Pharmacogenomic study of gemcitabine efficacy in patients with metastatic pancreatic cancer: A multicenter, prospective, observational cohort study (GENESECT study).

BACKGROUND: Genetic polymorphisms of molecules are known to cause individual differences in the therapeutic efficacy of anticancer drugs. However, to date, germline mutations (but not somatic mutations) for anticancer drugs have not been adequately studied. The objective of this study was to investigate the association between germline polymorphisms of gemcitabine metabolic and transporter genes with carbohydrate antigen 19-9 (CA 19-9) response (decrease ≥50% from the pretreatment level at 8 weeks) and overall survival (OS) in patients with metastatic pancreatic cancer who receive gemcitabine-based chemotherapy. METHODS: This multicenter, prospective, observational study enrolled patients with metastatic pancreatic cancer patients who were receiving gemcitabine monotherapy or gemcitabine plus nanoparticle albumin-bound paclitaxel combination chemotherapy. Thirteen polymorphisms that may be involved in gemcitabine responsiveness were genotyped, and univariate and multivariate logistic regression analyses were used to determine the association of these genotypes with CA 19-9 response and OS. The significance level was set at 5%. RESULTS: In total, 180 patients from 11 hospitals in Japan were registered, and 159 patients whose CA 19-9 response could be assessed were included in the final analysis. Patients who had a CA 19-9 response had significantly longer OS (372 vs. 241 days; p = .007). RRM1 2464A>G and RRM2 175T>G polymorphisms suggested a weak association with CA 19-9 response and OS, but it was not statistically significant. COX-2 -765G>C polymorphism did not significantly correlate with CA 19-9 response but was significantly associated with OS (hazard ratio, 2.031; p = .019). CONCLUSIONS: Genetic polymorphisms from the pharmacokinetics of gemcitabine did not indicate a significant association with efficacy, but COX-2 polymorphisms involved in tumor cell proliferation might affect OS.

Phase I trial of myeloablative conditioning with 3-day total marrow and lymphoid irradiation for leukemia.

This prospective phase I trial aimed to determine the recommended dose of 3-day total marrow and lymphoid irradiation (TMLI) for a myeloablative conditioning regimen by increasing the dose per fraction. The primary end-point of this single-institution dose escalation study was the recommended TMLI dose based on the frequency of dose-limiting toxicity (DLT) ≤100 days posthematopoietic stem cell transplantation (HSCT); a 3 + 3 design was used to evaluate the safety of TMLI. Three dose levels of TMLI (14/16/18 Gy in six fractions over 3 days) were set. The treatment protocol began at 14 Gy. Dose-limiting toxicities were defined as grade 3 or 4 nonhematological toxicities. Nine patients, with a median age of 42 years (range, 35-48), eight with acute lymphoblastic leukemia and one with chronic myeloblastic leukemia, received TMLI followed by unrelated bone marrow transplant. The median follow-up period after HSCT was 575 days (range, 253-1037). Three patients were enrolled for each dose level. No patient showed DLT within 100 days of HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. All patients achieved neutrophil engraftment at a median of 19 days (range, 14-25). One-year overall and disease-free survival rates were 83.3% and 57.1%, respectively. Three patients experienced relapse, and no nonrelapse mortality was documented during the observation period. One patient died due to disease relapse 306 days post-HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. The efficacy evaluation of this regimen is currently being planned in a phase II study.

Association of Four Types of Vascular Access Including Arterial Superficialization with Mortality in Maintenance Hemodialysis Patients: A Nationwide Cohort Study in Japan.

INTRODUCTION: Vascular access usage varies widely across countries. Previous studies have evaluated the association of clinical outcomes with the three types of vascular access, namely, arteriovenous fistula (AVF), arteriovenous graft (AVG), and tunneled and cuffed central venous catheter (TC-CVC). However, little is known regarding the association between arterial superficialization (AS) and the mortality of patients. METHODS: A nationwide cohort study was conducted using data from the Japanese Society for Dialysis Therapy Renal Data Registry (2006-2007). We included patients aged ≥20 years undergoing hemodialysis with a dialysis vintage ≥6 months. The exposures of interest were the four types of vascular access: AVF, AVG, AS, and TC-CVC. Cox proportional hazard models were used to evaluate the associations of vascular access types with 1-year all-cause and cause-specific mortality. RESULTS: A total of 183,490 maintenance hemodialysis patients were included: 90.7% with AVF, 6.9% with AVG, 2.0% with AS, and 0.4% with TC-CVC. During the 1-year follow-up period, 13,798 patients died. Compared to patients with AVF, those with AVG, AS, and TC-CVC had a significantly higher risk of all-cause mortality after adjustment for confounding factors: adjusted hazard ratios (95% confidence intervals) - 1.30 (1.20-1.41), 1.56 (1.39-1.76), and 2.15 (1.77-2.61), respectively. Similar results were obtained for infection-related and cardiovascular mortality. CONCLUSION: This nationwide cohort study conducted in Japan suggested that AVF usage may have the lowest risk of all-cause mortality. The study also suggested that the usage of AS may be associated with better survival rates compared to those of TC-CVC in patients who are not suitable for AVF or AVG.

