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Osteoarthritis and Cartilage May 2019This study was design to examine the diagnostic performance of cartilage oligomeric matrix protein (COMP), C-terminal cross-linking telopeptide of type II collagen... (Meta-Analysis)
Meta-Analysis
Cartilage oligomeric matrix protein, C-terminal cross-linking telopeptide of type II collagen, and matrix metalloproteinase-3 as biomarkers for knee and hip osteoarthritis (OA) diagnosis: a systematic review and meta-analysis.
OBJECTIVE
This study was design to examine the diagnostic performance of cartilage oligomeric matrix protein (COMP), C-terminal cross-linking telopeptide of type II collagen (CTX-II), and matrix metalloproteinase-3 (MMP-3) as biomarker for knee and hip OA.
METHODS
Systematic search on multiple databases was completed in January 2018 using certain keywords. COMP, CTX-II, MMP-3 levels in knee and hip OA patients and healthy individuals were collected and calculated. Differences between subgroups were expressed as standardized mean differences (SMD). Subgroup analyses were performed to compare COMP, CTX-II, and MMP-3 performance between measuring sources, genders, large and small sample size and diagnostic criteria for OA patients.
RESULTS
A moderate performance of COMP in distinguishing between knee (SMD: 0.68; 95% confidence intervals (CI): 0.43-0.93; P < 0.0001) or hip (SMD: 0.25; 95% CI, 0.10, 0.40; P = 0.0008) OA patients and controls were found. CTX-II showed a moderated standardised mean differences (SMD) of 0.48 (95% CI, 0.32, 0.64; P < 0.0001) in the detection of knee OA and a large SMD of 0.76 (95% CI, 0.09, 1.42; P = 0.03) in diagnosing hip OA. A small SMD of 0.32 (95% CI, -0.03, 0.67; P = 0.07) was found for MMP-3 performance and the results did not reach statistic significance. Progression study revealed potential effectiveness of serum COMP in predicting OA progression. Subgroup analysis showed that serum COMP and urinary CTX-II performed better in male than female. Study size and diagnostic criteria did not significantly influence the pooled SMD, but they might be the sources of heterogeneity among studies.
CONCLUSION
The overall results indicates that serum COMP and urinary CTX-II can distinguish between knee or hip OA patients and control subjects. Serum COMP is effective in predicting OA progression.Further researches with rigorous study design and a larger sample size are required to validate our findings.
Topics: Biomarkers; Cartilage Oligomeric Matrix Protein; Collagen Type II; Humans; Matrix Metalloproteinase 3; Osteoarthritis, Hip; Osteoarthritis, Knee; Peptide Fragments; Prognosis
PubMed: 30391538
DOI: 10.1016/j.joca.2018.10.009 -
Cureus Apr 2020Cerebral venous sinus thrombosis (CVST) is a rare condition characterized by elevated intracranial pressure due to impaired cerebral venous drainage, potentially... (Review)
Review
Cerebral venous sinus thrombosis (CVST) is a rare condition characterized by elevated intracranial pressure due to impaired cerebral venous drainage, potentially leading to life-threatening consequences. We searched the PubMed electronic database for 'cerebral venous sinus thrombosis' and 'prothrombotic' cases reported in adults (19+ years) and conducted a systematic review for the published literature in the English language pooled with a case from our institution. Data were analyzed regarding patient demographics, risk factors, clinical features, treatment modalities, and outcomes when available. Thirty cases of CVST were identified (29 case reports, of whom two were described in a case series, and the one case from our institution). The patients' mean age was 39 years (range: 19 - 65). The male: female ratio was 1.14:1. The majority (73.3%) had at least one preexisting risk factor, with prescription drug use being the most common risk factor (33.3%) shared among all patients. Most patients (83.3%) presented with at least two symptoms. The most common presenting symptoms were headache (70%), gastrointestinal disturbance (50%), and seizures (40%). Focal deficits (36.7%), vision disturbances (30%), and altered consciousness (20%) were the remaining presenting complaints. Twelve cases (40%) commented on papilledema, with 10 (83.3%) having papilledema present. Anticoagulation abnormalities were examined in 26 cases (86.7%), out of which four cases (15.4%) had isolated protein S (PS) deficiency, three cases (11.5%) had isolated antithrombin III (ATIII) deficiency, and one case (3.8%) had isolated protein C (PC) deficiency. The most common initial imaging modality (22 cases, 73.3%), and most commonly used overall (23 cases, 76.7%), was computed tomography (CT). Magnetic resonance imaging (MRI) was the second most common imaging modality for initial use (five cases, 16.7%), diagnosis or confirmation of CVST (eight cases, 26.7%), and overall (21 cases, 70%). Heparin treatment was involved in the treatment of 18 cases (60%), and warfarin treatment was used in 10 cases (33.3%). Heparin-warfarin combination treatment was utilized in eight cases (26.7%). Most patients survived (28 cases, 93.3%), while the two remaining patients died secondary to brain death from the CVST (6.7%). The findings from this study highlight the clinical characteristics of CVST. Therefore, this study aims to increase awareness of this rare entity. Physicians should maintain a high index of suspicion in order to diagnose patients presenting in the proper clinical context, given this case shares various forms of presentations with other common clinical conditions but requires long-term anticoagulation.
