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Objective: This study aimed to develop a Japanese version of the New Freezing of Gait Questionnaire (NFOG-Q) and investigate its validity and reliability., Methods: After translating the NFOG-Q according to a standardised protocol, 56 patients with Parkinson's disease (PD) were administered it. Additionally, the MDS-UPDRS parts II and III, Hoehn and Yahr (H&Y) stage, and number of falls over 1 month were evaluated. Spearman's correlation coefficients (rho) were used to determine construct validity, and Cronbach's alpha (α) was used to examine reliability., Results: The interquartile range of the NFOG-Q scores was 10.0-25.3 (range 0-29). The NFOG-Q scores were strongly correlated with the MDS-UPDRS part II, items 2.12 (walking and balance), 2.13 (freezing), 3.11 (freezing of gait), and 3.12 (postural stability) and the postural instability and gait difficulty score (rho = 0.515-0.669), but only moderately related to the MDS-UPDRS item 3.10 (gait), number of falls, disease duration, H&Y stage, and time of the Timed Up-and-Go test (rho = 0.319-0.434). No significant correlations were observed between age and the time of the 10-m walk test. The internal consistency was excellent (α = 0.96)., Conclusions: The Japanese version of the NFOG-Q is a valid and reliable tool for assessing the severity of freezing in patients with PD., (© 2024. The Author(s).)

Acute graft-versus-host disease (aGvHD) is a major complication after allogeneic hematopoietic stem cell transplantation in Japan and other countries. Nearly one-third of patients do not respond to standard systemic steroid therapy and no standard second-line treatment has been established in Japan. We report efficacy and safety findings of ruxolitinib versus best available therapy (BAT) from a subgroup analysis of the international, phase 3 REACH2 study in Japanese patients with steroid-refractory aGvHD. The primary endpoint was overall response rate (ORR) at day 28. Overall, 9 patients received ruxolitinib and 21 received BAT. The ORR at day 28 (88.9% vs 52.4%) and durable ORR at day 56 (66.7% vs 28.6%) were higher with ruxolitinib versus BAT. The estimated cumulative incidence of loss of response at 6 months was 12.5% with ruxolitinib and 18.2% with BAT. The median failure-free survival was longer with ruxolitinib versus BAT (2.73 vs 1.25 months). The most common adverse events up to day 28 in the ruxolitinib and BAT groups were anemia (55.6% vs 19.0%) and thrombocytopenia (44.4% vs 4.8%, respectively). Ruxolitinib showed better efficacy outcomes and a consistent safety profile compared with BAT in the Japanese subgroup, and the findings were consistent with overall study results., (© 2024. The Author(s).)

Purpose: This study aimed to evaluate the incidence of bloodstream infection (BSI) among patients undergoing hematopoietic stem cell transplantation (HSCT) for teeth indicated for extraction., Methods: Patients who underwent HSCT at Toranomon Hospital (Tokyo, Japan) between January 2017 and December 2019 were retrospectively evaluated. The incidence of BSI among patients with teeth indicated for extraction who did not undergo extraction (oral high-risk group) and patients who did not have this risk (oral low-risk group) was compared., Results: Among the 191 consecutive patients included in this study, 119 patients were classified as undergoing high-risk transplantation. BSI after HSCT was observed in 32 out of 60 (53.3%) patients and 56 out of 131 (42.7%) patients in the oral low-risk and oral high-risk groups, respectively (p = 0.173). Multivariable analyses revealed that the presence of > 3 teeth as intraoral sources of infection and age over 50 years were determinants of BSI originating from the oral cavity after engraftment (odds ratio [OR], 9.11; 95% confidential interval [CI] 2.27-36.61]; p = 0.002; OR, 3.22; CI [1.47-7.08], p = 0.004, respectively)., Conclusion: In patients undergoing HSCT, the presence of less than three intraoral sources of infection did not affect the incidence of BSI after HSCT., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study examined the non-inferior efficacy of telenutrition education compared with face-to-face nutrition education in managing glycemic control in people with type 2 diabetes mellitus (T2DM). Participants had T2DM and a glycated hemoglobin (HbA1c) ranged 6.5-9.5%. Thirty participants were randomly assigned to either the telenutrition or face-to-face nutrition education group. During the 32-week intervention period, the participants received four sessions on nutrition education from a registered dietitian at the hospital. The telenutrition group received remote education via a videoconferencing platform. Face-to-face nutrition education was conducted using paper-based instructions. The main outcome measure was the non-inferiority of HbA1c levels in the telenutrition group compared to the face-to-face nutrition group. The non-inferiority of telenutrition education was considered valid if the intergroup difference in the mean values of the change in HbA1c had a bilateral 95% confidence interval (CI) upper limit below 0.40%. The intergroup difference in the mean HbA1c change from baseline to the fourth nutrition education session was -0.11 (95% CI -0.54-0.32) for both groups. The upper limit of the bilateral 95% CI was 0.32%, which was below the 0.40% non-inferiority margin (non-inferiority test; p = 0.011). Telenutrition education was not inferior to face-to-face nutrition education for glycemic management in people with T2DM.

Background: Japan has the second highest prevalence of dialysis use in the world. Approximately 40% of patients who begin dialysis have diabetic kidney disease (DKD). Local governments and medical facilities are required to provide preventive measures against worsening diabetes mellitus (DM). However, the percentage of patients with DM who receive such screening or interventions for DKD is unclear. This study aimed to reveal to what extent screening for DKD and preventive measures against worsening DKD are performed in patients with DM, using an administrative database in a municipality., Methods: This was a cross-sectional study that used the Kyoto-city's administrative medical and long-term care database. Patients with a diagnosis of DM and receiving antidiabetic medication between 2013 and 2018 were defined as patients with DM and included. Patients with DKD were defined as those diagnosed with diabetic nephropathy or those with chronic kidney disease. We described the characteristics of patients with DM, diabetic complications, and extent of DKD screenings and preventive efforts against worsening of DM by fiscal year., Results: Across fiscal years, 25.8% to 27.5% of patient with DM had DKD. More than 3% of patients were on dialysis due DM in each fiscal year; approximately 15% started receiving dialysis that year. The percentage of patients who were regularly prescribed antidiabetic medication and received glycosylated hemoglobin testing ranged from 64.0% to 67.2% and from 30.6% to 36.5%, respectively. Urine microalbuminuria testing at least once a year occurred in 9.3% to 10.0%. The percentage of patients who received nutritional guidance ranged from 19.0% to 21.0%. Approximately 1% of patients received guidance for preventing DM from progressing to a disease that requires dialysis each fiscal year., Conclusion: This study from Japan, where a super-aging society has developed, using an administrative database in a municipality covering most of the elderly population clearly demonstrated an evidence-practice gap in efforts to prevent worsening of DKD. Strengthening cooperation between government and medical facilities and support for providing preventive measures against DKD are urgently needed., Competing Interests: Author MKU is employed by the company Healthtech Laboratory, Inc. TS and YuT are employed by the Kyoto University and HealthTech Laboratory Inc., Joint Research Fund. TI is an unpaid external director of HealthTech Laboratory Inc. and reported receiving joint research grants from Healthtech Laboratory Inc. and TIS Inc. YoT reported receiving grants from the Japan Society for the Promotion of Science during the study. TN reported receiving grants from I&H Co. Ltd. and Nakagawa Pharmacy Co. outside of the submitted work and fees from Otsuka Pharmaceutical Co., Pfizer Japan Inc., Merck & Co. KK, Chugai Pharmaceutical Co., Takeda Pharmaceutical Co., Janssen Pharmaceutical KK, Boehringer Ingelheim International GmbH, Eli Lilly Japan KK, Baxter Ltd., Mitsubishi Tanabe Pharma Co., Novartis Pharma KK, and Allergan Japan KK outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from a joint research grant from Healthtech Laboratory Inc. and Kyoto University, a joint research grant from Healthtech Laboratory Inc., Towa Pharmaceutical Co., Ltd., and TIS Inc., and a joint research grant from Kyoto University, Healthtech Laboratory Inc., and TIS Inc. The funders (Healthtech, Laboratory Inc., Towa Pharmaceutical Co., Ltd., and TIS Inc.) had the following involvement in the study: participation in the construction of the concept of the study, study design, analysis, and preparation of the manuscript., (Copyright © 2023 Tateyama, Shimamoto, Uematsu, Taniguchi, Nishioka, Yamamoto, Okada, Takahashi, Nakayama and Iwami.)

