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BJU International Dec 2023To compare radiographic progression-free survival (rPFS), overall survival (OS), and treatment-emergent adverse events (TEAEs) among patients with metastatic... (Meta-Analysis)
Meta-Analysis Review
Poly(adenosine diphosphate-ribose) polymerase inhibitor combinations in first-line metastatic castrate-resistant prostate cancer setting: a systematic review and meta-analysis.
OBJECTIVES
To compare radiographic progression-free survival (rPFS), overall survival (OS), and treatment-emergent adverse events (TEAEs) among patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving a combination of first-line poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) plus androgen receptor axis-targeted agents (ARAT) vs placebo/ARAT.
MATERIALS AND METHODS
We conducted a systematic review/meta-analysis of all published Phase III randomised controlled trials using EMBASE, MEDLINE, and Cochrane (inception until 6 June 2023). Published full-text manuscripts and conference abstracts were inclusion eligible. Study selection/data extraction were independently performed by two authors. The Cochrane Risk-of-Bias 2 Tool was used, and certainty of evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Pooled hazard ratios (HRs) and relative risks, with corresponding confidence intervals (CIs), were generated using random-effects models.
RESULTS
Three trials were identified: PROpel, MAGNITUDE, and TALAPRO-2. Compared to placebo/ARAT, the PARPi/ARAT combination was associated with a 35% rPFS improvement in the overall cohort (HR 0.65, 95% CI 0.56-0.76), with 68%, 45%, and 26% improvements in the BReast CAncer gene 1/gene 2 (BRCA1/2)-mutated (BRCA1/2m; P < 0.001), homologous recombination repair-mutated (HRRm; P < 0.001), and non-HRRm cohorts (P = 0.003), respectively. OS data maturity ranged from 31% to 48%, with overall cohort OS data unavailable from MAGNITUDE. The PROpel/TALAPRO-2 pooled analysis demonstrated a 16% OS improvement in the overall cohort (HR 0.84, 95 CI 0.72-0.98; P = 0.02). OS in the HRRm (HR 0.76, 95% CI 0.61-0.95) and the BRCA1/2m cohorts (HR 0.53, 95% CI 0.18-1.56) were improved, with a higher effect magnitude compared to the overall cohort. This combination was associated with a 45% relative risk increase in Grade ≥3 TEAEs, including 6.22-fold for Grade ≥3 anaemia (31.9% vs 4.9%).
CONCLUSIONS
The addition of PARPi to ARAT in the first-line mCRPC setting is associated with rPFS benefits across subgroups, with the greatest magnitude of benefit in BRCA1/2m patients. OS benefits remain inconsistent irrespective of HRRm status, with significant increases in Grade ≥3 TEAEs, particularly anaemia. Currently, we suggest this combined approach be selectively offered to HRRm patients, preferentially BRCA1/2m.
Topics: Male; Humans; BRCA1 Protein; Ribose; Prostatic Neoplasms, Castration-Resistant; BRCA2 Protein; Anemia; Adenosine Diphosphate
PubMed: 37461140
DOI: 10.1111/bju.16130 -
Critical Care Explorations Sep 2021Traumatic brain injury is associated with coagulopathy that increases mortality risk. Viscoelastic hemostatic assays such as thromboelastography (Haemonetics SA, Signy,... (Review)
Review
UNLABELLED
Traumatic brain injury is associated with coagulopathy that increases mortality risk. Viscoelastic hemostatic assays such as thromboelastography (Haemonetics SA, Signy, Switzerland) provide rapid coagulopathy assessment and may be particularly useful for goal-directed treatment of traumatic brain injury patients. We conducted a systematic review to assess thromboelastography in the evaluation and management of coagulopathy in traumatic brain injury patients.
DATA SOURCES
MEDLINE, PubMed Central, Embase, and CENTRAL.
STUDY SELECTION
Clinical studies of adult patients with traumatic brain injury (isolated or polytrauma) who were assessed by either standard thromboelastography or thromboelastography with platelet mapping plus either conventional coagulation assays or platelet function assays from January 1999 to June 2021.
DATA EXTRACTION
Demographics, injury mechanism and severity, diagnostic, laboratory data, therapies, and outcome data were extracted for analysis and comparison.
