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Background:Unlike the situation in the general population, most studies of patients receiving hemodialysis have reported lower uric acid (UA) as associated with higher mortality. However, the relationship between UA level and mortality remains unclear among patients receiving peritoneal dialysis (PD).Methods:We collected baseline data for 4742 prevalent PD patients (age, 63 ± 14 years; male, 61.5%; diabetes, 29.1%; median dialysis duration, 28 months) from a nationwide dialysis registry in Japan at the end of 2012. One-year all-cause and cardiovascular (CV) mortality and mortality caused by infectious disease were assessed using Cox regression analysis and competing-risks regression analysis, respectively. We used multiple imputation to deal with missing covariate data.Results:Within 1 year, 379 patients (8.0%) died, including 129 patients (2.7%) from CV causes and 95 patients (2.0%) from infectious disease. In multivariate analysis, serum UA, treated as a continuous variable, was not associated with any outcome. Conversely, both lower (Conclusions:A U-shaped relationship appears to exist between UA levels and all-cause mortality among Japanese PD patients. Additionally, lower BMI significantly enhanced the effect of UA levels on mortality.

Background and Aims Previous studies revealed the association between iron deficiency and thromboembolic events, whereas the association between high serum ferritin and poor prognosis of cerebral haemorrhage was reported in the general population. Since few reports have revealed the relationship between iron parameters and cardiovascular events in hemodialysis (HD) patients so far, our purpose was to examine whether iron parameters predict cardiovascular events in HD patients based on the nation-wide database of patients undergoing dialysis in Japan. Method We enrolled 126,560 patients aged between 20 and 100 who had been on maintenance HD more than 1 year and three times weekly at the end of 2012. We divided baseline transferrin saturation (TSAT) levels into 3 categories (T1: 25%) and serum ferritin levels into quartile (Q1: 158 ng/mL). The study outcomes were new onset of myocardial infarction (MI), cerebral infarction (CIF), and cerebral haemorrhage (CHM) and death due to these three diseases between 2012 and 2013. We performed multivariate logistic regression for the incident events and also employed Cox proportional hazards analyses for death. Multiple imputation method with 5 data sets was performed for missing values. Results During a 1-year follow-up, a total of 2,087 MI (373 deaths), 2,930 CIF (283 deaths), and 1,371 (359 deaths) CHM occurred. After adjustment for demographic and clinical factors, odd ratios (ORs) for MI and CIF were significantly higher among patients with T1 of TSAT than those with T3 (OR; 1.19 (95% confidence interval (CI), 1.07-1.33), 1.16 (95% CI, 1.06-1.27, respectively), and serum ferritin levels were not associated with those outcomes. On the other hand, TSAT was not associated with CHM, however, stepwise increase of OR with the increase of ferritin quartile was observed; patients with Q4 of ferritin had the highest risk for CHM (OR; 1.32 (95% CI, 1.12-1.57) as compared to Q1). In the multivariable Cox regression models, the hazard ratios (HRs) for death due to MI and CIF of the patients with T1 of TSAT were 1.28 (95% CI, 1.00-1.65) and 1.40 (95% CI, 1.06-1.86) as compared to T3, respectively. HR for death due to CHM in patients with Q1-Q4 of ferritin was 1.00 (Reference), 1.59 (95% CI, 1.12-2.25), 1.90 (95% CI, 1.35-2.67), 1.61 (95% CI, 1.13-2.29), respectively (Figure). Furthermore, high dose of erythropoietin stimulating agents was a risk factor of all three cardiovascular events and mortality. Conclusion Low TSAT levels predicted MI and CIF and high serum ferritin levels predicted CHM in HD patients. These results suggest that functional iron deficiency could affect thromboembolic events, while increase in storage iron could affect microvascular fragility.

Total body irradiation using intensity-modulated radiation therapy total body irradiation (IMRT-TBI) by helical tomotherapy in allogeneic hematopoietic stem cell transplantation (allo-HSCT) allows for precise evaluation and adjustment of radiation dosage. We conducted a single-center pilot study to evaluate the safety of IMRT-TBI for allo-HSCT recipients. Patients with hematological malignancies in remission who were scheduled for allo-HSCT with TBI-based myeloablative conditioning were eligible. The primary endpoint was the incidence of adverse events (AEs). Secondary endpoints were engraftment rate, overall survival, relapse rate, non-relapse mortality, and the incidence of acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively). Between July 2018 and November 2018, ten patients were recruited with a median observation duration of 571 days after allo-HSCT (range, 496–614). D80% for planning target volume (PTV) in all patients was 12.01 Gy. Average D80% values for lungs, kidneys and lenses (right/left) were 7.50, 9.03 and 4.41/4.03 Gy, respectively. Any early AEs (within 100 days of allo-HSCT) were reported in all patients. Eight patients experienced oral mucositis and gastrointestinal symptoms. One patient experienced Bearman criteria grade 3 regimen-related toxicity (kidney and liver). All cases achieved neutrophil engraftment. There was no grade III–IV aGVHD or late AE. One patient died of sinusoidal obstruction syndrome 67 days after allo-HSCT. The remaining nine patients were alive and disease-free at final follow-up. Thus, IMRT-TBI was well tolerated in terms of early AEs in adult patients who underwent allo-HSCT; this warrants further study with longer observation times to monitor late AEs and efficacy.

IntroductionDifferences in mortality and cause-specific mortality rates according to glycated albumin (GA) and hemoglobin A1c (HbA1c) levels among dialysis patients with diabetes based on hypoglycemic agent use and malnutrition status remain unclear. Here, we examine these associations using a nationwide cohort.Research design and methodsWe examined 40 417 dialysis patients with diabetes who met our inclusion criteria (female, 30.8%; mean age, 67.3±11.2 years; mean dialysis duration, 5.4±4.6 years). The Global Leadership Initiative on Malnutrition criteria were used to assess malnutrition. Adjusted HRs and 95% confidence limits were calculated for 3-year mortality after adjustment for 18 potential confounders. HRs and subdistribution HRs were used to explore cause-specific mortality.ResultsWe found a linear association between 3-year mortality and GA levels only in patients with GA ≥18% and not in patients with low GA levels, with a U-shaped association between HbA1c levels and the lowest morality at an HbA1c 6.0%–6.3%. This association differed based on patient conditions and hypoglycemic agent use. If patients using hypoglycemic agents were malnourished, mortality was increased with GA ≥24% and HbA1c ≥8%. In addition, patients with GA ≥22% and HbA1c ≥7.6% had significantly higher infectious or cardiovascular mortality rates. On the other hand, an inverse association was found between GA or HbA1c levels and cancer mortality. Patients with GA ≤15.8% had a higher risk of cancer mortality, especially those not using hypoglycemic agents (HR 1.63 (1.00–2.66)).ConclusionsTarget GA and HbA1c levels in dialysis patients may differ according to hypoglycemic agent use, nutritional status, and the presence of cancer. The levels may be higher in malnourished patients than in other patients, and a very low GA level in dialysis patients not taking hypoglycemic agents may be associated with a risk of cancer.Trial registration numberUMIN000018641.

Fracture dialysis patients have a higher risk of 1-year mortality compared with non-fracture dialysis patients. However, it is unclear whether excess mortality persists for more than a year. We conducted a nationwide cohort study in 162,360 hemodialysis patients in Japan. Study outcomes were 5-year all-cause mortality and cause-specific mortality. Cox proportional hazards regression was used to examine the association between hip fracture and mortality in two cohorts: the full cohort, which included potential confounders as covariates in multivariable-adjusted regression models, and the propensity score-matched cohort. Crude mortality rates for fracture patients were double those of non-fracture patients and persisted during the 5-year period. The association between hip fracture and mortality was significant even after adjusting for premorbid conditions (hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.13–1.32). Similar findings were observed in the propensity score-matched cohort of 2410 patients (HR 1.20, 95% CI 1.05–1.36). While cause-specific mortality rates for all categories, with the exception of sudden deaths, were higher for fracture patients relative to non-fracture patients in the full unmatched cohort, only the mortality rate for heart disease was significantly higher for fracture patients relative to non-fracture patients in the propensity score-matched cohort. Excess mortality persisted for many years after hip fracture in hemodialysis patients, and was still present after adjusting for several premorbid conditions and propensity score matching.