No studies showed the association between weight-loss behaviors before pregnancy and postpartum depression (PPD). We analyzed data from the nation-wide birth cohort study, the Japan Environment and Children's Study. Self-administrated questionnaires answered by 62,446 women was analyzed using logistic regression analysis. PPD was assessed using the Edinburgh Postnatal Depression Scale at 1 month after delivery. Women using at least one weight-loss method had higher risk of PPD than women using no weight-loss methods [women without antenatal psychological distress according to Kessler 6-Item Psychological Distress score: adjusted odds ratio (aOR) 1.318, 95% confidence interval (CI) 1.246-1.394; women with antenatal psychological distress: aOR 1.250, 95% CI 0.999-1.565]. Using extremely unhealthy weight-loss methods was associated with PPD compared with no use of each weight-loss method (vomiting after eating: aOR 1.743, 95% CI 1.465-2.065; smoking: aOR 1.432, 95% CI 1.287-1.591; taking diet pills: aOR 1.308, 95% CI 1.122-1.520). The association between weight-loss behaviors and PPD varied according to pre-pregnancy BMI. In normal-weight women, the weight-loss method score, which indicates the degree of weight-loss method use, was associated with PPD. These results indicate using weight-loss methods before pregnancy is associated with an increased risk of PPD in Japanese women., (© 2023. The Author(s).)

Objectives: Isavuconazole is a convenient triazole antifungal agent with a broad antifungal spectrum. A randomized, open-label study (ClinicalTrials.gov, NCT03471988) was conducted to evaluate the efficacy and safety of isavuconazole in Japanese patients with deep-seated mycoses., Patients and Methods: In Cohort A, patients with aspergillosis (chronic pulmonary aspergillosis and invasive aspergillosis) were randomized in a 2:1 ratio to isavuconazole or voriconazole, and in Cohort B, patients with cryptococcosis and mucormycosis were assigned to isavuconazole for up to 84 days of treatment. The overall outcome was evaluated according to the clinical, radiological, and mycological responses at Days 42 and 84 and at the end of treatment (EOT)., Results: A total of 103 participants were enrolled and received the study drug. The overall response rate of patients with chronic pulmonary aspergillosis in the isavuconazole (52 patients) and voriconazole (27 patients) groups was 82.7% and 77.8% at EOT, respectively. The response rate in patients with cryptococcosis (10 patients, isavuconazole group only) was 90.0%. One of three participants with invasive aspergillosis and one of three participants with mucormycosis responded in the isavuconazole group. In the safety evaluation, the incidence of adverse events in participants with chronic pulmonary aspergillosis was similar in both groups. Adverse drug reactions were reported in 32 (61.5%) patients receiving isavuconazole and 23 (85.2%) patients receiving voriconazole., Conclusions: Isavuconazole showed efficacy and safety in Japanese patients with chronic pulmonary aspergillosis and cryptococcosis, for which the drug is not currently indicated., Competing Interests: Declaration of competing interest K.I. has received financial support for the present manuscript from Asahi Kasei Pharma Corporation; grants, consulting fees, and honoraria from Asahi Kasei Pharma Corporation, and honoraria from Pfizer, outside the submitted work. T.T. has received non-financial support for the present manuscript from Asahi Kasei Pharma Corporation; grants from MSD, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and Shionogi Pharma; honoraria from Sumitomo Dainippon Pharma, Pfizer, Kyorin Pharmaceutical, Fisher & Paykel Healthcare, and MSD; and participated on the advisory boards of GlaxoSmithKline, Roche Diagnostics, and Pfizer, outside the submitted work. T.M. has received non-financial support for the present manuscript from Asahi Kasei Pharma Corporation; grants from Asahi Kasei Pharma Corporation, Pfizer, MSD, Astellas Pharma, Otsuka Pharmaceutical, Taisho Pharmaceutical, Daiichi Sankyo, Teijin Pharma, Mitsubishi Tanabe Pharma, Shionogi Pharma, Kyowa Kirin, Chugai Pharmaceutical, and AbbVie; consulting fees from Asahi Kasei Pharma Corporation, Pfizer, and Kyorin Pharmaceutical; honoraria and support for attending meetings from Asahi Kasei Pharma Corporation, Pfizer, MSD, Astellas Pharma, Sumitomo Dainippon Pharma, Janssen Pharmaceutical, AstraZeneca, GlaxoSmithKline, Taisho Pharmaceutical, Daiichi Sankyo, Meiji Seika Pharma, Eli Lilly, Novartis Pharma, Boehringer Ingelheim, Shionogi Pharma, Takeda Pharmaceutical, Gilead Sciences, Insmed, and Sanofi; and drugs and medical writing services from Pfizer and MSD, outside the submitted work. K.K. was a member of the Data Review Committee for Asahi Kasei Pharma Corporation during the conduct of the study; K.K. has received grants from Asahi Kasei Pharma Corporation, Sumitomo Dainippon Pharma, and MSD, outside the submitted work. K.A. has received grants from Asahi Kasei Pharma Corporation, Sumitomo Dainippon Pharma, and Takeda Pharmaceutical, and honoraria from Pfizer and Janssen Pharmaceutical, outside the submitted work. H.M. has received consulting fees and honoraria from Asahi Kasei Pharma Corporation, outside the submitted work. F.O. was a member of the Data Review Committee for Asahi Kasei Pharma Corporation during the conduct of the study; F.O. has received consulting fees from Asahi Kasei Pharma Corporation, outside the submitted work. Y.K. has received grants from Asahi Kasei Pharma Corporation, Sumitomo Dainippon Pharma, and Pfizer, and honoraria from Asahi Kasei Pharma Corporation, Sumitomo Dainippon Pharma, Pfizer, MSD, Astellas Pharma, and Janssen Pharmaceutical, outside the submitted work. H.K. was a member of the Data Review Committee for Asahi Kasei Pharma Corporation during the conduct of the study; H.K. has received honoraria from MSD, Sumitomo Dainippon Pharma, Astellas Pharma, Pfizer, and Shionogi Pharma, outside the submitted work. S.K. was a member of the Data Review Committee for Asahi Kasei Pharma Corporation during the conduct of the study; S.K. has received consulting fees from Asahi Kasei Pharma Corporation, and honoraria from MSD, Sumitomo Dainippon Pharma, Pfizer, Bristol-Myers Squibb, Eisai, Takeda Pharmaceutical, Janssen Pharmaceutical, Meiji Seika Pharma, Astellas Pharma, Kyowa Kirin, Chugai Pharmaceutical, Ono Pharmaceutical, Nippon Kayaku, SymBio Pharmaceuticals, and Nippon Shinyaku, outside the submitted work. M.K. is an employee and stockholder of Asahi Kasei Pharma Corporation; M.K. also has patent 2021-157676 pending with Asahi Kasei Pharma Corporation. M.M. is an employee of Asahi Kasei Pharma Corporation; M.M. also has patent 2021-157676 pending with Asahi Kasei Pharma Corporation. Y.N. was a member of the Data Review Committee for Asahi Kasei Pharma Corporation during the conduct of the study; Y.N. has received consulting fees from Asahi Kasei Pharma Corporation, outside the submitted work. All other authors: none to declare., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Total knee arthroplasty (TKA) is an established surgical treatment for advanced knee osteoarthritis by which patients can expect improvement of knee pain and function. Although many surgeons have investigated limb alignment after TKA, changes in coronal positional relation between the femur and tibia are not known well., Methods: Radiographs of 105 knees of young Japanese patients between 20 and 49 years-old (60 men and 45 women) without osteoarthritic changes who received arthroscopic surgeries at our hospital were used in this study. Using 2D-templates of the medial pivot design (the FINE total knee), we simulated TKA on a SYNAPSE-PACS software. First, the femoral component was placed in normal knee alignment and then was merged to the medial concave of the insert where the tibial component was placed in neutral alignment. The length of the mediolateral shift of the femoral component was measured as an estimate of lateral shift of the femoral condyle, of which association with radiographic parameters including the femorotibial angle (FTA), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA) was analyzed. Subjects were classified into three groups according to the femoral component size that was chosen in simulation of TKA, and the lateral shift of the femoral condyle was compared between groups., Results: The estimated mean lateral shift of the femoral condyle was 5.99 ± 1.98 mm and was greater in males than females (p < 0.05). Also, it was most highly correlated with the medial proximal tibial angle (MPTA) (r = - 0.553, p < 0.01). A group receiving larger component sizes significantly shifted more laterally compared with a group receiving smaller component sizes (p < 0.01)., Conclusions: These results suggest that the coronal positional relation between the femur and tibia is altered and subsequent ligament imbalance may occur after mechanically aligned TKA using the medial pivot design., (© 2022. The Author(s).)

