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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 -
The International Journal of Biological... Mar 2023Numerous studies have reported the clinical value of alkaline phosphatase (ALP) and its bone-specific isoforms (bone-specific alkaline phosphatase (BAP)) in breast... (Meta-Analysis)
Meta-Analysis Review
Numerous studies have reported the clinical value of alkaline phosphatase (ALP) and its bone-specific isoforms (bone-specific alkaline phosphatase (BAP)) in breast cancer. The purpose of this meta-analysis was to summarize the prognostic value of serum ALP and BAP in breast cancer, especially focused on bone metastasis and survival. PRISMA guidelines were followed to conduct this review. Observational studies were searched in PubMed, Cochcrane Library and EMBASE to January 1, 2022. Data were extracted to explore the prognostic value of ALP and BAP. The quality of the included studies was assessed and the outcome effects were evaluated. Subgroup and sensitivity analyses were performed to explore the potential sources of heterogeneity. Publication bias was assessed. There was a total of 53 studies with 22,436 patients included. For the primary outcome of survival, high levels of both ALP and BAP were associated with short survival time. The hazard ratio of high ALP level on overall survival was 1.72 (95% CI 1.37, 2.16, < 0.001). For the secondary outcomes, a high ALP level (not BAP) was detected in breast cancer compared with healthy controls, and high levels of both ALP and BAP were risk factors for bone metastasis, while ALP (not BAP) was a risk factor for non-bone metastasis. This study showed that high levels of both serum ALP and BAP were associated with metastasis (BAP was associated with bone metastasis) and survival in breast cancer. The biomarkers could provide useful information for the early diagnostic assessment and monitoring in the follow-up of breast cancer patients.
Topics: Humans; Female; Alkaline Phosphatase; Prognosis; Breast Neoplasms; Biomarkers; Bone Neoplasms
PubMed: 36775971
DOI: 10.1177/03936155231154662 -
International Journal of Clinical... Feb 2020To assess the prognostic value of alkaline phosphatase in patients with hormone-sensitive prostate cancer. (Meta-Analysis)
Meta-Analysis
PURPOSE
To assess the prognostic value of alkaline phosphatase in patients with hormone-sensitive prostate cancer.
METHODS
A systematic review and meta-analysis was performed using the PUBMED, Web of Science, Cochrane Library, and Scopus in April 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared hormone-sensitive prostate cancer patients with high vs. low alkaline phosphatase to determine its predictive value for overall survival, cancer-specific survival, and progression-free survival. We performed a formal meta-analysis of these outcomes.
RESULTS
42 articles with 7938 patients were included in the systematic review and 28 studies with 5849 patients for the qualitative assessment. High alkaline phosphatase was associated with worse overall survival (pooled HR 1.72; 95% CI 1.37-2.14) and progression-free survival (pooled HR 1.30; 95% CI 1.10-1.54). In subgroup analyses of patients with "high-volume" and "low-volume", alkaline phosphatase was associated with the overall survival (pooled HR 1.41; 95% CI 1.21-1.64 and pooled HR 1.64; 95% CI, 1.06-2.52, respectively).
CONCLUSIONS
In this meta-analysis, elevated serum levels of alkaline phosphatase were associated with an increased risk of overall mortality and disease progression in patients with hormone-sensitive prostate cancer. In contrast, those were not associated with an increased risk of cancer-specific mortality. Alkaline phosphatase was independently associated with overall survival in both patients with "high-volume" and "low-volume" hormone-sensitive prostate cancer. Alkaline phosphatase may be useful for being integrated into prognostic tools that help guide treatment strategy, thereby facilitating the shared decision making process.
Topics: Alkaline Phosphatase; Biomarkers, Tumor; Hormones; Humans; Male; Prognosis; Prostatic Neoplasms; Survival Analysis
PubMed: 31768692
DOI: 10.1007/s10147-019-01578-9 -
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 -
Medicine Jan 2020This systematic review and meta-analysis were performed to evaluate kidney function in patients with sepsis-associated acute kidney injury (SA-AKI) on alkaline... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and meta-analysis were performed to evaluate kidney function in patients with sepsis-associated acute kidney injury (SA-AKI) on alkaline phosphatase (AP) therapy.
METHODS
PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched electronically from inception until May 4, 2019 and randomized controlled studies assessing AP treatment in patients with SA-AKI were included. Pool analyses with fixed effects or random effects models calculated pooled mean, standard deviation, and odds ratio (OR) with 95% confidence interval (CI).
