Metabolic effects and disposition of sebacate, an alternate dicarboxylic fuel substrate.

Disodium sebacate is a 10-carbon-atom dicarboxylic acid, proposed as substrate for parenteral nutrition. We investigated its pharmacokinetic profile and thermogenic effect during a short-time infusion (5 h at 10 g/h) in 7 male volunteers. Sebacate in serum and urine was measured by high-performance liquid chromatography. A single-compartment model with two linear elimination routes was fitted. Metabolic measurements (VO2, VCO2, respiratory quotient, metabolic rate) were continuously performed for 8 h (5 h during and 3 h after the infusion) by a canopy indirect calorimeter. The apparent volume of distribution of sebacate was 8.39 +/- 0.69 liters, and the plasma fractional removal rate constant was 0.0086 +/- 0.00077 min-1. The average half-life and plasma clearance were 80.6 min and 72 ml/min, respectively. The increase in metabolic rate, the decrease in respiratory quotient and the changes in ketone body, glucagon and insulin levels during the infusion were not significant. 24-hour catecholamine excretion was within normal limits. Calories administered by sebacate seem to be available for utilization without relevant metabolic side effects.     

Influence of the timing of cardiac catheterization and the amount of contrast media on acute renal failure after cardiac surgery

Postoperative acute renal failure (ARF) is not uncommon after cardiac surgery and after angiography. However, limited information exists regarding the influence of the interval between cardiac catheterization and subsequent cardiac surgery and amount of contrast agent used during this procedure on the occurrence of postoperative ARF. Data for 423 consecutive adult patients who underwent elective cardiac surgery after cardiac catheterization were examined retrospectively. The influence of interval between cardiac catheterization and cardiac surgery on postoperative ARF (defined as postoperative serum creatinine > or =2 times baseline and >2 mg/dl and/or need for renal replacement therapy) was evaluated using multivariable logistic regression. ARF occurred in 24 patients (5.7%). Median time to angiography was 2 days (interquartile range 1 to 4.5), and median dose of contrast used was 1.36 ml/kg (interquartile range 1.12 to 1.69). Surgery on the day of cardiac catheterization was independently associated with increased risk of ARF (adjusted odds ratio 3.1, 95% confidence interval 1.1 to 8.8). This risk of ARF was highest in patients who underwent surgery on the same day as angiography and with a dose of contrast higher than median (14.6%) and lowest when surgery was delayed beyond 1 day of angiography and contrast dose was median or less (2.4%; adjusted odds ratio for same-day surgery and dose higher than median 4.2, 95% confidence interval 1.2 to 14.2). Cardiac surgery performed on the day of cardiac catheterization and higher dose of contrast agent used were both independently associated with increased risk of postoperative ARF. In conclusion, these findings suggest that delaying cardiac surgery beyond 24 hours of exposure to contrast agents (when feasible) and minimizing the use of these agents have significant potential to decrease the incidence of postoperative ARF in patients undergoing elective cardiac surgery.     

Prevalence of C282Y and E168X HFE mutations in an Italian population of Northern European ancestry

BACKGROUND AND OBJECTIVES: In Italy, the prevalence of C282Y is lower than in Northern European countries. We hypothesized a higher prevalence of C282Y in Northern than in Southern Italian populations. We previously identified a nonsense mutation (E168X) in hemochromatosis probands originating from a region in the north-west of Italy. We aimed to define the prevalence of C282Y and E168X in that region and the origin of the E168X mutation by haplotype analysis. DESIGN AND METHODS: Six-hundred and six blood donors were investigated for C282Y, H63D, S65C and E168X mutations by polymerase chain reaction (PCR)-restriction assays. Three hundred were also tested for rare HFE and TFR2 mutations by reverse-hybridization test strips. D6S265, D6S105 and D6S1281 microsatellites were analyzed to define E168X 6p-associated haplotypes. RESULTS: One C282Y homozygote, thirteen C282Y/ H63D compound heterozygotes, four E168X heterozygotes and three E168X/H63D compound heterozygotes were found. The allele frequencies of C282Y, H63D, S65C, and E168X were 4.7%, 14.9%, 0.74% and 0.58%, respectively. INTERPRETATION AND CONCLUSIONS: The prevalence of C282Y in the region investigated was much higher than that previously reported in Italy. This finding is probably due to the heavy Celtic component of this north-western population and suggests that in populations of Northern Italian descent screening studies for hemochromatosis could be cost-effective. The prevalence of E168X in this region, although low, suggests that the mutation probably originated here many years ago and its frequency increased as a result of a local founder effect. Given its severity, we suggest that the E168X mutation should be searched for in all hemochromatosis patients of Northern ancestry with an incomplete HFE genotype.     

Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study

Journal of Neurology - To identify baseline factors associated with disease activity in patients with relapsing–remitting multiple sclerosis (RRMS) under teriflunomide treatment. This was an...     

STIG study: real-world data of long-term outcomes of adults with Pompe disease under enzyme replacement therapy with alglucosidase alfa

Journal of Neurology - Pompe disease is one of the few neuromuscular diseases with an approved drug therapy, which has been available since 2006. Our study aimed to determine the real-world...     

The Unfabulous Four: Maladaptive Personality Functioning,Insecure Attachment,Dissociative Experiences,and Problematic Internet Use Among Young Adults

International Journal of Mental Health and Addiction - Even though positive associations among problematic Internet use (PIU), maladaptive personality traits, insecure attachment styles, and...     

Flow cytometry data mining by cytoChain identifies determinants of exhaustion and stemness in TCR-engineered T cells

The phenotype of infused cells is a major determinant of Adoptive T-cell therapy (ACT) efficacy. Yet, the difficulty in deciphering multiparametric cytometry data limited the fine characterization of cellular products. To allow the analysis of dynamic and complex flow cytometry samples, we developed cytoChain, a novel dataset mining tool and a new analytical workflow. CytoChain was challenged to compare state-of-the-art and innovative culture conditions to generate stem-like memory cells (T_SCM) suitable for ACT. Noticeably, the combination of IL-7/15 and superoxides scavenging sustained the emergence of a previously unidentified nonexhausted Fit-T_SCM signature, overlooked by manual gating and endowed with superior expansion potential. CytoChain proficiently traced back this population in independent datasets, and in T-cell receptor engineered lymphocytes. CytoChain flexibility and function were then further validated on a published dataset from circulating T cells in COVID-19 patients. Collectively, our results support the use of cytoChain to identify novel, functionally critical immunophenotypes for ACT and patients immunomonitoring.