Machine learning to predict major bleeding during anticoagulation for venous thromboembolism: possibilities and limitations.

Predictive tools for major bleeding (MB) using machine learning (ML) might be advantageous over traditional methods. We used data from the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) to develop ML algorithms to identify patients with venous thromboembolism (VTE) at increased risk of MB during the first 3 months of anticoagulation. A total of 55 baseline variables were used as predictors. New data prospectively collected from the RIETE were used for further validation. The RIETE and VTE-BLEED scores were used for comparisons. External validation was performed with the COMMAND-VTE database. Learning was carried out with data from 49 587 patients, of whom 873 (1.8%) had MB. The best performing ML method was XGBoost. In the prospective validation cohort the sensitivity, specificity, positive predictive value and F1 score were: 33.2%, 93%, 10%, and 15.4% respectively. F1 value for the RIETE and VTE-BLEED scores were 8.6% and 6.4% respectively. In the external validation cohort the metrics were 10.3%, 87.6%, 3.5% and 5.2% respectively. In that cohort, the F1 value for the RIETE score was 17.3% and for the VTE-BLEED score 9.75%. The performance of the XGBoost algorithm was better than that from the RIETE and VTE-BLEED scores only in the prospective validation cohort, but not in the external validation cohort.

Treating Inflammation Associated with Pulmonary Hypertension: An Overview of the Literature.

Pulmonary hypertension (PH) comprises five groups of serious clinical entities characterized by pulmonary artery vasoconstriction and vascular remodeling leading to right heart failure and death. In addition to vascular remodeling, recruitment and exaggerated accumulation of several perivascular inflammatory cells is also observed, including macrophages, monocytes, T and B-lymphocytes, dendritic cells and mast cells distributed in pulmonary perivascular spaces and around remodeling pulmonary vessels. Current pulmonary arterial hypertension (PAH)-targeted therapies aim to improve functional capacity, pulmonary hemodynamic conditions, and delay disease progression. Nevertheless, PAH remains incurable, with a poor prognosis and is often refractory to drug therapy, highlighting the need for further research. In the last three decades, the best pathophysiological understanding of PAH has allowed for progression from a disease of little-known pathogenesis, without specific and effective therapy to expanding the arsenal of drugs on a cellular, genetic and molecular basis. This article provides an overview on current knowledge and progress in recent advances in pharmacological therapy in PAH.

Circulating Plasma miRNA and Clinical/Hemodynamic Characteristics Provide Additional Predictive Information About Acute Pulmonary Thromboembolism, Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Hypertension.

Idiopathic pulmonary artery hypertension (IPAH), chronic thromboembolic pulmonary hypertension (CTEPH), and acute pulmonary embolism (APTE) are life-threatening cardiopulmonary diseases without specific surgical or medical treatment. Although APTE, CTEPH and IPAH are different pulmonary vascular diseases in terms of clinical presentation, prevalence, pathophysiology and prognosis, the identification of their circulating microRNA (miRNAs) might help in recognizing differences in their outcome evolution and clinical forms. The aim of this study was to describe the APTE, CTEPH, and IPAH-associated miRNAs and to predict their target genes. The target genes of the key differentially expressed miRNAs were analyzed, and functional enrichment analyses were carried out. The miRNAs were detected using RT-PCR. Finally, we incorporated plasma circulating miRNAs in baseline and clinical characteristics of the patients to detect differences between APTE and CTEPH in time of evolution, and differences between CTEPH and IPAH in diseases form. We found five top circulating plasma miRNAs in common with APTE, CTEPH and IPAH assembled in one conglomerate. Among them, miR-let-7i-5p expression was upregulated in APTE and IPAH, while miRNA-320a was upregulated in CTEP and IPAH. The network construction for target genes showed 11 genes regulated by let-7i-5p and 20 genes regulated by miR-320a, all of them regulators of pulmonary arterial adventitial fibroblasts, pulmonary artery endothelial cell, and pulmonary artery smooth muscle cells. AR (androgen receptor), a target gene of hsa-let-7i-5p and has-miR-320a, was enriched in pathways in cancer, whereas PRKCA (Protein Kinase C Alpha), also a target gene of hsa-let-7i-5p and has-miR-320a, was enriched in KEGG pathways, such as pathways in cancer, glioma, and PI3K-Akt signaling pathway. We inferred that CTEPH might be the consequence of abnormal remodeling in APTE, while unbalance between the hyperproliferative and apoptosis-resistant phenotype of pulmonary arterial adventitial fibroblasts, pulmonary artery endothelial cell and pulmonary artery smooth muscle cells in pulmonary artery confer differences in IPAH and CTEPH diseases form. We concluded that the incorporation of plasma circulating let-7i-5p and miRNA-320a in baseline and clinical characteristics of the patients reinforces differences between APTE and CTEPH in outcome evolution, as well as differences between CTEPH and IPAH in diseases form.