Glycated albumin to glycated hemoglobin ratio and mortality in diabetic patients on dialysis: a new association.

BACKGROUND: Hemoglobin A1c (A1c) and glycated albumin (GA) are two blood glycated proteins commonly used to monitor glycemic control in dialysis patients with diabetes. However, little is known about the association between the GA/A1c ratio and mortality in these populations. Here, we examine these associations using a nationwide cohort. METHODS: We enrolled 28 994 dialysis patients with diabetes who met our inclusion criteria (female, 32.9%; mean age, 67.4 ± 11.6 years; mean dialysis duration, 6.3 ± 5.8 years). After dividing the patients into groups based on GA/A1c quantiles and adjusting for 18 potential confounders, adjusted hazard ratios (HR) and 95% confidence limits were calculated for 3-year mortality and cause-specific mortalities. Additionally, propensity score matching analyses were used to compare mortalities between the low and high GA/A1c groups. RESULTS: After adjusting for possible confounders, significantly increased mortality was found in patients with GA/A1c ratios of 3.6-4.0 [HR 1.21 (1.10-1.34)] or higher [HR 1.43 (1.30-1.58)] than in those with GA/A1c ratios of 3.0-3.3. The risks of infectious and cardiovascular death were higher in these patients regardless of their nutritional status. In the propensity score matching analyses, significantly increased mortality was consistently found in those with a higher ratio (≥3.3) [HR 1.23 (1.14-1.33)] than in those with a lower ratio. CONCLUSIONS: The GA/A1c ratio was significantly associated with 3-year mortality, especially infectious and cardiovascular mortality, in dialysis patients with diabetes. This ratio may be a promising new clinical indicator of survival in these patients, independent of their current glycemic control and nutritional markers.

[A favorable clinical course of acute myeloid leukemia with t (6;21;8)(p23;q22;q22)].

Variants of the t (8;21) (q22;q22) involving chromosome 8, 21, and other chromosomes account for about 3% of all t (8;21) (q22;q22) in patients with acute myeloid leukemia (AML). However, the prognosis of AML with variant t (8;21) remains unknown due to the scarcity of reported cases. Herein we report a case of AML with t (6;21;8) (p23;q22;q22). Fluorescence in situ hybridization confirmed a RUNX1-RUNX1T1 fusion signal on the derivative chromosome 8. This is the first report on a variant of t (8;21) involving the breakpoint 6p23. After induction chemotherapy, our patient achieved complete remission and has been stable for four years.

[Klinefelter's syndrome diagnosed at the onset of acute myeloid leukemia with inv (16) following treatment for germ cell tumor].

A 22-year-old man with a history of mediastinal germ cell tumor, which was diagnosed at age 20 and remained disease-free after chemotherapy, was diagnosed with acute myeloid leukemia (AML) M2 in January 2020. Karyotype analysis of bone marrow (BM) specimen at diagnosis detected 47,XXY, inv (16) in all cells. Following induction treatment, he achieved complete remission with a remarkable decrease in the minimal residual disease marker. Although considered related to therapy, the AML had a prognostically favorable karyotype, and the initial treatment response was very good. He had no human leukocyte antigen-matched sibling donor candidate. Thus, allogeneic hematopoietic stem cell transplantation was not scheduled at the first complete remission. After three cycles of consolidation therapy, he remained disease-free for over one year. Karyotype analysis of BM during remission revealed that all analyzed cells harbored 47,XXY, and Klinefelter syndrome (KS) was diagnosed. Although the patient experienced an adjustment disorder on KS diagnosis, he had overcome the difficulty with the assistance of psycho-oncologists, clinical psychologists, and genetic counselors. Herein, we report this rare case of KS that manifested after AML diagnosis following mediastinal germ cell tumor treatment.

