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The Cochrane Database of Systematic... Apr 2022Patients with kidney failure require vascular access to receive maintenance haemodialysis (HD), which can be achieved by an arteriovenous fistula or a central venous... (Review)
Review
BACKGROUND
Patients with kidney failure require vascular access to receive maintenance haemodialysis (HD), which can be achieved by an arteriovenous fistula or a central venous catheter (CVC). CVC use is related to frequent complications such as venous stenosis and infection. Venous stenosis occurs mainly due to trauma caused by the entrance of the catheter into the venous lumen and repeated contact with the vein wall. A biofilm, a colony of irreversible adherent and self-sufficient micro-organisms embedded in a self-produced matrix of exopolysaccharides, is associated with the development of infections in patients with indwelling catheters. Despite its clinical relevance, the treatment of catheter-related bloodstream infections (CRBSIs) in patients receiving maintenance HD remains controversial, especially regarding catheter management. Antibiotic lock solutions may sterilise the catheter, treat the infection and prevent unnecessary catheter procedures. However, such treatment may also lead to antibiotic resistance or even clinical worsening in certain more virulent pathogens. Catheter removal and delayed replacement may remove the source of infection, improving infectious outcomes, but this approach may also increase vascular access stenosis, thrombosis or both, or even central vein access failure. Catheter guidewire exchange attempts to remove the source of infection while maintaining access to the same vein and, therefore, may improve clinical outcomes and preserve central veins for future access.
OBJECTIVES
To assess the benefits and harms of different interventions for CRBSI treatment in patients receiving maintenance HD through a permanent CVC, such as systemic antibiotics alone or systemic antibiotics combined with either lock solutions or catheter guidewire exchange or catheter replacement.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 21 December 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) and quasi-RCTs evaluating the management of CRBSI in permanent CVCs in people receiving maintenance HD.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies for inclusion, assessed their risk of bias, and performed data extraction. Results were expressed as risk ratios (RR) or hazard ratios (HR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, with their 95% confidence intervals (CI). The certainty of the evidence was assessed using GRADE.
MAIN RESULTS
We identified two RCTs and one quasi-RCT that enrolled 760 participants addressing the treatment of CRBSIs in people (children and adults) receiving maintenance HD through CVC. No two studies compared the same interventions. The quasi-RCT compared two different lock solutions (tissue plasminogen activator (TPA) and heparin) with concurrent systemic antibiotics. One RCT compared systemic antibiotics alone and in association with an ethanol lock solution, and the other compared systemic antibiotics with different catheter management strategies (guidewire exchange versus removal and replacement). The overall certainty of the evidence was downgraded due to the small number of participants, high risk of bias in many domains, especially randomisation, allocation, and other sources of bias, and missing outcome data. It is uncertain whether an ethanol lock solution used with concurrent systemic antibiotics improved CRBSI eradication compared to systemic antibiotics alone (RR 1.61, 95% CI 1.16 to 2.23) because the certainty of this evidence is very low. There were no reported differences between the effects of TPA and heparin lock solutions on cure rates (RR 0.92, 95% CI 0.74 to 1.15) or between catheter guidewire exchange versus catheter removal with delayed replacement, expressed as catheter infection-free survival (HR 0.88, 95% CI 0.43 to 1.79). To date, no results are available comparing other interventions. Outcomes such as venous stenosis and/or thrombosis, antibiotic resistance, death, and adverse events were not reported.
AUTHORS' CONCLUSIONS
Currently, there is no available high certainty evidence to support one treatment over another for CRBSIs. The benefit of using ethanol lock treatment in combination with systemic antibiotics compared to systemic antibiotics alone for CRBSIs in patients receiving maintenance HD remains uncertain due to the very low certainty of the evidence. Hence, further RCTs to identify the benefits and harms of CRBSI treatment options are needed. Future studies should unify CRBSI and cure definitions and improve methodological design.
Topics: Adult; Catheter-Related Infections; Central Venous Catheters; Child; Heparin; Humans; Renal Dialysis; Sepsis
PubMed: 35363884
DOI: 10.1002/14651858.CD013554.pub2 -
The Cochrane Database of Systematic... Jul 2014Most strokes are due to blockage of an artery in the brain by a blood clot. Prompt treatment with thrombolytic drugs can restore blood flow before major brain damage has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Most strokes are due to blockage of an artery in the brain by a blood clot. Prompt treatment with thrombolytic drugs can restore blood flow before major brain damage has occurred and improve recovery after stroke in some people. Thrombolytic drugs, however, can also cause serious bleeding in the brain, which can be fatal. One drug, recombinant tissue plasminogen activator (rt-PA), is licensed for use in selected patients within 4.5 hours of stroke in Europe and within three hours in the USA. There is an upper age limit of 80 years in some countries, and a limitation to mainly non-severe stroke in others. Forty per cent more data are available since this review was last updated in 2009.