Study Design: A prospective, multicenter study., Objective: To evaluate the usefulness of transcranial motor-evoked potentials (Tc-MEPs) during supine-to-prone position change for thoracic ossification of the posterior longitudinal ligament (T-OPLL)., Summary of Background Data: Supine-to-prone position change might be a risk of spinal cord injury in posterior decompression and fusion surgeries for T-OPLL., Methods: The subjects were 145 patients with T-OPLL surgically treated with posterior decompression and fusion using Tc-MEPs in 14 institutes. Tc-MEPs were monitored before surgery from supine-to-prone position and intraoperatively in seven institutes and only intraoperatively in the other seven institutes because of disapproval of the anesthesia department. In cases of Tc-MEP alert after position change, we adjusted the cervicothoracic posture. When the MEP did not recover, we reverted the position to supine and monitored the Tc-MEPs in supine position., Results: There were 83 and 62 patients with/without Tc-MEP before position change to prone (group A and B). The true-positive rate was lower in group A than group B, but without statistical significance (8.4% vs. 16.1%, P = 0.12). In group A, five patients who had Tc-MEP alert during supine-to-prone position change were all female and had larger body mass index values and upper thoracic lesions. Among the patients, three underwent surgeries after cervicothoracic alignment adjustment, and two had postponed operations to 1 week later with halo-vest fixation because of repeated Tc-MEP alerts during position change to prone. The Tc-MEP alert at exposure was statistically more frequent in group B than in group A ( P = 0.033)., Conclusion: Tc-MEP alert during position change is an important sign of spinal cord injury due to alignment change at the upper thoracic spine. Tc-MEP monitoring before supine-to-prone position change was necessary to prevent spinal cord injury in surgeries for T-OPLL., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Prospective multicenter study., Objective: To examine transcranial motor-evoked potential (Tc-MEP) waveforms in intraoperative neurophysiological monitoring in surgery for intradural extramedullary (IDEM) tumors, focused on the characteristics for cervical, thoracic, and conus lesions., Summary of Background Data: IDEM tumors are normally curable after resection, but neurological deterioration may occur after surgery. Intraoperative neurophysiological monitoring using Tc-MEPs during surgery is important for timely detection of possible neurological injury., Methods: The subjects were 233 patients with IDEM tumors treated surgically with Tc-MEP monitoring at 9 centers. The alarm threshold was ≥70% waveform deterioration from baseline. A case with a Tc-MEP alert that normalized and had no new motor deficits postoperatively was defined as a rescue case. A deterioration of manual muscle test score ≥1 compared to the preoperative value was defined as postoperative worsening of motor status., Results: The 233 patients (92 males, 39%) had a mean age of 58.1 ± 18.1 years, and 185 (79%), 46 (20%), and 2 (1%) had schwannoma, meningioma, and neurofibroma. These lesions had cervical (C1-7), thoracic (Th1-10), and conus (Th11-L2) locations in 82 (35%), 96 (41%), and 55 (24%) cases. There were no significant differences in preoperative motor deficit among the lesion levels. Thoracic lesions had a significantly higher rate of poor baseline waveform derivation (0% cervical, 6% thoracic, 0% conus, P < 0.05) and significantly more frequent intraoperative alarms (20%, 31%, 15%, P < 0.05). Use of Tc-MEPs for predicting neurological deficits after IDEM surgery had sensitivity of 87% and specificity of 89%; however, the positive predictive value was low., Conclusion: Poor derivation of waveforms, appearance of alarms, and worse final waveforms were all significantly more frequent for thoracic lesions. Thus, amplification of the waveform amplitude, using multimodal monitoring, and more appropriate interventions after an alarm may be particularly important in surgery for thoracic IDEM tumors.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: A prospective multicenter observational study., Objective: To elucidate the efficacy of transcranial motor-evoked potentials (Tc(E)-MEPs) in degenerative cervical myelopathy (DCM) surgery by comparing cervical spondylotic myelopathy (CSM) to cervical ossification of the posterior longitudinal ligament (OPLL) and investigate the timing of Tc(E)-MEPs alerts and types of interventions affecting surgical outcomes., Summary of Background Data: Although CSM and OPLL are the most commonly encountered diseases of DCM, the benefits of Tc(E)-MEPs for DCM remain unclear and comparisons of these two diseases have not yet been conducted., Methods: We examined the results of Tc(E)-MEPs from 1176 DCM cases (840 CSM /336 OPLL) and compared patients background by disease, preoperative motor deficits, and the type of surgical procedure. We also assessed the efficacy of interventions based on Tc(E)-MEPs alerts. Tc(E)-MEPs alerts were defined as an amplitude reduction of more than 70% below the control waveform. Rescue cases were defined as those in which waveform recovery was achieved after interventions in response to alerts and no postoperative paralysis., Results: Overall sensitivity was 57.1%, and sensitivity was higher with OPLL (71.4%) than with CSM (42.9%). The sensitivity of acute onset segmental palsy including C5 palsy was 40% (OPLL/CSM: 66.7%/0%) whereas that of lower limb palsy was 100%. The most common timing of Tc(E)-MEPs alerts was during decompression (63.16%), followed by screw insertion (15.79%). The overall rescue rate was 57.9% (OPLL/CSM: 58.3%/57.1%)., Conclusion: Since Tc(E)-MEPs are excellent for detecting long tract injuries, surgeons need to consider appropriate interventions in response to alerts. The detection of acute onset segmental palsy by Tc(E)-MEPs was partially possible with OPLL, but may still be difficult with CSM. The rescue rate was higher than 50% and appropriate interventions may have prevented postoperative neurological complications.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Prospective multicenter study., Objective: The purpose of the study is to examine cases with poor baseline waveform derivation for all muscles in multichannel monitoring of transcranial motor-evoked potentials (Tc-MEPs) in spine surgery., Summary of Background Data: Intraoperative neuromonitoring (IONM) is useful for identifying neurologic deterioration during spinal surgery. Tc-MEPs are widely used for IONM, but some cases have poor waveform derivation, even in multichannel Tc-MEP monitoring., Methods: The subjects were 3625 patients (mean age 60.1 years, range 4-95; 1886 females, 1739 males) who underwent Tc-MEP monitoring during spinal surgery at 16 spine centers between April 2017 and March 2020. Baseline Tc-MEPs were recorded from the deltoid, abductor pollicis brevis, adductor longus, quadriceps femoris, hamstrings, tibialis anterior, gastrocnemius, and abductor hallucis (AH) muscles after surgical exposure of the spine., Results: The 3625 cases included cervical, thoracic, and lumbar lesions (50%, 33% and 17%, respectively) and had preoperative motor status of no motor deficit, and motor deficit with manual muscle testing (MMT) ≥3 and MMT <3 (70%, 24% and 6%, respectively). High-risk surgery was performed in 1540 cases (43%). There were 73 cases with poor baseline waveform derivation (2%), and this was significantly associated with higher body weight, body mass index, thoracic lesions, motor deficit of MMT <3, high-risk surgery (42/1540 [2.7%] vs. 31/2085 [1.5%], P < 0.05), and surgery for ossification of the posterior longitudinal ligament (OPLL). Intraoperative waveform derivation occurred in 25 poor derivation cases (34%) and the AH had the highest rate., Conclusion: The rate of poor baseline waveform derivation in spine surgery was 2% in our series. This was significantly more likely in high-risk surgery for thoracic lesions and OPLL, and in cases with preoperative severe motor deficit. In such cases, it may be preferable to use multiple modalities for IONM to derive multichannel waveforms from distal limb muscles, including the AH.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Prospective multicenter cohort study., Objective: The aim of this study was to validate an alarm point of intraoperative neurophysiological monitoring () formulated by the Monitoring Working Group (WG) of the Japanese Society for Spine Surgery and Related Research (JSSR)., Summary of Background Data: The Monitoring WG of the JSSR formulated an alarm point of IONM using transcranial electrical stimulation-muscle motor evoked potentials (Tc(E)-MEPs) and has conducted a prospective multicenter study. The validity of the JSSR alarm point of ≥ 70% decreased in Tc(E)-MEPs for each high-risk surgery and any other spine surgeries has not been verified., Methods: Patients who underwent spine and spinal cord surgery with IONM in 16 Japanese spine centers in the Monitoring WG of the JSSR from 2017 to 2018 were enrolled. The patients were divided into the high-risk surgery group (Group HR) and the common surgery group (Group C). Group HR was defined by ossification of the posterior longitudinal ligament (OPLL), spinal deformity, and spinal cord tumor. Group C was classified as other spine surgeries. The alarm point was defined as a ≥70% decrease in the Tc(E)-MEPs., Results: In Group HR, the sensitivity and specificity were 94.4% and 87.0%, respectively. In Group C, the sensitivity and specificity were 63.6% and 91.9%. The sensitivity in Group C was statistically lower than that in Group HR (P < 0.05). In Group HR, the sensitivity and specificity in OPLL were 100% and 86.9%, respectively. The sensitivity and specificity in spinal deformity were 87.5% and 84.8%, respectively, and the sensitivity and specificity in spinal cord tumors were 92.9% and 89.9%, respectively. The sensitivity and specificity in each high-risk surgery showed no significant difference., Conclusion: The alarm point of IONM by the Monitoring WG of the JSSR appeared to be valid for each disease in Group HR. Meanwhile, applying the JSSR alarm point for Group C potentially needed attention.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Pharmacogenetics/pharmacogenomics have enabled the detection of risk of human leukocyte antigen (HLA) variants for clozapine-induced agranulocytosis/granulocytopenia (CIAG). To apply this evidence to the clinical setting, we compared the cost-effectiveness of the proposed "HLA-guided treatment schedule" and the "current schedule" being used in Japan and the United Kingdom (UK) (absolute neutrophil count (ANC) cutoff at 1500/mm 3 ); in the "HLA-guided treatment schedules," we considered a situation wherein the HLA test performed before clozapine initiation could provide "a priori information" by detecting patients harboring risk of HLA variants (HLA-B*59:01 and "HLA-B 158T/HLA-DQB1 126Q" for Japanese and Caucasian populations, respectively), a part of whom can then avoid CIAG onset (assumed 30% "prevention rate"). For the primary analysis, we estimated the incremental cost-effectiveness ratio (ICER) of "HLA-guided treatment schedule" and "current schedule" used in Japan and the UK, using a Markov model to calculate the cost and quality-adjusted life years (QALYs) over a 10-year time period. Furthermore, as an explorative analysis, we simulated several situations with various ANC cutoffs (1000/mm 3 and 500/mm 3 ) and plotted the cost/QALYs for each option to identify the best, or estimate the next best candidate option applicable in actual clinical settings. The primary probabilistic analysis showed that the "HLA-guided treatment schedule" was more cost effective than the "current schedule"; the ICER was £20,995 and £21,373 for the Japanese and the UK populations, respectively. Additional simulation revealed that the treatment option of ANC cutoff at 500/mm 3 without HLA screening was the most cost-effective option; however, several options may be candidates to break away from the "current schedule" of ANC cutoff at 1500/mm 3 . Owing to its cost-effectiveness, we propose such pharmacogenetic-guided/pharmacogenomic-guided clozapine treatment for use in the real-world setting, which provides key information for optimization of clinical guidelines for high-risk patients for gradual change of clozapine treatment schedule under the safety consideration.

