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PloS One 2017Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. (Review)
Review
INTRODUCTION
Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined.
AIM
The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia.
METHODS
A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia.
RESULTS
The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR.
CONCLUSION
Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk factors.
Topics: Antipsychotic Agents; Computational Biology; Genetic Predisposition to Disease; Humans; Pneumonia
PubMed: 29077727
DOI: 10.1371/journal.pone.0187034 -
Frontiers in Cardiovascular Medicine 2019Despite increasing technical improvement and extracorporeal membrane oxygenation (ECMO)-related knowledge over the past three decades, morbidity and mortality...
Despite increasing technical improvement and extracorporeal membrane oxygenation (ECMO)-related knowledge over the past three decades, morbidity and mortality associated with bleeding and clotting complications remain high in pediatric patients undergoing ECMO. Platelets, a key element of the coagulation system, have been proposed to be the main cause of coagulopathy in the setting of ECMO. This systematic review aims to summarize and discuss the existing knowledge of platelet phenotype and function in the pediatric ECMO population. A systematic review was conducted for the Embase, Medline, and PubMed databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The detailed study selection process yielded a total of 765 studies and only 3 studies that fulfilled the selection criteria were included in this review. Techniques used to assess platelet function in the three existing studies included platelet aggregometry, flow cytometry, and thromboelastography-platelet mapping. The finding that is common to the three studies is reduced platelet function in pediatric patients during ECMO either compared to before the initiation of ECMO or in non-survivors compared to survivors. Two studies demonstrated reduced platelet aggregation that are irreversible by platelet transfusion during ECMO. Two studies reported bleeding events and mortality in children on ECMO and none of the studies investigated thrombotic events. This systematic review demonstrates the extremely limited information available for platelet phenotype and function in the pediatric ECMO population. Evidence from the existing literature suggests reduced platelet aggregation and increased platelet activation in children during ECMO. However, this needs to be interpreted with care due to the limitations associated with the techniques used for platelet function testing. Furthermore, the association between platelet dysfunction and clinical outcomes in the pediatric ECMO population remains elusive. Multiple research gaps have been identified when it comes to the knowledge of platelet phenotype and function of children on ECMO, highlighting the need for robust, well-designed studies in this setting.
PubMed: 31620448
DOI: 10.3389/fcvm.2019.00137 -
PloS One 2022Preeclampsia (PE) is a pregnancy-specific disorder characterized by endothelial dysfunction, and activation of the coagulation system. Alteration of PLT parameters is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preeclampsia (PE) is a pregnancy-specific disorder characterized by endothelial dysfunction, and activation of the coagulation system. Alteration of PLT parameters is the common hematological abnormality observed in women with PE. The main aim of this study was to systematically review previous studies from around the world to generate evidence about the relationship between platelet count (PC) and PE, as well as mean platelet volume (MPV) and PE, by calculating the pooled weighted mean difference (WMD) of PC and MPV between PE and normotensive (NT) groups.
METHODS
Relevant articles which were published in the English language from January 10, 2011, to January 10, 2021, were systematically searched through PubMed, Web of Science, and African journals online. In addition, reference probing of published articles searching was employed through Google Scholar and Google for searching grey literature. The methodological qualities of articles were assessed using Joana Brigg's institute critical appraisal checklist. A random-effects model was used to estimate pooled WMD of PLT parameters between the two groups with the respective 95% confidence intervals (CI) using Stata version 11.0. The I2 statistics and Egger's regression test were used to assess heterogeneity and publication bias among included studies, respectively.
RESULTS
A total of 25 articles were included in this systematic review and meta-analysis. Of which, 23 studies were used in each PC and MPV analysis. The overall pooled WMD of PC and MPV between PE and NT groups were -41.45 × 109/L [95% CI; -51.8, -31.0] and 0.98 fl [95% CI; 0.8, 1.1], respectively. The pooled WMD revealed that PC decreased significantly in the PE group compared to the NT group while MPV increased significantly in the PE group.