OBJECTIVES
To determine whether, and in what circumstances, thrombolytic therapy might be an effective and safe treatment for acute ischaemic stroke.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (last searched November 2013), MEDLINE (1966 to November 2013) and EMBASE (1980 to November 2013). We also handsearched conference proceedings and journals, searched reference lists and contacted pharmaceutical companies and trialists.
SELECTION CRITERIA
Randomised trials of any thrombolytic agent compared with control in people with definite ischaemic stroke.
DATA COLLECTION AND ANALYSIS
Two review authors applied the inclusion criteria, extracted data and assessed trial quality. We verified the extracted data with investigators of all major trials, obtaining additional unpublished data if available.
MAIN RESULTS
We included 27 trials, involving 10,187 participants, testing urokinase, streptokinase, rt-PA, recombinant pro-urokinase or desmoteplase. Four trials used intra-arterial administration, while the rest used the intravenous route. Most data come from trials that started treatment up to six hours after stroke. About 44% of the trials (about 70% of the participants) were testing intravenous rt-PA. In earlier studies very few of the participants (0.5%) were aged over 80 years; in this update, 16% of participants are over 80 years of age due to the inclusion of IST-3 (53% of participants in this trial were aged over 80 years). Trials published more recently utilised computerised randomisation, so there are less likely to be baseline imbalances than in previous versions of the review. More than 50% of trials fulfilled criteria for high-grade concealment; there were few losses to follow-up for the main outcomes.Thrombolytic therapy, mostly administered up to six hours after ischaemic stroke, significantly reduced the proportion of participants who were dead or dependent (modified Rankin 3 to 6) at three to six months after stroke (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.78 to 0.93). Thrombolytic therapy increased the risk of symptomatic intracranial haemorrhage (OR 3.75, 95% CI 3.11 to 4.51), early death (OR 1.69, 95% CI 1.44 to 1.98; 13 trials, 7458 participants) and death by three to six months after stroke (OR 1.18, 95% CI 1.06 to 1.30). Early death after thrombolysis was mostly attributable to intracranial haemorrhage. Treatment within three hours of stroke was more effective in reducing death or dependency (OR 0.66, 95% CI 0.56 to 0.79) without any increase in death (OR 0.99, 95% CI 0.82 to 1.21; 11 trials, 2187 participants). There was heterogeneity between the trials. Contemporaneous antithrombotic drugs increased the risk of death. Trials testing rt-PA showed a significant reduction in death or dependency with treatment up to six hours (OR 0.84, 95% CI 0.77 to 0.93, P = 0.0006; 8 trials, 6729 participants) with significant heterogeneity; treatment within three hours was more beneficial (OR 0.65, 95% CI 0.54 to 0.80, P < 0.0001; 6 trials, 1779 participants) without heterogeneity. Participants aged over 80 years benefited equally to those aged under 80 years, particularly if treated within three hours of stroke.
AUTHORS' CONCLUSIONS
Thrombolytic therapy given up to six hours after stroke reduces the proportion of dead or dependent people. Those treated within the first three hours derive substantially more benefit than with later treatment. This overall benefit was apparent despite an increase in symptomatic intracranial haemorrhage, deaths at seven to 10 days, and deaths at final follow-up (except for trials testing rt-PA, which had no effect on death at final follow-up). Further trials are needed to identify the latest time window, whether people with mild stroke benefit from thrombolysis, to find ways of reducing symptomatic intracranial haemorrhage and deaths, and to identify the environment in which thrombolysis may best be given in routine practice.
Topics: Brain Ischemia; Drug Administration Schedule; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Randomized Controlled Trials as Topic; Stroke; Thrombolytic Therapy; Time-to-Treatment; Tissue Plasminogen Activator
PubMed: 25072528
DOI: 10.1002/14651858.CD000213.pub3 -
Lancet (London, England) Nov 2020Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers.
METHODS
We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903.
FINDINGS
Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22-25·50]; p=0·024).
INTERPRETATION
In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death.
FUNDING
None.