A fast interrogation method using a sinusoidal modulated laser diode for a fiber Fabry–Perot interferometric sensor consisting of Bragg gratings (FBG–FPI) is proposed.. The FBG–FPI has sharp transmittance peaks in the reflection band of the FBGs. Wavelength sweep produced by current modulation of a laser diode can be used to detect the peak position. This enables high-resolution strain or temperature measurement. To precisely control the current, the current modulation is realized using a laser diode controller (LDC) with external modulation function. In the modulation by a sawtooth wave, the possible speed of wavelength sweeping is limited to 100 kHz or less due to the bandwidth limitation of an LDC and thermal effect in a laser diodeUsing a sinusoidal wave as a modulation waveform enables wavelength sweeping at speeds exceeding 100 kHz. The modulation characteristics of the laser wavelength is evaluated experimentally and the operating wavelength is monitored using an asymmetric Mach–Zehnder interferometer. The resolution of 0.2 fm/ $$\sqrt{\mathrm{Hz}}$$ and measurement time of 1 $$\upmu$$ s were experimentally demonstrated in the present sensor.

Background For glycemic control in diabetic patients on dialysis it was unclear what level of glycated albumin (GA) was associated with the lowest mortality and GA's utility. Accordingly, we examined the difference in association between GA and hemoglobin A1c (HbA1c) with 1-year mortality in a cohort of the Japanese Society for Dialysis Therapy. Methods We examined 84 282 patients with prevalent diabetes who were on maintenance hemodialysis (HD) (female 30.3%; mean age 67.3 ± 11.2 years; mean dialysis vintage 6.4 ± 4.5 years). Of them, 22 441 had both GA and HbA1c. We followed these for a year, 2013-14, using Cox regression to calculate adjusted hazard ratios (HRs) and 95% confidence limits for 1-year mortality after adjusting for potential confounders such as baseline age, sex, smoking and diabetes type. Results One-year mortality was lowest in diabetic HD patients who had GA levels of 15.6-18.2% and HbA1c levels of 5.8-6.3%. The associations were linear or J-shaped for GA and U-shaped for HbA1c. Adjusted HRs were significantly higher in patients with GA

Fast and high-resolution simultaneous measurement of temperature and strain is experimentally demonstrated. A Fabry–Perot interferometer fabricated in a polarization-maintaining fiber has sharp transmission peaks, which are divided into two sets corresponding to the polarization of the transmitted light. The sharp transmission peaks shift in response to changes in temperature and strain, and because the dependence coefficients are different for each set, temperature and strain can be simultaneously measured with high resolution. To read the position of a sharp transmission peak, wavelength sweeping with narrowband light is necessary. By using injection current modulation in a laser diode, high-speed wavelength sweeping and short measuring time are realized. We performed simultaneous measurements with a measurement time of 20 $\mu$ s; measurement resolution of 0.1 $^\circ$ C and 0.8 $\mu \epsilon$ for temperature and strain, respectively; and noise spectral density of 30 n $\epsilon /\sqrt{\rm Hz}$ . We further experimentally demonstrated that vibration with an amplitude of 20 $\mu \epsilon$ and a frequency of 1 Hz and heating at a rate of 0.7 $^\circ$ C $/$ s can be simultaneously measured.

著者人数: 35名, 形態: カラー図版あり, Number of authors: 35, Physical characteristics: Original contains color illustrations, Accepted: 2018-01-22, 資料番号: PA1810022000

Background Contrary to observations of decreasing rates in Western nations for the past 2 decades, age-adjusted rates of hip fracture in the general population in Japan have continually increased. This study aimed to analyze recent changes in trends of hip fracture incidence among Japanese dialysis patients between 2008 and 2013. Study Design, Setting, & Participants Using data from the Japanese Society for Dialysis Therapy Renal Data Registry database from 2007 to 2013, we created a point-prevalent study cohort for each study year. Prevalent dialysis cohorts included patients 20 years or older without a history of hip fracture who were receiving maintenance dialysis in Japan on December 31 of each year. Factors Age, sex, and calendar year. Outcomes Hip fracture incidence rates. Measurements Unadjusted hip fracture rates were estimated using number of events per 1,000 patient-years in each year and then standardized for age to the 2013 dialysis population. Average annual percentage of change in rates and corresponding 95% CI were computed for trend by joinpoint regression analysis. Results During the study period, 6,615 and 4,963 hip fractures were recorded among female and male dialysis patients, respectively. Age-standardized hip fracture rates decreased steadily from 2008 (21.1/1,000 patient-years) to 2013 (17.7/1,000 patient-years) among women, but remained constant from 2008 (8.6/1,000 patient-years) through 2013 (8.2/1,000 patient-years) among men. Decreases in the joinpoint trend for hip fracture were significant among female (−3.6% [95% CI, −6.9 to −0.2] per year), but not among male, dialysis patients (−1.4% [95% CI, −5.7 to 3.0] per year) from 2008 through 2013. Limitations Only the first hip fracture event was considered in calculations of fracture rates. Conclusions In contrast to the increasing incidence of hip fracture in the general Japanese population, we found that the incidence of hip fracture in Japanese dialysis patients between 2008 and 2013 decreased among women, but did not change in men.

Background Recently, thoracoscopic resection of pulmonary sequestration has become more common, since resection of an aberrant artery using an end-stapler is a safe maneuver in many cases. However, injury of the vessels can lead to major hemorrhage. We reported our surgical experience based on thoracoscopic surgery, with five cases of interlobar pulmonary sequestration, focusing on precautions for aberrant arterial vessels. Object and methods We performed pulmonary resections for five patients with interlobar pulmonary sequestration in a lower lobe (left, n = 4; right, n = 1) between April 2004 and May 2020. All aberrant vessels were derived from the lower thoracic artery. Two patients had a single aberrant artery and three had multiple. In four patients, these vessels were detected before surgery, and pulmonary sequestration was diagnosed in four. In one elderly patient, the aberrant vessel was overlooked, and lung cancer was suspected before surgery. Angiography or multidetector-row computed tomography was subsequently performed in four cases. The surgical plan was determined according to the location and size of the pulmonary lesion and three-dimensional images of aberrant vessels. Result In all patients, approaches were made thoracoscopically. Hemorrhage from an anomalous vessel was encountered in one case. Pulmonary resections included two lobectomies and three limited resections. Angioplasty for the root of anomalous branches was performed following pulmonary resections under converted minimal lateral thoracotomy in two cases. Conclusion Preoperative assessment of the anatomical variations in abnormal vessels is essential to achieve safe surgical procedures. According to the situation of the aberrant vessels, selecting surgical procedures with consideration of potential subsequent complications arising over a long period of time is important.

Introduction Myelodysplastic syndromes (MDS), a heterogeneous group of acquired clonal hematopoietic stem cell disorders, is characterized by peripheral cytopenia and has a high tendency to progress to acute myeloid leukemia (AML). Serum ferritin (SF) level is a well-known indicator of iron stores and inflammation. Elevated SF levels is common in patients with MDS and appear to be largely related to regular red blood cell (RBC) transfusions. However, some patients with MDS showed high SF levels at the time of diagnosis, even before receiving RBC transfusions, although the exact mechanisms is unclear. The impact of SF elevation without RBC transfusion has not been well characterized. In this study, we assessed cytogenetic, molecular, and clinical characteristics of patients with MDS and SF elevation. Methods Patients with newly diagnosed MDS who visited our hospital between Jan 2011 and Jan 2020 were included in this study. Patients were defined as high-SF-MDS when SF values were >350 ng/mL (patients with Results Among the 112 patients with MDS, SF value were available for 87 patients. This study analyzed 28 women and 59 men with a median age of 69 years (range: 28-87 years). The median follow-up period was 540 days (range: 3-3618 days). A total of 17 patients died during the observational period (until Apr 2021). Patients were diagnosed with MDS with single lineage dysplasia (MDS-SLD, n = 9), MDS with multilineage dysplasia (MDS-MLD, n = 26), MDS with ring sideroblasts with SLD (MDS-RS-SLD, n = 5), MDS-RS-MLD (n = 6), MDS with excess blasts 1 (MDS-EB1, n = 25), MDS-EB2 (n = 13), MDS with isolated del(5q) (n=1), and MDS, unclassifiable (MDS-U, n = 2). The median SF value was 263 ng/mL (range: 3-1,245 ng/mL); 31 patients were classified as high-SF-MDS and 56 were classified as low-SF-MDS. The Proportion of MDS subtypes differed significantly between the groups (P=0.004, Table1). Compared to low-SF-MDS, MDS-EB1/2 (51.6% vs. 39.3%) and MDS-RS-SLD/MLD (22.6% vs. 1.8%) was more common in high-SF-MDS. In the laboratory data analysis, high-SF-MDS patients showed low Hb levels, high RBC distribution width values, and high bone marrow RS percentages. In patients with high-SF-MDS, as well as MDS-RS, the presence of bone marrow RS was also observed in seven out of 11 patients with MDS-EB1/2 (median 8%, range 2-19%). Complex karyotype ( was more common in patients with high-SF-MDS (46.4% vs. 16.0%, P=0.007) than those with low-SF-MDS. Trisomy 8 and del (5q) were also frequently detected among those with high-SF-MDS. Patients with high-SF-MDS had worse 2-year overall survival (OS) than those with low-SF-MDS. To clarify the molecular characteristics of high-SF-MDS in more detail, NGS analysis was performed on 11 patients with high-SF-MDS whose samples were available. Ten gene mutations were detected in eight patients. Interestingly, five among 11 patients harbored TP53 mutation; the median variant allele frequency was 53.9% (range, 39.7-64.1%). Subsequently, SF3B1 gene mutation was detected in three patients; and two of them also harbored TP53 mutation. Other gene mutations, RUNX1, STAG2, SRSF2, ASXL1, ATM, DNMT3A, BCOR, and DDX41 were detected in one patient each. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

