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There is little data comparing safety and efficacy outcomes in patients with pulmonary embolism (PE) receiving catheter directed therapies (CDT) compared to a similar-risk cohort of PE patients receiving anticoagulation alone. 1094 patients with acute PE were studied. CDT and conservatively-managed patients were compared using propensity score matching to assess safety outcomes, which included bleeding and acute kidney injury at 2 and 7 days after PE diagnosis. Efficacy outcomes included change in vital signs over 72 h and in-hospital mortality. PE patients with RV strain who underwent CDT (n = 76) had more bleeding at 2 days (additional 1.04 g/dL loss, 95% CI - 1.48 to - 0.60, p < 0.001) and 7 days (additional 1.36 g/dL loss, 95% CI - 1.88 to - 0.84, p < 0.001) compared to those receiving anticoagulation alone (n = 303). There was a significant increase in creatinine at 2 days (additional 0.22 mg/dL elevation, 95% CI 0.02 to 0.42, p = 0.03), but not at 7 days (additional 0.12 mg/dL elevation, 95% CI - 0.11 to 0.35, p = 0.30). In-hospital mortality for patients receiving CDT versus anticoagulation alone was similar (OR 1.21, 95% CI 0.53 to 2.77; p = 0.65). In patients with baseline abnormal vital signs who received CDT versus anticoagulation alone, heart rate, respiratory rate and oxygen requirement improved significantly faster and to levels closer to normal (p ≤ 0.001). CDT was associated with a small but increased risk of bleeding, but no significant worsening of renal function. CDT may be associated with more rapid improvements in heart rate, respiratory rate, and oxygen requirement.
Assuntos
Embolia Pulmonar , Doença Aguda , Anticoagulantes/efeitos adversos , Catéteres , Fibrinolíticos/uso terapêutico , Hemorragia/etiologia , Humanos , Oxigênio , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/etiologia , Estudos Retrospectivos , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
Right ventricular (RV) enlargement, determined via the ratio of the right to left ventricular diameters (RV/LV) by CT imaging is used to classify the severity of acute pulmonary embolism (PE) and impacts treatment decisions. The RV/LV ratio may be an unreliable marker of RV dysfunction, due in part to the complex RV geometry. This study compared the RV/LV ratio to a novel metric, the ratio of the right ventricular to aortic outflow tract diameters (RVOT/Ao) in patients with acute PE treated with catheter-directed therapies (CDT). RVOT/Ao and RV/LV ratios were measured on CT images from 103 patients who received CDT for acute submassive or massive PE and were compared to RV dysfunction severity determined by transthoracic echocardiography. Ratios and biomarkers on admission were assessed for correlation with invasively-measured hemodynamics [right atrial (RA) pressure, mean pulmonary artery (PA) pressure, cardiac output (CO)]. RVOT/Ao but not RV/LV ratios were increased in patients with moderate or severe RV dysfunction compared to those without RV dysfunction (p < 0.05). Neither ratio showed significant correlation with RA (r = 0.09 vs 0.055, p > 0.05), mean PA pressure (r = 0.167 vs 0.146, p > 0.05), or CO (r = 0.021 vs - 0.183, p > 0.05). proBNP correlated with mean PA pressure (r = 0.377, p < 0.05). The RVOT/Ao ratio may be better at assessing RV dysfunction than the RV/LV ratio in patients presenting with acute PE. Although currently accepted protocols rely on the RV/LV ratio in determining when CDT are of benefit, the RVOT/Ao ratio may be a more useful tool in identifying high risk patients.