Background: We evaluated cases of esophageal squamous cell carcinoma (ESCC) that developed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our institution., Methods: Allo-HSCT was performed in 1534 patients (1776 cases) at our institution from 2001 to 2016. Overall, 602 patients were confirmed to have survived for 2 or more years and 154 underwent upper gastrointestinal endoscopy at least 1-year post-transplantation. ESCC was discovered in 17 patients (1.1%), 15 of whom had 31 lesions discovered at our institution (ESCC group). A retrospective comparative study was conducted with the remaining 137 patients for whom no ESCC was noted (non-ESCC group), and we also evaluated the clinicopathological characteristics of the ESCC group., Results: History of TBI (total body irradiation) and bone marrow transplant was significantly higher in the ESCC group. The mean time from transplantation to detection of ESCC was 82.3 months. Localization was upper thoracic in 12 cases, middle thoracic in 10, cervical in 4, lower thoracic in 3, and upper to lower thoracic in 2. Treatment comprised endoscopic submucosal dissection in 23 cases, surgery in 4, untreated due to worsening primary disease in 3, and chemoradiotherapy in 1., Conclusions: In this study, lesions were located in the cervical to upper thoracic esophagus in approximately 60% of all secondary ESCC cases after allo-HSCT. History of TBI and bone marrow transplantation are high risk of ESCC, and proactive screening endoscopy is desirable.

Background: Venetoclax plus azacitidine is indicated in the USA for the treatment of newly diagnosed acute myeloid leukaemia in older patients (≥75 years) or those ineligible for induction chemotherapy due to co-morbidities., Methods: In this phase 1/2 study (NCT02265731), Japanese patients (≥60 years) with untreated (ineligible for induction chemotherapy) or relapsed/refractory acute myeloid leukaemia received oral venetoclax 400 mg/day (3-day ramp up in cycle 1) plus subcutaneous or intravenous azacitidine 75 mg/m2 on days 1-7 per 28-day cycle until disease progression or unacceptable toxicity., Results: As of 10 December 2019, six patients were enrolled (median age: 75 years; untreated: n = 5; relapsed/refractory: n = 1); median treatment duration: 10.3 months (range, 0.7-29.4). Most common grade ≥ 3 adverse events were lymphopaenia and febrile neutropaenia (n = 4 each). Four patients reported serious adverse events; only an event of grade 3 fungal pneumonia was considered possibly related to both study drugs, requiring dose interruption of venetoclax and delay of azacitidine. Five (83%) patients had responses (complete remission: n = 3). Median time to first response of complete remission/complete remission with incomplete count recovery was 1.0 month (range, 0.8-5.5); median overall survival: 15.7 months (95% confidence interval: 6.2, not reached)., Conclusions: Venetoclax plus azacitidine was well tolerated and showed high response rates in Japanese patients with acute myeloid leukaemia., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Dengue fever outbreaks have been repeatedly reported in Côte d'Ivoire. During the 2019 outbreak, DENV-1 was the predominant strain and phylogenetic analysis of the DENV-1 genome obtained from the present patient who returned to Japan in January 2019 revealed a high homology with the 2013-2014 Southeast Asian strains. In a previous outbreak in 2017, DENV-1 accounted for 5% of the DENV serotypes. The endemic DENV-1 strain in Abidjan in 2019 could be a strain that was imported from Southeast Asia. Dengue virus can spread globally, and imported dengue fever cases could serve as an alert for outbreaks in the exporting country.

Limited data are available on Stenotrophomonas maltophilia bloodstream infections (SM-BSIs) and the therapeutic efficacy of trimethoprim-sulfamethoxazole (SXT) against SM-BSI in umbilical cord blood transplant (uCBT) recipients. Medical and microbiological records of adult patients who received uCBTs between December 2008 and December 2015 at Toranomon Hospital (Tokyo, Japan) were reviewed. The efficacy and safety of SXT were evaluated only for recipients who were treated with ≥7 days of intravenous SXT for SM-BSI (evaluation cohort). Of 561 uCBT recipients, 34 developed SM-BSI. Diabetes mellitus (P = .005) and age ≥ 60 years (P = .013) were significant independent risk factors for SM-BSI. Moreover, SM-BSI was identified as an independent risk factor for all-cause mortality up to 100 days following uCBT (P = .025). Of the 34 recipients with SM-BSI, 24 were treated with an intravenous SXT-containing regimen (iSXT-CR). Septic shock (P = .0021), pneumonia (P = .011), neutropenia (P = .0015), and systemic steroid administration (P = .018) were identified as significant independent risk factors for 7-day crude mortality. The evaluation cohort included nine recipients. Doses of SXT were 2.4 to 6.9 mg/kg/day of the trimethoprim component. Of the nine recipients, five developed SM-BSI during the pre-engraftment phase. The 30-day crude-mortality rate and clinical cure rate of the cohort were 22% and 67%, respectively. Only one of the nine recipients experienced significant neutrophil toxicity. In this study, the epidemiology of SM-BSI in uCBT recipients was determined and its negative impact on survival was demonstrated. A low- to moderate-dose iSXT-CR appeared to be a tolerable and important therapeutic option for SM-BSI in the uCBT setting, including during the pre-engraftment phase., (Copyright © 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The Japanese archipelago is located at the periphery of the continent of Asia. Rivers in the Japanese archipelago, separated from the continent of Asia by about 17 Ma, have experienced an intermittent exchange of freshwater fish taxa through a narrow land bridge generated by lowered sea level. As the Korean Peninsula and Japanese archipelago were not covered by an ice sheet during glacial periods, phylogeographical analyses in this region can trace the history of biota that were, for a long time, beyond the last glacial maximum. In this study, we analyzed the phylogeography of four freshwater fish taxa, Hemibarbus longirostris , dark chub Nipponocypris temminckii , Tanakia ssp. and Carassius ssp., whose distributions include both the Korean Peninsula and Western Japan. We found for each taxon that a small component of diverse Korean clades of freshwater fishes migrated in waves into the Japanese archipelago to form the current phylogeographic structure of biota. The replacements of indigenous populations by succeeding migrants may have also influenced the phylogeography.

