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American Family Physician Nov 2023Pleural effusion affects 1.5 million patients in the United States each year. New effusions require expedited investigation because treatments range from common medical...
Pleural effusion affects 1.5 million patients in the United States each year. New effusions require expedited investigation because treatments range from common medical therapies to invasive surgical procedures. The leading causes of pleural effusion in adults are heart failure, infection, malignancy, and pulmonary embolism. The patient's history and physical examination should guide evaluation. Small bilateral effusions in patients with decompensated heart failure, cirrhosis, or kidney failure are likely transudative and do not require diagnostic thoracentesis. In contrast, pleural effusion in the setting of pneumonia (parapneumonic effusion) may require additional testing. Multiple guidelines recommend early use of point-of-care ultrasound in addition to chest radiography to evaluate the pleural space. Chest radiography is helpful in determining laterality and detecting moderate to large pleural effusions, whereas ultrasonography can detect small effusions and features that could indicate complicated effusion (i.e., infection of the pleural space) and malignancy. Point-of-care ultrasound should also guide thoracentesis because it reduces complications. Computed tomography of the chest can exclude other causes of dyspnea and suggest complicated parapneumonic or malignant effusion. When diagnostic thoracentesis is indicated, Light's criteria can help differentiate exudates from transudates. Pleural aspirate should routinely be evaluated using Gram stain, cell count with differential, culture, cytology, protein, l-lactate dehydrogenase, and pH levels. Additional assessments should be individualized, such as tuberculosis testing in high-prevalence regions. Parapneumonic effusions are the most common cause of exudates. A pH level less than 7.2 is indicative of complicated parapneumonic effusion and warrants prompt consultation for catheter or chest tube drainage, possible tissue plasminogen activator/deoxyribonuclease therapy, or thoracoscopy. Malignant effusions are another common cause of exudative effusions, with recurrent effusions having a poor prognosis.
Topics: Humans; Adult; Tissue Plasminogen Activator; Pleural Effusion; Exudates and Transudates; Neoplasms; Heart Failure
PubMed: 37983698
DOI: No ID Found -
Chemical Research in Toxicology Dec 2023Ischemic stroke is a major cause of death and disability worldwide. However, only intravenous thrombolysis using mechanical thrombectomy or tissue plasminogen activator... (Review)
Review
Ischemic stroke is a major cause of death and disability worldwide. However, only intravenous thrombolysis using mechanical thrombectomy or tissue plasminogen activator is considered an effective and approved treatment. Molecular hydrogen is an emerging therapeutic agent and has recently become a research focus. Molecular hydrogen is involved in antioxidative, anti-inflammatory, and antiapoptotic functions in normal physical processes and may play an important role in stroke management; it has been evaluated in numerous preclinical and clinical studies in several administration formats, including inhalation of hydrogen gas, intravenous or intraperitoneal injection of hydrogen-enriched solution, or drinking of hydrogen-enriched water. In addition to investigation of the underlying mechanisms, the safety and efficacy of using molecular hydrogen have been carefully evaluated, and favorable outcomes have been achieved. All available evidence indicates that molecular hydrogen may be a promising treatment option for stroke management in the future. This review aimed to provide an overview of the role of molecular hydrogen in the management of stroke and possible further modifications of treatment conditions and procedures in terms of dose, duration, and administration route.
Topics: Humans; Tissue Plasminogen Activator; Fibrinolytic Agents; Thrombolytic Therapy; Thrombectomy; Brain Ischemia; Stroke
PubMed: 37988743
DOI: 10.1021/acs.chemrestox.3c00259 -
Research and Practice in Thrombosis and... Mar 2024A State of the Art lecture entitled "Connecting Fibrinolysis and Dyslipidemia" was presented at the International Society on Thrombosis and Haemostasis Congress 2023....
A State of the Art lecture entitled "Connecting Fibrinolysis and Dyslipidemia" was presented at the International Society on Thrombosis and Haemostasis Congress 2023. Hemostasis balances the consequences of blood clotting and bleeding. This balance relies on the proper formation of blood clots, as well as the breakdown of blood clots. The primary mechanism that breaks down blood clots is fibrinolysis, where the fibrin net becomes lysed and the blood clot dissolves. Dyslipidemia is a condition where blood lipid and lipoprotein levels are abnormal. Here, we review studies that observed connections between impaired fibrinolysis and dyslipidemia. We also summarize the different correlations between thrombosis and dyslipidemia in different racial and ethnic groups. Finally, we summarize relevant and new findings on this topic presented during the 2023 International Society on Thrombosis and Haemostasis Congress. More studies are needed to investigate the mechanistic connections between impaired fibrinolysis and dyslipidemia and whether these mechanisms differ in racially and ethnically diverse populations.
