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PloS One 2015Lifespan and the proportion of older people in the population are increasing, with far reaching consequences for the social, political and economic landscape. Unless... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lifespan and the proportion of older people in the population are increasing, with far reaching consequences for the social, political and economic landscape. Unless accompanied by an increase in health span, increases in age-related diseases will increase the burden on health care resources. Intervention studies to enhance healthy ageing need appropriate outcome measures, such as blood-borne biomarkers, which are easily obtainable, cost-effective, and widely accepted. To date there have been no systematic reviews of blood-borne biomarkers of mortality.
AIM
To conduct a systematic review to identify available blood-borne biomarkers of mortality that can be used to predict healthy ageing post-retirement.
METHODS
Four databases (Medline, Embase, Scopus, Web of Science) were searched. We included prospective cohort studies with a minimum of two years follow up and data available for participants with a mean age of 50 to 75 years at baseline.
RESULTS
From a total of 11,555 studies identified in initial searches, 23 fulfilled the inclusion criteria. Fifty-one blood borne biomarkers potentially predictive of mortality risk were identified. In total, 20 biomarkers were associated with mortality risk. Meta-analyses of mortality risk showed significant associations with C-reactive protein (Hazard ratios for all-cause mortality 1.42, p<0.001; Cancer-mortality 1.62, p<0.009; CVD-mortality 1.31, p = 0.033), N Terminal-pro brain natriuretic peptide (Hazard ratios for all-cause mortality 1.43, p<0.001; CHD-mortality 1.58, p<0.001; CVD-mortality 1.67, p<0.001) and white blood cell count (Hazard ratios for all-cause mortality 1.36, p = 0.001). There was also evidence that brain natriuretic peptide, cholesterol fractions, erythrocyte sedimentation rate, fibrinogen, granulocytes, homocysteine, intercellular adhesion molecule-1, neutrophils, osteoprotegerin, procollagen type III aminoterminal peptide, serum uric acid, soluble urokinase plasminogen activator receptor, tissue inhibitor of metalloproteinases 1 and tumour necrosis factor receptor II may predict mortality risk. There was equivocal evidence for the utility of 14 biomarkers and no association with mortality risk for CD40 ligand, cortisol, dehydroepiandrosterone, ferritin, haemoglobin, interleukin-12, monocyte chemoattractant protein 1, matrix metalloproteinase 9, myelopereoxidase, P-selectin, receptor activator of nuclear factor KappaB ligand, sex hormone binding globulin, testosterone, transferrin, and thyroid stimulating hormone and thyroxine.
CONCLUSIONS
Twenty biomarkers should be prioritised as potential predictors of mortality in future studies. More studies using standardised protocols and reporting methods, and which focus on mortality rather than risk of disease or health status as an outcome, are needed.
Topics: Aged; Biomarkers; Cardiovascular Diseases; Cohort Studies; Female; Humans; Longevity; MEDLINE; Male; Middle Aged; Neoplasms
PubMed: 26039142
DOI: 10.1371/journal.pone.0127550 -
Neurologia Medico-chirurgica 2013Ischemic stroke is uncommon during pregnancy, but decision making for acute revascularization therapy including intravenous recombinant tissue plasminogen activator... (Review)
Review
Ischemic stroke is uncommon during pregnancy, but decision making for acute revascularization therapy including intravenous recombinant tissue plasminogen activator (rt-PA) is difficult. The use of rt-PA remains controversial, but a systematic review of 16 patients (mean age 31.7 years) showed good results for both maternal (77.8%) and fetal (56.3%) outcomes. Pregnancy alone is not a solid contraindication for acute revascularization therapy including rt-PA. An endovascular approach might be beneficial for reducing the hemorrhagic complication; however, the treatment strategy should be considered based on the available treatment facility. Close cooperation with obstetrics is essential for the successful management of saving the lives of both the mother and the fetus.
