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Frontiers in Neurology 2021Mechanical thrombectomy (MT) is now the standard-of-care treatment for acute ischemic stroke (AIS) of the anterior circulation and may be performed irrespective of...
Mechanical thrombectomy (MT) is now the standard-of-care treatment for acute ischemic stroke (AIS) of the anterior circulation and may be performed irrespective of intravenous tissue plasminogen activator (IV-tPA) eligibility prior to the procedure. This study aims to understand better if tPA leads to higher rates of reperfusion and improves functional outcomes in AIS patients after MT and to simultaneously evaluate the functionality and efficiency of a novel semi-automated systematic review platform. The Nested Knowledge AutoLit semi-automated systematic review platform was utilized to identify randomized control trials published between 2010 and 2021 reporting the use of mechanical thrombectomy and IV-tPA (MT+tPA) vs. MT alone for AIS treatment. The primary outcome was the rate of successful recanalization, defined as thrombolysis in cerebral infarction (TICI) scores ≥2b. Secondary outcomes included 90-day modified Rankin Scale (mRS) 0-2, 90-day mortality, distal embolization to new territory, and symptomatic intracranial hemorrhage (sICH). A separate random effects model was fit for each outcome measure. We subjectively found Nested Knowledge to be highly streamlined and effective at sourcing the correct literature. Four studies with 1,633 patients, 816 in the MT+tPA arm and 817 in the MT arm, were included in the meta-analysis. In each study, patient populations consisted of only tPA-eligible patients and all imaging and clinical outcomes were adjudicated by an independent and blinded core laboratory. Compared to MT alone, patients treated with MT+tPA had higher odds of eTICI ≥2b (OR = 1.34 [95% CI: 1.10; 1.63]). However, there were no statistically significant differences in the rates of 90-day mRS 0-2 (OR = 0.98 [95% CI: 0.77; 1.24]), 90-day mortality (OR = 0.94 [95% CI: 0.67; 1.32]), distal emboli (OR = 0.94 [95% CI: 0.25; 3.60]), or sICH (OR = 1.17 [95% CI: 0.80; 1.72]). Administering tPA prior to MT may improve the rates of recanalization compared to MT alone in tPA-eligible patients being treated for AIS, but a corresponding improvement in functional and safety outcomes was not present in this review. Further studies looking at the role of tPA before mechanical thrombectomy in different cohorts of patients could better clarify the role of tPA in the treatment protocol for AIS.
PubMed: 34975722
DOI: 10.3389/fneur.2021.759759 -
Frontiers in Neurology 2021Acute ischemic stroke (AIS) is a common devastating disease that has increased yearly in absolute number of cases since 1990. While mechanical thrombectomy and tissue...
Acute ischemic stroke (AIS) is a common devastating disease that has increased yearly in absolute number of cases since 1990. While mechanical thrombectomy and tissue plasminogen activator (tPA) have proven to be effective treatments, their window-of-efficacy time is very short, leaving many patients with no viable treatment option. Over recent years there has been a growing interest in stimulating the facial nerves or ganglions to treat AIS. Pre-clinical studies have consistently demonstrated an increase in collateral blood flow (CBF) following ganglion stimulation, with positive indications in infarct size and neurological scores. Extensive human trials have focused on trans-oral electrical stimulation of the sphenopalatine ganglion, but have suffered from operational limitations and non-significant clinical findings. Regardless, the potential of ganglion stimulation to treat AIS or elongate the window-of-efficacy for current stroke treatments remains extremely promising. This review aims to summarize results from recent trial publications, highlight current innovations, and discuss future directions for the field. Importantly, this review comes after the release of four important clinical trials that were published in mid 2019.
PubMed: 34867737
DOI: 10.3389/fneur.2021.753182 -
Wiener Klinische Wochenschrift Jan 2022The relationship between acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) and levels of certain inflammatory factors remains controversial. The purpose... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The relationship between acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) and levels of certain inflammatory factors remains controversial. The purpose of this meta-analysis was to summarize the available studies evaluating the association between levels of inflammatory factors and ARDS/ALI incidence.
METHODS
We searched the PubMed, EmBase, and Cochrane databases for studies published up to July 2017. For each inflammatory factor, a random effects model was employed to pool results from different studies.
