Associations between multiple sclerosis and in-hospital outcomes of patients with hemorrhagic stroke.

OBJECTIVE: To determine the influence of multiple sclerosis (MS) on in-hospital outcomes of patients with hemorrhagic strokes using a large, nationally representative database. MATERIALS AND METHODS: This population-based, retrospective study extracted data of adults with hemorrhagic stroke from the US Nationwide Inpatient Sample (NIS) database from 2016 to 2018. Patients with/without MS were then compared. Hemorrhagic stroke and MS were identified by the International Classification of Diseases, Tenth editions (ICD-10) codes. In-hospital outcomes (i.e., in-hospital mortality, discharge destination, length of stay [LOS], total hospital cost, and major complications) were compared between subjects with and without MS using logistic regression analysis. RESULTS: Among 107,573 patients with hemorrhagic stroke, 0.3% (n=337) had MS. After 1:10 propensity-score (PS) matching, 3,707 patients remained in the analytic sample. Multivariable analysis revealed that patients with MS had significantly shorter LOS (adjusted ß=-1.34 days; 95% CI: -2.41 to -0.26, p=0.015), and lower total hospital costs (adjusted ß=-28.82; 95% CI: -43.57 to -14.06, p<0.001) than those without MS. No significant different risks of any major complications, in-hospital mortality, or transfer to nursing homes/long-term care facilities were observed. For major complications, patients with MS had a significantly lower risk of cerebral edema than those without MS (adjusted odds ratio [aOR] = 0.66, 95%CI: 0.51 to 0.86, p =0.002) CONCLUSIONS: In hospitalized patients with hemorrhagic stroke, those with MS have shorter LOS, lower costs, and a lower risk of cerebral edema compared to no MS. More relevant experiments and studies are needed to confirm results of this study.

Spinal neurofibromatosis with NF1 mutation in a classic neurofibromatosis type 1 family: A case report and literature review.

BACKGROUND: Spinal neurofibromatosis (SNF) is a related form of Neurofibromatosis type 1 (NF1) with a low incidence. Here, we report a SNF patient with NF1 (OMIM *613113) mutation in a classic NF1 family to enrich the case data. METHODS: We presented the clinical data of a 27-year-old female suffered from SNF. Two NF1 individuals (the mother and the brother) in the patient's family were also described. In the SNF patient, tumors in cervical were removed by surgical operation after the spinal MRI evaluation. Hematoxylin-eosin staining and immunohistochemistry were performed to better characterize the excised tumors. NF1 exons of the patient and her NF1 families were further sequenced by the next-generation sequencing technology. RESULTS: The patient developed irregular café-au-lait macules, multi-subcutaneous nodules, recurrent numbness, and weakness of both lower extremities. Multiple neurofibromas were found in the whole spine by spinal MRI. Tumor-like cells and hyperplasia of ganglion cells were found in the excised tissue by H&E staining and immunohistochemistry, respectively. One-year follow-up on the SNF patient showed that after the surgery lower limb pain, numbness and convulsion were completely relieved. A common germ-line pathogenic mutation (NM_000267.3:c.1721 + 3A>G) was found in both the SNF patient and her classic NF1 families. CONCLUSION: A case of SNF with classic NF1 mutation in a classic NF1 family was identified for the first time, indicating that SNF may share the same gene mutation with NF1, while the different manifestation of NF1 and SNF may be related to gene modification.

LRRC8A potentiates temozolomide sensitivity in glioma cells via activating mitochondria-dependent apoptotic pathway.

Chloride (Cl-), a primary anion in the extracellular fluid, plays an important role in a variety of physiological and pathological processes, such as cell apoptosis and proliferation. However, the information about Cl- in cancer cell apoptosis and chemoresistance is poorly understood. In the present study, we found that temozolomide (TMZ) treatment led to a decrease in intracellular concentration of Cl- ([Cl-]i) in both U87 and TMZ-resistant U87/R glioma cells. The decrease in [Cl-]i was more noticeable in U87 cells than in U87/R cells. Moreover, the expression of LRRC8A was reduced in U87/R cells compared with U87 cells. LRRC8A downregulation inhibited TMZ, induced the decrease in [Cl-]i and abolished the difference of [Cl-]i between U87 cells and U87/R cells. Knockdown of LRRC8A using small interfering RNA attenuated TMZ-induced U87 cell growth inhibition and apoptosis, while overexpression of LRRC8A by adenoviral infection enhanced the effect of TMZ on U87 and U87/R cell viability and apoptosis. Furthermore, LRRC8A downregulation inhibited TMZ-induced mitochondria-dependent apoptosis, including elevated Bcl-2 expression, reduced Bax expression, cytochrome c release, and caspase nine and caspase three activation. On the contrary, upregulation of LRRC8A augmented the activation of mitochondria-dependent apoptotic pathway in U87 and U87/R cells. In conclusion, this study demonstrates that LRRC8A potentiates TMZ-induced glioma cell apoptosis via promoting mitochondria-dependent apoptosis, suggesting that LRRC8A can be represented as a novel target for drug resistance treatment in glioma cells.