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Annals of Translational Medicine Dec 2023Increased plasma levels of alkaline phosphatase (ALP) have been associated to a worse prognosis in several types of diseases. In the present review, the authors aimed to... (Review)
Review
BACKGROUND
Increased plasma levels of alkaline phosphatase (ALP) have been associated to a worse prognosis in several types of diseases. In the present review, the authors aimed to study the relationship between plasma levels of ALP and overall mortality in patients with stroke.
METHODS
A systematic review was carried out, searching two databases: Web of Science and Medline/PubMed.
RESULTS
A total of nine studies that included data on overall mortality in stroke patients were selected. The selected studies were published between 2010 and 2022 and were predominantly from Asia. The articles reviewed quantified ALP levels through different methods: highest versus lowest quintiles of plasma ALP (three reports); highest versus lowest quartiles of plasma ALP (four reports); and plasma ALP levels in deceased versus in surviving patients (two reports). All selected studies showed an increased mortality associated to elevated ALP levels, irrespective of stroke type and length of follow-up, from a mean of 10 days to 2.5 years. The studies comparing the highest to the lowest ALP quintiles showed an aggregate value of 1.8 times greater risk of mortality for the former, when compared to the latter. Whereas, the studies comparing the highest to the lowest ALP quartiles showed an aggregate value of 2.4 times greater risk of mortality for the former, when compared to the latter.
CONCLUSIONS
Elevated ALP levels are associated with increased mortality in stroke patients and provide cost effective prognostic indicators of mortality in stroke.
PubMed: 38213797
DOI: 10.21037/atm-23-1627 -
Journal of Clinical and Experimental... 2023Post-COVID-19 cholangiopathy (PCC) is a rare but poorly understood and serious complication of COVID-19 infection. We sought to better understand the epidemiology,... (Review)
Review
OBJECTIVES
Post-COVID-19 cholangiopathy (PCC) is a rare but poorly understood and serious complication of COVID-19 infection. We sought to better understand the epidemiology, mechanism of action, histology, imaging findings, and outcomes of PCC.
METHODS
We searched PubMed, Cochrane Library, Embase, and Web of Science from December 2019 to December 2021. Mesh words used "post-Covid-19 cholangiopathy," "COVID-19 liver injury," "Covid-19 and cholangiopathy," and "COVID-19 liver disease." The data on epidemiology, mechanism of action, histology, imaging findings, and outcomes were collected.
RESULTS
PCC was reported in 30 cases during the study period. The mean (standard deviation [SD]) age was 53.7 (5). Men accounted for cases (83.3%). All patients had required intensive level of care and mechanical ventilation. Mean (SD) number of days from COVID infection to severe disease or liver disease was 63.5 (38). Peak mean (SD) alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and total bilirubin were 2014 (831.8) U/L, 1555 (2432.8) U/L, 899.72 (1238.6) U/L, and 10.32 (9.32) mg/dl, respectively. Four patients successfully underwent liver transplantation.
CONCLUSION
PCC is a severe and progressive complication of COVID-19 infection. More research is needed to better understand the pathophysiology and best treatment approach. Clinicians should suspect PCC in patients with cholestatic liver injury following COVID-19 infection.
PubMed: 36337085
DOI: 10.1016/j.jceh.2022.10.009 -
Annals of Hepatology 2022We performed a systematic review and meta-analysis to evaluate the prevalence of concomitant Sjögren's syndrome (SS) with primary biliary cholangitis (PBC) in adults... (Meta-Analysis)
Meta-Analysis
INTRODUCTION AND OBJECTIVES
We performed a systematic review and meta-analysis to evaluate the prevalence of concomitant Sjögren's syndrome (SS) with primary biliary cholangitis (PBC) in adults and quantify the impact of SS on PBC.
METHODS
PubMed, Web of Science and Cochrane library were searched using subject terms and predefined inclusion and exclusion criteria.