In patients with diabetes on hemodialysis (HD), glycemic control improves spontaneously, leading to normal glycated hemoglobin (HbA1c) levels; this phenomenon is known as "burnt-out diabetes." However, glycated albumin (GA) might be a better indicator of glycemic control than HbA1c in HD patients. Therefore, the aim of this study was to identify how many patients experience "burnt-out diabetes" using HbA1c and GA levels and to examine the association between cardiovascular comorbidity risk and GA levels.Patients with diabetes on HD whose HbA1c levels were measured and whose antidiabetic therapy was recorded were included. First, the "burnt-out diabetes" phenomenon was investigated in patients whose HbA1c levels were measured (HbA1c cohort). Then, it was investigated in patients who were assessed for both HbA1c and GA levels (GA cohort). Risk of cardiovascular comorbidity was assessed using multivariable logistic regression models.In the HbA1c cohort, 60,019 patients were included. When "burnt-out diabetes" was defined as HbA1c6.0% without treatment with antidiabetic medication, it was noted in 11,159 patients (18.6%). In the GA cohort, 23,668 patients were included, and it was found in 4899 patients (20.7%). However, when "burnt-out diabetes" was defined as HbA1c6.0% and GA16.0% without treatment with antidiabetic medication, it was found in 1286 patients (5.4%). Patients with GA18% had a higher risk of cardiovascular comorbidity.Although the "burnt-out diabetes" phenomenon might be present in 20.7% of patients with diabetes on HD in terms of HbA1c, the rate was significantly decreased to 5.4% in terms of GA.UMIN000018641.

Pathological stage is the most important prognostic factor in patients with lung cancer, and is defined according to the tumor node metastasis classification system. The present study aimed to investigate the clinicopathological significance of lymphatic invasion in 103 patients who underwent surgical resection of lung squamous cell carcinoma (SqCC). The patients were divided into two groups, according to the degree of lymphatic invasion: Those with no or mild lymphatic invasion (ly0-1) and those with moderate or severe lymphatic invasion (ly2-3). Ly2-3 was associated with tumor size (P=0.028), lymph node metastasis (P

Since 2009, the peritoneal dialysis (PD) registry has been carried out as part of the annual nationwide survey conducted by the Statistical Survey Committee of the Japanese Society for Dialysis Therapy with the cooperation of the Japanese Society for Peritoneal Dialysis. In this study, the current status of PD patients is reported on the basis of the results of the survey conducted at the end of 2013. The subjects were PD patients who lived in Japan and participated in the 2013 survey. Descriptive analysis was performed for various items including the current status of the combined use of PD and another dialysis method such as hemodialysis (HD) or hemodiafiltration (HDF), the method of exchanging dialysate, the use of an automated peritoneal dialysis (APD) machine, and the incidences of peritonitis and catheter exit-site infection. From the results of the facility survey in 2013, the number of PD patients was 9392, a decrease of 122 from that in 2012. Among the entire dialysis patient population, 3.0% were PD patients, a decrease of 0.1%. Among the studied patients, 292 had a peritoneal catheter and underwent peritoneal lavage, 174 were started on PD in 2013 but introduced to other blood purification methods in 2013, and 1920 underwent both PD and another dialysis method such as HD or HDF. The percentage of patients who underwent PD and another dialysis method increased with the number of years on PD

Whether higher serum uric acid (UA) values comprise a risk factor for death and whether treatment for high UA is effective in patients undergoing hemodialysis (HD) are essentially unknown. To determine associations between UA and all-cause or cardiovascular (CV) mortality, interactions between UA or medication and effects on mortality, and significance of treatment for hyperuricemia in patients undergoing hemodialysis (HD). We collected the baseline data of 222,434 patients undergoing three HD sessions per week, extracted from a nationwide dialysis registry at the end of 2011 in Japan. Then we evaluated the interaction between serum uric acid level and all-cause and cardiovascular (CV) mortality by the end of 2012. Univariate and multivariate logistic regression and Cox regression analyses found higher all-cause and CV mortality rates among patients with lower, than higher UA values. Hazard ratios (HR) for all-cause and CV mortality were significantly lower in a group with, than without medication for hyperuricemia (HR, 0.837; 95% confidence interval (CI), 0.789-0.889 and HR, 0.830; 95%CI 0.758-0.909, respectively). Lower UA values remained associated with all-cause and CV mortality rates even when in patients taking medication for hyperuricemia. The chief interacting factors for higher mortality rates due to lower UA were higher BMI and diabetes mellitus. In conclusion, lower UA levels were independently associated with higher all-cause and CV mortality among Japanese patients undergoing HD. Intervention for hyperuricemia is considered to improve patient outcomes.

Some have raised concerns that longer and more frequent hemodialysis (HD) would be associated with bone fractures due to excess phosphate removal. We examined the effects of hemodialysis product (HDP) on hip fracture incidence among Japanese HD patients using registry data of the Japanese Society for Dialysis Therapy. During a 1-year study period, 1411 hip fractures occurred among 135 984 patients. After adjusting for demographic and clinical factors, patients with a high HDP did not show a significant risk of hip fracture. Interestingly, patients with polycystic kidney disease had a lower risk of hip fracture. Our findings did not support the hypothesis that patients undergoing longer and more frequent HD would face a higher risk of hip fracture than those undergoing shorter and less frequent HD. Polycystic kidney disease was identified as a new significant factor for hip fracture; relative to glomerulonephritis, this condition was associated with a lower risk of hip fracture.

Multipoint vibration sensing is demonstrated using fiber Bragg gratings and optical-frequency-domain reflectometry (OFDR). Using OFDR, a few thousand arrayed sensors can be monitored with a measurement time limited by the wavelength-scanning rate of the light source. Here, a laser diode serves as the source. Its wavelength can be modulated by varying the injection current at high frequency using a laser-diode controller, so that high-speed scanning can be achieved. It is experimentally demonstrated that the proposed sensor achieves vibration measurement with a noise density of 7 fm/ $\sqrt{\rm Hz}$ , measurement time of 10 $\mu$ s.

Iron-chelating agents, which are frequently prescribed to transfusion-dependent patients, have various useful biological effects in addition to chelation. Reactive oxygen species (ROS) produced by neutrophils can cause pulmonary endothelial cell damage, which can lead to acute lung injury (ALI). We previously reported that deferasirox (DFS), an iron-chelating agent, inhibits phorbol myristate acetate (PMA) or formyl-methionyl-leucyl-phenylalanine (fMLP)-induced ROS production in neutrophils, in vitro. Here, we investigate whether DFS inhibits vacuolization in neutrophils and neutrophil extracellular trap (NET) formation. Human neutrophils were incubated with DFS and stimulated with PMA or fMLP. Human neutrophils were separated from heparinized peripheral blood using density gradient centrifugation, and subsequently incubated with DFS. After 10 minutes, neutrophils were stimulated by PMA or fMLP. Vacuole formation was observed by electron microscopy. For observing NET formations using microscopes, immunohistological analyses using citrullinated histone H3 and myeloperoxidase antibodies, and SYTOX Green (an impermeable DNA detection dye) staining, were conducted. NET formation was measured as the quantity of double-stranded DNA (dsDNA), using the AccuBlue Broad Range dsDNA Quantitation Kit. DFS (50 μmol/L) inhibited vacuole formation in the cytoplasm and NET formation. Additionally, 5-100 μmol/L concentration of DFS inhibited the release of dsDNA in a dose-independent manner. We demonstrate that DFS inhibits not only ROS production but also vacuolization and NET formation in neutrophils. These results suggest the possibility of protective effects of DFS against NET-related adverse effects, including ALI and thrombosis.