Topics: Diffusion Magnetic Resonance Imaging; Fibrinolytic Agents; Humans; Infusions, Intravenous; Ischemic Stroke; Recovery of Function; Time-to-Treatment; Tissue Plasminogen Activator; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 33176180
DOI: 10.1016/S0140-6736(20)32163-2 -
Journal of Thrombosis and Thrombolysis Feb 2023Tenecteplase (TNK) is a promising candidate to replace alteplase as the standard of care for acute ischemic stroke (AIS); however, the optimal dosage is still to be... (Meta-Analysis)
Meta-Analysis Review
The efficacy and safety of tenecteplase versus alteplase for acute ischemic stroke: an updated systematic review, pairwise, and network meta-analysis of randomized controlled trials.
Tenecteplase (TNK) is a promising candidate to replace alteplase as the standard of care for acute ischemic stroke (AIS); however, the optimal dosage is still to be investigated. Therefore, we aim to evaluate the safety and efficacy of TNK versus alteplase and to investigate the optimal TNK dosage. A systematic review, pairwise, and network meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, SCOPUS, EMBASE, and PubMed until July 26, 2022. We used the risk ratio (RR) for dichotomous outcomes presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022352038. Nine RCTs with a total of 3,707 patients were included. TNK significantly led to complete recanalization (RR: 1.27 with 95% CI [1.02, 1.57], P = 0.03); however, we found no difference regarding early neurological improvement (RR: 1.07 with 95% CI [0.94, 1.21], P = 0.33) and excellent neurological recovery (RR: 1.03 with 95% CI [0.96, 1.10], P = 0.42). Also, TNK was similar to alteplase regarding mortality (RR: 0.99 with 95% CI [0.82, 1.18], P = 0.88), intracranial haemorrhage (RR: 1.00 with 95% CI [0.85, 1.18], P = 0.99), and parenchymal hematoma (RR: 1.13 with 95% CI [0.83, 1.54], P = 0.44). TNK in the dose of 0.25 mg is a viable candidate to displace alteplase as the standard of care in patients with an AIS within 4.5 h of presentation due to its better rate of early neurological recovery and non-inferiority in terms of safety outcomes. However, the evidence regarding TNK's role in AIS presenting after 4.5 h from symptoms onset, wake-up stroke, and minor stroke/TIA is still lacking, necessitating further double-blinded pragmatic RCTs in this regard.
Topics: Humans; Tissue Plasminogen Activator; Tenecteplase; Fibrinolytic Agents; Network Meta-Analysis; Randomized Controlled Trials as Topic; Stroke; Ischemic Stroke; Treatment Outcome; Brain Ischemia
PubMed: 36449231
DOI: 10.1007/s11239-022-02730-5 -
Scientific Reports Jan 2016An emerging body of evidence has implicated plasminogen activator inhibitor-1 (PAI-1) in the development of type 2 diabetes (T2D), though findings have not always been... (Meta-Analysis)
Meta-Analysis Review
An emerging body of evidence has implicated plasminogen activator inhibitor-1 (PAI-1) in the development of type 2 diabetes (T2D), though findings have not always been consistent. We systematically reviewed epidemiological studies examining the association of PAI-1 with T2D. EMBASE, PubMed, Web of Science, and the Cochrane Library were searched to identify studies for inclusion. Fifty-two studies (44 cross-sectional with 47 unique analytical comparisons and 8 prospective) were included. In pooled random-effects analyses of prospective studies, a comparison of the top third vs. bottom third of baseline PAI-1 values generated a RR of T2D of 1.67 (95% CI 1.28-2.18) with moderate heterogeneity (I(2) = 38%). Additionally, of 47 cross-sectional comparisons, 34(72%) reported significantly elevated PAI-1 among diabetes cases versus controls, 2(4%) reported significantly elevated PAI-1 among controls, and 11(24%) reported null effects. Results from pooled analyses of prospective studies did not differ substantially by study design, length of follow-up, adjustment for various putative confounding factors, or study quality, and were robust to sensitivity analyses. Findings from this systematic review of the available epidemiological literature support a link between PAI-1 and T2D, independent of established diabetes risk factors. Given the moderate size of the association and heterogeneity across studies, future prospective studies are warranted.
Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 2; Humans; Odds Ratio; Plasminogen Activator Inhibitor 1; Prospective Studies
PubMed: 26813008
DOI: 10.1038/srep17714 -
Stroke May 2023Prior systematic reviews have compared the efficacy of intravenous tenecteplase and alteplase in acute ischemic stroke, assigning their relative complications as a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prior systematic reviews have compared the efficacy of intravenous tenecteplase and alteplase in acute ischemic stroke, assigning their relative complications as a secondary objective. The objective of the present study is to determine whether the risk of treatment complications differs between patients treated with either agent.