Clinical characteristics and outcomes of venous thromboembolic events after hallux valgus surgery: insights from the RIETE registry.

Hallux valgus surgery (HVS) is one of the most common orthopedic procedures, often occurring in older adults. Guidelines provide inconsistent recommendations about venous thromboembolism (VTE) prophylaxis after HVS and data are scarce regarding VTE presentation and outcomes in this population. We reported the clinical characteristics and outcomes of VTE following HVS among patients enrolled in Registro Informatizado Enfermedad TromboEmbolica (RIETE), a prospective multicenter VTE registry. We compared the findings with those of other patients in RIETE. Consecutive patients with VTE post HVS were included in the study. Baseline characteristics, administration of VTE prophylaxis prior to diagnosis, presenting symptoms and signs, risk factors for VTE, and 90-day outcomes including recurrent VTE, major bleeding and death were determined. A total of 54 patients with VTE post HVS were identified in RIETE [median age: 64 (interquartile range 56-71) years; 85.2% female] and were compared with 74,111 VTE patients who had not undergone HVS. Among those with VTE post HVS, 63.0% had received VTE prophylaxis, in contrast to 35.6% in the rest of the RIETE cohort. Simplified Pulmonary Embolism Severity Index was zero in 66.7% of the patients with pulmonary embolism post HVS and 33.3% of other RIETE patients (P = 0.011). Compared with other VTE patients, use of estrogens was higher in HVS group (13.0% vs 5.4%, P = 0.01). All patients with VTE post HVS (100%) and most of other VTE patients (99.6%) were treated with anticoagulation, most commonly with low-molecular weight heparins. In contrast to the rest of the patients in RIETE, the absolute number of all fatal and non-fatal outcomes at 90 days was zero in the post HVS group (i.e. no deaths, no recurrence of VTE, and no major bleeding). In a large registry of patients with VTE, all patients with VTE post HVS underwent anticoagulation. These patients had much better outcomes than the rest of VTE patients, with no deaths, recurrences or major bleeding events at 90-day follow-up.

Enhanced expression of NLRP3 inflammasome components by monocytes of patients with pulmonary paracoccidioidomycosis is associated with smoking and intracellular hypoxemia.

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by thermally dimorphic fungi of the genus Paracoccidioides that affects predominantly 30-60-year-old male rural workers. The main clinical forms of the disease are acute/subacute, chronic (CF); almost all CF patients develop pulmonary fibrosis, and they also exhibit emphysema due to smoke. An important cytokine in this context, IL-1ß, different from the others, is produced by an intracellular multimolecular complex called inflammasome that is activated by pathogens and/or host signs of damage. Inflammasome has been recognized for its contribution to chronic inflammatory diseases, from that, we hypothesized that this activation could be involved in paracoccidioidomycosis, contributing to chronic inflammation. While inflammasome activation has been demonstrated in experimental models of Paracoccidioides brasiliensis infection, no information is available in patients, leading us to investigate the participation of NLRP3-inflammasome machinery in CF/PCM patients from a Brazilian endemic area. Our findings showed increased priming in mRNA levels of NLRP3 inflammasome genes by monocytes of PCM patients in vitro than healthy controls. Similar intracellular protein expression of NLRP3, CASP-1, ASC, and IL-1ß were also observed in freshly isolated monocytes of PCM patients and smoker controls. Increased expression of NLRP3 and ASC was observed in monocytes from PCM patients under hypoxia in comparison with smoker controls. For the first time, we showed that primed monocytes of CF-PCM patients were associated with enhanced expression of components of NLRP3-inflammasome due to smoke. Also, hypoxemia boosted this machinery. These findings reinforce the systemic low-grade inflammation activation observed in PCM during and after treatment.

