Heart failure with a preserved ejection fraction and the EMPEROR-Preserved Trial: a review of how we got here.

Heart failure with a preserved ejection fraction (HFpEF), previously known as diastolic heart failure, was first recognized more than 50 years ago. In spite of all the advances in the knowledge of HFpEF, important questions remain, namely the fact that no therapy has been shown to improve outcomes in these patients. The EMPEROR-Preserved Trial, a trial on the use of empagliflozin on patients with HFpEF, published in October 2021, was the first trial to ever show a change in outcomes in these patients. This article reviews the history of HFpEF and the problems related to its definition and diagnosis over time, and critically reviews the results of the EMPEROR-Preserved Trial in light of these.

Feline blood donation adverse reactions: classification and description of acute and delayed reactions in a donor population.

OBJECTIVES: This article aims to analyse the safety of feline blood donation by describing the frequency and nature of any adverse reactions and their causes, as well as propose measures to decrease the incidence of adverse reactions. METHODS: In this prospective study, any blood donor adverse reactions detected by the clinical staff during and immediately after donation were recorded. The owners of the cats were also surveyed by a veterinary practitioner or veterinary nurse 5 days after donation, using a predefined questionnaire to assess for any clinical or behavioural changes. Data were collected between January 2019 and March 2020 from blood donors enrolled in an animal blood bank programme. RESULTS: Of 3690 blood donations from 1792 feline donors assessed, post-donation reactions were reported in 1.14% (n = 42): 0.22% (n = 8) were acute reactions, which included weakness, pallor, tachypnoea and open-mouth breathing; and 0.92% (n = 34) were delayed post-donation reactions, with 0.16% involving cutaneous (haematomas and skin rashes, n = 6), 0.68% involving behavioural (n = 25) and 0.08% involving digestive (emesis and inappetence, n = 3) signs. CONCLUSIONS AND RELEVANCE: The low incidence of post-donation reactions in this study is encouraging, suggesting that a well-established protocol and competent staff can help to ensure a high level of safety in a feline donor programme and, in turn, increase the confidence of cat owners.

Comparative analysis of the bronchoalveolar microbiome in Portuguese patients with different chronic lung disorders.

The lung is inhabited by a diverse microbiome that originates from the oropharynx by a mechanism of micro-aspiration. Its bacterial biomass is usually low; however, this condition shifts in lung cancer (LC), chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). These chronic lung disorders (CLD) may coexist in the same patient as comorbidities and share common risk factors, among which the microbiome is included. We characterized the microbiome of 106 bronchoalveolar lavages. Samples were initially subdivided into cancer and non-cancer and high-throughput sequenced for the 16S rRNA gene. Additionally, we used a cohort of 25 CLD patients where crossed comorbidities were excluded. Firmicutes, Proteobacteria and Bacteroidetes were the most prevalent phyla independently of the analyzed group. Streptococcus and Prevotella were associated with LC and Haemophilus was enhanced in COPD versus ILD. Although no significant discrepancies in microbial diversity were observed between cancer and non-cancer samples, statistical tests suggested a gradient across CLD where COPD and ILD displayed the highest and lowest alpha diversities, respectively. Moreover, COPD and ILD were separated in two clusters by the unweighted UniFrac distance (P value = 0.0068). Our results support the association of Streptoccocus and Prevotella with LC and of Haemophilus with COPD, and advocate for specific CLD signatures.

Evaluation of telemonitoring of continuous positive airway pressure therapy in obstructive sleep apnoea syndrome: TELEPAP pilot study.

