Activated clotting time value as an independent predictor of postoperative bleeding and transfusion.

OBJECTIVES: Activated clotting time (ACT) is commonly used to monitor anticoagulation during cardiac surgeries. Final ACT values may be essential to predict postoperative bleeding and transfusions, although ideal values remain unknown. Our aim was to evaluate the utility of ACT as a predictor of postoperative bleeding and transfusion use. METHODS: Retrospective study (722 patients) submitted to surgery between July 2018-October 2021. We compared patients with final ACT < basal ACT and final ACT ≥ basal ACT and final ACT < 140 s with ≥140 s. Continuous variables were analysed with the Wilcoxon rank-sum test; categorical variables using Chi-square or Fisher's exact test. A linear mixed regression model was used to analyse bleeding in patients with final ACT < 140 and ≥140. Independent variables were analysed with binary logistic regression models to investigate their association with bleeding and transfusion. RESULTS: Patients with final ACT ≥ 140 s presented higher postoperative bleeding than final ACT < 140 s at 12 h (P = 0.006) and 24 h (**P = 0.004). Cardiopulmonary bypass (CPB) time [odds ratio (OR) 1.009, 1.002-1.015, 95% confidence interval (CI)] and masculine sex (OR 2.842,1.721-4.821, 95% CI) were significant predictors of bleeding. Patients with final ACT ≥ 140 s had higher risk of UT (OR 1.81, 1.13-2.89, 95% CI; P = 0.0104), compared to final ACT < 140 s. CPB time (OR 1.019,1.012-1.026, 95% CI) and final ACT (OR 1.021,1.010-1.032, 95% CI) were significant predictors of transfusion. Female sex was a predictor of use of transfusion, with a probability for use of 27.23% (21.84-33.39%, 95% CI) in elective surgeries, and 60.38% (37.65-79.36%, 95% CI) in urgent surgeries, higher than in males. CONCLUSIONS: Final ACT has a good predictive value for the use of transfusion. Final ACT ≥ 140 s correlates with higher risk of transfusion and increased bleeding. The risk of bleeding and transfusion is higher with longer periods of CPB. Males have a higher risk of bleeding, but females have a higher risk of transfusion.

Assessment and practical science: identifying generalizable characteristics of written assessments that reward and incentivise effective practices in practical science lessons.

High-stakes assessments prominently influence what is done in secondary school science lessons ('washback' effects). It is therefore important that assessments of knowledge and understanding gained from practical work are constructed to reward and incentivise effective practices in practical work. To do that, they must differentiate between pupils who have experienced practical work in different ways. This empirical, mixed-methods study identifies generalizable characteristics of written assessments that differentially reward pupils who experienced practical activities through hands-on work, teacher demonstration, video demonstration, or reading about the activity. Conclusions are drawn from 1486 post-intervention tests completed by pupils aged 14-15 in England, from lesson observations and teacher interviews. This study also identifies pedagogical practices that were more noticeable in practical work that was most rewarded by the written assessments: the work was teacher-guided; and pupils were encouraged to be active participants. Existing literature describes negative washback effects of high-stakes, written assessments that limit the use and effectiveness of practical work as a pedagogical tool. We describe ways in which written assessments could be constructed to better reward effective practices in practical work (practices that better support learning), with the intention of having positive washback effects on pedagogy by better incentivising these practices.

Quality Standards in Upper Gastrointestinal Endoscopy: Can Deep Sedation Influence It?

Introduction: According to the guideline published by ESGE/UEG, a high-quality esophagogastroduodenoscopy (EGD) implies the application of some criteria that enable better healthcare outcomes. Although intra-procedural performance measures are dependent on patient factors, there is no reference to sedation practices in the guideline mentioned above. Objective: This study aimed to evaluate whether deep sedation influences EGD performance measures established by ESGE/UEG. Methods: This was a cross-sectional study, with a prospective enrollment, that considered for inclusion consecutive patients referred for EGD. Two questionnaires were used to assess performance measures and patient satisfaction after EGD. Results: Sedation had a statistically significant impact on most quality indicators, including complete examination (77.2% without sedation vs. 97.8% with sedation), inspection time (6.17 ± 3.45 vs. 8.39 ± 2.67 min), photodocumentation (78% vs. 97.8%), biopsies (39.3% vs. 60.7%), and patient satisfaction (5.42 ± 2.93 vs. 9.1 ± 1.19). The main reason for an incomplete procedure was patient intolerance (82.6%). Discussion: Deep sedation of patients submitted to EGD proved to be a determinant in the applicability of the ESGE/UEG quality indicators. Patient intolerance was eliminated in the group with sedation, enhancing procedure completeness, adequate pathology identification, management, and consequently, the effectiveness of the exam. Conclusion: Sedation administration should be considered in patients undergoing EGD since it ensures a high-quality procedure.