Background Activated human eosinophils, as well as neutrophils, can release extracellular chromatin to form DNA traps through cytolytic extracellular trap cell death (ETosis). Although formations of neutrophil DNA traps are recognized in patients with various inflammatory conditions, neither the presence of ETosis-derived eosinophil DNA traps in human allergic diseases nor the characteristics of these DNA traps have been studied. Objective We investigated the presence of ETosis-derived DNA traps in eosinophil-rich sinus and ear secretions and the functional attributes of ETosis DNA traps. Methods Eosinophil-rich secretions obtained from patients with eosinophilic chronic rhinosinusitis and eosinophilic otitis media were studied microscopically. In vitro studies of ETosis and DNA trap formation used blood-derived eosinophils and neutrophils, and studies of the binding capacities of DNA traps used labeled bacteria and fluorescent microbeads. Stabilities of DNA traps were evaluated by using fluorescence microscopy. Results Abundant nuclear histone H1–bearing DNA traps formed in vivo in the eosinophilic secretions and contributed to their increased viscosity. In vitro , after brief shear flow, eosinophil ETosis-elicited DNA traps assembled to form stable aggregates. Eosinophil DNA traps entrapped bacteria and fungi and, through hydrophobic interactions, microbeads. In comparison with neutrophil-derived DNA traps, eosinophil DNA traps ultrastructurally exhibited thicker fibers with globular structures and were less susceptible to leukocyte-derived proteolytic degradation, likely because of the lesser protease activities of eosinophils. Conclusions In human allergic diseases local cytolysis of eosinophils not only releases free eosinophil granules but also generates nuclear-derived DNA traps that are major extracellular structural components within eosinophil-rich secretions.

Since 2009, the peritoneal dialysis (PD) registry survey has been carried out as part of the annual nationwide survey conducted by the Statistical Survey Committee of the Japanese Society for Dialysis Therapy with the cooperation of the Japanese Society for Peritoneal Dialysis. In this report, the current status of PD patients is presented on the basis of the results of the survey conducted at the end of 2012. The subjects were PD patients who lived in Japan and participated in the 2012 survey. Descriptive analysis of various items was performed, which included the current status of the combined use of PD and another dialysis method such as hemodialysis (HD) or hemodiafiltration (HDF), the method of exchanging dialysate, the use of an automated peritoneal dialysis (APD) machine, and the rates of peritonitis and catheter exit-site infection. From the results of the facility survey in 2012, the number of PD patients was 9514, a decrease of 128 from 2011. Among the entire dialysis patient population, 3.1% were PD patients, a decrease of 0.1%. Among the studied patients, 347 had a peritoneal catheter and underwent peritoneal lavage, 175 were started on PD in 2012 but introduced to other blood purification methods in the same year, and 1932 underwent both PD and another dialysis method such as HD or HDF. The percentage of patients who underwent PD and another dialysis method increased with PD vintage

A nationwide survey of 4325 dialysis facilities was conducted at the end of 2013, among which 4268 (98.7%) responded. The number of new dialysis patients was 38,095 in 2013. Since 2008, the number of new dialysis patients has remained almost the same without any marked increase or decrease. The number of dialysis patients who died in 2013 was 30,751. The dialysis patient population has been growing every year in Japan; it was 314,438 at the end of 2013. The number of dialysis patients per million at the end of 2013 was 2470. The crude death rate of dialysis patients in 2013 was 9.8%. The mean age of new dialysis patients was 68.7 years and the mean age of the entire dialysis patient population was 67.2 years. The most common primary cause of renal failure among new dialysis patients was diabetic nephropathy (43.8%). The actual number of new dialysis patients with diabetic nephropathy has almost been unchanged for the last few years. Diabetic nephropathy was also the most common primary disease among the entire dialysis patient population (37.6%), followed by chronic glomerulonephritis (32.4%). The percentage of dialysis patients with diabetic nephropathy has been increasing continuously, whereas the percentage of dialysis patients with chronic glomerulonephritis has been decreasing. The number of patients who underwent hemodiafiltration (HDF) at the end of 2013 was 31,371, a marked increase from that in 2012. This number is more than twice that at the end of 2011 and approximately 1.5 times the number at the end of 2012. In particular, the number of patients who underwent online HDF increased approximately fivefold over the last 2 years. Among 151,426 dialysis patients with primary causes of renal failure other than diabetic nephropathy, 10.8% had a history of diabetes. Among those with a history of diabetes, 26.8% used glycoalbumin as an indicator of blood glucose level; and 33.0 and 27.6% were administered insulin and dipeptidyl peptidase (DPP)-4 inhibitor, respectively, as a medication of diabetes. The facility survey showed that 9392 patients underwent peritoneal dialysis (PD). The patient survey revealed that 1920 of these PD patients also underwent another dialysis method using extracorporeal circulation, such as hemodialysis (HD) or HDF. The number of patients who underwent HD at home at the end of 2013 was 461, a marked increase from that at the end of 2012 (393).

A fiber Bragg grating (FBG)-based multi-point sensing system for the simultaneous measurement of strain and temperature is proposed, with a Fabry-Perot interferometer (FPI) consisting of low reflective FBGs inscribed inside a polarization-maintaining (PM) fiber is introduced as a sensor head. A multi-point sensing method with high dynamic range and short measurement time can be realized by analyzing the reflection spectrum of low reflective FBG-FPIs, and a simultaneous measurement of strain and temperature using two orthogonal polarization modes is enabled by the high birefringence of a PM fiber. An experimental demonstration of multi-point measurement utilizing the proposed system is reported.

Autologous stem-cell transplantation is an effective procedure for the treatment of multiple myeloma, and involves the collection of hematopoietic stem cells (HSCs). However, in some patients, HSCs in the bone marrow fail to mobilize. Pomalidomide upregulates CXCR4 in hematopoietic stem cells, in a manner similar to that of lenalidomide, and is, thus, likely to have a negative impact on hematopoietic stem-cell mobilization in multiple myeloma patients. Here, we report the two cases in which hematopoietic stem cells were mobilized using plerixafor plus granulocyte-colony stimulating factor after exposure to lenalidomide and pomalidomide. Use of plerixafor with a sufficient washout period may lead to successful mobilization following pomalidomide use, although further study of this potential use is needed.