Study Design: Prospective, multicenter, observational study., Objective: The aim of this study was to investigate the efficacy of intervention after an alert in intraoperative neurophysiological monitoring (IONM) using transcranial motor-evoked potentials (Tc-MEPs) during surgery for thoracic ossification of the posterior longitudinal ligament (T-OPLL)., Summary of Background Data: T-OPLL is commonly treated with posterior decompression and fusion with instrumentation. IONM using Tc-MEPs during surgery reduces the risk of neurological complications., Methods: The subjects were 79 patients with a Tc-MEP alert during posterior decompression and fusion surgery for T-OPLL. Preoperative muscle strength (manual muscle testing [MMT]), waveform derivation rate at the start of surgery (baseline), intraoperative waveform changes; and postoperative motor paralysis were examined. A reduction in MMT score of ≥1 on the day after surgery was classified as worsened postoperative motor deficit. An alert was defined as a decrease in Tc-MEP waveform amplitude of ≥70% from baseline. Alerts were recorded at key times during surgery., Results: The patients (35 males, 44 females; age 54.6 years) had OPLL at T1-4 (n = 27, 34%), T5-8 (n = 50, 63%), and T9-12 (n = 16, 20%). The preoperative status included sensory deficit (n = 67, 85%), motor deficit (MMT ≤4) (n = 59, 75%), and nonambulatory (n = 26, 33%). At baseline, 76 cases (96%) had a detectable Tc-MEP waveform for at least one muscle, and the abductor hallucis had the highest rate of baseline waveform detection (n = 66, 84%). Tc-MEP alerts occurred during decompression (n = 47, 60%), exposure (n = 13, 16%), rodding (n = 5, 6%), pedicle screw insertion (n = 4, 5%), posture change (n = 4, 5%), dekyphosis (n = 2, 3%), and other procedures (n = 4, 5%). After intraoperative intervention, the rescue rate (no postoperative neurological deficit) was 57% (45/79), and rescue cases had a significantly better preoperative ambulatory status and a significantly higher baseline waveform derivation rate., Conclusion: These results show the efficacy of intraoperative intervention following a Tc-MEP alert for prevention of neurological deficit postoperatively.Level of Evidence: 2., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Recent progress in genetic analysis technology has helped researchers understand the pathogenesis of acute myeloid leukemia (AML). Considering this progress, AML karyotype is still one of the most significant prognostic factors that provides risk-adapted treatment approaches. Karyotype changes during treatment have been observed at times, but their prognostic impact is sparse, especially on allogeneic stem cell transplantation (allo-SCT). Here, we retrospectively investigated the effect of chromosomal changes between diagnosis and pretransplantation on the prognosis of allo-SCT by analyzing the outcomes of 212 consecutive patients who underwent allo-SCT for the first time at Toranomon Hospital, Tokyo, Japan, between 2008 and 2018. Cytogenetic abnormalities at diagnosis and pretransplantation were categorized based on the 2017 European Leukemia Net risk stratification. Genetic abnormalities such as FLT3-ITD and NPM1 were not considered in this study due to lack of genetic information in most patients. We defined cytogenetic evolution as chromosomal changes classified from lower category to higher category. Seventeen patients (8%) had cytogenetic evolution between diagnosis and pretransplantation, and they showed a significantly worse relapse rate than those who were categorized in the intermediate group based on the karyotype at diagnosis (3-year confidence interval [CI] of relapse, 57.4% versus 24.9%; P < .01). In multivariate analysis, cytogenetic evolution before allo-SCT had a significant impact on the CI of relapse (hazard ratio [HR], 3.89; CI, 1.75 to 8.67; P < .01), as well as the high score of the hematopoietic cell transplantation-specific comorbidity index (HR, 0.54; CI, 0.31 to 0.94; P = .03), but had no significant impact on overall survival or nonrelapse mortality. These results indicate that cytogenetic evolution has a significant impact after allo-SCT and should be considered during AML treatment., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76 to 2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, times to defervescence were 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95% CI, 0.81 to 4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.)., (Copyright © 2020 Doi et al.)

Primary effusion-based lymphoma (EBL) presents as a malignant effusion in a body cavity. The clinicopathologic features and prognosis of primary human herpesvirus 8 (HHV8)-negative EBL remain unclear. We therefore conducted a retrospective study of 95 patients with EBL, regardless of HHV8 status, in Japan. Of 69 patients with EBL tested for HHV8, a total of 64 were negative. The median age of patients with primary HHV8-negative EBL at diagnosis was 77 years (range, 57-98 years); all 58 tested patients were negative for HIV. Primary HHV8-negative EBL was most commonly diagnosed in pleural effusion (77%). Expression of at least 1 pan B-cell antigen (CD19, CD20, or CD79a) was observed in all cases. According to the Hans algorithm, 30 of the 38 evaluated patients had nongerminal center B-cell (non-GCB) tumors. Epstein-Barr virus-encoded small RNA was positive in 6 of 45 patients. In 56 of 64 HHV8-negative patients, systemic therapy was initiated within 3 months after diagnosis. Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) or CHOP-like regimens with or without rituximab (n = 48) were the most common primary treatments. The overall response and complete response rates were 95% and 73%, respectively. Three patients did not progress without systemic treatment for a median of 24 months. With a median 25-month follow-up, the 2-year overall survival and progression-free survival rates were 84.7% and 73.8%. Sixteen patients died; 12 were lymphoma-related deaths. Thus, most EBL cases in Japan are HHV8-negative and affect elderly patients. The non-GCB subtype is predominant. Overall, primary HHV8-negative EBL exhibits a favorable prognosis after anthracycline-based chemotherapy., (© 2020 by The American Society of Hematology.)

A psychiatric ward in a general hospital might be suitable for people with dementia because of the comprehensive medical care available. The aim was to investigate the characteristics of 86 patients with dementia admitted to psychiatric ward in a general hospital. About 40% of the patients were admitted due to a diagnosis of dementia and the need for treatment of a physical disease. The expected roles of psychiatric ward in a general hospital for patients with dementia include the acute care of physical and psychological problems and a differential diagnosis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In July 2018, a Japanese traveler returning from Saudi Arabia was diagnosed with dengue. The dengue virus type 2 gene was detected from a whole blood sample. Phylogenetic analysis revealed that the strain was clustered with isolates from Singapore and India. Travelers to Saudi Arabia should be cautious about mosquito bites.

Aims/introduction: Advanced glycation end-products (AGEs), which are a major cause of diabetic vascular complications, accumulate in various tissues under chronic hyperglycemic conditions, as well as with aging in patients with diabetes. The loss of muscle mass and strength, so-called sarcopenia and dynapenia, has recently been recognized as a diabetic complication. However, the influence of accumulated AGEs on muscle mass and strength remains unclear. The present study aimed to evaluate the association of sarcopenia and dynapenia with accumulated AGEs in patients with type 2 diabetes., Materials and Methods: We recruited 166 patients with type 2 diabetes aged ≥30 years (mean age 63.2 ± 12.3 years; body mass index 26.3 ± 4.9 kg/m 2 ; glycated hemoglobin 7.1 ± 1.1%). Skin autofluorescence as a marker of AGEs, limb skeletal muscle mass index, grip strength, knee extension strength and gait speed were assessed., Results: Sarcopenia and dynapenia were observed in 7.2 and 13.9% of participants, respectively. Skin autofluorescence was significantly higher in patients with sarcopenia and dynapenia. Skin autofluorescence was the independent determinant for skeletal muscle mass index, grip strength, knee extension strength, sarcopenia and dynapenia., Conclusions: Accumulated AGEs could contribute to reduced muscle mass and strength, leading to sarcopenia and dynapenia in patients with type 2 diabetes., (© 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objectives: The aim of this study was to determine the appropriate height of a dental chair for the administration of effective chest compressions by female dentists., Materials and Methods: We asked 19 female dentists to perform metronome-guided chest compressions at a rate of 100 compressions per minute for 2 min on the floor and on a dental chair. We set the height of the dental chair to 76, 73, 70, 67, and 64 cm. We measured the compression depth and proportion of compressions performed at an adequate depth. We then compared the quality of chest compressions between the tall and short (relative to the average body height) groups of participants. We also asked the participants to specify their preferred compression height or condition for chest compression administration., Results: The participants recorded their maximum chest compression depth (35.0 ± 8.8 mm) at a height of 67 cm. There was no significant difference in chest compression depth between the tall and short groups, irrespective of the compression height. The maximum depth of chest compressions was achieved at a height of 67 cm (from the floor to the compression surface) in both groups, with no significant difference. The participants most frequently identified 67 cm as the most suitable height for the administration of chest compressions., Conclusion: For female dentists, a height of 67 cm is considered suitable for the administration of chest compressions in the standing position, regardless of physique., Competing Interests: All authors report no conflict of interests related to the manuscript., (©2019 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Despite recent developments in treatment modalities and diagnosis, the prognosis of advanced hepatocellular carcinoma (HCC) remains unsatisfactory. To gain insight into treatment decisions for HCC patients, their characteristics and treatment flow in the early and advanced stages were examined. HCC patients' characteristics and treatment flow were retrospectively analyzed using the Japanese medical claims database. The 8999 patients' mean age at HCC diagnosis was 71.1 years, with no difference between early (Stage I/II) and advanced (Stage III/IV) stages. The mean observation period was 26.2 months, shorter in advanced than in early stages. HCV hepatitis was reported in 52.0% of HCC patients, with concomitant hypertension in 53.4%, type 2 diabetes in 45.8%, cirrhosis in 39.3%, and hyperlipidemia in 15.5%. The rates of HCV hepatitis, hypertension, and hyperlipidemia decreased with stage progression. Analysis of treatment flow showed that, at all disease stages, transcatheter arterial chemoembolization (TACE) was the most common first to fourth-line treatment. Epirubicin was the most frequently (44.1%) used chemotherapeutic agent for first-line TACE, followed by miriplatin (23.6%) and cisplatin (12.3%). With stage progression, cisplatin use increased. Sorafenib was used concomitantly for first-line TACE in 3.2% of patients, and its use increased significantly in advanced stages. Clear differences in baseline characteristics and treatment flow between early and advanced stages were identified. Continuous analysis of the database with longer follow-up may provide useful information about treatment selection and prediction of outcome such as survival., Competing Interests: All authors are employees of Eisai Co., Ltd., Tokyo, Japan.

