Lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli: Differential and interactive effects on novelty-induced hyperlocomotion, blood cytokine levels and TLR4-related processes.

Lipopolysaccharide (LPS), a component of the Gram-negative bacterial cell wall, activates Toll-like receptors (TLRs). Porphyromonas gingivalis (Pg) may be involved in the progression of periodontal disease. Mice exposed to a novel environment show hyperlocomotion that is inhibited by systemic administration of LPS derived from Escherichia coli (Ec-LPS). However, whether Pg-LPS influences novelty-induced locomotion is unknown. Accordingly, we carried out an open field test to analyse the effects of Pg-LPS. For comparison, effects of Ec-LPS were also studied. We additionally investigated the influence of systemic administration of Pg-LPS or Ec-LPS on IL-6, TNF-alpha, and IL-10 levels in blood, as they could be involved in the changes in locomotion. The TLR4 receptor antagonist TAK-242 was used to study the involvement of TLR4. Since Pg-LPS may block TLR4 in vitro, we analysed the effects of Pg-LPS on Ec-LPS-induced changes in behavioural and biochemical parameters. Male ddY mice were used. Pg- or Ec-LPS and TAK-242 were administered intraperitoneally. Ec-LPS (840 µg/kg), but not Pg-LPS (100, 500 and 840 µg/kg), inhibited novelty-induced locomotion, which was antagonized by TAK-242 (3.0 mg/kg). Ec-LPS (840 µg/kg) increased blood levels of IL-6 and IL-10, which were antagonized by TAK-242 (3.0 mg/kg). However, TAK-242 did not inhibit Ec-LPS-induced increases in TNF-alpha levels in blood. Pg-LPS (100, 500, and 840 µg/kg) did not alter blood IL-6, TNF-alpha, or IL-10 levels. The Ec-LPS-induced increase in blood IL-10, but not IL-6 and TNF-alpha, levels was inhibited by Pg-LPS (500 µg/kg). These results suggest that TLR4 stimulation mediates the inhibition of novel environment-induced locomotion in mice following systemic administration of Ec-LPS, while also increasing blood IL-6 and IL-10 levels. In contrast, Pg-LPS did not exhibit these effects. The present study also provides in vivo evidence that Pg-LPS can inhibit TLR4-mediated increases in blood levels of IL-10, a cytokine thought to prevent the development of periodontal disease.

Use of Unidirectional Porous ß-Tricalcium Phosphate in the Tibial Tunnel for Anterior Cruciate Ligament Reconstruction: A Case Series.

Bone defects in the tibial tunnel for anterior cruciate ligament (ACL) reconstruction can cause adverse events. The unidirectional porous tricalcium ß-phosphate (UDPTCP) has the potential to be used as a filling substitute for bone defects. In this case series, we present the first nine cases in which UDPTCP was used as a bone substitute in the tibial tunnel during ACL reconstruction. The patients comprised six males and three females, with an average age of 32 years (range: 16-50 years). A cylindrical UDPTCP measuring 10 x 20 mm was molded to fit the tibial tunnel and then implanted. At the one-year postoperative follow-up, none of the patients demonstrated any complications, and bone remodeling was observed on radiographs. Therefore, UDPTCP may provide a safe and reliable filling substitute for the tibial tunnel in ACL reconstruction.

Slitrk4 is required for the development of inhibitory neurons in the fear memory circuit of the lateral amygdala.

The Slitrk family consists of six synaptic adhesion molecules, some of which are associated with neuropsychiatric disorders. In this study, we aimed to investigate the physiological role of Slitrk4 by analyzing Slitrk4 knockout (KO) mice. The Slitrk4 protein was widely detected in the brain and was abundant in the olfactory bulb and amygdala. In a systematic behavioral analysis, male Slitrk4 KO mice exhibited an enhanced fear memory acquisition in a cued test for classical fear conditioning, and social behavior deficits in reciprocal social interaction tests. In an electrophysiological analysis using amygdala slices, Slitrk4 KO mice showed enhanced long-term potentiation in the thalamo-amygdala afferents and reduced feedback inhibition. In the molecular marker analysis of Slitrk4 KO brains, the number of calretinin (CR)-positive interneurons was decreased in the anterior part of the lateral amygdala nuclei at the adult stage. In in vitro experiments for neuronal differentiation, Slitrk4-deficient embryonic stem cells were defective in inducing GABAergic interneurons with an altered response to sonic hedgehog signaling activation that was involved in the generation of GABAergic interneuron subsets. These results indicate that Slitrk4 function is related to the development of inhibitory neurons in the fear memory circuit and would contribute to a better understanding of osttraumatic stress disorder, in which an altered expression of Slitrk4 has been reported.