PubMed: 38706781
DOI: 10.1016/j.rpth.2024.102394 -
JAMA Internal Medicine Jan 2024Current guidelines advise against intravenous alteplase therapy for treatment of acute ischemic stroke in patients previously treated with non-vitamin K antagonist oral... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Current guidelines advise against intravenous alteplase therapy for treatment of acute ischemic stroke in patients previously treated with non-vitamin K antagonist oral anticoagulants (NOACs).
OBJECTIVE
To evaluate the risk of bleeding and mortality after alteplase treatment for acute ischemic stroke among patients treated with NOACs compared to those not treated with NOACs.
DESIGN, SETTING, AND PARTICIPANTS
This nationwide, population-based cohort study was conducted in Taiwan using data from Taiwan's National Health Insurance Research Database from January 2011 through November 2020 and included 7483 patients treated with alteplase for acute ischemic stroke. A meta-analysis incorporating the results of the study with those of previous studies was performed, and the review protocol was prospectively registered with PROSPERO.
EXPOSURES
NOAC treatment within 2 days prior to stroke, compared to either no anticoagulant treatment or warfarin treatment.
MAIN OUTCOMES AND MEASURES
The primary outcome was intracranial hemorrhage after intravenous alteplase during the index hospitalization (the hospitalization subsequent to alteplase administration). Secondary outcomes were major bleeding events and mortality during the index hospitalization. Propensity score matching was used to control potential confounders. Logistic regression was used to estimate the odds ratio (OR) of outcome events. Meta-analysis was performed using a random-effects model.
RESULTS
Of the 7483 included patients (mean [SD] age, 67.4 [12.7] years; 2908 [38.9%] female individuals and 4575 [61.1%] male individuals), 91 (1.2%), 182 (2.4%), and 7210 (96.4%) received NOACs, warfarin, and no anticoagulants prior to their stroke, respectively. Compared to patients who were not treated with anticoagulants, those treated with NOACs did not have significantly higher risks of intracranial hemorrhage (risk difference [RD], 2.47% [95% CI, -4.23% to 9.17%]; OR, 1.37 [95% CI, 0.62-3.03]), major bleeding (RD, 4.95% [95% CI, -2.56% to 12.45%]; OR, 1.69 [95% CI, 0.83-3.45]), or in-hospital mortality (RD, -4.95% [95% CI, -10.11% to 0.22%]; OR, 0.45 [95% CI, 0.15-1.29]) in the propensity score-matched analyses. Furthermore, the risks of bleeding and mortality were not significantly different between patients treated with NOACs and those treated with warfarin. Similar results were obtained in the meta-analysis.
CONCLUSIONS AND RELEVANCE
In this cohort study with meta-analysis, compared to no treatment with anticoagulants, treatment with NOACs prior to stroke was not associated with a higher risk of intracranial hemorrhage, major bleeding, or mortality in patients receiving intravenous alteplase for acute ischemic stroke.
Topics: Humans; Male; Female; Aged; Anticoagulants; Warfarin; Tissue Plasminogen Activator; Ischemic Stroke; Cohort Studies; Administration, Oral; Atrial Fibrillation; Hemorrhage; Stroke; Intracranial Hemorrhages
PubMed: 37983035
DOI: 10.1001/jamainternmed.2023.6160 -
Phytomedicine : International Journal... Nov 2023Hemorrhagic transformation (HT) seriously affects the clinical application of recombinant tissue plasminogen activator (rt-PA). The main strategy for combating HT is to...
BACKGROUND
Hemorrhagic transformation (HT) seriously affects the clinical application of recombinant tissue plasminogen activator (rt-PA). The main strategy for combating HT is to keep the blood-brain barrier (BBB) stable. Escin is the active ingredient of Aesculus hippocastanum and a natural mixture of triterpene saponins, and may play a part in mitigation of HT.
PURPOSE
This study sought to investigate the effect of Escin in improving rt-PA-induced HT, explore possible mechanisms, and provide new ideas for the treatment of clinical HT.