Assuntos
Aorta , Ventrículos do Coração , Embolia Pulmonar , Disfunção Ventricular Direita/diagnóstico , Aorta/diagnóstico por imagem , Aorta/patologia , Aorta/fisiopatologia , Débito Cardíaco , Angiografia por Tomografia Computadorizada/métodos , Ecocardiografia/métodos , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Tamanho do Órgão , Seleção de Pacientes , Prognóstico , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidade , Embolia Pulmonar/fisiopatologia , Valva Pulmonar/diagnóstico por imagem , Medição de Risco/métodos , Estados Unidos , Disfunção Ventricular Direita/fisiopatologiaRESUMO
Several studies shed light on the size and diversity of the lipidome, along with its role in physiological and pathological processes in human health. Besides that, lipids also function as important signaling mediators. This review focuses on discussing the role of arachidonic acid (AA) derived lipids as mediators in diseases with special emphasis on viral infections. Structurally, arachidonic acid derived lipids, also referred to as lipid mediators, can be classified into three specific classes: Class 1-eicosanoids derived from arachidonic acid metabolism; Class 2-lysophospholipids consisting of either a glycerol or a sphingosine backbone; Class 3-AA and ω-3 polyunsaturated fatty acid (PUFA) derivatives. Class 1 and 2 lipids are commonly referred to as pro-inflammatory molecules, which are found upregulated in diseases like cancer and viral infection. Class 3 lipids are anti-inflammatory molecules, which could be potentially used in treatment of diseases associated with inflammation. The function of each class has been elucidated as unique and contributory to an overall cellular homeostasis. Current work in this field is promising and will surely usher in a new era of lipid understanding and control not only at the molecular level, but also in terms of holistic patient care.
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Ácido Araquidônico/metabolismo , Neoplasias/metabolismo , Humanos , Inflamação/metabolismoRESUMO
Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). KS lesions are characterized by endothelial cells with multiple copies of the latent KSHV episomal genome, lytic replication in a low percentage of infiltrating monocytes, and inflammatory cytokines plus growth factors. We demonstrated that KSHV utilizes inflammatory cyclooxygenase 2/prostaglandin E2 to establish and maintain latency (Sharma-Walia, N., A. G. Paul, V. Bottero, S. Sadagopan, M. V. Veettil, N. Kerur, and B. Chandran, PLoS Pathog 6:e1000777, 2010 [doi:10.1371/journal.ppat.1000777]). Here, we evaluated the role of 5-lipoxygenase (5LO) and its chemotactic metabolite leukotriene B4 (LTB4) in KSHV biology. Abundant staining of 5LO was detected in human KS tissue sections. We observed elevated levels of 5LO and high levels of secretion of LTB4 during primary KSHV infection of endothelial cells and in PEL B cells (BCBL-1 and BC-3 cells). Blocking the 5LO/LTB4 cascade inhibited viral latent ORF73, immunomodulatory K5, viral macrophage inflammatory protein 1 (MIP-1), and viral MIP-2 gene expression, without much effect on lytic switch ORF50, immediate early lytic K8, and viral interferon-regulatory factor 2 gene expression. 5LO inhibition significantly downregulated latent viral Cyclin and latency-associated nuclear antigen 2 levels in PEL cells. 5LO/LTB4 inhibition downregulated TH2-related cytokine secretion, elevated TH1-related cytokine secretion, and reduced human monocyte recruitment, adhesion, and transendothelial migration. 5LO/LTB4 inhibition reduced fatty acid synthase (FASN) promoter activity and its expression. Since FASN, a key enzyme required in lipogenesis, is important in KSHV latency, these findings collectively suggest that 5LO/LTB4 play important roles in KSHV biology and that effective inhibition of the 5LO/LTB4 pathway could potentially be used in treatment to control KS/PEL.
Assuntos
Araquidonato 5-Lipoxigenase/metabolismo , Herpesvirus Humano 8/enzimologia , Leucotrieno B4/metabolismo , Lipogênese/fisiologia , Latência Viral/fisiologia , Adesão Celular/fisiologia , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Primers do DNA , Dinoprostona/metabolismo , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Regulação Viral da Expressão Gênica/fisiologia , Humanos , Imuno-Histoquímica , Luciferases , Monócitos/imunologia , Monócitos/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Latência Viral/genéticaRESUMO
OBJECTIVES: To construct a new scoring system utilizing biomarkers, vitals, and imaging data to predict 30-day mortality in acute pulmonary embolism (PE). BACKGROUND: Acute PE, a well-known manifestation of venous thromboembolic disease, is responsible for over 100,000 deaths worldwide yearly. Contemporary management algorithms rely on a multidisciplinary approach to care via PE response teams (PERT) in the identification of low, intermediate, and high-risk patients. The PESI and sPESI scores have been used as cornerstones of the triage process in assigning risk of 30-day mortality for patients presenting with acute PE; however, the specificity of these scoring systems has often come into question. METHODS: This study retrospectively analyzed 488 patients with acute PE who were managed at a tertiary care institution with either conservative therapy consisting of low molecular weight or unfractionated heparin, advanced therapies consisting of catheter directed therapies, aspiration thrombectomy, or a combination of these therapies, or surgical embolectomy. The CLOT-5 score was designed to include vital signs, biomarkers, and imaging data to predict 30-day mortality in patients presenting with acute PE. RESULTS: The CLOT-5 score had an area under the curve (AUC) of 0.901 with a standard error of 0.29, while the PESI and sPESI scores had an AUC and standard errors of 0.793 ±- 0.43 and 0.728 ± 0.55, respectively. CONCLUSIONS: When incorporated into the management algorithms of national PERT programs, the CLOT-5 score may allow for rapid and comprehensive assessment of patients with acute PE at high risk for clinical decompensation, leading to early escalation of care where appropriate.