RESULTS
Seventeen articles were included. The prevalence of SS in PBC patients ranged from 3.5 to 73% (35% pooled) (95% CI: 28-41%; p < 0.01). Seven studies included various biochemical indicators, including alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (γ-GT), total bilirubin (TBiL), albumin (ALB) and platelet (PLT), and immunological indexes including IgG, IgM, antinuclear antibody (ANA), anti-mitochondrial antibody (AMA), AMA-M2 and anti-Ro/Sjögren's syndrome antigen A (SSA) antibodies. Meta-analysis showed that there were no significant differences in ALT, AST, ALP, γ-GT, TBiL and IgM levels between PBS and PBC with SS. Pooled analysis showed that ALB (MD=0.82; 95% CI: 0.08-1.56) and PLT (MD=30.41; 95% CI: 10.16-50.66) levels were lower, IgG levels (MD=-1.55; 95% CI: -2.39 to -0.72) were higher, and the positive ratios of ANA (RR=0.92; 95% CI: 0.87-0.98), AMA (RR=0.94; 95% CI: 0.89-0.98), AMA-M2 (RR=0.77; 95% CI: 0.70-0.85) and anti-Ro/SSA antibodies (RR=0.29; 95% CI: 0.08-1.01) were significantly higher in PBC patients with SS than in PBC patients.
CONCLUSIONS
Our study confirms that SS is common in PBC. Comorbid SS appears to influence the clinical phenotype of PBC and may therefore influence the management of PBC.
Topics: Humans; Sjogren's Syndrome; Liver Cirrhosis, Biliary; Autoantibodies; Prevalence; Antibodies, Antinuclear; gamma-Glutamyltransferase; Alkaline Phosphatase; Alanine Transaminase; Immunoglobulin M; Immunoglobulin G
PubMed: 35970319
DOI: 10.1016/j.aohep.2022.100746 -
Alimentary Pharmacology & Therapeutics Jan 2023Primary sclerosing cholangitis (PSC) is a progressive liver disease with poor prognosis and no effective therapies to prevent progression. An aetiopathological link... (Review)
Review
BACKGROUND
Primary sclerosing cholangitis (PSC) is a progressive liver disease with poor prognosis and no effective therapies to prevent progression. An aetiopathological link between PSC and gastrointestinal microbial dysbiosis has been suggested.
AIM
To evaluate all potential medical therapies which may exert their effect in PSC by modulation of the gut-liver axis.
METHODS
We conducted a comprehensive scoping review of PubMed and Cochrane Library, including all articles evaluating an intervention aimed at manipulating the gastrointestinal microbiome in PSC.
RESULTS
A wide range of therapies proposed altering the gastrointestinal microbiome for the treatment of PSC. In particular, these considered antibiotics including vancomycin, metronidazole, rifaximin, minocycline and azithromycin. However, few therapies have been investigated in randomised, placebo-controlled trials. Vancomycin has been the most widely studied antibiotic, with improvement in alkaline phosphatase reported in two randomised controlled trials, but with no data on disease progression. Unlike antibiotics, strategies such as faecal microbiota transplantation and dietary therapy can improve microbial diversity. However, since these have only been tested in small numbers of patients, robust efficacy data are currently lacking.
CONCLUSIONS
The gut-liver axis is increasingly considered a potential target for the treatment of PSC. However, no therapies have been demonstrated to improve transplant-free survival. Innovative and well-designed clinical trials of microbiome-targeted therapies with long-term follow-up are required for this orphan disease.
Topics: Humans; Cholangitis, Sclerosing
PubMed: 36324251
DOI: 10.1111/apt.17251 -
Frontiers in Pharmacology 2022Pruritus is a common complication in patients with primary biliary cholangitis (PBC). The pathogenesis is not clear, and also the precise therapeutic measures remain...
