-
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 -
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 -
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