Background: Sarcopenia, the loss of muscle mass, has been recognized as a prognostic factor for cancer patients. For example, low body mass index (BMI) was reported to be a risk of poor overall survival (OS) among allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. However, low BMI was not associated with high non-relapse mortality (NRM) rate, and BMI may not directly reflect the physical condition. (Bone Marrow Transplant. 2014;49:1505-12). To evaluate the clinical impact of the muscle volume on the prognosis of allo-HSCT recipients, other biomarkers that directly reflect muscle mass may be warranted. Urinary creatinine excretion (UCE) has been reported to estimate muscle mass and have prognostic value for kidney transplant patients (Transplantation. 2008;86:391-8.). There is no report to evaluate clinical impact of UCE on the prognosis of allo-HSCT recipients. Therefore, we retrospectively analyzed the association between pre-transplant UCE and the transplant outcomes. Methods: We included 173 adult patients with acute myeloid leukemia (AML) in complete remission (CR) who underwent first allo-HSCT from 2006 to 2017 at our institute and measured UCE before allo-HSCT. Concerned the possibility of urine storage failure, two patients with low total daily urine volume ( We used receiver operating characteristics curve in order to determine the cutoff value of the WA-UCE and classified the patients into the high and low WA-UCE group. We evaluated transplant outcomes such as OS, progression-free survival (PFS), NRM, and cumulative incidence of relapse (CIR) between two groups. Results: The median age at allo-HSCT was 52 (range, 18-73) and there were more male patients (n=111) than female patients (n=60). Regarding cytogenetic risk, 15 (9.1%), 112 (65.8%), and 38 (23.0%) were categorized as favorable, intermediate, and poor risk, respectively (There were five patients without cytogenetic data). The median follow-up period of survivors was 704 (range, 9 to 3,857) days. We defined the cutoff value of the weight adjusted UCE as 148 μmol/kg/day in male and 128 μmol/kg/day in female. Among 171 patients, 90 patients (male = 59, female = 31) were in the high WA-UCE group and 81 patients (male = 52, female = 29) were in the low WA-UCE group. We found no significant differences between two groups in terms of the number of relapse before allo-HSCT, cytogenetic risks, conditioning regimens, hematopoietic cell transplantation comorbidity index, donor-recipient HLA matching, donor source, or estimated glomerular filtration rate. On the other hand, patient's age at allo-HSCT was significantly younger (low vs. high WA-UCE group: median, 53 [range, 18 - 73] vs. 48 [range, 19 - 68] years, P = 0.02) and BMI was lower (low vs. high WA-UCE group: median, 22.3 [range, 15.4 - 38.8] vs. 21.9 [range, 15.4 - 29.3] kg/m2, P = 0.003) in high WA-UCE group. In univariate analysis, we observed a significant difference in OS, PFS, and NRM between two groups (low vs. high WA-UCE group: 1-year OS, 60.1% vs. 80.9%, P < 0.01; 1-year PFS, 54.1% vs. 70.9%, P = 0.02; 1-year NRM, 24.8% vs. 12.3%, P = 0.02) (Figure1). On the other hand, there was no significant difference in 1-year CIR between two groups (low vs. high WA-UCE group: 21.1% vs. 16.8%, P = 0.63). In our cohort, the low BMI (< 18.5 kg/m2) was not significantly associated with OS, PFS, CIR, and NRM (low vs. high BMI group: 1-year OS, 77.6% vs. 69.9%, P = 0.51; 1-year PFS, 74.1% vs. 60.9%, P = 0.45; 1-year CIR, 14.8% vs. 19.5%, P = 0.02, 1-year NRM, 11.1% vs. 19.5%, P = 0.70) In multivariate analysis, the low WA-UCE was an independent risk factor for OS (Hazard ratio (HR) [95% confidence interval (CI)]; 2.29 [1.38 - 3.80], P < 0.01), PFS (HR [95% CI]; 1.76 [1.11 - 2.79], P = 0.02), and NRM (HR [95% CI]; 2.22 [1.13 - 4.36], P = 0.02) (table1). Conclusion: In allo-HSCT adult recipients with AML in CR, low WA-UCE before transplantation was associated with poor prognosis, which related to high NRM within 1 year. WA-UCE can be an independent, objective, simple, and reliable biomarker for evaluating muscle mass and predicting transplant outcome. Disclosures No relevant conflicts of interest to declare.

Background Myelodysplastic syndromes (MDS), commonly seen in elderly patients, represent a heterogeneous group of clonal hematopoietic stem cell disorders caused by the accumulation of gene mutations. By contrast, congenital bone marrow failure syndromes and genetic predispositions associated with MDS are known in pediatric patients. However, little is known about the pathogenesis of MDS in adolescent and young adult (AYA) patients. Previous reports showed the patients with MDS aged under 40 or 41.5 years at allo-HSCT were associated with good survival compared to those among the older population (N Engl J Med. 2017;376:536-547, Blood. 2017;129:2347-2358). However, AYA-MDS is rare, and its clinical features and genetic abnormalities have not been analyzed enough. It is suspected that the clinical and genetic features of AYA-MDS patients might be different from those of elderly patients or pediatric patients. Therefore, we investigated the gene abnormalities of AYA-MDS patients and aimed to elucidate the genetic characteristics associated with the good outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We analyzed the patients younger than 50 years of age in order to reduce the variation of patient-related factors. Methods We analyzed the outcomes of all consecutive patients aged under 50 years who were diagnosed with MDS or acute myeloid leukemia evolving from MDS in our hospital between January 2005 and July 2018. The study was approved by the institutional review board, and patients gave written informed consent for the study, according to the Declaration of Helsinki. Cytogenetic analysis and genomic DNA extraction were carried out using diagnostic bone marrow samples. We performed targeted next-generation sequencing to identify mutations in 68 driver genes using AmpliSeq for Illumina Myeloid Panel and On-Demand Panel on the MiniSeq system (Illumina). Gene variants were detected by in-house analysis pipeline. Overall survival (OS) was analyzed for all patients, and the Kaplan-Meier survival curve was used to assess OS using the log-rank test. Additionally, the cumulative incidence of relapse (CIR) was analyzed for patients who underwent allo-HSCT. Gray's test was used to evaluate the CIR. Results A total of 85 patients with MDS aged under 50 years (U40 between 15 and 39 years old: N=37, 40s between 40 and 49 years old: N=48) were analyzed. The median follow-up time of survivors was 2,041 days (range 176-5,085). There were no significant differences in patient characteristics between U40 and 40s. The 3-year OS of U40 were superior to 40s (79.9% vs. 58.1%, P=0.018), especially lower risk IPSS categories (3-year OS, 95.5% vs. 50.8%, P=0.002). In total, 69 of 85 patients (U40: N=31, 40s: N=38) had undergone allo-HSCT. U40 patients had lower percentage of bone marrow blasts at just before HSCT than 40s patients (over 10%, 12.9% vs. 36.8%, P=0.048), and better 3-year OS from HSCT in lower-IPSS (88.8% vs. 53.8%, P=0.024); but not in higher-IPSS (45.0% vs. 43.2%, P=0.834). In this cohort, at least one driver mutation was detected in 61% of allo-HSCT recipients. Frequently mutated genes (more than 10%) were ASXL1 and RUNX1; however, both of the genes did not have significant impact on the outcomes. While, only one patient in 40s had TP53 mutation. We detected 0.8 (range 0-3) and 1.8 (range 0-6) mutations at average in U40 and 40s, respectively (P=0.06). The proportions of the patients without any gene mutations were 52% in U40 and 30% in 40s. Transplanted patients with 0 or 1 mutation showed lower relapse rate than those with 2 or more mutations (3-year CIR, 23.3% vs. 45.2%, P=0.049). Conclusions The clinical outcomes of U40 patients with MDS were favorable than those in the 40s, especially in lower disease risk. The number of driver mutations in U40 tended to be lower than that in 40s. MDS in adult is regarded as a stem-cell aging disease with gene mutations; however, MDS-associated mutations were not detected in the half of U40. Moreover, TP53 mutation that is associated with extremely poor posttransplant survival was not detected in U40 patients. MDS patients with less than 2 mutations showed lower relapse rate, which maybe indicate genetic mutations have a great impact on transplant outcomes between 15 and 49 years old. Disclosures No relevant conflicts of interest to declare.

