BACKGROUND/AIMS: Cyclic vomiting syndrome (CVS) is a disabling migraine variant manifesting as severe episodes of nausea and vomiting and often refractory to many therapies. Gastric electrical stimulation (GES), which can reduce nausea and vomiting in gastroparesis, may provide symptomatic relief for drug-refractory CVS. This study assessed the utility GES in reducing the symptoms of CVS and improving the quality of life. METHODS: A one-year, non-randomized, clinical study was conducted. Eleven consecutive patients with drug refractory, cyclic vomiting syndrome based on Rome III criteria and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), underwent treatment with temporary GES (Temp GES) and permanent GES (Perm GES). Post-treatment follow up was done up to one year after permanent gastric electrical stimulation therapy. RESULTS: Total symptom score decreased by 68% and 40% after temporary and permanent GES therapies, respectively. Hospital admission events significantly decreased to 1.50 (± 1.00) events from 9.14 (± 7.21) annual admissions prior to treatment with permanent GES. Vomiting episodes fell by 83% post Temp GES and 69% after Perm GES treatments. Mucosal electrogram values also changed after temporary stimulation. CONCLUSIONS: In a small group of drug-refractory CVS patients, treatments with temporary and permanent GES significantly reduced the severity of gastrointestinal symptoms and frequency of hospital admissions.
Clinical Study ; Electric Stimulation Therapy ; Electric Stimulation* ; Follow-Up Studies ; Gastroenterology ; Gastroparesis ; Humans ; Migraine Disorders ; Nausea ; Quality of Life ; Vomiting*

Glioblastoma multiforme (GBM) is the most common primary brain cancer. Even with aggressive combination therapy, the median life expectancy for patients with GBM remains approximately 14 months. In order to improve the outcomes of patients with GBM, the development of newer treatments is critical. The concept of using the immune system as a therapeutic option has been suggested for several decades; by harnessing the body's adaptive immune mechanisms, immunotherapy could provide a durable and targeted treatment against cancer. However, many cancers, including GBM, have developed mechanisms that protect tumor cells from being recognized and eliminated by the immune system. For new immunotherapeutic regimens to be successful, overcoming immunosuppression via immune checkpoint signaling should be taken into consideration.
Brain Neoplasms ; Glioblastoma* ; Humans ; Immune System ; Immunosuppression ; Immunotherapy ; Life Expectancy ; Radiosurgery

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily of cytokines, is one of the most promising candidates for cancer therapeutics. However, many osteosarcomas are resistant to TRAIL. Bisphosphonates are very effective in the treatment of bone problems associated with malignancies; the antitumor effects are due to the inhibition of protein prenylation that is essential for cell function and survival. The purpose of this study was to determine the effects of bisphosphonates on TRAIL-resistant MG 63 human osteosarcoma cells. The cells showed no response to TRAIL alone; however, pre-treatment with bisphosphonates significantly increased TRAIL-mediated apoptosis and cellular activation of caspase-3. Bisphosphonates significantly induced mRNA and protein expression of the TRAIL receptor, DR5. Bisphosphonates induced protein unprenylation in MG 63 cells; in addition, co-treatment with TRAIL also significantly increased protein unprenylation. Blocking of protein unprenylation using geranylgeraniol attenuated the cellular responses, including cell apoptosis and protein unprenylation induced by bisphosphonates and TRAIL. This is the first study to demonstrate that bisphosphonates markedly enhanced TRAIL-induced apoptosis in human osteosarcoma cells. These findings suggest that bisphosphonates may be a new and effective anticancer treatment with TRAIL proteins for TRAIL-resistant cancer cells.
*Apoptosis ; Blotting, Western ; Bone Density Conservation Agents/*pharmacology ; Bone Neoplasms/*drug therapy/metabolism/pathology ; Cell Proliferation ; Diphosphonates/*pharmacology ; Fluorescent Antibody Technique ; Humans ; Osteosarcoma/*drug therapy/metabolism/pathology ; Receptors, TNF-Related Apoptosis-Inducing Ligand/*metabolism ; TNF-Related Apoptosis-Inducing Ligand/*metabolism ; Tumor Cells, Cultured ; Up-Regulation

Methods: We assessed baseline neutral upright, standing flexion, seated lateral radiographs, and magnetic resonance imaging (MRI) for patients identified with spondylolisthesis from January 2021 to May 2022 by a single spine surgeon. DS was classified by Meyerding and Clinical and Radiographic Degenerative Spondylolisthesis classifications. A difference of >10° or >8% between views, respectively, was used to characterize angular and translational instability. Analysis of variance and paired chi-square tests were utilized to compare modalities. Results: A total of 136 patients were included. Seated lateral and standing flexion radiographs showed the greatest slip percentage (16.0% and 16.7%), while MRI revealed the lowest (12.2%, p <0.001). Standing flexion and lateral radiographs when seated produced more kyphosis (4.66° and 4.97°, respectively) than neutral upright and MRI (7.19° and 7.20°, p <0.001). Seated lateral performed similarly to standing flexion in detecting all measurement parameters and categorizing DS (all p >0.05). Translational instability was shown to be more prevalent when associated with seated lateral or standing flexion than when combined with neutral upright (31.5% vs. 20.2%, p =0.041; and 28.1% vs. 14.6%, p =0.014, respectively). There were no differences between seated lateral or standing flexion in the detection of instability (all p >0.20). Conclusions Seated lateral radiographs are appropriate alternatives for standing flexion radiographs. Films taken when standing up straight do not offer any more information for DS detection. Rather than standing flexion-extension radiographs, instability can be detected using an MRI, which is often performed preoperatively, paired with a single seated lateral radiograph.

Androgen deprivation in men leads to increased adiposity, but the mechanisms underlying androgen regulation of fat mass have not been fully defined. Androgen receptor (AR) is expressed in monocytes/macrophages, which are resident in key metabolic tissues and influence energy metabolism in surrounding cells. Male mice bearing a cell-specific knockout of the AR in monocytes/macrophages (M-ARKO) were generated to determine whether selective loss of androgen signaling in these cells would lead to altered body composition. Wild-type (WT) and M-ARKO mice (12-22 weeks of age, n = 12 per group) were maintained on a regular chow diet for 8 weeks and then switched to a high-fat diet for 8 additional weeks. At baseline and on both the regular chow and high-fat diets, no differences in lean mass or fat mass were observed between groups. Consistent with the absence of differential body weight or adiposity, no differences in food intake (3.0 ± 0.5 g per day for WT mice vs 2.8 ± 0.4 g per day for M-ARKO mice) or total energy expenditure (0.6 ± 0.1 Kcal h^-1 for WT mice vs 0.5 ± 0.1 Kcal h^-1 for M-ARKO mice) were evident between groups during high-fat feeding. Liver weight was greater in M-ARKO than that in WT mice (1.5 ± 0.1 g vs 1.3 ± 0.0 g, respectively, P = 0.02). Finally, M-ARKO mice did not exhibit impairments in glucose tolerance or insulin sensitivity relative to WT mice at any study time point. In aggregate, these findings suggest that AR signaling specifically in monocytes/macrophages does not contribute to the regulation of systemic energy balance, adiposity, or insulin sensitivity in male mice.
Adiposity/genetics* ; Animals ; Blood Glucose/metabolism* ; Energy Metabolism/genetics* ; Glucose Tolerance Test ; Homeostasis/genetics* ; Liver/anatomy & histology* ; Macrophages/metabolism* ; Male ; Mice ; Mice, Knockout ; Monocytes/metabolism* ; Organ Size ; Receptors, Androgen/metabolism* ; Signal Transduction