Publications by authors named "Naoto Fujita"

67 Publications

Impact of event-free survival status after stem cell transplantation on subsequent survival of patients with lymphoma.

Blood Adv 2021 Mar;5(5):1412-1424

Department of Oncology and Hematology, Shimane University Hospital, Izumo, Japan.

We evaluated the impact of event-free survival (EFS) status at 24 months (EFS24) and 60 months (EFS60) after hematopoietic stem cell transplantation (HSCT) using registry data. Patients who underwent their first autologous HSCT (auto-HSCT) or allogeneic HSCT (allo-HSCT) for lymphoma between 1981 and 2018 were included. Overall survival was compared with that of the age-, sex, and calendar period-matched general population. A total of 14 977 patients, including 10 964 and 4013 who underwent auto-HSCT and allo-HSCT, respectively, were analyzed. Although patients who achieved EFS24 and EFS60 had favorable outcomes, most had significantly poorer survival rates than the general population. The standardized mortality ratios (SMRs) of patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) were significantly higher than that of the general population even after achieving EFS24 or EFS60. The SMRs of those after auto-HSCT were 2.5 to 3.5 and 2.7 to 3.7, respectively. The SMR was consistently highest in Hodgkin lymphoma (HL) patients after HSCT. By contrast, subsequent survival of patients with primary mediastinal large B-cell lymphoma, intravascular large B-cell lymphoma, or peripheral T-cell lymphoma, not otherwise specified, who achieved EFS60 after auto-HSCT, and those with extranodal natural killer/T-cell lymphoma who achieved EFS60 after allo-HSCT did not significantly differ from that of the general population, with SMRs of 1.6, 1.2, 1.8, and 1.3, respectively. Our results suggest that EFS24 and EFS60 were clinically useful end points after HSCT for lymphoma patients. Furthermore, patients with certain lymphoma subtypes who achieved EFS had a comparable prognosis with that of the general population and were potentially cured after HSCT.
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http://dx.doi.org/10.1182/bloodadvances.2020003735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948259PMC
March 2021

Propofol midazolam for sedation during radiofrequency ablation in patients with hepatocellular carcinoma.

JGH Open 2021 Feb 22;5(2):273-279. Epub 2020 Dec 22.

Departmetn of Anesthesiology, Graduate School of Medicine Chiba University Chiba Japan.

Background And Aim: Standardization of the sedation protocol during radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC) is needed. This randomized, single-blind, investigator-initiated trial compared clinical outcomes during and after RFA using propofol and midazolam, respectively, in patients with HCC.

Methods: Few- and small-nodule HCC patients (≤3 nodules and ≤3 cm) were randomly assigned to either propofol or midazolam. Patient satisfaction was assessed using a 100-mm visual analog scale (VAS) (1 mm = not at all satisfied, 100 mm = completely satisfied). Sedation recovery rates 1, 2, 3, and 4 h after RFA were evaluated based on Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores; full recovery was defined as a MOAA/S score of 5.

Results: Between July 2013 and September 2017, 143 patients with HCC were enrolled, and 135 patients were randomly assigned to the treatment group. Compared with midazolam, propofol exhibited similar median procedural satisfaction (propofol: 73.1 mm, midazolam: 76.9 mm, = 0.574). Recovery rates 1 and 2 h after RFA were higher in the propofol group than in the midazolam group. Meanwhile, recovery rates observed 3 and 4 h after RFA were similar in the two groups. The safety profiles during and after RFA were almost identical in the two groups.

Conclusion: Patient satisfaction was almost identical in patients receiving propofol and midazolam sedation during RFA. Propofol sedation resulted in reduced recovery time compared with midazolam sedation in patients with HCC. The safety profiles of both propofol and midazolam sedation during and after RFA were acceptable.
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http://dx.doi.org/10.1002/jgh3.12483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857294PMC
February 2021

Region-specific brain area reductions and increased cholecystokinin positive neurons in diabetic OLETF rats: implication for anxiety-like behavior.

J Physiol Sci 2020 Sep 16;70(1):42. Epub 2020 Sep 16.

Department of Musculoskeletal Functional Research and Regeneration, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.

Metabolic disorders can induce psychiatric comorbidities. Both brain and neuronal composition imbalances reportedly induce an anxiety-like phenotype. We hypothesized that alterations of localized brain areas and cholecystokinin (CCK) and parvalbumin (PV) expression could induce anxiety-like behavior in type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Twenty-week-old OLETF and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats were used. The areas of corticolimbic regions were smaller in OLETF rats. The densities of CCK positive neurons in the lateral and basolateral amygdala, hippocampal cornu ammonis area 2, and prelimbic cortex were higher in OLETF rats. The densities of PV positive neurons were comparable between OLETF and LETO rats. Locomotion in the center zone in the open field test was lower in OLETF rats. These results suggest that imbalances of specific brain region areas and neuronal compositions in emotion-related areas increase the prevalence of anxiety-like behaviors in OLETF rats.
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http://dx.doi.org/10.1186/s12576-020-00771-0DOI Listing
September 2020

Conditioning regimen for allogeneic bone marrow transplantation in children with acquired bone marrow failure: fludarabine/melphalan vs. fludarabine/cyclophosphamide.

Bone Marrow Transplant 2020 07 23;55(7):1272-1281. Epub 2020 May 23.

Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Fludarabine/cyclophosphamide-based conditioning regimens are standard in bone marrow transplantation (BMT) for acquired bone marrow failure in children, however, graft failure may occur. Using the data from a nationwide transplantation registry, we compared the outcomes of children aged <16 years with acquired aplastic anemia and refractory cytopenia of childhood who underwent allogeneic BMT with either fludarabine/melphalan (n = 71) or fludarabine/cyclophosphamide (n = 296) between 2000 and 2016. The fludarabine/melphalan regimen provided excellent outcomes, with 3-year overall survival and failure-free survival rates of 98% and 97%, respectively. The 83% 3-year failure-free survival in the fludarabine/cyclophosphamide group was significantly inferior (P = 0.002), whereas the overall survival did not differ between the two groups. Late graft failure was the most common cause of treatment failure in the fludarabine/cyclophosphamide group, which experienced a significantly higher incidence of late graft failure than the fludarabine/melphalan group (11% vs. 3%; P = 0.035). Multivariate analyses showed that the fludarabine/melphalan regimen was associated with a better failure-free survival (hazard ratio [HR] 0.12; P = 0.005) and lower risk of late graft failure (HR 0.16; P = 0.037). Fludarabine/melphalan-based conditioning regimen can be a promising option for children with acquired bone marrow failure receiving BMT.
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http://dx.doi.org/10.1038/s41409-020-0948-8DOI Listing
July 2020

Nationwide study of pediatric B-cell precursor acute lymphoblastic leukemia with chromosome 8q24/MYC rearrangement in Japan.

Pediatr Blood Cancer 2020 07 23;67(7):e28341. Epub 2020 Apr 23.

Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.

Background: Rearrangements of chromosome 8q24/MYC (8q24/MYC-r), resulting from t(8;14)(q24;q32), t(2;8)(p11;q24), or t(8;22)(q24;q11), are mainly associated with Burkitt lymphoma/leukemia (BL) and rarely observed in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The characteristics of BCP-ALL with 8q24/MYC-r are poorly understood.

Procedure: A retrospective nationwide study of data from patients with pediatric BCP-ALL with 8q24/MYC-r in Japan was conducted to clarify the clinical and biological characteristics associated with 8q24/MYC-r BCP-ALL.

Results: Ten patients with BCP-ALL with 8q24/MYC-r, including three with double-hit leukemia (DHL) (two with t(8;14)(q24;q32) and t(14;18)(q32;q21) and one with t(8;14) and t(3;22)(q27;q11)), were identified. Patients with BCP-ALL with 8q24/MYC-r had higher median age and uric acid and lactate dehydrogenase levels, than those without 8q24/MYC-r. All patients were initially treated with ALL-type chemotherapy; however, four, including one with DHL, were switched to BL-type chemotherapy, based on cytogenetic findings. One patient relapsed after standard-risk ALL-type chemotherapy, and two patients with DHL did not attain complete remission with chemotherapy; all three died within 11 months. The other seven patients treated with BL-type or high-risk ALL-type chemotherapy are alive without disease.

Conclusions: The clinical and laboratory features of BL with IG-MYC rearrangement, displaying a BCP immunophenotype (Wagener et al. and Herbrueggen et al. termed it as pre-BLL), are similar to those of BCP-ALL with 8q24/MYC-r. Low-risk ALL-type chemotherapy may not be appropriate for them, and further studies are required to establish an adequate therapeutic strategy. Further studies of DHL to identify new treatment strategies are also needed.
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http://dx.doi.org/10.1002/pbc.28341DOI Listing
July 2020

A Multicenter, Open-label, Clinical Trial to Assess the Effectiveness and Safety of Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced-intensity Conditioning in Relapsed/refractory Anaplastic Large-cell Lymphoma in Children.

Acta Med Okayama 2020 Feb;74(1):89-94

Department of Pediatrics and Adolescence, Sapporo Hokuyu Hospital, Sapporo 003-0006, Japan.

No standard treatment for relapsed or refractory anaplastic large-cell lymphoma (ALCL) has been established. This study is a multicenter, open-label trial to examine the effectiveness and safety of transplantation with reduced-intensity conditioning (RIC) for patients under 20 years old with relapsed or refractory ALCL. We defined RIC as the administration of fludarabine (30 mg/m2/day) for five days plus melphalan (70 mg/m2/day) for two days and total body irradiation at 4 Gy, followed by allogeneic hematopoietic stem cell transplantation.
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http://dx.doi.org/10.18926/AMO/57959DOI Listing
February 2020

Hemodynamic response during hyperbaric treatment on skeletal muscle in a type 2 diabetes rat model.

Biomed Res 2020 ;41(1):23-32

Department of Musculoskeletal Functional Research and Regeneration, Graduate School of Biomedicine and Health Sciences, Hiroshima University.

Mild hyperbaric treatment prevents type 2 diabetes progression due to increased oxygen concentration and blood flow in skeletal muscle. However, it remains unknown whether this treatment is effective during all stages of type 2 diabetes. This study aimed to investigate the influences of hyperbaric treatment at 1.3 atmospheres absolute (ATA) on hemodynamic response in various stages of type 2 diabetes. Otsuka Long-Evans Tokushima fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats were used as models of type 2 diabetes and healthy controls, respectively. Glucose levels were significantly higher in OLETF rats than in LETO rats at all ages. Glucose intolerance gradually increased with age in OLETF rats. Insulin levels in OLETF rats were significantly higher at 20-week-old, however, were significantly lower at 60-week-old than in LETO rats. Oxy-Hb, total Hb, and StO in skeletal muscle were increased during hyperbaric treatment in both rats. The hemodynamic changes were significantly higher in OLETF rats than LETO rats, and those changes were also pronounced at 8-week-old compared with other age in OLETF rats. These results suggest that hyperbaric treatment at 1.3 ATA acts on pathophysiological factors and the efficacy could be found only in the early stage of type 2 diabetes.
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http://dx.doi.org/10.2220/biomedres.41.23DOI Listing
January 2020

Effects of appropriate-intensity treadmill exercise on skeletal muscle and respiratory functions in a rat model of emphysema.

Biomed Res 2020 ;41(1):13-22

Graduate School of Health Sciences, Kio University.