DATA SYNTHESIS
Database search revealed 1,169 sources; eight additional articles were identified by the authors. After review, 31 publications were used for qualitative analysis, and of these, 16 were used for quantitative analysis. Qualitative and quantitative analysis found unique patterns of thromboelastography and thromboelastography with platelet mapping parameters in traumatic brain injury patients. Patterns were distinct compared with healthy controls, nontraumatic brain injury trauma patients, and traumatic brain injury subpopulations including those with severe traumatic brain injury or penetrating traumatic brain injury. Abnormal thromboelastography K-time and adenosine diphosphate % inhibition on thromboelastography with platelet mapping are associated with decreased survival after traumatic brain injury. Subgroup meta-analysis of severe traumatic brain injury patients from two randomized controlled trials demonstrated improved survival when using a viscoelastic hemostatic assay-guided resuscitation strategy (odds ratio, 0.39; 95% CI, 0.17-0.91; = 0.030).
CONCLUSIONS
Thromboelastography and thromboelastography with platelet mapping characterize coagulopathy patterns in traumatic brain injury patients. Abnormal thromboelastography profiles are associated with poor outcomes. Conversely, treatment protocols designed to normalize abnormal parameters may be associated with improved traumatic brain injury patient outcomes. Current quality of evidence in this population is low; so future efforts should evaluate viscoelastic hemostatic assay-guided hemostatic resuscitation in larger numbers of traumatic brain injury patients with specific focus on those with traumatic brain injury-associated coagulopathy.
PubMed: 34549189
DOI: 10.1097/CCE.0000000000000526 -
Biotechnology Advances 2023Polyphenolic compounds (such as quercetin and resveratrol) possess potential medicinal values due to their various bioactivities, but poor water solubility hinders their... (Review)
Review
Polyphenolic compounds (such as quercetin and resveratrol) possess potential medicinal values due to their various bioactivities, but poor water solubility hinders their health benefits to humankind. Glycosylation is a well-known post-modification method to biosynthesize natural product glycosides with improved hydrophilicity. Glycosylation has profound effects on decreasing toxicity, increasing bioavailability and stability, together with changing bioactivity of polyphenolic compounds. Therefore, polyphenolic glycosides can be used as food additives, therapeutics, and nutraceuticals. Engineered biosynthesis provides an environmentally friendly and cost-effective approach to generate polyphenolic glycosides through the use of various glycosyltransferases (GTs) and sugar biosynthetic enzymes. GTs transfer the sugar moieties from nucleotide-activated diphosphate sugar (NDP-sugar) donors to sugar acceptors such as polyphenolic compounds. In this review, we systematically review and summarize the representative polyphenolic O-glycosides with various bioactivities and their engineered biosynthesis in microbes with different biotechnological strategies. We also review the major routes towards NDP-sugar formation in microbes, which is significant for producing unusual or novel glycosides. Finally, we discuss the trends in NDP-sugar based glycosylation research to promote the development of prodrugs that positively impact human health and wellness.
Topics: Humans; Glycosides; Carbohydrates; Glycosylation; Glycosyltransferases; Sugars; Nucleotides
PubMed: 37028465
DOI: 10.1016/j.biotechadv.2023.108146 -
Orthopaedic Journal of Sports Medicine Apr 2020Platelet-rich plasma (PRP) has wide applications in orthopaedic care. Its beneficial effects are attributed to the growth factor profile from the platelet secretome. In... (Review)
Review
BACKGROUND
Platelet-rich plasma (PRP) has wide applications in orthopaedic care. Its beneficial effects are attributed to the growth factor profile from the platelet secretome. In theory, these effects would be diminished by medications that inhibit platelet activation and/or the subsequent release of growth factors.
PURPOSE
To determine whether commonly used antiplatelets, nonsteroidal anti-inflammatory drugs (NSAIDs), or anticoagulant medications affect platelet growth factor release in PRP.
STUDY DESIGN
Systematic review; Level of evidence, 2.
METHOD
A systematic review of the literature related to antiplatelet, anti-inflammatory, and anticoagulant drugs was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We used the Downs and Black objective quality scoring system. The literature search consisted of PubMed and Cochrane Library databases. Search terms consisted of 1 item selected from "platelet-rich plasma," "platelet-derived growth factor," and "platelet-rich plasma AND growth factor" combined with 1 item from "antiplatelet," "aspirin," "anticoagulant," and "NSAID." Only studies published within the past 25 years were included.
