Analysis of nivolumab related interstitial lung disease in patient with non-small-cell lung cancer.

ニボルマブに関連した間質性肺疾患（以下，ILD）の発現については，死亡例が報告され注意喚起がなされている。ILD 等の異常が認められた場合には，ニボルマブを中止し副腎皮質ステロイド剤の投与等の処置を行うこととされているが，十分なデータが得られているとは言えない。平成28年１～12月の間に非小細胞肺癌に対してニボルマブ投与を開始した患者の中でGrade 2及びGrade 3のILD各１名を経験し，メチルプレドニゾロンコハク酸エステルナトリウム１ g/day ×３日間投与後，経口プレドニゾロン投与し漸減することで軽快した。ILD の発現時期については，ニボルマブ２～ 12回目の投与時（中央値８回目）に発現しており定まっていなかった。今回経験したGrade ２以上の症例においては，副腎皮質ステロイドに対する反応性を認めた。The attention is given to Nivolumab induced interstitial lung disease （refered to as ILD）. In some cases, even deaths have been reported. The standard protocol is that once a sign of ILD is seen, stop Nivolumab and switch to corticosteriod, but there is no enough data to back up this protocol. Among the non-small cell lung cancer patients who were given Nivolumab between January 2016 and December 2016, there was one patient who experienced grade 2 ILD and another patient with grade 3 ILD. Both of these patients’ symptoms of ILD were mostly contained after given 1g/day of Methyprednisolone Soduim Succinate for 3 days, then oral prednisolones with gradually decreasing the dosage of it. Regarding the manifestation of ILD, it varied and it was somewhere bewteen second to 12th doses of Nivolumab with the median of 8th doses. This study was able to confirm the effective response to corticosteriod for grade 2 or higher cases of ILD

Second nationwide surveillance of bacterial pathogens in patients with acute uncomplicated cystitis conducted by Japanese Surveillance Committee from 2015 to 2016: antimicrobial susceptibility of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus

The Japanese Surveillance Committee conducted a second nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for acute uncomplicated cystitis (AUC) in premenopausal patients aged 16–40 years old at 31 hospitals throughout Japan from March 2015 to February 2016. In this study, the susceptibility of causative bacteria (Escherichia coli, Klebsiella pneumoniae, Staphylococcus saprophyticus) for various antimicrobial agents was investigated by isolation and culturing of organisms obtained from urine samples. In total, 324 strains were isolated from 361 patients, including E. coli (n = 220, 67.9%), S. saprophyticus (n = 36, 11.1%), and K. pneumoniae (n = 7, 2.2%). The minimum inhibitory concentrations (MICs) of 20 antibacterial agents for these strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) manual. At least 93% of the E. coli isolates showed susceptibility to fluoroquinolones and cephalosporins, whereas 100% of the S. saprophyticus isolates showed susceptibility to fluoroquinolones and aminoglycosides. The proportions of fluoroquinolone-resistant and extended-spectrum β-lactamase (ESBL)-producing E. coli strains were 6.4% (13/220) and 4.1% (9/220), respectively. The antimicrobial susceptibility of K. pneumoniae was retained during the surveillance period, while no multidrug-resistant strains were identified. In summary, antimicrobial susceptibility results of our second nationwide surveillance did not differ significantly from those of the first surveillance. Especially the numbers of fluoroquinolone-resistant and ESBL-producing E. coli strains were not increased in premenopausal patients with AUC in Japan

The Valproate Serum Level in Maintenance Therapy for Bipolar Disorder in Japan

The appropriate therapeutic serum valproate level in maintenance therapy for bipolar disorder is not well known. We studied the serum valproate levels in seventeen bipolar I and twenty-four bipolar II disorder outpatients who had been treated with stable doses of valproate successfully for at least 12 months as prophylactic therapy. The trough serum valproate levels were 52.2 ± 20.4 μg/ml in bipolar I, and 41.0 ± 18.3 μg/ml in bipolar II disorder patients, respectively. A greater trend towards a higher trough level (p=0.07) was indicated in the bipolar I disorder group. We speculate that these valproate levels may be an approximation to the appropriate valproate levels in maintenance therapy and that there may be a correlation between the level of valproate required for stabilization and the subtype of the bipolar disorder. However, when interpreting these findings, certain limitations to this study?need to be taken into account as follows. The sample size was small. We could not look at a group on valproate that had relapsed and a group that had dropped out of maintenance therapy. Further studies are needed