RESULTS
We identified 63 studies that included 6243 patients in our meta-analysis. Overall, the results indicated that the levels of angiopoietin (ANG)-2 (standard mean difference, SMD: 1.34; P < 0.001), interleukin (IL)-1β (SMD: 0.92; P = 0.012), IL‑6 (SMD: 0.66; P = 0.005), and tumor necrosis factor (TNF)-α (SMD: 0.98; P = 0.001) were significantly higher in patients with ARDS/ALI than in unaffected individuals. No significant differences were observed between patients with ARDS/ALI and unaffected individuals in terms of the levels of IL‑8 (SMD: 0.61; P = 0.159), IL-10 (SMD: 1.10; P = 0.231), and plasminogen activator inhibitor (PAI)-1 (SMD: 0.70; P = 0.060).
CONCLUSIONS
ARDS/ALI is associated with a significantly elevated levels of ANG‑2, IL-1β, IL‑6, and TNF‑α, but not with IL‑8, IL-10, and PAI‑1 levels.
Topics: Acute Lung Injury; Biomarkers; Humans; Respiratory Distress Syndrome; Tumor Necrosis Factor-alpha
PubMed: 34860273
DOI: 10.1007/s00508-021-01971-3 -
Trends in Psychiatry and Psychotherapy 2023Major depressive disorder (MDD) is a severe mental health condition that affects millions of people worldwide. Etiologically, several factors may play a role in its... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Major depressive disorder (MDD) is a severe mental health condition that affects millions of people worldwide. Etiologically, several factors may play a role in its development. Previous studies have reported elevated plasminogen activator inhibitor-1 (PAI-1) levels in patients with depression, suggesting that PAI-1 levels might be linked to the etiology of MDD.
METHODS
We systematically searched the following online databases: MEDLINE, Scopus, and Web of Science up to September 10, 2020, to identify studies in which PAI-1 levels were reported in subjects with MDD. Subsequently we used RevMan 5.3 to perform a meta-analysis of data extracted from the included studies using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and PICO criteria for the search and analysis.
RESULTS
Six studies that reported mean ± standard deviation (SD) were included in the analysis, with a total of 507 MDD patients and 3,453 controls. The overall standardized mean difference (SMD) was 0.27 (95% confidence interval [95% CI] 0.01-0.53). PAI-1 serum levels were 0.27 SDs higher in MDD patients than in controls. The test for overall effect was significant (z = 2.04, p = 0.04). Substantial heterogeneity was detected among the studies, demonstrated by the inconsistency test (I² = 72%) and the chi-square test (χ² = 18.32; p = 0.003).
CONCLUSIONS
This systematic review and meta-analysis showed that MDD might be related to elevated PAI-1 levels. We propose larger prospective clinical studies to further investigate this clinical correlation and validate the clinical significance of these observations.
Topics: Humans; Depressive Disorder, Major; Plasminogen Activator Inhibitor 1; Prospective Studies
PubMed: 34798692
DOI: 10.47626/2237-6089-2021-0338 -
Journal of Clinical Medicine Oct 2021Prostate-specific membrane antigen (PSMA) is not sufficiently overexpressed in a small proportion of prostate cancer (PCa) patients, who require other strategies for... (Review)
Review
BACKGROUND
Prostate-specific membrane antigen (PSMA) is not sufficiently overexpressed in a small proportion of prostate cancer (PCa) patients, who require other strategies for imaging and/or treatment. We reviewed potential targets other than PSMA for PCa theranostics in nuclear medicine that have already been tested in humans.
METHODS
We performed a systematic web search in the PubMed and Cochrane databases, with no time restrictions by pooling terms ("prostate cancer", "prostatic neoplasms") and ("radioligand", "radiotracer"). Included articles were clinical studies. The results were synthetized by the target type.
RESULTS
We included 38 studies on six different targets: gastrin-releasing peptide receptors (GRPRs) ( = 23), androgen receptor ( = 11), somatostatin receptors ( = 6), urokinase plasminogen activator surface receptor ( = 4), fibroblast activation protein ( = 2 studies) and integrin receptors ( = 1). GRPRs, the most studied target, has a lower expression in high-grade PCa, CRPC and bone metastases. Its use might be of higher interest in treating earlier stages of PCa or low-grade PCa. Radiolabeled fibroblast activation protein inhibitors were the most recent and promising molecules, but specific studies reporting their interest in PCa are needed.