RESULTS
A total of 15 studies met the inclusion criteria: 7 studies detected no significant decrease in growth factors or mitogenesis, whereas 6 detected a decrease with antiplatelet agents, 1 detected mixed results with an antiplatelet agent, and 1 had mixed results with an antiplatelet agent/vasodilator. In terms of PRP activation, all 3 studies assessing collagen, the 2 studies analyzing adenosine diphosphate alone, and the 1 study investigating arachidonic acid found a decrease in growth factor concentration.
CONCLUSION
Antiplatelet medications may decrease the growth factor release profile in a cyclooxygenase 1- and cyclooxygenase 2-dependent manner. Eight of 15 studies found a decrease in growth factors or mitogenesis. However, more studies are needed to comprehensively understand antiplatelet effects on the PRP secretome.
PubMed: 32426401
DOI: 10.1177/2325967120912841 -
PloS One 2016To assess the effectiveness and safety of Chinese herbal medicine (CHM) for the treatment of aspirin resistance (AR). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the effectiveness and safety of Chinese herbal medicine (CHM) for the treatment of aspirin resistance (AR).
METHODS
A comprehensive research of seven electronic databases was performed for comparative studies evaluating CHM for AR. Two authors independently extracted data and assessed the methodological quality of the included trials using the Cochrane risk of bias tool. Data wasere synthesized by using RevMan 5.3 software. (PROSPERO Registration #CRD42015020182).
RESULTS
18 randomized controlled trials (RCTs) involving 1,460 patients were included. 15 RCTs reported significant difference in the reduction of platelet aggregation rate (PAR) induced by adenosine diphosphate (ADP) (P<0.05), and 11 reported significant effect of CHM plus aspirin to reduce PAR induced by arachidonic acid (AA) (P<0.05) compared with aspirin 100mg/d treatment. The pooling data of 3 RCTs showed the thromboxane B2 (TXB2) in patients with CHM plus aspirin versus aspirin were significantly reduced (Random Effect model (RE), Standard Deviation (SD) = -95.93, 95% Confidential Interval (CI)[-118.25,-73.61], P<0.00001). Subgroup analysis showed that TXB2 (Fixed Effect model (FE), SD = -89.23, 95%CI[-121.96,-56.49], P<0.00001) had significant difference in Tongxinluo capsule plus aspirin versus aspirin. 2 RCTs reported the clinical effective rate, and the meta-analysis result showed a significant difference in intervention and control group (FE, Relative Risk (RR) = 1.67, 95%CI[1.15, 2.42], P = 0.007<0.05). In 4 trials, CHM plus aspirin had better effects of reducing the reoccurrence of cerebral infarction than aspirin (FE, RR = 0.24, 95%CI [0.11, 0.49], P<0.0001). And one trial showed that CHM plus aspirin could decrease the National Institutes of Health Stroke Scale (NHISS) score (P<0.05) and increase the Barthel Index (BI) score (P<0.05). 4 trials stated that there were no adverse effects occurred in intervention group, and analysis showed significant difference of CHM or CHM plus aspirin in reducing the occurrence of adverse events (FE, RR = 0.22, 95%CI[0.13, 0.39], P<0.00001). 5 trials claimed that the CHM monotherapy and CHM adjunctive therapy for AR did not add the risk of bleeding (FE, RR = 0.50, 95%CI[0.20, 1.22], P = 0.13>0.05).
CONCLUSIONS
CHM may be effective and safe as an alternative and collaborative therapy for AR. However, the current evidence and potential promising findings should be interpreted with caution due to poor and varying methodological quality of included studies and the heterogeneity of interventions. Thus, further exploration of this strategy with adequately powered RCTs is warranted.
Topics: Aspirin; Drug Resistance; Drugs, Chinese Herbal; Humans; Observer Variation
PubMed: 27153119
DOI: 10.1371/journal.pone.0154897 -
Shell Versus Core Architecture and Biology of Thrombi in Acute Ischemic Stroke: A Systematic Review.Clinical and Applied... 2023The presence of an outer shell has been recently described as a common feature of acute ischemic stroke (AIS) thrombi. We performed a systematic review of the current... (Review)
Review
BACKGROUND
The presence of an outer shell has been recently described as a common feature of acute ischemic stroke (AIS) thrombi. We performed a systematic review of the current literature on shell genesis, structure, and clinical significance.
