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Cartilage Dec 2023There are many intra-articular hyaluronic acid (IA-HA) products on the market that have known intrinsic differences in molecular size, source, and structure. The current...
INTRODUCTION
There are many intra-articular hyaluronic acid (IA-HA) products on the market that have known intrinsic differences in molecular size, source, and structure. The current review summarizes existing evidence describing and assessing these differences, while also identifying whether these differences have an impact on clinical outcomes.
METHODS
This systematic review summarized all literature that specifically addresses IA-HA product differences. Included studies summarized basic science and mechanism of action comparisons of IA-HA product differences, or systematic reviews that assess differences in clinical outcomes between IA-HA product differences.
RESULTS
A total of 20 investigations assessed basic science differences between IA-HA products, while 20 investigations provided assessments of the clinical outcome differences between IA-HA product characteristics. The published basic science literature provided a differentiation between low molecular weight (LMW) and high molecular weight (HMW) HA with regard to changes within the synovial fluid, driven by the interactions that these molecules have with receptors in the joint space. These differences in receptor interaction manifest within clinical outcomes, as meta-analyses comparing pain relief after IA-HA suggest that pain reduction is superior in patients who receive HMW HA as opposed to LMW HA.
CONCLUSION
This review highlights differences between IA-HA characteristics, and how important the molecular weight, derivation of the product, and structure are to variances in reported clinical outcomes to treat osteoarthritis (OA) of the knee. HMW IA-HAs have shown greater efficacy compared to the alternative of LMW products, while avian-derived and cross-linked products have potentially demonstrated an increase in inflammatory events over non-avian-derived, non-cross-linked HAs.
Topics: Humans; Hyaluronic Acid; Osteoarthritis, Knee; Viscosupplements; Injections, Intra-Articular; Pain
PubMed: 37314014
DOI: 10.1177/19476035231154530 -
Obesity Reviews : An Official Journal... Dec 2023The extent to which genetic variations contribute to interindividual differences in weight loss and metabolic outcomes after bariatric surgery is unknown. Identifying... (Review)
Review
The extent to which genetic variations contribute to interindividual differences in weight loss and metabolic outcomes after bariatric surgery is unknown. Identifying genetic variants that impact surgery outcomes may contribute to clinical decision making. This review evaluates current evidence addressing the association of genetic variants with weight loss and changes in metabolic parameters after bariatric surgery. A search was conducted using Medline, Embase, Scopus, Web of Science, and Cochrane Library. Fifty-two eligible studies were identified. Single nucleotide polymorphisms (SNPs) at ADIPOQ (rs226729, rs1501299, rs3774261, and rs17300539) showed a positive association with postoperative change in measures of glucose homeostasis and lipid profiles (n = 4), but not with weight loss after surgery (n = 6). SNPs at FTO (rs11075986, rs16952482, rs8050136, rs9939609, rs9930506, and rs16945088) (n = 10) and MC4R (rs11152213, rs476828, rs2229616, rs9947255, rs17773430, rs5282087, and rs17782313) (n = 9) were inconsistently associated with weight loss and metabolic improvement. Four studies examining the UCP2 SNP rs660339 reported associations with postsurgical weight loss. In summary, there is limited evidence supporting a role for specific genetic variants in surgical outcomes after bariatric surgery. Most studies have adopted a candidate gene approach, limiting the scope for discovery, suggesting that the absence of compelling evidence is not evidence of absence.
Topics: Humans; Bariatric Surgery; Weight Loss; Polymorphism, Single Nucleotide; Alpha-Ketoglutarate-Dependent Dioxygenase FTO
PubMed: 37632325
DOI: 10.1111/obr.13626 -
Indian Heart Journal 2016This systematic review with meta-analysis sought to determine the efficacy and safety of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) on clinical... (Meta-Analysis)
Meta-Analysis Review
This systematic review with meta-analysis sought to determine the efficacy and safety of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) on clinical outcomes following percutaneous coronary intervention. Medline, Embase, Elsevier, and web of knowledge as well as Google scholar literature were used for selecting appropriate studies with randomized controlled design. After screening 445 studies, a total of 23 trials (including a total of 43,912 patients) were identified that reported outcomes. Pooled analysis revealed that LMWH compared to UFH could significantly increase thrombolysis in myocardial infarction grade 3 flow (p<0.001), which was associated with similar target vessel revascularization (p=0.6), similar incidence of stroke (p=0.7), and significantly lower incidence of re-myocardial infarction (p<0.001), major bleeding (p=0.02) and mortality (p<0.001). Overall, LMWH was shown to be a useful type of heparin for patients with MI undergoing PCI, due to its higher efficacy and lower rate of complication compared to UFH. It is also associated with increased myocardial perfusion, decreased major hemorrhage, and mortality.
