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Journal of Gastroenterology and... Apr 2020Crigler-Najjar syndrome (CNS) results from biallelic mutations of UGT1A1 causing partial or total loss of uridine 5'-diphosphate glucuronyltransferase activity leading...
BACKGROUND AND AIM
Crigler-Najjar syndrome (CNS) results from biallelic mutations of UGT1A1 causing partial or total loss of uridine 5'-diphosphate glucuronyltransferase activity leading to unconjugated hyperbilirubinemia and its attendant risk for irreversible neurological injury (kernicterus). CNS is exceedingly rare and has been only partially characterized through relatively small studies, each comprising between two and 57 patients.
METHODS
A systematic literature review was conducted to consolidate data on the patient, caregiver, and societal burden of CNS.
RESULTS
Twenty-eight articles on clinical aspects of CNS were identified, but no published data on its humanistic or economic burden were found. In patients with complete UGT1A1 deficiency (type 1 CNS [CNS-I]), unconjugated bilirubin levels increase 3-6 mg/dL/day during the newborn period and reach neurologically dangerous levels between 5 and 14 days of age. Phototherapy is the mainstay of treatment but poses significant challenges to patients and their families. Despite consistent phototherapy, patients with CNS-I have worsening hyperbilirubinemia with advancing age. Liver transplantation is the only definitive therapy for CNS-I and is increasingly associated with excellent long-term survival but also incurs high costs, medical and surgical morbidities, and risks of immunosuppression.
CONCLUSIONS
Crigler-Najjar syndrome is associated with a substantial burden, even with existing standards of care. The development of novel disease-modifying therapies has the potential to reduce disease burden and improve the lives of CNS patients and their families.
Topics: Bilirubin; Cost of Illness; Crigler-Najjar Syndrome; Female; Gene Deletion; Glucuronosyltransferase; Humans; Hyperbilirubinemia; Infant, Newborn; Liver Transplantation; Male; Phototherapy; Rare Diseases
PubMed: 31495946
DOI: 10.1111/jgh.14853 -
Cardiovascular Drugs and Therapy Feb 2020
Meta-Analysis
Chewed or Crushed Administration of Adenosine Diphosphate Receptor Inhibitors in Acute Coronary Syndromes: a Systematic Review and Meta-analysis of Randomized Controlled Trials.
Topics: Acute Coronary Syndrome; Administration, Oral; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Randomized Controlled Trials as Topic; Tablets; Ticagrelor; Treatment Outcome
PubMed: 31485881
DOI: 10.1007/s10557-019-06905-w -
Cerebrovascular Diseases (Basel,... 2019A rapid serum biomarker that confirms or rules out a transient ischemic attack (TIA) would be of great value in clinical practice. We aimed to systematically review...
BACKGROUND AND PURPOSE
A rapid serum biomarker that confirms or rules out a transient ischemic attack (TIA) would be of great value in clinical practice. We aimed to systematically review current evidence for the diagnostic accuracy of blood biomarkers in the early diagnosis of TIA.
METHODS
This is a systematic review with quality appraisal of individual studies using the QUADAS-2 tool. MEDLINE and EMBASE databases were searched up to May 1, 2017, to select primary diagnostic accuracy studies evaluating potential biomarkers in blood for the diagnosis of TIA or ischemic stroke.
RESULTS
Of 4,215 studies retrieved, 78 met our eligibility criteria. Forty-five studies restricted their population to ischemic stroke patients, 32 included both TIA and ischemic stroke patients, and only one study was restricted to TIA patients. In total 62/78 (79.5%) studies had a case-control design comparing TIA or stroke patients with healthy subjects. Overall, 125 single biomarkers and 5 biomarker panels were studied, with a median number of participants per study of 92.0 (interquartile range 44.8-144.5), varying from 8 to 915. Sufficient information to extract 2 × 2 tables was available for 35 (44.9%) articles, and for 60 (48.0 %) biomarkers. Several markers, such as NR2A/B (antibodies), Parkinson 7, nucleoside diphosphate kinase A, ubiquitin fusion degradation protein-1, and heart-type fatty acid binding protein, have shown moderate to high diagnostic accuracy in multiple studies.
CONCLUSIONS
Although the methodological quality of studies evaluating biomarkers of brain ischemia was poor, several biomarkers have shown the potential to detect transient brain ischemia in an early phase. Diagnostic accuracy studies in suspected cases of TIA are needed to determine their true clinical value.
