Fluoropyrimidine-induced toxicity and DPD deficiency.. A case report of early onset, lethal capecitabine-induced toxicity and mini review of the literature. Uridine triacetate: Efficacy and safety as an antidote. Is it accessible outside USA?

2019 ◽  
Vol 26 (3) ◽  
pp. 747-753 ◽  
Author(s):  
Dimitra Ioanna Lampropoulou ◽  
Konstantinos Laschos ◽  
Anna-Lea Amylidi ◽  
Ariadni Angelaki ◽  
Nikolaos Soupos ◽  
...  
Keyword(s):  
Early Onset ◽  
Dehydrogenase Deficiency ◽  
Colorectal Cancer Patient ◽  
Dihydropyrimidine Dehydrogenase ◽  
Efficacy And Safety ◽  
Review Of The Literature ◽  
Time Restrictions ◽  
Timely Access ◽  
Life Threatening ◽  
Chemotherapy Dose

Fluoropyrimidine-based regimens are among the most commonly used chemotherapy combinations for the treatment of solid tumors. Several genetic polymorphisms that are implicated with fluoropyrimidine anabolism and catabolism have been associated with the development of life-threatening toxicities. Uridine triacetate is an FDA-approved antidote for 5-fluorouracil or capecitabine overdose and early-onset, life-threatening toxicity within 96 h of last chemotherapy dose. To date, it is not accessible for Greek patients as per the current summary of product characteristic's time restrictions. We report and discuss the course and outcome of capecitabine toxicity in a 66-year-old female colorectal cancer patient with heterozygous dihydropyrimidine dehydrogenase deficiency. This paper highlights the difficulty in timely access of this lifesaving medication for Greek and possibly other European patients.

Successful use of uridine triacetate (Vistogard) three weeks after capecitabine in a patient with homozygous dihydropyrimidine dehydrogenase mutation: A case report and review of the literature

2017 ◽  
Vol 25 (1) ◽  
pp. 234-238 ◽  
Author(s):  
Mira Zurayk ◽  
Yi-Kong Keung ◽  
David Yu ◽  
Eddie HL Hu
Keyword(s):  
Dehydrogenase Deficiency ◽  
Dihydropyrimidine Dehydrogenase ◽  
Female Breast Cancer ◽  
Chemotherapeutic Agents ◽  
Review Of The Literature ◽  
Female Breast ◽  
Solid Malignancies ◽  
Life Threatening ◽  
Dihydropyrimidine Dehydrogenase Deficiency ◽  
Increased Susceptibility

5-fluorouracil and capecitabine are chemotherapeutic agents commonly used to treat solid malignancies. Increased susceptibility to 5-fluorouracil or capecitabine, caused by impaired clearance, dihydropyrimidine dehydrogenase deficiency, or other genetic mutations in the enzymes that metabolize 5-fluorouracil can lead to severe life-threatening toxicities and are typically manifested by an early onset of symptoms. We report and discuss the management and outcome of capecitabine toxicity with the recently FDA approved antidote, uridine triacetate (Vistogard), in a 57-year-old female breast cancer patient with homozygous dihydropyrimidine dehydrogenase deficiency who received treatment beyond the recommended 96 h window from the last dose of capecitabine.

scholarly journals DPYD Exome, mRNA Expression and Uracil Levels in Early Severe Toxicity to Fluoropyrimidines: An Extreme Phenotype Approach

2021 ◽  
Vol 11 (8) ◽  
pp. 792
Author(s):  
Priscila Villalvazo ◽  
Belén Marzal-Alfaro ◽  
Pilar García-Alfonso ◽  
José Luis Revuelta-Herrero ◽  
Fabienne Thomas ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Adverse Reactions ◽  
Dehydrogenase Deficiency ◽  
Dihydropyrimidine Dehydrogenase ◽  
Severe Toxicity ◽  
Exon Sequence ◽  
Extreme Phenotypes ◽  
Life Threatening ◽  
Early Toxicity