Topics: Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; Injections, Intravenous; Intraoperative Complications; Intraoperative Period; Myocardial Infarction; Treatment Outcome
PubMed: 27133344
DOI: 10.1016/j.ihj.2016.01.014 -
Clinical Nephrology Jun 2017The relationship between the sieving coefficient (SC) or extraction ratio (ER) and the molecular weight (MW) of peptide and protein solutes during hemofiltration has not... (Review)
Review
The relationship between the sieving coefficient (SC) or extraction ratio (ER) and the molecular weight (MW) of peptide and protein solutes during hemofiltration has not been investigated; it is possible that the SC and ER correlate with MW, permitting an estimate of peptide and protein clearance by hemofiltration in the absence of empiric data. A search for studies of the SC and/or ER for peptide and protein solutes during hemofiltration identified data for β-microglobulin, brain natriuretic peptide, carperitide, IL-1β, IL-1RA, IL-6, IL-8, lysozyme, myoglobin, neutrophil gelatinase-associated lipocalin, procalcitonin, retinol-binding protein, TNF-α, soluble TNFR-1, soluble TNFR-II, and vasopressin using polyacrylonitrile, polysulfone, polyamide, and cellulose hemofilters. The SC correlated with MW using polyacrylonitrile, polyamide, and cellulose hemofilters. With fewer data, the ER did not correlate with MW using polyacrylonitrile hemofilters, and not enough data were available to assess the ER with any other hemofilters. These results may help predict peptide and protein convective clearance during hemofiltration with polyacrylonitrile, polyamide, and cellulose hemofilters when empiric data are not available. .
Topics: Acrylic Resins; Blood Proteins; Hemofiltration; Humans
PubMed: 28211786
DOI: 10.5414/CN108841 -
Journal of Thrombosis and Haemostasis :... Feb 2023Severe high-molecular-weight kininogen (HK) deficiency is a poorly studied autosomal recessive contact system defect caused by pathogenic, biallelic KNG1 variants.
BACKGROUND
Severe high-molecular-weight kininogen (HK) deficiency is a poorly studied autosomal recessive contact system defect caused by pathogenic, biallelic KNG1 variants.
AIM
We performed the first comprehensive analysis of diagnostic, clinical, genetic, and epidemiological aspects of HK deficiency.
METHODS
We collected clinical information and blood samples from a newly detected HK-deficient individual and from published cases identified by a systematic literature review. Activity and antigen levels of coagulation factors were determined. Genetic analyses of KNG1 and KLKB1 were performed by Sanger sequencing. The frequency of HK deficiency was estimated considering truncating KNG1 variants from GnomAD.
RESULTS
We identified 48 cases of severe HK deficiency (41 families), of these 47 have been previously published (n = 19 from gray literature). We genotyped 3 cases and critically appraised 10 studies with genetic data. Ten HK deficiency-causing variants (one new) were identified. All of them were truncating mutations, whereas the only known HK amino acid substitution with a relevant phenotype instead causes hereditary angioedema. Conservative estimates suggest an overall prevalence of severe HK deficiency of approximately one case per 8 million population, slightly higher in Africans. Individuals with HK deficiency appeared asymptomatic and had decreased levels of prekallikrein and factor XI, which could lead to misdiagnosis.
CONCLUSION
HK deficiency is a rare condition with only few known pathogenic variants. It has an apparently good prognosis but is prone to misdiagnosis. Our understanding of its clinical implications is still limited, and an international prekallikrein and HK deficiency registry is being established to fill this knowledge gap.