The number of patients with chronic obstructive pulmonary disease (COPD), a typical respiratory disorder, is rapidly increasing globally. The purpose of this study was to determine the effects of appropriate-intensity treadmill exercise on skeletal muscle and respiratory functions in a rat model of emphysema. Twenty-one Wistar rats were randomly divided into three groups: the sham (SH) group, pulmonary emphysema (PE) group, and emphysema + exercise (EX) group. Cigarette smoke solution and lipopolysaccharide were intratracheally administered for 4 weeks in the PE and EX groups. The rats in the EX group were made to run on treadmills in the latter 2 weeks of the experiment. Lung tissue was stained with anti-macrophage antibodies; the specific force (contractile force per unit cross-sectional area) of the diaphragm and hind-limb muscles was measured, and blood was analyzed for serum cytokine levels. Many macrophages were observed in the lung tissue of the PE group. In the EX group, the population of macrophages was smaller, and the specific force of the diaphragm and extensor digitorum longus muscles was higher than in the PE group. Moreover, the degree of inflammation in the pulmonary tissue was reduced in the EX group. These results suggest that adaptive exercise may improve not only respiratory and muscle functions but also inflammation of the pulmonary tissue associated with emphysema.
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http://dx.doi.org/10.2220/biomedres.41.13DOI Listing
January 2020

The effect of graft-versus-host disease on outcomes after allogeneic stem cell transplantation for refractory lymphoblastic lymphoma in children and young adults.

Pediatr Blood Cancer 2020 04 26;67(4):e28129. Epub 2019 Dec 26.

Department of Pediatrics, Sapporo Hokuyu Hospital, Sapporo, Japan.

Background: Patients with relapsed or refractory lymphoblastic lymphoma (LBL) have a poor prognosis. The efficacy of allogeneic blood stem cell transplantation for treatment of this disease remains unclear in terms of transplantation-related toxicity. Acute and chronic graft-versus-host diseases (GVHD) are both harmful to patients after allogeneic transplantation, but may have some positive effects through a substitute graft-versus-lymphoma effect.

Methods: To investigate the effect of GVHD on the survival of patients with refractory LBL, we retrospectively studied the outcomes of 213 patients with LBL who underwent first allogeneic stem cell transplantation before the age of 18 years, between 1990 and 2015 in Japan.

Results: The five-year overall survival (OS) and event-free survival rates after stem cell transplantation were 50.3% (95% confidence interval [CI], 43.2-56.9) and 47.8% (95% CI, 40.8-54.4), respectively. In univariate landmark analyses, the probability of OS was significantly better in patients with aGVHD than in those without (P = 0.002, five-year OS 58.1% vs 39.0%). The probability of OS was also better in patients with cGVHD than in those without (P = 0.036, five-year OS 72.2% vs 54.7%). Multivariate analysis demonstrated that only aGVHD was associated with better OS (hazard ratio, 0.63; 95% CI, 0.42-0.94, P = 0.024). Progression and recurrence statuses at SCT were associated with poor prognosis. The patients with grade II aGVHD showed the best prognosis (five-year OS: 65.6%).

Conclusion: Our results suggest that the occurrence of aGVHD may be associated with better outcomes in patients with relapsed/refractory LBL who undergo allogeneic transplantation.
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http://dx.doi.org/10.1002/pbc.28129DOI Listing
April 2020

Hyperbaric Normoxia Improved Glucose Metabolism and Decreased Inflammation in Obese Diabetic Rat.

J Diabetes Res 2019 19;2019:2694215. Epub 2019 Nov 19.

Department of Musculoskeletal Functional Research and Regeneration, Graduate School of Biomedicine and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.

Hyperbaric treatment improves hyperglycemia and hyperinsulinemia in type 2 diabetes associated with obesity. However, its mode of action is unknown. The purpose of the present study was to investigate the influences of regular hyperbaric treatment with normal air at 1.3 atmospheres absolute (ATA) on glucose tolerance in type 2 diabetes with obesity. The focus was directed on inflammatory cytokines in the adipose tissue and skeletal muscle. Otsuka Long-Evans Tokushima Fatty (OLETF) rats were used as models of type 2 diabetes with obesity and Long-Evans Tokushima Otsuka (LETO) rats served as healthy controls. The rats were randomly assigned to untreated or hyperbaric treatment groups exposed to 1.3 ATA for 8 h d and 5 d wk for 16 wks. Glucose levels were significantly higher in the diabetic than in the healthy control rats. Nevertheless, glucose levels at 30 and 60 min after glucose administration were significantly lower in the diabetic rats treated with 1.3 ATA than in the untreated diabetic rats. Insulin levels at fasting and 120 min after glucose administration were significantly lower in the diabetic rats treated with 1.3 ATA than in the untreated diabetic rats. Hyperbaric treatment also increased interleukin-10 (IL-10) expression in the skeletal muscle and decreased tumor necrosis factor (TNF) expression in adipose tissue. These results suggested that TNF downregulation and IL-10 upregulation in diabetic rats subjected to hyperbaric treatment participate in the crosstalk between the adipose and skeletal muscle tissues and improve glucose intolerance.
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http://dx.doi.org/10.1155/2019/2694215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885850PMC
June 2020

Hematopoietic stem cell transplantation for pediatric acute myeloid leukemia patients with KMT2A rearrangement; A nationwide retrospective analysis in Japan.

Leuk Res 2019 12 25;87:106263. Epub 2019 Oct 25.

Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

Objective: Pediatric acute myeloid leukemia (AML) with KMT2A rearrangement is detected in 15-20% of all pediatric AML patients and is associated with adverse outcomes even after allogeneic hematopoietic stem cell transplantation (HSCT). To investigate outcomes and prognostic factors, we investigated 90 pediatric AML patients with KMT2A rearrangement after allogeneic HSCT.

Methods: We retrospectively analyzed Japanese registration data for patients who had received allogeneic HSCT between 1988 and 2011. Median age was 3 years (range, 0-15 years), and no gender difference was evident. Median observation period was 119 months.