INTRODUCTION: Continuous positive airway pressure is an effective treatment for obstructive sleep apnoea syndrome. However, positive airway pressure compliance rates are disappointingly low, so effective interventions are needed to improve compliance in sleep apnoea. Telemonitoring has been used to improve compliance, but results have been inconsistent. This study aimed to determine outcomes of telemonitoring positive airway pressure compliance and efficacy data compared to usual care and phone-call care. METHODS: Randomized controlled study in which 51 patients (82.4% male; between 25 and 78 years), diagnosed with moderate to severe obstructive sleep apnoea were consecutively randomized to usual care, weekly phone-call care or telemonitored care with the use of Restraxx™. All patients were submitted to a comprehensive educational programme during positive airway pressure adaptation. Patients were followed for the first four weeks of treatment with automatic positive airway pressure (AutoSet Spirit S8®; ResMed), and compliance and efficacy data were analyzed. RESULTS: Telemonitored care group used automatic positive airway pressure an average of 5.0 ± 1.8 hours/night, usual care patients 5.1 ± 2.5 hours and phone-call care patients 3.9 ± 2.6 hours. The residual Apnoea--Hypopnoea Index was 5.3 ± 3.0 in telemonitored care, 5.0 ± 2.5 in usual care and 5.6 ± 3.8 in phone-call care. No statistically significant differences were found between groups regarding positive airway pressure compliance or efficacy (p = 0.296 and p = 0.825, respectively). DISCUSSION: In the presence of a comprehensive educational programme during positive airway pressure adaptation, telemonitoring patients did not show benefits concerning compliance and efficacy. A larger follow-up period is needed to evaluate the long-term results of a telemonitoring programme.

Is the Proteome of Bronchoalveolar Lavage Extracellular Vesicles a Marker of Advanced Lung Cancer?

Acellular bronchoalveolar lavage (BAL) proteomics can partially separate lung cancer from non-lung cancer patients based on principal component analysis and multivariate analysis. Furthermore, the variance in the proteomics data sets is correlated mainly with lung cancer status and, to a lesser extent, smoking status and gender. Despite these advances BAL small and large extracellular vehicles (EVs) proteomes reveal aberrant protein expression in paracrine signaling mechanisms in cancer initiation and progression. We consequently present a case-control study of 24 bronchoalveolar lavage extracellular vesicle samples which were analyzed by state-of-the-art liquid chromatography-mass spectrometry (LC-MS). We obtained evidence that BAL EVs proteome complexity correlated with lung cancer stage 4 and mortality within two years´ follow-up (p value = 0.006). The potential therapeutic target DNMT3B complex is significantly up-regulated in tumor tissue and BAL EVs. The computational analysis of the immune and fibroblast cell markers in EVs suggests that patients who deceased within the follow-up period display higher marker expression indicative of innate immune and fibroblast cells (four out of five cases). This study provides insights into the proteome content of BAL EVs and their correlation to clinical outcomes.

Profiling of lung microbiota discloses differences in adenocarcinoma and squamous cell carcinoma.

The lung is a complex ecosystem of host cells and microbes often disrupted in pathological conditions. Although bacteria have been hypothesized as agents of carcinogenesis, little is known about microbiota profile of the most prevalent cancer subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC). To characterize lung cancer (LC) microbiota a first a screening was performed through a pooled sequencing approach of 16S ribosomal RNA gene (V3-V6) using a total of 103 bronchoalveaolar lavage fluid samples. Then, identified taxa were used to inspect 1009 cases from The Cancer Genome Atlas and to annotate tumor unmapped RNAseq reads. Microbial diversity was analyzed per cancer subtype, history of cigarette smoking and airflow obstruction, among other clinical data. We show that LC microbiota is enriched in Proteobacteria and more diverse in SCC than ADC, particularly in males and heavier smokers. High frequencies of Proteobacteria were found to discriminate a major cluster, further subdivided into well-defined communities' associated with either ADC or SCC. Here, a SCC subcluster differing from other cases by a worse survival was correlated with several Enterobacteriaceae. Overall, this study provides first evidence for a correlation between lung microbiota and cancer subtype and for its influence on patient life expectancy.

Iatrogenic Takotsubo Cardiomyopathy Secondary to Norepinephrine by Continuous Infusion for Shock.