Pruritus is a common complication in patients with primary biliary cholangitis (PBC). The pathogenesis is not clear, and also the precise therapeutic measures remain alluring. In order to systematically evaluate the efficacy and safety of drug interventions in the treatment of pruritus associated with PBC, this systemic review and meta-analysis was conducted. The randomized controlled trials (RCTs) on drug interventions in the treatment of pruritus associated with primary cholangitis were searched in the electronic databases of PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov. Two researchers independently screened the literature, extracted and integrated the data, and assessed the bias risk of the selected literature, according to the . Finally, the STATA 15.0 software was used for the meta-analysis. A total of 23 RCTs involving 2,194 patients were studied, that included 12 pharmacological interventions. In terms of itching relief, compared with placebo, UDCA, methotrexate and GSK2330672 had a definite effect in improving pruritus (pruritus remission rate before and after treatment, 0.05). In terms of serum indexes, compared with placebo group, UDCA, OCA, rifampicin, cyclosporine, NGM282, seladelpar and colchicine may improve blood alkaline phosphatase (ALP) ( 0.05), but only rifampicin showed low heterogeneity. UDCA, bezafibrate, OCA, rifampicin, NGM282 and others may improve blood γ-glutamyl transpeptidase (γ-GGT) ( 0.05), but due to the high heterogeneity and the limitation of research samples, a clear conclusion cannot be drawn. In terms of adverse events, except high (>15 mg/kg/day) and low doses (<13 mg/kg/day) of UDCA increased the incidence of adverse events, there were no risk of increasing the incidence of adverse events compared with placebo ( 0.05), and a moderate dose of UDCA (13-15 mg/kg/day) and malotilate (1,500 mg/day) may also help in reducing the incidence of adverse events ( 0.05). UDCA, methotrexate and GSK2330672 may relieve itching in patients with PBC, but there is a lack of robust evidence to support their effect on ALP or γ-GGT. Due to the heterogeneity in the published studies, based on the present review, we cannot explicitly recommend any specific drug for the treatment of PBC-related pruritus. link-https://osf.io/2g8ya, identifier 10.17605/OSF.IO/2G8YA.
PubMed: 36339545
DOI: 10.3389/fphar.2022.835991 -
Cureus Jan 2023The prevalence of osteoporosis in individuals with cirrhosis varies based on the diagnostic approach and etiology of the underlying liver disease. This systematic review... (Review)
Review
The prevalence of osteoporosis in individuals with cirrhosis varies based on the diagnostic approach and etiology of the underlying liver disease. This systematic review aims to evaluate the prevalence of osteoporosis in individuals with cirrhosis. Electronic databases were searched for studies reporting the prevalence of osteoporosis among patients with cirrhosis. The primary outcome was the presence of osteoporosis, as determined by a dual-energy x-ray absorptiometry (DEXA) scan. Secondary outcomes were levels of biochemical markers of bone metabolism, including calcium, vitamin D, phosphorus, and parathormone (PTH) levels. A cohort of 836 patients from 10 studies was included in the final analysis. The pooled rate of osteoporosis was 14.80% (95% CI: 14.19-15.49). Pooled levels of biochemical markers of bone metabolism were as follows: calcium 9.09 mg/dL (95% CI: 8.73-9.45), 25-hydroxyvitamin D (25-OH vitamin D) 15.41 ng/mL (95% CI: 14.79-16.03), phosphorus 15.41 mg/dL (95% CI: 2.99-3.51), and PTH 26.58 pg/mL (95% CI: 25.45-27.71). Pooled levels of liver biochemistries were: bilirubin 3.04 mg/dL (95% CI: 2.84-3.25), aspartate aminotransferase (AST) 65.35 U/L (95% CI: 61.39-69.31), alanine aminotransferase (ALT) 50.17 U/L (95% CI: 46.18-54.10), alkaline phosphatase 133.31 U/L (95% CI: 124.89-141.73), and albumin 3.25 g/dL (95% CI: 3.05-3.45). Cirrhosis appears to be associated with an increased risk for osteoporosis, with a pooled prevalence of 15%. This can include men and individuals younger than 50 years of age, a cohort not typically considered to be at an increased risk of osteoporosis. Levels of 25-hydroxyvitamin D and insulin-like growth factor-1 (IGF-1) were also significantly low. Further studies are required to evaluate the risk of osteoporosis based on the etiology and stage of cirrhosis, especially in younger males, to incorporate this into future prediction models for fragility fractures.
PubMed: 36788896
DOI: 10.7759/cureus.33721 -
BMJ Open Jun 2023Metformin is associated with osteoblastogenesis and osteoclastogenesis. This study aims to investigate the impacts of metformin therapy on bone mineral density (BMD) and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Metformin is associated with osteoblastogenesis and osteoclastogenesis. This study aims to investigate the impacts of metformin therapy on bone mineral density (BMD) and bone turnover markers.
DESIGN
Systematic review and meta-analysis of randomised controlled trials.
