Cripto‐1 Expression in Glioblastoma Multiforme

Human glioblastoma multiforme (GBM) is an aggressive cancer with a very poor prognosis. Cripto‐1 (CR‐1) has a key regulatory role in embryogenesis, while in adult tissue re‐expression of CR‐1 has been correlated to malignant progression in solid cancers of non‐neuronal origin. As CR‐1 expression has yet to be described in cerebral cancer and CR‐1 is regulated by signaling pathways dysregulated in GBM, we aimed to investigate CR‐1 in the context of expression in GBM. The study was performed using enzyme‐linked immunosorbent assay (ELISA), Western blotting, polymerase chain reaction (PCR) and immunohistochemistry to analyze the blood and tissue from 28 GBM and 4 low‐grade glioma patients. Within the patient cohort, we found high CR‐1 protein levels in blood plasma to significantly correlate with a shorter overall survival. We identified CR‐1 in different areas of GBM tissue, including perivascular tumor cells, and in endothelial cells. Collectively, our data suggest that CR‐1 could be a prognostic biomarker for GBM with the potential of being a therapeutic target.     

Variation and association to diabetes in 2000 full mtDNA sequences mined from an exome study in a Danish population

In this paper, we mine full mtDNA sequences from an exome capture data set of 2000 Danes, showing that it is possible to get high-quality full-genome sequences of the mitochondrion from this resource. The sample includes 1000 individuals with type 2 diabetes and 1000 controls. We characterise the variation found in the mtDNA sequence in Danes and relate the variation to diabetes risk as well as to several blood phenotypes of the controls but find no significant associations. We report 2025 polymorphisms, of which 393 have not been reported previously. These 393 mutations are both very rare and estimated to be caused by very recent mutations but individuals with type 2 diabetes do not possess more of these variants. Population genetics analysis using Bayesian skyline plot shows a recent history of rapid population growth in the Danish population in accordance with the fact that >40% of variable sites are observed as singletons.     

Improvement of anticoagulant treatment using a dynamic decision support algorithm: A Danish Cohort study

Introduction

Warfarin is the most widely prescribed vitamin K antagonist and in the United States and Europe more than 10 million people are currently in long-term oral anticoagulant treatment. This study aims to retrospectively validate a dynamic statistical model providing dosage suggestions to patients in warfarin treatment.

Materials and methods

The model was validated on a cohort of 553 patients with a mean TTR of 83%. Patients in the cohort were self-monitoring and managed by a highly specialised anticoagulation clinic. The predictive model essentially consists of three parts handling INR history, warfarin dosage and biological noise, which allows for prediction of future INR values and optimal warfarin dose to stay on INR target. Further, the model is based on parameters initially being set to population values and gradually individualised during monitoring of patients.

Primary outcome

Time in therapeutic range was used as surrogate quality measure of the treatment, and model-suggested dosage of warfarin was used to assess the accuracy of the model performance.

Results

The accuracy of the model predictions measured as median absolute error was 0.53 mg/day (interquartile range from 0.25 to 1.0). The model performance was evaluated by the difference between observed and predicted warfarin intake in the preceding week of an INR measurement. In more than 70% of the cases where INR measurements were outside the therapeutic range, the model suggested a more reasonable dose than the observed intake.

Conclusion

Applying the proposed dosing algorithm can potentially further increase the time in INR target range beyond 83%.     

ULNAR NEUROPATHY AT THE ELBOW: CLINICAL AND ELECTROPHYSIOLOGICAL OUTCOME OF SURGICAL AND CONSERVATIVE TREATMENT

The objective was to evaluate and compare the clinical and electrophysiological outcome of treatment in patients with ulnar neuropathy at the elbow in 32 consecutive patients who were studied prospectively. Based on the electrophysiological findings 15 patients were treated by surgical decompression and 17 were treated conservatively. Sensory and motor nerve conduction studies across and below the elbow were done in all patients before treatment and again after one year. Postoperatively 10/15 patients (67%) improved clinically and 12 patients (80%) had improved nerve conduction results. There was clinical and electrophysiological agreement in eight patients in the surgically-treated group, all of whom improved both clinically and electrophysiologically. In the conservatively-treated group six patients (35%) showed clinical improvement, 10 patients had no improvement, and one patient was worse. The nerve conduction studies improved in six patients (35%), were unchanged in eight patients, and worse in three. There was clinical and electrophysiological agreement in 11 patients. We conclude that the electrophysiological examination was valuable in deciding which patients to operate on, and that most of the patients improved clinically or electrophysiologically postoperatively.     

Muscle phenotype in patients with myotonic dystrophy type 1

Introduction: The pathogenesis of muscle involvement in patients with myotonic dystrophy type 1 (DM1) is not well understood. In this study, we characterized the muscle phenotype in patients with confirmed DM1. Methods: In 38 patients, muscle strength was tested by hand‐held dynamometry. Myotonia was evaluated by a handgrip test and by analyzing the decrement of the compound muscle action potential. Muscle biopsies were assessed for morphological changes and Na⁺‐K⁺ pump content. Results: Muscle strength correlated with a decline in Na⁺‐K⁺ pump content (r = 0.60, P < 0.001) and with CTG expansion. CTG expansion did not correlate with severity of myotonia, proximal histopathological changes, or Na⁺‐K⁺ pump content. Histopathologically, we found few centrally placed nuclei (range 0.2–6.9%). Conclusions: The main findings of this study are that muscle weakness correlated inversely with CTG expansion and that central nuclei are not a prominent feature of proximal muscles in DM1. Muscle Nerve 47:409‐415, 2013