Topics: Cerebral Infarction; Cerebral Revascularization; Contraindications; Cooperative Behavior; Female; Humans; Infant, Newborn; Interdisciplinary Communication; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 23979048
DOI: 10.2176/nmc.53.531 -
European Journal of Medical Research Feb 2023At the end of 2021, the European Medicines Agency (EMA) expanded its approval for the recombinant human interleukin-1 (IL-1) receptor antagonist Anakinra for the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
At the end of 2021, the European Medicines Agency (EMA) expanded its approval for the recombinant human interleukin-1 (IL-1) receptor antagonist Anakinra for the treatment of COVID-19 patients with elevated soluble urokinase plasminogen activator receptor (suPAR). However, the role of Anakinra in COVID-19 remains unanswered, especially in patients receiving different forms of respiratory support. Therefore, the objective of this systematic review is to assess the safety and effects of Anakinra compared to placebo or standard care alone on clinical outcomes in adult hospitalized patients with SARS-CoV-2 infection.
METHODS
We searched the Cochrane COVID-19 Study Register (comprising MEDLINE, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, medRxiv, and the Cochrane Central Register of Controlled Trials (CCSR)) and the WHO COVID-19 Global literature on coronavirus disease database to identify completed and ongoing studies from inception of each database to December 13, 2021. Since then, we monitored new published studies weekly up to June 30, 2022 using the CCSR. We included RCTs comparing treatment with Anakinra to placebo or standard care alone in adult hospitalized patients with SARS-CoV-2 infection.
RESULTS
We included five RCTs with 1,627 patients (n = 888, n = 739, mean age 59.63 years, 64% male). Random-effects meta-analysis was used to pool data. We found that Anakinra makes little or no difference to all-cause mortality at up to day 28 compared to placebo or standard care alone (RR 0.96, 95% CI 0.64-1.45; RD 9 fewer per 1000, 95% CI 84 fewer to 104 more; 4 studies, 1593 participants; I = 49%; low certainty of evidence).
CONCLUSIONS
Anakinra has no effect on adult hospitalized patients with SARS-CoV-2 infection regarding mortality, clinical improvement and worsening as well as on safety outcomes compared to placebo or standard care alone.
TRIAL REGISTRATION
PROSPERO Registration Number: CRD42021257552.
Topics: Adult; Humans; Male; Middle Aged; Female; COVID-19; Interleukin 1 Receptor Antagonist Protein; SARS-CoV-2
PubMed: 36841793
DOI: 10.1186/s40001-023-01072-z -
Biomedicines Jun 2022Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic... (Review)
Review
Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic cancer. Identifying non-invasive markers for their early distinction is of utmost importance to avoid unnecessary surgery or a delay in steroid therapy. Thus, this systematic review was conducted to revisit all current evidence on the clinical utility of different serum biomarkers in diagnosing AIP, distinguishing AIP from pancreatic cancer, and predicting disease course, steroid therapy response, and relapse. A systematic review was performed for articles published up to August 2021 by searching electronic databases such as MEDLINE, Web of Science, and EMBASE. Among 5123 identified records, 92 studies were included in the qualitative synthesis. Apart from immunoglobulin (Ig) G4, which was by far the most studied biomarker, we identified autoantibodies against the following: lactoferrin, carboanhydrase II, plasminogen-binding protein, amylase-α2A, cationic (PRSS1) and anionic (PRSS2) trypsinogens, pancreatic secretory trypsin inhibitor (PSTI/SPINK1), and type IV collagen. The identified novel autoantigens were laminin 511, annexin A11, HSP-10, and prohibitin. Other biomarkers included cytokines, decreased complement levels, circulating immune complexes, -glycan profile changes, aberrant miRNAs expression, decreased IgA and IgM levels, increased IgE levels and/or peripheral eosinophil count, and changes in apolipoprotein isoforms levels. To our knowledge, this is the first systematic review that addresses biomarkers in AIP. Evolving research has recognized numerous biomarkers that could help elucidate the pathophysiological mechanisms of AIP, bringing us closer to AIP diagnosis and its preoperative distinction from pancreatic cancer.
