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Pediatric Critical Care Medicine : a... Jan 2022Critically ill children frequently receive plasma and platelet transfusions. We sought to determine evidence-based recommendations, and when evidence was insufficient,...
Executive Summary of Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB).
OBJECTIVES
Critically ill children frequently receive plasma and platelet transfusions. We sought to determine evidence-based recommendations, and when evidence was insufficient, we developed expert-based consensus statements about decision-making for plasma and platelet transfusions in critically ill pediatric patients.
DESIGN
Systematic review and consensus conference series involving multidisciplinary international experts in hemostasis, and plasma/platelet transfusion in critically ill infants and children (Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding [TAXI-CAB]).
SETTING
Not applicable.
PATIENTS
Children admitted to a PICU at risk of bleeding and receipt of plasma and/or platelet transfusions.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
A panel of 29 experts in methodology, transfusion, and implementation science from five countries and nine pediatric subspecialties completed a systematic review and participated in a virtual consensus conference series to develop recommendations. The search included MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020, using a combination of subject heading terms and text words for concepts of plasma and platelet transfusion in critically ill children. Four graded recommendations and 49 consensus expert statements were developed using modified Research and Development/UCLA and Grading of Recommendations, Assessment, Development, and Evaluation methodology. We focused on eight subpopulations of critical illness (1, severe trauma, intracranial hemorrhage, or traumatic brain injury; 2, cardiopulmonary bypass surgery; 3, extracorporeal membrane oxygenation; 4, oncologic diagnosis or hematopoietic stem cell transplantation; 5, acute liver failure or liver transplantation; 6, noncardiac surgery; 7, invasive procedures outside the operating room; 8, sepsis and/or disseminated intravascular coagulation) as well as laboratory assays and selection/processing of plasma and platelet components. In total, we came to consensus on four recommendations, five good practice statements, and 44 consensus-based statements. These results were further developed into consensus-based clinical decision trees for plasma and platelet transfusion in critically ill pediatric patients.
CONCLUSIONS
The TAXI-CAB program provides expert-based consensus for pediatric intensivists for the administration of plasma and/or platelet transfusions in critically ill pediatric patients. There is a pressing need for primary research to provide more evidence to guide practitioners.
Topics: Anemia; Child; Critical Care; Critical Illness; Erythrocyte Transfusion; Evidence-Based Medicine; Humans; Infant; Platelet Transfusion
PubMed: 34989711
DOI: 10.1097/PCC.0000000000002851 -
Periodontology 2000 Feb 2024Platelet-rich fibrin (PRF) has been characterized as a regenerative biomaterial that is fully resorbed within a typical 2-3 week period. Very recently, however, a...
Platelet-rich fibrin (PRF) has been characterized as a regenerative biomaterial that is fully resorbed within a typical 2-3 week period. Very recently, however, a novel heating process was shown to extend the working properties of PRP/PRF from a standard 2-3 week period toward a duration of 4-6 months. Numerous clinicians have now utilized this extended-PRF (e-PRF) membrane as a substitute for collagen barrier membranes in various clinical applications, such as guided tissue/bone regeneration. This review article summarizes the scientific work to date on this novel technology, including its current and future applications in periodontology, implant dentistry, orthopedics and facial aesthetics. A systematic review was conducted investigating key terms including "Bio-Heat," "albumin gel," "albumin-PRF," "Alb-PRF," "extended-PRF," "e-PRF," "activated plasma albumin gel," and "APAG" by searching databases such as MEDLINE, EMBASE and PubMed. Findings from preclinical studies demonstrate that following a simple 10-min heating process, the transformation of the liquid plasma albumin layer into a gel-like injectable albumin gel extends the resorption properties to at least 4 months according to ISO standard 10 993 (subcutaneous animal model). Several clinical studies have now demonstrated the use of e-PRF membranes as a replacement for collagen membranes in GTR/GBR procedures, closing lateral windows in sinus grafting procedures, for extraction site management, and as a stable biological membrane during recession coverage procedures. Furthermore, Alb-PRF may also be injected as a regenerative biological filler that lasts extended periods with advantages in joint injections, osteoarthritis and in the field of facial aesthetics. This article highlights the marked improvement in the stability and degradation properties of the novel Alb-PRF/e-PRF technology with its widespread future potential use as a potential replacement for collagen membranes with indications including extraction site management, GBR procedures, lateral sinus window closure, recession coverage among others, and further highlights its use as a biological regenerative filler for joint injections and facial aesthetics. It is hoped that this review will pioneer future opportunities and research development in the field, leading to further progression toward more natural and less costly biomaterials for use in medicine and dentistry.