METHODS
We performed a systematic review including interventional studies and prospective and retrospective, observational studies enrolling adult patients treated with intravenous tenecteplase for ischemic stroke (both comparative and noncomparative with alteplase). We searched MEDLINE, Embase, the Cochrane Library, Web of Science, and the www.
CLINICALTRIALS
gov registry from inception through June 3, 2022. The primary outcome was symptomatic intracranial hemorrhage, and secondary outcomes included any intracranial hemorrhage, angioedema, gastrointestinal hemorrhage, other extracranial hemorrhage, and mortality. We performed random effects meta-analyses where appropriate. Evidence was synthesized as relative risks, comparing risks in patients exposed to tenecteplase versus alteplase and absolute risks in patients treated with tenecteplase.
RESULTS
Of 2226 records identified, 25 full-text articles (reporting 26 studies of 7913 patients) were included. Sixteen studies included alteplase as a comparator, and 10 were noncomparative. The relative risk of symptomatic intracranial hemorrhage in patients treated with tenecteplase compared with alteplase in the 16 comparative studies was 0.89 ([95% CI, 0.65-1.23]; I=0%). Among patients treated with low dose (<0.2 mg/kg; 4 studies), medium dose (0.2-0.39 mg/kg; 13 studies), and high dose (≥0.4 mg/kg; 3 studies) tenecteplase, the RRs of symptomatic intracranial hemorrhage were 0.78 ([95% CI, 0.22-2.82]; I=0%), 0.77 ([95% CI, 0.53-1.14]; I=0%), and 2.31 ([95% CI, 0.69-7.75]; I=40%), respectively. The pooled risk of symptomatic intracranial hemorrhage in tenecteplase-treated patients, including comparative and noncomparative studies, was 0.99% ([95% CI, 0%-3.49%]; I=0%, 7 studies), 1.69% ([95% CI, 1.14%-2.32%]; I=1%, 23 studies), and 4.19% ([95% CI, 1.92%-7.11%]; I=52%, 5 studies) within the low-, medium-, and high-dose groups. The risks of any intracranial hemorrhage, mortality, and other studied outcomes were comparable between the 2 agents.
CONCLUSIONS
Across medium- and low-dose tiers, the risks of complications were generally comparable between those treated with tenecteplase versus alteplase for acute ischemic stroke.
Topics: Humans; Tissue Plasminogen Activator; Tenecteplase; Fibrinolytic Agents; Ischemic Stroke; Prospective Studies; Retrospective Studies; Stroke; Intracranial Hemorrhages; Treatment Outcome; Brain Ischemia
PubMed: 36951049
DOI: 10.1161/STROKEAHA.122.042335 -
Journal of Gastrointestinal and Liver... Jun 2022Several studies have investigated the role of multiple proteins in nonalcoholic fatty liver disease (NAFLD); one that has recently gained attention is plasminogen... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Several studies have investigated the role of multiple proteins in nonalcoholic fatty liver disease (NAFLD); one that has recently gained attention is plasminogen activator inhibitor-1 (PAI-1). However, studies evaluating PAI-1 levels in NAFLD demonstrated conflicting results. Our objective was to understand the role of PAI-1 in NAFLD more clearly by carrying out a systematic review and meta-analysis.
METHODS
We gathered evidence by performing a systematic search on PubMed, EMBASE, and Cochrane Library, through using a predefined search string. The included studies diagnosed NAFLD through either liver biopsy, ultrasonography, computed tomography (CT), magnetic resonance spectroscopy, or using one of the latter methods with blood parameters. Studies had to fulfill predefined inclusion and exclusion criteria. To assess the quality of the studies included, we used the NHLBI quality assessment tools. The main summary outcome was the mean difference (MD) in serum PAI-1 levels reported as ng/mL Results: 33 articles involving 10,840 subjects fulfilled our inclusion criteria and were systematically reviewed. 11 studies were included in our meta-analyses. We found a significant MD in PAI-1 levels in NAFLD patients vs. controls [17.147 (95%CI: 7.720-26.574)]. Moreover, subgroup analysis evaluating PAI-1 levels in biopsy- proven NAFLD vs. controls remained significant [24.086 (95%CI: 3.812-44.361)], as well as in CT-diagnosed NAFLD [15.523 (95%CI: 7.163-23.883)]. However, no significant MD in PAI-1 levels was found in ultrasound- diagnosed NAFLD patients vs. controls [10.394 (95%CI: -13.335-34.123)]. No significant MD in PAI-1 levels in NASH patients vs. controls was observed [26.835 (95%CI: -0.879-54.549)].