[Haploidentical hematopoietic stem cell transplantation for graft failure in myelodysplastic syndrome/myeloproliferative neoplasm-unclassifiable complicated with Stenotrophomonas maltophilia bacteremia].

A 60-year-old woman with myelodysplastic syndrome/myeloproliferative neoplasm-unclassifiable underwent unrelated bone marrow transplantation from a human leukocyte antigen (HLA) 8/8 allele-matched male donor. Neutrophil engraftment was achieved on day 29. Fluorescence in situ hybridization of sex chromosomes demonstrated complete donor chimerism. The red blood cell and platelet transfusion dependence continued, and the neutrophil count decreased gradually. Despite prolonged administration of broad-spectrum antibiotics for febrile neutropenia, blood cultures on days 46 and 58 returned positive for Stenotrophomonas maltophilia (SM). Contrast-enhanced computed tomography revealed multiple nodules of septic emboli in the lungs and kidneys, suggesting a disseminated SM infection. Antibiotic therapy was conducted based on antimicrobial susceptibility testing. However, the blood cell count failed to normalize and a secondary graft failure was diagnosed. A HLA-haploidentical peripheral-blood stem-cell transplantation from the patient's son was performed on day 134 after the initial transplantation. Neutrophil engraftment was achieved on day 11. Red blood cells and platelets were also engrafted. After the resolution of the SM bacteremia, the patient was discharged on day 63. The prognosis of the SM bacteremia with neutropenia is poor. Antibiotic treatment based on antimicrobial susceptibility testing and a second transplant from an HLA-haploidentical donor likely contributed to the successful outcome in this patient.

[Tisagenlecleucel for relapsed/refractory diffuse large B-cell lymphoma: real-world data from single institute experience].

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the approach to patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). This study retrospectively analyzed patients treated with commercially available tisagenlecleucel at our hospital and evaluated its safety and effectiveness. Of the 21 patients evaluated, any grade and grade ≥3 cytokine release syndrome (CRS) occurred in 85.7% and 9.5% of the patients, respectively. A total of 66.7% received tocilizumab and 28.6% received glucocorticoids for the treatment of CRS. The complete response (CR) rate at 3 months was 61.9% (95% confidence interval [CI] 38.4-81.9). After a median follow-up of 6.3 months following CAR-T infusion, the progression-free survival (PFS) and overall survival rates at 6 months were 53.1% (95%CI 28.3-72.7) and 69.2% (95%CI 43.7-84.9), respectively. Severe cytopenia and hypogammaglobulinemia occurred frequently following CAR-T infusion. Eight patients (38.1%) had comorbidities that would have made them ineligible for leukapheresis in the JULIET trial. However, the presence of comorbidities at the time of leukapheresis had no significant effect on the rates of CR, PFS, and adverse events. Tisagenlecleucel for r/r DLBCL in the real-world setting showed high efficacy and manageable safety profile comparable with the pivotal trial.

Loss-Modulation-Based Wavelength-Range Shifting of Tunable EDF Ring Laser with Cascaded-Chirped Long-Period Fiber Grating for Temperature Measurement.

A novel tunable Erbium-doped fiber ring laser (EDFRL) with a cascaded-chirped long-period fiber grating (C-CLPG) as a wavelength selection filter is proposed from the viewpoint of the sensor use, in which a variable optical attenuator (VOA) is employed as an intracavity loss modulator to change the oscillation wavelength region so that the resultant tuning wavelength range is widened. In the demonstrative experiment for temperature measurements, oscillation over the wavelength range of 12.85 nm (1557.62~1570.47 nm), which is more than three times range of the previously presented laser and is equivalent to 64 °C in terms of temperature change, was achieved, while a single-wavelength oscillation was maintained. In addition, a practical technique for realizing a temperature measurement by combining with the VOA control is also discussed.

Facial radiance influences facial attractiveness and affective impressions of faces.