METHODS
Searches were carried out in PubMed, EMBASE, Web of science, Cochrane library, ClinicalTrials.gov from database inception to 26 September 2022. Two review authors assessed trial eligibility in accordance with established inclusion criteria. The risk of bias was assessed using the Cochrane Risk of Bias tool (RoB V.2.0). Data analysis was conducted with Stata Statistical Software V.16.0 and Review Manager Software V.5.3.
RESULTS
A total of 15 studies with 3394 participants were identified for the present meta-analysis. Our pooled results indicated that metformin had no statistically significant effects on BMD at lumbar spine (SMD=-0.05, 95% CI=0.19 to 0.09, p=0.47, participants=810; studies=7), at femoral (MD=-0.01 g/cm, 95% CI=-0.04 to 0.01 g/cm, p=0.25, participants=601; studies=3) and at hip (MD=0.01 g/cm, 95% CI=0.02 to 0.03 g/cm, p=0.56, participants=634; studies=4). Metformin did not lead to significant change in osteocalcin, osteoprotegerin and bone alkaline phosphatase. Metformin induced decreases in N-terminal propeptide of type I procollagen (MD=-6.09 µg/L, 95% CI=9.38 to -2.81 µg/L, p=0.0003, participants=2316; studies=7) and C-terminal telopeptide of type I collagen (MD=-55.80 ng/L, 95% CI=97.33 to -14.26 ng/L, p=0.008, participants=2325; studies=7).
CONCLUSION
This meta-analysis indicated that metformin had no significant effect on BMD. Metformin decreased some bone turnover markers as N-terminal propeptide of type I procollagen and C-terminal telopeptide of type I collagen. But the outcomes should be interpreted with caution due to several limitations.
Topics: Humans; Bone Density; Metformin; Lumbar Vertebrae; Bone Remodeling
PubMed: 37355276
DOI: 10.1136/bmjopen-2023-072904 -
Frontiers in Nutrition 2023Resveratrol is a natural polyphenol compound that is widely present in herbal medicines such as , , and Catsiatora Linn and is used in traditional Chinese medicine to...
BACKGROUND
Resveratrol is a natural polyphenol compound that is widely present in herbal medicines such as , , and Catsiatora Linn and is used in traditional Chinese medicine to treat metabolic bone deseases. Animal experiments have shown that resveratrol may have a strong treatment effect against osteoporosis (OP). The purpose of this study was to explore the efficacy of resveratrol in treating OP animal models based on preclinical research data.
METHODS
This study was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases from inception to May 8, 2023, to identify animal experiments on the treatment of OP with resveratrol. The effect sizes of bone mineral density (BMD), parameters of micro-CT, serum calcium, phosphorus, alkaline phosphatase (ALP) and osteocalcin were expressed as the mean differences (MDs) and 95% confidence intervals (CIs). RevMan 5.4 software was used for data analysis.
RESULTS
This meta-analysis included a total of 15 animal experiments, including 438 OP rats. The meta-analysis results showed that compared with the control group, resveratrol (<10, 10-25, 40-50, ≥ 60 mg/kg/day) significantly increased femoral and lumbar bone mineral density (BMD) in OP rats ( < 0.05). Resveratrol (<10 mg/kg/day) significantly increased the BMD of the total body (MD = 0.01, 95% CI: 0.01 to 0.01, < 0.001). In terms of improving the parameters related to micro-CT, resveratrol (40-50 mg/kg/day) can increase trabecular thickness and trabecular number and reduce trabecular spacing ( < 0.05). Compared with the control group, resveratrol can reduce the concentration of calcium and phosphorus in serum but has no significant effect on serum ALP and osteocalcin ( > 0.05). The results of subgroup analysis showed that resveratrol increased the whole-body BMD of SD rats ( = 0.002) but did not improve the whole-body BMD of 3-month-old rats ( = 0.17).
CONCLUSION
Resveratrol can increase BMD in OP rat models, and its mechanism of action may be related to improving bone microstructure and regulating calcium and phosphorus metabolism. The clinical efficacy of resveratrol in the treatment of OP deserves further research.