PubMed: 32411555
DOI: 10.7759/cureus.7654 -
Annals of Translational Medicine Nov 2017Pneumonia, inhalation trauma and acute respiratory distress syndrome (ARDS), typical causes of lung injury in critically ill patients, are all three characterized by... (Review)
Review
Pneumonia, inhalation trauma and acute respiratory distress syndrome (ARDS), typical causes of lung injury in critically ill patients, are all three characterized by dysregulated inflammation and coagulation in the lungs. Nebulized anticoagulants are thought to have beneficial effects as they could attenuate pulmonary coagulopathy and maybe even affect pulmonary inflammation. A systematic search of the medical literature was performed using terms referring to aspects of the condition ('pneumonia', 'inhalation trauma' and 'ARDS'), the intervention ('nebulized', 'vaporized', and 'aerosolized') and anticoagulants limited to agents that are commercially available and frequently given or tested in critically ill patients ['heparin', 'danaparoid', 'activated protein C' (APC), 'antithrombin' (AT) and 'tissue factor pathway inhibitor' (TFPI)]. The systematic search identified 16 articles reporting on preclinical studies and 11 articles reporting on human trials. All nebulized anticoagulants attenuate pulmonary coagulopathy in preclinical studies using various models for lung injury, but the effects on inflammation are less consistent. Nebulized heparin, danaparoid and TFPI, but not APC and AT also reduced systemic coagulation. Nebulized heparin in lung injury patients shows contradictory results, and there is concern over systemic side effects of this strategy. Future studies need to focus on the way to nebulize anticoagulants, as well as on efficient but safe dosages, and other side effects.
PubMed: 29264361
DOI: 10.21037/atm.2017.08.23 -
Thrombosis and Haemostasis Jun 2017Data on paediatric pulmonary embolism (PE) are scarce. We sought to systematically review the current literature on childhood PE and conducted a search on paediatric PE... (Review)
Review
Data on paediatric pulmonary embolism (PE) are scarce. We sought to systematically review the current literature on childhood PE and conducted a search on paediatric PE via PubMed (1946-2013) and Embase (1980-2013). There was significant heterogeneity in reported data. Two patterns were noted: classic thromboembolic PE (TE-PE) and in situ pulmonary artery thrombosis (ISPAT). Mean age of presentation for TE-PE was 14.86 years, and 51 % of cases were males. The commonest method for diagnosis of TE-PE was contrast CT with angiography (74 % of patients). The diagnosis of TE-PE was often delayed. Although 85 % of children with TE-PE had an elevated D-dimer at presentation, it was non-discriminatory for the diagnosis. In paediatric TE-PE, the prevalence of central venous catheters was 23 %, immobilisation 38 %, systemic infection 31 % and obesity 13 %, elevated Factor VIII or von Willebrand factor levels 27 %, Protein C deficiency 17 %, Factor V Leiden 14 % and Protein S deficiency 7 %. In patients with TE-PE, pharmacologic thrombolysis was used in 29 %; unfractionated heparin was the most common initial anticoagulant treatment in 64 % and low-molecular-weight heparins the most common follow-up treatment in 83 %. Duration of anticoagulant therapy was variable and death was reported in 26 % of TE-PE patients. In contrast to TE-PE, patients with ISPAT were not investigated systematically for presence of thrombophilia, had more surgical interventions as the initial management and were often treated with anti-platelet medications. This review summarises important data and identifies gaps in the knowledge of paediatric PE, which may help to design future studies.