RESULTS
Four randomized controlled trials involving AP therapy for 392 patients with SA-AKI were included. AP had a positive effect on endogenous creatinine clearance (ECC) in patients with SA-AKI at day 14 (random effects: mean difference = 10.56, 95% CI = 2.27-18.84, P = .01) and day 28 (random effects: mean difference = 14.30, 95% CI = 6.27-22.33, P = .0005). All-cause mortality at day 28 (fixed effects: OR = 0.62, 95% CI = 0.40-0.97, P = .04) and day 90 (fixed effects: OR = 0.61, 95% CI = 0.39-0.96, P = .03) improved. Plasma creatinine level (fixed effects: mean difference = -76.83, 95% CI = -146.92 to -6.74, P = .03) and biomarkers level (random effects: mean difference = -6.57, 95% CI = -10.74 to -2.40, P < .00001) also improved in the therapy group compared with placebo.
CONCLUSION
In patients with SA-AKI, AP showed a relatively late protective effect by improving ECC at days 7, 14, and 28. ECC level improved when patients received AP dose of 0.212 mg/kg. Mortality improved at days 28 and 90, respectively, when patients received AP dose of 1.6 mg/kg. Levels of overall AKI biomarkers were improved in short term.
Topics: Acute Kidney Injury; Alkaline Phosphatase; Creatinine; Dose-Response Relationship, Drug; Humans; Randomized Controlled Trials as Topic; Sepsis
PubMed: 31977869
DOI: 10.1097/MD.0000000000018788 -
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 -
BMC Oral Health Apr 2020Bisphosphonate coating of dental implants is a promising tool for surface modification aiming to improve the osseointegration process and clinical outcome. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bisphosphonate coating of dental implants is a promising tool for surface modification aiming to improve the osseointegration process and clinical outcome. The biological effects of bisphosphonates are thought to be mainly associated with osteoclasts inhibition, whereas their effects on osteoblast function are unclear. A potential of bisphosphonate coated surfaces to stimulate osteoblast differentiation was investigated by several in vitro studies with contradictory results. The purpose of this systematic review and meta-analysis was to evaluate the effect of bisphosphonate coated implant surfaces on alkaline phosphatase activity in osteoblasts.
METHODS
In vitro studies that assessed alkaline phosphatase activity in osteoblasts following cell culture on bisphosphonate coated titanium surfaces were searched in electronic databases PubMed/MEDLINE, Scopus and ISI Web of Science. Animal studies and clinical trials were excluded. The literature search was restricted to articles written in English and published up to August 2019. Publication bias was assessed by the construction of funnel plots.
RESULTS
Eleven studies met the inclusion criteria. Meta-analysis showed that coating of titanium surfaces with bisphosphonates increases alkaline phosphatase activity in osteoblasts after 3 days (n = 1), 7 (n = 7), 14 (n = 6) and 21 (n = 3) days. (7 days beta coefficient = 1.363, p-value = 0.001; 14 days beta coefficient = 1.325, p-value < 0.001; 21 days beta coefficient = 1.152, p-value = 0.159).
CONCLUSIONS
The meta-analysis suggests that bisphosphonate coatings of titanium implant surfaces may have beneficial effects on osteogenic behaviour of osteoblasts grown on titanium surfaces in vitro. Further studies are required to assess to which extent bisphosphonates coating might improve osseointegration in clinical situations.
Topics: Alkaline Phosphatase; Animals; Cell Differentiation; Cells, Cultured; Dental Implants; Diphosphonates; Osseointegration; Osteoblasts; Surface Properties; Titanium
PubMed: 32334598
DOI: 10.1186/s12903-020-01089-4 -
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 -
Scientific Reports Jan 2023The prognostic value of albumin-to-alkaline phosphatase ratio (AAPR) in patients with hepatocellular carcinoma (HCC) remains controversial. This meta-analysis aims to... (Meta-Analysis)
Meta-Analysis
The prognostic value of albumin-to-alkaline phosphatase ratio (AAPR) in patients with hepatocellular carcinoma (HCC) remains controversial. This meta-analysis aims to evaluate the prognostic role of AAPR in patients with HCC. The databases of Web of Science, Embase, Cochrane Library and PubMed were comprehensively searched from inception to April 25, 2022. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated with Stata 16.0 software for the assessment of the relationship between AAPR and overall survival (OS) as well as recurrence-free survival (RFS) in patients with HCC. A total of 2634 patients from 12 cohorts were included in this meta-analysis. The pooled results showed that lower AAPR predicted poorer OS (HR 2.02, 95% CI 1.78-2.30). Similarly, pooled results demonstrated that lower AAPR also predicted poorer RFS (HR 1.88, 95% CI 1.37-2.57). The heterogeneity for RFS by multivariate analytic results and the publication bias for OS existed, however, the subgroup analysis, meta-regression analysis as well as adjustment using trim-and-fill analysis confirmed an association between AAPR and OS as well as RFS. This meta-analysis proves that lower AAPR in patients with HCC predicted inferior survival outcomes, and AAPR might be a promising indicator for the prognosis of HCC.
Topics: Humans; Albumins; Alkaline Phosphatase; Carcinoma, Hepatocellular; Liver Neoplasms; Prognosis
PubMed: 36720974
DOI: 10.1038/s41598-023-28889-2 -
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