CONCLUSIONS
In summary, elevated serum PAI-1 levels are associated with adult NAFLD (biopsy-proven and CT-diagnosed). However, no significant difference was found in ultrasound-diagnosed NAFLD and NASH patients. Nonetheless, the included studies have methodological variance, dictating that the obtained results should be carefully interpreted.
Topics: Adult; Biopsy; Humans; Non-alcoholic Fatty Liver Disease; Plasminogen Activator Inhibitor 1
PubMed: 35574617
DOI: 10.15403/jgld-4091 -
Lancet (London, England) Jun 2012Recombinant tissue plasminogen activator (rt-PA, alteplase) improved functional outcome in patients treated soon after acute ischaemic stroke in randomised trials, but... (Review)
Review
BACKGROUND
Recombinant tissue plasminogen activator (rt-PA, alteplase) improved functional outcome in patients treated soon after acute ischaemic stroke in randomised trials, but licensing is restrictive and use varies widely. The IST-3 trial adds substantial new data. We therefore assessed all the evidence from randomised trials for rt-PA in acute ischaemic stroke in an updated systematic review and meta-analysis.
METHODS
We searched for randomised trials of intravenous rt-PA versus control given within 6 h of onset of acute ischaemic stroke up to March 30, 2012. We estimated summary odds ratios (ORs) and 95% CI in the primary analysis for prespecified outcomes within 7 days and at the final follow-up of all patients treated up to 6 h after stroke.
FINDINGS
In up to 12 trials (7012 patients), rt-PA given within 6 h of stroke significantly increased the odds of being alive and independent (modified Rankin Scale, mRS 0-2) at final follow-up (1611/3483 [46·3%] vs 1434/3404 [42·1%], OR 1·17, 95% CI 1·06-1·29; p=0·001), absolute increase of 42 (19-66) per 1000 people treated, and favourable outcome (mRS 0-1) absolute increase of 55 (95% CI 33-77) per 1000. The benefit of rt-PA was greatest in patients treated within 3 h (mRS 0-2, 365/896 [40·7%] vs 280/883 [31·7%], 1·53, 1·26-1·86, p<0·0001), absolute benefit of 90 (46-135) per 1000 people treated, and mRS 0-1 (283/896 [31·6%] vs 202/883 [22·9%], 1·61, 1·30-1·90; p<0·0001), absolute benefit 87 (46-128) per 1000 treated. Numbers of deaths within 7 days were increased (250/2807 [8·9%] vs 174/2728 [6·4%], 1·44, 1·18-1·76; p=0·0003), but by final follow-up the excess was no longer significant (679/3548 [19·1%] vs 640/3464 [18·5%], 1·06, 0·94-1·20; p=0·33). Symptomatic intracranial haemorrhage (272/3548 [7·7%] vs 63/3463 [1·8%], 3·72, 2·98-4·64; p<0·0001) accounted for most of the early excess deaths. Patients older than 80 years achieved similar benefit to those aged 80 years or younger, particularly when treated early.
INTERPRETATION
The evidence indicates that intravenous rt-PA increased the proportion of patients who were alive with favourable outcome and alive and independent at final follow-up. The data strengthen previous evidence to treat patients as early as possible after acute ischaemic stroke, although some patients might benefit up to 6 h after stroke.
FUNDING
UK Medical Research Council, Stroke Association, University of Edinburgh, National Health Service Health Technology Assessment Programme, Swedish Heart-Lung Fund, AFA Insurances Stockholm (Arbetsmarknadens Partners Forsakringsbolag), Karolinska Institute, Marianne and Marcus Wallenberg Foundation, Research Council of Norway, Oslo University Hospital.
Topics: Brain Ischemia; Fibrinolytic Agents; Humans; Randomized Controlled Trials as Topic; Recombinant Proteins; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 22632907
DOI: 10.1016/S0140-6736(12)60738-7 -
Journal of the American Society of... Sep 2022Sensitive and specific biomarkers are needed to provide better biologic insight into the risk of incident and progressive CKD. However, studies have been limited by... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sensitive and specific biomarkers are needed to provide better biologic insight into the risk of incident and progressive CKD. However, studies have been limited by sample size and design heterogeneity.
