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Indian Heart Journal Jun 2024Left-sided mechanical prosthetic heart valve thrombosis (PVT) occurs because of suboptimal anticoagulation and is common in low-resource settings. Urgent surgery and...
BACKGROUND
Left-sided mechanical prosthetic heart valve thrombosis (PVT) occurs because of suboptimal anticoagulation and is common in low-resource settings. Urgent surgery and fibrinolytic therapy (FT) are the two treatment options available for this condition. Urgent surgery is a high-risk procedure but results in successful restoration of valve function more often and is the treatment of choice in developed countries. In low-resource countries, FT is used as the default treatment strategy, though it is associated with lower success rates and a higher rate of bleeding and embolic complications. There are no randomized trials comparing the two modalities.
METHODS
We performed a single center randomized controlled trial comparing urgent surgery (valve replacement or thrombectomy) with FT (low-dose, slow infusion tissue plasminogen activator, tPA) in patients with symptomatic left-sided PVT. The primary outcome was the occurrence of a complete clinical response, defined as discharge from hospital with completely restored valve function, in the absence of stroke, major bleeding or non-CNS systemic embolism. Outcome assessment was done by investigators blinded to treatment allocation. The principal safety outcome was the occurrence of a composite of in-hospital death, non-fatal stroke, non-fatal major bleed or non-CNS systemic embolism. Outcomes will be assessed both in the intention-to-treat, and in the as-treated population. We will also report outcomes at one year of follow-up. The trial has completed recruitment.
CONCLUSION
This is the first randomized trial to compare urgent surgery with FT for the treatment of left-sided PVT. The results will provide evidence to help clinicians make treatment choices for these patients. (Clinical trial registration: CTRI/2017/10/010159).
PubMed: 38879396
DOI: 10.1016/j.ihj.2024.06.013 -
Neurology Jul 2024
Topics: Humans; Cerebral Hemorrhage; Tissue Plasminogen Activator
PubMed: 38875509
DOI: 10.1212/WNL.0000000000209614 -
Turkish Neurosurgery Feb 2024Extraventricular drainage (EVD) combined with fibrinolytics may prove effective in reducing morbidity and mortality rates associated with intraventricular cerebral...
INTRODUCTION
Extraventricular drainage (EVD) combined with fibrinolytics may prove effective in reducing morbidity and mortality rates associated with intraventricular cerebral hemorrhage (IVH). This efficacy is primarily attributed to increased drainage capacity and a decreased risk of EVD obstruction when fibrinolytics are employed. This systematic review and meta-analysis aimed to determine the effectiveness of thrombolytics in this context.
METHODS
A literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO registration number: CRD42022332152). Articles were selected from various sources, including PubMed, Trip Database, LILACS, Cochrane Library, and ScienceDirect. Clinical trials focusing on IVH treatment using EVD and/or fibrinolytics were considered. The Risk of Bias in Non-randomized Studies of Interventions (ROB 2) tool was employed for bias assessment. A fixed-effects regression model was used following heterogeneity analysis. Treatment effectiveness was evaluated based on mortality outcomes.
RESULTS
A total of 531 patients from four studies were included. The use of fibrinolytics significantly decreased IVH mortality compared with a placebo. The odds ratio (OR) for recombinant tissue plasminogen activator (rtPA) or alteplase was 0.54 [0.36; 0.82]. For urokinase (UK), the OR was 0.21 [0.03; 1.54], rendering it statistically non-significant. The overall OR was 0.52 [0.35; 0.78], and the heterogeneity I2 was 0% (indicating low heterogeneity).
CONCLUSION
While EVD alone is a common approach for managing hydrocephalus, its effectiveness is limited by potential blockages and infections. Combining EVD with UK or rtPA demonstrated improved patient outcomes. rtPA stands out as a reliable and effective option, while limited data are available regarding UK\'s effectiveness in reducing IVH mortality.
PubMed: 38874256
DOI: 10.5137/1019-5149.JTN.45919-23.1 -
Journal of the American Heart... Jun 2024Pulmonary arterial hypertension (PAH) ultimately leads to right ventricular failure and premature death. The identification of circulating biomarkers with prognostic...
BACKGROUND
Pulmonary arterial hypertension (PAH) ultimately leads to right ventricular failure and premature death. The identification of circulating biomarkers with prognostic utility is considered a priority. As chronic inflammation is recognized as key pathogenic driver, we sought to identify inflammation-related circulating proteins that add incremental value to current risk stratification models for long-term survival in patients with PAH.