Introdução: Uma endoscopia digestiva alta (EDA) de qualidade proporciona melhores resultados em termos de saúde e implica a aplicação dos critérios descritos pelas recomendações da ESGE/UEG. Embora os critérios perprocedimento sejam dependentes da colaboração e tolerância do doente, não está explicito o papel da anestesia. Objetivos: Este estudo pretende avaliar se o recurso a anestesia influencia o cumprimento dos critérios de qualidade para a EDA publicados pela ESGE/UEG. Materiais e métodos: Estudo transversal, com recrutamento prospetivo, que incluiu pacientes consecutivamente encaminhados para realização de EDA. Foram utilizados 2 questionários para avaliar medidas de desempenho e satisfação dos pacientes após realização de EDA. Resultados: A anestesia teve um impacto estatisticamente significativo na maioria dos indicadores de qualidade: exame completo (77,2% sem anestesia vs. 97,8% com anestesia); tempo de inspeção (6,17 ± 3,45 vs. 8,39 ± 2,67 minutos); fotodocumentação (78% vs. 97,8%); biópsias (39,3% vs. 60,7%); satisfação do paciente (5,42 ± 2,93 vs. 9,1 ± 1,19). O principal motivo para um procedimento incompleto foi a intolerância do paciente (82,6%). Discussão: A sedação profunda dos doentes submetidos a EDA provou ser determinante na aplicabilidade dos critérios de qualidade da ESGE/UEG. Eliminando por completo a intolerância por parte do doente, proporcionou a realização de exames completos, com correta identificação e gestão de patologias, potenciando assim a efetividade do exame. Conclusão: A administração de anestesia deve ser ponderada, sempre que possível, nos doentes submetidos a EDA, visto que permite garantir a alta qualidade do procedimento.

Anticoagulation Management in V-V ECMO Patients: A Multidisciplinary Pragmatic Protocol.

(1) Background: Extracorporeal membrane oxygenation (ECMO) is a complex procedure affecting both the risk of thrombosis and bleeding. High-quality data to personalize anticoagulation management in ECMO are lacking, resulting in a high variability in practice among centers. For this reason, we review coagulation methods and monitoring and share a pragmatic proposal of coagulation management, as performed in our high-volume ECMO Referral Centre; (2) Methods: We revised the anticoagulation options and monitoring methods available for coagulation management in ECMO through PubMed search based on words including "anticoagulation," "coagulation assays," "ECMO," "ELSO," and "ISTH"; (3) Results: Actual revision of the literature was described as our routine practice regarding ECMO anticoagulation and monitoring; (4) Conclusions: No coagulation test is exclusively predictive of bleeding or thrombotic risk in patients undergoing ECMO support. An approach that allows for a tailored regimen of anticoagulation (regardless of agent used) and monitoring is mandatory. To accomplish this, we propose that the titration of anticoagulation therapies should include multiple laboratory tests, including anti-Xa, aPTT, ACT, viscoelastic tests, AT levels, platelet count, fibrinogen, and FXIII levels. Anticoagulation regimens should be tailored to a specific patient and personalized based on this complex array of essays.

Full-Dose Azacitidine in 5 Days Versus 7 Days With a Weekend Break in Myelodysplastic Syndromes: A Retrospective Cohort Study.

INTRODUCTION: Apart from transplantation, only azacitidine demonstrated a survival benefit in a phase III study in higher-risk myelodysplastic syndromes (MDS). The approved regimen is 75 mg/m2/day for 7 consecutive days, imposing a logistic challenge for outpatient weekend administration. Schedules with 5 days and 7 days with a weekend break (5 + 2) have been used for convenience despite the lack of strong scientific support. Most studies of alternative schedules were performed in lower-risk MDS and with dose reduction in the 5-day schedules. METHODS: We performed a single-center, retrospective cohort study to compare full-dose azacitidine (7 × 75 mg/m2) administration in 5-day and 5 + 2-day schedules in a higher-risk MDS cohort. We evaluated 100 patients for overall survival and a subsample (49 patients) for acute myeloid leukemia-free survival (AMLFS), probability of infections and transfusion burden. Kaplan-Meier analysis and Cox models were used for survival analyses. Linear and logistic regressions were applied for univariate and multivariate assessment. RESULTS: After a median follow-up of 10.8 months, patients treated with a 5-day schedule had a median overall survival of 12.5 months versus 15.0 months in the 5+2 group: HR 0.95 (95% CI, 0.57-1.56); P= .83. AMLFS was also similar between groups: HR 1.70 (95% CI, 0.70-4.14); P = .24. Azacitidine schedules were not predictive of infections nor number of red blood cell or platelet transfusions in multivariate analyses. CONCLUSIONS: In higher-risk MDS, full-dose azacitidine (7 × 75 mg/m2) can be administered both in 5 days and in 7 days with a weekend break with no significant difference in survival, infection or transfusional outcomes.