Dihydropyrimidine dehydrogenase deficiency is a major cause of severe fluoropyrimidine-induced toxicity and could lead to interruption of chemotherapy or life-threatening adverse reactions. This study aimed to characterize the DPYD exon sequence, mRNA expression and in vivo DPD activity by plasma uracil concentration. It was carried out in two groups of patients with extreme phenotypes (toxicity versus control) newly treated with a fluoropyrimidine, during the first three cycles of treatment. A novel nonsense gene variant (c.2197insA) was most likely responsible for fluoropyrimidine-induced toxicity in one patient, while neither DPYD mRNA expression nor plasma uracil concentration was globally associated with early toxicity. Our present work may help improve pharmacogenetic testing to avoid severe and undesirable adverse reactions to fluoropyrimidine treatment and it also supports the idea of looking beyond DPYD.

Case report of capecitabine toxicity and use of uridine triacetate

2017 ◽  
Vol 25 (2) ◽  
pp. 470-473 ◽  
Author(s):  
Wesley D Oliver ◽  
Alison P Duffy ◽  
Petr F Hausner
Keyword(s):  
Case Report ◽  
Cancer Treatment ◽  
Thymidylate Synthase ◽  
Early Onset ◽  
Emergency Treatment ◽  
Dihydropyrimidine Dehydrogenase ◽  
Life Threatening ◽  
Chemotherapy Agents

Fluorouracil and capecitabine are fluoropyrimidine chemotherapy agents that are commonly used for various cancers. These agents are generally well tolerated at standard doses; however, it has been reported that 31–34% of patients develop dose-limiting toxicities. Dihydropyrimidine dehydrogenase and thymidylate synthase play a major role in fluorouracil and capecitabine activity and toxicity. Uridine triacetate has shown promising results for the emergency treatment of patients who either receive an overdose of the cancer treatment fluorouracil or capecitabine or to treat patients who exhibit early-onset, severe, or life-threatening toxicity. We describe a case of a patient who developed capecitabine toxicity and was unsuccessfully treated with uridine triacetate.

scholarly journals Prevention and management of major complications in percutaneous endoscopic gastrostomy

2021 ◽  
Vol 8 (1) ◽  
pp. e000628
Author(s):  
Kurt Boeykens ◽  
Ivo Duysburgh
Keyword(s):  
Clinical Practice ◽  
Abdominal Wall ◽  
Percutaneous Endoscopic Gastrostomy ◽  
Early Recognition ◽  
Endoscopic Technique ◽  
Abdominal Wound ◽  
Review Of The Literature ◽  
Endoscopic Gastrostomy ◽  
Major Complications ◽  
Life Threatening

BackgroundPercutaneousendoscopic gastrostomy is a commonly used endoscopic technique where a tube isplaced through the abdominal wall mainly to administer fluids, drugs and/orenteral nutrition. Several placement techniques are described in the literaturewith the ‘pull’ technique (Ponsky-Gardener) as the most popular one.Independent of the method used, placement includes a ‘blind’ perforation of thestomach through a small acute surgical abdominal wound. It is a generally safetechnique with only few major complications. Nevertheless these complicationscan be sometimes life-threatening or generate serious morbidity.MethodAnarrative review of the literature of major complications in percutaneousendoscopic gastrostomy.ResultsThis review was written from a clinical viewpoint focussing on prevention andmanagement of major complications and documentedscientific evidence with real cases from more than 20 years of clinical practice.ConclusionsMajorcomplications are rare but prevention, early recognition and popper management areimportant.

scholarly journals A Review of Biophysiological and Biochemical Indicators of Stress for Connected and Preventive Healthcare

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 556
Author(s):  
Talha Iqbal ◽  
Adnan Elahi ◽  
Pau Redon ◽  
Patricia Vazquez ◽  
William Wijns ◽  
...  
Keyword(s):  
Cardiovascular Events ◽  
Medical Conditions ◽  
Review Of The Literature ◽  
Stress Monitoring ◽  
Preventive Healthcare ◽  
Connected Health ◽  
Root Cause ◽  
Chemical Indicators ◽  
Life Threatening ◽  
Assessment Of Stress