Topics: Animals; Humans; Biocompatible Materials; Bone Regeneration; Guided Tissue Regeneration, Periodontal; Membranes, Artificial; Platelet-Rich Fibrin
PubMed: 37986559
DOI: 10.1111/prd.12537 -
Molecular Psychiatry Aug 2023The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin... (Meta-Analysis)
Meta-Analysis
The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT gene-environment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression) were excluded. Two independent reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. The certainty of study results was assessed using a modified version of the GRADE. We did not synthesise results of individual meta-analyses because they included overlapping studies. The review was registered with PROSPERO (CRD42020207203). 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review. Quality of reviews was variable with some genetic studies of high quality. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n = 1002). One meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and evidence that lowered serotonin concentration was associated with antidepressant use (n = 1869). Two meta-analyses of overlapping studies examining the 5-HT receptor (largest n = 561), and three meta-analyses of overlapping studies examining SERT binding (largest n = 1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. However, effects of prior antidepressant use were not reliably excluded. One meta-analysis of tryptophan depletion studies found no effect in most healthy volunteers (n = 566), but weak evidence of an effect in those with a family history of depression (n = 75). Another systematic review (n = 342) and a sample of ten subsequent studies (n = 407) found no effect in volunteers. No systematic review of tryptophan depletion studies has been performed since 2007. The two largest and highest quality studies of the SERT gene, one genetic association study (n = 115,257) and one collaborative meta-analysis (n = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.
Topics: Humans; Depression; Serotonin; Receptor, Serotonin, 5-HT1A; Tryptophan; Hydroxyindoleacetic Acid; Antidepressive Agents; Serotonin Plasma Membrane Transport Proteins
PubMed: 35854107
DOI: 10.1038/s41380-022-01661-0 -
Autoimmunity Reviews Nov 2019Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease; the clinical manifestations are correlated with continuum multiarticular synovitis, cartilage and...
BACKGROUND AND AIM
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease; the clinical manifestations are correlated with continuum multiarticular synovitis, cartilage and bone damage, and defeat of joint function, that causes disability. Involvement of internal organs is also frequent. Between the inflammatory cells involved in RA, macrophages play a key role. These cells can polarize in different phenotype and mediate the immune/inflammatory reaction as well as the reparatory phase when possible. The properties of these cells are mediate by the body's environmental factors. In this systematic review, all English-speaking articles concerning the role of M1 (pro-inflammatory) or M2 (anti-inflammatory) macrophages in RA were systematically reviewed and categorized according to their polarized-function in RA, especially in the synovial tissue. Analyses of the endogenous molecules and the drugs that could modulate M1 and M2 activity in RA were achieved.
METHODS
A sensitive search was developed in Pubmed, Web of Science, Ovid Med-Line, Embase Database and Science Direct Database (la both from Elsevier) to identify articles to increase the highlighting on the role of macrophages M1 and M2 in RA using the following terms: ((M1 AND M2) AND Rheumatoid Arthritis). All selected papers were read and discussed by two independent reviewers. The selection process was based on title, abstract and full text level. Relevant data were extracted and analyzed using a standardized template designed for this review.
RESULTS
In total 39 resulting articles were selected and categorized according to description of M1/M2's role in RA. Data from humans, mice and rats were subcategorized, thus in every section were highlighted the contribute, in peripheral blood and synovial tissue, of both polarized macrophages; section for endogenous molecules and drugs that favor the switch from M1 to M2 macrophages were carried out. The most evinced relevant results, were that in RA blood and in the synovial tissue, there isn't a clear distinction phase with M1 or M2 macrophages (by membrane marker analysis); rather there is M1 and M2 subset disequilibrium and by deeply analyses of mRNA gene and cytokine produced, it emerged that a non-coherent expression inner marker match with membrane molecules, and also the tissue section can define the marker expressed.
