Long‐term follow up of nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma

The immune checkpoint inhibitor nivolumab inhibits the programmed death 1 receptor and suppresses the immune resistance of cancer cells. This is a long-term follow up of a single-arm, open-label, multicenter, phase II study of nivolumab in untreated Japanese patients with stage III/IV or recurrent melanoma. In addition, a post-hoc subgroup analysis stratified by melanoma types was performed. Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), best overall response, the disease control rate and change in tumor diameter. Safety was assessed by recording treatment-related adverse events (TRAE), including select immune-related adverse events. Of the 24 patients initially included in the primary phase II study, 10 survived for over 3 years (41.7%). The ORR was 34.8% (90% confidence interval [CI]: 20.8, 51.9) for all patients. When analyzing by melanoma type, the ORR was 66.7% (90% CI: 34.7, 88.3) for superficial spreading, 33.3% (90% CI: 11.7, 65.3) for mucosal, and 28.6% (90% CI: 10.0, 59.1) for acral lentiginous tumors. The median OS was 32.9 months, the 3-year OS rate was 43.5%, and the 3-year PFS rate was 17.2%. A long-term response was observed in all the tumor types. The most common TRAE included skin toxicity (45.8%) and endocrine disorders (29.2%). This study demonstrated the long-term efficacy and tolerability of nivolumab in patients with advanced or recurrent melanoma, irrespective of melanoma type

Cytokine biomarkers to predict antitumor responses to nivolumab suggested in a phase 2 study for advanced melanoma

Promising antitumor activities of nivolumab, a fully humanized IgG4 inhibitor antibody against the programmed death-1 protein, were suggested in previous phase 1 studies. The present phase 2, single-arm study (JAPIC-CTI #111681) evaluated the antitumor activities of nivolumab and explored its predictive correlates in advanced melanoma patients at 11 sites in Japan. Intravenous nivolumab 2 mg/kg was given repeatedly at 3-week intervals to 35 of 37 patients enrolled from December 2011 to May 2012 until they experienced unacceptable toxicity, disease progression, or complete response. Primary endpoint was objective response rate. Serum levels of immune modulators were assessed at multiple time points. As of 21 October 2014, median response duration, median progression-free survival, and median overall survival were 463 days, 169 days, and 18.0 months, respectively. The overall response rate and 1- and 2-year survival rates were 28.6%, 54.3%, and 42.9%, respectively. Thirteen patients remained alive at the end of the observation period and no deaths were drug related. Grade 3–4 drug-related adverse events were observed in 31.4% of patients. Pretreatment serum interferon-γ, and interleukin-6 and -10 levels were significantly higher in the patients with objective tumor responses than in those with tumor progression. In conclusion, giving repeated i.v. nivolumab had potent and durable antitumor effects and a manageable safety profile in advanced melanoma patients, strongly suggesting the usefulness of nivolumab for advanced melanoma and the usefulness of pretreatment serum cytokine profiles as correlates for predicting treatment efficacy

Reliability and validity of the patient disability-oriented diagnostic nomenclature system for prosthetic dentistry

Purpose: The Japan Prosthodontic Society (JPS) has proposed a new diagnostic nomenclature system (DNS), based on pathogenesis and etiology, to facilitate and improve prosthodontic treatment. This systemspecifies patient disability and the causative factor (i.e. ‘‘B (disability) caused by A (causative factor)’’). The purpose of this study was to examine the reliability and validity of this DNS. Study selection: The JPS Clinical Guideline Committee assessed mock patient charts and formulated disease names using the new DNS. Fifty validators, comprising prosthodontic specialists and dental residents, made diagnoses using the same patient charts. Reliability was evaluated as the consistency of the disease names among the validators, and validity was evaluated using the concordance rate of the disease names with the reference disease names. Results: Krippendorff’s α was 0.378 among all validators, 0.370 among prosthodontic specialists, and 0.401 among dental hospital residents. Krippendorff’s α for 10 validators (3 specialists and 7 residents) with higher concordance rates was 0.524. Two validators (1 specialist and 1 resident) with the highest concordance rates had a Krippendorff’s α of 0.648. Common disease names had higher concordance rates, while uncommon disease names showed lower concordance rates. These rates did not show correlation with clinical experience of the validator or time taken to devise the disease name. Conclusions: High reliability was not found among all validators; however, validators with higher concordance rates showed better reliability. Furthermore, common disease names had higher concordance rates. These findings indicate that the new DNS for prosthodontic dentistry exhibits clinically acceptable reliability and validity

Association between iron status markers and kidney outcome in patients with chronic kidney disease