METHODS
In this assessment of the prognostic value of preclinical plasma and urine biomarkers for CKD outcomes, we searched Embase (Ovid), MEDLINE ALL (Ovid), and Scopus up to November 30, 2020, for studies exploring the association between baseline kidney biomarkers and CKD outcomes (incident CKD, CKD progression, or incident ESKD). We used random-effects meta-analysis.
RESULTS
After screening 26,456 abstracts and 352 full-text articles, we included 129 studies in the meta-analysis for the most frequently studied plasma biomarkers (TNFR1, FGF23, TNFR2, KIM-1, suPAR, and others) and urine biomarkers (KIM-1, NGAL, and others). For the most frequently studied plasma biomarkers, pooled RRs for CKD outcomes were 2.17 (95% confidence interval [95% CI], 1.91 to 2.47) for TNFR1 (31 studies); 1.21 (95% CI, 1.15 to 1.28) for FGF-23 (30 studies); 2.07 (95% CI, 1.82 to 2.34) for TNFR2 (23 studies); 1.51 (95% CI, 1.38 to 1.66) for KIM-1 (18 studies); and 1.42 (95% CI, 1.30 to 1.55) for suPAR (12 studies). For the most frequently studied urine biomarkers, pooled RRs were 1.10 (95% CI, 1.05 to 1.16) for KIM-1 (19 studies) and 1.12 (95% CI, 1.06 to 1.19) for NGAL (19 studies).
CONCLUSIONS
Studies of preclinical biomarkers for CKD outcomes have considerable heterogeneity across study cohorts and designs, limiting comparisons of prognostic performance across studies. Plasma TNFR1, FGF23, TNFR2, KIM-1, and suPAR were among the most frequently investigated in the setting of CKD outcomes.
Topics: Humans; Lipocalin-2; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Renal Insufficiency, Chronic; Receptors, Urokinase Plasminogen Activator; Biomarkers
PubMed: 35858701
DOI: 10.1681/ASN.2022010098 -
Thrombosis Journal May 2024We conducted this systematic review and meta-analysis to better understand the association between rs1799762 PAI-1 gene polymorphism and the risk of RPL. (Review)
Review
BACKGROUND
We conducted this systematic review and meta-analysis to better understand the association between rs1799762 PAI-1 gene polymorphism and the risk of RPL.
METHODS
A systematic search for studies that assessed the association between PAI-1 4G/5G polymorphism and RPL risk published in search sources, PubMed/Medline, ISI Web of Knowledge, Scopus, and Google Scholar till January 2024 was conducted.
RESULTS
There were 23 case-control studies in total, with a high degree of statistical heterogeneity among them which indicated the need for subgroup analysis. We found a significant positive association between the risk of RPL and 4G/4G PAI-1 (OR: 2.57; 95% CI: 1.69-3.90), likewise 4G/5G (OR: 2/02 95% CI: 1.39-2.92) and mixed genotype (4G/4G+4G/5G) (OR: 2.31 95% CI: 1.81-2.93). Considering the ethnicity, the 4G/4G polymorphism is significantly associated with Asian descent (OR: 2.10; CI: 1.65-2.69) while the strong association (OR: 6.47; CI: 3.23-12.97) observed in the Greater Middle East descent is not statistically significant (P=0.16). PAI-1 4G/5G polymorphism association with RPL was only significant in Greater Middle East descent (OR: 2.93; CI: 2.41-3.56), and mixed genotype was significantly associated with RPL in Asian (OR: 2.37; CI: 1.55-3.61), Greater Middle East (OR: 3.01; CI: 2.16-4.19), and European populations (OR: 1.38; CI: 0.91-2.10). The association between RPL and PAI-1 4G/4G was significant for RPLs both under 12 weeks (OR: 1.82; 95% CI: 1.34-2.47), and under 24 weeks (OR: 1.46; 95% CI: 1.11-1.92), while considering heterozygote form the association was only significant for RPLs under 24 weeks (OR: 1.91; 95% CI: 1.58-2.31). Regarding the mixed genotype, there is a significant positive association between PAI-1 and RPL for RPLs under 12 weeks (OR: 2.09; 95% CI: 1.49-2.93), and under 24 weeks (OR: 2.10; 95% CI: 1.52-2.92).
CONCLUSIONS
Our findings indicate a significant association between the rs1799762 PAI-1 polymorphism and the risk of RPL.
PubMed: 38807142
DOI: 10.1186/s12959-024-00612-9