Topics: Biomarkers; Early Diagnosis; Humans; Ischemic Attack, Transient; Predictive Value of Tests; Prognosis; Reproducibility of Results
PubMed: 31473737
DOI: 10.1159/000502449 -
BMC Cancer Aug 2019Positron emission tomography (PET) and PET/computed tomography (PET/CT) imaging with 3,4-dihydroxy-6-[F] fluoro-L-phenylalanine (F-FDOPA) has been used in the evaluation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Positron emission tomography (PET) and PET/computed tomography (PET/CT) imaging with 3,4-dihydroxy-6-[F] fluoro-L-phenylalanine (F-FDOPA) has been used in the evaluation of gliomas. We performed a meta-analysis to obtain the diagnostic and grading accuracy of F-FDOPA PET and PET/CT in patients with gliomas.
METHODS
PubMed, Embase, Cochrane Library and Web of Science were searched through 13 May 2019. We included studies reporting the diagnostic performance of F-FDOPA PET or PET/CT in glioma patients. Pooled sensitivity, specificity, and area under the summary receiver operating characteristic (SROC) curve were calculated from eligible studies on a per-lesion basis.
RESULTS
Eventually, 19 studies were included. Across 13 studies (370 patients) for glioma diagnosis, the pooled sensitivity and specificity of F-FDOPA PET and PET/CT were 0.90 (95%CI: 0.86-0.93) and 0.75 (95%CI: 0.65-0.83). Across 7 studies (219 patients) for glioma grading, F-FDOPA PET and PET/CT showed a pooled sensitivity of 0.88 (95%CI: 0.81-0.93) and a pooled specificity of 0.73 (95%CI: 0.64-0.81).
CONCLUSIONS
F-FDOPA PET and PET/CT demonstrated good performance for diagnosing gliomas and differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs). Further studies implementing standardized PET protocols and investigating the grading parameters are needed.
Topics: Adolescent; Adult; Aged; Brain Neoplasms; Child; Data Accuracy; Female; Fluorine Radioisotopes; Formycins; Glioma; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Publication Bias; ROC Curve; Radiopharmaceuticals; Ribonucleotides; Sensitivity and Specificity; Young Adult
PubMed: 31382920
DOI: 10.1186/s12885-019-5938-0 -
World Journal of Gastroenterology Jun 2019Changes in N-linked glycosylation have been observed in the circulation of individuals with hepatocellular carcinoma. In particular, an elevation in the level of core...
BACKGROUND
Changes in N-linked glycosylation have been observed in the circulation of individuals with hepatocellular carcinoma. In particular, an elevation in the level of core fucosylation has been observed. However, the mechanisms through which core fucose is increased are not well understood. We hypothesized that a review of the literature and related bioinformatic review regarding six genes known to be involved in the attachment of core fucosylation, the synthesis of the fucosylation substrate guanosine diphosphate (GDP)-fucose, or the transport of the substrate into the Golgi might offer mechanistic insight into the regulation of core fucose levels.
AIM
To survey the literature to capture the involvement of genes regulating core N-linked fucosylation in hepatocellular carcinoma.
METHODS
The PubMed biomedical literature database was searched for the association of hepatocellular carcinoma and each of the core fucose-related genes and their protein products. We also queried The Cancer Genome Atlas Liver hepatocellular carcinoma (LIHC) dataset for genetic, epigenetic and gene expression changes for the set of six genes using the tools at cBioportal.
RESULTS
A total of 27 citations involving one or more of the core fucosylation-related genes (FPGT, FUK, FUT8, GMDS, SLC35C1, TSTA3) and hepatocellular carcinoma were identified. The same set of gene symbols was used to query the 371 patients with liver cancer in the LIHC dataset to identify the frequency of mRNA over or under expression, as well as non-synonymous mutations, copy number variation and methylation level. Although all six genes trended to more samples displaying over expression relative to under-expression, it was noted that a number of tumor samples had undergone amplification of the genes of the synthesis pathway, GMDS (27 samples) and TSTA3 (78 samples). In contrast, the other four genes had undergone amplification in 2 or fewer samples.
CONCLUSION
Amplification of genes involved in the pathway for generation of GDP-fucose, GMDS and TSTA3, likely contributes to the elevated core fucose observed in hepatocellular carcinoma.
Topics: Carbohydrate Epimerases; Carcinoma, Hepatocellular; DNA Copy Number Variations; DNA Methylation; Gene Expression Regulation, Neoplastic; Glycoproteins; Glycosylation; Guanosine Diphosphate Fucose; Humans; Hydro-Lyases; Ketone Oxidoreductases; Liver Neoplasms; Metabolic Networks and Pathways; Mutation
PubMed: 31249452
DOI: 10.3748/wjg.v25.i23.2947 -
Critical Reviews in Food Science and... 2020Masked mycotoxins are biologically modified phase II metabolites formed by plant defense mechanisms through glucosylation catalyzed by uridine diphosphate...
