4 research outputs found
Management of peripheral facial nerve palsy
Peripheral facial nerve palsy (FNP) may (secondary FNP) or may not have a detectable cause (Bell’s palsy). Three quarters of peripheral FNP are primary and one quarter secondary. The most prevalent causes of secondary FNP are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immunological disorders, or drugs. The diagnosis of FNP relies upon the presence of typical symptoms and signs, blood chemical investigations, cerebro-spinal-fluid-investigations, X-ray of the scull and mastoid, cerebral MRI, or nerve conduction studies. Bell’s palsy may be diagnosed after exclusion of all secondary causes, but causes of secondary FNP and Bell’s palsy may coexist. Treatment of secondary FNP is based on the therapy of the underlying disorder. Treatment of Bell’s palsy is controversial due to the lack of large, randomized, controlled, prospective studies. There are indications that steroids or antiviral agents are beneficial but also studies, which show no beneficial effect. Additional measures include eye protection, physiotherapy, acupuncture, botulinum toxin, or possibly surgery. Prognosis of Bell’s palsy is fair with complete recovery in about 80% of the cases, 15% experience some kind of permanent nerve damage and 5% remain with severe sequelae
Comprehensive molecular characterization of the hippo signaling pathway in cancer
Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era
Thrombin-receptor antagonist vorapaxar in acute coronary syndromes
BACKGROUND
Vorapaxar is a new oral protease-activated–receptor 1 (PAR-1) antagonist that inhibits
thrombin-induced platelet activation.
METHODS
In this multinational, double-blind, randomized trial, we compared vorapaxar with
placebo in 12,944 patients who had acute coronary syndromes without ST-segment
elevation. The primary end point was a composite of death from cardiovascular causes,
myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent
coronary revascularization.
RESULTS
Follow-up in the trial was terminated early after a safety review. After a median follow-up
of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031
of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo
(Kaplan–Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval
[CI], 0.85 to 1.01; P = 0.07). A composite of death from cardiovascular causes,
myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group
versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89;
95% CI, 0.81 to 0.98; P = 0.02). Rates of moderate and severe bleeding were 7.2% in the
vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58;
P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard
ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events
were similar in the two groups.
CONCLUSIONS
In patients with acute coronary syndromes, the addition of vorapaxar to standard
therapy did not significantly reduce the primary composite end point but significantly
increased the risk of major bleeding, including intracranial hemorrhage