Topics: Adolescent; Angiography; Anticoagulants; Comorbidity; Female; Heparin; Humans; Male; Pneumoradiography; Prevalence; Pulmonary Artery; Pulmonary Embolism; Survival Analysis; Thromboembolism; Thrombosis
PubMed: 28331932
DOI: 10.1160/TH16-07-0529 -
Medicine Mar 2017Methotrexate (MTX) is widely used and considered a first-line disease modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). However, 10%... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Methotrexate (MTX) is widely used and considered a first-line disease modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). However, 10% to 30% of patients discontinue therapy within a year of starting the treatment, usually because of undesirable side effects. Many of the relevant genes have been investigated to estimate the association between gene polymorphisms and MTX toxicity in RA patients, although inconsistent results have been reported.
METHODS
We searched EMBASE and PubMed in February 2016 for polymorphisms and pharmacogenomics study of the toxicity of MTX monotherapy in RA patients. The meta-analysis was stratified by whether genetic variants associated with MTX toxicity.
RESULTS
A total of 42 publications that included 28 genes with 88 gene SNPs associated with the transporters, enzymes, and metabolites of MTX or the progression of RA were included in the SR, and 31 studies were included in 7 meta-analyses. The meta-analysis showed a significant association between the toxicity of MTX and the RFC-1 80G > A (rs1051266) polymorphism in the European RA patients.
CONCLUSION
RFC-1 80G > A (rs1051266) polymorphism was associated with MTX toxicity, and larger and more stringent study designs may provide more accurate results for the effect of these SNPs on the MTX toxicity.
Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; ATP Binding Cassette Transporter, Subfamily B; Antirheumatic Agents; Arthritis, Rheumatoid; Biomarkers; Ferredoxin-NADP Reductase; Humans; Hydroxymethyl and Formyl Transferases; Methotrexate; Methylenetetrahydrofolate Reductase (NADPH2); Multienzyme Complexes; Nucleotide Deaminases; Pharmacogenetics; Polymorphism, Single Nucleotide; Replication Protein C
PubMed: 28296761
DOI: 10.1097/MD.0000000000006337 -
Frontiers in Cardiovascular Medicine 2023The antiphospholipid syndrome (APS) is classified by the presence of antiphospholipid antibodies (aPL) and thrombotic and/or adverse obstetric outcomes. The diagnosis... (Review)
Review
BACKGROUND
The antiphospholipid syndrome (APS) is classified by the presence of antiphospholipid antibodies (aPL) and thrombotic and/or adverse obstetric outcomes. The diagnosis and risk assessment of APS is challenging. This systematic review investigated if the thrombin generation (TG) assay could be helpful for APS diagnosis and risk assessment.
METHODS
A systemic review was performed by searching two databases (MEDLINE and Embase) until March 31, 2022, using a search strategy with two concepts: APS and TG, and related keywords. Two reviewers independently screened the articles based on predefined inclusion and exclusion criteria. Data extraction and quality assessment with the Newcastle-Ottawa Scale (NOS) were performed independently. Synthesis Without Meta-analysis guidelines were followed for data synthesis reporting.
RESULTS
Fourteen studies with 677 APS and 1,349 control subjects were included with variable quality according to the NOS. Twelve studies measured TG the calibrated automated thrombogram (CAT) method using a fluorogenic substrate, whereas two used a chromogenic substrate-based TG assay. One study compared the CAT assay to the fully-automated ST Genesia® (Stago, France). Two studies initiated TG using platelet-rich plasma, whereas the rest of the studies used platelet-poor plasma. Resistance to activated protein C (aPC) was examined in ten studies. They reported a significant increase in aPC-resistance in APS patients compared to healthy controls, aPL-carriers, and thrombotic controls. Based on two studies, the prevalence of aPC-resistance was higher in APS patients compared to healthy controls and thrombotic controls with odds ratios of 5.9 and 6.8-12.8, respectively ( < 0.05). In contrast, no significant difference in aPC-resistance was found between APS patients and autoimmune disease controls. Furthermore, 7/14 studies reported TG-parameters including peak height, endogenous thrombin potential, lag time, and time to peak, but these outcomes were highly variable between studies. Furthermore, TG methodology between studies differed greatly, impacting the comparability of the studies.
CONCLUSION
aPC-resistance measured with TG was increased in APS patients compared to healthy and thrombotic controls, but the diagnostic and prognostic value is unclear compared to current diagnostic strategies. Studies of other TG-parameters were heterogeneous and more research is needed to identify their potential added value in APS diagnosis.
SYSTEMATIC REVIEW REGISTRATION
https://www.PROSPERO/, identifier: CRD42022308363.