Impact of Surgical Timing on Functional Outcomes after Anterior Cruciate Ligament Reconstruction.

Objectives: Although acute anterior cruciate ligament reconstruction (ACLR) is often avoided because of postoperative joint stiffness, delayed ACLR can lead to a longer recovery time and can have a negative impact on physical function due to detraining. This study aimed to determine the effects of acute ACLR on postoperative outcomes, including muscle strength, performance, and return to sports. Methods: A total of 110 patients who underwent anatomical ACLR using hamstring autografts were included in this study and were divided into three groups: acute (ACLR performed within 2 weeks after ACL injury), 2-6 weeks (ACLR performed between 2 and 6 weeks after injury), and 6-12 weeks (ACLR performed between 6 and 12 weeks after injury). Several parameters were evaluated, including range of motion, knee joint stability, isokinetic knee strength, performance, and return to sports. Results: No significant differences were found in the range of motion or knee joint stability between the groups. The acute group exhibited significantly greater quadriceps strength at 3 months postoperatively than the other groups (p < 0.05). The single-leg hop test showed that 66.7%, 38.7%, and 33.3% of the patients in the acute, 2-6 weeks, and 6-12 weeks groups, respectively, recovered to an LSI of 90% or greater (p = 0.09, Cramer's V = 0.27). All patients in the acute group were able to return to sports (p = 0.14; Cramer's V = 0.28). Conclusions: Acute ACLR is advantageous for the early recovery of strength and performance without adverse events. Acute ACLR may shorten the time spent away from sports activities.

Fractalkine's dual role in inflammation and hard tissue formation in cultured human dental pulp cells.

This study aimed to explore the potential roles of fractalkine/CX3CR1, primarily expressed in vascular endothelial cells and has recently been identified in dental pulp cells at sites of pulp tissue inflammation, not only in inflammation but also in pulp hard tissue formation. To this end, cultured human dental pulp cells were grown in 10% FBS-supplemented α-MEM. Fractalkine was introduced to the culture, and COX-2 and dentin sialophosphoprotein (DSPP) expression levels were evaluated via western blotting. Real-time PCR was used to examine BMP-2 and Osterix mRNA expression. Calcified nodule formation was evaluated with Alizarin red staining. Results revealed that fractalkine increased COX-2 protein expression, calcified nodule formation, and BMP-2 and Osterix mRNA expression in a concentration- and time-dependent manner. DSPP protein expression also increased upon fractalkine addition. This effect of fractalkine on expression of DSPP protein was inhibited in the presence of the CX3CR1 inhibiter ADZ8797. In conclusion, our findings suggest a dual role for fractalkine in promoting pulp inflammation via COX-2 production and contributing to pulp hard tissue formation by stimulating the expression of hard tissue formation markers.

Nelarabine, intensive L-asparaginase, and protracted intrathecal therapy for newly diagnosed T-cell acute lymphoblastic leukaemia in children and young adults (ALL-T11): a nationwide, multicenter, phase 2 trial including randomisation in the very high-risk group.