METHODS AND RESULTS
Plasma levels of 384 inflammatory proteins were measured with the proximity extension assay technology in patients with PAH (n=60) and controls with normal hemodynamics (n=28). Among these, 51 analytes were significantly overexpressed in the plasma of patients with PAH compared with controls. Cox proportional hazard analyses and C-statistics were performed to assess the prognostic value and the incremental prognostic value of differentially expressed proteins. A panel of 6 proteins (CRIM1 [cysteine rich transmembrane bone morphogenetic protein regulator 1], HGF [hepatocyte growth factor], FSTL3 [follistatin-like 3], PLAUR [plasminogen activator, urokinase receptor], CLSTN2 [calsyntenin 2], SPON1 [spondin 1]) were independently associated with death/lung transplantation at the time of PAH diagnosis after adjustment for the 2015 European Society of Cardiology/European Respiratory Society guidelines, the REVEAL (Registry to Evaluate Early and Long-Term PAH Disease Management) 2.0 risk scores, and the refined 4-strata risk assessment. CRIM1, PLAUR, FSTL3, and SPON1 showed incremental prognostic value on top of the predictive models. As determined by Western blot, FSTL3 and SPON1 were significantly upregulated in the right ventricle of patients with PAH and animal models (monocrotaline-injected and pulmonary artery banding-subjected rats).
CONCLUSIONS
In addition to revealing new actors likely involved in cardiopulmonary remodeling in PAH, our screening identified promising circulating biomarkers to improve risk prediction in PAH, which should be externally confirmed.
Topics: Humans; Male; Female; Biomarkers; Proteomics; Middle Aged; Prognosis; Pulmonary Arterial Hypertension; Adult; Animals; Risk Assessment; Case-Control Studies; Receptors, Urokinase Plasminogen Activator; Follistatin-Related Proteins; Disease Models, Animal; Predictive Value of Tests; Inflammation; Inflammation Mediators; Risk Factors; Bone Morphogenetic Protein Receptors, Type II; Pulmonary Artery
PubMed: 38874078
DOI: 10.1161/JAHA.123.032888 -
Radiology Case Reports Aug 2024Situs inversus is a rare congenital abnormality characterized by mirror-image transposition of the major visceral organs and vessels. Few reports have discussed the use...
Situs inversus is a rare congenital abnormality characterized by mirror-image transposition of the major visceral organs and vessels. Few reports have discussed the use of mechanical thrombectomy in acute ischemic stroke with situs inversus. We present such a case, to raise awareness and deepen the knowledge on these cases. A 44-year-old man was admitted to our hospital with sudden-onset dysarthria and left-sided paresis. Computed tomography (CT) angiography revealed situs inversus and occlusion in the internal carotid artery. First, intravenous tissue plasminogen activator was administered, followed by immediate reperfusion with mechanical thrombectomy. We achieved thrombolysis in cerebral infarction grade 3. After the procedure, the patient fully recovered. Prompt diagnosis is crucial for rapid recanalization in patients with vascular anomalies such as situs inversus.
PubMed: 38872738
DOI: 10.1016/j.radcr.2024.05.012 -
Zhonghua Yi Xue Za Zhi Jun 2024To investigate the efficacy and safety of intravenous thrombolysis with Tenecteplase (TNK) in patients with post-awakening branch atheromatous disease (BAD). A...
To investigate the efficacy and safety of intravenous thrombolysis with Tenecteplase (TNK) in patients with post-awakening branch atheromatous disease (BAD). A retrospective collection was conducted on 178 patients with post-awakening BAD admitted to the Stroke Centre of Zhengzhou People's Hospital from January 2017 to June 2023, who had a mismatch in DWI/FLAIR on magnetic resonance imaging. The patients were divided into thrombolysis group (60 patients) and control group (118 patients) according to whether or not they were applied to intravenous thrombolysis by TNK. Propensity score matching (PSM) was used to pair and balance the confounding factors at 1∶1 between the two groups, and the 90-d long-term prognosis of the patients was assessed using the modified Rankin Scale (mRS) and the Barthel Index (BI). The National Institutes of Health Stroke Scale (NIHSS) score was used to compare the early neurological changes between the two groups.The differences in clinical outcomes were compared between the two groups. Fifty-two pairs of patients, 65 males and 39 females, aged (60±9) years, were successfully matched by PSM. The thrombolysis group had lower NIHSS score than that of the control group at 24 h, 7 d, 14 d after treatment or at discharge [3(2, 5) vs 4(3, 7), 3(2, 5) vs 4(3, 5), and 2(1, 4) vs 3(2, 4)], and shorter hospital stay than that of the control group [9(7, 12) d vs 11(9, 13) d], and at the same time, the thrombolysis group was less likely to experience early neurological deterioration (END) [9.6% (5/52) vs 28.9% (15/52)], and the proportion of 90 d mRS≤1, mRS≤2, and BI scores were higher than those in the control group [63.5% (33/52) vs 30.8% (16/52), 82.7% (43/52) vs 59.6% (31/52), and (91±8) points vs (82±8) points ], all differences were statistically significant (0.05). The percentage of mRS≥4 points was higher in the control group than that in the thrombolysis group [23.1% (12/52) vs 7.7% (4/52)]. One case of intracranial haemorrhage occurred in the thrombolysis group, and 1 case in the control group died of pulmonary infection within 90 d of follow-up, with a case-fatality rate of 1.9% (1/52). In the patients with post-awakening BAD screened by MRI, TNK intravenous thrombolysis can significantly reduce the risk of END, improving long-term prognosis and has a high safety.