Background Constitutional partial trisomy 8 mosaicism (CT8M) is a congenital chromosomal abnormality with an estimated occurrence rate as one out of 25,000-50,000 pregnancies. CT8M has a wide variability in physical manifestation ranging from apparently normal to severe disablement. However, diagnosis of CT8M in adult without physical abnormality is difficult . Acquired trisomy 8, which is restricted to the malignant cells, is one of the most common chromosomal abnormalities in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), and clinical implication of carrying isolated trisomy 8 is considered as intermediate cytogenetic risk in MDS. However, isolated trisomy 8 without morphological dysplastic features is not definitive evidence for MDS. 15 to 20% of trisomy 8 in MDS are supposed to be derived from CT8M. We therefore diagnosed CT8M patients among patients with cytopenia and analyzed clinical and genetic features to uncover the association with MDS. Methods . Clinical features including cytogenetic analysis were analyzed regularly. Genomic DNA was extracted from whole PB cells or BM mononuclear cells. We performed targeted next-generation sequencing to identify mutations in 68 driver genes of myeloid neoplasms using AmpliSeq for Illumina Myeloid Panel and On-Demand Panel on the MiniSeq system (Illumina). Gene variants were detected by in-house analysis pipeline. The study was approved by the institutional review board and patients gave written informed consent for the study. Results We identified nine CT8M patients with cytopenia.They comprised 3 males and 6 females at a median age of 56 years (range 24-84 years) (Table). All the patients carried no physical abnormality nor conspicuous phenotypic features. Four patients (Patient #3, #4, #6 and #7) did not show apparent morphological dysplasia at the initial BM examination, and they were not diagnosed as MDS. Their cytopenia has not been exacerbated until now without any treatment, and the duration of stable cytopenia was from 2 to 12 years in these patients. By contrast, five patients with CT8M were diagnosed as MDS . Two patients (#5 and #8) were diagnosed as MDS-single lineage dysplasia (SLD), and their cytopenia has not become worse without any treatment for about 4 years. Other three patients diagnosed as MDS-multilineage dysplasia (MLD) showed various clinical courses. Patient #1 was treated with azacitidine and maintains complete hematological improvement after 34 courses of the treatment. Patient #2 was treated with erythropoietin stimulating agent and azacytidine but developed to AML 3 years after initial diagnosis but leukemic blasts has del(20), not +8. Patient #9 developed advanced pancytopenia in 3 months from initial diagnosis and received red blood cell transfusion regularly. Gene mutations were detected in five out of nine patients with CT8M. In three patients, gene mutations were detected at high (20 to 50%) variant allele frequency (VAF). Patient #2 who was analyzed at the AML phase had gene mutations of SRSF2, SF3B1, STAG2 and NOTCH1. BM sample from patient #9 showed ASXL1 mutation and two TET2 mutations. Patient #4 who did not show apparent myelodysplasia had a high VAF ASXL1 mutation, indicating clonal idiopathic cytopenias of undetermined significance. Two patients had low (2 to 5%) VAF mutations; patient #1 was analyzed after 34 courses of azacitidine had a TET2 mutation; patient #5 with MDS-SLD had a WT1 mutation and two PHF6 mutations. Four patients (#3, #6, #7 and #8) did not have any mutations. The clinical and genetic features showed that CT8M with cytopenia without MDS-related mutations were under 56 years old and did not develop to MDS or stayed at MDS-SLD. Patients with low VAF mutations were also stable. By contrast, patients with advanced diseases gained multiple MDS-related gene mutations with high VAF. One patient without dysplasia had a high VAF ASXL1 mutation. All the patients with gene mutations were age of 56 to 84 years. Conclusion Our results indicated that isolated trisomy 8 may cause cytopenia, but the cytopenia is not exacerbated without MDS-related driver gene mutations. CT8M patients with cytopenia might get gene mutations gradually with age, which leads to MDS or AML. Disclosures No relevant conflicts of interest to declare.

[Background] Philadelphia chromosome positive (Ph+) leukemia is characterized by highly proliferative nature and clone instability that evokes the emergence of mutated clones, including BCR-ABL1 T315I mutated clone. Established evidence on the use of tyrosine kinase inhibitors (TKIs) after allogeneic hematopoietic stem cell transplantation (HSCT) is still lacking. The use of second-generation TKIs as a maintenance treatment after HSCT has been studied, and it is expected that their use would improve the prognosis by suppressing recurrence. The advent of ponatinib (PON), a potent inhibitor of tyrosine kinase including T315I mutated BCR-ABL1, is expected to improve clinical outcome of Ph+leukemia. However, there are few reports of a maintenance treatment using PON after HSCT. [Methods] We retrospectively reviewed data of 13 patients (pts) who received PON for Ph+leukemia after HSCT while in hematological complete remission (CR) between April 1, 2016 and July 15, 2019. Prophylactic treatment (Pro) was defined as post-transplant administration of PON while in minimal residual disease (MRD) negative CR. Pre-emptive treatment (Pre) was defined as starting PON when the bcr-abl transcript was detected by either quantitative or nested qualitative PCR after HSCT. ABL1 mutation was analyzed through the direct sequencing method. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events version 5.0. Overall survival (OS) was estimated using Kaplan-Meier method. Non-relapse mortality (NRM) and cumulative incidence of hematological relapse (CIR) were calculated using Gray's test. This study protocol was approved by the ethics committee of Tokyo Metropolitan Komagome Hospital. [Results] Underlying diseases were Ph+ALL in 8 pts (5 in CR, 3 in non-CR at HSCT), CML in 5 (all in second chronic phase). ABL1 mutations were analyzed in 12 pts and T315I mutation was detected in 4 pts with Ph+ALL and 2 with CML. Furthermore, compound mutations (CMs) in BCR-ABL1 were detected in 4 pts before HSCT. PON was used in 6 only after HSCT, and in 7 both before and after HSCT. During the median observation after HSCT of 584 days (range, 116-1,110) for survivors, no vascular occlusion event occurred. With regard to adverse events (AEs), grade 3 AEs occurred in 2 pts (15.4%) and no grade 4 AE was observed. Two had liver dysfunction and one of them discontinued PON due to grade 3 abnormalities in liver function tests. One suffered from grade 3 thrombocytopenia. Four had skin rashes lower than grade 3 that were indistinguishable from skin graft-versus-host disease, and all of them resolved through topical steroid therapy. Of all, 6 were in Pro group and 7 were in Pre group. The initial dose of PON was median 15mg (range 45mg/twice a week - 15mg/day) in Pro and median 30mg (range, 15-45mg) in Pre. The median days from HSCT to the start of PON was 107 days (range, 32-174) in Pro and 208 days (range, 50-364) in Pre. The median duration of PON treatment was 297 days (range, 20-699) in Pro and 188 days (range, 5-608) in Pre. At final observation in Pro group, 2 pts relapsed and died during the salvage therapy, 1 pt discontinued PON due to hepatic adverse event, and 3 pts were still on PON. Meanwhile, in Pre group, 5 pts achieved MRD negative CR after PON administration (1 pt also received donor lymphocyte infusion and stop PON due to liver dysfunction, 1 discontinued PON by the patient's request, and 3 of them were still on PON). One pt with CM relapsed but achieved CR through salvage therapy and 1 pt with low performance status (KPS 60) died at home of unknown cause six days after taking PON 30mg daily. For all the 13 pts receiving PON maintenance therapy, OS was 74.6% (95%CI; 39.8-91.1), CIR was 23.1% (95%CI; 5.1-48.5), and NRM was 7.7% (95%CI; 0.4-30.6) at 1 year after transplant (Figure 1). Two out of 4 pts with CMs (V299L/F317L and E255K/T315I/F317L) remains in MRD negative CR. The other 2 with CMs (E255K/T315I and D276G/T315I) had progressed to hematological relapse, suggesting the resistance to PON. In contrast, only one out of 9 without CMs relapsed on PON treatment. [Conclusion] Our results suggested that post-transplant maintenance treatment using PON was tolerable in the majority of patients with Ph+leukemia, although the optimal dose or the initiation strategy (Pre or Pro) are still undetermined. Furthermore, some patients with T315I-inclusive CMs seemed to be resistant to PON. The longer observation in a larger cohort is warranted. Disclosures No relevant conflicts of interest to declare.

[Background] Cytomegalovirus (CMV) disease is a major complication after allogeneic stem cell transplantation (SCT). However, mechanisms of adoptive immunity against CMV are not fully elucidated. Recently, high-throughput next-generation sequencing (NGS) technology made it possible to shed light on the detailed and comprehensive landscape of T-cell receptor (TCR) repertoire. In this study, we analyzed TCR repertoire of CMV-specific cytotoxic T-cells (CMV-CTLs) in patients who suffered from CMV reactivation after SCT to clarify the diversity and dynamics of CMV-specific T-cell immunity. [Methods] We sequentially collected peripheral blood mononuclear cells from patients with HLA-A*24:02 who received SCT in our institution. Samples were collected weekly or every two weeks from their neutrophil engraftment until approximately 100 days after SCT. CMV reactivation was evaluated weekly with CMV antigenemia test. CD8 and CMV pp65 tetramer positive cells were sorted and unbiased next-generation sequencing-based analyses of TRBV/TRBJ gene segments were performed at the timing of CMV reactivation in 16 patients, and TRA gene segments were also analyzed in 10 patients. In addition, TCR beta repertoires after 2-4 weeks were analyzed in 12 patients. In the 12 patients, the dynamics of TCR repertoire diversity and proportional changes of each clone were assessed. We evaluated the diversity by Shannon-Weber index, and we defined TCR beta clonotypes found in two or more patients using the same TRBV/TRBJ gene segments and CDR3 amino acid sequences as public. This study was approved by the ethics committee of Tokyo Metropolitan Komagome Hospital. [Results] Among 16 patients, 11 received bone marrow, 3 received peripheral blood stem cells, and 2 received cord blood transplant. Underlying diseases were acute myeloid leukemia in 7, acute lymphoblastic leukemia in 7, and myelodysplastic syndromes in 2 patients. Median age at SCT was 50 years old (range: 20-71). Median duration from SCT to first CMV reactivation was 39 days (range: 16-55) and 7 patients (43.8%) were administered systemic corticosteroid at the time of reactivation (prednisolone 10-30mg/day). Median peripheral blood CMV-CTLs count at that time was 29.47/uL (range: 4.65-229.6). In most patients TCR beta repertoire of CMV-specific CTLs when CMV reactivated was highly skewed (median Shannon-Weber index was 1.44 [range: 0.542-3.164]). TCR alpha and beta were analyzed together in 10 patients and their diversity correlated well (p [Conclusion] TCR repertoire of CMV-CTLs at the time of CMV reactivation after SCT is highly oligoclonal and frequently shared among different patients, but can dynamically change in a short period in some patients. Functional analyses of the dominant TCRs to understand their reactivity against CMV epitope and elucidation of the clinical significance and developmental mechanisms of clone shift are strongly warranted. Figure Disclosures Kitaura: Repertoire Genesis Inc.: Employment. Suzuki:Repertoire Genesis Inc.: Equity Ownership.

