Prevalence and Intra-Family Phylogenetic Divergence of Burkholderiaceae-Related Endobacteria Associated with Species of Mortierella.

Endofungal bacteria are widespread within the phylum Mucoromycota, and these include Burkholderiaceae-related endobacteria (BRE). However. the prevalence of BRE in Mortierellomycotinan fungi and their phylogenetic divergence remain unclear. Therefore, we examined the prevalence of BRE in diverse species of Mortierella. We surveyed 238 isolates of Mortierella spp. mainly obtained in Japan that were phylogenetically classified into 59 species. BRE were found in 53 isolates consisting of 22 species of Mortierella. Among them, 20 species of Mortierella were newly reported as the fungal hosts of BRE. BRE in a Glomeribacter-illycoavidus Glade in the family Burkholderiaceae were separated phylogenetically into three groups. These groups consisted of a group containing Mycoavidus cysteinexigens, which is known to be associated with M. elongata, and two other newly distinguishable groups. Our results demonstrated that BRE were harbored by many species of Mortierella and those that associated with isolates of Mortierella spp. were more phylogenetically divergent than previously reported

S-1 Plus Cisplatin with Concurrent Radiotherapy for Locally Advanced Non-small Cell Lung Cancer: A Multi-Institutional Phase II Trial (West Japan Thoracic Oncology Group 3706)

Purpose:To evaluate the combination chemotherapy using oral antimetabolite S-1 plus cisplatin (SP) with concurrent thoracic radiotherapy (RT) followed by the consolidation SP for locally advanced non-small cell lung cancer.Patients and Methods:Patients with stage III non-small cell lung cancer, 20 to 74 years of age, and Eastern Cooperative Oncology Group performance status 0 to 1 were eligible. The concurrent phase consisted of full dose S-1 (orally at 40 mg/m2/dose twice daily, on days 1–14) and cisplatin (60 mg/m2 on day 1) repeated every 4 weeks for two cycles with RT delivered beginning on day 1 (60 Gy/30 fractions over 6 weeks). After SP-RT, patients received an additional two cycles of SP as the consolidation phase.Results:Fifty-five patients were registered between November 2006 and December 2007. Of the 50 patients for efficacy analysis, the median age was 64 years; male/female 40/10; Eastern Cooperative Oncology Group performance status 0/1, 21/29; clinical stage IIIA/IIIB 18/32; and adenocarcinoma/others 20/30. There were 42 clinical responses including one complete response with an objective response rate of 84% (95% confidence interval [CI], 71–93%). The 1- and 2-year overall survival rates were 88% (95% CI, 75–94%) and 70% (95% CI, 55–81%), respectively. The median progression-free survival was 20 months. Of the 54 patients for safety analysis, common toxicities in the concurrent phase included grade 3/4 neutropenia (26%), thrombocytopenia (9%), and grade 3 esophagitis (9%) and febrile neutropenia (9%). In one patient, grade 3 pneumonitis was observed in the consolidation phase. There were two treatment-related deaths caused by infection in the concurrent phase.Conclusions:SP-RT showed a promising efficacy against locally advanced NCSLC with acceptable toxicity

Epidemiology of Infectious Hepatitis 2nd Report. Epidemic Observation on the Infectious Hepatitis in Akaiwa District (No. 2)

Comparing the epidemic of infectious hepatitis that took place in Toyoda, Onoda, as well as Kumayama in Akaiwa County, during the period ranging from march 1951 to sept. do., with the previous report on the epidemic of malignant hepatitis submitted by february 1951, following results were obtained: 1. Number of patients, 120; total ever since the first. occurence, 213 cases; For the total populace, rate of occurence, Toyoda-39%, Onoda-3.1%, Kama-mura, 2.4%. 2. As for the type of disease. contrary to the previous occasion in which typical form was predominant, this time saw the predominaney of abortive form, of which the mortality rate proved only 0.83%, in comparison to 13.9% estimated in the former time. 3. As for state of starting estimated by month, as previous occasion, maximum occurrence took place in July and August. 4. As for age, showing similar trend as before, 21-30 occupying most cases, evenly has diffused from 10 to 60. There were actually 7 cases that were above 61, which verifies that contamination in old age is not so seldom. 5. As has been in the previous occasion, as to state of contamination, what may be called village infection occupied the majority of cases; where, a special increase of familiary infection has drawn our attention, amounting to the rate of 38.3%, in comparison to former 20.4%, Which, as the infection spread itself, increases in number. 6. Familiary infection may be explained by propagated epidemic form. Its three cases had been delivered. 7. On taking a bird's'-eye-view over the whole area that was infected, the special phase for this season will come under two heads; area in which new patients have emerged around those affected formerly., and the other, which has been contaminated with a fixed current toward areas not yet. infected. The latter is considered to take shift into the former form after a while. 8. Though rare, sporadic infection could be found in this epidemic too, each of which was a case infections being pressed onward into uncontaminated area, and 6 out of 9 cases have become the source for later infection. If theses poradic infections were considered in detail, these would be clear to have a connection with that of epidemic places and also able to come under propagated epidemic form

RELAY Subgroup Analyses by EGFR Ex19del and Ex21L858R Mutations for Ramucirumab Plus Erlotinib in Metastatic Non–Small Cell Lung Cancer