Stress is a known contributor to several life-threatening medical conditions and a risk factor for triggering acute cardiovascular events, as well as a root cause of several social problems. The burden of stress is increasing globally and, with that, is the interest in developing effective stress-monitoring solutions for preventive and connected health, particularly with the help of wearable sensing technologies. The recent development of miniaturized and flexible biosensors has enabled the development of connected wearable solutions to monitor stress and intervene in time to prevent the progression of stress-induced medical conditions. This paper presents a review of the literature on different physiological and chemical indicators of stress, which are commonly used for quantitative assessment of stress, and the associated sensing technologies.

scholarly journals Novel HAX1 Gene Mutation in a Vietnamese Boy with Severe Congenital Neutropenia

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Tham Thi Tran ◽  
Quang Van Vu ◽  
Taizo Wada ◽  
Akihiro Yachie ◽  
Huong Le Thi Minh ◽  
...  
Keyword(s):  
Early Onset ◽  
Bacterial Infections ◽  
Complete Blood Count ◽  
Hereditary Diseases ◽  
Severe Neutropenia ◽  
Sequencing Analysis ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Direct Dna Sequencing ◽  
Life Threatening

Severe congenital neutropenia (SCN) is a rare disease that involves a heterogeneous group of hereditary diseases. Mutations in the HAX1 gene can cause an autosomal recessive form of SCN-characterized low blood neutrophil count from birth, increased susceptibility to recurrent and life-threatening infections, and preleukemia predisposition. A 7-year-old boy was admitted due to life-threatening infections, mental retardation, and severe neutropenia. He had early-onset bacterial infections, and his serial complete blood count showed persistent severe neutropenia. One older sister and one older brother of the patient died at the age of 6 months and 5 months, respectively, because of severe infection. Bone marrow analysis revealed a maturation arrest at the promyelocyte/myelocyte stage with few mature neutrophils. In direct DNA sequencing analysis, we found a novel homozygous frameshift mutation (c.423_424insG, p.Gly143fs) in the HAX1 gene, confirming the diagnosis of SCN. The patient was successfully treated with granulocyte colony-stimulating factor (G-CSF) and antibiotics. A child with early-onset recurrent infections and neutropenia should be considered to be affected with SCN. Genetic analysis is useful to confirm diagnosis. Timely diagnosis and suitable treatment with G-CSF and antibiotics are important to prevent further complication.

scholarly journals mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jingsong Cao ◽  
Minjung Choi ◽  
Eleonora Guadagnin ◽  
Maud Soty ◽  
Marine Silva ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Murine Model ◽  
Storage Disease ◽  
Liver Tumors ◽  
Glycogen Storage ◽  
Human Condition ◽  
Efficacy And Safety ◽  
Current Standard ◽  
Enzyme Replacement ◽  
Life Threatening

AbstractGlycogen Storage Disease 1a (GSD1a) is a rare, inherited metabolic disorder caused by deficiency of glucose 6-phosphatase (G6Pase-α). G6Pase-α is critical for maintaining interprandial euglycemia. GSD1a patients exhibit life-threatening hypoglycemia and long-term liver complications including hepatocellular adenomas (HCAs) and carcinomas (HCCs). There is no treatment for GSD1a and the current standard-of-care for managing hypoglycemia (Glycosade®/modified cornstarch) fails to prevent HCA/HCC risk. Therapeutic modalities such as enzyme replacement therapy and gene therapy are not ideal options for patients due to challenges in drug-delivery, efficacy, and safety. To develop a new treatment for GSD1a capable of addressing both the life-threatening hypoglycemia and HCA/HCC risk, we encapsulated engineered mRNAs encoding human G6Pase-α in lipid nanoparticles. We demonstrate the efficacy and safety of our approach in a preclinical murine model that phenotypically resembles the human condition, thus presenting a potential therapy that could have a significant therapeutic impact on the treatment of GSD1a.

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