METHODS
Following PRISMA guidelines, we searched Ovid Cochrane Central Register of Controlled Trials, Embase, Medline, Scopus, and Web of Science for studies reporting the composition and structure of AIS thrombi and clot analogs. Identified studies were added to Covidence software for primary screening. Two reviewers independently screened titles and abstracts followed by full-text screening.
RESULTS
From 1290 identified studies, 10 were included in this review. Studies using histology/immunohistochemistry/immunofluorescence described fibrin, platelets, von Willebrand factor, and neutrophil extracellular traps as the main components of the shell. Scanning electron microscopy demonstrated a dense, compact fibrin/platelet-rich shell, and a core rich in polyhedrocytes. Microfluidics studies identified highly activated P-selectin-positive platelets and fibrin forming the core while secondary agonists adenosine diphosphate and thromboxane, along with loosely packed P-selectin-negative platelets constituted the shell.
CONCLUSIONS
The composition, compaction, and integrity of the shell may impact thrombolysis and revascularization outcomes. The preponderance of studies supported this conclusion.
Topics: Humans; Ischemic Stroke; P-Selectin; Thrombosis; Fibrin; Biology; Stroke
PubMed: 37960892
DOI: 10.1177/10760296231213632 -
Journal of Gynecology Obstetrics and... Apr 2022This meta-analysis evaluated the correlation between poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) expression and prognosis in patients with ovarian cancer. (Meta-Analysis)
Meta-Analysis
PURPOSE
This meta-analysis evaluated the correlation between poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) expression and prognosis in patients with ovarian cancer.
METHODS
Eligible studies were extracted from the electronic databases of PubMed, Web of Science, and EMBASE until 1 August 2019. The included studies investigated the correlation between PARP expression and clinical outcomes in patients with ovarian cancer. Clinical outcomes are overall survival (OS) and progression free survival (PFS). The clinical data of patients, such as clinicopathologic characteristics and survival, were analyzed. The language was limited to English, and studies conducted at the cellular level, animal studies, and non-original research were excluded. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were used for this meta-analysis.
RESULTS
A total of 9 eligible studies involving 1230 patients were included in our meta-analysis. Based on the analysis, higher PARP expression was correlated with worse overall survival [OS] (HR,1.64; 95% CI, 1.08-2.49; P = 0.020) in the univariate analysis, whereas results from multivariate analysis indicated that PARP overexpression wasn't statistically associated with worse OS (HR, 1.36; 95% CI, 0.98-1.90; P = 0.069). Moreover, the pooled results revealed that patients with PARP overexpression were not associated with worse histologic grade (OR,2.22; 95% CI, 0.98-5.02; P = 0.06).
CONCLUSION
PARP overexpression maybe associated with poor prognosis and survival in patients with ovarian cancer. The patients with PARP over expression were not tended to have a worse histologic grade. Findings require further validation.
Topics: Adenosine Diphosphate; Adenosine Diphosphate Ribose; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Prognosis; Ribose
PubMed: 35218983
DOI: 10.1016/j.jogoh.2022.102344 -
Archives of Academic Emergency Medicine 2020Currently, the basis of acute coronary syndrome (ACS) therapy is dual antiplatelet therapy (DAPT) with Aspirin as a nonsteroidal anti-inflammatory drug and clopidogrel... (Review)
Review
INTRODUCTION
Currently, the basis of acute coronary syndrome (ACS) therapy is dual antiplatelet therapy (DAPT) with Aspirin as a nonsteroidal anti-inflammatory drug and clopidogrel as adenosine diphosphate receptor antagonists. Therefore, the aim of the present systematic review is to answer that should DAPT with Aspirin and clopidogrel be continued until coronary artery bypass grafting (CABG) in patients who have ACS?
METHODS
The search for relevant studies in the present meta-analysis is based on three approaches: A) systematic searches in electronic databases, B) manual searches in Google and Google Scholar, and C) screening of bibliography of related original and review articles. The endpoints included mortality rate, myocardial infarction (MI), cerebrovascular accident (CVA), reoperation, re-exploration, other cardiac events, renal failure, length of ICU and hospital stay, chest tube drainage and blood product transfusion after CABG.
RESULTS
After the initial screening, 41 articles were studied in detail, and finally the data of 15 studies were included in the meta-analysis. DAPT before CABG in patients with ACS does not increase the rate of mortality, CVA, renal failure, MI, and other cardiac events, but increases reoperation, re-exploration, length of ICU, and hospital stay. Chest tube drainage and blood product transfusion rate significantly increased in the DAPT group compared to the control group (non-antiplatelet or Aspirin alone). Increase in chest tube drainage and blood product transfusion rate indicates an increase in bleeding, so increase in reoperation, re-exploration to control bleeding, and, subsequently, increase in the length of ICU and hospital stay are expected.