OBJECTIVE: Facial attractiveness has been reported to be influenced by visual features such as facial shape and the colour and texture of the skin. However, no empirical studies have examined the effects of facial skin radiance on facial attractiveness. The present study investigated whether types of skin reflection (i.e. radiant, oily and shiny, and matte) and the position of the reflection on the face influence facial attractiveness and other affective impressions. METHODS: A total of 160 female participants (1) estimated the ages and (2) evaluated attractiveness and other impressions of unfamiliar female faces in a total of seven skin reflection conditions. These conditions incorporated three types of reflection (i.e. radiant, oily and shiny, and matte) and three positions of the reflection on the face (i.e. entire facial skin, only cheeks, and only T-zone). RESULTS: The facial images of radiance on entire faces were rated as appearing younger than the facial images of oily shine on entire faces and the matte faces. Attractiveness ratings and other positive impressions increased in the order of the matte (ranked lowest), the oily shine on entire face, and the radiance on entire face (ranked highest) conditions. The reflection position also influenced facial attractiveness: attractiveness ratings and other positive impressions were higher in the radiance on entire face condition than in the radiant cheeks and the radiant T-zone conditions. Interestingly, the radiant cheek faces were rated more radiant and healthier but less feminine and less bright than the radiant T-zone faces. CONCLUSION: These results suggest that facial radiance enhances facial attractiveness and conveys a wide variety of positive impressions on the observer. The magnitude of the effects of cheek radiance and T-zone radiance differs across various affective impressions. Nevertheless, the results demonstrate that cheek and the T-zone radiance both contribute to higher attractiveness and other positive impressions of the radiance on entire faces. We believe that our findings can contribute as a guide to the enhancement of positive facial impressions by means of skin radiance, thereby leading to a better understanding of the value of skincare and base makeup.

OBJECTIF: Selon certaines études, l'attractivité du visage viendrait de caractéristiques visuelles telles que la forme du visage ainsi que la couleur et la texture de la peau. Cependant, aucune étude empirique n'a examiné les effets de l'éclat de la peau sur l'attractivité du visage. La présente étude s'est intéressée aux divers types de reflets de la peau (par exemple une peau lumineuse, une peau grasse et luisante ou une peau mate) et à leur position sur le visage, et a cherché à savoir s'ils influençaient l'attractivité du visage et d'autres impressions d'ordre affectif. MÉTHODES: Au total, 160 participantes 1) ont estimé l'âge et 2) ont évalué l'attractivité et d'autres impressions de visages féminins inconnus sur sept types de reflets de la peau au total. Ces états comprenaient trois types de reflets (lumineux, gras et mat) et trois positions des reflets sur le visage (toute la peau du visage, joues uniquement et partie yeux-nez [« zone T ¼] uniquement). RÉSULTATS: Les photos de visages caractérisées par un éclat sur tout le visage ont été considérées comme étant plus jeunes que celles dont la peau était grasse-luisante sur l'ensemble du visage et que les visages à peau mate. Les notes attribuées pour l'attractivité et les autres impressions positives augmentent dans l'ordre suivant : peau mate (note la plus basse), peau grasse-luisante sur tout le visage et luminosité sur tout le visage (note la plus haute). La position du reflet a elle aussi joué un rôle sur les notes attribuées à l'attractivité des visages, et les autres impressions positives ont obtenu des scores plus élevés pour une luminosité de tout le visage que pour des joues lumineuses et une zone T lumineuse. Il est intéressant de noter que les visages aux joues lumineuses ont été jugés plus lumineux et plus sains, mais moins féminins et moins éclatants que les visages présentant une zone T lumineuse. CONCLUSION: Ces résultats suggèrent que l'éclat du visage améliore l'attractivité du visage et communique toutes sortes d'impressions positives à l'observateur. L'ampleur des effets de l'éclat sur les joues et sur la zone T diffère selon les différentes impressions d'ordre affectif. Néanmoins, les résultats démontrent que la luminosité des joues et de la zone T contribue à rendre le visage plus séduisant ainsi qu'à d'autres impressions positives suscitées par la luminosité de l'ensemble du visage. Nous sommes convaincus que nos résultats peuvent servir à guider la façon de renforcer l'impression positive produite par un visage en faisant ressortir la luminosité de la peau, et amener ainsi à mieux comprendre la valeur des soins de la peau et des bases de maquillage.

[Clinical features of tuberculosis among allogeneic hematopoietic stem cell transplantation recipients].