Association of Pulmonary Hypertension With Inflammation and Fluid Overload in Hemodialysis Patients.

INTRODUCTION: Pulmonary hypertension (PH) has been reported in hemodialysis patients, but data regarding its pathogenesis are scarce. This study aimed to evaluate the role of fluid overload in PH and its interrelationships with the usual biomarkers of micro-inflammatory state in hemodialysis patients. MATERIALS AND METHODS: In is a cross-sectional and prospective study, 119 consecutive hemodialysis patients at a Brazilian referral university hospital were evaluated between March 2007 and February 2013. Based on the presence of echocardiographic parameters of PH, patients were allocated to two groups of the PH group and the non-PH group. Clinical parameters, site and type of vascular access, bio-impedance, and laboratory findings were compared between the two groups and a logistic regression model was elaborated. RESULTS: Pulmonary hypertension was found in 23 (19.0%) of 119 patients. The groups significantly differed in extracellular water, ventricular thickness, left atrium diameter, and ventricular filling. Additionally, laboratory data associated with PH were alpha-1-acid glycoprotein (140.0 ± 32.9 versus 116.0 ± 35.5; P < .001); C-reactive protein (median, 1.1 versus 1.6; P = .01) and B-type natriuretic peptide (median, 328 versus 77; P = .03). The adjusted logistic regression model, including alpha-1-acid glycoprotein and B-type natriuretic peptide, showed significant associations for both (odds ratio, 1.023; 95% confidence interval, 1.008 to 1.043;  P = .004 and odds ratio, 3.074; 95% confidence interval, 1.49-6.35; P = .002, respectively). CONCLUSIONS: Pulmonary hypertension, cardiac hypertrophy, fluid overload, and inflammation were associated to each other in hemodialysis patients, providing insight into its pathogenesis. Longitudinal studies are warranted.

Evaluating respiratory musculature, quality of life, anxiety, and depression among patients with indeterminate chronic Chagas disease and symptoms of pulmonary hypertension.

INTRODUCTION:: Chagas disease (CD) is progressive and incapacitating, especially when cardiopulmonary function is affected. For example, respiratory muscle weakness can cause dyspnea upon exertion and fatigue, which may be exacerbated when it is associated with pulmonary hypertension (PH). The present study aimed to evaluate respiratory musculature, quality of life, anxiety, and depression among patients with indeterminate chronic CD and symptoms of PH. METHODS:: All individuals completed a clinical evaluation, spirometry, a 6-min walking test, respiratory musculature testing using maximum inspiratory pressure (PImax) and maximum expiratory pressure (PEmax), the Hospital Anxiety and Depression Scale, and the SF-36 questionnaire. RESULTS:: We evaluated 107 patients who were assigned to a control group with only CD (G1, 8 patients), a group with CD and possible PH (G2, 93 patients), and a group with CD and echocardiography evidence of PH (G3, 6 patients). The three groups had similar values for PImax and PEmax. Compared to the G1 and G2 groups, the G3 group covered significantly less distance during the 6-min walking test and had a significantly shorter predicted distance (p < 0.05 vs. the G1 group). All three groups had similar values for their spirometry results, Hospital Anxiety and Depression Scale scores, and SF-36 questionnaire results. CONCLUSIONS:: Patients with indeterminate chronic CD and symptoms of PH did not experience significant impairment in the studied variables, with the exception of the 6-min walking test, which suggests a low exercise tolerance.

