Intra-patient variability in tacrolimus exposure in pediatric liver transplant recipients: Evolution, risk factors, and impact on patient outcomes.

BACKGROUND: This study aims to investigate the evolution and factors associated with TAC IPV and its impact on patient outcomes in pediatric LT recipients. METHODS: This is a retrospective study including 41 children. The TAC IPV was expressed as the coefficient of variation and was calculated for years 1-5 following LT. The number of missed clinic appointments was used as a surrogate marker for therapy adherence. RESULTS: We identified a decrease in the TAC IPV during the first 3 years after LT (P < 0.01). Serum albumin in the first year (P = 0.03), hematocrit (P = 0.02) and total bilirubin (P = 0.04) in the third year, and therapy adherence (P < 0.01) in the fifth year were associated with TAC IPV. High TAC IPV was associated with biopsy-proven acute allograft rejection (P = 0.04) and the need for biopsy during the first year (P = 0.02). There was a borderline association between TAC IPV and donor-specific antibodies (P = 0.08) and CMV viremia (P = 0.07). High TAC IPV was a predictor of need for liver biopsy and AR with an odds ratio of 1.04 (95% CI 1.0-1.1; P = 0.03) and 1.04 (95% CI 1.0-1.1; P = 0.05), respectively. CONCLUSIONS: Our results highlight the impact of biological factors on TAC IPV during the early LT follow-up and later also therapy adherence. High TAC IPV may be associated with adverse patient outcomes.

Brain activity during phonation in healthy female singers with supraglottic compression: an fMRI pilot study.

This pilot study evaluated the usability of functional magnetic resonance imaging (fMRI) to detect brain activation during phonation in healthy female singers with supraglottic compression. Four healthy female classical singers (mean age: 26 years) participated in the study. All subjects had normal vocal folds and vocal characteristics and showed supraglottic compression. The fMRI experiment was carried out using a block design paradigm. Brain activation during phonation and exhalation was analyzed using Brain Voyager software (Brain Innovation B.V., Maastricht, The Netherlands). An fMRI data analysis showed a significant effect of phonation control in the bilateral pre/postcentral gyrus, and in the frontal, cingulate, superior and middle temporal gyrus, as well as in the parietal lobe, insula, lingual gyrus, cerebellum, thalamus and brainstem. These activation areas are consistent with previous reports using other fMRI protocols. In addition, a significant effect of phonation compared to exhalation control was found in the bilateral superior temporal gyrus, and the pre/postcentral gyrus. This fMRI pilot study allowed to detect a normal pattern of brain activity during phonation in healthy female singers with supraglottic compression using the proposed protocol. However, the pilot study detected problems with the experimental material/procedures that would necessitate refining the fMRI protocol. The phonation tasks were not capable to show brain activation difference between high-pitched and comfortable phonation. Further fMRI studies manipulating vocal parameters during phonation of the vowels /a/ and /i/ may elicit more distinctive hemodynamic response (HDR) activity patterns relative to voice modulation.