Masked mycotoxins are biologically modified phase II metabolites formed by plant defense mechanisms through glucosylation catalyzed by uridine diphosphate -glucosyltransferases. Most of the current reports focus on the occurrence of masked mycotoxins in Europe, America, Africa, and cover other geographic regions, e.g. China and Japan. High proportions of masked mycotoxins co-occurring with their parent forms in various cereal-based food and feedstuff could clearly increase total exposures and pose additional health risks to humans and animals. In contrast to the parent mycotoxins, the data on the toxicity of masked mycotoxins are still scarce, however, the poor existing information showed that masked mycotoxins generally exhibit significant toxicities lower than those of their parent forms, especially for deoxynivalenol-3-glucoside, which is the only thoroughly investigated masked mycotoxin. Although the lower toxicity level of masked mycotoxins, these are probably hydrolyzed into their free forms by intestinal microorganisms in the digestive tract of mammals and thus contribute to unpredicted toxicity. The metabolic characteristics of reported masked mycotoxins are species-specific. The most relevant animal model of human sensitivity, the pig, is most sensitive to masked mycotoxins. This review focuses on updates in the current knowledge on country-specific natural-occurrence data in global surveys, as well as and toxicology and metabolic investigations of masked mycotoxins.
Topics: Animals; Food Contamination; Gastrointestinal Microbiome; Humans; Mycotoxins; Plants
PubMed: 30806521
DOI: 10.1080/10408398.2019.1578944 -
Cardiovascular Diabetology Jan 2019Carotid artery intima-media thickness (cIMT) progression is a surrogate marker of atherosclerosis with a high predictive value for future CVD risk. This study evaluates... (Meta-Analysis)
Meta-Analysis
Comparative effects of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on carotid artery intima-media thickness progression: a network meta-analysis.
BACKGROUND
Carotid artery intima-media thickness (cIMT) progression is a surrogate marker of atherosclerosis with a high predictive value for future CVD risk. This study evaluates the comparative efficacies of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on cIMT progression.
METHODS
We conducted a network meta-analysis (NMA) to evaluate the relative efficacies of several drug classes in modifying cIMT progression. After a literature search in several electronic databases, studies were selected by following predetermined eligibility criteria. An inverse variance-heterogeneity model was used for NMA. Sensitivity analyses were performed to check the reliability of the overall NMA, and transitivity analyses were performed to examine the effects of modifiers on the NMA outcomes.
RESULTS
Data were taken from 47 studies (15,721 patients; age: 60.2 years [95% confidence interval (CI) 58.8, 61.6]; BMI: 27.2 kg/m [95% CI 26.4, 28.0]; and gender: 58.3% males [95% CI 48.3, 68.3]). Treatment duration was 25.8 months [95% CI 22.9, 28.7]. Of the 13 drug classes in the network, treatment with phosphodiesterase III inhibitors was the most effective in retarding annual mean cIMT against network placebo (weighted mean difference (WMD) - 0.059 mm [95% CI - 0.099, - 0.020) followed by the calcium channel blockers (WMD - 0.055 mm [95% CI - 0.099, 0.001]) and platelet adenosine diphosphate inhibitors (WMD - 0.033 mm [95% CI - 0.058, 0.008]). These 3 drug classes also attained the same positions when the NMA was conducted by using first-year changes in mean cIMT. In transitivity analyses, longer treatment duration, higher body mass index (BMI), and a higher baseline cIMT were found to be independently associated with a lesser reduction in annual mean cIMT. However, in a multivariate analysis with these 3 modifiers, none of these factors was significantly associated with annual change in mean cIMT. In the placebo group, age was inversely associated with annual change in mean cIMT independently.
CONCLUSION
Phosphodiesterase III inhibitors and calcium channel blockers are found more effective than other drug classes in retarding cIMT progression. Age, BMI, and baseline cIMT may have some impact on these outcomes.
Topics: Antihypertensive Agents; Calcium Channel Blockers; Carotid Artery Diseases; Carotid Intima-Media Thickness; Disease Progression; Female; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Male; Middle Aged; Phosphodiesterase 3 Inhibitors; Platelet Aggregation Inhibitors; Predictive Value of Tests; Time Factors; Treatment Outcome
PubMed: 30700294
DOI: 10.1186/s12933-019-0817-1 -
Journal of Geriatric Oncology May 2019
Meta-Analysis
Secondary hematologic malignancies with poly adenosine diphosphate ribose polymerase inhibitors: Is the buzz real? -Insights from a meta-analysis of phase 3 randomized controlled trials.