PubMed: 37057100
DOI: 10.3389/fcvm.2023.1075121 -
Journal of Cardiothoracic and Vascular... Oct 2019Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques,...
OBJECTIVE
Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques, strategies) shown by randomized trials to increase mortality in these clinical settings.
DESIGN
A systematic review of the literature followed by a consensus-based voting process.
SETTING
A web-based international consensus conference.
PARTICIPANTS
Two hundred fifty-one physicians from 46 countries.
INTERVENTIONS
The authors performed a systematic literature search and identified all randomized controlled trials (RCTs) showing a significant increase in unadjusted landmark mortality among surgical or critically ill patients. The authors reviewed such studies during a meeting by a core group of experts. Studies selected after such review advanced to web-based voting by clinicians in relation to agreement, clinical practice, and willingness to include each intervention in international guidelines.
MEASUREMENTS AND MAIN RESULTS
The authors selected 12 RCTs dealing with 12 interventions increasing mortality: diaspirin-crosslinked hemoglobin (92% of agreement among web voters), overfeeding, nitric oxide synthase inhibitor in septic shock, human growth hormone, thyroxin in acute kidney injury, intravenous salbutamol in acute respiratory distress syndrome, plasma-derived protein C concentrate, aprotinin in high-risk cardiac surgery, cysteine prodrug, hypothermia in meningitis, methylprednisolone in traumatic brain injury, and albumin in traumatic brain injury (72% of agreement). Overall, a high consistency (ranging from 80% to 90%) between agreement and clinical practice was observed.
CONCLUSION
The authors identified 12 clinical interventions showing increased mortality supported by randomized controlled trials with nonconflicting evidence, and wide agreement upon clinicians on a global scale.
Topics: Cardiac Surgical Procedures; Critical Care; Critical Illness; Humans; Internet; Mortality; Perioperative Care; Physicians; Randomized Controlled Trials as Topic; Surveys and Questionnaires
PubMed: 31064730
DOI: 10.1053/j.jvca.2019.03.022 -
Viral Immunology 2021We aimed to verify the influence of intrinsic and extrinsic cell apoptotic pathways on the inhibition of cellular apoptosis in patients with tropical spastic...
We aimed to verify the influence of intrinsic and extrinsic cell apoptotic pathways on the inhibition of cellular apoptosis in patients with tropical spastic paralysis/myelopathy related to human T cell lymphotropic virus type 1. The databases accessed were PubMed, Scopus, Science Direct, and Web of Science. Neither the time of publishing nor the language of the articles was limited. The descriptors used for this systematic literature review were: Tropical Paraparesis, Proto-Oncogenic Protein C, Bcl-2, Bcl-X Protein, Bax protein, Fas ligand (FasL) protein, Fas receptor, TNF-related apoptosis-inducing ligand and Fas-associated protein with death domain (FADD)-like apoptosis regulating. The search resulted in 546 articles from which 9 articles were selected for analysis; ranging from serum levels of Bcl-2, Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) measured by enzyme-linked immunosorbent assay and the levels of cellular expression of Bcl-2 and Bcl-xL the TCD4+ lymphocytes accessed by western blot. Most studies accessed either gene expression or polymorphism of Fas, FasL, and TRAIL in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), whereas one study used flow cytometry and fluorescence to determine Fas expression. Increased Bcl-xL expression inhibited T lymphocyte apoptosis, whereas Bcl-2, serum levels, and cellular expression did not influence T lymphocyte apoptosis and serum levels of Fas were significantly higher and associated with markers of leukocyte activation in patients with HAM/TSP. In addition, Fas polymorphism (FAS-670AA) was associated with higher proviral load. There is a need for additional research on this issue since the number of patients was small and the studies presented higher heterogeneity.
Topics: Apoptosis; Human T-lymphotropic virus 1; Humans; Paraparesis, Tropical Spastic
PubMed: 33470891
DOI: 10.1089/vim.2020.0131 -
Journal of Evidence-based Complementary... Oct 2017This systematic review is aimed at evaluating the literature on the efficacy of naturally available extracts that inhibit cancer.
AIM
This systematic review is aimed at evaluating the literature on the efficacy of naturally available extracts that inhibit cancer.
METHODS
A literature search was performed to strengthening the reporting of observational studies in epidemiology analysis. Approximately 3000 research articles were initially selected. Of these articles, 200 were included, and 2800 were excluded. On further scrutiny, 150 of the 200 studies were reviews, seminars, and presentations, and 50 were original study articles. Among these articles, 20 studies were selected for the systematic review.