CONCLUSIONS
This systematic review and meta-analysis indicated that there is a significant decrease in PC and a significant increase in MPV during PE development among pregnant women. As a result, a change in these parameters among pregnant women may indicate the development of PE.
Topics: Blood Coagulation; Female; Humans; Mean Platelet Volume; Platelet Count; Pre-Eclampsia; Pregnancy
PubMed: 36103491
DOI: 10.1371/journal.pone.0274398 -
BMC Nutrition May 2022Obesity is a major risk factor for atherosclerotic cardiovascular disease (ASCVD) and is associated with altered platelet function. The mean platelet volume (MPV) is a...
BACKGROUND
Obesity is a major risk factor for atherosclerotic cardiovascular disease (ASCVD) and is associated with altered platelet function. The mean platelet volume (MPV) is a rapid measure of platelet activation and a prognostic marker in patients with cardiovascular disease. However, no meta-analysis on the association between MPV and obesity has been conducted, and the value of monitoring the MPV in patients with obesity remains unclear.
OBJECTIVE
To provide cumulative evidence on whether the mean platelet volume (MPV) is increased in individuals with obesity and to describe associations between the ASCVD-risk factors and the MPV in individuals with obesity.
METHODS
This meta-analysis was prepared following the Meta-analysis Of Observational Studies (MOOSE) guidelines. We searched the PubMed and Embase database from inception until the 31st of March 2021. Studies were included when they reported the mean platelet volume in individuals with obesity and provided a suitable non-obese comparator group. The risk of bias was independently assessed by two reviewers using the Newcastle-Ottawa scale. The primary outcome of the meta-analysis was the MPV, while we considered the atherosclerotic risk profiles as a secondary outcome.
RESULTS
We identified 178 citations through the PUBMED and 255 citations through EMBASE database search. In all, 13 studies met the inclusion criteria. Firstly, we report an increased mean platelet volume in individuals with obesity compared to non-obese individuals (MD 0.79; [95%CI: 0.42 to 1.16], I2 = 93.4%). Moreover, the reported increase in the MPV was inversely associated with the body mass index (Coefficient: -0.57, standard error (SE): 0.18, p < 0.001) and directly related to changes in triglyceride levels (Coefficient: 4.99, standard error (SE): 1.14, p < 0.001).
CONCLUSION
This meta-analysis and meta-regression showed an increased MPV in nondiabetic individuals living with obesity. Moreover, the MPV was associated with hypertriglyceridemia, an independent predictor of atherosclerotic cardiovascular disease. Overall, the findings suggest that MPV may be a valuable rapid marker for the monitoring and risk-stratification of individuals with obesity who may be at risk of developing cardiovascular disease.
PubMed: 35578358
DOI: 10.1186/s40795-022-00541-8 -
Heliyon Feb 2024Type 2 diabetes (T2D) is a complex metabolic ailment marked by a global high prevalence and significant attention in primary healthcare settings due to its elevated...
BACKGROUND
Type 2 diabetes (T2D) is a complex metabolic ailment marked by a global high prevalence and significant attention in primary healthcare settings due to its elevated morbidity and mortality rates. The pathophysiological mechanisms underlying the onset and progression of this disease remain subjects of ongoing investigation. Recent evidence underscores the pivotal role of the intricate intercellular communication network, wherein cell-derived vesicles, commonly referred to as extracellular vesicles (EVs), emerge as dynamic regulators of diabetes-related complications. Given that the protein cargo carried by EVs is contingent upon the metabolic conditions of the originating cells, particular proteins may serve as informative indicators for the risk of activating or inhibiting signaling pathways crucial to the progression of T2D complications.
METHODS
In this study, we conducted a systematic review to analyze the published evidence on the proteome of EVs from the plasma or serum of patients with T2D, both with and without complications (PROSPERO: CRD42023431464).