STUDY DESIGN AND METHODS
In in vivo experiments, transient middle cerebral artery occlusion (tMCAO) was undertaken in 6-week-old and 12-month-old mice, and rt-PA was administered to induce HT injury. The inhibitory effect of Escin on HT and its protective effect on neurobehavior, the BBB, and cerebrovascular endothelial cells was determined. In in vitro experiments, bEnd.3 cells were injured by oxygen-glucose deprivation/reperfusion (OGD/R) and rt-PA. The protective effect of Escin was measured by the CCK8 assay, release of lactate dehydrogenase (LDH), and expression of tight junction (TJ) proteins. In mechanistic studies, the effect of Escin on the adenosine monophosphate-activated kinase / caveolin-1 / matrix metalloprotease-9 (AMPK/Cav-1/MMP-9) pathway was investigated by employing AMPK inhibitor and Cav-1 siRNA.
RESULTS
In mice suffering from ischemia, rt-PA caused HT as well as damage to the BBB and cerebrovascular endothelial cells. Escin reduced the infarct volume, cerebral hemorrhage, improved neurobehavioral deficits, and maintained BBB integrity in rt-PA-treated tMCAO mice while attenuating bEnd.3 cells damage caused by rt-PA and OGD/R injury. Under physiological and pathological conditions, Escin increased the expression of p-AMPK and Cav-1, leading to decreased expression of MMP-9, which further attenuated damage to cerebrovascular endothelial cells, and these effects were verified with AMPK inhibitor and Cav-1 siRNA.
CONCLUSION
We revealed important details of how Escin protects cerebrovascular endothelial cells from HT, these effects were associated with the AMPK/Cav-1/MMP-9 pathway. This study provides experimental foundation for the development of new drugs to mitigate rt-PA-induced HT and the discovery of new clinical application for Escin.
Topics: Animals; Mice; Ischemic Stroke; Escin; AMP-Activated Protein Kinases; Endothelial Cells; Matrix Metalloproteinase 9; Tissue Plasminogen Activator; Blood-Brain Barrier
PubMed: 37716034
DOI: 10.1016/j.phymed.2023.155071 -
Pharmaceuticals (Basel, Switzerland) Jan 2024Fibrinolysis is the process of the fibrin-platelet clot dissolution initiated after bleeding has been stopped. It is regulated by a cascade of proteolytic enzymes with...
Fibrinolysis is the process of the fibrin-platelet clot dissolution initiated after bleeding has been stopped. It is regulated by a cascade of proteolytic enzymes with plasmin at its core. In pathological cases, the balance of normal clot formation and dissolution is replaced by a too rapid lysis, leading to bleeding, or an insufficient one, leading to an increased thrombotic risk. The only approved therapy for emergency thrombus lysis in ischemic stroke is recombinant tissue plasminogen activator, though streptokinase or urokinase-type plasminogen activators could be used for other conditions. Low molecular weight compounds are of great interest for long-term correction of fibrinolysis dysfunctions. Their areas of application might go beyond the hematology field because the regulation of fibrinolysis could be important in many conditions, such as fibrosis. They enhance or weaken fibrinolysis without significant effects on other components of hemostasis. Here we will describe and discuss the main classes of these substances and their mechanisms of action. We will also explore avenues of research for the development of new drugs, with a focus on the use of computational models in this field.
PubMed: 38256925
DOI: 10.3390/ph17010092 -
Journal Der Deutschen Dermatologischen... Nov 2023Bradykinin-mediated angioedema is a rare, non-allergic, potentially life-threatening disease. ACE inhibitor-induced angioedema and hereditary angioedema (HAE) are the... (Review)
Review
Bradykinin-mediated angioedema is a rare, non-allergic, potentially life-threatening disease. ACE inhibitor-induced angioedema and hereditary angioedema (HAE) are the two most common presentations. Therapeutic options, pathophysiology and diagnosis continue to be investigated, with considerable progress in HAE over the last few decades. For all patients with bradykinin-mediated angioedema, there are several medications that should be avoided or administered with caution. Some of the triggering medications are well known, while others are suspected or of unknown significance. A common denominator is that there is no approved therapy for bradykinin-mediated angioedema as a drug side effect. Some medications, such as tissue plasminogen activator, have a higher incidence of angioedema with potential airway compromise than ACE inhibitors, although this fact is widely underappreciated. In this review, we aim to summarize what is currently known and recommended about concomitant medication in HAE patients and the interaction of other bradykinin-influencing drugs.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Tissue Plasminogen Activator; Angioedema; Angioedemas, Hereditary; Complement C1 Inhibitor Protein
PubMed: 37483139
DOI: 10.1111/ddg.15154 -
Neurologic and Psychiatric Manifestations of Bradykinin-Mediated Angioedema: Old and New Challenges.International Journal of Molecular... Jul 2023Neurologic manifestations have been occasionally described in patients with bradykinin-mediated angioedema. The existing literature is currently limited to case series... (Review)
Review
Neurologic manifestations have been occasionally described in patients with bradykinin-mediated angioedema. The existing literature is currently limited to case series and case reports mainly described in the hereditary forms (HAE) concerning central nervous system (CNS) involvement. On the contrary, very little is known about peripheral and autonomic nervous system manifestations. CNS involvement in HAE may present with symptoms including severe headaches, visual disturbance, seizures, and various focal and generalized deficits. In addition, a stroke-like clinical picture may present in HAE patients. In turn, some drugs used in patients with cardiovascular and neurologic disorders, such as recombinant tissue plasminogen activator (r-tPA) and angiotensin-converting enzyme inhibitors (ACEI), may produce medication-induced angioedema, resulting in a diagnostic challenge. Finally, most patients with HAE have higher levels of psychological distress, anxiety, and depression. With this review, we aimed to provide an organized and detailed analysis of the existing literature on neurologic and psychiatric manifestations of HAE to shed light on these potentially invalidating symptoms and lay the foundation for further personalized diagnostic pathways for patients affected by this protean disease.