The incidence of tuberculosis (TB) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients is 10-40 times higher than that in the general population, which ranges from 0.1% to 5.5%. However, the clinical features of TB among allo-HSCT recipients in Japan remain unknown. We retrospectively analyzed the incidence of TB and the clinical features of culture-positive TB among allo-HSCT recipients at our hospital between 2002 and 2018. Of 1,047 recipients, 5 (0.4%) developed pulmonary TB (with an incidence rate of 472 per 100,000 population) at a median of 1,730 (range: 586-2,526) days after allo-HSCT. Three patients had chronic graft-versus-host disease upon the onset of TB, which was well-controlled with tacrolimus and/or steroid. Three of five patients completed TB treatment, and the disease did not flare up after therapy completion. The incidence of TB was higher in allo-HSCT recipients than in the general population (0.01%, with an incidence rate of 12.3 per 100,000 population). Therefore, TB should be considered a late complication among allo-HSCT recipients.

EDF ring laser using cascaded-chirped long period fiber grating for temperature measurement.

A novel tunable erbium-doped fiber ring laser (EDFRL) using a cascaded-chirped long period fiber grating (C-CLPG) as a wavelength selection element is proposed. The oscillation wavelength is determined by the one of the spectral peaks of the C-CLPG used, and the oscillation output provides a high signal to noise (S/N) ratio detection and a highly sensitive measurement of the temperature due to its high power and narrow spectral output. In the experiment, it is confirmed that the wavelength of the output shifts in accordance with the temperature-induced spectral shift of the C-CLPG transmittance spectrum and the temperature sensitivity is obtained to be ∼-0.2 nm/°C within the wavelength range of 1567.30 ∼ 1575.78 nm. The oscillation wavelength range is to be limited depending on the fringe spacing of the channeled spectrum of C-CLPG, which limits the temperature measurement range, but a data processing approach to solve this problem is additionally proposed and its availability is also presented.

Simultaneous multi-point measurement of strain and temperature utilizing Fabry-Perot interferometric sensors composed of low reflective fiber Bragg gratings in a polarization-maintaining fiber.

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.

Geriatric nutritional risk index as a useful prognostic factor in second allogeneic hematopoietic stem cell transplantation.

Second allogeneic hematopoietic stem cell transplantation (allo-HSCT) has a low survival outcome and a high non-relapse mortality (NRM) rate which is a major obstacle to this treatment. We hypothesized that the status of malnourishment after first allo-HSCT as represented by the geriatric nutritional risk index (GNRI) could be used as a prognostic factor to determine the outcomes of second allo-HSCT. A total of 108 patients with a median age of 42 (range, 17-69) years, who received second allo-HSCT for disease recurrence after first allo-HSCT from our institution, were included in this study. Low GNRI had a significant impact on NRM at 2 years after second allo-HSCT: 56.9% in patients with GNRI ≤ 92 compared with 27.5% in patients with GNRI > 92 (P = 0.002). In multivariate analysis, GNRI of ≤ 92 was the only significant factor for NRM (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.15-4.56, P = 0.018). High-risk disease status at second allo-HSCT (HR 2.74, 95% CI 1.46-5.14, P = 0.002) and GNRI of ≤ 92 (HR 1.70, 95% CI 1.02-2.82, P = 0.042) were identified as significant factors for overall survival (OS). A score of 1 was assigned to each factor, and the OS rate at 2 years after second allo-HSCT decreased according to the score: 53.0% in patients with score 0, 32.3% with score 1, and 2.5% with score 2 (P < 0.001). In conclusion, GNRI could be a useful predictor for the outcomes of second allo-HSCT. A prospective study in other cohorts is warranted to validate the findings of our study.

Long-term excess mortality after hip fracture in hemodialysis patients: a nationwide cohort study in Japan.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Identification of the novel odor active compounds "p-menthane lactones" responsible for the characteristic aroma of fresh peppermint leaf.

The comparative aroma extract dilution analysis (cAEDA) applied to the volatile fractions of two types of fresh mint leaves (Peppermint and Spearmint) revealed 20 odor-active peaks with high FD factors (≥64). Among the perceived odorants, five "sweet/milky" and "caramel-like/spicy" notes showing high FD factors were characteristic for the peppermint aroma, and were identified as p-menthane lactone derivatives. Especially, the three p-menthane lactone derivatives, "rel-(3S,3aS,6R,7aS)-dihydromintlactone, (3S,3aS,6R)-epoxymenthofurolactone, and 2E-ethylidene-5-methylcyclohexanone", were newly identified compounds in the peppermint. The biosynthetic routes of the p-menthane lactone derivatives have been suggested to be closely related to menthofuran. Therefore, these findings strongly suggest the possibility that the biosynthetic pathway leading to the p-menthane lactone derivatives via menthofuran plays a significantly important role in the formation of the characteristic aroma of peppermint.