CONCLUSION
This systematic review emphasizes that the rigid classical subdivision of M1 and M2 macrophages, as well as the different samples' results comparison, might be questionable. In addition, it is suggested, when taking samples from RA patients, to carefully consider their therapies in order to analyze the M1 and M2 macrophages behavior without drug influence. In line with the advances in M1 and M2 knowledge, and the progression in the single-cell methodologies by identification of individual cell molecular markers, therapeutic approaches seem possible to favor the anti-inflammatory macrophage response in RA (e.g. M2 polarization).
Topics: Animals; Arthritis, Rheumatoid; Humans; Macrophages
PubMed: 31520798
DOI: 10.1016/j.autrev.2019.102397 -
Molecular Psychiatry Jul 2016The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies... (Meta-Analysis)
Meta-Analysis Review
The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies in clinical samples as well as twin studies suggest a familial liability and consequently different genes were investigated in association studies. Pharmacotherapy with methylphenidate (MPH) seems to be the first-line treatment of choice in adults with attention-deficit hyperactive disorder (ADHD) and some studies were conducted on the genes influencing the response to this drug. Finally some peripheral biomarkers were identified in ADHD adult patients. We believe this work is the first systematic review and meta-analysis of candidate gene association studies, pharmacogenetic and biochemical (metabolomics) studies performed in adults with ADHD to identify potential genetic, predictive and peripheral markers linked specifically to ADHD in adults. After screening 5129 records, we selected 87 studies of which 61 were available for candidate gene association studies, 5 for pharmacogenetics and 21 for biochemical studies. Of these, 15 genetic, 2 pharmacogenetic and 6 biochemical studies were included in the meta-analyses. We obtained an association between adult ADHD and the gene BAIAP2 (brain-specific angiogenesis inhibitor 1-associated protein 2), even after Bonferroni correction, with any heterogeneity in effect size and no publication bias. If we did not apply the Bonferroni correction, a trend was found for the carriers allele 9R of dopamine transporter SLC6A3 40 bp variable tandem repeat polymorphism (VNTR) and for 6/6 homozygotes of SLC6A3 30 bp VNTR. Negative results were obtained for the 9-6 haplotype, the dopamine receptor DRD4 48 bp VNTR, and the enzyme COMT SNP rs4680. Concerning pharmacogenetic studies, no association was found for the SLC6A3 40 bp and response to MPH with only two studies selected. For the metabolomics studies, no differences between ADHD adults and controls were found for salivary cortisol, whereas lower serum docosahexaenoic acid (DHA) levels were found in ADHD adults. This last association was significant even after Bonferroni correction and in absence of heterogeneity. Other polyunsaturated fatty acids (PUFAs) such as AA (arachidonic acid), EPA (eicosapentaenoic acid) and DyLA (dihomogammalinolenic acid) levels were not different between patients and controls. No publication biases were observed for these markers. Genes linked to dopaminergic, serotoninergic and noradrenergic signaling, metabolism (DBH, TPH1, TPH2, DDC, MAOA, MAOB, BCHE and TH), neurodevelopment (BDNF and others), the SNARE system and other forty genes/proteins related to different pathways were not meta-analyzed due to insufficient data. In conclusion, we found that there were not enough genetic, pharmacogenetic and biochemical studies of ADHD in adults and that more investigations are needed. Moreover we confirmed a significant role of BAIAP2 and DHA in the etiology of ADHD exclusively in adults. Future research should be focused on the replication of these findings and to assess their specificity for ADHD.
Topics: Adult; Alleles; Attention Deficit Disorder with Hyperactivity; Biomarkers; Docosahexaenoic Acids; Dopamine Plasma Membrane Transport Proteins; Female; Gene Frequency; Genetic Association Studies; Genotype; Humans; Male; Methylphenidate; Minisatellite Repeats; Nerve Tissue Proteins; Pharmacogenetics; Polymorphism, Genetic; Receptors, Dopamine D4
PubMed: 27217152
DOI: 10.1038/mp.2016.74 -
Clinics in Sports Medicine Jan 2020Meniscus injuries are among the most common athletic injuries and result in functional impairment in the knee. Repair is crucial for pain relief and prevention of...