BACKGROUND: T-cell acute lymphoblastic leukaemia has distinct biological characteristics and a poorer prognosis than B-cell precursor acute lymphoblastic leukaemia. This trial aimed to reduce the rate of radiation and haematopoietic stem-cell transplantation (HSCT) while improving outcomes by adding nelarabine, intensified L-asparaginase, and protracted intrathecal therapy in the Berlin-Frankfurt-Münster (BFM)-type treatment. METHODS: In this nationwide, multicenter, phase 2 trial, we enrolled patients with newly diagnosed T-cell acute lymphoblastic leukaemia (age <25 years at diagnosis) conducted by Japan Children's Cancer Group and Japan Adult Leukemia Study Group. Patients were stratified into standard-risk, high-risk, and very-high-risk groups according to prednisolone response, CNS status, and end-of-consolidation minimal residual disease. We used the Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP)-BFM-ALL 2000-backbone chemotherapy. Nelarabine (650 mg/m2 per day for 5 days) was given to high-risk and very high-risk patients. All patients received, until the measurement of end-of-consolidation minimal residual disease, an identical therapy schedule, which included the prednisolone pre-phase remission induction therapy with dexamethasone (10 mg/m2 per day, for 3 weeks [for patients <10 years] or for 2 weeks including a 7-day off interval [for patients ≥10 years]) instead of prednisolone, and consolidation therapy added with Escherichia coli-derived L-asparaginase. On the basis of the stratification, patients received different intensities of treatment; L-asparaginase-intensified standard BFM-type therapy for standard risk and nelarabine-added high risk BFM-type therapy for high risk. In the very high-risk group, patients were randomly assigned (1:1) to group A (BFM-based block therapy) and group B (another block therapy, including high-dose dexamethasone) stratified by hospital, age (≥18 years or <18 years), and end-of-induction bone marrow blast percentage of M1 (<5%) or M2 (≥5%, <25%)+M3 (≥25%). Cranial radiotherapy was limited to patients with overt CNS disease at diagnosis (CNS3; >5 white blood cells per µL with blasts) and patients with no evidence of CNS disease received protracted triple intrathecal therapy. Only very high-risk patients were scheduled to receive HSCT. The primary endpoint was 3-year event-free survival for the entire cohort and the proportion of patients with disappearance of minimal residual disease between randomly assigned groups A and B in the very high-risk group. Secondary endpoints were overall survival, remission induction rate, and occurrence of adverse events. 3 years after the completion of patient accrual, a primary efficacy analysis was performed in the full analysis set and the per-protocol set. This study is registered with the Japan Registry of Clinical Trials, jRCTs041180145. FINDINGS: Between Dec 1, 2011, and Nov 30, 2017, of 349 eligible patients (median age 9 years [IQR 6-13]), 238 (68%) were male, and 28 (8%) patients had CNS3 status. 168 (48%) patients were stratified as standard risk, 103 (30%) as high risk, 39 (11%) as very high risk, and 39 (11%) as no risk (patients who had off protocol treatment before risk assessment. The composite complete remission (complete remission plus complete remission in suppression) rate after remission induction therapy was 89% (298 of 335 patients). HSCT was performed in 35 (10%) of 333 patients. With a median follow-up of 5·2 years (IQR 3·6-6·7), 3-year event-free survival was 86·4% (95% CI 82·3-89·7%) and 3-year overall survival was 91·3% (87·7-93·8%). The proportion of minimal residual disease disappearance was 0·86 (12 of 14 patients; 95% CI 0·57-0·98) in group A and 0·50 (6 of 12 patients, 0·21-0·79) in group B. Grade 3 peripheral motor neuropathy was seen in 11 (3%) of 349 patients and sensory neuropathy was seen in 6 (2%) patients. The most common grade 3 or worse adverse event was febrile neutropenia (294 [84%] of 349 patients). Treatment-related death occurred in three patients due to sepsis, gastric perforation, or intracranial haemorrhage during remission induction. INTERPRETATION: The ALL-T11 protocol produced encouraging outcomes with acceptable toxicities despite limited cranial radiotherapy and HSCT use. FUNDING: Ministry of Health, Labor and Welfare of Japan, and Japan Agency for Medical Research and Development. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

Utility of axial magnetic resonance images for detecting meniscal ramp lesions associated with anterior cruciate ligament injuries.

Background: Ramp lesions (RLs), associated with anterior cruciate ligament (ACL) injuries, should be repaired to ensure postoperative knee stability. However, it is difficult to identify all RLs before surgery using conventional sagittal magnetic resonance (MR) images and arthroscopy from the anterior, medial, and lateral portals that are usually used during ACL reconstruction. We report the effectiveness of axial images for detecting RL. Methods: From January 2018, a total of 316 knees underwent primary ACL reconstruction with preoperative magnetic resonance imaging (MRI) examination at our hospital. Among these, 149 knees, which required meniscal suturing at the same time, were retrospectively investigated. This study evaluated 22 knees with confirmed RLs around the posterior horn of the medial meniscus. The effectiveness of the preoperative sagittal and axial MR images for detecting RL was assessed. With the MR image, a three-dimensional double-echo steady-state image with a flip angle of 25° was reconstructed into the sagittal and axial planes, respectively. Reconstructed images with 3-mm slices for sagittal slices and 1-mm slices for axial sections were used. The diagnosis was made based on the presence of RL (RL was present, RL may be present, and RL was not present) by four knee surgeons with more than 10 years of experience. Results: Approximately 53% of knee cases were diagnosed with RLs using sagittal images. Meanwhile, a diagnosis was achieved using axial images in 89% of cases. Conclusion: Axial MRI may be superior in detecting RLs.