Takotsubo cardiomyopathy is a condition characterized by transient left ventricular systolic and diastolic dysfunction, with a possible direct causal role of catecholamine in its pathophysiology. We present a case of a woman with shock and adrenal insufficiency in whom Takotsubo cardiomyopathy developed after treatment with norepinephrine. This case confirms the direct causal role of catecholamine in the pathophysiology of Takotsubo cardiomyopathy. An 82-year-old woman presented with asthenia, anorexia, nausea and abdominal pain. The patient had been on chronic corticosteroid therapy until 3 months before, when she underwent abdominal surgery and corticosteroids were stopped. She now presented with acute kidney injury, hyponatremia and hyperkalemia and shock. A norepinephrine continuous infusion was administered to maintain a mean arterial pressure over 65 mmHg. An echocardiogram showed severe hypokinesis in the apical segments and hyperdynamic basal segments, with an ejection fraction of 25%. Plasma cortisol level was 4.5 µg/dL (reference range 5-25). Corticosteroid therapy was begun and norepinephrine was tapered and stopped. A new echocardiogram showed normalization of cardiac wall motion and an ejection fraction of 70%. This case highlights the importance of the correction of the cause of shock, as well as the risks associated with the use of norepinephrine if hypotension is severe or if it persists despite fluid administration, as usually recommended. It also confirms the direct causal role of catecholamine in the pathophysiology of Takotsubo cardiomyopathy. To the best of our knowledge, this is the first report of stress-induced cardiomyopathy secondary to norepinephrine by continuous infusion for shock. LEARNING POINTS: Takotsubo cardiomyopathy is a condition characterized by transient left ventricular dysfunction of the apex and midventricle in the absence of attributable coronary artery disease.In patients with shock and adrenal insufficiency, who can be erroneously interpreted as septic shock, Takotsubo cardiomyopathy can develop after treatment with norepinephrine.In the management of shock, there are risks associated with recommending the use of norepinephrine if hypotension is severe or if it persists despite fluid administration, when the cause of shock is other than septic shock and is not corrected.There is a direct causal role of catecholamine in the pathophysiology of Takotsubo cardiomyopathy.

Bronchoalveolar Lavage Proteomics in Patients with Suspected Lung Cancer.

Lung cancer configures as one of the deadliest types of cancer. The future implementation of early screening methods such as exhaled breath condensate analysis and low dose computed tomography (CT) as an alternative to current chest imaging based screening will lead to an increased burden on bronchoscopy units. New approaches for improvement of diagnosis in bronchoscopy units, regarding patient management, are likely to have clinical impact in the future. Diagnostic approaches to address mortality of lung cancer include improved early detection and stratification of the cancers according to its prognosis and further response to drug treatment. In this study, we performed a detailed mass spectrometry based proteome analysis of acellular bronchoalveolar lavage (BAL) fluid samples on an observational prospective cohort consisting of 90 suspected lung cancer cases which were followed during two years. The thirteen new lung cancer cases diagnosed during the follow up time period clustered, based on liquid chromatography-mass spectrometry (LC-MS) data, with lung cancer cases at the time of BAL collection. Hundred and thirty-tree potential biomarkers were identified showing significantly differential expression when comparing lung cancer versus non-lung cancer. The regulated biomarkers showed a large overlap with biomarkers detected in tissue samples.

Mortality Predictive Factors in Subjects With COPD After a Pulmonary Rehabilitation Program: A 3-Year Study.

BACKGROUND: COPD is a high-mortality disease and projected to become the third leading cause of death worldwide by 2030. Our aim was to evaluate predictors of 3-y mortality and factors associated with early (1 y) and late (second and third year) mortality in subjects with severe COPD who completed a pulmonary rehabilitation program. METHODS: A historical cohort study was performed with subjects with COPD who were admitted to a day-hospital for chronic respiratory failure for a pulmonary rehabilitation program, from January 2008 to December 2010. The population was characterized based on sociodemographic factors, body mass index, smoking habits, lung function tests, respiratory failure, comorbidities, bacterial colonization, Modified Medical Research Council dyspnea index, 6-min walk test, mechanical ventilation, noninvasive ventilation, long-term oxygen therapy, hospital admissions, and mortality. RESULTS: From 183 patients who completed a pulmonary rehabilitation program, 93 had COPD. Our cohort had 78 male and 15 female subjects. The mean age ± SD was 68.6 ± 8.9 y, ranging from 43 to 85 y. After the pulmonary rehabilitation program, there were fewer, although not statistically significantly different hospital admissions (2.1 vs 1.7, P = .17). Three years after the pulmonary rehabilitation program, 34 subjects died (36.6%). Hypercapnic respiratory failure (P = .02), noninvasive ventilation (P = .002), lung cancer (P = .001), shorter 6-min walk distance (P = .03), and higher number of previous hospital admissions (P < .001) were associated with a higher mortality rate. CONCLUSION: There is a high mortality rate in late-stage patients with COPD. The most relevant factors associated with mortality were lung cancer, respiratory failure and noninvasive ventilation, severe exacerbations with hospitalization, and lower functional exercise capacity.