Topics: Kininogen, High-Molecular-Weight; Prekallikrein; Prevalence; Blood Coagulation Factors
PubMed: 36700498
DOI: 10.1016/j.jtha.2022.11.011 -
Journal of Clinical Medicine Nov 2019International guidelines recommend low-molecular-weight heparin (LMWH) as first-line pharmacological option for the prevention of venous thromboembolism (VTE) in many... (Review)
Review
International guidelines recommend low-molecular-weight heparin (LMWH) as first-line pharmacological option for the prevention of venous thromboembolism (VTE) in many patient categories. Guidance on the optimal prophylactic dose is lacking. We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials to assess benefits and harms of low-dose LMWH versus placebo or no treatment for thrombosis prophylaxis in patients at risk of VTE. PubMed, Cochrane Library, Web of Science, and Embase were searched up to June 2019. Results were presented as relative risk (RR) with conventional and TSA-adjusted confidence intervals (CI). Forty-four trials with a total of 22,579 participants were included. Six (14%) had overall low risk of bias. Low-dose LMWH was not statistically significantly associated with all-cause mortality (RR 0.99; 95%CI 0.85-1.14; TSA-adjusted CI 0.89-1.16) but did reduce symptomatic VTE (RR 0.62; 95%CI 0.48-0.81; TSA-adjusted CI 0.44-0.89) and any VTE (RR 0.61; 95%CI 0.50-0.75; TSA-adjusted CI 0.49-0.82). Analyses on major bleeding (RR 1.07; 95%CI 0.72-1.59), as well as serious adverse events (SAE) and clinically relevant non-major bleeding were inconclusive. There was very low to moderate-quality evidence that low-dose LMWH for thrombosis prophylaxis did not decrease all-cause mortality but reduced the incidence of symptomatic and asymptomatic VTE, while the analysis of the effects on bleeding and adverse events remained inconclusive.
PubMed: 31766453
DOI: 10.3390/jcm8122039 -
Acta Neurochirurgica Nov 2023In neurosurgical patients, the risk of developing venous thromboembolism (VTE) is high due to the relatively long duration of surgical interventions, usually long... (Review)
Review
BACKGROUND
In neurosurgical patients, the risk of developing venous thromboembolism (VTE) is high due to the relatively long duration of surgical interventions, usually long immobilization time after surgery, and possible neurological deficits which can negatively influence mobility. In neurosurgical clinical practice, there is lack of consensus on optimal prophylaxis against VTE, mechanical or pharmacological.
OBJECTIVE
To systematically review available literature on the incidence of VTE in neurosurgical interventions and to establish an optimum prevention strategy.
METHODS
A literature search was performed in PubMed, Embase, Web of Science, Cochrane Library, and EmCare, based on a sensitive search string combination. Studies were selected by predefined selection criteria, and risk of bias was assessed by Newcastle-Ottawa Quality Assessment Scale and Cochrane risk of bias.
RESULTS
Twenty-five studies were included, half of which had low risk of bias (21 case series, 3 comparative studies, 1 RCT). VTE was substantially higher if the evaluation was done by duplex ultrasound (DUS), or another systematic screening method, in comparison to clinical evaluation (clin). Without prophylaxis DVT, incidence varied from 4 (clin) to 10% (DUS), studies providing low molecular weight heparin (LMWH) reported an incidence of 2 (clin) to 31% (DUS), providing LMWH and compression stockings (CS) reported an incidence of 6.4% (clin) to 29.8% (DUS), and providing LMWH and intermittent pneumatic compression devices (IPC) reported an incidence of 3 (clin) to 22.3% (DUS). Due to a lack of data, VTE incidence could not meaningfully be compared between patients with intracranial and spine surgery. The reported incidence of pulmonary embolism (PE) was 0 to 7.9%.
CONCLUSION
Low molecular weight heparin, compression stockings, and intermittent pneumatic compression devices were all evaluated to give reduction in VTE, but data were too widely varying to establish an optimum prevention strategy. Systematic screening for DVT reveals much higher incidence percentages in comparison to screening solely on clinical grounds and is recommended in follow-up of neurosurgical procedures with an increased risk for DVT development in order to prevent occurrence of PE.
Topics: Humans; Heparin, Low-Molecular-Weight; Anticoagulants; Venous Thromboembolism; Postoperative Complications; Pulmonary Embolism
PubMed: 37796296
DOI: 10.1007/s00701-023-05792-3 -
Diabetes & Metabolic Syndrome 2015There are three definitions belong to metabolic syndrome (MetS). These definitions have some differences that make some problem for MetS diagnosis criteria. So a new... (Review)
Review
AIMS
There are three definitions belong to metabolic syndrome (MetS). These definitions have some differences that make some problem for MetS diagnosis criteria. So a new diagnosis marker can help to MetS diagnosis. The aim of this study was the assess of serum levels of leptin, total adiponectin, high molecular weight (HMW) adiponectin, and their ratio with MetS.