Evaluating respiratory musculature, quality of life, anxiety, and depression among patients with indeterminate chronic Chagas disease and symptoms of pulmonary hypertension

Abstract INTRODUCTION: Chagas disease (CD) is progressive and incapacitating, especially when cardiopulmonary function is affected. For example, respiratory muscle weakness can cause dyspnea upon exertion and fatigue, which may be exacerbated when it is associated with pulmonary hypertension (PH). The present study aimed to evaluate respiratory musculature, quality of life, anxiety, and depression among patients with indeterminate chronic CD and symptoms of PH. METHODS: All individuals completed a clinical evaluation, spirometry, a 6-min walking test, respiratory musculature testing using maximum inspiratory pressure (PImax) and maximum expiratory pressure (PEmax), the Hospital Anxiety and Depression Scale, and the SF-36 questionnaire. RESULTS: We evaluated 107 patients who were assigned to a control group with only CD (G1, 8 patients), a group with CD and possible PH (G2, 93 patients), and a group with CD and echocardiography evidence of PH (G3, 6 patients). The three groups had similar values for PImax and PEmax. Compared to the G1 and G2 groups, the G3 group covered significantly less distance during the 6-min walking test and had a significantly shorter predicted distance (p < 0.05 vs. the G1 group). All three groups had similar values for their spirometry results, Hospital Anxiety and Depression Scale scores, and SF-36 questionnaire results. CONCLUSIONS: Patients with indeterminate chronic CD and symptoms of PH did not experience significant impairment in the studied variables, with the exception of the 6-min walking test, which suggests a low exercise tolerance.

[Time for cleaning and room preparation: connection between surgery size and professional perspectives]. / Tempo de limpeza e preparo de sala: relação com o porte cirúrgico e perspectivas profissionais.

The objective was to verify the association between time needed for room cleaning (TLPS) and the surgery size, and related advantages and difficulties faced by the circulator of the room asszgned to this task. A mixed method, with a transverse quantitative, retrospective approach, using a sample of 3095 surgeries performed,from January to June 2011, and a qualitative approach using a Thematic Content Analysis of statements from 11 circulators, was used. The average TLPS was smaller in size 1 surgeries, increasing in sizes 2, 3 and 4, with a significant difference. Advantages reported included organization and size of staff and difficulties reported related to sharp, bladed materials mixed with surgical instruments and a reduced number of cleaning professionals. The larger the size, the higher the TLPS. Surgical teams operating in the Surgical Center interfere directly in the process, facilitating or hindering the achievement of institutional goals related to quality and productivity.

Time for cleaning and room preparation: connection between surgery size and professional perspectives / Tiempo de limpieza y preparación de quirófano: relación con el porte quirúrgico, facilidades y dificultades / Tempo de limpeza e preparo de sala: relação com o porte cirúrgico e perspectivas profissionais

The objective was to verify the association between time needed for room cleaning (TLPS) and the surgery size, and related advantages and difficulties faced by the circulator of the room assigned to this task. A mixed method, with a transverse quantitative, retrospective approach, using a sample of 3095 surgeries performed, from January to June 2011, and a qualitative approach using a Thematic Content Analysis of statements from 11 circulators, was used. The average TLPS was smaller in size 1 surgeries, increasing in sizes 2, 3 and 4, with a significant difference. Advantages reported included organization and size of staff, and difficulties reported related to sharp, bladed materials mixed with surgical instruments and a reduced number of cleaning professionals. The larger the size, the higher the TLPS. Surgical teams operating in the Surgical Center interfere directly in the process, facilitating or hindering the achievement of institutional goals related to quality and productivity.

El objetivo de comprobar la asociación entre el tiempo de limpieza y preparación de la sala quirúrgica (TLPS) con el porte quirúrgico y relacionar con las ventajas y dificultades asignadas a esta tarea por los circulantes de la sala. Método mezclado con enfoque cuantitativo transversal, retrospectivo, con muestra de 3095 cirugías realizadas de enero a junio de 2011 y; enfoque cualitativo de Análisis de Contenido Temático sobre el discurso de 11 circulantes. El promedio del TLPS fue menor en las cirugías de porte 1 aumentando en portes de 2, 3 y 4, con diferencia significativa. Las facilidades divulgadas fueron sobre organización y dimensionamiento de personal, y las dificultades en materiales afilados mezclados con instrumentos quirúrgicos y número reducido de profesionales de la limpieza. Cuanto mayor sea el porte más grande el TLPS. Los equipos quirúrgicos que operan en el Centro de Cirugía interfieren directamente en el proceso, facilitando o dificultando el logro de objetivos institucionales de calidad y productividad.