Venous thromboembolism risk factors and practices of prophylaxis: ENDORSE study results in Portugal.

BACKGROUND: Venous thromboembolism (VTE) risk assessment is a cornerstone for the achievement of best practices and outcomes. Epidemiologic data and practices related to venous thromboprophylaxis as considered by the global ENDORSE study, (Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting), enrolled 68,183 patients from 32 countries, in which Portugal. Within ENDORSE, data from all participant countries analyzed to determine their risk of VTE and to evaluate the suitability of prophylaxis. METHODS: European patients were enrolled from randomly selected hospitals in Portugal (European Hospital Register), according to ENDORSE study inclusion/exclusion criteria. The Seventh ACCP evidence-based consensus guidelines were employed to evaluate VTE risk and prophylaxis use. RESULTS: From a total of 3,145 beds assessed, 2,183 were considered eligible and 1,632 met all criteria. Of these, 860 (52.7%; 95% CI 50.3-55.1) were at risk of VTE: 525 surgical patients (68.9%; 95% CI 65.5-72.1) and 335 medical patients (38.5%; 95% CI 35.3-41.2). The rate of prophylaxis according to ACCP guidelines in overall patients at risk was 58.5% (503 patients). The prophylaxis rate for VTE was 59% (310 patients) in surgical patients and 57.6% (n=193) in medical patients. 39.7% of surgical patients and 39.4 % of medical patients who did not meet the criteria for prophylaxis were also on prophylaxis with an anticoagulant, which was considered to be inappropriate. CONCLUSIONS: More than a half of these hospitalized patients in Portugal were deemed at risk of VTE and less than two-thirds of them received appropriate prophylaxis. New strategies are required for implementation of venous thromboprophylaxis in Portuguese hospitals.

Therapeutic implications of transesophageal echocardiography after transthoracic echocardiography on acute stroke patients.

BACKGROUND: The role of transesophageal echocardiography (TEE) in the evaluation of acute stroke patients is still ill-defined. We conducted a prospective observational study to find the prevalence of TEE findings that indicate anticoagulation as beneficial, in acute ischemic stroke patients without indication for anticoagulation based on clinical, electrocardiographic and transthoracic echocardiography (TTE) findings. METHODS: We prospectively studied all patients referred to our laboratory for TTE and TEE. Patients were excluded if the diagnosis was not acute ischemic stroke or if they had an indication for anticoagulation based on clinical, electrocardiographic, or TTE data. Patients with TEE findings that might indicate anticoagulation as beneficial were identified. RESULTS: A total of 84 patients with acute ischemic stroke and without indication for anticoagulation based on clinical and electrocardiographic or TTE data were included in the study. Findings indicating anticoagulation as beneficial were found in 32.1%: spontaneous echo contrast (1.2%), complex aortic atheroma (27.4%), thrombus (8.3%), and simultaneous patent foramen ovale and atrial septal aneurysm (2.4%). CONCLUSIONS: The results of our study show that TEE can have therapy implications in 32.1% of ischemic stroke patients in sinus rhythm and with TTE with no indication for anticoagulation.

Host- and microbe-related risk factors for and pathophysiology of fatal Rickettsia conorii infection in Portuguese patients.