Results: The 3-year overall survival (OS) rate of KMT2A-rearranged AML was 52.1% (95% confidence interval (CI), 42.4-64%, n = 90), and the 3-year disease-free survival (DFS) rate was 46.7% (95%CI, 36.8-58.2%). The 3-year DFS of KMT2A-rearranged AML was not significantly poorer than that of other AML (P = 0.09), and no significant difference was also seen in 3-year OS rate (P = 0.21). Multivariate analysis showed disease status (complete remission) at HSCT was associated with better outcomes. A significant difference in treatment-related mortality (TRM) was apparent between HSCT from a HLA full-matched related donor and that from a haploidentical donor (P = 0.001).

Discussion: HSCT is a curative option for pediatric AML with KMT2A rearrangement. Pretransplant status was the most significant prognostic indicator for relapse and survival. Enhancing supportive therapy to reduce TRM will further improve treatment outcomes of KMT2A-rearranged pediatric AML.
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http://dx.doi.org/10.1016/j.leukres.2019.106263DOI Listing
December 2019

Successful outcome with reduced-intensity condition regimen followed by allogeneic hematopoietic stem cell transplantation for relapsed or refractory anaplastic large-cell lymphoma.

Int J Hematol 2019 Dec 16;110(6):723-728. Epub 2019 Oct 16.

Division of Pediatrics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.

We report a retrospective analysis of 38 patients (age ≤ 30 years) who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT) for relapsed or refractory anaplastic large-cell lymphoma (ALCL). Median follow-up for survivors after undergoing allo-SCT was 72 months (range, 35-96 months). Eight patients received reduced-intensity conditioning (RIC) regimens, including three patients with fludarabine plus melphalan-based regimens and five patients with fludarabine plus busulfan-based regimens. The remaining 30 patients received myeloablative conditioning (MAC) regimens. Median ages in the RIC and MAC groups were 24 and 15 years, respectively. The 5-year overall survival rates in the RIC and MAC groups were 100% and 49%, respectively (P = 0.018). The 5-year event-free survival rates in the RIC and MAC groups were 88% and 43%, respectively (P = 0.039). In the RIC group, four of the eight patients showed residual disease at allo-SCT, but all eight patients survived with complete remission (CR), including one patient with relapse. This result suggests that allo-SCT using the RIC regimen may be effective for relapsed or refractory ALCL in children, adolescents, and young adults, even in non-CR cases.
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http://dx.doi.org/10.1007/s12185-019-02748-1DOI Listing
December 2019

The effectiveness of busulfan-based conditioning regimens for stem cell transplantation against lymphomas in children, adolescents, and young adults in Japan.

Pediatr Blood Cancer 2019 10 12;66(10):e27918. Epub 2019 Jul 12.

Department of Pediatrics, Yamagata University Hospital, Yamagata, Yamagata Prefecture, Japan.

Conditioning regimens for stem cell transplantation (SCT) involving total body irradiation (TBI) are generally preferred over busulfan (BU)-based ones for lymphoid malignancies. However, reports of favorable results using BU against lymphomas have recently emerged. This study sought to compare the effectiveness of BU and TBI regimens for SCT against lymphomas. We retrospectively analyzed 893 lymphoma patients who underwent primary SCT in Japan between 1980 and 2015. The median age of all patients was 18 years (range, 0-30 years) with 589 males, 303 females, and 1 patient whose sex was unknown. Overall survival (OS) was not different between those receiving BU and TBI (P = 0.672). OS in patients receiving autologous SCT was significantly better with BU over TBI regimens (P = 0.038), particularly in children (0-15 years) (P = 0.024). Conversely, OS in adolescents and young adults (AYAs; 16-30 years) receiving allogeneic SCT was significantly worse with BU over TBI regimens (P = 0.035). Overall, BU regiments had comparable effectiveness to TBI conditioning regimens, and, although less effective for AYAs with allogeneic SCT, were particularly more effective than TBI regimens for children who received autologous SCT.
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http://dx.doi.org/10.1002/pbc.27918DOI Listing
October 2019

The Relationship between Knee Biomechanics and Clinical Assessments in ACl Deficient Patients.

Int J Sports Med 2019 Jul 12;40(7):477-483. Epub 2019 Jun 12.

Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

The purpose of this study was to clarify the relationship between knee biomechanics and clinical assessments in ACL deficient patients. Subjects included 22 patients with unilateral ACL rupture and 22 healthy controls. Knee kinematics and kinetics during walking and running were examined using a 3-dimensional motion analysis system. The passive knee joint laxity, range of motion of knee joint, and knee muscle strength were also measured. Correlations between the knee kinematic and kinetic data and clinical assessments were evaluated. In the ACL deficient patients, there were no significant relationships between tibial translation during walking and running and passive knee joint laxity. The correlations between knee kinematics and kinetics and range of motion of knee joint were also not significant. Additionally, there were no significant correlations between knee kinematics during walking and knee muscle strength. However, there were several significant correlations between knee kinematics during running and knee muscle strength. The results demonstrate the importance of knee muscle strength for knee kinematics and kinetics during running in ACL deficient patients. Patients with stronger knee muscle strength may demonstrate more nearly normal knee joint movement during dynamic activities such as running.
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http://dx.doi.org/10.1055/a-0809-5366DOI Listing
July 2019

Hematopoietic stem cell transplantation in children and adolescents with relapsed or refractory B-cell non-Hodgkin lymphoma.

Int J Hematol 2019 Apr 30;109(4):483-490. Epub 2019 Jan 30.

Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.

We undertook a retrospective study using the national registry data of hematopoietic stem cell transplantation (HSCT) in Japan to investigate the effect of graft source, particularly autologous or allogeneic tissue, on the treatment outcome in patients aged less than 18 years with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL). Survival analysis was conducted on 31 autologous HSCT (auto-HSCT) and 48 allogeneic HSCT (allo-HSCT) recipients between 1990 and 2013. The 5-year survival rates were significantly lower for allo-HSCT compared to auto-HSCT recipients (32% vs. 55%; P = 0.036). Multivariate analysis of survival rates identified allogeneic graft, Burkitt histology, and lack of response to chemotherapy as poor prognostic factors for survival. The cumulative incidence of treatment-related mortality (TRM) was significantly higher in allo-HSCT compared to auto-HSCT recipients (P = 0.017), explaining the difference in survival rates. In patients with Burkitt lymphoma (BL), overall survival was significantly inferior in the group of patients undergoing HSCT within 12 months from the initial diagnosis (P = 0.039). These data indicate that treatment outcomes for HSCT in children and adolescents with B-NHL were better in autograft recipients, suggesting that greater attention should be paid to the risk of TRM, especially after allografts, for patients with BL.
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http://dx.doi.org/10.1007/s12185-019-02608-yDOI Listing
April 2019

Oxygen therapy may worsen the survival rate in rats with monocrotaline-induced pulmonary arterial hypertension.

