Late leukoencephalopathy in patients with methanol intoxication / Leucoencefalopatía tardía posterior a intoxicación por metanol

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Prediction of Symptomatic Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage Using Early Transcranial Doppler.

BACKGROUND: Symptomatic vasospasm (sVSP) is a common complication during the course of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to evaluate the efficacy and accuracy of transcranial Doppler ultrasound (TCD), performed within the first 3 days of aSAH to predict the development of sVSP. METHODS: We performed a retrospective analysis of our institutional prospectively collected database of patients with aSAH. Patients with aSAH and World Federation of Neurosurgical Societies (WFNS) grades I-III were included in the analysis. A receiver operating characteristic (ROC) curve was generated to determine cut-off values for mean flow velocities (MFVs) in the middle cerebral artery (MCA) and anterior cerebral artery (ACA) bilaterally to predict sVSP. RESULTS: Fifty-one patients were included in the study. Mean age was 49.8 ± 10.2 years, and 84.3% (43 patients) were women. The accuracy of measured MFVs to predict sVSP was 0.79 [95% confidence interval (CI), 0.69-0.89] and 0.77 (95% CI, 0.64-0.91) for the MCA and the ACA, respectively. In the MCA, an MFV ≥ 74 cm/s was significantly associated with a six-fold increased risk of sVSP, achieving sensitivity greater than 70%. In the ACA, an MFV ≥ 64 cm/s was significantly associated with a nine-fold increased risk of sVSP. CONCLUSION: Early TCD evaluation of MFVs in the MCA and ACA is a useful tool to predict the development of sVSP in patients with acute aSAH.

Polymorphisms of CYP2C8 Alter First-Electron Transfer Kinetics and Increase Catalytic Uncoupling.

Cytochrome P450 2C8 (CYP2C8) epoxygenase is responsible for the metabolism of over 60 clinically relevant drugs, notably the anticancer drug Taxol (paclitaxel, PAC). Specifically, there are naturally occurring polymorphisms, CYP2C8*2 and CYP2C8*3, that display altered PAC hydroxylation rates despite these mutations not being located in the active site. Herein, we demonstrate that these polymorphisms result in a greater uncoupling of PAC metabolism by increasing the amount of hydrogen peroxide formed per PAC turnover. Anaerobic stopped-flow measurements determined that these polymorphisms have altered first electron transfer kinetics, compared to CYP2C8*1 (wildtype), that suggest electron transfer from cytochrome P450 reductase (CPR) is disfavored. Therefore, these data demonstrate that these polymorphisms affect the catalytic cycle of CYP2C8 and suggest that redox interactions with CPR are disrupted.

Evaluation of STESS, mRSTESS, and EMSE to Predict High Disability and Mortality at Hospital Discharge in Ecuadorian Patients with Status Epilepticus.

BACKGROUND: Adequate identification of the severity of status epilepticus (SE) contributes to individualized treatment. The scales most widely used for this purpose are: Status Epilepticus Severity Score (STESS), Epidemiology-Based Mortality Score in Status Epilepticus (EMSE) and modified Rankin Scale STESS (mRSTESS). The aim of this study was to evaluate the performance of the STESS, EMSE and mRSTESS scales to predict high disability and hospital mortality at discharge (HD/HM). METHODS: A prospective study was conducted in which total of 41 patients were registered from November 2015 to January 2018 at Eugenio Espejo Hospital. Clinical variables such as age, sex, clinical status at the beginning of the SE, initial symptom of SE, as well as the STESS, mRSTESS and EMSE variant scales were studied at the time of the diagnosis of SE. RESULTS: A total of 41 patients were evaluated, of which 8 (19.5%) had HD at hospital discharge and died 13 (31.7%) during their care. The area under the receiver operating characteristic curve to predict HD/HM was 0.71 (95% CI (confidence interval) 0.55-0.87), 0.81 (95% CI 0.67-0.94), 0.89 (95% CI 0.79-0.99), 0.90 (95% CI 0.80-1.0), 0.89 (95% CI 0.78-0.99) for the STESS, mRSTESS, EMSE-EAC (etiology, age, comorbidities), EMSE-EACEG (etiology, age, comorbidities, electroencephalography) and EMSE-ECLEG (etiology, age, level of consciousness at pre-treatment, electroencephalography), variants of EMSE, respectively. The binary logistic regression demonstrated how the following cut-off points were determined: STESS OR (odd ratio) 4.80 (p = 0.02), mRSTESS OR 7.89 (p = 0.00), EMSE-EAC OR 22.16 (p = 0.00), EMSE-ECLEG OR 18.00 (p = 0.00), EMSE-EACEG OR 14 (p = 0.00). CONCLUSIONS: All of the evaluated scales (STESS, mRSTESS, and EMSE) were shown to be useful in predicting HD/HM. EMSE was observed to be the most effective of the scales, with relative similarities among the variants.