Objetivou-se verificar a associação entre tempo de limpeza e preparo de sala cirúrgica (TLPS) com o porte cirúrgico, bem como relacionar facilidades e dificuldades atribuídas a essa tarefa pelos circulantes de sala. Método misto com abordagem quantitativa transversal, retrospectiva, com amostra de 3095 cirurgias realizadas de janeiro a junho de 2011, e abordagem qualitativa pela Análise de Conteúdo Temática acerca do discurso de 11 circulantes. A média do TLPS foi menor nas cirurgias de porte 1, aumentando nos portes 2, 3 e 4 com diferença significativa. As facilidades relatadas foram sobre organização e dimensionamento de pessoal, e as dificuldades, sobre materiais perfurocortantes misturados ao instrumental cirúrgico e número reduzido de profissionais da limpeza. Quanto maior o porte cirúrgico, maior o TLPS. As equipes atuantes no Centro Cirúrgico interferem diretamente no processo, facilitando ou dificultando o alcance das metas institucionais de qualidade e produtividade.

Proposal to utilize simplified Swensen protocol in diagnosis of isolated pulmonary nodule.

BACKGROUND: The problem of diagnosing whether a solitary pulmonary nodule is benign or malignant is even greater in developing countries due to a higher prevalence of infectious diseases. These infections generate a large number of patients who are generally asymptomatic and with a pulmonary nodule that cannot be accurately defined as having benign or malignant etiology. PURPOSE: To verify the percentages of benign versus malignant non-calcified nodules, the length of time after contrast agent injection is spiral computed tomography (CT) most sensitive and specific, and whether three postcontrast phases are necessary. MATERIAL AND METHODS: We studied 23 patients with solitary pulmonary nodules identified on chest radiographs or CT. Spiral scans were obtained with Swensen protocol, but at 3, 4, and 5 min after contrast injection onset. Nodules were classified as benign or malignant by histopathological examination or by an absence or presence of growth after 2 years of follow-up CT. RESULTS: Of the 23 patients studied, 18 (78.2%) showed a final diagnosis of benign and five (21.7%) malignant nodules. Despite the small sample size, we obtained results similar to those of Swensen et al., with 80.0% sensitivity, 55.5% specificity, and 60.8% accuracy. Four minutes gave the greatest mean enhancement in both malignant and benign lesions. CONCLUSION: Small non-calcified benign nodules were much more frequent than malignant nodules. The best time for dynamic contrast-enhanced CT density analysis was 4 min postcontrast. As well as saving time and money, this simplified Swensen protocol with only precontrast and 4 min postcontrast phases also reduces patient exposure to ionizing radiation.

Systematic reviews showed insufficient evidence for clinical practice in 2004: what about in 2011? The next appeal for the evidence-based medicine age.

RATIONALE AND AIM: The aims of the Cochrane systematic reviews are to make readily available and up-to-date information for clinical practice, offering consistent evidence and straightforward recommendations. In 2004, we evaluated the conclusions from Cochrane systematic reviews of randomized controlled trials in terms of their recommendations for clinical practice and found that 47.83% of them had insufficient evidence for use in clinical practice. We proposed to reanalyze the reviews to evaluate whether this percentage had significantly decreased. METHODS: A cross-sectional study of systematic reviews published in the Cochrane Library (Issue 7, 2011) was conducted. We randomly selected reviews across all 52 Cochrane Collaborative Review Groups. RESULTS: We analyzed 1128 completed systematic reviews. Of these, 45.30% concluded that the interventions studied were likely to be beneficial, of which only 2.04% recommended no further research. In total, 45.04% of the reviews reported that the evidence did not support either benefit or harm, of which 0.8% did not recommend further studies and 44.24% recommended additional studies; the latter has decreased from our previous study with a difference of 3.59%. CONCLUSION: Only a small number of the Cochrane collaboration's systematic reviews support clinical interventions with no need for additional research. A larger number of high-quality randomized clinical trials are necessary to change the 'insufficient evidence' scenario for clinical practice illustrated by the Cochrane database. It is recommended that we should produce higher-quality primary studies in active collaboration and consultation with global scholars and societies so that this can represent a major component of methodological advance in this context.