PLoS One 2018 20;13(9):e0204254. Epub 2018 Sep 20.

Graduate School of Health Sciences, Kio University, Umaminaka, Koryo-cho, Kitakatsuragi-gun, Nara, Japan.

Although oxygen therapy rapidly improves arterial oxygen saturation in idiopathic pulmonary arterial hypertension, the effects of chronic administration of oxygen are unknown. The purpose of the present study was to investigate the effects of chronic oxygen therapy on the histological changes and survival rate in rats with idiopathic pulmonary arterial hypertension. Idiopathic pulmonary arterial hypertension was induced by monocrotaline injection. The rats were then randomly assigned to receive or not receive oxygen therapy (O2 group and non-O2 group, respectively). The rats in the O2 group were exposed to a high (90%) oxygen environment from day 17 following injection of monocrotaline, when hypoxemia was first observed. The pulmonary arteriole walls were significantly thicker in monocrotaline-injected rats than in saline-injected rats as vehicle on day 19 and were significantly thicker in the rats that received oxygen therapy than in the rats that did not. Right ventricular inflammations were significantly higher in monocrotaline-injected rats than in saline-injected rats on day 19 and were significantly higher in the rats that received oxygen therapy than in the rats that did not. By day 20 after injection of monocrotaline, the survival rate was significantly lower in the rats that received oxygen therapy than in those that did not. Superoxide dismutase activity in the lungs was higher in monocrotaline-injected rats than in saline-injected rats on day 19 after monocrotaline injection and was also higher in the saline-injected rats that received oxygen therapy than in the saline-injected rats that did not. No interaction was detected between monocrotaline injection and oxygen therapy. These results suggest that chronic oxygen therapy worsens the histological changes and survival rate in idiopathic pulmonary arterial hypertension. The fact that degradation of the histological changes and survival rate was accompanied by increase in superoxide dismutase activity suggests that antioxidant capacity may contribute to the degradation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204254PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147559PMC
March 2019

The Effect of Interim FDG-PET-guided Response-Adapted Therapy in Pediatric Patients with Hodgkin's Lymphoma (HL-14) : Protocol for a Phase II Study.

Acta Med Okayama 2018 Aug;72(4):437-440

Department of Pediatrics, Graduate School of Medical Sciences Kyushu University, Fukuoka 812-8582,

This trial enrolls patients with untreated Hodgkin's lymphoma aged<20 years at diagnosis and examines the effects of omitting radiation therapy if the FDG-positron emission tomography (PET) findings after two completed cycles of combination chemotherapy are negative. It thereby aims to determine whether patients who truly require radiation therapy can be identified by FDG-PET. If so, this modality could be used to omit radiation therapy for all other patients, decreasing the risk of serious long-term complications without affecting survival rates. The outcomes of patients for whom FDG-PET is used to assess early treatment response will also be determined.
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http://dx.doi.org/10.18926/AMO/56185DOI Listing
August 2018

Changes in lipid metabolism and capillary density of the skeletal muscle following low-intensity exercise training in a rat model of obesity with hyperinsulinemia.

PLoS One 2018 2;13(5):e0196895. Epub 2018 May 2.

Department of Musculoskeletal Functional Research and Regeneration, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.

Although exercise is effective in improving obesity and hyperinsulinemia, the exact influence of exercise on the capillary density of skeletal muscles remains unknown. The aim of this study was to investigate the effects of low-intensity exercise training on metabolism in obesity with hyperinsulinemia, focusing specifically on the capillary density within the skeletal muscle. Otsuka Long-Evans Tokushima fatty (OLETF) rats were used as animal models of obesity with hyperinsulinemia, whereas Long-Evans Tokushima Otsuka (LETO) rats served as controls (no obesity, no hyperinsulinemia). The animals were randomly assigned to either non-exercise or exercise groups (treadmill running for 60 min/day, for 4 weeks). The exercise groups were further divided into subgroups according to training mode: single bout (60 min, daily) vs. multiple bout (three bouts of 20 min, daily). Fasting insulin levels were significantly higher in OLETF than in LETO rats. Among OLETF rats, there were no significant differences in fasting glucose levels between the exercise and the non-exercise groups, but the fasting insulin levels were significantly lower in the exercise group. Body weight and triacylglycerol levels in the liver were significantly higher in OLETF than in LETO rats; however, among OLETF rats, these levels were significantly lower in the exercise than in the non-exercise group. The capillary-to-fiber ratio of the soleus muscle was significantly higher in OLETF than in LETO rats; however, among OLETF rats, the ratio was lower in the exercise group than in the non-exercise group. No significant differences in any of the studied parameters were noted between the single-bout and multiple-bout exercise training modes among either OLETF or LETO rats. These results suggest that low-intensity exercise training improves insulin sensitivity and fatty liver. Additionally, the fact that attenuation of excessive capillarization in the skeletal muscle of OLETF rats was accompanied by improvement in increased body weight.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196895PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931644PMC
August 2018

Validity of motion analysis using the Kinect system to evaluate single leg stance in patients with hip disorders.

Gait Posture 2018 May 7;62:458-462. Epub 2018 Apr 7.