MATERIALS AND METHODS
We searched Science direct, Pubmed, and Google Scholar for related articles in English. Review studies excluded.
RESULTS
Of 1827 articles found, 16 articles met our inclusion criteria. leptin is higher in MetS group but adiponectin is lower (<4 μg/ml) and it shows the paradoxical effect of them in MetS. Higher L/A ratio is a better biomarker for MetS diagnosis criteria than leptin and adiponectin separately. HMW adiponectin (<2.5 μg/ml) can be the most reliable biomarker for MetS diagnosis criteria.
CONCLUSION
Our systematic review showed that HMW adiponectin and Leptin to adiponectin ratio should be the best biomarkers for MetS.
Topics: Biomarkers; Humans; Metabolic Syndrome; Prognosis
PubMed: 25470629
DOI: 10.1016/j.dsx.2013.06.014 -
BMC Nephrology Jun 2017Low molecular weight heparins (LMWH) have been extensively studied and became the treatment of choice for several indications including pulmonary embolism. While their... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Low molecular weight heparins (LMWH) have been extensively studied and became the treatment of choice for several indications including pulmonary embolism. While their efficacy in hemodialysis is considered similar to unfractionated heparin (UFH), their safety remains controversial mainly due to a risk of bioaccumulation in patients with renal impairment. The aim of this systematic review was to evaluate the safety of LMWH when compared to UFH for extracorporeal circuit (ECC) anticoagulation.
METHODS
We used Pubmed, Embase, Cochrane central register of controlled trials, Trip database and NICE to retrieve relevant studies with no language restriction. We looked for controlled experimental trials comparing LMWH to UFH for ECC anticoagulation among end-stage renal disease patients undergoing chronic hemodialysis. Studies were kept if they reported at least one of the following outcomes: bleeding, lipid profile, cardiovascular events, osteoporosis or heparin-induced thrombocytopenia. Two independent reviewers conducted studies selection, quality assessment and data extraction with discrepancies solved by a third reviewer. Relative risk and 95% CI was calculated for dichotomous outcomes and mean weighted difference (MWD) with 95% CI was used to pool continuous variables.
RESULTS
Seventeen studies were selected as part of the systematic. The relative risk for total bleeding was 0.76 (95% CI 0.26-2.22). The WMD calculated for total cholesterol was -28.70 mg/dl (95% CI -51.43 to -5.98), a WMD for triglycerides of -55.57 mg/dl (95% CI -94.49 to -16.66) was estimated, and finally LDL-cholesterol had a WMD of -14.88 mg/dl (95% CI -36.27 to 6.51).
CONCLUSIONS
LMWH showed to be at least as safe as UFH for ECC anticoagulation in chronic hemodialysis. The limited number of studies reporting on osteoporosis and HIT does not allow any conclusion for these outcomes. Larger studies are needed to evaluate properly the safety of LMWH in chronic hemodialysis.
Topics: Anticoagulants; Clinical Trials as Topic; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Kidney Failure, Chronic; Osteoporosis; Pulmonary Embolism; Renal Dialysis
PubMed: 28592259
DOI: 10.1186/s12882-017-0596-4 -
The Cochrane Database of Systematic... May 2020Aspirin and heparin are widely used as preventive strategy to reduce the high risk of recurrent pregnancy loss in women with antiphospholipid antibodies (aPL). This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Aspirin and heparin are widely used as preventive strategy to reduce the high risk of recurrent pregnancy loss in women with antiphospholipid antibodies (aPL). This review supersedes a previous, out-of-date review that evaluated all potential therapies for preventing recurrent pregnancy loss in women with aPL. The current review focusses on a narrower scope because current clinical practice is restricted to using aspirin or heparins, or both for women with aPL in an attempt to reduce pregnancy complications.
OBJECTIVES
To assess the effects of aspirin or heparin, or both for improving pregnancy outcomes in women with persistent (on two separate occasions) aPL, either lupus anticoagulant (LAC), anticardiolipin (aCL) or aβ-glycoprotein-I antibodies (aβGPI) or a combination, and recurrent pregnancy loss (two or more, which do not have to be consecutive).
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (3 June 2019), and reference lists of retrieved studies. Where necessary, we attempted to contact trial authors.