Seroprevalences Against Paracoccidioides cetii: A Causative Agent for Paracoccidiomycosis Ceti (PCM-C) and Coccidioides posadasii; for Coccidioidomycosis (CCM) in Dall's Porpoise (Phocoenoides dalli) and Harbor Porpoise (Phocoena phocoena) Stranded at Hokkaido, Japan.

Paracoccidiodomycosis ceti (PCM-C) is a zoonotic mycosis characterized by chronic granulomatous cutaneous lesions in cetaceans. It is distributed worldwide and is caused by an unculturable fungus; Paracoccidioides cetii. On the other hand, coccidioidomycosis (CCM), caused by Coccidioides spp., is also a zoonotic and highly pathogenic fungal infection endemic in both American continents. Even though the Far East is not an endemic area of CCM, an autochthonous case has been reported in China. Although the seroprevalence against P. cetii in captive dolphins was 61.0%, there is no information on wild dolphins living in cold waters. The present study aimed to investigate the seroprevalence against P. cetii and C. posadasii in 15 Dall's porpoises (Phocoenoides dalli) and 11 harbor porpoises (Phocoena phocoena) stranded in Hokkaido, Japan. The seroprevalence against P. cetii in the above dolphins was 26.9% (7/26), which was recorded only in Dall's porpoises (7/15), and that against C. posadasii was 15.4% (4/26), three in Dall's porpoises and one in harbor porpoise. The present study demonstrated positive seroprevalence against P. cetii and C. posadasii in wild cetaceans living in the subarctic areas of the Far East as the first records, and would issue the warning those who live in the area were exposed to the causative agent of CCM from seawater.

Influence of Self-Efficacy on Cancer-Related Fatigue and Health-Related Quality of Life in Young Survivors of Childhood Cancer.

This study aims to elucidate how self-efficacy influences cancer-related fatigue and health-related quality of life (HRQoL) in young survivors of childhood cancer. Forty-six young survivors (age range, 8-18 years) of childhood cancer who were currently in complete remission completed measures for self-efficacy (Pediatric General Self-Efficacy Scale (PedsSE)), cancer-related fatigue (Cancer-related Fatigue Score (CRFS)), and HRQoL (Pediatric Quality of Life Inventory 4.0 Generic Core Scale, Pediatric Quality of Life Inventory (PedsQL)). Structural relationships between the PedsSE and CRFS or PedsQL, including the effects of potential demographic or clinical confounders, were examined by machine learning random forest algorithms and structural equation modeling. According to the distribution of the PedsQL, six survivors with PedsQL < 70 were determined to have compromised HRQoL (referred to as "low-PedsQL survivors"). The random forest model identified six variables for the prediction of the CRFS, with the PedsSE being the most important, and eight variables for the distinction of low-PedsQL survivors, with the CRFS being the most and the PedsSE the third most important variable. The structural equation model indicated that a direct influence of the PedsSE on the PedsQL was less detectable (ß = -0.049), whereas an indirect influence of the PedsSE on the PedsQL via the CRFS was evident (ß = 0.333). The model explained 51% of the variation of the CRFS and 28% of the variation of the PedsQL. The PedsSE was strongly correlated with "altered mood" in the subclass of the CRFS (r = -0.470), and "altered mood" was strongly correlated with the PedsQL (r = 0.737). In conclusion, self-efficacy is a major determinant of cancer-related fatigue and influences HRQoL via cancer-related fatigue in survivors of childhood cancer. The main pathway from self-efficacy to HRQoL is thought to be via the emotional aspect of cancer-related fatigue. However, unlike adult survivors of cancer, self-efficacy for young survivors may not contribute much to self-management behaviors that maintain HRQoL.

In-Hospital Management Might Reduce Induction Deaths in Pediatric Patients With Acute Lymphoblastic Leukemia: Results From a Japanese Cohort.