Topics: Aged; Clinical Trials, Phase III as Topic; Female; Hematologic Neoplasms; Humans; Ovarian Neoplasms; Poly Adenosine Diphosphate Ribose; Randomized Controlled Trials as Topic
PubMed: 30665875
DOI: 10.1016/j.jgo.2019.01.008 -
BioMed Research International 2018Graves' ophthalmopathy (GO) is a complicated autoimmune disease. Various therapies have been used to manage GO; however the optimum therapy is not clear. Glucocorticoids... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Graves' ophthalmopathy (GO) is a complicated autoimmune disease. Various therapies have been used to manage GO; however the optimum therapy is not clear. Glucocorticoids (GCs) therapy is the mainstay of treatment especially for active moderate to severe patients, which needs evidence-based support.
METHOD
We searched all the randomized controlled trials (RCTs) involving corticosteroid treatment for patients diagnosed with GO from EMBASE, Medline, and the Cochrane library and then conducted a system review and meta-analysis. The electronic search covered the period from April 1966 to March 2018.
RESULT
Twenty-nine trials were included. GCs were proved to be beneficial for GO patients [response rate, risk ratio (RR) = 1.72, 95% confidence interval (CI): 1.28~2.31, P=0.0003], and intravenous corticosteroids worked significantly better than oral corticosteroids as ever reported. When compared with the single treatment of GCs, the combination of radiotherapy and GCs showed similar effects on response rate (RR=1.25, 95%CI: 0.91~1.73). A study proved the advantage of mycophenolate mofetil over GCs in three outcomes (response rate, RR=0.74, 95%CI: 0.63~0.88). Additional treatments such as technetium-99 methylene diphosphate (Tc-MDP) or cyclosporine enhanced the effect of GCs on proptosis reduction, respectively (P<0.00001 and P=0.02).
CONCLUSION
Our meta-analysis confirmed the effects of GCs in the management of GO and intravenous GCs are proved to be better than oral GCs as ever reported. Combination of radiotherapy and GCs did not enhance the effects of GCs. However, if proptosis is the main issue, combination of Tc-MDP or cyclosporine with GCs may be taken into consideration. The reported advantages of mycophenolate mofetil over GCs are noteworthy and need more RCTs to confirm.
Topics: Adrenal Cortex Hormones; Cyclosporine; Graves Ophthalmopathy; Humans; Mycophenolic Acid; Randomized Controlled Trials as Topic
PubMed: 30596092
DOI: 10.1155/2018/4845894 -
Medicine Dec 2018The current standard of chemotherapy response evaluation holds the most important prognostic factor to be the histological assessment of the tumor necrosis of the... (Meta-Analysis)
Meta-Analysis
Conventional 99mTc-(hydroxy) methylene diphosphate remains useful to predict osteosarcoma response to neoadjuvant chemotherapy: Individual patient data and aggregate data meta-analyses.
BACKGROUND
The current standard of chemotherapy response evaluation holds the most important prognostic factor to be the histological assessment of the tumor necrosis of the excised lesion, but the major challenge is to find an early prognostic factor that will allow the adjuvant treatment regimen to be adjusted. The objective of this systematic review is to provide an up-to-date and unprecedented summary of the value of Technetium-methylene diphosphate or -hydroxymethylene diphosphate (Tc-MDP/HMDP) scintigraphy for the preoperative evaluation of osteosarcoma response to chemotherapy.
METHODS
Studies evaluating the alteration ratio (percentage change of the Tc-99m -MDP/HMDP uptake between before and after neoadjuvant chemotherapy) to predict the histological response of osteosarcoma to chemotherapy were searched for in MEDLINE, EMBASE, and Web of Science. A meta-analysis of individual patient data (IPD) was performed to determine the optimal cut-off point from the receiver operating characteristic (ROC) curve. Additionally, aggregate data (AD) meta-analysis was performed to compare the value of Tc-MDP/HMDP scintigraphy with that of other quantitative modalities, such as dynamic magnetic resonance imaging (MRI), Tl scintigraphy, and F-FDG PET-CT.
RESULTS
Seven studies with 154 patients were included for the IPD meta-analysis. The optimal cut-off point of the alteration ratio was 31.0%. Five studies with 123 patients were considered for the AD meta-analysis. The pooled sensitivity and specificity were 0.76 (95% CI, 0.63-0.86) and 0.89 (95% CI, 0.79-0.95), respectively. There was a significant difference between the good and poor responders in terms of the diagnostic odds ratio. The summary ROC curve demonstrated that the area under curve (AUC) was 0.892, indicating excellent diagnostic accuracy.
CONCLUSION
Our findings have suggested that conventional Tc-MDP/HMDP scintigraphy remains as useful as recent quantitative modalities to predict the histological response of osteosarcoma to neoadjuvant chemotherapy.
Topics: Bone Neoplasms; Humans; Neoadjuvant Therapy; Osteosarcoma; Prognosis; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Medronate
PubMed: 30572434
DOI: 10.1097/MD.0000000000013308