Background: In two phase 3 trials, elobixibat, a locally acting ileal bile acid transporter inhibitor, resolved constipation and was well tolerated in Japanese patients with chronic constipation. We analyzed the efficacy, safety, and impact on quality of life (QOL) of elobixibat in patients with symptomatically more severe constipation in the two phase 3 trials., Methods: This post hoc analysis of elobixibat treatment outcomes included data from a 2-week, randomized, placebo-controlled, phase 3 trial (10 mg/d), and a 52-week, open-label trial (5-15 mg/d) in subgroups with severe constipation defined as ≤2 spontaneous bowel movements (SBMs) and ≤3 Bristol Stool Form Scale score during the second week of the 2-week run-in period. We also analyzed the rates of abdominal pain, diarrhea, and QOL in subgroups according to sex, presence of constipation-predominant irritable bowel syndrome (IBS-C) and side effects., Key Results: In patients with severe constipation, there was significant improvement in the 10 mg elobixibat group compared to the placebo group in change in SBMs from baseline at week 1 (primary endpoint) of the 2-week trial. The differences between groups were reduced in patients with more severe constipation. Increasing the dose to 15 mg was effective for more severe constipation in improving the number of SBMs per week in the 52-week trial. Overall, elobixibat was well tolerated and improved QOL scores, irrespective of gender, presence of IBS-C or side effects., Conclusions & Inferences: Elobixibat is effective for symptomatically severe constipation, is well tolerated and improves QOL, irrespective of potentially confounding patient characteristics., (© 2019 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.)

Introduction: Recently, more and more generic drugs have been used for immunosuppressive drugs in the field of organ transplantation. Some reports have indicated that blood concentration of most generic drugs is difficult to maintain stability, and it may cause the difference in graft survival of transplanted organs between original drugs and generic drugs. In this article, we report the cases could not maintain blood concentration of generic drugs of mycophenolate mofetil (MMF)., Results: In 4 cases out of 5 cases that we had to change original MMF to generic MMF, there were cases that blood concentration level was not stabilized. There were possibility that the lowered blood concentration level of MMF caused a rejection, in two cases. Mean MMF trough level was decreased from 3.6 ± 1.9 μg/mL to 0.6 ± 0.4 μg/mL. Due to the early detection, it did not become severe or failure of graft function, however, we cannot deny the possibilities that side effects were increased and rejection rose. In these cases, we discontinued to use the generic drugs thereafter due to unstable plasma concentration of MMF., Discussion: Some reports have indicated that failure to maintain plasma concentration of MMF leads to rejection. Therefore, maintenance of effective plasma concentration and prevention of rejection are essential to long-term graft survival in kidney transplant., Conclusion: Generic drug formulations may exhibit differences in effects and absorption compared to the brand-name drug. If the generic drug should be used, patients should be closely monitored., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Severe fever with thrombocytopenia syndrome (SFTS) was first identified as an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV) in China and has also been found to be endemic to Japan and South Korea, indicating that SFTS is of great concern in East Asia. The aim of the present study was to determine the seroprevalence of SFTSV antibodies in humans and animals in SFTS-endemic regions of Japan. One of 694 (0.14%) healthy persons over 50 years of age and 20 of 107 (18.7%) wild and domestic animals in Ehime prefecture of western Japan were determined to be seropositive for SFTSV antibodies by virus neutralization test and ELISA, respectively. The seropositive person, a healthy 74-year-old woman, was a resident of the southwest part of Ehime prefecture engaged in citriculture and field work. This woman's sample exhibited neutralizing activity against SFTSV although she had neither a clear experience with tick bites nor SFTS-like clinical illness. These findings indicate that most people living in the endemic regions are not infected with SFTSV and suggest that most of the SFTS patients reported so far do not reflect the tip of an iceberg of people infected with SFTSV, but at the same time, that SFTSV infection does not always induce severe SFTS-associated symptoms. These findings also suggested that SFTSV has been maintained in nature within animal species and ticks., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Aim: To identify environmental and physical factors that predispose middle-aged and older Japanese adults to falls and fall-related fractures in the home., Methods: A cross-sectional survey was carried out in 2014. Self-administered questionnaires were distributed to 15 000 community-dwelling adults in Japan. The overall crude response rate was 13%. Response data were analyzed from 1561 individuals aged ≥40 years using multiple imputation to analyze missing data. We evaluated falls without fractures and fall-related fractures during the previous 3 years according to demographic, physical and environmental factors, including age, sex, long-term care insurance certification, type of house and barrier-free housing., Results: Of the 1561 adults (mean age 68.1 ± 13.0 years), 28% experienced a fall in the home. Among the individuals who experienced a fall, 11% experienced fall-related fractures. These individuals were more likely to be women (OR 2.4, 95.0% CI 1.1-5.1), have LTCI certification (OR 3.9, 95.0% CI 1.6-9.4) and be living in a barrier home (OR 4.0, 95.0% CI 1.6-9.8), after adjustment for covariates., Conclusions: Environmental factors, such as living in a barrier home, are critical for fall-related fractures, in addition to demographic and physical factors. A multidisciplinary approach that considers both physical and environmental factors is necessary for reducing the incidence of fall-related fractures among middle-aged and older Japanese adults. Geriatr Gerontol Int 2018; 18: 1372-1377., (© 2018 Japan Geriatrics Society.)

The Japan Marrow Donor Program (JMDP), established in 1991, has continued to grow in its capacity to facilitate unrelated bone marrow (BMT) and peripheral blood stem cell transplantation (PBSCT) for the past 25 years in Japan. The current donor pool is 463,465 (as of 31 December 2016) and 20,237 transplants were performed with the help of the Japanese Red Cross, government, and supporters. As JMDP introduced PBSCT in 2010, the vast majority of transplants are BMT. All donors are fully typed for HLA-A, B, C, and DR. The peak age of registered donors is around 40 years. The 8/8 HLA-matched donors are found in our registry for 96% of the patients and 54% of the patients receive a transplant. The median time between the initiation of donor search and the transplantation is approximately 122 days. The median interval between the initiation of donor search and identification of the first potential donor is 40 days. The most common diseases for which unrelated BMT/PBSCT is indicated are acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS), and malignant lymphoma. In recent years we have seen a marked increase in elderly patients who received BMT.

Objective: Nurses in cancer care are considered to be at risk for compassion fatigue because they are frequently exposed to patients' traumatic experiences. However, only a few effective empirical studies have been conducted in this field, and cognitive factors in particular have not been sufficiently studied. This study aims to describe the components of nurses' cognitive reactions from their exposure to cancer patients' traumatic experience to the onset of compassion fatigue., Methods: In this qualitative study, 30 nurses in cancer care were purposively selected. Data were collected through semistructured interviews and analyzed by using content analysis and the constant comparative method., Results: Forty attributes were identified from 613 statements and classified into 11 categories: sense of professional inadequacy, compassion for patients and their families, desire to support patients and their families, rumination on oneself or one's family, sense of professional mission, dissatisfaction with medical staff, desire to integrate with colleagues, desire to avoid one's duties, conflict between one's belief and reality, reconsideration of the meaning of life, and sense of powerlessness over cancer., Conclusions: This study identified important components of cognitive reactions of nurses who encounter the traumatic experiences of cancer patients in Japan. This information can contribute to the understanding of the onset of compassion fatigue and provide the foundation for nurses in cancer care to avoid and recover from compassion fatigue., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Cases of acute respiratory tract infection caused by Pteropine orthoreovirus (PRV) of the genus Orthoreovirus (family: Reoviridae) have been reported in Southeast Asia, where it was isolated from humans and bats. It is possible that PRV-associated respiratory infections might be prevalent in Southeast Asia. The clinical course of PRV is not fully elucidated., Methods: The virulence, pathology, and pathogenesis of two PRV strains, a human-borne PRV strain (isolated from a patient, who returned to Japan from Bali, Indonesia in 2007) and a bat-borne PRV (isolated from a bat [Eonycteris spelaea] in the Philippines in 2013) were investigated in BALB/c mice using virological, pathological, and immunological study methods., Results: The intranasal inoculation of BALB/c mice with human-borne PRV caused respiratory infection. In addition, all mice with immunity induced by pre-inoculation with a non-lethal dose of PRV were completely protected against lethal PRV infection. Mice treated with antiserum with neutralizing antibody activity after inoculation with a lethal dose of PRV showed a reduced fatality rate. In this mouse model, bat-borne PRV caused respiratory infection similar to human-borne PRV. PRV caused lethal respiratory disease in an animal model of PRV infection, in which BALB/c mice were used., Conclusions: The BALB/c mouse model might help to accelerate research on the virulence of PRV and be useful for evaluating the efficacy of therapeutic agents and vaccines for the treatment and prevention of PRV infection. PRV was shown for the first time to be a causative virus of respiratory disease on the basis of Koch's postulations by the additional demonstration that PRV caused respiratory disease in mice through their intranasal inoculation with PRV.

