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Crizotinib shows antitumor activity against C-ros oncogene 1-rearranged non-small-cell lung cancer (NSCLC). While corrected QT interval (QTc) prolongation and bradycardia are known cardiac adverse effects, little is known about crizotinib-related heart failure. Our patient with C-ros oncogene 1-rearranged NSCLC on a reduced dose of crizotinib (200 mg twice daily) after initially experiencing bradycardia and QTc prolongation developed crizotinib-induced heart failure. With further dose reduction (250 mg once daily), there was no recurrence of any cardiac adverse effects, and the patient achieved a long-term response. Although crizotinib can cause heart failure, continuation of crizotinib at a low dose may be an effective treatment option.

Mounting evidence suggests that preoperative nutritional status can predict postoperative outcomes in patients with non-small cell lung cancer. However, a consensus on the optimal evaluation tool among the various nutritional assessment methods has not been reached. This study aimed at validating the predictive value of 3 nutritional scoring systems for clinical outcomes in patients with completely resected non-small cell lung cancer.We retrospectively reviewed the preoperative data of 475 consecutive patients with completely resected non-small cell lung cancer to assess the following 3 albumin-based nutritional methods: prognostic nutritional index, controlling nutritional status score, and geriatric nutritional risk index.Receiver operating characteristic curves of the prognostic nutritional index, controlling nutritional status score, and geriatric nutritional risk index identified the optimal cutoff values for predicting the postoperative complications as 47, 2, and 101, respectively. Stratification of patients using these cutoff values indicated a higher postoperative complication rate in the malnutrition group than in the group with proper nutrition (P .05 for all nutritional assessment methods). Additionally, patients with malnutrition exhibited significantly lower 5-year overall and recurrence-free survivals, regardless of the assessment method (P .05 for all 3 nutritional assessment methods). Multivariate analyses showed that all 3 nutritional parameters were independent prognostic factors for overall survival after lung resection.The 3 nutritional assessment methods we used were found to have high predictive values for postoperative complications and survival. Preoperative nutritional conditioning may improve the postoperative outcomes in patients with resectable non-small cell lung cancer.

Satoshi Iraha,1–5Yasuhiko Hirami,1,2 Sachiko Ota,1,2 Genshiro A Sunagawa,3 Michiko Mandai,1–3 Hidenobu Tanihara,5 Masayo Takahashi,1–4 Yasuo Kurimoto1,2 1Department of Ophthalmology, Institute of Biomedical Research andInnovation Hospital, 2Department of Ophthalmology, Kobe City Medical Center General Hospital, 3Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, Kobe, 4Application Biology and Regenerative Medicine, Graduate School of Medicine, KyotoUniversity, Kyoto, 5Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan Purpose: The purpose of this study was to examine the efficacy and safety of valproic acid (VPA) use in patients with retinitis pigmentosa (RP).Patients and methods: This was a prospective, interventional, noncomparative case study. In total, 29 eyes from 29 patients with RP whose best-corrected visual acuities (BCVAs) in logarithm of the minimum angle of resolution (logMAR) ranged from 1.0 to 0.16 with visual fields (VFs) of ≤10° (measured using Goldmann perimeter with I4) were recruited. The patients received oral supplementation with 400mg of VPA daily for 6months and were followed for an additional 6months. BCVAs, VFs (measured with the Humphrey field analyzer central 10-2 program), and subjective questionnaires were examined before, during, and after the cessation of VPA supplementation.Results: The changes in BCVA and VF showed statistically significant differences during the internal use of VPA, compared with after cessation (P=0.001). With VPA intake, BCVA in logMAR significantly improved from baseline to 6months (P=0.006). The mean deviation value of the VF significantly improved from baseline to 1month (P=0.001), 3months (P=0.004), and 6months (P=0.004). These efficacies, however, were reversed to the baseline levels after the cessation of VPA intake. There were no significant relations between the mean blood VPA concentrations of each patient and the changes in BCVA and VF. During the internal use of VPA, 15 of 29 patients answered “easier to see”, whereas blurred vision was registered in 21 of 29 patients on cessation. No systemic drug-related adverse events were observed.Conclusion: While in use, oral intake of VPA indicated a short-term benefit to patients with RP. It is necessary to examine the effect of a longer VPA supplementation in a controlled study design. Keywords: retinitis pigmentosa, valproic acid, clinical trial, retina