BACKGROUND: The pathophysiologic mechanisms that determine the severity of Mediterranean spotted fever (MSF) and the host-related and microbe-related risk factors for a fatal outcome are incompletely understood. METHODS: This prospective study used univariate and multivariate analyses to determine the risk factors for a fatal outcome for 140 patients with Rickettsia conorii infection admitted to 13 Portuguese hospitals during 1994-2006 with documented identification of the rickettsial strain causing their infection. RESULTS: A total of 71 patients (51%) were infected with the Malish strain of Rickettsia conorii, and 69 (49%) were infected with the Israeli spotted fever (ISF) strain. Patients were admitted to the intensive care unit (40 [29%]), hospitalized as routine inpatients (95[67%]), or managed as outpatients (5[4%]). Death occurred in 29 adults (21%). A fatal outcome was significantly more likely for patients infected with the ISF strain, and alcoholism was a risk factor. The pathophysiology of a fatal outcome involved significantly greater incidence of petechial rash, gastrointestinal symptoms, obtundation and/or confusion, dehydration, tachypnea, hepatomegaly, leukocytosis, coagulopathy, azotemia, hyperbilirubinemia, and elevated levels of hepatic enzymes and creatine kinase. Some, but not all, of these findings were observed more often in ISF strain-infected patients. CONCLUSIONS: Although fatalities and similar clinical manifestations occurred among both groups of patients, the ISF strain was more virulent than the Malish strain. Multivariate analysis revealed that acute renal failure and hyperbilirubinemia were most strongly associated with a fatal outcome.

Análise das características higiênico-sanitárias e microbiológicas de pescado comercializado na grande São Paulo / Analysis of characteristics sanitary and microbiological characteristics of fish sold in Sao Paulo

O Brasil é nacionalmente conhecido pela sua riqueza e diversidade de alimentos provenientes do ambiente marinho. A carne de pescado é rica em proteínas de alto valor nutritivo, vitaminas, principalmente A e D, além de possuir alta digestibilidade devido à qualidade da fração lipídica, rica em ácidos graxos insaturados e baixo teor de colesterol. Entretanto, os peixes são altamente susceptíveis ao processo de deterioração devido ao pH próximo à neutralidade, à elevada atividade de água nos tecidos e ao elevado teor de nutrientes, que são facilmente utilizados pelo microrganismos presentes em sua superfície, facilitando sua decomposição por bactérias. Com o propósito de avaliar as qualidades higiênico-sanitárias e microbiológicas dos peixes adquiridos na Grande São Paulo, foram analisadas 88 amostras de peixes do tipo pescada e atum provenientes de três estabelecimentos comerciais (feira-livre, supermercados e CEAGESP) na condição de consumidores. As amostras foram analisadas de acordo com as recomendações do Ministério da Saúde para avaliação microbiológica dos produtos adquiridos. Os resultados obtidos nas análises microbiológicas de coliformes fecais foram de 79,6 por cento de amostras contaminadas; os que se encontravam fora do padrão exigido pela legislação foram de 57,1 por cento, 50,0 por cento e 50,0 por cento nos estabelecimentos CEAGESP, supermercado e feira-livre respectivamente...

Therapy implications of transthoracic echocardiography in acute ischemic stroke patients.

BACKGROUND AND PURPOSE: Stroke is the third leading cause of death in most Western countries. Cardioembolism might be responsible for 15% to 20% of ischemic strokes. Although atrial fibrillation can be diagnosed by electrocardiography, the remaining causes of cardioembolic stroke are diagnosed by echocardiography. Recent recommendations on the management of acute ischemic stroke fail to consider echocardiography as an essential test in all patients. METHODS: We conducted a prospective observational study, performing transthoracic echocardiography on all patients admitted in our hospital with ischemic stroke, in sinus rhythm, from January 7, 2002, to October 16, 2003. Findings compatible with heart diseases that would indicate anticoagulation as beneficial were identified. RESULTS: Of the 853 patients admitted with ischemic stroke, transthoracic echocardiography was performed on 846 (99.2%). Of the 435 patients with ischemic stroke, in sinus rhythm, 37.2% had findings indicating anticoagulation as beneficial: dilated cardiopathy (19.1%), previous anterior wall myocardial infarction (6.2%), left ventricular systolic dysfunction with an ejection fraction <35% (3.7%), mitral valve stenosis with enlarged left atria (1.6%), intracardiac masses (0.5%), valvular prosthesis (0.2%), and >1 abnormality (5.5%). CONCLUSIONS: In our study, transthoracic echocardiography had therapy implications in 37.2% of ischemic stroke patients in sinus rhythm. Transthoracic echocardiography should be considered an essential test in all ischemic stroke patients in sinus rhythm.