Tiotropium/olodaterol versus tiotropium in Japanese patients with COPD: results from the DYNAGITO study.

Background: The DYNAGITO study was a Phase IIIb, randomized, double-blind, multicenter, active-controlled, parallel-group, 52-week study designed to determine the efficacy and safety of tiotropium and olodaterol combination therapy (TIO+OLO 5/5 µg) versus tiotropium monotherapy (TIO 5 µg) for reducing moderate-to-severe exacerbations of COPD. This is a prespecified analysis of the DYNAGITO data in Japanese patients. Patients and methods: Enrolled patients had a diagnosis of COPD with at least one moderate-to-severe exacerbation in the previous 12 months. Of the total 7,880 treated patients in the DYNAGITO study, 461 (TIO+OLO 5/5 µg: n=226, TIO 5 µg: n=235) were Japanese. The primary endpoint was the annualized rate of moderate-to-severe COPD exacerbations. The key secondary endpoint was the time to first moderate-to-severe COPD exacerbation, and other secondary endpoints included the annualized rate of exacerbations leading to hospitalization, time to first COPD exacerbation leading to hospitalization, and all-cause mortality. Safety data were analyzed descriptively. Results: Combination therapy with TIO+OLO resulted in a 29% lower rate of moderate-to-severe COPD exacerbations relative to TIO monotherapy (rate ratio 0.71; 99% CI: 0.46, 1.10; p=0.0434). The risk of a first moderate-to-severe COPD exacerbation was 19% lower with TIO+OLO combination therapy than with TIO monotherapy (HR 0.81; 99% CI: 0.57, 1.17; p=0.1379), although this difference was not statistically significant. The annualized rate of COPD exacerbations requiring hospitalization was 14% lower in the TIO+OLO arm than in the TIO arm (rate ratio 0.86; 95% CI: 0.52, 1.42; p=0.5654). The adverse event incidence was balanced between treatment arms. Conclusion: In a prespecified subgroup analysis of Japanese patients in the DYNAGITO study, combination therapy with TIO+OLO was more effective than TIO in reducing exacerbations. Both treatments were well tolerated.

Mycoplasma pneumoniae-associated mild encephalitis/encephalopathy with a reversible splenial lesion: report of two pediatric cases and a comprehensive literature review.

BACKGROUND: No literature review exists on Mycoplasma pneumoniae-associated mild encephalitis/encepharopathy with a reversible splenial lesion (MERS). METHODS: M.pneumoniae-associated MERS cases were searched till August 2016 using PubMed/Google for English/other-language publications and Ichushi ( http://www.jamas.or.jp/ ) for Japanese-language publications. Inclusion criteria were children fulfilling definition for encephalitis, M.pneumoniae infection, and neuroimaging showing hyperintensity in the splenium of the corpus callosum (SCC) alone (type I) or SCC/other brain areas (type II). RESULTS: We described two children with type I and II M.pneumoniae-associated MERS. Thirteen cases found by the search and our 2 cases were reviewed. Mean age, male/female ratio, duration of prodromal illness was 8.3 years, 1.5 and 3.5 days. The most common neurological symptom was drowsiness, followed by abnormal speech/behavior, ataxia, seizure, delirium, confusion, tremor, hallucination, irritability, muscle weakness, and facial nerve paralysis. Fever was the most common non-neurological symptom, followed by cough, headache, gastrointestinal symptoms, headache, lethargy and dizziness. Seizure and respiratory symptoms were less common. All were diagnosed for M.pneumoniae by serology. Cerebrospinal fluid (CSF) M.pneumoniae was undetectable by PCR in the 3 patients. Three patients were clarithromycin-resistant. Leukocytosis, positive C-reactive protein, hyponatremia, CSF pleocytosis and slow wave on electroencephalography frequently occurred. All except 2 were type I MERS. Neuroimaging abnormalities disappeared within 18 days in the majority of patients. All type I patients completely recovered within 19 days. Two type II patients developed neurological sequelae, which recovered 2 and 6 months after onset. CONCLUSIONS: Prognosis of M.pneumoniae-associated MERS is excellent. Type II MERS may increase a risk of neurological sequelae.

Small renal oncocytoma with central cystic degeneration.

A case of a small renal oncocytoma with central cystic degeneration, 15 mm in diameter, is reported. Contrast-enhanced computed tomography showed the tumor contained a central hypoattenuating region and had an irregular, heterogeneously enhanced wall. Magnetic resonance images showed a well-circumscribed lesion and the T(1)-weighted image indicated medium signal intensity, whereas the T(2)-weighted image indicated slight hypointensity. Both T(1)- and T(2)-weighted images showed central hyperintensity. Our preoperative diagnosis was renal cell carcinoma originating in a renal cyst wall or cystic renal cell carcinoma. Nephrectomy was performed because frozen-section examination did not completely rule out malignancy. The final pathological diagnosis of the entire surgical specimen was renal oncocytoma with cystic degeneration. To our knowledge, this is the 14th case of renal oncocytoma with central cystic degeneration reported in the published works. We discuss herein the variant forms of oncocytoma and difficulties with their preoperative diagnosis, especially when the tumor is small.