No abstract

Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and DNA sequencing on 32 RIG tumors and an in vitro drug screen in two RIG cell lines. We report that based on DNA methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I high-grade glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, and Ch. 13q and Ch. 14q loss; focal alterations include PDGFRA and CDK4 gain and CDKN2A and BCOR loss. Transcriptomically, RIGs comprise a stem-like subgroup with lesser mutation burden and Ch. 1p loss and a pro-inflammatory subgroup with greater mutation burden and depleted DNA repair gene expression. Chromothripsis in several RIG samples is associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. Drug screening suggests microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors, as potentially effective therapies.

No abstract

The high prevalence of arterial calcification in end-stage renal disease (ESRD) is far beyond the explanation by common cardiovascular risk factors such as aging, diabetes, hypertension, and dyslipidemia. The finding relies on the fact that vascular and valvular calcifications are predictors of cardiovascular diseases and mortality in persons with chronic renal failure. In addition to traditional cardiovascular risk factors such as diabetes mellitus and blood pressure control, other ESRD-related risks such as phosphate retention, excess calcium, and prolonged dialysis time also contribute to the development of vascular calcification. The strategies are to reverse “calcium paradox” and lower vascular calcification by decreasing procalcific factors including minimization of inflammation (through adequate dialysis and by avoiding malnutrition, intravenous labile iron, and positive calcium and phosphate balance), correction of high and low bone turnover, and restoration of anticalcification factor balance such as correction of vitamin D and K deficiency; parathyroid intervention is reserved for severe hyperparathyroidism. The role of bone antiresorption therapy such as bisphosphonates and denosumab in vascular calcification in high-bone-turnover disease remains unclear. The limited data on sodium thiosulfate are promising. However, if calcification is to be targeted, ensure that bone health is not compromised by the treatments.

TT on DSA correlates with cerebral AVM flow measured using QMRA and with AVM angioarchitecture and hemorrhagic presentation. Thus, TT may be used to indirectly estimate AVM flow during angiography in real-time and may also be an indicator of important AVM characteristics associated with outflow resistance and increased rupture risk, such as venous stenosis.

No abstract

Current image processing techniques capture large vessels reliably but often fail to preserve connectivity in bifurcations and small vessels. Imaging artifacts and noise can create gaps and discontinuity of intensity that hinders segmentation of vascular trees. However, topological analysis of vascular trees require proper connectivity without gaps, loops or dangling segments. Proper tree connectivity is also important for high quality rendering of surface meshes for scientific visualization or 3D printing. We present a fully automated vessel enhancement pipeline with automated parameter settings for vessel enhancement of tree-like structures from customary imaging sources, including 3D rotational angiography, magnetic resonance angiography, magnetic resonance venography, and computed tomography angiography. The output of the filter pipeline is a vessel-enhanced image which is ideal for generating anatomical consistent network representations of the cerebral angioarchitecture for further topological or statistical analysis. The filter pipeline combined with computational modeling can potentially improve computer-aided diagnosis of cerebrovascular diseases by delivering biometrics and anatomy of the vasculature. It may serve as the first step in fully automatic epidemiological analysis of large clinical datasets. The automatic analysis would enable rigorous statistical comparison of biometrics in subject-specific vascular trees. The robust and accurate image segmentation using a validated filter pipeline would also eliminate operator dependency that has been observed in manual segmentation. Moreover, manual segmentation is time prohibitive given that vascular trees have more than thousands of segments and bifurcations so that interactive segmentation consumes excessive human resources. Subject-specific trees are a first step toward patient-specific hemodynamic simulations for assessing treatment outcomes.

AimHyperkalemia increases the risk of sudden cardiac death (SCD) in hemodialysis patients. Our objective was to determine the association between administering low potassium dialysate to hyperkalemic hemodialysis patients and SCD.MethodsWe conducted a retrospective cohort study with patients undergoing maintenance hemodialysis from May 1, 2006, through December 31, 2013. The dialysate composition was adjusted over time according to monthly laboratory results. A 1.0 mEq/L potassium dialysate was applied in patients with predialysis hyperkalemia (>5.5 mEq/L) and was included as a time-dependent confounding factor. The clinical characteristics of enrolled patients, the incidence and timing of SCD and risk factors for all-cause mortality and SCD were analyzed.ResultsThere were 312 patients on maintenance hemodialysis during the study period. One hundred and fifty-seven patients had been dialyzed against a 1.0 mEq/L potassium dialysate at least once. The rates of all-cause mortality and SCD were 48.17 and 20.74 per 1000 patient-years, respectively. A 1.12-fold increase in the risk of SCD in the 24-hour period starting with the hemodialysis procedure and a 1.36-fold increase in the 24 hours preceding a weekly cycle were found (p = 0.017). Multivariate Cox proportional hazards models showed that age, diabetes mellitus and predialysis hyperkalemia (>5.0 mEq/L) were significant predictors of all-cause mortality and SCD. Exposure to 1.0 mEq/L potassium dialysate, Kt/V, and serum albumin were independent protective factors against all-cause mortality. Only exposure to 1.0 mEq/L potassium dialysate significantly prevented SCD (hazard ratio = 0.33, 95% CI = 0.13–0.85).ConclusionsUsing low potassium dialysate in hyperkalemic hemodialysis patients may prevent SCD.