PubMed: 37575330
DOI: 10.3389/fnut.2023.1234756 -
Frontiers in Veterinary Science 2023Canine osteoarthritis (OA) is a degenerative disease with chronic inflammation of internal and external joint structures in dogs. spp. contains cannabidiol (CBD), a...
INTRODUCTION
Canine osteoarthritis (OA) is a degenerative disease with chronic inflammation of internal and external joint structures in dogs. spp. contains cannabidiol (CBD), a substance known for various potential indications, such as pain relief and anti-inflammatory in various types of animals, including dogs with OA. As CBD is increasingly in the spotlight for medical use, we aimed to perform a systematic review and meta-analysis to evaluate the efficacy and safety of CBD in treating canine OA.
METHODS
We searched PubMed, Embase, Scopus, and CAB Direct for animal intervention studies investigating the effects of CBD for canine OA from database inception until February 28, 2023. Study characteristics and findings were summarized. A risk of bias in the included studies was assessed. Meta-analyses were performed using a random-effects model to estimate the effects of CBD on pain scores (0-10), expressed as mean difference (MD) and 95% confidence interval (95% CI). Certainty of evidence was assessed using GRADE.
RESULTS
Five articles were included, which investigated the effects of CBD in 117 dogs with OA. All studies were rated as having a high risk of bias. CBD products varied substantially, i.e., oral full-spectrum CBD oil in four studies, and isolated CBD oil and liposomal CBD oil in another study. Treatment duration varied from 4-12 weeks. Meta-analyses of three studies found that, in dogs with OA, treatment with oral full-spectrum CBD oil may reduce pain severity scores (MD; -0.60, 95% CI; -1.51 to 0.31, = 45.64%, = 0.19) and pain interference scores (MD; -1.52, 95% CI; -3.84 to 0.80, = 89.59%, = 0.20) but the certainty of evidence was very low. CBD is generally considered safe and well-tolerated in the short-run, with few mild adverse events observed, such as vomiting and asymptomatic increase in alkaline phosphatase level.
CONCLUSION
CBD is considered safe for treating canine OA. CBD may reduce pain scores, but the evidence is very uncertain to conclude its clinical efficacy. High-quality clinical trials are needed to further evaluate the roles of CBD in canine OA.
PubMed: 37781283
DOI: 10.3389/fvets.2023.1248417 -
Hepatology Communications Jan 2024Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving treatment. Several studies have evaluated the effect of different biologic therapies on PSC with inconclusive findings. We conducted a systematic review and meta-analysis to assess the effects of biologics in PSC and associated inflammatory bowel disease (IBD).
METHODS
MEDLINE, Scopus, and Embase were searched up to July 31, 2023, for studies reporting the effects of biologics in patients with PSC-IBD. Effects of biologic therapy on alkaline phosphatase, total bilirubin, ulcerative colitis response score, and adverse events were calculated and expressed as standardized difference of means (SMD), proportions, and 95% CI using a random-effects model.
RESULTS
Six studies, including 411 PSC-IBD patients who received biologics, were included. Biologic treatment was associated with no change in alkaline phosphatase (SMD: 0.1, 95% CI: -0.07 -0.17, p=0.43), but a small and statistically significant increase in total bilirubin (SMD: 0.2, 95% CI: 0.05-0.35, p<0.01). 31.2% (95% CI: 23.8-39.7) of patients with IBD achieved endoscopic response, and there was a significant improvement in ulcerative colitis response score (SMD: -0.6,95% CI: -0.88 to 0.36, p<0.01). Furthermore, 17.6% (95% CI: 13.0-23.5) of patients experienced adverse events severe enough to discontinue therapy, and 29.9% (95% CI: 25.2-34.8) had a loss of response to biologics.
CONCLUSIONS
Treatment of patients with PSC-IBD with biologics (vedolizumab, infliximab, and adalimumab) was not associated with improvement of biochemical markers of cholestasis. Biologics are effective in treating the colitis associated with PSC. Vedolizumab was associated with worsening liver enzymes in contrast to other biologics, a finding that warrants further study.
Topics: Humans; Colitis, Ulcerative; Alkaline Phosphatase; Cholangitis, Sclerosing; Inflammatory Bowel Diseases; Bilirubin; Cholestasis; Biological Products
PubMed: 38206197
DOI: 10.1097/HC9.0000000000000347