Abstract Several studies conducted in patients with various stages of chronic kidney disease (CKD) have investigated the association of iron status markers, such as transferrin saturation (TSAT) and serum ferritin, with kidney outcomes. However, the associations were inconsistent and remain strongly debated. Therefore, we aimed to investigate whether TSAT and serum ferritin levels were associated with kidney outcome in such a population. In this study, 890 patients who were admitted for the evaluation of and education for CKD were prospectively followed. Primary kidney outcome was a composite of doubling of serum creatinine, end-stage kidney disease, or death due to kidney failure. Participants were divided into quartiles (Q1–Q4) according to TSAT or serum ferritin levels. During a median follow-up period of 2.8 years, kidney events occurred in 358 patients. In the multivariable Cox analyses, compared with Q3 of TSAT, the hazard ratios (95% confidence intervals) for Q1, Q2, and Q4 were 1.20 (0.87, 1.66), 1.38 (1.01, 1.87), and 1.14 (0.82, 1.59), respectively. Compared with Q2 of serum ferritin, lower and higher quartiles had a significantly increased risk for kidney outcome; hazard ratios (95% confidence intervals) for Q1, Q3, and Q4 were 1.64 (1.18, 2.27), 1.71 (1.24, 2.37), and 1.52 (1.10, 2.10), respectively. A Fine-Gray model with death before kidney events as a competing risk showed results similar to the above. In CKD, lower and higher ferritin levels were independent risk factors for kidney disease progression

Outcomes of carbon ion radiotherapy compared with segmentectomy for ground glass opacity-dominant early-stage lung cancer

Abstract Purpose This study aimed to compare the outcomes of patients with ground-grass opacity (GGO)-dominant non-small cell lung cancer (NSCLC) who were treated with carbon ion radiotherapy (CIRT) versus segmentectomy. Methods A retrospective review of medical records was conducted. The study included 123 cases of clinical stage 0/IA peripheral NSCLC treated with single-fraction CIRT from 2003 to 2012, 14 of which were determined to be GGO-dominant and were assigned to CIRT group. As a control, 48 consecutive patients who underwent segmentectomy for peripheral GGO-dominant clinical stage IA NSCLC were assigned to segmentectomy group. Results The patients in CIRT group, compared with segmentectomy group, were significantly older (75 ± 7.2 vs. 65 ± 8.2 years, P = 0.000660), more likely to be male (13/14 vs. 22/48, P = 0.00179), and had a lower forced vital capacity (91 ± 19% vs. 110 ± 13%, P = 0.0173). There was a significant difference in the 5-years overall survival rate (86% vs. 96%, P = 0.000860), but not in the 5-years disease-specific survival rate (93% vs. 98%, P = 0.368). Discussion Compared with segmentectomy, CIRT may be an alternative option for patients with early GGO-dominant NSCLC who are poor candidates for, or who refuse, surgery

A study of latent mastitis of cattle : I. Results of detection of mastitis by the modified California mastitis test (CMT)(Department of Animal Science)

沖縄県における乳牛の潜在性乳房炎の発生状況を知る目的で, 本島南部地区(1980年, 同一地域を夏季と秋季に, 延べ201頭, 780試料)および北部地区(1981年, 2地域の計148頭, 575試料)の搾乳中のウシから分房ごとに採取した試料について, 調査を行なった。CMTで凝集程度が十以上を陽性とすると, 分房別では南部地区29.7%, 北部地区28.3%, 頭数別ではそれぞれ61.2%と63.5%であり, 両地区に大きな違いはなかった。また, 南部地区における夏季と秋季の陽性率は, 分房別および頭数別ともにほぼ同じであった。しかし, 北部地区の陽性率では地域によって大きく異なり, A地域は分房別で33.8%, 頭数別で72.8%であったのに対し, B地域はそれぞれ16.0%と42.2%であった。なお, これらの陽性率は, 南部地区および北部地区ともに酪農家によって大きく異なった。陽性牛では, 1分房または2分房陽性のものが多く, これら両者で78.9∿82.9%を占め, 4分房とも陽性のウシは少なかった。CMTによる凝集程度とブリード法による細胞数との関係では, 凝集程度が強いほど細胞数は増加し, 凝集+で平均細胞数は50万/mlを越えた。しかし, この+では, 過半数の試料が細胞数49万/ml以下であった。CMTと細菌数またはpHとの関係では, 凝集程度が強いほど細菌数の多い試料が多く, また凝集程度が強い試料ではpH6.7以上のものが多かった。For the purporse of knowing the conditions of developing latent mastitis of dairy cattle in Okinawa Prefecture, the authors made an investigation of samples obtained from each quarter of the udder of dairy cattle in the Southern district (780 samples, a total of 201 cows in the summer and autumn seasons in the same district, 1980) and the Northern district (575 samples, 148 cows, a total of two areas, 1981). Assuming that agglutination above plus one by the modified method of CMT is defined as a positive, the Southern district showed 29.7% and the Northern district 28.3% classified by the quarter; the corresponding figures in terms of the number of cattle was 61.2% and 63.5%, respectively. Thus there was seen no great difference between the two districts. The positive rate in the summer and autumn seasons in the Southern district was almost the same for both the quarter and the number of cattle. However, the positive rate in the Northern district varied greatly with the area. A area had 33.8% by quarter and 72.8% by the number of cattle, whereas B area had 16.0% and 42.2%, respectively. Dairy cattle that were positive were mostly positive in one or two quarters, occupying 78.9%-82.9%. Dairy cattle showing positive in all of the quarters were very few. The relationship between agglutination degree by the modified CMT and the number of cells according to the Breed method was as follows : The greater the degree of the agglutination, the greater the number of cells, and the average number of cells with plus one agglutination exceeded 500,000/ml of cell number. However, with this plus one agglutination, the majoirity of the samples had below 490,000/ml of cell number