Acute Rejection in Kidney Transplantation and Early Beginning of Tacrolimus

BackgroundAlthough tacrolimus is an effective immunosuppressive drug used for preventing biopsy proven acute rejection (BPAR) in kidney transplanted patients, its nephrotoxicity may compromise renal function and lead to delayed initiation because of its side effects. This study aimed to evaluate the safety of early initiation of tacrolimus in the occurrence of BPAR during the first 90 days post transplant.MethodsWe conducted a retrospective cohort study involving 315 patients who underwent kidney transplantation from 2015 to 2017. Comparisons were performed between 2 groups according to whether the start time of tacrolimus therapy was delayed or not delayed. Cox proportional hazards models were used to examine the association between variables and the occurrence of BPAR.ResultsThe incidence of BPAR was 14.9% (n = 47) and it was significantly higher in the delayed group (19.4% vs 6.4%; P = .002). Delayed initiation tacrolimus group was significantly associated with the risk of BPAR (hazard ratio: 2.95; P < .036). The overall mortality rate was 2.5% (n = 8) and there was no association between delayed initiation therapy and death (P = .56).ConclusionOur study confirmed that delayed initiation of tacrolimus in patients with delayed graft function is associated with a high risk of BPAR.     

Age-dependent effects of dopamine receptor inactivation on cocaine-induced behaviors in male rats: Evidence of dorsal striatal D2 receptor supersensitivity

N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), which irreversibly inactivates dopamine (DA) receptors, causes pronounced age-dependent behavioral effects in rats. For example, EEDQ either augments or does not affect the DA agonist-induced locomotor activity of preweanling rats while attenuating the locomotion of adolescent and adult rats. The twofold purpose of this study was to determine whether EEDQ would: (a) potentiate or attenuate the cocaine-induced locomotor activity of preweanling, adolescent, and adult rats; and (b) alter the sensitivity of surviving D2 receptors. Rats were treated with vehicle or EEDQ (2.5 or 7.5 mg/kg) on postnatal day (PD) 17, PD 39, and PD 84. In the behavioral experiments, saline- or cocaine-induced locomotion was assessed 24 hr later. In the biochemical experiments, dorsal striatal samples were taken 24 hr after vehicle or EEDQ treatment and later assayed for NPA-stimulated GTPγS receptor binding, G protein-coupled receptor kinase 6 (GRK6), and β-arrestin-2 (ARRB2). GTPγS binding is a direct measure of ligand-induced G protein activation, while GRK6 and ARRB2 modulate the internalization and desensitization of D2 receptors. Results showed that EEDQ potentiated the locomotor activity of preweanling rats, while attenuating the locomotion of older rats. NPA-stimulated GTPγS binding was elevated in EEDQ-treated preweanling rats, relative to adults, indicating enhanced functional coupling between the G protein and receptor. EEDQ also reduced ARRB2 levels in all age groups, which is indicative of increased D2 receptor sensitivity. In sum, the present results support the hypothesis that D2 receptor supersensitivity is a critical factor mediating the locomotor potentiating effects of EEDQ in cocaine-treated preweanling rats.     

Vitamin D levels and fracture risk among Hispanic children

European Journal of Orthopaedic Surgery & Traumatology - There is a lack of knowledge about whether low vitamin D levels increase the risk of pediatric low-energy fractures among Hispanic...     

IDH mutation status trumps the Pignatti risk score as a prognostic marker in low-grade gliomas

Management of low-grade gliomas (LGG) is based on clinical and radiologic features, including the Pignatti prognostic scoring system, which classifies patients as low- or high-risk. To determine whether molecular data can offer advantages over these features, we have examined the prognostic impact of several molecular alterations in LGG. In a cohort of 58 patients with LGG, we have retrospectively analyzed clinical and molecular characteristics, including the Pignatti criteria, IDH mutations, TP53 mutations, the 1p/19q deletion, and MGMT methylation, and correlated our findings with progression-free survival (PFS) and overall survival (OS). Mean age of patients was 45 years; 71% were classified as low-risk by the Pignatti system. IDH mutations were detected in 62%, p53 mutations in 17%, the 1p/19q codeletion in 46%, and MGMT methylation in 40% of patients. Survival analyses were performed in the 49 patients without contrast enhancement. In the univariate analysis, IDH mutations, the 1p/19q codeletion, and the combination of IDH mutations with the 1p/19q codeletion were associated with both longer PFS (P?=?0.006, P?=?0.037, and P?=?0.003, respectively) and longer OS (P?<?0.001, P?=?0.02, and P?<?0.001, respectively). The multivariate analysis identified absence of IDH mutations as a factor for greater risk of progression [hazard ratio (HR)?=?3.1; P?=?0.007]and death (HR?=?6.4; P?<?0.001). We suggest that IDH mutations may be more effective than the Pignatti score in discriminating low- and high-risk patients with LGG.