Accumulation of advanced glycation end-products (AGEs) is thought to contribute to muscle weakness in a diabetic animal model. Skin autofluorescence is a proposed marker for accumulation of AGEs in the skin. We aimed to investigate the relationship between AGEs accumulation, sarcopenia and muscle function of Japanese patients with type 1 diabetes. A total of 36 patients with type 1 diabetes participated in the present cross-sectional study. Sarcopenia parameters (skeletal muscle mass index and knee extension strength) were compared with subcutaneous AGEs accumulation using skin autofluorescence. The prevalence of sarcopenia and impaired knee extension strength was 16.6% (men 0.0%, women 22.2%) and 47.2% (men 22.2%, women 55.6%), respectively. Knee extension strength was negatively correlated with skin autofluorescence (r² = 0.14, P < 0.05), but not with skeletal muscle mass index. In conclusion, the AGEs accumulation might be one of the reasons of impaired lower limb muscle function in Japanese patients with type 1 diabetes., (© 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Few data on breakthrough candidemia (BC), defined as candidemia that develops on administration of antifungal agents (AFAs), in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are available. The medical and microbiological records of recipients of an allo-HSCT obtained between December 2008 and December 2014 were reviewed. Of 768 allo-HSCT cases, 26 developed BC. Among the 26 causative strains, 22 strains were stored and identified by sequencing. The following species were isolated: Candida parapsilosis (9 strains), C. glabrata (4 strains), C. guilliermondii (3 strains), and other Candida species (6 strains). The AFAs being used when BC developed were micafungin (17 cases), liposomal amphotericin B (5 cases), itraconazole (2 cases), and voriconazole (2 cases). All 17 cases who developed BC during micafungin administration were administered 150 mg/day of micafungin. The susceptibilities of the causative Candida species to the administered AFAs when breakthrough occurred ranged from susceptible to resistant. Especially, 85% of the Candida species that caused BC during micafungin administration were susceptible to micafungin. Additionally, 75% of the strains were wild type for susceptibility to the administered AFAs when breakthrough occurred. Systemic steroid administration and a longer severe neutropenic phase (≥5 days) were independent risk factors for BC ( P = 0.016 and P = 0.015, respectively). BC developed in allo-HSCT recipients even when they received a sufficient dose of AFA, including micafungin, to which the causative Candida species were susceptible and/or had wild-type susceptibility in vitro Systemic steroid administration and a longer severe neutropenic phase were host-based factors associated with BC., (Copyright © 2017 American Society for Microbiology.)

Background: In some patients, non-tuberculous mycobacteria (NTM) infections manifest in solitary nodules (solitary nodular [SN] type) generally caused by Mycobacterium avium complex (MAC). In patients treated using surgical resection, the American Thoracic Society guidelines state that postoperative chemotherapy is not necessary in the absence of lesions, although there have been a few reports of such cases., Methods: Twenty-eight patients diagnosed with NTM who underwent solitary pulmonary nodule resection at Toneyama Hospital, Osaka, Japan, between January 2000 and October 2012 were enrolled. We evaluated the influence of the surgical procedure and chemotherapy on outcomes in this retrospective study., Results: Of the 28 patients, 12 were males and 16 were females; the mean age was 58.6 ± 13.2 years. Twenty-five patients were asymptomatic and bronchoscopy was performed in 18; only 2 had a definitive diagnosis of NTM. The pathogen responsible was MAC in 27 patients and M. kansasii in 1. The surgical procedure used was wedge resection in 22 patients, segmentectomy in 1 and lobectomy in 5. Postoperative chemotherapy was administered to 9 patients. Twenty-six patients had no recurrence., Conclusion: We believe that wedge resection is a valid surgical intervention for SN type NTM; additional postoperative chemotherapy is unnecessary in cases with no residual lesions in the operated lung lobe.

Allogeneic hematopoietic stem cell transplantation (HSCT)-related membranous glomerulonephritis (MGN) is poorly understood. A total of 830 patients who underwent HSCT at Toranomon Hospital from 2000 to 2012 were evaluated retrospectively, including 621 patients receiving umbilical cord blood transplantation (UCBT) and 208 patients receiving unrelated bone marrow transplantation. MGN was diagnosed in 5 patients after UCBT (versus none after bone marrow transplantation) and occurred concomitantly with chronic graft-versus-host disease after cessation of immunosuppression. Light microscopy did not show any definite spikes or bubbling of the glomerular basement membrane (GBM) in all 5 patients. In 1 patient (case 5), endocapillary proliferative lesions with fibrin-like deposits were noted in addition to MGN findings. Immunofluorescence demonstrated granular deposits of immunoglobulin G (IgG; IgG1 and IgG4) along the GBM with negativity for C3, C4, and C1q in 4 patients (cases 1-4), whereas case 5 showed positivity for IgG (IgG1, IgG2, IgG3, and IgG4) as well as for C3, C4, and C1q. Electron microscopy revealed electron-dense deposits in the subepithelial space of the GBM in cases 1-4. In case 5, electron-dense deposits were present in the mesangium and the subendothelial space of the GBM, as well as in the subepithelial space. After treatment with immunosuppressants (prednisolone and/or cyclosporin) or angiotensin-converting enzyme inhibitors, complete remission with disappearance of proteinuria was achieved 12.2 months in all 5 patients, but nephrotic-range proteinuria relapsed in 2 patients during follow-up. Serum anti-PLA2R autoantibody was negative in 3 patients. HSCT-related MGN only occurred after UCBT. We believe that there were 2 morphologic patterns: early MGN and membranoproliferative pattern glomerulonephritis., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne acute infectious disease caused by the SFTS virus (SFTSV). SFTS has been reported in China, South Korea, and Japan as a novel Bunyavirus. Although several molecular epidemiology and phylogenetic studies have been performed, the information obtained was limited, because the analyses included no or only a small number of SFTSV strains from Japan., Methods: The nucleotide sequences of 75 SFTSV samples in Japan were newly determined directly from the patients' serum samples. In addition, the sequences of 7 strains isolated in vitro were determined and compared with those in the patients' serum samples. More than 90 strains that were identified in China, 1 strain in South Korea, and 50 strains in Japan were phylogenetically analyzed., Results: The viruses were clustered into 2 clades, which were consistent with the geographic distribution. Three strains identified in Japan were clustered in the Chinese clade, and 4 strains identified in China and 26 in South Korea were clustered in the Japanese clade., Conclusions: Two clades of SFTSV may have evolved separately over time. On rare occasions, the viruses were transmitted overseas to the region in which viruses of the other clade were prevalent., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

This prospective, multicenter phase I/II study of unmanipulated HLA-haploidentical reduced-intensity stem cell transplantation using a low dose of anti-T lymphocyte globulin (ATG) and steroid was conducted in 5 institutions in Japan. Thirty-four patients with hematologic malignancies who were in an advanced stage or at a high risk of relapse at the time of transplantation were enrolled. Among them, 7 patients underwent transplantation as a second transplantation because of relapse after the previous allogeneic stem cell transplantation. The conditioning regimen consisted of fludarabine, busulfan, and ATG (Fresenius, 8 mg/kg), and graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methylprednisolone (1 mg/kg). All patients except 1 (97.1%) achieved donor-type engraftment. Rapid hematopoietic engraftment was achieved, with neutrophils > .5 × 10(9)/L on day 11 and platelets > 20 × 10(9)/L on day 17.5. Treatment was started for ≥grade I GVHD, and the cumulative incidences of acute grade I and grade II to IV GVHD were 27.5% and 30.7%, respectively. The incidence of chronic GVHD (extensive type) was 20%. Fourteen patients (41.2%) had a relapse. The cumulative incidence of transplantation-related mortality at 1 year after transplantation was 26.5%. The survival rate at day 100 was 88.2%. The survival rates at 1 year for patients with complete remission (CR)/chronic phase (n = 8) and non-CR (n = 26) status before transplantation were 62.5% and 42.3%, respectively. In the multivariate analysis, non-CR status before transplantation was the only factor significant prognostic factor of increased relapse (P = .0424), which tended to be associated with a lower survival rate (P = .0524). This transplantation protocol is safe and feasible, if a suitable donor is not available in a timely manner. As the main cause of death was relapse and not GVHD, more intensified conditioning or attenuation of GVHD prophylaxis and/or donor lymphocyte infusion may be desirable for patients with non-CR status., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

We retrospectively analyzed 2682 patients who developed grade II-IV acute graft-versus-host disease (GVHD). On analysis with stratification into five age groups (20-29, 30-39, 40-49, 50-59 and ≥60), 2-year non-relapse mortality rates (NRM) after the onset of GVHD were 20.7, 26.2, 26.6, 37.0 and 40.4%, respectively (p<0.001). We found a significant interaction between the patient's age and GVHD severity with respect to NRM (p=0.004). On multivariate analyses stratified by GVHD severity, the hazard ratio (HR) for NRM in the groups aged 50 years or more (reference: age group 20-29) was about twice as great in patients with grade II acute GVHD when compared with grade III-IV disease (HR in those aged 50-59 years: 2.9 for grade II and 1.5 [p=0.03 and 0.04] for grades III-IV; HR if ≥60 years: 3.3 for grade II and 1.5 for grades III-IV [p<0.001 for both]).