Acute Deletion of the Glucocorticoid Receptor in Hepatocytes Disrupts Postprandial Lipid Metabolism in Male Mice.

Hepatic lipid metabolism is highly dynamic, and disruption of several circadian transcriptional regulators results in hepatic steatosis. This includes genetic disruption of the glucocorticoid receptor (GR) as the liver develops. To address the functional role of GR in the adult liver, we used an acute hepatocyte-specific GR knockout model to study temporal hepatic lipid metabolism governed by GR at several preprandial and postprandial circadian timepoints. Lipidomics analysis revealed significant temporal lipid metabolism, where GR disruption results in impaired regulation of specific triglycerides, nonesterified fatty acids, and sphingolipids. This correlates with increased number and size of lipid droplets and mildly reduced mitochondrial respiration, most noticeably in the postprandial phase. Proteomics and transcriptomics analyses suggest that dysregulated lipid metabolism originates from pronounced induced expression of enzymes involved in fatty acid synthesis, ß-oxidation, and sphingolipid metabolism. Integration of GR cistromic data suggests that induced gene expression is a result of regulatory actions secondary to direct GR effects on gene transcription.

COVID-19-associated Coagulopathy Characterization using Rotational Thromboelastometry in a Prospective, Observational Cohort Study: The HemoCoV Study.

INTRODUCTION: COVID-19-associated coagulopathy includes systemic and endothelial inflammation with coagulation dysregulation related to immunothrombosis. The aim of this study was to characterize this complication of SARS-CoV-2 infection in patients with moderate to severe COVID-19. METHODS: An open-label, prospective observational study conducted in patients with COVID-19 moderate to severe acute respiratory failure admitted to an intensive care unit (ICU). Coagulation testing, including thromboelastometry, biochemical analysis and clinical variables, were collected at prespecified time points during the 30 days of ICU stay. RESULTS: The study included 145 patients, 73.8% male, with a median age of 68 years (interquartile range - IQR 55 - 74). The most prevalent comorbidities were arterial hypertension (63.4%), obesity (44.1%) and diabetes (22.1%). Simplified acute physiology score II (SAPS II) was on average 43.5 (11 - 105) and sequential organ failure assessment (SOFA) at admission was 7.5 (0 - 14). During ICU stay, 66.9% of patients underwent invasive mechanical ventilation and 18.4% extracorporeal membrane oxygenation support; thrombotic and hemorrhagic events occurred in 22.1% and 15.1% of the patients respectively; anticoagulation with heparin was present in 99.2% of patients since early ICU stay. Death occurred in 35% of patients. Longitudinal studies revealed changes in almost all coagulation tests during the ICU stay. SOFA score, lymphocyte counts, some biochemical, inflammatory and coagulation parameters, including hypercoagulability and hypofibrinolysis seen in thromboelastometry, differed significantly (p < 0.05), between ICU admission and discharge. Hypercoagulability and hypofibrinolysis persisted throughout ICU hospitalization, showing higher incidence and severity in non-survivors. CONCLUSION: COVID-19-associated coagulopathy is characterized by hypercoagulability and hypofibrinolysis from ICU admission, and persisted throughout the clinical course in severe COVID-19. These changes were more pronounced in patients with higher disease burden and in non-survivors.

Paraneoplastic or treatment-associated dermatomyositis: a diagnostic challenge.

Dermatomyositis (DM) is a systemic autoimmune disorder characterized by proximal myopathy and dermatological findings. Approximately 15-30% of DM cases emerge as a paraneoplastic syndrome caused by a concomitant malignancy. Although more rare, in cancer patients DM has also been reported as a possible result of toxicity of some antineoplastic agents, such as taxanes and monoclonal antibodies. Herein, we report a 35-year-old woman with metastatic breast cancer who presented with skin lesions after initiation of paclitaxel and anti-HER2 agents. Clinical, laboratory, and histological findings were consistent with the diagnosis of DM.

Varenicline-induced drug eruption: case and review of the literature.

Cutaneous side-effects of varenicline, a selective partial agonist of the a4B2 nicotinic acetylcholine receptor used to treat smoking addiction, are relatively rare and mainly consist of acute generalized exanthematous pustulosis. We describe an atypical clinical presentation of a varenicline-induced drug eruption, which occurred one day after drug initiation. We report this case since we believe no drug reaction to varenicline has had this clinical presentation or rapidity of onset. Clinicians should be aware of this potential adverse cutaneous reaction in patients taking varenicline for smoking cessation.