Meniscus injuries are among the most common athletic injuries and result in functional impairment in the knee. Repair is crucial for pain relief and prevention of degenerative joint diseases like osteoarthritis. Current treatments, however, do not produce long-term improvements. Thus, recent research has been investigating new therapeutic options for regenerating injured meniscal tissue. This review comprehensively details the current methodologies being explored in the basic sciences to stimulate better meniscus injury repair. Furthermore, it describes how these preclinical strategies may improve current paradigms of how meniscal injuries are clinically treated through a unique and alternative perspective to traditional clinical methodology.
Topics: Adipose Tissue; Biomechanical Phenomena; Bone Marrow Cells; Cartilage; Chondrocytes; Humans; Intercellular Signaling Peptides and Proteins; Menisci, Tibial; Platelet-Rich Fibrin; Platelet-Rich Plasma; Regeneration; Stem Cell Transplantation; Synovial Membrane; Tibial Meniscus Injuries; Tissue Engineering; Tissue Scaffolds
PubMed: 31767102
DOI: 10.1016/j.csm.2019.08.003 -
Frontiers in Pharmacology 2022Insulin secretory agents are commonly used to treat type 2 diabetes. However, traditional insulin secretory agents such as sulfonylureas and glinides have side effects...
Insulin secretory agents are commonly used to treat type 2 diabetes. However, traditional insulin secretory agents such as sulfonylureas and glinides have side effects of hypoglycemia. In recent years, researchers have discovered that berberine can inhibit the voltage-gated k channels of pancreatic β cell membrane and promote insulin secretion without causing hypoglycemia, because the glucose-lowering effects of berberine are only under hyperglycemic conditions or in a high-glucose-dependent manner. In order to shed light on the glucose-lowing effects of berberine in type 2 diabetes with different baseline fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c), we conducted a meta-analysis of randomized controlled trials. We searched eight databases, which included PubMed, EMBASE, Web of Science, the Cochrane Library, and the Chinese databases such as Sino-Med, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Database for Chinese Technical Periodicals, for randomized controlled trials, with berberine as the intervention and patients with type 2 diabetes mellitus as subjects, published up until November 2021. We analyzed the glucose-lowing effects of berberine, including its effects on FPG, HbA1c and 2-h plasma blood glucose (2hPBG), by calculating weighted mean differences (WMD) and 95% confidence interval (CI). To assess the safety of berberine, we analyzed the incidence of total adverse events and hypoglycemia by calculating relative risk (RR) and 95% CI. Thirty-seven studies involving 3,048 patients were included in the meta-analysis. The results showed that berberine could reduce FPG (WMD = -0.82 mmol/L, 95% CI (-0.95, -0.70)), HbA1c (WMD = -0.63%, 95% CI (-0.72, -0.53)), and 2hPBG (WMD = -1.16 mmol/L, 95% CI (-1.36, -0.96)), with all results being statistically significant. Subgroup analyses revealed that the glucose-lowering effect of berberine was associated with baseline mean FPG and HbA1c in type 2 diabetes. In addition, berberine alone or in combination with oral hypoglycemic agents (OHAs) in the treatment of T2DM did not significantly increase the incidence of total adverse events (RR = 0.73, 95% CI (0.55, 0.97), = 0.03) and the risk of hypoglycemia (RR = 0.48, 95% CI (0.21, 1.08), = 0.08). Berberine has a glucose-lowering effect, which is related to the baseline FPG and HbA1c levels of patients. Treatment with berberine may be safe since it does not increase the incidence of total adverse events and the risk of hypoglycemia. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=292975, identifier CRD42021292975.
PubMed: 36467075
DOI: 10.3389/fphar.2022.1015045 -
Experimental and Molecular Pathology Feb 2018This review summarizes recent studies on plasma-membrane ecto-ATP synthase from structural and functional standpoints to possible pathophysiological roles. This review... (Review)
Review
This review summarizes recent studies on plasma-membrane ecto-ATP synthase from structural and functional standpoints to possible pathophysiological roles. This review discusses significant new contributions and perspectives in the area of ecto-ATP synthase since the topic was last reviewed in 2015. Following an extensive summary of the cell types in which the ecto-ATP synthase is present, its structural and functional mechanism are discussed and physiological and pathological roles of the ecto-ATP synthase are reviewed and evaluated. Attempts to define the possible role of ecto-ATP synthase as possible target for anti-cancer and anti-obesity interventions are discussed.