Central nervous system (CNS) involvement in adult acute myeloid leukemia (AML) is rare and associated with poor outcomes. Therefore, CNS involvement in AML is an indicator for allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the impact of CNS involvement in AML on the outcome of allo-HSCT remains unclear. We performed a large-scale nationwide retrospective analysis to elucidate the outcomes of allo-HSCT on AML with CNS involvement (CNS+AML). Clinical data were collected from a registry database of the Japan Society for Hematopoietic Cell Transplantation. CNS involvement was defined as the infiltration of leukemia cells into the CNS or myeloid sarcoma in the CNS identified at any time from diagnosis to transplantation. One hundred fifty-seven patients with CNS+AML underwent allo-HSCT between 2006 and 2011. The estimated overall survival, cumulative incidence of relapse and nonrelapse mortality at 2 years for CNS+AML (51.2%, 30.2%, and 14.5%, respectively) were comparable with those for AML without CNS involvement (48.6%, 27.4%, and 22.0%, respectively). Univariate and multivariate analyses indicated that the development of chronic graft-versus-host disease, disease status, and cytogenetic risk category were independent prognostic factors for overall survival for CNS+AML. These results suggest that allo-HSCT may improve outcomes in patients with CNS+AML., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Allogeneic bone marrow and peripheral blood stem cell transplantations are curative treatment modalities for adult T cell leukemia/lymphoma (ATLL) because of the intrinsic graft-versus-ATLL effect. However, limited information is available regarding whether cord blood transplantation (CBT) induces a curative graft-versus-ATLL effect against aggressive ATLL. To evaluate the effect of CBT against ATLL, we retrospectively analyzed data from 175 patients with ATLL who initially underwent single-unit CBT. The 2-year overall survival (OS) rate was 20.6% (95% confidence interval [CI], 13.8% to 27.4%). A multivariate analysis revealed that the development of graft-versus-host disease (GVHD) was a favorable prognostic factor for OS (hazard ratio, .10; 95% CI, .01 to .94; P = .044). Furthermore, the 2-year OS (42.7%; 95% CI, 28.1% to 56.6%) of patients with grade 1 to 2 acute GVHD was higher than that of patients without acute GVHD (24.2%; 95% CI, 11.2% to 39.8%; P = .048). However, the cumulative incidence of treatment-related mortality (TRM) was high (46.1%; 95% CI, 38.2% to 53.7%), and early death was particularly problematic. In conclusion, CBT cures patients with ATLL partly through a graft-versus-ATLL effect. However, novel interventions will be required, particularly in the early phase, to reduce TRM and optimize GVHD., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high case fatality risk and is caused by the SFTS virus (SFTSV). A retrospective study conducted after the first identification of an SFTS patient in Japan revealed that SFTS is endemic to the region, and the virus exists indigenously in Japan. Since the nucleotide sequence of Japanese SFTSV strains contains considerable differences compared with that of Chinese strains, there is an urgent need to establish a sensitive and specific method capable of detecting the Chinese and Japanese strains of SFTSV. A conventional one-step reverse transcription-PCR (RT-PCR) (cvPCR) method and a quantitative one-step RT-PCR (qPCR) method were developed to detect the SFTSV genome. Both cvPCR and qPCR detected a Chinese SFTSV strain. Forty-one of 108 Japanese patients suspected of having SFTS showed a positive reaction by cvPCR. The results from the samples of 108 Japanese patients determined by the qPCR method were in almost complete agreement with those determined by cvPCR. The analyses of the viral copy number level in the patient blood samples at the acute phase determined by qPCR in association with the patient outcome confirmed that the SFTSV RNA load in the blood of the nonsurviving patients was significantly higher than that of the surviving patients. Therefore, the cvPCR and qPCR methods developed in this study can provide a powerful means for diagnosing SFTS. In addition, the detection of the SFTSV genome level by qPCR in the blood of the patients at the acute phase may serve as an indicator to predict the outcome of SFTS., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

The aim of this study was to prospectively evaluate the PK and safety of ivBU in 25 Japanese children (median age six yr; range, five months-17 yr) as one of a combination of drugs in a pretransplant regimen. The patients had acute leukemia (n = 14), CML (2), JMML (5), solid tumors (2), chronic granulomatous disease (1), or metachromatic leukodystrophy (1). Five different dose schedules were used according to the patient's ABW: <9 kg (1.0 mg/kg), 9 to <16 (1.2 mg/kg), 16-23 (1.1 mg/kg), >23-34 (0.95 mg/kg), and >34 kg of BW (0.8 mg/kg). Each dose was given over two h, and sample blood was drawn at nine or 11 separate points for analysis by gas chromatography-mass spectrometry. The AUC varied from 796 to 1905 μmol min/L, and 19 of the 25 patients (76%) remained within the target range without dose adjustment. Two were diagnosed with engraftment failure. Hepatic VOD developed in four, and only one of these showed high AUC (>1500 μmol min/L). Toxicities did not correlate with the BU level. Our data showed very similar PK to those in previous studies, and these dose schedules are applicable to Japanese children., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A Japanese man suffered from acute respiratory tract infection after returning to Japan from Bali, Indonesia in 2007. Miyazaki-Bali/2007, a strain of the species of Nelson Bay orthoreovirus, was isolated from the patient's throat swab using Vero cells, in which syncytium formation was observed. This is the sixth report describing a patient with respiratory tract infection caused by an orthoreovirus classified to the species of Nelson Bay orthoreovirus. Given the possibility that all of the patients were infected in Malaysia and Indonesia, prospective surveillance on orthoreovirus infections should be carried out in Southeast Asia. Furthermore, contact surveillance study suggests that the risk of human-to-human infection of the species of Nelson Bay orthoreovirus would seem to be low.

To determine whether a difference in donor source affects the outcome of transplantation for patients with primary myelofibrosis (PMF), a retrospective study was conducted using the national registry data on patients who received first allogeneic hematopoietic cell transplantation (HCT) with related BM (n=19), related PBSCs (n=25), unrelated BM (n=28) or unrelated umbilical cord blood (UCB; n=11). The 5-year OS rates after related BM, related PBSC and unrelated BM transplantation were 63%, 43% and 41%, respectively, and the 2-year OS rate after UCB transplantation was 36%. On multivariate analysis, the donor source was not a significant factor for predicting the OS rate. Instead, performance status (PS) ≥2 (vs PS 0-1) predicted a lower OS (P=0.044), and RBC transfusion ≥20 times before transplantation (vs transfusion ≤9 times) showed a trend toward a lower OS (P=0.053). No advantage of nonmyeloablative preconditioning regimens in terms of decreasing nonrelapse mortality or increasing OS was found. Allogeneic HCT, and even unrelated BM and UCB transplantation, provides a curative treatment for PMF patients.

Few studies have evaluated the risk factors for chronic GVHD and organ involvement associated with different graft types, including unrelated cord blood (U-CB). We retrospectively studied 4818 adult patients who received their first allogeneic transplantation and survived for at least 100 days. The incidence of chronic GVHD at 2 years was 37%. The following factors were associated with the development of chronic GVHD: female donor/male recipient, CMV-Ab seropositivity, matched related peripheral blood grafts vs matched related BM grafts, no in vivo T-cell depletion and the occurrence of grade II-IV acute GVHD. Among these factors, the association with acute GVHD occurrence was consistently significant across donor subtypes. The use of U-CB was not associated with chronic GVHD, but was associated with a low incidence of extensive chronic GVHD. Chronic GVHD patients who had received U-CB transplants showed less frequent involvement of the oral cavity (28% vs 55%), eye (12% vs 26%), liver (20% vs 44%), lung (11% vs 25%) and joint (0% vs 6%) than those with matched related BM grafts. In conclusion, we found that U-CB transplants were associated with a low incidence of extensive chronic GVHD and less frequent involvement of the oral cavity, eye, liver, lung and joints.