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.

IgG4-Related Esophageal Disease Presenting as Esophagitis with Chronic Strictures.

IgG4-related disease is a recently recognized autoimmune systemic disorder that has been described in various organs. The disease is characterized histologically by a dense lymphoplasmacytic infiltrate with IgG4-positive cells, storiform fibrosis, obliterative phlebitis, and can be associated with space-occupying lesions. IgG4-related disease involving the upper gastrointestinal tract is rare. We report the case of a 30-year-old female patient with a long-standing history of severe dysphagia and odynophagia. Symptoms persisted despite anti-acid therapy, and control esophagogastroduodenoscopy revealed endoscopic images consistent with a nontransposable stenosis in the proximal esophagus. An underlying autoimmune process was suspected, and topical immunosuppressants were tried to control her disease. The patient maintained disabling dysphagia secondary to chronic esophageal strictures. A diagnosis of probable IgG4-related disease was made after esophageal biopsies. Treatment attempts with topical corticosteroids was not associated with a significant improvement of the symptoms of dysphagia and odynophagia, possibly because of the chronic nature of the disease associated with a high fibrotic component. This report describes a case of IgG4-related esophageal disease presenting as chronic esophagitis with strictures. We also briefly review the main histopathological features and treatment options in IgG4-related disease.

A doença relacionada com IgG4 é uma doença sistémica, autoimune, que pode acometer vários órgãos. Caracteriza-se histologicamente por um denso infiltrado linfoplasmocítico com células IgG4-positivas, fibrose e flebite obliterante, podendo estar associada a lesões ocupantes de espaço. A doença relacionada com IgG4 envolvendo o trato gastrointestinal superior é rara. Relatamos o caso de uma paciente de 30 anos com história de disfagia e odinofagia com vários anos de evolução, em que apesar da instituição de terapêutica antiácida, os sintomas persistiram. A endoscopia digestiva alta revelou imagens endoscópicas consistentes com uma estenose não transponível no esófago proximal. Suspeitou-se de um processo autoimune subjacente sendo tentada terapêutica imunossupressora tópica para controlo da doença. A paciente manteve disfagia incapacitante secundária a estenose esofágica crónica. O diagnóstico de provável doença relacionada com IgG4 foi feito após biópsias esofágicas. As tentativas de tratamento com corticosteroides tópicos não foram associadas a uma melhora significativa dos sintomas de disfagia e odinofagia, possivelmente devido à natureza crónica da doença associada a um elevado componente fibrótico. Este caso pretende ilustrar uma situação de doença esofágica relacionada com IgG4 apresentando-se como esofagite crónica estenosante. Apresentamos ainda, uma breve revisão das principais características histopatológicas e opções de tratamento em doenças relacionadas com IgG4.

Hemophagocytic Lymphohistiocytosis Secondary to Chronic Lymphocytic Leukemia Progression.

Hemophagocytic lymphohistiocytosis (HLH) is an acute, rare systemic hyperinflammatory disorder caused by a dysregulated immune cell function and massive cytokine release, often leading to multiple organ involvement and failure. Fever, hepatosplenomegaly, cytopenia, elevated liver enzymes, hypertriglyceridemia, and hyperferritinemia are the hallmarks of the disease. Its primary (genetic) form is typically observed in pediatric patients and its secondary, acquired form is seen in adult patients with an underlying autoimmune, malignant, or infectious disease. It is not frequently reported in patients with chronic lymphocytic leukemia (CLL) without an infectious or pharmacological trigger. We present a case of a 71-year-old patient with hemophagocytic lymphohistiocytosis due to the progression of chronic lymphocytic leukemia.

Levosimendan in outpatients with advanced heart failure: Single-center experience of 200 intermittent perfusions.

INTRODUCTION: Patients with advanced heart failure (HF) have high morbidity and mortality, with only a small proportion being eligible for advanced therapies. Intermittent outpatient levosimendan infusion has been shown to provide symptomatic relief and reduce the rate of HF events. Our aim was to assess the safety and efficacy of outpatient levosimendan administration in an advanced HF population. METHODS: This is a report of a single-center experience of consecutive advanced HF patients referred for intermittent intravenous outpatient administration of levosimendan, between January 2018 and March 2021. Baseline and follow-up evaluation included clinical assessment, laboratory tests, transthoracic echocardiography and cardiopulmonary exercise testing. Baseline and clinical follow-up data were compared using the Wilcoxon signed-rank test. RESULTS: A total of 24 patients (60.8 years, 83% male, mean left ventricular ejection fraction [LVEF] 24%), with a median of 1.5 HF hospitalizations in the previous six months, were referred for outpatient levosimendan pulses, the majority as a bridge to transplantation or due to clinical deterioration. At six-month follow-up there was a significant reduction in HF hospitalizations to 0.4±0.7 (p<0.001). NYHA class IV (52.2% to 12.5%, p=0.025) and NT-proBNP (8812.5 to 3807.4 pg/ml, p=0.038) were also significantly reduced. Exercise capacity was significantly improved, including peak oxygen uptake (p=0.043) and VE/VCO2 slope (p=0.040). LVEF improved from 24.0% to 29.7% (p=0.008). No serious adverse events were reported. CONCLUSION: Repeated levosimendan administration in advanced HF patients is a safe procedure and was associated with a reduction in HF hospitalizations, functional and LVEF improvement, and reduction in NT-proBNP levels during follow-up.