Background: The incidence of suicide has increased markedly in Japan since 1998. As psychological autopsy is not generally accepted in Japan, surveys of suicide attempts, an established risk factor of suicide, are highly regarded. We have carried out this study to gain insight into the psychiatric aspects of those attempting suicide in Japan.

BackgroundProgressive familial intrahepatic cholestasis type 1 (PFIC1), an inherited liver disease caused by mutations in ATP8B1, progresses to severe cholestasis with a sustained intractable itch. Currently, no effective therapy has been established for PFIC1. Decreased function of the bile salt export pump (BSEP) in hepatocytes is suggested to be responsible for the severe cholestasis observed in PFIC1. We found a previously unidentified pharmacological effect of 4-phenylbutyrate (4PB) that increases the expression and function of BSEP. Here, we tested 4PB therapy in three patients with PFIC1.MethodsThe therapeutic potency of 4PB in these patients was tested by oral administration of this drug with gradually increasing dosage (200, 350, and 500 mg/kg/day) for 6 months. Biochemical, histological, and clinical data were collected.Results4PB therapy had no beneficial effect on the patients’ liver functions, as assessed by biochemical and histological analyses, despite an increase in hepatic BSEP expression. However, therapy with 4PB at a dosage of 350 or 500 mg/kg/day significantly relieved the intractable itch. Serum levels of potential pruritogens in cholestasis were much higher than the reference ranges during the 4PB therapy.Conclusions4PB therapy may be a new medication for patients with intractable cholestatic pruritus and may improve quality of life for patients and their families.

This is the first study to measure the CYP7A1 mRNA levels in human BA HET. Fibroblast growth factor 19 was increased in BA hepatocytes. By focusing on its regulation in hepatocytes, we showed that the FGF19 pathway did not suppress bile acid synthesis, probably due to an altered mechanism involving upregulated SPRY2 in BA patients.

Highlights We report here a case of JC virus granule cell neuronopathy associated with Ruxolitinib It is worthwhile considering the possibility of JCV-GCN in myelofibrosis patients receiving ruxiolitinib, who present with progressive cerebellar symptoms and cerebellar atrophy. Combination therapy using mefloquine and mirtazapine may be an effective treatment.

Objective: This study aimed to retrospectively assess the efficacy and safety of anagrelide in cytoreduction therapy-naïve essential thrombocythemia (ET) patients in a real-world setting.Method: Data from 53 ET patients who received anagrelide as a first-line therapy were reviewed for patient characteristics, antiplatelet status, cytoreduction status, therapeutic effects, adverse events, thrombohemorrhagic event development, progression to myelofibrosis or acute leukemia, and cause of death. Results:The rate of achieving a platelet count of <600 × 10 9 /L during anagrelide monotherapy was 83.0%. Adverse events occurred in 32 of 53 patients, and tended to be slightly more severe in patients with cardiac failure; however, they were mostly tolerable. The therapeutic effect of anagrelide was consistent, regardless of genetic mutation profiles. The incidence of anemia as an adverse event was significantly higher in the CALR mutation-positive group. Favorable platelet counts were also achieved in patients for whom hydroxyurea was introduced as a replacement for anagrelide or in addition to anagrelide because of unresponsiveness or intolerance to treatment. Conclusion:In Japanese cytoreduction therapy-naïve ET patients, anagrelide administration as a first-line therapy demonstrated favorable effects in reducing platelet counts, and its safety profile that was generally consistent with those in previous reports. K E Y W O R D S anagrelide, essential thrombocythemia, first-line, treatment | 117 ITO eT al. Complete response, n (%) 27 (50.9) Partial response, n (%) 18 (34.0) No response, n (%) 8 (15.1) AEs (≥5% of patients) Palpitations, n (%) 14 (26.4) Headache, n (%) 11 (20.8) Anemia, n (%) 10 (18.9) Diarrhea, n (%) 4 (7.5) Cardiac failure, n (%) 3 (5.7) AEs (grade 3) Anemia, n (%) 2 (3.8) Cardiac failure, n (%) 2 (3.8) Abbreviations: AE: adverse event; SD: standard deviation.