Topics: Humans; Female; Male; Middle Aged; Retrospective Studies; Thrombolytic Therapy; Tenecteplase; Fibrinolytic Agents; Administration, Intravenous; Treatment Outcome; Stroke; Aged; Tissue Plasminogen Activator; Prognosis; Propensity Score
PubMed: 38871476
DOI: 10.3760/cma.j.cn112137-20231110-01054 -
Liver Transplantation : Official... Jun 2024Current graft evaluation during normothermic ex situ liver perfusion lacks real-time parameters for predicting posttransplant hepatocyte and biliary function....
Current graft evaluation during normothermic ex situ liver perfusion lacks real-time parameters for predicting posttransplant hepatocyte and biliary function. Indocyanine green (ICG) imaging has been widely used in liver surgery, enabling the visualization of hepatic uptake and excretion through bile using near-infrared light. In this research, porcine livers under various ischemic conditions were examined during a 5-hour normothermic ex situ liver perfusion procedure, introducing ICG at 1 hour through the hepatic artery. These conditions included livers from heart-beating donors, donation after circulatory death (DCD) with warm ischemic durations of 60 minutes (DCD60) and 120 minutes (DCD120), as well as interventions utilizing tissue plasminogen activator in DCD120 cases (each n = 5). Distinct hepatic fluorescence patterns correlated with different degrees of ischemic injury (p = 0.01). Low ICG uptake in the parenchyma (less than 40% of maximum intensity) was more prevalent in DCD120 (21.4%) compared to heart-beating donors (6.2%, p = 0.06) and DCD60 (3.0%, p = 0.02). Moreover, ICG clearance from 60 minutes to 240 minutes was significantly higher in heart-beating donors (69.3%) than in DCD60 (17.5%, p < 0.001) and DCD120 (32.1%, p = 0.01). Furthermore, thrombolytic intervention using tissue plasminogen activator in DCD120 resulted in noteworthy outcomes, including significantly reduced ALP levels (p = 0.04) and improved ICG clearance (p = 0.02) with a trend towards mitigating fibrin deposition similar to DCD60, as well as enhancements in bile production (p = 0.09). In conclusion, ICG fluorescence imaging during normothermic ex situ liver perfusion provides real-time classification of hepatic vascular and biliary injuries, offering valuable insights for the more accurate selection and postintervention evaluation of marginal livers in transplantation.
PubMed: 38869990
DOI: 10.1097/LVT.0000000000000416 -
Current Heart Failure Reports Jun 2024This article summarizes the role of coagulation factors in the pathophysiology of heart failure including D-dimer, fibrinogen and fibrin, prothrombin, p-selectin, tissue... (Review)
Review
PURPOSE OF REVIEW
This article summarizes the role of coagulation factors in the pathophysiology of heart failure including D-dimer, fibrinogen and fibrin, prothrombin, p-selectin, tissue factor, tissue plasminogen activator, von Willebrand factor, β-thromboglobulin, Factor XI, tissue thromboplastin, plasminogen activator inhibitor-1 (PAI-1), thrombomodulin, soluble urokinase-type plasminogen activator receptor (suPAR) and stuart-prower factor.
RECENT FINDINGS
The D-dimer, P-selectin, prothrombin, von Willebrand factor, tissue plasminogen activator, fibrinogen, suPAR, tissue factor, thrombomodulin and Factor XI play significant roles the pathophysiology of heart failure. However, no associations were found between β-thromboglobulin, tissue thromboplastin, PAI-1 and stuart-prower factor in the context of heart failure. Coagulation factors play significant role in the pathophysiology of heart failure. Consequently, the underlying pathophysiological mechanisms that explain changes in the cascade are closely related to the diagnostic, prognostic and therapeutic roles of coagulation cascade factors, which help physicians identify and treat heart failure.