RESULTS
Nine eligible articles were systematically identified from the databases, and the proteins featured in these articles underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We identified changes in the level of 426 proteins, with CST6, CD55, HBA1, S100A8, and S100A9 reported to have high levels, while FGL1 exhibited low levels.
CONCLUSION
These proteins are implicated in pathophysiological mechanisms such as inflammation, complement, and platelet activation, suggesting their potential as risk markers for T2D development and progression. Further studies are required to explore this topic in greater detail.
PubMed: 38356516
DOI: 10.1016/j.heliyon.2024.e25537 -
International Journal of Molecular... Jul 2021In severe COVID-19, which is characterized by blood clots and neutrophil-platelet aggregates in the circulating blood and different tissues, an increased incidence of...
In severe COVID-19, which is characterized by blood clots and neutrophil-platelet aggregates in the circulating blood and different tissues, an increased incidence of cardiovascular complications and venous thrombotic events has been reported. The inflammatory storm that characterizes severe infections may act as a driver capable of profoundly disrupting the complex interplay between platelets, endothelium, and leukocytes, thus contributing to the definition of COVID-19-associated coagulopathy. In this frame, P-selectin represents a key molecule expressed on endothelial cells and on activated platelets, and contributes to endothelial activation, leucocyte recruitment, rolling, and tissue migration. Briefly, we describe the current state of knowledge about P-selectin involvement in COVID-19 pathogenesis, its possible use as a severity marker and as a target for host-directed therapeutic intervention.
Topics: Blood Coagulation Disorders; Blood Platelets; COVID-19; Endothelial Cells; Humans; Leukocytes; P-Selectin
PubMed: 34360707
DOI: 10.3390/ijms22157942 -
The Cochrane Database of Systematic... Oct 2014Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age-matched controls, people with intermittent claudication have a three- to six-fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007.
OBJECTIVES
To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication.
SEARCH METHODS
For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9).
SELECTION CRITERIA
Double-blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta-analysis as a fixed-effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data.
MAIN RESULTS
We included fifteen double-blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta-analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta-analysis, for initial claudication distance (ICD - the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD - the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI -43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI.There was no association between treatment type and all-cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups.
AUTHORS' CONCLUSIONS
Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all-cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study.
Topics: Aged; Cilostazol; Humans; Intermittent Claudication; Middle Aged; Myocardial Infarction; Pentoxifylline; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Tetrazoles; Walking
PubMed: 25358850
DOI: 10.1002/14651858.CD003748.pub4 -
Journal of Thrombosis and Thrombolysis Aug 2023Heparin-induced thrombocytopenia (HIT) occurs in approximately 3% of patients receiving heparinoids. About 30-75% of patients with type 2 of HIT develop thrombosis as a... (Meta-Analysis)
Meta-Analysis Review
Heparin-induced thrombocytopenia (HIT) occurs in approximately 3% of patients receiving heparinoids. About 30-75% of patients with type 2 of HIT develop thrombosis as a result of platelet activation. The most important clinical symptom is thrombocytopenia. Patients with severe COVID-19 are among those receiving heparinoids. This meta-analysis performed to picture the current knowledge and results of published studies in this field. Three search engines were searched and 575 papers were found. After evaluation, 37 articles were finally selected of which 13 studies were quantitatively analyzed. The pooled frequency rate of suspected cases with HIT in 13 studies with 11,241 patients was 1.7%. The frequency of HIT was 8.2% in the extracorporeal membrane oxygenation subgroup with 268 patients and 0.8% in the hospitalization subgroup with 10,887 patients. The coincidence of these two conditions may increase the risk of thrombosis. Of the 37 patients with COVID-19 and confirmed HIT, 30 patients (81%) were treated in the intensive care unit or had severe COVID-19. The most commonly used anticoagulants were UFH in 22 cases (59.4%). The median platelet count before treatment was 237 (176-290) x 10/µl and the median nadir platelet count was 52 (31-90.5) x 10/µl.
