Morphological changes after cranial fractionated photon radiotherapy: Localized loss of white matter and grey matter volume with increasing dose

Purpose: Numerous brain MR imaging studies have been performed to understand radiation-induced cognitive decline. However, many of them focus on a single region of interest, e.g. cerebral cortex or hippocampus. In this study, we use deformation-based morphometry (DBM) and voxel-based morphometry (VBM) to measure the morphological changes in patients receiving fractionated photon RT, and relate these to the dose. Additionally, we study tissue specific volume changes in white matter (WM), grey matter (GM), cerebrospinal fluid and total intracranial volume (TIV). Methods and materials: From our database, we selected 28 patients with MRI of high quality available at baseline and 1 year after RT. Scans were rigidly registered to each other, and to the planning CT and dose file. We used DBM to study non-tissue-specific volumetric changes, and VBM to study volume loss in grey matter. Observed changes were then related to the applied radiation dose (in EQD2). Additionally, brain tissue was segmented into WM, GM and cerebrospinal fluid, and changes in these volumes and TIV were tested. Results: Performing DBM resulted in clusters of dose-dependent volume loss 1 year after RT seen throughout the brain. Both WM and GM were affected; within the latter both cerebral cortex and subcortical nuclei show volume loss. Volume loss rates ranging from 5.3 to 15.3%/30 Gy were seen in the cerebral cortical regions in which more than 40% of voxels were affected. In VBM, similar loss rates were seen in the cortex and nuclei. The total volume of WM and GM significantly decreased with rates of 5.8% and 2.1%, while TIV remained unchanged as expected. Conclusions: Radiotherapy is associated with dose-dependent intracranial morphological changes throughout the entire brain. Therefore, we will consider to revise sparing of organs at risk based on future cognitive and neurofunctional data

Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: A multicentre cohort analysis

Objective Serrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC risk. We aimed to assess risk factors for CRC in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance. Design In this retrospective cohort analysis, all patients with SPS from seven centres in the Netherlands and two in the UK were enrolled. WHO criteria were used to diagnose SPS. Patients who only fulfilled WHO criterion-2, with IBD and/or a known hereditary CRC syndrome were excluded. Results In total, 434 patients with SPS were included for analysis; 127 (29.3%) were diagnosed with CRC. In a per-patient analysis =1 serrated polyp (SP) with dysplasia (OR 2.07; 95% CI 1.28 to 3.33), =1 advanced adenoma (OR 2.30; 95% CI 1.47 to 3.67) and the fulfilment of both WHO criteria 1 and 3 (OR 1.60; 95% CI 1.04 to 2.51) were associated with CRC, while a history of smoking was inversely associated with CRC (OR 0.36; 95% CI 0.23 to 0.56). Overall, 260 patients underwent surveillance after clearing of all relevant lesions, during which two patients were diagnosed with CRC, corresponding to 1.9 events/1000 person-years surveillance (95% CI 0.3 to 6.4). Conclusion The presence of SPs containing dysplasia, advanced adenomas and/or combined WHO criteria 1 and 3 phenotype is associated with CRC in patients with SPS. Patients with a history of smoking show a lower risk of CRC, possibly due to a different pathogenesis of disease. The risk of developing CRC during surveillance is lower than previously reported in literature, which may reflect a more mature multicentre cohort with less selection bias

Two cases of a pharmacokinetic interaction between (val)acyclovir and mycophenolate mofetil

Background: Administration of (val)acyclovir in combination with mycophenolate mofetil (MMF) can result in increased acyclovir plasma levels due to competition with acyclovir for renal tubular secretion. Several studies of pharmacokinetic interactions between acyclovir and MMF have been previously described, however, they present conflicting results. Case report: We present two cases of male patients to whom a pharmacokinetic interaction occurred between (val)acyclovir and mycophenolate mofetil. Results: Case A developed an acyclovir through level of 3.5 mg/L on day 3 of his acyclovir treatment, which resulted in neurotoxicity attributed to acyclovir overdosing because of the pharmacokinetic interaction with MMF. Case B developed an acyclovir through level of 3.2 mg/L on day 4 of his acyclovir treatment, which was attributed to the pharmacokinetic interaction with MMF in combination with his poor renal function. No adverse side-effects occurred. Conclusion: Clinical decision support systems should be used to generate alerts when (val)acyclovir and MMF are co-administered in patients with renal impairment (eGFR < 60 ml/min/1,73 m2). By using early-stage therapeutic drug monitoring, dosages can be adjusted if necessary

Pancuronium masks the prejunctional muscarinic autoreceptor in guinea pig tracheal smooth muscle

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Circadian sleep-wake rhythm disturbances in end-stage renal disease

End-stage renal disease (ESRD) is an increasing health problem worldwide. Given the increasing prevalence of this disease, the high cost of hemodialysis treatment and the burden of hemodialysis on a patient's life, more research on improving the clinical outcomes and the quality of life of hemodialysis-treated patients is warranted. Sleep disturbances are much more prevalent in the dialysis population than in the general population. Several studies investigating the effect and importance of sleep problems on quality of life in dialysis patients revealed that sleep disturbances have a major influence on the vitality and general health of these patients. Sleep disturbances in this patient group are caused both by the pathology of the renal disease and by the dialysis treatment itself. This Review focuses on circadian sleep-wake rhythm disturbances in individuals with ESRD. The possible external and internal influences on sleep-wake rhythmicity in patients with ESRD, such as the effect of dialysis, medications, melatonin and biochemical parameters, are presented. In addition, possible approaches for strengthening the synchronization of the circadian sleep-wake rhythm, such as nocturnal hemodialysis, exogenous melatonin, dialyzate temperature, exogenous erythropoietin, use of bright light and exercise during dialysis treatment, are explored. Further research in this area is warranted, and a greater awareness of sleep problems is needed to improve the quality of life of patients with ESRD