PubMed: 38869806
DOI: 10.1007/s11897-024-00671-z -
Arteriosclerosis, Thrombosis, and... Jun 2024Plasma concentration of PAI-1 (plasminogen activator inhibitor-1) correlates with arterial stiffness. Vascular smooth muscle cells (SMCs) express PAI-1, and the...
BACKGROUND
Plasma concentration of PAI-1 (plasminogen activator inhibitor-1) correlates with arterial stiffness. Vascular smooth muscle cells (SMCs) express PAI-1, and the intrinsic stiffness of SMCs is a major determinant of total arterial stiffness. We hypothesized that PAI-1 promotes SMC stiffness by regulating the cytoskeleton and that pharmacological inhibition of PAI-1 decreases SMC and aortic stiffness.
METHODS
PAI-039, a specific inhibitor of PAI-1, and small interfering RNA were used to inhibit PAI-1 expression in cultured human SMCs. Effects of PAI-1 inhibition on SMC stiffness, F-actin (filamentous actin) content, and cytoskeleton-modulating enzymes were assessed. WT (wild-type) and PAI-1-deficient murine SMCs were used to determine PAI-039 specificity. RNA sequencing was performed to determine the effects of PAI-039 on SMC gene expression. In vivo effects of PAI-039 were assessed by aortic pulse wave velocity.
RESULTS
PAI-039 significantly reduced intrinsic stiffness of human SMCs, which was accompanied by a significant decrease in cytoplasmic F-actin content. PAI-1 gene knockdown also decreased cytoplasmic F-actin. PAI-1 inhibition significantly increased the activity of cofilin, an F-actin depolymerase, in WT murine SMCs, but not in PAI-1-deficient SMCs. RNA-sequencing analysis suggested that PAI-039 upregulates AMPK (AMP-activated protein kinase) signaling in SMCs, which was confirmed by Western blotting. Inhibition of AMPK prevented activation of cofilin by PAI-039. In mice, PAI-039 significantly decreased aortic stiffness and tunica media F-actin content without altering the elastin or collagen content.
CONCLUSIONS
PAI-039 decreases intrinsic SMC stiffness and cytoplasmic stress fiber content. These effects are mediated by AMPK-dependent activation of cofilin. PAI-039 also decreases aortic stiffness in vivo. These findings suggest that PAI-1 is an important regulator of the SMC cytoskeleton and that pharmacological inhibition of PAI-1 has the potential to prevent and treat cardiovascular diseases involving arterial stiffening.
PubMed: 38868940
DOI: 10.1161/ATVBAHA.124.320938 -
Neurological Research and Practice Jun 2024To examine the influence of interpreter service needs (IS) on rt-PA administration time metrics.
AIM
To examine the influence of interpreter service needs (IS) on rt-PA administration time metrics.
METHODS
Retrospectively reviewed prospectively collected data from Comprehensive Stroke Center database (January 2011- April 1, 2021) and EMR.
INCLUSION
Subjects for whom a "stroke code" was activated. Excluded in-house strokes. Baseline characteristics, frequency of rt-PA, rt-PA exclusions and time metrics, NIHSS were compared between patients who did or did not require IS. Analyses utilized ANOVA, t-Test, Brown-Mood Median Test, or Pearson's Chi-squared test as appropriate.
RESULTS
Of 2,191 patients with stroke code activations, 81 had a documented need for IS. Rt-PA was administered in 9 IS and 358 non-IS patients. Median baseline NIHSS was higher in rt-PA group (9±8 vs 3±9, p<0.005). In IS patients, there were no differences in baseline characteristics between those who received rt-PA and those who did not, including median score for NIHSS aphasia (0±1 vs 0±1, p = 0.46). There were no rt-PA rate differences between those that did not and did require IS (17% vs 11%, p = 0.22). In patients with final diagnosis acute ischemic stroke, patients excluded from rt-PA solely due to being out of the window were more likely to have required IS (59% vs 35%, p = 0.003). Time metrics of rt-PA administration were not different in IS patients.
CONCLUSIONS
There was no significant difference in frequency or time metrics of rt-PA administration in patients requiring interpreter services during an acute stroke code. AIS patients requiring an interpreter were more likely to be excluded from rt-PA on the basis of time.
PubMed: 38867340
DOI: 10.1186/s42466-024-00319-2