Topics: Animals; Cell Membrane; Humans; Proton-Translocating ATPases
PubMed: 29305066
DOI: 10.1016/j.yexmp.2017.12.006 -
Frontiers in Pharmacology 2017Bilirubin is a highly-hydrophobic tetrapyrrole which binds to plasma albumin. It is conjugated in the liver to glucuronic acid, and the water-soluble glucuronides are... (Review)
Review
Bilirubin is a highly-hydrophobic tetrapyrrole which binds to plasma albumin. It is conjugated in the liver to glucuronic acid, and the water-soluble glucuronides are excreted in urine and bile. The membrane transporters of bilirubin diglucuronide are well-known. Still undefined are however the transporters performing the uptake of bilirubin from the blood into the liver, a process known to be fast and not rate-limited. The biological importance of this process may be appraised by considering that in normal adults 200-300 mg of bilirubin are produced daily, as a result of the physiologic turnover of hemoglobin and cellular cytochromes. Nevertheless, research in this field has yielded controversial and contradicting results. We have undertaken a systematic review of the literature, believing in its utility to improve the existing knowledge and promote further advancements. We have sourced the PubMed database until 30 June 2017 by applying 5 sequential searches. Screening and eligibility criteria were applied to retain research articles reporting results obtained by using bilirubin molecules in membrane transport assays or by assessing serum bilirubin levels in experiments. We have identified 311 articles, retaining 44, reporting data on experimental models having 6 incremental increases of complexity (isolated proteins, membrane vesicles, cells, organ fragments, rodents, and human studies), demonstrating the function of 19 membrane transporters, encoded by either or genes. Three other bilirubin transporters have no gene, though one, i.e., bilitranslocase, is annotated in the Transporter Classification Database. This is the first review that has systematically examined the membrane transporters for bilirubin and its conjugates. Paradoxically, the remarkable advancements in the field of membrane transport of bilirubin have pointed to the elusive mechanism(s) enabling bilirubin to diffuse into the liver as if no cellular boundary existed.
PubMed: 29259555
DOI: 10.3389/fphar.2017.00887 -
Journal of the American Academy of... Oct 2011Several studies have demonstrated differences in omega-3 fatty acid composition in plasma and in erythrocyte membranes in patients with attention-deficit/hyperactivity... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Several studies have demonstrated differences in omega-3 fatty acid composition in plasma and in erythrocyte membranes in patients with attention-deficit/hyperactivity disorder (ADHD) compared with unaffected controls. Omega-3 fatty acids have anti-inflammatory properties and can alter central nervous system cell membrane fluidity and phospholipid composition. Cell membrane fluidity can alter serotonin and dopamine neurotransmission. The goal of this meta-analysis was to examine the efficacy of omega-3 fatty acid supplementation in children with ADHD.
METHOD
PubMed was searched for randomized placebo-controlled trials examining omega-3 fatty acid supplementation in children with ADHD symptomatology. The primary outcome measurement was standardized mean difference in rating scales of ADHD severity. Secondary analyses were conducted to determine the effects of dosing of different omega-3 fatty acids in supplements.
RESULTS
Ten trials involving 699 children were included in this meta-analysis. Omega-3 fatty acid supplementation demonstrated a small but significant effect in improving ADHD symptoms. Eicosapentaenoic acid dose within supplements was significantly correlated with supplement efficacy. No evidence of publication bias or heterogeneity between trials was found.
CONCLUSION
Omega-3 fatty acid supplementation, particularly with higher doses of eicosapentaenoic acid, was modestly effective in the treatment of ADHD. The relative efficacy of omega-3 fatty acid supplementation was modest compared with currently available pharmacotherapies for ADHD such as psychostimulants, atomoxetine, or α(2) agonists. However, given its relatively benign side-effect profile and evidence of modest efficacy, it may be reasonable to use omega-3 fatty supplementation to augment traditional pharmacologic interventions or for families who decline other psychopharmacologic options.
Topics: Attention Deficit Disorder with Hyperactivity; Child; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Humans
PubMed: 21961774
DOI: 10.1016/j.jaac.2011.06.008