重篤な心不全のため血液透析 (HD) の施行は困難と判断しCAPDを施行したところ, 良好に尿毒症をコントロールし得た慢性関節リウマチ (RA) に続発したアミロイドーシスの腎不全患者を2例経験したので報告する.症例1は75歳, 女性. 昭和56年にRAと診断され, 昭和58年に蛋白尿が出現した. 昭和62年より腎機能が低下し, 平成元年7月より腎機能が増悪した. 心不全が高度なためHDの施行は困難と判断し, 8月にCAPDへ導入した. 以後, 良好に尿毒症や浮腫, 心不全症状はコントロールし得た. 平成2年3月に胃生検でアミロイドの沈着を認めたが, その頃より心不全が再び増悪し血圧が低下した. 5月1日には徐脈傾向となり7日に死亡した. 剖検の結果, AA型のアミロイドが心臓, 腎臓, 甲状腺, 膵臓, 消化管, 全身の中小動脈に高度に認められた.症例2は72歳, 女性. 昭和57年にRAと診断され, 昭和63年に蛋白尿, 腎機能低下を認めた. 平成元年9月に小唾液腺生検と甲状腺生検でAA型のアミロイドの沈着を認め, 続発性アミロイドーシスと診断した. DMSO (dimethylsulfoxide) の投与によりやや改善傾向を認めたが, 本人が服用を拒否した平成2年2月末より急激に腎機能が悪化した. 重篤な心不全を伴ったため, HDの施行は困難と判断し3月にCAPDへ導入したところ尿毒症や心不全は良好にコントロールし得た. しかし7月より再び心不全が悪化し, 8月より血圧の低下を認め, 9月12日に死亡した.2例共に重篤な心不全が存在したが, CAPDにより良好に尿毒症をコントロールし得た. しかし心不全の悪化のため, 導入後それぞれ8か月と6か月で死亡した. その心不全の主因として心アミロイドーシスの悪化が考えられた. CAPDへ導入した後も, 心アミロイドーシスの進展を予防するための治療を継続して行う必要があると考えられた.

Porcine TCRbeta-chain cDNA clones were isolated from thymic and peripheral blood lymphocytes of piglets. Using these nucleotide sequences, a genomic 18kbp sequence stretch covering Dbeta1 to Cbeta2 gene segments was identified, which revealed that the porcine TCRbeta-chain locus consists of two sets of Dbeta-Jbeta-Cbeta gene groups with each set having a Dbeta gene segment, seven Jbeta gene segments and a down stream Cbeta gene segment composed of four exons. This structure is consistent with other known mammalian TCRbeta-chain loci. With this genomic information, TCRbeta-chain clones from cDNA libraries were analyzed. Sixteen Vbeta gene segments were obtained accompanied by either Dbeta1 or Dbeta2 and by one of the nine Jbeta gene segments. Five different Cbeta cDNA sequences were obtained including four types of Cbeta1 sequences and one type of Cbeta2 sequence. The differences among the Cbeta1 sequences are either allelic polymorphisms or two splice variants, one being a product of exon1 splicing to exon3 (exon2 skipping), and another being an alternative splicing using a splice acceptor site newly discovered inside Cbeta1 exon4. The latter splice acceptor site was also found in human, mouse and horse all giving short cytoplasmic domain with Phe at their C-terminal ends. Other splicing products included trans-splicing of Jbeta2 to Cbeta1, non-functional splicing of two Jbeta gene segments in tandem and a part of Jbeta2.7-Cbeta2 intron to Cbeta2 exon1. Numerous examples of splice variants may suggest the involvement of splicing in generating TCRbeta-chain functional diversity.

Background The presence of metabolic syndrome has been shown to be predictors of cardiovascular morbidity and mortality in patients with type 2 diabetes. In a cross-sectional clinical study, we investigated the association of metabolic syndrome with asymptomatic lacunar strokes and cardiovascular disease (CVD) and we compared its significance with urinary protein markers. Methods We studied Japanese type 2 diabetes patients ( n = 233, men = 124, women = 109). The diagnosis of metabolic syndrome was made according to WHO and International Diabetes Federation (IDF) criteria. Cardiovascular events were recorded and asymptomatic lacunar lesions were evaluated with magnetic resonance imaging (MRI). We also measured urinary levels of albumin, type IV collagen, β2-microglobulin (β2MG), N -acetyl-β- d -glucosaminidase (NAG) and lipocalin-type prostaglandin D synthase (PGDS). Results The prevalence of metabolic syndrome is 31.3% (IDF) and 52% (WHO) in 233 patients and microalbuminuria was present in 62 subjects (26.6%). Metabolic syndrome (WHO) significantly associated with asymptomatic lacunar lesions ( p = 0.035, OR = 2.854, CI 1.075–7.579), while metabolic syndrome (IDF) or urinary markers failed to associate with presence of asymptomatic lacunar lesions. The presence of metabolic syndrome or microalbuminuria did not show significant association with CVD; however, the elevation of β2MG, NAG and PGDS showed significant association with CVD. By a logistic regression analysis using urinary proteins as independent variables, the presence of higher PGDS excretion independently associated with history of CVD ( p = 0.025, OR = 3.847, CI 1.180–12.545). Conclusions In type 2 diabetes patients, the elevation of urinary PGDS secretion closely associated with cardiovascular events and may be a supplemental or additional marker to the criteria of metabolic syndrome.