A Novel Combination of Prion Strain Co-Occurrence in Patients with Sporadic Creutzfeldt-Jakob Disease.

Six subgroups of sporadic Creutzfeldt-Jakob disease have been identified by distinctive clinicopathologic features, genotype at polymorphic codon 129 [methionine (M)/valine (V)] of the PRNP gene, and type of abnormal prion proteins (type 1 or 2). In addition to the pure subgroups, mixed neuropathologic features and the coexistence of two types of abnormal prion proteins in the same patient also have been reported. Here, we found that a portion of the patients previously diagnosed as MM1 had neuropathologic characteristics of the MM2 thalamic form (ie, neuronal loss of the inferior olivary nucleus of the medulla). Furthermore, coexistence of biochemical features of the MM2 thalamic form also was confirmed in the identified cases. In addition, in transmission experiments using prion protein-humanized mice, the brain material from the identified case showed weak infectivity and generated characteristic abnormal prion proteins in the inoculated mice resembling those after inoculation with brain material of MM2 thalamic form. Taken together, these results show that the co-occurrence of MM1 and MM2 thalamic form is a novel entity of sporadic Creutzfeldt-Jakob disease prion strain co-occurrence. The present study raises the possibility that the co-occurrence of the MM2 thalamic form might have been overlooked so far because of the scarcity of abnormal prion protein accumulation and restricted neuropathology.

High Relapse Rate in Patients with Polymyalgia Rheumatica despite the Combination of Immunosuppressants and Prednisolone: A Single Center Experience of 89 patients.

Polymyalgia rheumatica (PMR) is an inflammatory disorder in the elderly and is characterized by pain in the shoulders and lower back. Previous studies from western countries have shown that relapse is frequent; however, there are only a few reports on the relapse rate in Japan. Here we examined the relapse rate, and sought to identify factors that predict recurrence in patients with PMR. Of 110 patients who fulfilled the Bird's criteria for PMR between May 2011 and June 2019, 21 patients were excluded, and the remaining 89 patients were followed up until July 2019. Relapse was defined when clinical symptoms were exacerbated and serum C-reactive protein level increased. The relapse-free survival curves were plotted using the Kaplan-Meier method, and log-rank test was used for statistical analysis. The mean age of the 89 patients (50 males and 39 females) was 71.8 years. The mean dose of initial prednisolone (PSL) was 11.8 mg/day. The 1-, 3-, and 5-year relapse-free survival rates were 81.6%, 58.0%, and 52.3% (N = 59, 21, and 7), respectively. In patients who experienced recurrence, the 1- and 3-year second relapse-free survival rates were 58.3% and 27.3% (N = 18 and 3), respectively. Immunosuppressants, such as methotrexate and tacrolimus, were added to PSL in 19 of 30 patients who experienced relapse at the discretion of the attending physicians; however, none of the immunosuppressants worked for preventing second relapses and had steroid-sparing effects. These results indicate that effective immunosuppressants are required to suppress relapse in the treatment of PMR.

Multidisciplinary Approach to Prevent de novo Hepatitis B in Patients with Rheumatoid Arthritis.

The reactivation of hepatitis B virus (HBV) in patients with rheumatoid arthritis (RA) is currently a social problem. Our hospital has established a project team, which consisted of medical staff including doctors, nurses, pharmacists, and technicians, to prevent HBV reactivation and subsequent de novo hepatitis B in 2015. To verify the usefulness of the team, we aimed to examine the implementation rate of HBV screening tests in patients with RA in 2011, 2015, and 2018. We also examined the rate of HBV infection, as well as the rate of HBV reactivation during the course. In this study, medical records of patients who visited our hospital in 2011, 2015, and 2018 were retrospectively reviewed. HBV screening was completed when hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), and hepatitis B core antibody (HBcAb) were all examined. The prevalence of patients who completed HBV screening dramatically increased from 2.4% in 2011 to 79.1% in 2015 and 86.9% in 2018. Patients who completed the screening had significantly higher rates of liver dysfunction, methotrexate use, and use of biological disease-modifying antirheumatic drugs than those who did not. Of the 767 patients who completed HBV screening in 2018, 157 patients (20.5%) had previously resolved HBV infection (HBsAg-negative but HBsAb- and/or HBcAb-positive). During a mean follow-up of 41.0 months, reactivation of HBV was observed in 10 out of the 157 patients (6.4%); however, none developed de novo hepatitis B. In conclusion, our multidisciplinary approach to prevent de novo hepatitis B is considered useful.

A case of Duchenne muscular dystrophy recovered from prolonged ischemic kidney injury which emerged with a normal creatinine level.

Duchenne muscular dystrophy (DMD) is an inherited disease characterized by progressive degeneration of the skeletal muscles. Renal dysfunction in patients with DMD has recently become more apparent as life expectancy has increased owing to advances in respiratory devices and heart failure therapies. A 23-year-old man with DMD who required nasal tube feeding was referred to our hospital with a 4-month history of renal dysfunction and anemia. The patient's serum creatinine (sCr) level was within the normal range (0.84 mg/dL), but his serum cystatin C level and estimated glomerular filtration rate calculated by cystatin C (5.90 mg/L and 7.5 mL/min/1.73 m2, respectively) indicated severe renal impairment. A urinalysis revealed elevated levels of protein and tubular markers. The patient's hemoglobin and erythropoietin levels indicated renal anemia. Hypotension, a collapsed inferior vena cava, and a poor tube feeding episode suggested that the kidney injury was due to renal ischemia, which progressed to tubulointerstitial kidney injury, an intrinsic kidney injury. The angiotensin-converting enzyme inhibitors and beta-blockers were discontinued, and extracellular fluid was infused. Thereafter, the patient's renal function recovered. Subsequently, the patient's urinary findings and anemia improved. Although advances in cardioprotective agents are expected to improve the prognosis of patients with DMD, it is important to consider that the number of patients with kidney injury due to renal ischemia may increase and that it is difficult to evaluate renal function using sCr level in patients with DMD because of decreased skeletal muscle mass.

JAK2 mutation-positive polycythaemia vera associated with IgA vasculitis and nephrotic syndrome: a case report.

We report a case of polycythaemia vera (PV) associated with IgA vasculitis. A 45-year-old man was admitted for evaluation of abdominal pain and palpable purpura. IgA vasculitis was diagnosed, and oral prednisolone therapy (30 mg/day) was initiated. On day 6, the patient developed left hemiparesis, and magnetic resonance imaging revealed acute cerebral infarction. Bone marrow biopsy results and the identification of a Janus kinase 2 (JAK2) mutation led to the diagnosis of PV. Despite steroid therapy, urine protein levels increased to 15 g/g・Cre. Renal biopsy demonstrated mild mesangial proliferation with IgA deposits, but immunosuppressive therapy was partially effective. This case suggests that PV can be a complication of IgA vasculitis and that preventive measures for thrombosis should be taken in such cases.