Could albumin level explain the higher mortality in hemodialysis patients with pulmonary hypertension?

BACKGROUND: The pathogenesis of pulmonary hypertension (PH) in hemodialysis is still unclear. The aim of this study was to identify the risk factors associated with the presence of PH in chronic hemodialysis patients and to verify whether these factors might explain the highest mortality among them. METHODS: We conducted a retrospective study of hemodialysis patients who started treatment from August 2001 to October 2007 and were followed up until April 2011 in a Brazilian referral medical school. According to the results of echocardiography examination, patients were allocated in two groups: those with PH and those without PH. Clinical parameters, site and type of vascular access, bioimpedance, and laboratorial findings were compared between the groups and a logistic regression model was elaborated. Actuarial survival curves were constructed and hazard risk to death was evaluated by Cox regression analysis. RESULTS: PH > 35 mmHg was found in 23 (30.6%) of the 75 patients studied. The groups differed in extracellular water, ventricular thickness, left atrium diameter, and ventricular filling. In a univariate analysis, extracellular water was associated with PH (relative risk = 1.194; 95% CI of 1.006 - 1.416; p = 0.042); nevertheless, in a multiple model, only left atrium enlargement was independently associated with PH (relative risk =1.172; 95% CI of 1.010 - 1.359; p = 0.036). PH (hazard risk = 3.008; 95% CI of 1.285 - 7.043; p = 0.011) and age (hazard risk of 1.034 per year of age; 95% CI of 1.000 - 7.068; p = 0.047) were significantly associated with mortality in a multiple Cox regression analysis. However, when albumin was taken in account the only statistically significant association was between albumin level and mortality (hazard risk = 0.342 per g/dL; 95% CI of 0.119 - 0.984; p = 0.047) while the presence of PH lost its statistical significance (p = 0.184). Mortality was higher in patients with PH (47.8% vs 25%) who also had a statistically worse survival after the sixth year of follow up. CONCLUSIONS: PH in hemodialysis patients is associated with parameters of volume overload that sheds light on its pathophysiology. Mortality is higher in hemodialysis patients with PH and the low albumin level can explain this association.

Tromboembolia pulmonar aguda: tratamento clínico / Acute pulmonary thromboembolism: clinical treatment

Tromboembolia pulmonar (TEP) é uma doença comum associada a alta taxa de mortalidade. A morte decorrente de TEP ocorre mais comumente em pacientes não diagnosticados durante o período inicial de internação hospitalar. Assim, a mortalidade pode ser reduzida com o diagnóstico rápido, com estratificação de prognóstico mais precoce e tratamento mais intensivo em pacientes com prognóstico desfavorável. A mortalidade é particularmente elevada em TEP maciça que resulta em choque cardiogênico ou parada cardíaca. Muitos pacientes com TEP apresentam pressão sanguínea normal. No entanto, alguns podem deteriorar-se e apresentar hipotensão sistêmica, choque cardiogênico e morte súbita, apesar do nível terapêutico de anticoagulação. A estratégia da estratificação de risco para identificar tais pacientes com TEP tem surgido como elemento crítico e pode influenciar no tratamento e no prognóstico. Neste artigo o autor aborda diferentes aspectos do tratamento na TEP aguda

Pulmonary thromboembolism (PTE) is a common disease associated with a high mortality rate. Death due to PTE occurs more commonly in undiagnosed patients during the initial in-hospital stay. Thus, mortality could be reduced by prompt diagnosis, early prognostic stratification and more intensive treatment in patients with adverse prognosis. Mortality is particularly high in massive PTE resulting in cardiogenic shock or cardiac arrest. Most patients with PTE present with normal blood pressure. However, some may rapidly deteriorate and manifest systemic hypotension, cardiogenic shock, and sudden death despite therapeutic levels of anticoagulation. Risk stratification strategy to identify such patients has emerged as a critical component of care and may have an influence on treatment and prognosis. In this article the author approaches about different aspects of the treatment in acute PTE