Ultrastructure analysis of immature platelets is difficult because of the lack of a suitable marker and their relatively low concentration in total platelets. We investigated the morphological and optical properties of human immature platelets produced and enriched in immunodeficient mice via human CD34-positive cell administration. Immunodeficient mice were injected with human CD34-positive cells and administered eltrombopag orally for 14 days (eltro-mice). Some of these mice were maintained for 2-3 months (steady-state-mice). Platelets were double-stained with a human CD41 antibody and a nuclear staining dye (Sysmex hematology analyzer XN series reagent), and then analyzed by flowcytometry FCM to identify human immature platelets. Human CD41-positive cells were isolated from citrated blood by magnetic cell sorting with human CD41 antibody, and examined using electron microscopy. Flow cytometric analysis with the XN reagent demonstrated that peripheral blood from eltro-mice had a higher percentage of immature platelet fraction in human platelets than that from steady-state-mice. The geometric mean of XN reagent fluorescence for human platelets, divided with that for mouse platelets, revealed that the ratios in eltro-mice were significantly higher than those in steady-state-mice, thus indicating that immature platelets were highly enriched in eltro-mice. Scanning and transmission electron microscopy revealed that human citrated platelets isolated from eltro-mice tended to be larger (n = 15, p = 0.276) and contained more mitochondria than those isolated from steady-state-mice (n = 10, p = 0.0002). Therefore, an increased number of mitochondria, rather than platelet size, is a distinctive feature of immature platelets.

In some diabetes patients on dialysis, glycemic control improves spontaneously, leading to normal HbA1c levels; this phenomenon is known as "burnt-out diabetes." Glycated albumin (GA) might be a better indicator of glycemic control than HbA1c in hemodialysis patients, but it has not been assessed in peritoneal dialysis (PD) patients.This study involved diabetes patients on PD, with HbA1c level and antidiabetes therapy records. First, the "burnt-out diabetes" phenomenon was investigated in patients with HbA1c measurements alone (HbA1c cohort). Then, it was investigated in patients with both HbA1c and GA measurements (GA cohort).A total of 1296 patients were included in the HbA1c cohort. When "burnt-out diabetes" was defined as HbA1c 6.0% without treatment, it was noted in 269 patients (20.8%). A total of 413 patients were subsequently included in the GA cohort. "Burnt-out diabetes," using the same definition, was found in 73 patients (17.7%). However, when defined as HbA1c 6.0% and GA 16.0% without treatment, "burnt-out diabetes" was found in 45 patients (10.9%).Although the "burnt-out diabetes" phenomenon was present in 17.7% of patients with diabetes on PD based on HbA1c, the rate was significantly decreased to 10.9% when taking GA into account.

著者人数: 270名（所属. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS): 高橋, 忠幸; 国分, 紀秀; 満田, 和久; Baluta, Chris; 坂東, 信尚; 堂谷, 忠靖; 海老沢, 研; 林, 克洋; 廣瀬, 和之; 飯塚, 亮; 石田, 学; 石川, 久美; 石村, 康生; 岩井, 将親; 岩田, 直子; 河野, 太郎; 川崎, 繁男; 小山, 志勇; 前田, 良知; 峯杉, 賢治; 中川, 貴雄; 夏苅, 権; 小川, 博之; 小川, 美奈; 太田, 方之; 岡崎, 健; 尾崎, 正伸; 坂井, 真一郎; 鮫島, 寛明; 佐藤, 悟郎; 佐藤, 理江; 柴野, 靖子; 志田, 真樹; 嶋田, 貴信; Simionescu, Aurora; 菅原, 泰晴; 竹井, 洋; 田村, 隆幸; 田中, 靖郎; 田代, 信; 冨田, 洋; 辻本, 匡弘; 上田, 周太朗; 上野, 史郎; 和田, 篤始; 渡辺, 伸; 山田, 隆弘; 山崎, 典子）, Number of authors: 270 (Affiliation. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency (JAXA)(ISAS): Takahashi, Tadayuki; Kokubun, Motohide; Mitsuda, Kazuhisa; Baluta, Chris; Bando, Nobutaka; Dotani, Tadayasu; Ebisawa, Ken; Hayashi, Katsuhiro; Hirose, Kazuyuki; Iizuka, Ryo; Ishida, Manabu; Ishikawa, Kumi; Ishimura, Kosei; Iwai, Masachika; Iwata, Naoko; Kawano, Taro; Kawasaki, Shigeo; Koyama, Shu; Maeda, Yoshitomo; Minesugi, Kenji; Nakagawa, Takao; Natsukari, Chikara; Ogawa, Hiroyuki; Ogawa, Mina; Ohta, Masayuki; Okazaki, Tsuyoshi; Ozaki, Masanobu; Sakai, Shinichiro; Sameshima, Hiroaki; Sato, Goro; Sato, Rie; Shibano, Yasuko; Shida, Maki; Shimada, Takanobu; Simionescu, Aurora; Sugawara, Yasuharu; Takei, Yoh; Tamura, Takayuki; Tanaka, Yasuo; Tashiro, Makoto; Tomida, Hiroshi; Tsujimoto, Masahiro; Ueda, Shutaro; Ueno, Shiro; Wada, Atsushi; Watanabe, Shin; Yamada, Takahiro; Yamasaki, Noriko Y.), Accepted: 2018-02-05, 資料番号: SA1170333000

Background Both functional impairment and abnormalities in mineral and bone disorder (MBD) parameters are well-known predictors of mortality in dialysis patients. However, previous studies have not evaluated whether functional impairment modifies the association between MBD parameters and mortality. Methods A nationwide prospective cohort study was conducted using data from the Japanese Society for Dialysis Therapy Renal Data Registry collected at the end of 2009 and 2010. The Eastern Cooperative Oncology Group performance status (PS) was used to assess functional status. Cox proportional hazards models were used to assess the associations of baseline functional status, serum phosphate, albumin-corrected calcium and intact parathyroid hormone (PTH) with 1-year all-cause mortality Results By 31 December 2010, 18 447 of 220 054 prevalent dialysis patients (8.4%) had died. Mortality significantly increased with worsening PS grade. PS grade modified the association of serum phosphate levels with mortality (Pinteraction = 0.001). Worsening PS grade attenuated the association of hyperphosphatemia (≥7.4 mg/dL) with mortality, and hyperphosphatemia was no longer significant on mortality among patients with the worst PS grade (hazard ratio = 1.1, 95% confidence interval 0.88–1.39), compared with the level between 3.5 and 4.7 mg/dL. In contrast, hypophosphatemia ( Conclusions Functional impairment was significantly associated with 1-year mortality and attenuated the effect of hyperphosphatemia on mortality among prevalent dialysis patients.

Cascaded chirped long period fiber gratings (C-CLPG) are provided as sensing elements for use in intensity-based underwater acoustic fiber-optic sensors, in which C-CLPGs are inscribed in photosensitive fiber by means of point-by-point technique with UV radiation. For a demonstration, C-CLPGs are immersed in a water vessel and exerted by underwater acoustic waves. In the demonstration, higher sensitive underwater acoustic detection is obtained by employing a C-CLPG with the steeper channeled spectrum.