Topics: Humans; Angioedemas, Hereditary; Bradykinin; Tissue Plasminogen Activator; Angioedema; Angiotensin-Converting Enzyme Inhibitors
PubMed: 37569559
DOI: 10.3390/ijms241512184 -
Pediatric Nephrology (Berlin, Germany) Nov 2023Nephrotic syndrome (NS) consists of the clinical triad of hypoalbuminaemia, high levels of proteinuria and oedema, and describes a heterogeneous group of disease... (Review)
Review
Nephrotic syndrome (NS) consists of the clinical triad of hypoalbuminaemia, high levels of proteinuria and oedema, and describes a heterogeneous group of disease processes with different underlying drivers. The existence of circulating factor disease (CFD) as a driver of NS has been epitomised by a subset of patients who exhibit disease recurrence after transplantation, alongside laboratory work. Several circulating factors have been proposed and studied, broadly grouped into protease components such as soluble urokinase-type plasminogen activator (suPAR), hemopexin (Hx) and calcium/calmodulin-serine protease kinase (CASK), and other circulating proteases, and immune components such as TNF-α, CD40 and cardiotrophin-like cytokine-1 (CLC-1). While currently there is no definitive way of assessing risk of CFD pre-transplantation, promising work is emerging through the study of 'multi-omic' bioinformatic data from large national cohorts and biobanks.
Topics: Humans; Nephrotic Syndrome; Proteinuria; Receptors, Urokinase Plasminogen Activator
PubMed: 36952039
DOI: 10.1007/s00467-023-05928-8 -
Neuroscience Mar 2024The neurovascular unit (NVU) is assembled by endothelial cells (ECs) and pericytes, and encased by a basement membrane (BM) surveilled by microglia and surrounded by... (Review)
Review
The neurovascular unit (NVU) is assembled by endothelial cells (ECs) and pericytes, and encased by a basement membrane (BM) surveilled by microglia and surrounded by perivascular astrocytes (PVA), which in turn are in contact with synapses. Cerebral ischemia induces the rapid release of the serine proteinase tissue-type plasminogen activator (tPA) from endothelial cells, perivascular astrocytes, microglia and neurons. Owning to its ability to catalyze the conversion of plasminogen into plasmin, in the intravascular space tPA functions as a fibrinolytic enzyme. In contrast, the release of astrocytic, microglial and neuronal tPA have a plethora of effects that not always require the generation of plasmin. In the ischemic brain tPA increases the permeability of the NVU, induces microglial activation, participates in the recycling of glutamate, and has various effects on neuronal survival. These effects are mediated by different receptors, notably subunits of the N-methyl-D-aspartate receptor (NMDAR) and the low-density lipoprotein receptor-related protein-1 (LRP-1). Here we review data on the role of tPA in the NVU under non-ischemic and ischemic conditions, and analyze how this knowledge may lead to the development of potential strategies for the treatment of acute ischemic stroke patients.
Topics: Humans; Tissue Plasminogen Activator; Fibrinolysin; Ischemic Stroke; Endothelial Cells; Brain Ischemia; Brain; Fibrinolytic Agents
PubMed: 37574107
DOI: 10.1016/j.neuroscience.2023.08.011