Topics: Humans; Heparin; Heparinoids; COVID-19; Thrombocytopenia; Anticoagulants; Thrombosis
PubMed: 37219826
DOI: 10.1007/s11239-023-02827-5 -
Advances in Medical Sciences Sep 2023Periodontitis is an infectious disease characterized by the inflammatory destruction of the tooth supporting tissues. In multi-rooted teeth, this process leads to... (Review)
Review
Periodontitis is an infectious disease characterized by the inflammatory destruction of the tooth supporting tissues. In multi-rooted teeth, this process leads to periodontal destruction within furcations creating defects demanding in terms of treatment. Regeneration of class II furcation involvement, although possible, is considered an unpredictable procedure, especially in terms of the bone fill. The interest in wound healing improvement by additional use of autologous concentrates of growth factors remains high in many fields of dentistry. Platelet-rich fibrin (PRF) is a second-generation platelet concentrate and biomaterial. PRF forms a solid fibrin matrix, which is slowly remodeled comparable to the natural blood clot. Its utilization is associated with release of growth factors and glycoproteins over a long period of time. PRF activates alkaline phosphates, which show osteoblastic activity and this activation influences the bone formation. The aim of this review of randomized controlled trials (RCTs) was to evaluate the adjunctive use of platelet-rich fibrin in surgical treatment of furcation defects.
Topics: Humans; Platelet-Rich Fibrin; Furcation Defects; Wound Healing
PubMed: 37757664
DOI: 10.1016/j.advms.2023.09.009 -
BMC Pregnancy and Childbirth Aug 2021Currently, we suffer from an increasing diabetes pandemic and on the other hand from the SARS-CoV-2 pandemic. Already at the beginning of the SARS-CoV-2 pandemic, it was...
BACKGROUND
Currently, we suffer from an increasing diabetes pandemic and on the other hand from the SARS-CoV-2 pandemic. Already at the beginning of the SARS-CoV-2 pandemic, it was quickly assumed that certain groups are at increased risk to suffer from a severe course of COVID-19. There are serious concerns regarding potential adverse effects on maternal, fetal, and neonatal outcomes. Diabetic pregnancies clearly need special care, but clinical implications as well as the complex interplay of diabetes and SARS-CoV-2 are currently unknown. We summarized the evidence on SARS-CoV-2 in diabetic pregnancies, including the identification of novel potential pathophysiological mechanisms and interactions as well as clinical outcomes and features, screening, and management approaches.
METHODS
We carried out a systematic scoping review in MEDLINE (PubMed), EMBASE, CINAHL, Cochrane Library, and Web of Science Core Collection in September 2020.
RESULTS
We found that the prognosis of pregnant women with diabetes mellitus and COVID-19 may be associated with potential underlying mechanisms such as a simplified viral uptake by ACE2, a higher basal value of pro-inflammatory cytokines, being hypoxemic as well as platelet activation, embolism, and preeclampsia. In the context of "trans-generational programming" and COVID-19, life-long consequences may be "programmed" during gestation by pro-inflammation, hypoxia, over- or under-expression of transporters and enzymes, and epigenetic modifications based on changes in the intra-uterine milieu. COVID-19 may cause new onset diabetes mellitus, and that vertical transmission from mother to baby might be possible.
CONCLUSIONS
Given the challenges in clinical management, the complex interplay between COVID-19 and diabetic pregnancies, evidence-based recommendations are urgently needed. Digital medicine is a future-oriented and effective approach in the context of clinical diabetes management. We anticipate our review to be a starting point to understand and analyze mechanisms and epidemiology to most effectively treat women with SARS-COV-2 and diabetes in pregnancy.
Topics: COVID-19; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Maternal Health; Pregnancy; Pregnancy Complications, Infectious; Pregnancy in Diabetics; Prenatal Care; Primary Prevention
PubMed: 34416856
DOI: 10.1186/s12884-021-03975-3