CONCLUSIONS
DAPT with Aspirin and clopidogrel before CABG in patients with ACS does not increase the rate of mortality, CVA, renal failure, MI, and other cardiac events despite more bleedings, and it may be suggested before CABG for better graft patency.
PubMed: 32613203
DOI: No ID Found -
Archives of Gynecology and Obstetrics Aug 2021To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy... (Meta-Analysis)
Meta-Analysis Review
Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors as maintenance therapy in women with newly diagnosed ovarian cancer: a systematic review and meta-analysis.
PURPOSE
To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy in women with newly diagnosed ovarian cancer, and to explore whether this therapy produces a survival benefit in a subgroup population with specific clinical characteristics.
METHODS
We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science and relevant clinical research registry platforms on October 1, 2019, and included randomized controlled trials (RCTs) that compared PARP inhibitors with placebo in women (aged ≥ 18 years) with newly diagnosed epithelial ovarian cancer.
RESULTS
We identified four RCTs with 3,070 participants. Compared with placebo, PARP inhibitor maintenance therapy showed a clinically significant benefit on progression free survival (PFS) in homologous recombination deficiency (HRD) positive population (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.29-0.53). In contrast, no clear differences were identified between the groups in the HRD negative population (HR, 0.83; 95% CI 0.67-1.03). Further, there was no clear difference between the groups in terms of other outcomes (overall survival, health-related quality of life, and adverse events).
CONCLUSIONS
PARP inhibitor maintenance therapy significantly prolongs the PFS of patients with newly diagnosed ovarian cancer, especially in HRD positive patients. The diagnostic test used to determine HRD status plays an important role in guiding PARP inhibitor maintenance therapy. Compared with placebo, the effect of PARP inhibitors on ovarian cancer was probably not affected by the International Federation of Gynecology and Obstetrics stage status, response to first-line chemotherapy, and residual macroscopic disease after debulking surgery.
Topics: Adenosine Diphosphate; Antineoplastic Agents; Carcinoma, Ovarian Epithelial; Female; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Ribose; Treatment Outcome
PubMed: 34021367
DOI: 10.1007/s00404-021-06070-2 -
Journal of Gastroenterology and... Apr 2020Crigler-Najjar syndrome (CNS) results from biallelic mutations of UGT1A1 causing partial or total loss of uridine 5'-diphosphate glucuronyltransferase activity leading...
BACKGROUND AND AIM
Crigler-Najjar syndrome (CNS) results from biallelic mutations of UGT1A1 causing partial or total loss of uridine 5'-diphosphate glucuronyltransferase activity leading to unconjugated hyperbilirubinemia and its attendant risk for irreversible neurological injury (kernicterus). CNS is exceedingly rare and has been only partially characterized through relatively small studies, each comprising between two and 57 patients.
METHODS
A systematic literature review was conducted to consolidate data on the patient, caregiver, and societal burden of CNS.
RESULTS
Twenty-eight articles on clinical aspects of CNS were identified, but no published data on its humanistic or economic burden were found. In patients with complete UGT1A1 deficiency (type 1 CNS [CNS-I]), unconjugated bilirubin levels increase 3-6 mg/dL/day during the newborn period and reach neurologically dangerous levels between 5 and 14 days of age. Phototherapy is the mainstay of treatment but poses significant challenges to patients and their families. Despite consistent phototherapy, patients with CNS-I have worsening hyperbilirubinemia with advancing age. Liver transplantation is the only definitive therapy for CNS-I and is increasingly associated with excellent long-term survival but also incurs high costs, medical and surgical morbidities, and risks of immunosuppression.
CONCLUSIONS
Crigler-Najjar syndrome is associated with a substantial burden, even with existing standards of care. The development of novel disease-modifying therapies has the potential to reduce disease burden and improve the lives of CNS patients and their families.
Topics: Bilirubin; Cost of Illness; Crigler-Najjar Syndrome; Female; Gene Deletion; Glucuronosyltransferase; Humans; Hyperbilirubinemia; Infant, Newborn; Liver Transplantation; Male; Phototherapy; Rare Diseases
PubMed: 31495946
DOI: 10.1111/jgh.14853