Sports Medical Center, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan; Department of Orthopaedic Surgery, Division of Medicine, Biomedical Sciences Major, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. Electronic address:

Background: Abnormal movements during single leg stance in patients with hip disorders could be detected by the Kinect system as well as the three-dimensional motion analysis system. However, validity of the Kinect system to evaluate single leg stance in patients with hip disorders remains unknown.

Research Question: To investigate the concurrent validity of the Kinect system, relative to the VICON three-dimensional system which is considered as the gold standard for motion analysis, to measure trunk and pelvis alignment during single leg stance. To investigate the discriminant validity of the Kinect system between with and without hip disorders.

Methods: For evaluation of the concurrent validity of the Kinect system, the intra-class correlation coefficient (ICC ) was calculated for the angle of inclination of the pelvis and trunk in 5 healthy individuals. For evaluation of the discriminant validity of the Kinect system, the angle of inclination of the pelvis and trunk during single leg stance were measured in 27 individuals with hip disorders and 100 healthy individuals. Differences in the maximum angle of inclination of the pelvis and trunk were evaluated between hip disorders and healthy individuals using the Mann-Whitney U test.

Results: ICC values were between 0.83-0.93 for the pelvic and 0.63-0.81 for the trunk angle, respectively. The maximum trunk inclination angle calculated using the Kinect system was significantly higher in patients with hip disorders than healthy individuals, with no significant between-group difference in the angle of inclination of the pelvis.

Significance: The Kinect system was adequate to detect certain abnormal movements during single leg stance among patients with hip disorders. Therefore, the Kinect system could provide a convenient motion analysis tool for the assessment of patients with hip disorders.
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http://dx.doi.org/10.1016/j.gaitpost.2018.04.010DOI Listing
May 2018

Effects of lateral wedge insole application on medial compartment knee osteoarthritis severity evaluated by ultrasound.

Knee 2017 Dec 30;24(6):1408-1413. Epub 2017 Sep 30.

Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.

Background: It is known that a lateral wedge insole (LWI) decreases medial loading stress in the knee. Medial meniscus pathology, such as a degenerative tear or a root tear, leading to malfunction and medial meniscus extrusion (MME), is a critical condition that leads to severe osteoarthritis (OA). However, the effect of LWI on MME is still unknown. The objective of this study was to investigate the effect of LWI use on MME in knee OA using ultrasonography.

Methods: Thirty-one knees from 18 patients with knee OA diagnosed radiographically were allocated to the OA group (mean age, 73.6years; sex M:F, 2:16). Twenty-two knees from 11 volunteers without knee OA were also enrolled as an age-matched control group. MME was evaluated using ultrasonography with the patients in three positions: supine, standing without LWI, and standing with LWI.

Results: In both groups, the mean values of the MME increased significantly when patients were in the standing position compared to the supine position. In the OA group, MME significantly decreased with LWI use. There was no significant difference in MME between use and non-use of an LWI in the control group.

Conclusions: The LWI could significantly decrease MME in patients with knee OA.
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http://dx.doi.org/10.1016/j.knee.2017.09.001DOI Listing
December 2017

Azacitidine successfully maintained the second remission in an infant with KMT2A-rearranged acute lymphoblastic leukemia who relapsed after unrelated cord blood transplantation.

Pediatr Blood Cancer 2017 Dec 4;64(12). Epub 2017 Jul 4.

Department of Pediatrics, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan.

The outcome for infants with KMT2A (MLL)-rearranged acute lymphoblastic leukemia (MLL-r ALL) is dismal despite intensive therapy, including hematopoietic stem cell transplantation (HSCT). Epigenetic dysregulation is considered a key driver of MLL-r leukemogenesis, which theoretically supports the use of epigenetic modifiers as a treatment option. We report an infant MLL-r ALL case with post-HSCT relapse. After achieving a second remission, which was maintained for 10 months using only the DNA methyltransferase inhibitor, azacitidine, the patient successfully received the second HSCT. This report describes the clinical effectiveness of azacitidine for the treatment of infant MLL-r ALL.
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http://dx.doi.org/10.1002/pbc.26697DOI Listing
December 2017

Primary hepatic choriocarcinoma in an 83-year-old woman.

Pathol Int 2017 Aug 11;67(8):425-430. Epub 2017 Jun 11.

Department of Pathology, Numazu City Hospital, 550 Higashishiiji Harunoki, Numazu, Shizuoka 410-0302, Japan.

We present a case of primary hepatic choriocarcinoma in an 83-year-old Japanese woman with gastric wall and lymph node metastases and a splenic vein tumor thrombus. Multiple irregular hepatic tumors with massive necrosis and hemorrhage were observed during autopsy. Syncytiotrophoblast-like and mononucleated cytotrophoblast-like cell morphology with focal hepatocellular carcinoma (HCC)-like trabecular structures was observed. In immunohistochemical analyses, the tumor cells expressed human chorionic gonadotropin (hCG) and cytokeratins (AE1/AE3, CK7, CK19) but were negative for alpha-fetoprotein (AFP), glypican-3, and vimentin. Immunohistochemical findings did not reveal evidence of HCC or angiosarcoma. We concluded the liver tumor was primary hepatic choriocarcinoma.
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http://dx.doi.org/10.1111/pin.12552DOI Listing
August 2017

Pediatric follicular lymphoma in Japan.

Int J Hematol 2017 Jun 7;105(6):849-853. Epub 2017 Mar 7.

Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Japan.

Follicular lymphoma (FL) is quite rare in children. There have been only two major reports on pediatric FL. The present retrospective study on pediatric FL in Japan, including FL with diffuse large B cell lymphoma (DLBCL), analyzed data from 1991 to 2014. Twenty-two patients with pediatric FL were analyzed. Sixteen patients were boys and six were girls. Median age of onset was 9 years (range 4-17 years). In 11 patients, DLBCL co-existed with FL. The initial lesions involved cervical lesions in 16 patients, and the abdomen in six. With regard to stage of disease at diagnosis, 17 patients were at stage I or II, four were at stage III, and one was at stage IV. Chemotherapy was administered in 18 patients, and only resection was performed in four patients. Mature B lymphoma regimens were selected for 17 patients who received chemotherapy. Although two patients relapsed, all patients are currently alive and disease free. The median follow-up period was 54.5 months (range 6-126 months). Patients having FL with DLBCL were younger compared with those having FL, and this disease was more frequently observed in female patients. Our data revealed that FL in Japanese children is a tumor with good prognosis, as in reports from the United States and Europe.
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http://dx.doi.org/10.1007/s12185-017-2209-1DOI Listing
June 2017

Gender differences in the restoration of knee joint biomechanics during gait after anterior cruciate ligament reconstruction.