By using the optical frequency reflectometry method and modulated laser diode, it is possible to read many fiber Bragg grating (FBG) sensors at high speed. In this method, the measurement range by the sensor is limited by the wavelength sweep range of the light source. Since the range of the wavelength sweep by the modulated laser diode is as narrow as several hundreds of pm, the measurement range also becomes narrow. In order to overcome this limitation, we are considering using multiple modulated laser diodes at the same time. Light beams from multiple modulated laser diodes modulated with different frequencies are superimposed and used for sensor reading. Signals for each light source can be separated by using frequency analysis. In experiments, light of multiple laser diodes was superimposed and made incident on the sensor, and frequency analysis of the reflected light from the sensor was successfully performed to separate the signals for each light source.

Flow cytometry and microscopy are equally important in cell analysis. However, few reports have compared the optical data (cell size, internal complexity and fluorescent signal) from flow cytometry and microscopy. In this study, we compared the scattergram from XN-series, a flow cytometry based hematology analyzer with microscopic images of similarly treated leukocytes, and investigated the correlation between the appearance in the scattergram and cell size, internal complexity and fluorescence intensity. Healthy human peripheral blood was analyzed using the XN analyzer. For microscopic comparison, five types of leukocytes (monocytes, lymphocytes, basophils, neutrophils and eosinophils) were isolated from the peripheral blood by centrifugation and magnetic cell sorting, treated with a specific reagent and analyzed using electron microscopy, laser microscopy and confocal laser microscopy. Cell size, residual internal structures and fluorescence intensity correlated with intensity of forward-scattering, side scattering and fluorescent light. In this study, optical data from a clinically used hematology analyzer was clarified using microscopic images.

A nationwide statistical survey of 4279 dialysis facilities was conducted at the end of 2012, among which 4238 responded (99.0%). The number of new dialysis patients was 38055 in 2012. Since 2008, the number of new dialysis patients has remained almost the same without any marked increase or decrease. The number of dialysis patients who died in 2012 was 30710; a slight decrease from 2011 (30743). The dialysis patient population has been growing every year in Japan; it was 310007 at the end of 2012, which exceeded 310000 for the first time. The number of dialysis patients per million at the end of 2012 was 2431.2. The crude death rate of dialysis patients in 2012 was 10.0%, a slight decrease from that in 2011 (10.2%). The mean age of new dialysis patients was 68.5 years and the mean age of the entire dialysis patient population was 66.9 years. The most common primary cause of renal failure among new dialysis patients was diabetic nephropathy (44.2%). The actual number of new dialysis patients with diabetic nephropathy has been approximately 16000 for the last few years. Diabetic nephropathy was also the most common primary disease among the entire dialysis patient population (37.1%), followed by chronic glomerulonephritis (33.6%). The percentage of dialysis patients with diabetic nephropathy has been continuously increasing, whereas not only the percentage but also the actual number of dialysis patients with chronic glomerulonephritis has decreased. The number of patients who underwent hemodiafiltration (HDF) at the end of 2012 was 21725, a marked increase from that in 2011 (14115). In particular, the number of patients who underwent on-line HDF increased threefold from 4890 in 2011 to 14069 in 2012. From the results of the facility survey, the number of patients who underwent peritoneal dialysis (PD) was 9514 and that of patients who did not undergo PD despite having a PD catheter in the abdominal cavity was 347. From the results of the patient survey, among the PD patients, 1932 also underwent another dialysis method using extracorporeal circulation, such as hemodialysis (HD) and HDF. The number of patients who underwent HD at home in 2012 was 393, a marked increase from that in 2011 (327).

We encountered blood specimens from a patient with MYH9 related diseases, which gave falsely high white blood cell (WBC) counts during laboratory analysis using Sysmex XN-series automated hematology analyzers. This overcount was revealed to be caused by the overlapping of platelet (PLT) distribution with the WBC area in the WNR channel, which was used for routine WBC count with the XN-series. On the other hand, the WBC count obtained through the WDF channel of the XN-series seemed more accurate in such a case. We then created and introduced alert message settings for such rare but critical specimens, which gives a warning when the discrepancy in WBC counts between the WNR and WDF channels is higher than 1.0×10

On-line hemodiafiltration is an increasingly common alternative to chronic hemodialysis in some countries, based on the results of randomized controlled trials of post-dilution on-line hemodiafiltration. There are now more than 60,000 patients treated with on-line hemodialfiltration in Japan, over 95% of whom use predilution on-line hemodiafiltration; however, large-scale data on clinical outcomes with this modality are lacking. We created a propensity-matched cohort of 5,000 pairs of patients treated with conventional hemodialysis or predilution on-line hemodiafiltration, using the Japanese Society for Dialysis Therapy Renal Data Registry database from December 31, 2012 to December 31, 2013. One-year all-cause and cardiovascular mortality were compared between the groups. Predilution on-line hemodiafiltration was associated with improved overall survival compared to hemodialysis (hazard ratio for all cause-mortality 0.83, 95% confidence interval 0.705-0.986), with a trend towards improved cardiovascular survival. Among patients treated with predilution on-line hemodiafiltration, those treated with high substitution volumes (≥40.0 L per session) had improved all-cause and cardiovascular survival compared to those treated with low substitution volumes (40.0 L per session) or those on hemodialysis. The optimal substitution volume associated with improved overall survival was estimated to be 50.5 L [95% confidence interval 39.0-63.5 L]. This observational study suggests that predilution on-line hemodiafiltration, especially with high substitution volumes, may improve all-cause and cardiovascular survival, but randomized controlled trials are needed.

Ischemia-reperfusion injury resulting in post-transplant lung dysfunction involves a complicated network of cytokines that has yet to be fully investigated. We analyzed temporal changes in cytokine levels in epithelial lining fluid (ELF) from the distal airways of a canine lung transplantation model.Ischemic time was set to 18 hours to enhance lung injury in a left single-lung transplantation model. ELF was collected via bronchoscopic microsampling, a minimally-invasive technique allowing repeated sampling, hourly up to 5 hours after reperfusion started. We compared levels of pro-inflammatory cytokines in ELF with those at baseline (time zero), and with a sham-operated control group.Concentrations of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) significantly increased immediately after the start of lung reperfusion in the transplant group relative to the sham group (P0.005 and P0.05, respectively); both were sustained through the 5 hours. Interferon gamma (IFN-γ levels were significantly reduced 3 h after reperfusion started (P0.05).We found time- and cytokine-dependent changes in TNF-α, IL-6, and IFN-γ in ELF from the lung transplantation model. These specific changes in the cytokine profile may relate to the mechanism underlying post-transplant lung dysfunction.

Magnesium is an essential mineral for bone metabolism. However, little is known about the relationship between magnesium and the risk of fractures. In this cohort study, we elucidated the association between serum magnesium level and the risk of incident hip fracture among patients undergoing hemodialysis. We identified 113,683 patients undergoing hemodialysis with no history of hip fracture from a nation-wide database of patients undergoing dialysis in Japan. During a 2-year follow-up, a total of 2305 (2%) new hip fractures occurred. The crude incidence rate was significantly higher among patients in the lower quartiles of serum magnesium levels (2.63%, 2.08%, 1.76%, and 1.49% in Q1–Q4, respectively; P2.9. After adjustment for demographic and clinical factors, patients in Q1 had a 1.23-fold higher risk for hip fracture than those in Q4 (95% confidence interval, 1.06 to 1.44; P

A precise measurement technique of long period of fiber grating sensor (LPG) is demonstrated by employing a cascaded chirp LPG (C-CLPG) as a sensing device and by adopting a Fourier transform method for an interrogation technique. In this approach, transmittance of the C-CLPG exhibits periodic channeled spectrum and its strain- and/or temperature-dependent wavelength shift is analyzed by obtaining a cross-spectrum function between the original and the shifted channeled spectra, in which the phase term of the cross-spectrum corresponds to the wavelength shift. Since the phase component is determined by using all the channeled spectrum over a wider bandwidth of the C-CLPG, more precise measurements of the strain and temperature are expected than that of the peak search method in that the wavelength shift is determined by the shift of one of peaks of the channeled spectrum. In the experiment, the highly precise strain and temperature measurements are presented by comparing with the results of the peak search method.