PubMed: 35884816
DOI: 10.3390/biomedicines10071511 -
Journal of Cerebral Blood Flow and... Sep 2012Animal models have been developed to simulate angiographic vasospasm secondary to subarachnoid hemorrhage (SAH) and to test pharmacologic treatments. Our aim was to... (Meta-Analysis)
Meta-Analysis Review
Animal models have been developed to simulate angiographic vasospasm secondary to subarachnoid hemorrhage (SAH) and to test pharmacologic treatments. Our aim was to evaluate the effect of pharmacologic treatments that have been tested in humans and in preclinical studies to determine if animal models inform results reported in humans. A systematic review and meta-analysis of SAH studies was performed. We investigated predictors of translation from animals to humans with multivariate logistic regression. Pharmacologic reduction of vasospasm was effective in mice, rats, rabbits, dogs, nonhuman primates (standard mean difference of -1.74; 95% confidence interval -2.04 to -1.44) and humans. Animal studies were generally of poor methodologic quality and there was evidence of publication bias. Subgroup analysis by drug and species showed that statins, tissue plasminogen activator, erythropoietin, endothelin receptor antagonists, calcium channel antagonists, fasudil, and tirilazad were effective whereas magnesium was not. Only evaluation of vasospasm >3 days after SAH was independently associated with successful translation. We conclude that reduction of vasospasm is effective in animals and humans and that evaluation of vasospasm >3 days after SAH may be preferable for preclinical models.
Topics: Animals; Cerebral Angiography; Data Interpretation, Statistical; Disease Models, Animal; Dogs; Female; Humans; Macaca; Male; Mice; Publication Bias; Rabbits; Randomized Controlled Trials as Topic; Rats; Species Specificity; Subarachnoid Hemorrhage; Treatment Outcome; Vasospasm, Intracranial
PubMed: 22534672
DOI: 10.1038/jcbfm.2012.57 -
Cerebrovascular Diseases (Basel,... 2014The cause of cerebral small vessel disease is not fully understood, yet it is important, accounting for about 25% of all strokes. It also increases the risk of having... (Meta-Analysis)
Meta-Analysis Review
Blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-lacunar stroke and non-stroke: systematic review and meta-analysis.
BACKGROUND
The cause of cerebral small vessel disease is not fully understood, yet it is important, accounting for about 25% of all strokes. It also increases the risk of having another stroke and contributes to about 40% of dementias. Various processes have been implicated, including microatheroma, endothelial dysfunction and inflammation. A previous review investigated endothelial dysfunction in lacunar stroke versus mostly non-stroke controls while another looked at markers of inflammation and endothelial damage in ischaemic stroke in general. We have focused on blood markers between clinically evident lacunar stroke and other subtypes of ischaemic stroke, thereby controlling for stroke in general.
SUMMARY
We systematically assessed the literature for studies comparing blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-stroke controls or other ischaemic stroke subtypes. We assessed the quality of included papers and meta-analysed results. We split the analysis on time of blood draw in relation to the stroke. We identified 1,468 full papers of which 42 were eligible for inclusion, including 4,816 ischaemic strokes, of which 2,196 were lacunar and 2,500 non-stroke controls. Most studies subtyped stroke using TOAST. The definition of lacunar stroke varied between studies. Markers of coagulation/fibrinolysis (tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), fibrinogen, D-dimer) were higher in lacunar stroke versus non-stroke although fibrinogen was no different to non-stroke in the acute phase. tPA and PAI were no different between lacunar and non-lacunar stroke. Fibrinogen and D-dimer were significantly lower in lacunar stroke compared to other ischaemic strokes, both acutely and chronically. Markers of endothelial dysfunction (homocysteine, von Willebrand Factor (vWF), E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM), vascular cellular adhesion molecule-1 (VCAM)) were higher or had insufficient or conflicting data (P-selectin, VCAM) in lacunar stroke versus non-stroke. Compared to other ischaemic stroke subtypes, homocysteine did not differ in lacunar stroke while vWF was significantly lower in lacunar stroke acutely [atherothrombotic standardized mean difference, SMD, -0.34 (-0.61, -0.08); cardioembolic SMD -0.38 (-0.62, -0.14)], with insufficient data chronically. Markers of inflammation (C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6)) were higher in lacunar stroke versus non-stroke, although there were no studies measuring TNF-α chronically and the sole study measuring IL-6 chronically showed no difference between lacunar stroke and non-stroke. Compared to other ischaemic stroke subtypes, there was no difference (CRP) or insufficient or conflicting data (TNF-α) to lacunar stroke. IL-6 was significantly lower [atherothrombotic SMD -0.37 (-0.63, -0.10); cardioembolic SMD -0.52 (-0.82, -0.22)] in lacunar stroke acutely, with insufficient data chronically.