Knee 2017 Mar 4;24(2):280-288. Epub 2017 Feb 4.

Department of Orthopaedic Surgery, Integrated Health Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.

Background: The aim of our study was to evaluate the effects of gender on recovery of knee joint biomechanics over the stance phase of gait after reconstruction of the anterior cruciate ligament (ACL).

Methods: Gait parameters and knee joint kinematics and kinetics were compared in 32 patients (16 male and 16 female) who underwent ACL reconstruction for a unilateral ACL deficiency, with comparison to an age-, height-, and weight-matched Control group. Knee flexion, adduction and tibial rotation angles were measured and knee extension and abduction moment was calculated by inverse dynamics methods.

Results: Females exhibited more tibial external rotation, in both the Control and ACL groups (P<0.05), which was not changed after ACL reconstruction. Prior to reconstruction, sagittal plane biomechanics were changed, in both males and females, compared to the Control groups (P<0.05). These abnormal sagittal plane mechanics were recovered at 12months, but not six months post-reconstruction.

Conclusions: We identified gender-based differences in tibial rotation that influenced the kinematics and kinetics of the knee over the stance phase of gait, both pre-operatively and post-ACL reconstruction. Evaluation of biomechanical effects of ACL injury, before and after reconstruction, should be separately evaluated for females and males.
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http://dx.doi.org/10.1016/j.knee.2017.01.001DOI Listing
March 2017

Characteristics of thoracic and lumbar movements during gait in lumbar spinal stenosis patients before and after decompression surgery.

Clin Biomech (Bristol, Avon) 2016 Dec 29;40:45-51. Epub 2016 Oct 29.

Department of Orthopaedic Surgery, Hiroshima University, Hiroshima, Japan.

Background: Although gait analysis has been previously conducted for lumbar spinal stenosis patients, the vertebral segmental movements, such as of the thoracic and lumbar regions, and whether the spinal movement during gait changes after decompression surgery remain unclear.

Methods: Ten patients with lumbar spinal stenosis and 10 healthy controls participated. Clinical outcomes were assessed using the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire and Visual Analogue Scale. Spinal kinematic data of the participants during gait were acquired using a three-dimensional motion analysis system. The trunk (whole spine), thoracic, and lumbar flexion and pelvic tilting values were calculated. Spinal kinematic data and clinical outcomes were collected preoperatively and 1month postoperatively for the patients.

Findings: Compared to that observed preoperatively, the clinical outcomes significantly improved at 1month postoperatively. In the standing position, the preoperative lumbar extension of the patients was significantly smaller than that of the controls. Moreover, during gait, the lumbar flexion relative to the standing position of the patients was smaller than that of the controls preoperatively, and increased at 1month postoperatively. The sum of the thoracic and lumbar flexion values during gait negatively correlated with the score for leg pain.

Interpretation: The epidural pressure of lumbar spinal stenosis patients is known to be higher than that of normal subjects during gait, and to decrease during walking with lumbar flexion. Preoperatively, smaller thoracic and lumbar flexion movements during gait relative to the standing position cannot decrease epidural pressure; as a result, severe leg pain might be induced.
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http://dx.doi.org/10.1016/j.clinbiomech.2016.10.016DOI Listing
December 2016

Outcome differences between children and adolescents and young adults with non-Hodgkin lymphoma following stem cell transplantation.

Int J Hematol 2017 Mar 27;105(3):369-376. Epub 2016 Oct 27.

Shimane University Hospital Cancer Center, Oncology/Hematology, Izumo, Japan.

Several studies of patients with acute lymphoblastic leukemia and acute myeloid leukemia who received stem cell transplantation (SCT) have reported that adolescents and young adults (AYAs) experience higher transplant-related mortality than that in younger children. However, to the best of our knowledge, there have been no reports of a similar comparison of non-Hodgkin lymphoma (NHL) patients who received SCT. We analyzed 918 patients aged 30 years and younger who received their first stem cell transplantation for NHL. Of the allogeneic transplant patients, children and AYAs did not significantly differ in survival rate, event-free survival rate, relapse rate, or transplant-related mortality. However, 5-year transplant-related mortality after autologous transplantation was significantly higher in children than in AYAs (5.1% in children vs. 0.8% in AYAs, P = 0.0043). The cause of transplant-related death in three of four children was interstitial pneumonitis. In NHL patients, transplantation results in AYAs were not inferior than those in children.
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http://dx.doi.org/10.1007/s12185-016-2120-1DOI Listing
March 2017

Relapsed/refractory pediatric B-cell non-Hodgkin lymphoma treated with rituximab combination therapy: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group.

Pediatr Blood Cancer 2016 10 17;63(10):1794-9. Epub 2016 Jun 17.

Department of Pediatrics, Sapporo Hokuyu Hospital.

Background: Pediatric relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) has been reported to be extremely difficult to cure, but rituximab is expected to be effective in improving the prognosis of pediatric R/R B-NHL patients. Here, we assessed the treatment and prognosis of pediatric R/R B-NHL in the rituximab era in Japan.

Methods: We collected information on patients with R/R B-NHL who were registered with the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) B-NHL03 protocol, a nationwide multicenter trial for newly diagnosed patients. We assessed the treatment and outcome of 33 pediatric R/R B-NHL cases.