SELECTION CRITERIA
Randomised, cluster-randomised and quasi-randomised controlled trials that assess the effects of aspirin, heparin (either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH]), or a combination of aspirin and heparin compared with no treatment, placebo or another, on pregnancy outcomes in women with persistent aPL and recurrent pregnancy loss were eligible. All treatment regimens were considered.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion criteria and risk of bias. Two review authors independently extracted data and checked them for accuracy and the certainty of the evidence was assessed using the GRADE approach.
MAIN RESULTS
Eleven studies (1672 women) met the inclusion criteria; nine randomised controlled trials and two quasi-RCTs. The studies were conducted in the USA, Canada, UK, China, New Zealand, Iraq and Egypt. One included trial involved 1015 women, all other included trials had considerably lower numbers of participants (i.e. 141 women or fewer). Some studies had high risk of selection and attrition bias, and many did not include sufficient information to judge the risk of reporting bias. Overall, the certainty of evidence is low to very low due to the small numbers of women in the studies and to the risk of bias. The dose and type of heparin and aspirin varied among studies. One study compared aspirin alone with placebo; no studies compared heparin alone with placebo and there were no trials that had a no treatment comparator arm during pregnancy; five studies explored the efficacy of heparin (either UFH or LMWH) combined with aspirin compared with aspirin alone; one trial compared LMWH with aspirin; two trials compared the combination of LMWH plus aspirin with the combination of UFH plus aspirin; two studies evaluated the combination of different doses of heparin combined with aspirin. All trials used aspirin at a low dose. Aspirin versus placebo We are very uncertain if aspirin has any effect on live birth compared to placebo (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.71 to 1.25, 1 trial, 40 women, very low-certainty evidence). We are very uncertain if aspirin has any effect on the risk of pre-eclampsia, pregnancy loss, preterm delivery of a live infant, intrauterine growth restriction or adverse events in the child, compared to placebo. We are very uncertain if aspirin has any effect on adverse events (bleeding) in the mother compared with placebo (RR 1.29, 95% CI 0.60 to 2.77, 1 study, 40 women). The certainty of evidence for these outcomes is very low because of imprecision, due to the low numbers of women involved and the wide 95% CIs, and also because of risk of bias. Venous thromboembolism and arterial thromboembolism were not reported in the included studies. Heparin plus aspirin versus aspirin alone Heparin plus aspirin may increase the number of live births (RR 1.27, 95% CI 1.09 to 1.49, 5 studies, 1295 women, low-certainty evidence). We are uncertain if heparin plus aspirin has any effect on the risk of pre-eclampsia, preterm delivery of a live infant, or intrauterine growth restriction, compared with aspirin alone because of risk of bias and imprecision due to the low numbers of women involved and the wide 95% CIs. We are very uncertain if heparin plus aspirin has any effect on adverse events (bleeding) in the mother compared with aspirin alone (RR 1.65, 95% CI 0.19 to 14.03, 1 study, 31 women). No women in either the heparin plus aspirin group or the aspirin alone group had heparin-induced thrombocytopenia, allergic reactions, or venous or arterial thromboembolism. Similarly, no infants had congenital malformations. Heparin plus aspirin may reduce the risk of pregnancy loss (RR 0.48, 95% CI 0.32 to 0.71, 5 studies, 1295 women, low-certainty evidence). When comparing LMWH plus aspirin versus aspirin alone the pooled RR for live birth was 1.20 (95% CI 1.04 to 1.38, 3 trials, 1155 women). In the comparison of UFH plus aspirin versus aspirin alone, the RR for live birth was 1.74 (95% CI 1.28 to 2.35, 2 trials, 140 women).
AUTHORS' CONCLUSIONS
The combination of heparin (UFH or LMWH) plus aspirin during the course of pregnancy may increase live birth rate in women with persistent aPL when compared with aspirin treatment alone. The observed beneficial effect of heparin was driven by one large study in which LMWH plus aspirin was compared with aspirin alone. Adverse events were frequently not, or not uniformly, reported in the included studies. More research is needed in this area in order to further evaluate potential risks and benefits of this treatment strategy, especially among women with aPL and recurrent pregnancy loss, to gain consensus on the ideal prevention for recurrent pregnancy loss, based on a risk profile.
Topics: Abortion, Habitual; Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; Anticoagulants; Aspirin; Bias; Drug Therapy, Combination; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Live Birth; Lupus Coagulation Inhibitor; Placebos; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Randomized Controlled Trials as Topic; beta 2-Glycoprotein I
PubMed: 32358837
DOI: 10.1002/14651858.CD012852.pub2