Because of the increased use of contrast media, the potential risk of contrast-induced acute kidney injury (CIAKI) has also increased. CIAKI often results in chronic kidney disease (CKD), an affliction with increasing incidence in modern society. The current prevalence of CIAKI is difficult to estimate because most victims are asymptomatic. The first Japanese guidelines regarding contrast agent examinations were recently announced, but their only recommendation is to provide classic fluid replacement with saline 6–12 h before and after the contrast procedure. According to a review summarizing the recent literature, little evidence supports this suggestion. To obtain early diagnoses and to treat emergent patients, it is appropriate to perform procedures using contrast media without knowledge of patients’ renal function. Prevention of CIAKI is the most important consideration, and the usefulness of risk scores predicting the development of CIAKI has been reported. However, no prospective studies have been performed to date, and, therefore, such studies will be necessary in the future. Furthermore, the development of novel preventative interventions for CIAKI is also required.
Intracerebral hemorrhage is a well-known complication resulting from warfarin use; however, warfarin-associated intraspinal hematoma is very rare. Warfarin-associated intraspinal hematoma may exhibit delayed progression, and patients may present with atypical symptoms, occasionally resulting in delayed diagnosis. We report the case of a 65-year-old man who visited our emergency department (ED) with acute urinary retention. He had been previously diagnosed with non-valvular atrial fibrillation, arterial hypertension, and benign prostatic hyperplasia, and he used warfarin for the prevention of systemic embolism. The patient was initially diagnosed with worsening of the prostatic hyperplasia. After 2 days, he revisited the ED with painless paraparesis. Magnetic resonance imaging of the thoracic spine revealed an intraspinal hematoma at Th7–8, and blood coagulation tests indicated a prothrombin time-international normalized ratio of 3.33. Despite attempts to reverse the effects of warfarin with vitamin K administration, the paraparesis progressed to paraplegia, necessitating urgent surgical removal of the hematoma. Partial recovery of motor function was evident after surgery. From the present case, we learned that intraspinal hematoma should be included in the differential diagnosis of patients using warfarin who present with acute urinary retention. Although there are no evidence-based treatment guidelines for warfarin-associated intraspinal hematoma, surgical treatment may be warranted for those who exhibit neurological deterioration.
Our group investigates early and late stages in the development of squamous cell carcinomas (SCCs), in order to identify new approaches to diagnosis and therapy. The principal themes are:
1. Transcriptional deregulation of high-risk human papillomavirus (HRHPV)
We study mechanisms of HRHPV transcriptional deregulation and competitive cell selection during SCC progression, focussing on the causes and effects of integration of HPV16 into the host genome. We showed that HPV16 integration does not necessarily lead to a competitive growth advantage or increased levels of virus oncogenes. Selection of individual cells is determined through multiple layers of epigenetic regulation of the integrated virus genome. We are currently studying whether the epigenetic landscape of integrated HPV16 reflects that of the host genome at the integration site and/or sites of long-range chromatin interactions of the virus DNA. This work may ultimately identify targets for epigenetic therapies in SCCs containing integrated HRHPV.
2. The oncostatin-M receptor (OSMR) in metastasis
The cell-surface oncostatin-M receptor (OSMR) has emerged as an exciting therapeutic target in SCCs. Both copy number gain and over-expression of OSMR have a strong adverse prognostic effect in SCCs. Carcinoma cells that over-expressed OSMR were more sensitive to the major ligand OSM, which induced multiple pro-malignant effects, including epithelial-mesenchymal transition, increased metastasis and the ability to induce pro-malignant changes in cells from the tumour microenvironment (TME). We are now studying the effectiveness of OSM:OSMR blockade on the growth and metastasis of SCC cells in vivo, as well as effects on the TME in immunocompetent hosts.
(Presented at the 1923th Meeting, August 10, 2016)