Results: Twenty-eight patients received rituximab combination therapy as salvage treatment. R-ICE (rituximab, ifosfamide, carboplatin, and etoposide), the most common regimen, was used in 22 patients as first-line salvage therapy. Twenty-three patients received hematopoietic stem cell transplantation (HSCT). Among all 33 patients, 23 (70.0%) achieved partial remission or complete remission. Their 5-year overall survival rate was 48.5%, which was far superior to that in both our previous study and in another study on pediatric R/R B-NHL. Four toxic deaths associated with viral infection occurred after allogeneic HSCT following on rituximab combined salvage therapy. Risk factor multivariate analysis for survival in patients receiving rituximab combination therapy showed central nervous system combined relapse had inferior outcome.

Conclusions: The prognosis of pediatric R/R B-NHL in a Japanese cohort remained poor but is showing improvement in the rituximab era. Rituximab combination therapy is effective for R/R B-NHL patients who did not receive rituximab as primary treatment. We need to consider possible viral infections in allogeneic HSCT after rituximab treatment.
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http://dx.doi.org/10.1002/pbc.26105DOI Listing
October 2016

Knee biomechanics during walking in recurrent lateral patellar dislocation are normalized by 1 year after medial patellofemoral ligament reconstruction.

Knee Surg Sports Traumatol Arthrosc 2016 Oct 11;24(10):3254-3261. Epub 2016 Feb 11.

Department of Orthopaedic Surgery, Integrated Health Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Purpose: Gait kinematics and kinetics of the knee before and after medial patellofemoral ligament (MPFL) reconstruction in patients with recurrent lateral patellar dislocation (RPD) are unknown. The purpose of this study was to measure knee kinematics and kinetics during gait before and 1 year after anatomical MPFL reconstruction in patients with RPD and compare the results to healthy individuals.

Methods: Eleven RPD patients were treated using an anatomical MPFL reconstruction procedure. Gait analysis was conducted before and at 3, 6, and 12 months after surgery. For comparison, 15 healthy volunteers with no history of orthopaedic problems in their lower limbs were included as the control group. Knee kinematics and kinetics were analysed during gait.

Results: Before surgery, the internal knee extension moment in RPD patients was significantly lower than in controls (P = 0.025). At 3 months post-operatively, there was an additional decrease in knee extension moment compared to before surgery, and so it was still significantly lower than in the control group (P < 0.01). One year post-operatively, knee extension moment in the RPD group was significantly increased compared to 3 months post-operatively (P < 0.01). The knee flexion angle in the early stance phase in the RPD group at 3 months post-operatively was significantly lower than that of controls (P < 0.01). Knee kinematics and kinetics were similar to that of controls 1 year after surgery.

Conclusion: Initially, RPD patients had lower knee extension moments during gait compared with controls, but by 1 year after MPFL reconstruction, knee kinematics and kinetics of gait in the RPD patients had returned to normal. These observations indicate that MPFL reconstruction may help to delay prospective knee OA as long as possible by restoring the conformation of the patellofemoral joint and gait biomechanics by surgery.
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http://dx.doi.org/10.1007/s00167-016-4040-2DOI Listing
October 2016

Time course of ubiquitin-proteasome and macroautophagy-lysosome pathways in skeletal muscle in rats with heart failure.

Biomed Res 2015 ;36(6):383-92

Department of Musculoskeletal Functional Research and Regeneration, Graduate School of Biomedicine and Health Sciences, Hiroshima University.

Patients with heart failure have limited exercise capacity due to not only the myocardial dysfunction but also skeletal muscle atrophy. However, the mechanisms and time course of protein degradation in skeletal muscle during heart failure remain unclear, and there is no established standard treatment. The purpose of the present study was to investigate the time course of major protein degradation pathways in skeletal muscle during heart failure. Four-week-old male Wistar rats were randomly assigned to heart failure induced by monocrotaline or control groups. At 14 and 21 days after monocrotaline injection, the lungs, heart, and gastrocnemius and soleus muscles were removed and analyzed. There was no significant difference in body weight between the groups at 14 days after monocrotaline injection. Although there were no morphological changes in the skeletal muscle of the monocrotaline group at this time point, ubiquitin-proteasome and macroautophagylysosome pathways were activated in the monocrotaline group. Additionally, the pathways were less strongly activated in the soleus muscle than in the gastrocnemius muscle. These results suggest that physical exercise that shifts to slow muscle characteristics should begin when there is no indication of skeletal muscle atrophy to prevent exercise intolerance with heart failure.
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http://dx.doi.org/10.2220/biomedres.36.383DOI Listing
September 2016

Randomized study of granulocyte colony stimulating factor for childhood B-cell non-Hodgkin lymphoma: a report from the Japanese pediatric leukemia/lymphoma study group B-NHL03 study.

Leuk Lymphoma 2016 07 23;57(7):1657-64. Epub 2015 Dec 23.

p Clinical Research Center , National Hospital Organization Nagoya Medical Center , Nagoya , Japan ;

The objective of this study was to assess the impact of the primary prophylaxis of granulocyte colony-stimulating factor (G-CSF) in the management of childhood B-cell non-Hodgkin lymphoma (B-NHL). Patients with advanced-stage mature B-NHL were randomized to receive prophylactic G-CSF (G-CSF+) or not receive G-CSF (G-CSF-) based on protocols of the B-NHL03 study. The G-CSF group received 5 μg/kg/d Lenograstim from day 2 after each course of six chemotherapy courses. Fifty-eight patients were assessable, 29 G-CSF + and 29 G-CSF-. G-CSF + patients showed a positive impact on the meantime to neutrophil recovery and hospital stay. On the other hand, they had no impact in the incidences of febrile neutropenia, serious infections, stomatitis and total cost. Our study showed that administration of prophylactic G-CSF through all six chemotherapy courses for childhood B-NHL showed no clinical and economic benefits for the management of childhood B-NHL treatment.
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http://dx.doi.org/10.3109/10428194.2015.1106534DOI Listing
July 2016