CONCLUSION
Theranostics in nuclear medicine will continue to develop in the future, especially for PCa patients. Targets other than PSMA exist and deserve to be promoted.
PubMed: 34768432
DOI: 10.3390/jcm10214909 -
BMC Endocrine Disorders Sep 2021The serine protease inhibitor-1 (SERPINE1) rs1799889 single nucleotide polymorphism (SNP) has been constantly associated with diabetes mellitus (DM) and its vascular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The serine protease inhibitor-1 (SERPINE1) rs1799889 single nucleotide polymorphism (SNP) has been constantly associated with diabetes mellitus (DM) and its vascular complications. The aim of this meta-analysis was to evaluate this association with combined evidences.
METHODS
The systematic search was performed for studies published up to March 2021 which assess the associations between SERPINE1 rs1799889 SNP and the risks of DM, diabetic retinopathy (DR), diabetic cardiovascular disease (CVD) and diabetic nephropathy (DN). Only case-control studies were identified, and the linkage between SERPINE1 rs1799889 polymorphism and diabetic vascular risks were evaluated using genetic models.
RESULTS
51 comparisons were enrolled. The results revealed a significant association with diabetes risk in overall population (allelic: OR = 1.34, 95 % CI = 1.14-1.57, homozygous: OR = 1.66, 95 % CI = 1.23-2.14, heterozygous: OR = 1.35, 95 % CI = 1.08-1.69, dominant: OR = 1.49, 95 % CI = 1.18-1.88, recessive: OR = 1.30, 95 % CI = 1.06-1.59) as well as in Asian descents (allelic: OR = 1.45, 95 % CI = 1.16-1.82, homozygous: OR = 1.88, 95 % CI = 1.29-2.75, heterozygous: OR = 1.47, 95 % CI = 1.08-2.00, dominant: OR = 1.64, 95 % CI = 1.21-2.24, recessive: OR = 1.46, 95 % CI = 1.09-1.96). A significant association was observed with DR risk (homozygous: OR = 1.25, 95 % CI = 1.01-1.56, recessive: OR = 1.20, 95 % CI = 1.01-1.43) for overall population, as for the European subgroup (homozygous: OR = 1.32, 95 % CI = 1.02-1.72, recessive: OR = 1.38, 95 % CI = 1.11-1.71). A significant association were shown with DN risk for overall population (allelic: OR = 1.48, 95 % CI = 1.15-1.90, homozygous: OR = 1.92, 95 % CI = 1.26-2.95, dominant: OR = 1.41, 95 % CI = 1.01-1.97, recessive: OR = 1.78, 95 % CI = 1.27-2.51) and for Asian subgroup (allelic: OR = 1.70, 95 % CI = 1.17-2.47, homozygous: OR = 2.46, 95 % CI = 1.30-4.66, recessive: OR = 2.24, 95 % CI = 1.40-3.59) after ethnicity stratification. No obvious association was implied with overall diabetic CVD risk in any genetic models, or after ethnicity stratification.
CONCLUSIONS
SERPINE1 rs1799889 4G polymorphism may outstand for serving as a genetic synergistic factor in overall DM and DN populations, positively for individuals with Asian descent. The association of SERPINE1 rs1799889 SNP and DR or diabetic CVD risks was not revealed.
Topics: Case-Control Studies; China; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Female; Genetic Linkage; Genetic Predisposition to Disease; Humans; Male; Plasminogen Activator Inhibitor 1; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 34592988
DOI: 10.1186/s12902-021-00837-z -
Cerebrovascular Diseases (Basel,... 2022Hemorrhagic transformation (HT) is a complication that occurs spontaneously or after thrombolysis in acute ischemic stroke (AIS) and can increase morbidity and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hemorrhagic transformation (HT) is a complication that occurs spontaneously or after thrombolysis in acute ischemic stroke (AIS) and can increase morbidity and mortality. The association of biomarkers with the risk of HT has been variably reported. We conducted a systematic review of the literature and meta-analysis and sought to compare blood biomarkers associated with HT and its subtypes by evaluating its predictability and correlation with outcome in AIS.