KEY MESSAGES
Lacunar stroke is an important stroke subtype. More studies comparing lacunar stroke to non-lacunar stroke specifically, rather than to non-stroke controls, are needed. Prospective studies with measurements taken well after the acute event are more likely to be helpful in determining pathogenesis. The available data in this review were limited and do not exclude the possibility that peripheral inflammatory processes including endothelial dysfunction are associated with lacunar stroke and cerebral small vessel disease.
Topics: Biomarkers; Blood Coagulation; Blood Proteins; Brain Ischemia; Cell Adhesion Molecules; Cytokines; Endothelium, Vascular; Fibrinolysis; Homocysteine; Humans; Inflammation; Stroke; Stroke, Lacunar
PubMed: 24401164
DOI: 10.1159/000356789 -
Neurology May 2023The safety and efficacy of tenecteplase (TNK) in patients with tandem lesion (TL) stroke is unknown. We performed a comparative analysis of TNK and alteplase in patients... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
The safety and efficacy of tenecteplase (TNK) in patients with tandem lesion (TL) stroke is unknown. We performed a comparative analysis of TNK and alteplase in patients with TLs.
METHODS
We first compared the treatment effect of TNK and alteplase in patients with TLs using individual patient data from the EXTEND-IA TNK trials. We evaluated intracranial reperfusion at initial angiographic assessment and 90-day modified Rankin scale (mRS) with ordinal logistic and Firth regression models. Because 2 key outcomes, mortality and symptomatic intracranial hemorrhage (sICH), were few in number among those who received alteplase in the EXTEND-IA TNK trials, we generated pooled estimates for these outcomes by supplementing trial data with estimates of incidence obtained through a meta-analysis of studies identified in a systematic review. We then calculated unadjusted risk differences to compare the pooled estimates for those receiving alteplase with the incidence observed in the trial among those receiving TNK.
RESULTS
Seventy-one of 483 patients (15%) in the EXTEND-IA TNK trials possessed a TL. In patients with TLs, intracranial reperfusion was observed in 11/56 (20%) of TNK-treated patients vs 1/15 (7%) alteplase-treated patients (adjusted odds ratio 2.19; 95% CI 0.28-17.29). No significant difference in 90-day mRS was observed (adjusted common odds ratio 1.48; 95% CI 0.44-5.00). A pooled study-level proportion of alteplase-associated mortality and sICH was 0.14 (95% CI 0.08-0.21) and 0.09 (95% CI 0.04-0.16), respectively. Compared with a mortality rate of 0.09 (95% CI 0.03-0.20) and an sICH rate of 0.07 (95% CI 0.02-0.17) in TNK-treated patients, no significant difference was observed.
DISCUSSION
Functional outcomes, mortality, and sICH did not significantly differ between patients with TLs treated with TNK and those treated with alteplase.
CLASSIFICATION OF EVIDENCE
This study provides Class III evidence that TNK is associated with similar rates of intracranial reperfusion, functional outcome, mortality, and sICH compared with alteplase in patients with acute stroke due to TLs. However, the CIs do not rule out clinically important differences. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov/ct2/show/NCT02388061; clinicaltrials.gov/ct2/show/NCT03340493.
