Introduction Acute subdural hematomas (ASDHs) have a high mortality rate and unfavorable outcomes especially in the elderly population even after surgery is performed. The conventional recommended surgeries by the Brain Trauma Foundation in 2006 were craniotomies or craniectomies for ASDH. As the world population ages, and endoscopic techniques improve, endoscopic surgery should be utilized to improve the outcomes in elderly patients with ASDH. Materials and Methods This was a single-center retrospective report on our series of six patients that underwent endoscopic ASDH evacuation (EASE). Demographic data, the contralateral global cortical atrophy (GCA) score, evacuation rates, and outcomes were analyzed. Results All patients' symptoms and Glasgow Coma Scale improved or were similar after EASE with no complications. Good outcome was seen in 4 (66.7%) patients. Patients with poor outcome had initial low Glasgow Coma Scale scores on admission. The higher the contralateral GCA score, the higher the evacuation rate ( r = 0.825, p ≤ 0.043). All the patients had a GCA score of ≥7. Conclusion EASE is at least not inferior to craniotomy for the elderly population in terms of functional outcome for now. Using the contralateral GCA score may help identify suitable patients for this technique instead of just using a cut-off age as a criteria.
Osteomodulin (OMD) and proline/arginine-rich end leucine repeat protein (PRELP) are secreted extracellular matrix proteins belonging to the small leucine-rich proteoglycans family. We found that OMD and PRELP were specifically expressed in umbrella cells in bladder epithelia, and their expression levels were dramatically downregulated in all bladder cancers from very early stages and various epithelial cancers. Our in vitro studies including gene expression profiling using bladder cancer cell lines revealed that OMD or PRELP application suppressed the cancer progression by inhibiting TGF-β and EGF pathways, which reversed epithelial-mesenchymal transition (EMT), activated cell-cell adhesion, and inhibited various oncogenic pathways. Furthermore, the overexpression of OMD in bladder cancer cells strongly inhibited the anchorage-independent growth and tumorigenicity in mouse xenograft studies. On the other hand, we found that in the bladder epithelia, the knockout mice of OMD and/or PRELP gene caused partial EMT and a loss of tight junctions of the umbrella cells and resulted in formation of a bladder carcinoma in situ-like structure by spontaneous breakdowns of the umbrella cell layer. Furthermore, the ontological analysis of the expression profiling of an OMD knockout mouse bladder demonstrated very high similarity with those obtained from human bladder cancers. Our data indicate that OMD and PRELP are endogenous inhibitors of cancer initiation and progression by controlling EMT. OMD and/or PRELP may have potential for the treatment of bladder cancer.
We describe four families with affected siblings showing unique clinical features: early-onset (before 1 year of age) progressive diffuse brain atrophy with regression, postnatal microcephaly, postnatal growth retardation, muscle weakness/atrophy, and respiratory failure. By whole-exome sequencing, we identified biallelic TBCD mutations in eight affected individuals from the four families. TBCD encodes TBCD (tubulin folding co-factor D), which is one of five tubulin-specific chaperones playing a pivotal role in microtubule assembly in all cells. A total of seven mutations were found: five missense mutations, one nonsense, and one splice site mutation resulting in a frameshift. In vitro cell experiments revealed the impaired binding between most mutant TBCD proteins and ARL2, TBCE, and β-tubulin. The in vivo experiments using olfactory projection neurons in Drosophila melanogaster indicated that the TBCD mutations caused loss of function. The wide range of clinical severity seen in this neurodegenerative encephalopathy may result from the residual function of mutant TBCD proteins. Furthermore, the autopsied brain from one deceased individual showed characteristic neurodegenerative findings: cactus and somatic sprout formations in the residual Purkinje cells in the cerebellum, which are also seen in some diseases associated with mitochondrial impairment. Defects of microtubule formation caused by TBCD mutations may underlie the pathomechanism of this neurodegenerative encephalopathy.