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?

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.

Health-related quality of life and rehabilitation cost following intensive care unit stay in multiple trauma patients.

OBJECTIVES: The objective of this study was to assess changes in health-related quality of life (HRQOL) in multiple trauma patients due to motor vehicle crashes during a follow-up period of 2 years after discharge from an intensive care unit (ICU) and the effect of income and financial cost of rehabilitation in HRQOL. METHODS: The study was a prospective observational study of multiple trauma patients from January 2009 to January 2011 who were hospitalized in a general, medical, and surgical ICU of a district hospital in Athens, Greece. Eighty-five patients with multiple traumas due to motor vehicle crashes and with an ICU stay of more than 24 hours were included in the study. HRQOL was assessed by a general questionnaire, the EuroQol 5D. RESULTS: Increased monthly household income and absence of traumatic brain injuries were associated with an improved EQ-VAS score. The frequency of severe problems in mobility, self-care, usual activities, pain/discomfort, and anxiety/depression decreased over time. The financial cost of rehabilitation was initially high but decreased over time. CONCLUSIONS: Severely injured victims of motor vehicle crashes suffer from serious problems in terms of HRQOL which is gradually improved even 2 years after hospital discharge. In addition, HRQOL is significantly related to income. Resources used for rehabilitation decrease over time, but even at 24 months, the patients still use half of the amount as compared with the cost of the first 6 months after trauma.

Quality of life outcome of critical care survivors eighteen months after discharge from intensive care.

AIM: To assess the changes in health-related quality of life in patients discharged from the intensive care unit (ICU). METHODS: At the General University ICU, Trauma Hospital in Athens, 242 patients were enrolled prospectively over a study period of 18 months. Out of these, 116 participants (47.9%) completed all survey components at 6, 12, and 18 months. We used Quality of Life-Spanish (QOL-SP) to assess the health-related quality of life. Patients or their relatives were interviewed on ICU admission and at 6, 12, and 18 months after discharge from the ICU. RESULTS: Mean quality of life score of the patients increased from 2.9+/-4.8 (out of maximum 25 points) on ICU admission to 7.0+/-7.2 points at 6 months after discharge, and then decreased to 5.6+/-6.9 points at 18 months (P<0.001; Friedman Test). Multilinear regression analysis showed that the variables which had the strongest association with the quality of life on admission were age (P=0.002) and male sex (P=0.001), whereas age (P<0.001), length of ICU stay (P<0.001), and male sex (P=0.002) had the strongest association 18 months after discharge from the ICU. Survival rate was 66.9% at discharge from ICU and 61.6% at hospital discharge. There were 33% deaths in the ICU, 5.3% in the hospital, and 6.2% after ICU discharge. There were 7.4% patients lost to follow-up. CONCLUSIONS: After discharge from the ICU, patients' quality of life was poor and showed an improvement at 18 months after discharge, but was still worse than on admission. Age, ICU length of stay, and male sex were the factors that had the strongest impact on the quality of life on admission and at 18 months after discharge from the ICU.

Whole blood pro-inflammatory cytokines and adhesion molecules post-lipopolysaccharides exposure in hyperbaric conditions.

Hyperbaric oxygen (HBO) is a therapeutic intervention with applications in a large variety of diseases, including traumatic injuries and acute or chronic infections. The presence of pro-inflammatory cytokines regulates certain factors including adhesion molecules, which play a significant role in HBO effects. We have investigated the effect of HBO on pro-inflammatory cytokine release [tumor necrosis factor-alpha (TNF-alpha), interleukin 6 and 8 (IL-6 and IL-8)], and the regulation of adhesion molecules [soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule (sVCAM)] after lipopolysaccharide (LPS) stimulation in 16 healthy individuals, originating from an urban area. A total number of 64 samples were treated, divided into four groups: Group A: not stimulated with LPS and not exposed to HBO. Group B: stimulated with LPS and not exposed to HBO. Group C: not stimulated with LPS and exposed to HBO. Group D: stimulated with LPS and exposed to HBO. The LPS stimulation dose was 100 pg\ml for 0.1 ml whole blood diluted 1:10. After incubation, samples were exposed to HBO with 100% O2 at 2.4 atmospheres absolute (ATA) for 90 min. TNF-alpha, IL-6, IL-8 and sICAM-1, sVCAM levels were determined in culture supernatant, with ELISA. We observed an enhanced effect of LPS stimulation following exposure to HBO, which caused an increase in cytokine production (TNF-alpha, IL-6, IL-8), a reduction in sICAM, and no change to sVCAM, while their levels without stimulation remained almost invariable. The decrease in sICAM levels could be related to the increased levels of IL-8, as the production of this chemokine is involved in the regulation of adhesion molecules.