RESULTS
The predominant molecular pathways followed by natural extracts were nuclear factor kappa B ligand, suppression of the protein kinase B-Akt/P13K pathway (an intracellular signaling pathway important in regulating cell cycle), vascular endothelial growth factor downregulation, and tumor protein-P53 tumor suppressor upregulation.
CONCLUSIONS
It is evident that natural extracts have the ability to inhibit cancer progression. Continued research in this field could facilitate the use of natural extracts with currently available anticancer agents.
Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Humans; NF-kappa B; Neoplasms; Plant Extracts; Proto-Oncogene Mas; Proto-Oncogene Proteins c-akt; Vascular Endothelial Growth Factor A
PubMed: 29279018
DOI: 10.1177/2156587217744914 -
The Cochrane Database of Systematic... Jun 2015Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by systemic intravascular activation of coagulation, leading to deposition of fibrin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by systemic intravascular activation of coagulation, leading to deposition of fibrin in the bloodstream. It may occur in patients with acute and chronic leukemia and is particularly associated with acute promyelocytic leukemia (a subtype of acute myeloid leukemia).
OBJECTIVES
To assess the clinical benefits and harms of any pharmacological intervention for treating DIC in patients with acute or chronic leukemia.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2015, Issue 05), MEDLINE (1946 to 7 May 2015), LILACS (1982 to 7 May 2015) and African Index Medicus (7 May 2015). There was no language restrictions. We sought additional randomized controlled trials (RCTs) from the World Health Organization International Clinical Trials Registry Platform and the reference lists of primary studies identified.
SELECTION CRITERIA
RCTs assessing the clinical benefits and harms of interventions for treating DIC in patients with acute and chronic leukemia.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed trial selection, 'Risk of bias' assessment and data extraction. Primary outcomes were overall mortality, in-hospital mortality from any cause (15-day and 30-day) and adverse events.
MAIN RESULTS
In this Cochrane Review update we did not include any new RCT compared with the first review version. Accordingly, four RCTs (388 participants) met the inclusion criteria. These trials evaluated the human activated protein C, recombinant human soluble thrombomodulin, tranexamic acid and dermatan sulphate. Included trials reported data on mortality and bleeding. The studies were conducted in Japan, Italy and the Netherlands. We classified the included trials as: 1) including patients with or without leukemia which did not report data for the leukemia subgroup (366 participants); and 2) only including patients with leukemia (22 participants). Overall, the risk of bias of the included trials was high, since the trial authors did not provide a detailed description about trial design and execution.According to the GRADE recommendations, we judged the overall quality of the body of evidence for all prefixed outcomes as 'very low', due to methodological limitations and very small sample size.One trial, including 10 participants with leukemia and comparing dermatan sulphate with heparin, reported no deaths during trial treatment.In terms of bleeding data, we were unable to pool results from two studies that were only conducted with leukemia patients due to the inconsistency in the measurement and reporting of this outcome. One trial, including 12 participants with leukemia, found very low quality evidence that tranexamic acid can reduce the cumulative hemorrhagic score in participants compared with those assigned to placebo (P = 0.0015, very low quality evidence). On the contrary, there is no evidence that dermatan sulphate compared with placebo reduces new events of hemorrhagic diathesis (1/5 (20%) versus 2/5 (40%); RR 0.50; 95% CI 0.06 to 3.91; P = 0.51, very low quality evidence).No thromboembolic complications were reported in either trial that included patients with leukemia only (very low quality evidence). The safety profile was inconclusive.The included trials did not assess overall mortality, resolution of respiratory failure, renal failure or shock.
AUTHORS' CONCLUSIONS
Due to a lack of new RCTs, our conclusions in this Cochrane Review update are the same as the previous review version. We included four RCTs which reported mortality and bleeding data. It is not possible to determine whether human activated protein C, recombinant human soluble thrombomodulin, tranexamic acid and dermatan sulphate are effective or harmful for patients presenting with DIC related to acute or chronic leukemia. The quality of the evidence was low to very low. Therefore, prescription of these interventions for treating DIC in patients with acute and chronic leukemia can neither be supported nor rejected, unless new evidence from a large high-quality trial alters this conclusion.
Topics: Acute Disease; Anticoagulants; Chronic Disease; Dermatan Sulfate; Disseminated Intravascular Coagulation; Humans; Leukemia; Protein C; Randomized Controlled Trials as Topic; Thrombomodulin; Tranexamic Acid
PubMed: 26107113
DOI: 10.1002/14651858.CD008562.pub3