METHODS
The study protocol was registered in the PROSPERO database (CRD42020201334) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Among 2,230 articles identified from Cochrane Library, PubMed, and Web of Science databases, 30 quality-appraised articles were found eligible. Meta-analysis was conducted for matrix metalloproteinase-9 (MMP-9), cellular fibronectin (c-Fn), ferritin, S100 calcium-binding protein B (S100B), and neutrophil-lymphocyte ratio (NLR). We also reviewed biomarkers for correlation with the functional outcome at 90 days from stroke onset (poor outcome modified Rankin scale >2).
RESULTS
The pooled diagnostic odds ratio (DORpooled) was the highest for baseline c-Fn levels (299.253 [95% CI, 20.508-4,366.709]), followed by MMP-9 (DORpooled, 29.571 [95% CI 17.750-49.267]) and ferritin (DORpooled, 24.032 [95% CI 2.557-225.871]). However, wide confidence intervals for ferritin and c-Fn suggested lesser reliability of the markers. Patients with MMP-9 levels ≥140 ng/mL were 29.5 times at higher risk of developing symptomatic HT after AIS (area under the curve = 0.881). S100B (DORpooled, 6.286 [95% CI, 1.861-21.230]) and NLR (DORpooled, 5.036 [95% CI, 2.898-8.749]) had lower diagnostic accuracies. Among the markers not included for meta-analysis, caveolin-1, thrombin-activated fibrinolysis inhibitor, plasminogen activator inhibitor-1, and soluble ST2 were highly sensitive. Elevated levels of MMP-9, ferritin, and NLR were found to be associated with poor functional outcomes and mortality.
CONCLUSION
Of the 5 biomarkers, there was enough evidence that MMP-9 has higher diagnostic accuracy for predicting the risk of HT before thrombolysis. MMP-9, ferritin, and NLR also predicted poor short-term outcomes.
Topics: Biomarkers; Brain Ischemia; Ferritins; Hemorrhage; Humans; Ischemic Stroke; Matrix Metalloproteinase 9; Prognosis; Reproducibility of Results; Stroke
PubMed: 34569521
DOI: 10.1159/000518570 -
Iranian Journal of Pharmaceutical... 2021Reperfusion therapies are recommended for patients with hemodynamic instability or high-risk acute pulmonary embolism (PE). Lower doses of tissue plasminogen activator... (Review)
Review
Efficacy and Safety of Different Dosage of Recombinant Tissue-type Plasminogen Activator (rt-PA) in the Treatment of Acute Pulmonary Embolism: A Systematic Review and Meta-analysis.
Reperfusion therapies are recommended for patients with hemodynamic instability or high-risk acute pulmonary embolism (PE). Lower doses of tissue plasminogen activator (rt-PA) could be considered to improve bleeding complications. The aim of this study was to evaluate the efficacy and safety of a reduced dose of rt-PA for the treatment of acute PE, compared with anticoagulation and standard dose. PubMed Central, Scopus, Web of Science and Embase were searched for all relevant randomized studies and prospective observational studies that compared reduced dose of rt-PA with anticoagulation alone or standard dose of rt-PA in patients with acute PE. The risk ratios (RR, with 95% CI) were calculated according to the value of I2. Outcomes were described as bleeding events, all-cause death, and recurrence of PE. Thirteen articles, including four observational studies (4223 patients) and nine RCTs (780 patients), were included. In comparing reduced dose of rt-PA with anticoagulant, a greater incidence of total bleeding events in low dose was showed (RR, 5.08 (95% CI, (1.39-18.6), I2 = 0.0%). In the standard dose rt-PA reduced dose, there was a greater incidence of total bleeding events in the standard dose of rt-PA, RR 1.48 (95% CI, (1.00-2.19), I2 = 0.0%) was shown. There were no statistical differences in recurrent PE or all-cause mortality. It concluded that in the absence of the benefit of a standard dose of rt-PA in comparison with dose reduction, a reduced dose of rt-PA showed a lower rate of total bleeding events and similar efficacy regarding mortality and PE recurrence rate.