Topics: Humans; Tissue Plasminogen Activator; Tenecteplase; Fibrinolytic Agents; Treatment Outcome; Stroke; Intracranial Hemorrhages; Brain Ischemia
PubMed: 36878701
DOI: 10.1212/WNL.0000000000207138 -
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 -
Journal of the Neurological Sciences Sep 2020Accumulating clinical evidence has indicated that sonothrombolysis can aid in the treatment of ischemic stroke; however, these findings remain controversial. The purpose... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Accumulating clinical evidence has indicated that sonothrombolysis can aid in the treatment of ischemic stroke; however, these findings remain controversial. The purpose of the present meta-analysis was to assess randomized clinical studies concerning the effects of sonothrombolysis on ischemic stroke to evaluate its safety and efficacy.
METHODS
We systematically searched the Cochrane Library, PubMed, and EMBASE databases for literature published between the inception of electronic data and May 2019 regarding sonothrombolysis for acute ischemic stroke. Only randomized controlled trials were included. Data extraction was based on patient characteristics, ultrasound variables (any duration or frequency, without microbubble), and outcome variables (safety and efficacy).
RESULTS
Five trials were included in the present study. Clinical functional recovery was evaluated at different time points (several days or 3 months), and heterogeneity was low. Sonothrombolysis did not lead to an increase in symptomatic intracranial hemorrhagic complications or death. Our results demonstrated that patients treated with sonothrombolysis had significantly higher rates of recanalization and asymptomatic intracerebral hemorrhage than patients treated with intravenous thrombolysis alone. In the subgroup of middle cerebral artery (MCA) occlusion patients, sonothrombolysis was found to greatly increase the efficacy outcomes compared to intravenous thrombolysis.
CONCLUSIONS
Evidence suggests that sonothrombolysis is a technically feasible and potentially effective treatment that has beneficial effects on recanalization and increases the rate of asymptomatic intracerebral hemorrhage in stroke patients. Additionally, short- and long-term clinical outcome analyses were improved in the MCA occlusion sonothrombolysis subgroup. Larger clinical trials of MCA occlusion patients are necessary to verify these findings.
Topics: Brain Ischemia; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Ischemic Stroke; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 32623143
DOI: 10.1016/j.jns.2020.116998 -
Current Problems in Cardiology Oct 2023Twelve CCI patients were studied with confirmed or suspected COVID-19 infection. The majority of these patients were males (83.3%) with a median age of 55 years from... (Review)
Review
Twelve CCI patients were studied with confirmed or suspected COVID-19 infection. The majority of these patients were males (83.3%) with a median age of 55 years from three geographical locations, constituting the Middle East (7), Spain (3), and the USA (1). In 6 patients, IgG/IgM was positive for COVID-19, 4 with high pretest probability and 2 with positive RT-PCR. Type 2 DM, hyperlipidemia, and smoking were the primary risk factors. Right-sided neurological impairments and verbal impairment were the most common symptoms. Our analysis found 8 (66%) synchronous occurrences. In 58.3% of cases, neuroimaging showed left Middle Cerebral Artery (MCA) infarct and 33.3% right. Carotid artery thrombosis (16.6%), tandem occlusion (8.3%), and carotid stenosis (1%) were also reported in imaging. Dual antiplatelet therapy (DAPT) and anticoagulants were conservative therapies (10). Two AMI patients had aspiration thrombectomy, while three AIS patients had intravenous thrombolysis/tissue plasminogen activator (IVT-tPA), 2 had mechanical thrombectomy (MT), and 1 had decompressive craniotomy. Five had COVID-19-positive chest X-rays, whereas 4 were normal. four of 8 STEMI and 3 NSTEMI/UA patients complained chest pain. LV, ICA, and pulmonary embolism were further complications (2). Upon discharge, 7 patients (70%) had residual deficits while 1 patient unfortunately died.
Topics: Female; Humans; Male; Middle Aged; Anticoagulants; COVID-19; Infarction, Middle Cerebral Artery; Stroke; Thrombectomy; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome; Case Reports as Topic
PubMed: 37209804
DOI: 10.1016/j.cpcardiol.2023.101814