Urine volume to hydration volume ratio is associated with pharmacokinetics of high-dose methotrexate in patients with primary central nervous system lymphoma.

High-dose methotrexate (HD-MTX)-based chemotherapy is the first-line treatment for primary central nervous system lymphoma (PCNSL), but is associated with severe adverse effects, including myelosuppression and renal impairment. MTX is primarily excreted by the kidneys. Renal function calculated using serum creatinine (Scr) derived from muscle may be overestimated in elderly PCNSL patients. Therefore, we aimed to construct a population pharmacokinetic model in PCNSL patients and explore the factors associated with MTX clearance. Sixteen PCNSL patients (median age, 66 years) treated with HD-MTX were included, and serum MTX concentrations were measured at 193 points in 49 courses. A population pharmacokinetic analysis was performed using NONMEM. A Monte Carlo simulation was conducted, in which serum MTX concentrations were stratified into three groups of creatine clearance (Ccr) (50, 75, and 100 ml/min) with three groups of the urine volume to hydration volume (UV/HV) ratio (<1, 1-2, and >2). The final model was constructed as follows: MTX clearance = 4.90·(Ccr/94.5)0.456 ·(UV/HV)0.458 . In the Monte Carlo simulation, serum MTX concentrations were below the standard values (10, 1, and 0.1 µM at 24, 48, and 72 h, respectively, after the start of the MTX administration) in most patients with UV/HV >2, even with Ccr of 50 ml/min. Conversely, half of the patients with UV/HV <1 and Ccr of 50 ml/min failed to achieve the standard values. The present results demonstrated that the UV/HV ratio was useful for describing the pharmacokinetics of MTX in PCNSL patients.

Gait Assessment Using Three-Dimensional Acceleration of the Trunk in Idiopathic Normal Pressure Hydrocephalus.

Background: The subjective evaluation of pathological gait exhibits a low inter-rater reliability. Therefore, we developed a three-dimensional acceleration of the trunk during walking to assess the pathological gait quantitatively. Methods: We evaluated 97 patients who underwent the cerebrospinal tap test and were diagnosed with idiopathic normal pressure hydrocephalus (iNPH) and 68 healthy elderlies. The gait features of all patients were evaluated and classified as one of the following: freezing of gait, wide-based gait, short-stepped gait, shuffling gait, instability, gait festination, difficulty in changing direction, and balance disorder in standing up. All gait features of 68 healthy elderlies were treated as normal. Trunk acceleration was recorded automatically by a smartphone placed on the umbilicus during a 15-foot walking test. Two novel indices were created. The first index was a trunk acceleration index, which was defined as (forward acceleration fluctuation) + (vertical acceleration fluctuation) - (lateral acceleration fluctuation) based on the multivariate logistics regression model, and the second index was created by multiplying the forward acceleration with the vertical acceleration. Additionally, 95% confidence ellipsoid volume of the three-dimensional accelerations was assessed. Results: Forward and vertical acceleration fluctuations were significantly associated with the probability of an iNPH-specific pathological gait. The trunk acceleration index demonstrated the strongest association with the probability of an iNPH-specific pathological gait. The areas under the receiver-operating characteristic curves for detecting 100% probability of an iNPH-specific pathological gait were 86.9% for forward acceleration fluctuation, 88.0% for vertical acceleration fluctuation, 82.8% for lateral acceleration fluctuation, 89.0% for trunk acceleration index, 88.8% for forward × vertical acceleration fluctuation, and 87.8% for 95% confidence ellipsoid volume of the three-dimensional accelerations. Conclusions: The probability of a pathological gait specific to iNPH is high at the trunk acceleration fluctuation, reduced in the forward and vertical directions, and increased in the lateral direction.

Incidence, Management and Short-Term Outcome of Stroke in a General Population of 1.4 Million Japanese　- Shiga Stroke Registry.

BACKGROUND: This study determined the current status of the incidence, management, and prognosis of stroke in Japan using a population-based stroke registry.Methods and Results:Shiga Stroke Registry is an ongoing population-based registry that covers approximately 1.4 million residents of Shiga Prefecture. Cases of acute stroke were identified using standard definitions through surveillance of both all acute-care hospitals with neurology/neurosurgery facilities and death certificates in 2011. A total of 2,956 stroke cases and 2,176 first-ever stroke cases were identified. The age- and sex-adjusted incidence rate for first-ever stroke using the 2013 European Standard Population as standard was per 100,000 person-years: 91.3 for ischemic stroke, 36.4 for intracerebral hemorrhage, and 13.7 for subarachnoid hemorrhage. It was estimated that approximately 220,000 new strokes occurred in 2011 in Japan. Among the 2,956 cases, most stroke patients underwent neuroimaging, 268 received surgical or endovascular treatment, and 2,158 had rehabilitation therapy; 78 patients received intravenous thrombolysis. A total of 1,846 stroke patients had died or were dependent at hospital discharge, and 390 died within 28 days of onset. CONCLUSIONS: Incidence rates of stroke by subtypes were clarified and the total number of new strokes in Japan was estimated. More than half of stroke patients die or become dependent after a stroke. This study re-emphasized the importance of public health measures in reducing the burden of stroke in Japan.

Contrast-enhanced carotid color-coded duplex sonography for carotid stenting follow-up assessment.

Proper assessment of endovascular patency after carotid stent (CS) placement with carotid color-coded duplex sonography (CCCD) can be difficult. We investigated the usefulness of contrast-enhanced (CE) CCCD for post-CS follow-up. CCCD images could not depict the entire bloodstream in overlapped stents and in highly positioned stents. CE-CCCD images, however, did provide anatomic information almost equivalent to that of intra-arterial angiography. CE-CCCD is useful in screening for post-CS restenosis.