Synergic Impact of Body Mass Index, Diabetes, and Age on Long-Term Mortality in Japanese Incident Hemodialysis Patients: A Cohort Study on a Large National Dialysis Registry.

OBJECTIVES: The relationships among body mass index (BMI), diabetes, age, and all-cause mortality in hemodialysis patients remain unclear. We examined BMI-stratified relationships between diabetes, age, and the risk of long-term mortality in incident hemodialysis patients. METHODS: This is a cohort study. Data were obtained from the national dialysis registry in Japan 2007 that included 35,415 incident hemodialysis patients and 6,061 patients aged ≥20 years with BMI data. Patients were divided into 6 categories according to baseline BMI (low: <18.5, normal: 18.5-25, Obesity: ≥25) and the presence or absence of diabetes. The primary outcome was all-cause mortality during a 5-year follow-up. Hazard ratios were estimated using Cox's model for the relationships among diabetes, BMI categories, and all-cause mortality, and adjusted for potential confounders. Patients with a normal BMI and non-diabetic were the reference category. We also examined the effects of age on these relationships. RESULTS: A total of 6,061 patients, including 3,239 with diabetes, were enrolled. During the follow-up, 31.0% and 30.7% of all and diabetic patients, respectively, died. Cox's regression analysis showed that low BMI, but not obesity, was independently associated with an increased risk of all-cause death in patients with and without diabetes. When patients were divided into 2 groups-younger and older than 60 years-the risk of mortality in both groups was increased in low BMI with diabetes. CONCLUSIONS: Among Japanese incident hemodialysis patients, low BMI increases the risk of all-cause mortality. The markedly high mortality rate in diabetic patients with low BMI regardless of age warrants attention.

Types of Erythropoietin-Stimulating Agents and Mortality among Patients Undergoing Hemodialysis.

BACKGROUND: Despite the widespread use of erythropoietin-stimulating agents (ESAs) to treat anemia in patients undergoing hemodialysis, the relative mortality risks associated with use of different types of ESAs are unknown. METHODS: To compare the mortality risk associated with use of short-acting ESAs versus long-acting ESAs, we conducted a nationwide cohort study of 194,698 hemodialysis patients in Japan who received either a short-acting (epoetin α/ß or epoetin κ) or a long-acting (darbepoetin or epoetin ß pegol) ESA. Study outcomes were 2-year all-cause and cause-specific mortality. In addition to Cox proportional hazards models, we performed an instrumental variable analysis in which facility-level long-acting ESA prescription rates were taken as the instrumental variable. RESULTS: During the 2-year follow-up period, 31,557 deaths occurred. In a multivariable Cox model, long-acting ESA users had a 13% higher rate of deaths compared with short-acting ESA users, a significant difference (P<0.001). Similar results were obtained in other analyses. This difference in risk was pronounced among patients receiving high doses of ESA (for whom the adjusted 2-year number needed to harm for death was 30.8). Long-acting ESA use was associated with an increased rate of death from cardiovascular diseases, infection, and malignancies. In the instrumental variable analysis, long-acting ESA users remained at a significantly higher risk of death. Compared with anemic (hemoglobin 9.0-9.9 g/dl) short-acting ESA users, long-acting ESA users who achieved more optimal hemoglobin levels (10.0-10.9 g/dl) showed a higher mortality rate. CONCLUSIONS: Among patients undergoing hemodialysis, use of long-acting ESAs might be associated with a higher risk of death than use of short-acting ESAs.

[Vacuolar myelopathy after allogeneic bone marrow transplantation in a patient with acute lymphoblastic leukemia].

Vacuolar myelopathy (VM) is known to be a neurological complication in patients with acquired immunodeficiency syndrome (AIDS). In autopsy-based studies, VM was reported in approximately 20-50% of patients with AIDS. It manifests in various says, mainly presenting as a painless spastic paraparesis with a sensory ataxia. We present a rare case of VM after bone marrow transplantation (BMT) in a patient without AIDS. A 50-year-old man developed weakness in the lower legs, leg muscle atrophy, and difficulty in walking 86 days after BMT. The patient died from septic shock on day 309. The autopsy revealed intralamellar vacuolation in the spinal white matter, which was compatible with VM.

Predilution online hemodiafiltration is associated with improved survival compared with hemodialysis.

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.