Purpose: In E GFR-mutated metastatic non-small cell lung cancer (NSCLC), outcomes from EGFR tyrosine kinase inhibitors have differed historically by mutation type present, with lower benefit reported in patients with ex21L858R versus ex19del mutations. We investigated if EGFR-activating mutation subtypes impact treatment outcomes in the phase III RELAY study. Associations between EGFR mutation type and preexisting co-occurring and treatment-emergent genetic alterations were also explored. Patients and Methods: Patients with metastatic NSCLC, an EGFR ex19del or ex21L858R mutation, and no central nervous system metastases were randomized (1:1) to erlotinib (150 mg/day) with either ramucirumab (10 mg/kg; RAM+ERL) or placebo (PBO+ERL), every 2 weeks, until RECIST v1.1-defined progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary and exploratory endpoints included overall response rate (ORR), duration of response (DOR), PFS2, time-to-chemotherapy (TTCT), safety, and next-generation sequencing analyses. Results: Patients with ex19del and ex21L858R mutations had similar clinical characteristics and comutational profiles. One-year PFS rates for ex19del patients were 74% for RAM+ERL versus 54% for PBO+ERL; for ex21L858R rates were 70% (RAM+ERL) versus 47% (PBO+ERL). Similar treatment benefits (ORR, DOR, PFS2, and TTCT) were observed in RAM+ERL-treated patients with ex19del and ex21L858R. Baseline TP53 comutation was associated with superior outcomes for RAM+ERL in both ex19del and ex21L858R subgroups. EGFR T790M mutation rate at progression was similar between treatment arms and by mutation type. Conclusions: RAM+ERL provided significant clinical benefit for both EGFR ex19del and ex21L858R NSCLC, supporting this regimen as suitable for patients with either of these EGFR mutation types

Epidemiology of Infectious Hepatitis 3rd Report. On the Mass Examination Taken for Shakurenzi Hamlet

The mass examination was carried out in Shakurenji, Kama- Village, Akaiwa Connty, Okayama Pref., where great many deathes have been taken place by infectious hepatitis; results were as follows: 1. 127 persons received the examination; it has covered 94.1% of the entire people. 2. Those who have had jaundice previously were enumerated as 5 cases; as it was just the season when infectious hepatitis was in vogue in other parts of the Prefecture, though slight in degree, it was imagined that probably in the past there might have occurred a few sporadic cases. Among those, 3 were taken record of as new victims of disease, 3. In 6 cases, the patients complained of certain pain, each having some sort of liver disturbance more or less. 4. There were 24 cases in which liver enlargement could be detected; its rate, 18.9%, while splenomegaly been discovered in only one case. 5. Two women in pregnancy were recognized, one sickened case, the other inapparent infection case. 6. As for wide-range judgment taken after the examinaton, must-be-treated case, 5, must-be taken-care-of case 5. inapparent infection 60, 70 in total. percentage of contraction, 55.1%, adding 3 cases starting disease as well as 3 deaths; thus, great total, 76 cases; its rate, 57.1%. 7. Percentage of contraction has proved high in thirties and above 50. By sex, females superseded, but as to age, no definite conclusion could be established. 8. In case those patients exposed would be divided by respective family and investigated, it has been revealed thus: (a) with families which have used a well in common with the family in which death case or at least patient was found, Percentage of contraction has proved high and almost in like degree, since many were adviced to receive treatment, or, be taken care of. (b) Families which employed a well in common, were recognized to have proved about the same ratio in infection, containing not a few ought to be treated or taken care of, which suggests us an infection due to a well. (c) Among the group of families, whose relatives died of this disease, master of the house who had presented himasdlf over the funeral diet has been found to have taken infection alone

肝硬変例における呼吸同期肝イメージングおよびフーリエ解析による肝運動性評価の試み

金沢大学大学院医学系研究

Clinical activity of ASP8273 in Asian patients with non‐small‐cell lung cancer with EGFR activating and T790M mutations

Epidermal growth factor receptor (EGFR)‐activating mutations confer sensitivity to tyrosine kinase inhibitor (TKI) treatment for non‐small‐cell lung cancer (NSCLC). ASP8273 is a highly specific, irreversible, once‐daily, oral, EGFR TKI that inhibits both activating and resistance mutations. This ASP8273 dose‐escalation/dose‐expansion study (NCT02192697) was undertaken in two phases. In phase I, Japanese patients (aged ≥20 years) with NSCLC previously treated with ≥1 EGFR TKI received escalating ASP8273 doses (25‐600 mg) to assess safety/tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) by the Bayesian Continual Reassessment Method. In phase II, adult patients with T790M‐positive NSCLC in Japan, Korea, and Taiwan received ASP8273 at RP2D to further assess safety/tolerability and determine antitumor activity, which was evaluated according to Simon's two‐stage design (threshold response = 30%, expected response = 50%, α = 0.05, β = 0.1). Overall, 121 (n = 45 [33W/12M] phase I, n = 76 [48W/28M]) phase 2) patients received ≥1 dose of ASP8273. In phase I, RP2D and MTD were established as 300 and 400 mg, respectively. As 27 of the 63 patients treated with ASP8273 300 mg achieved a clinical response, ASP8273 was determined to have antitumor activity. The overall response rate at week 24 in all patients was 42% (n = 32/76; 95% confidence interval, 30.9‐54.0). Median duration of progression‐free survival was 8.1 months (95% confidence interval, 5.6, upper bound not reached). The most commonly reported treatment‐related adverse event in phase II was diarrhea (57%, n = 43/76). ASP8273 300 mg was generally well tolerated and showed antitumor activity in Asian patients with both EGFR‐activating and T790M mutations