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Room make use of habits associated with sharks regarding boat activity in an urbanized seaside river.
At a median follow-up of 24 months, all patients had progressed and 6 patients were alive. Median treatment duration was 11.0 weeks (95%CI 6.0-15.9) in the regorafenib group and 6.3 weeks (95%CI 3.9-7.0) in the placebo group (p=0.002). Fourteen of 33 patients (42%) in the regorafenib group had a dose reduction. Stable disease rates were 74% (95%CI 59-90) in the regorafenib group and 34% with placebo (95%CI 18-51; p=0.002). Median PFS in the regorafenib group was 3.0 months (95%CI 2.3-4.9) and 1.5 months (95%CI 1.2-2.0) in the placebo group (hazard ratio 0.49; 95%CI 0.29-0.81; p=0.004) and median OS was 5.3 months (95%CI 2.7-10.5) and 5.1 months (95% CI 3.0-6.4), respectively (p=0.28). There were no unexpected/new safety signals. Conclusion Regorafenib significantly improved PFS and tumor control in patients with previously treated metastatic/unresectable BTC in the second- or third-line setting.Mitochondrial respiratory chain dysfunction may be predisposing for the development of migraine, reflected in high migraine prevalence in patients with mitochondrial disease. Prevalence and impact of migraine in patients with proven mitochondrial disease and the current treatment efficacy were studied using online questionnaires. Patients were selected at the Internal Medicine Department. Headache was reported by 34 (55%) out of 62 patients. Migraine-criteria were met by 85% of them. Efficacy of migraine treatment was achieved in 4 patients. Given the high prevalence of migraine and current treatment insufficiency, migraine is a major threat of quality of life patients with mitochondrial disease.Objective The optimal time after hip fracture to start prophylactic anti-osteoporosis medications (AOMs) remains uncertain, especially in real-world practice. Therefore, we investigated how timing of AOMs initiation affects the risk of subsequent osteoporotic fractures, and what factors influence timing of AOMs prescription. Method Patients ≥50 years old with diagnostic codes indicating hospitalization for hip fracture (n = 77,930) were identified from the Taiwan National Health Insurance Research Database; 9986 who were prescribed AOMs ≤1 year after a newly-diagnosed hip fracture were grouped into those who started AOMs from ≤14 days (very early); 15-84 days (early); 85-252 days (late); and 253-365 days (very late). Associations with fracture-related hospitalizations after an index fracture were analyzed using a multivariate, time-dependent Cox proportional hazards model, and between-group differences compared by log-rank testing. Factors influencing timing of AOMs initiation were elucidated using multivariate logistic regression analyses. Results Compared to AOMs initiation from 15 to 84 days, initiation after 252 days was associated with significantly increased risk of fracture-related hospitalization (HR = 1.93, 95% CI 1.29-2.89). Both sensitivity and pre-specified subgroup analyses yield similar results. Among patients with high adherence to AOMs, the increased risk of subsequent fracture-related hospitalization among very late users was profound (HR = 2.56, 95% CI 1.41-4.64). Conclusion Timing of AOMs initiation was significantly associated with age, index year, index hospital length of stay as well as the accreditation level and geographic region of index hospital. After adjusting factors associated with timing of AOMs initiation and patients' adherence, the anti-fracture benefit of AOMs still depends crucially on the timely initiation of AOMs.Objective To describe bone densitometry results using lumbar spine dual-energy X-ray absorptiometry and forearm peripheral quantitative computed tomography (pQCT) in children with arthrogryposis multiplex congenita (AMC). Study design Prospective study. click here Results Lumbar spine areal bone mineral density (BMD) was measured in 58 participants (mean age 6.8 years, range 1 month to 19.7 years; 26 males). The diagnostic subgroup was Amyoplasia in 27 participants, distal arthrogryposis (unclassified, n = 13; type 2A, n = 1; type 2B, n = 2; type 8, n = 2) in 18 patients, an unclassified form of arthrogryposis in 6 patients, and a syndromic form of arthrogryposis in 7 patients. The mean lumbar spine areal BMD was -0.4 (SD 1.5) which was significantly below 0 (p 0.05). A subset of 22 patients aged 6 years or older (mean age 10.9 years, 11 males) had forearm pQCT analysis. Mean z-scores for trabecular and cortical volumetric BMD at the radius were similar to healthy controls. Radius periosteal bone circumference and bone mineral content were appropriate for height. These densitometric results did not differ between patients with Amyoplasia or individuals with other diagnoses. Conclusions Low areal BMD in children and adolescents with AMC reflects their smaller bone size rather than a specific bone mass deficit. These data do not suggest that children and adolescents with AMC in general require regular monitoring by bone densitometry unless there are specific clinical concerns.Fibroblast growth factor receptor 4 (FGFR4) aberrant expression and activity have been linked to the pathogenesis of a variety of cancers including rhabdomyosarcomas (RMS). We found that treatment of alveolar rhabdomyosarcoma (aRMS) cells with Guadecitabine (SGI-110), a next-generation DNA methyltransferase inhibitor (DNMTi), resulted in a significant reduction of FGFR4 protein levels, 5 days post treatment. Chromatin immunoprecipitation-sequencing (ChIP-seq) in aRMS cells revealed attenuation of the H3K4 mono-methylation across the FGFR4 super enhancer without changes in tri-methylation of either H3K4 or H3K27. These changes were associated with a significant reduction in FGFR4 transcript levels in treated cells. These decreases in H3K4me1 in the FGFR4 super enhancer were also associated with a 240-fold increase in KDM5B (JARID1B) mRNA levels. Immunoblot and immunofluorescent studies also revealed a significant increase in the KDM5B protein levels after treatment in these cells. KDM5B is the only member of KDM5 (JARID1) family of histone lysine demethylases that catalyzes demethylation of H3K4me1. These data together suggest a pleiotropic effect of DNMTi therapy in aRMS cells, converging to significantly lower FGFR4 protein levels in these cells.
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