellular rejection. Further research on the impact of graft preservation and early immunosuppression on tissue-level remodeling of the allograft is necessary to delineate the clinical implications of these findings.

Atazanavir (ATV) has already been considered as a potential repurposing drug to 2019 coronavirus disease (COVID-19); however, there are controversial reports on its mechanism of action and effectiveness as anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Through the pre-clinical chain of experiments: enzymatic, molecular docking, cell-based and in vivo assays, it is demonstrated here that both SARS-CoV-2 B.1 lineage and variant of concern gamma are susceptible to this antiretroviral. Enzymatic assays and molecular docking calculations showed that SARS-CoV-2 main protease (Mpro) was inhibited by ATV, with Morrison’s inhibitory constant (Ki) 1.5-fold higher than GC376 (a positive control) dependent of the catalytic water (H2Ocat) content. ATV was a competitive inhibitor, increasing the Mpro’s Michaelis–Menten (Km) more than sixfold. Cell-based assays indicated that different lineages of SARS-CoV-2 is susceptible to ATV. Using oral administration of ATV in mice to reach plasmatic exposure similar to humans, transgenic mice expression in human angiotensin converting enzyme 2 (K18-hACE2) were partially protected against lethal challenge with SARS-CoV-2 gamma. Moreover, less cell death and inflammation were observed in the lung from infected and treated mice. Our studies may contribute to a better comprehension of the Mpro/ATV interaction, which could pave the way to the development of specific inhibitors of this viral protease.

This study aims to report the dietary and daily management, clinical signs, complementary exams, and pathological findings related to an acute and fatal case of gastric dilatation and volvulus (GDV) in a captive Linnaeus’s two-toed sloth (Choloepus didactylus) in the Amazon Biome. An adult female sloth, rescued after being electrocuted, was housed at the Wildlife Section of the Veterinary Hospital (WSVH) of the Institute of Veterinary Medicine (IVM) at the Universidade Federal do Pará (UFPA). It was fed a diverse diet that included animal protein, fruits, vegetables, and greens, with vitamin and mineral supplementation. After five years, the sloth was found in its enclosure hyporesponsive, dehydrated, hypothermic, and hyperventilating, with an abdominal dilation of firm consistency. During emergency care, the animal died. Fecal samples collected two days before death were positive only for Clostridium perfringens type A. Necropsy findings included dilatation of the squamous gastric compartment due to gas accumulation, with necrotic and hemorrhagic mucosa, a 180–270° volvulus obstructing the gastroesophageal region, and intestinal mucosal hyperemia. Histopathology revealed marked congestion with hemorrhage and gastric mucosal necrosis, along with tertiary lymphoid follicles in the submucosa. To the authors’ knowledge, this is the first report of GDV in a sloth in Brazil. Further research is needed to develop appropriate approaches to GDV in captive sloths.

This study compared clinical, echocardiographic, and prognostic characteristics among patients with aortic dissection (AD) with (HypHist) and without (No-HypHist) hypertension history and evaluated the association of blood pressure (BP) at presentation with 1-year mortality, left ventricular (LV) remodeling and renal dysfunction. We investigated clinical and echocardiographic characteristics and 1-year mortality among 367 patients with AD (81% HypHist, 66% Type-A) from three Brazilian centers. Patients with No-HypHist were more likely to have Marfan syndrome, bicuspid aortic valve, to undergo surgical therapy, were less likely to have LV hypertrophy and concentricity, and had similar mortality compared with HypHist patients. Adjusted restricted cubic spline analysis showed that systolic BP (SBP) and diastolic BP (DBP) at presentation had a J-curve association with mortality among patients with No-HypHist, but did not associate with death among patients with HypHist ( for interaction = 0.001 for SBP and = 0.022 for DBP). Conversely, the association between SBP at presentation and mortality was influenced by previous use of antihypertensive medications in the HypHist group ( for interaction = 0.002). Results of multivariable logistic regression analysis comprising the whole sample showed direct associations of SBP and DBP at presentation with LV hypertrophy ( = 0.009) and LV concentricity ( = 0.015), respectively, and an inverse association between pulse pressure at presentation and estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m ( = 0.008). Combined information on BP at presentation, previous diagnosis of hypertension, and use of antihypertensive medications might be useful to predict mortality risk and to estimate extra-aortic end-organ damage among patients with AD.

Risk stratification in secondary prevention has emerged as an unmet clinical need in order to mitigate the Number-Needed-to-Treat and make expensive therapies both clinically relevant and cost-effective. P wave indices reflect atrial conduction, which is a sensitive marker for inflammatory, metabolic, and pressure overload myocardial cell remodeling; the three stimuli are traditional mechanisms for adverse clinical evolution. Accordingly, we sought to investigate the predictive role of P-wave indices to estimate residual risk in patients with chronic coronary artery disease (CAD). The cohort included 520 post-Coronary Artery Bypass Grafting patients with a median age of 60 years who were followed for a median period of 1025 days. The primary endpoint was long-term all-cause death. Cubic spline model demonstrated a linear association between P-wave duration and incidence rate of long-term all-cause death (p = 0.023). P-wave >110ms was a marker for an average of 425 days shorter survival as compared with P-wave under 80ms (Logrank p = 0.020). The Cox stepwise regression models retained P-wave duration as independent marker (HR:1.37; 95%CI:1.05-1.79,p = 0.023). In conclusion, the present study suggests that P-wave measurement may constitute a simple, inexpensive and accessible prognostic tool to be added in the bedside risk estimation in CAD patients.