Assuntos
Embolia Pulmonar , Humanos , Embolia Pulmonar/mortalidade , Embolia Pulmonar/terapia , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Masculino , Feminino , Projetos Piloto , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Doença AgudaRESUMO
Acute pulmonary embolism (PE) is a manifestation of venous thromboembolic disease with potential serious and life-threatening complications. Management options for acute PE have drastically improved over the last 15 years with the introduction of multidisciplinary pulmonary embolism response teams throughout the world. We present the case of an 18-year-old woman diagnosed with acute PE complicated by near-complete occlusion of her left common femoral artery from a paradoxical embolus in the setting of patent foramen ovale (PFO), managed with surgical pulmonary embolectomy and surgical PFO repair.
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Acute pulmonary embolism (PE) is a potentially life-threatening manifestation of venous thromboembolic disease. Severe acute respiratory syndrome-coronavirus-2, a novel coronavirus that causes coronavirus disease-2019 (COVID-19), has been associated with an increased risk of thrombosis. We describe the therapeutic challenges of 3 patients presenting with PE and suspected or confirmed COVID-19. (Level of Difficulty: Beginner.).
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Lipoxin A4 (LXA4) is an endogenously produced host molecule with anti-inflammatory resolution effects. Previous studies demonstrated it to be involved in anti-vascular endothelial growth factor (VEGF)-mediated angiogenesis and in a possible anticancer role via interaction with its receptor, lipoxin A 4 receptor (ALXR). Here, we examined the effects of LXA4 and its epimer 15-epi-LXA4 in inhibiting proinflammatory and angiogenic functions in a human Kaposi's sarcoma tumor-derived cell line (KS-IMM). KS-IMM cells expressed increased levels of inflammatory cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LO) pathway enzymes when compared with human microvascular dermal endothelial cells (HMVEC-d). KS-IMM cells secreted high levels of prostaglandin E2 (PGE2) and chemotactic leukotriene B4 (LTB4). Treatment with LXA4 or 15-epi-LXA4 effectively reduced the levels of COX-2, 5-LO proteins, and secretion of PGE2 and LTB4 in KS-IMM cells. LXA4 or 15-epi-LXA4 treatment also decreased secretion of proinflammatory interleukin 6 (IL-6) and IL-8 cytokines but induced the secretion of anti-inflammatory IL-10. LXA4 treatment reduced the phosphorylation of VEGF receptor (VEGFR) and ephrin family receptor tyrosine kinases. LXA4 treatment effectively induced dephosphorylation of multiple cellular kinases such as Focal Adhesion Kinase, Protein kinase B, nuclear factor kappa-light-chain-enhancer of activated B cells, and Extracellular signal-regulated kinases (ERK)1/2, and reduced angiogenic factor VEGF-C secretion in KS cells. LX treatment drastically induced the Src-homology 2 domain-containing phosphatase tyrosine (Y542) phosphatase and reduced VEGFR-2 phosphorylation at sites Y1059, Y1175, and Y1212. Treatment of KS-IMM cells with LXA4 resulted in selective localization of VEGFR-2 in nonlipid raft (non-LR) and ALXR to LR fractions. These results demonstrated that LXA4 or 15-epi-LXA4 induce anti-inflammatory and antiangiogenic effects in KS cells and suggest that treatment with LXs is an attractive novel strategy against KS.