PubMed: 34567173
DOI: 10.22037/ijpr.2021.114142.14688 -
World Journal of Nephrology Jul 2021Chronic kidney disease (CKD) is a common medical condition that is increasing in prevalence. Existing published evidence has revealed through regression analyses that...
BACKGROUND
Chronic kidney disease (CKD) is a common medical condition that is increasing in prevalence. Existing published evidence has revealed through regression analyses that several clinical characteristics are associated with mortality in CKD patients. However, the predictive accuracies of these risk factors for mortality have not been clearly demonstrated.
AIM
To demonstrate the accuracy of mortality predictive factors in CKD patients by utilizing the area under the receiver operating characteristic (ROC) curve (AUC) analysis.
METHODS
We searched Ovid MEDLINE, EMBASE, and the Cochrane Library for eligible articles through January 2021. Studies were included based on the following criteria: (1) Study nature was observational or conference abstract; (2) Study populations involved patients with non-transplant CKD at any CKD stage severity; and (3) Predictive factors for mortality were presented with AUC analysis and its associated 95% confidence interval (CI). AUC of 0.70-0.79 is considered acceptable, 0.80-0.89 is considered excellent, and more than 0.90 is considered outstanding.
RESULTS
Of 1759 citations, a total of 18 studies ( = 14579) were included in this systematic review. Eight hundred thirty two patients had non-dialysis CKD, and 13747 patients had dialysis-dependent CKD (2160 patients on hemodialysis, 370 patients on peritoneal dialysis, and 11217 patients on non-differentiated dialysis modality). Of 24 mortality predictive factors, none were deemed outstanding for mortality prediction. A total of seven predictive factors [N-terminal pro-brain natriuretic peptide (NT-proBNP), BNP, soluble urokinase plasminogen activator receptor (suPAR), augmentation index, left atrial reservoir strain, C-reactive protein, and systolic pulmonary artery pressure] were identified as excellent. Seventeen predictive factors were in the acceptable range, which we classified into the following subgroups: predictors for the non-dialysis population, echocardiographic factors, comorbidities, and miscellaneous.
CONCLUSION
Several factors were found to predict mortality in CKD patients. Echocardiography is an important tool for mortality prognostication in CKD patients by evaluating left atrial reservoir strain, systolic pulmonary artery pressure, diastolic function, and left ventricular mass index.
PubMed: 34430385
DOI: 10.5527/wjn.v10.i4.59 -
Saudi Pharmaceutical Journal : SPJ :... Jul 2021Arterial catheterization is frequently performed in neonatal intensive care units with an inherent risk of peripheral ischemic injury, especially in preterm infants. The... (Review)
Review
BACKGROUND
Arterial catheterization is frequently performed in neonatal intensive care units with an inherent risk of peripheral ischemic injury, especially in preterm infants. The treatment options following vascular damage involve invasive and non-invasive modalities. The primary objective of this systematic review was to evaluate the evidence of the use of topical nitroglycerine (TNG) either alone or as adjunctive therapy. The secondary aim was to develop an approach to the treatment of catheter induced ischemia in infants based on the available evidence.
METHODS
A comprehensive search was conducted of available databases for relevant articles that involved the treatment of peripheral tissue ischemia in neonates with the use of TNG. Citations were restricted to human subjects.
RESULTS
Six hundred and eighty-nine articles were identified, and twenty-seven case reports and case series were compatible with the inclusion and exclusion criteria. Sixty-eight infants out of the 76 published cases (89%) experienced a favorable outcome and 79% (n = 60) demonstrated complete recovery with the topical application of TNG to the ischemic site.
CONCLUSION
The available evidence demonstrates that TNG is effective for the treatment of peripheral ischemia in neonates after standard conservative measures have failed. However, due to the absence of robust evidence for this therapeutic modality, there are no uniform guidelines regarding the frequency, duration, and safety of TNG use. Planning the management of peripheral ischemia in neonates with TNG should be a multidisciplinary decision that includes close surveillance of blood pressure, methemoglobin levels, and follow up cranial ultrasound.
PubMed: 34400871
DOI: 10.1016/j.jsps.2021.05.008