Induction deaths (ID) remain a critical issue in the treatment of pediatric patients with acute lymphoblastic leukemia (ALL). The reported rate of ID in this population is 1% or higher. We speculate that this proportion might be lower in Japan because of mandatory hospitalization during induction therapy to manage complications. We retrospectively analyzed the incidence of ID among children with ALL enrolled in 4 Japanese study groups between 1994 and 2013. Among 5620 children, 41 (0.73%) cases of ID were noted. The median age was 6.5 years; 24 children were female, and 7 had T-cell ALL. Infection was the most common cause of ID (n=22), but the incidence (0.39%) was lower than that reported in western countries. Mortality within 48 hours from the onset of infection was low, comprising 25% of infection-related deaths. The incidence of infections caused by Bacillus species was low. Only 1 patient died because of Aspergillus infection. Fatal infections mostly occurred during the third week of induction therapy. Our findings suggest that close monitoring, stringent infection control, and immediate administration of appropriate antibiotics through hospitalization might be important strategies in reducing the rate of infection-related ID in pediatric patients with ALL.

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

Nationwide survey of pediatric hypodiploid acute lymphoblastic leukemia in Japan.

BACKGROUND: Ploidy is a highly significant prognostic factor for pediatric acute lymphoblastic leukemia (ALL). Children with hypodiploid ALL have poor outcomes despite current intensive chemotherapy. Little has been investigated with regard to hypodiploid ALL in Japanese children. METHODS: We retrospectively collected clinical data on hypodiploid ALL cases from the registries of prospective multicenter trials conducted by the four independent clinical study groups in Japan between 1997 and 2012. RESULTS: A total of 117 ALL patients with hypodiploidy were analyzed in this study. There were 101, eight, and eight patients with 45, 44, and fewer than 44 chromosomes, respectively. The 5 year overall survival rates differed significantly: 86.0%, 87.5%, and 62.5% for patients with 45, 44, and fewer than 44 chromosomes, respectively (P = 0.037). Of the eight patients with 44 chromosomes, seven were alive, including five patients who maintained complete remission without undergoing hematopoietic stem cell transplantation (HSCT). Of the eight patients with fewer than 44 chromosomes, six were good responders to prednisolone and none had induction failure, but the relapse rate was high (5/8). No patients had central nervous system relapse. Four patients underwent HSCT after relapse, but only one survived. CONCLUSIONS: Outcomes of Japanese ALL patients with fewer than 44 chromosomes were poor, as previously reported in other countries. Although the sample size was small, patients with 44 chromosomes had better prognoses than those previously reported. Further studies including international collaboration are needed to improve outcomes for pediatric ALL patients with fewer than 44 chromosomes.

Radiolucent lines are decreased at 3 years following total knee arthroplasty using trabecular metal tibial components.

Objective To analyse location and frequency, and change over time, of radiolucent lines (RLLs) around trabecular metal tibial components in total knee arthroplasty (TKA). Methods Osteoarthritic knees in patients who had undergone TKA were retrospectively evaluated via analysis of RLLs on anteroposterior and lateral X-rays obtained at 2 and 6 months, and 1, 2 and 3 years following TKA. Results In 125 osteoarthritic knees from 90 patients (mean age, 75.0 ± 6.2; 21 male/69 female), frequency of RLLs around trabecular metal tibial components was generally highest at 2 and 6 months, and 1 year following TKA, then gradually decreased over the 3-year follow-up. Frequency of RLLs around trabecular metal tibial components was greater at the tip of the two pegs, particularly the medial peg, and around the pegs, versus other zones. No postoperative revisions were performed for loosening. Conclusions Over 3 years following TKA, RLLs were most frequently observed up to 1 year, then gradually decreased. RLLs were significantly more frequent in the medial peg zone and zones close to the medial peg than in other zones.

Integrated molecular profiling of juvenile myelomonocytic leukemia.

Juvenile myelomonocytic leukemia (JMML), a rare and aggressive myelodysplastic/myeloproliferative neoplasm that occurs in infants and during early childhood, is characterized by excessive myelomonocytic cell proliferation. More than 80% of patients harbor germ line and somatic mutations in RAS pathway genes (eg, PTPN11, NF1, NRAS, KRAS, and CBL), and previous studies have identified several biomarkers associated with poor prognosis. However, the molecular pathogenesis of 10% to 20% of patients and the relationships among these biomarkers have not been well defined. To address these issues, we performed an integrated molecular analysis of samples from 150 JMML patients. RNA-sequencing identified ALK/ROS1 tyrosine kinase fusions (DCTN1-ALK, RANBP2-ALK, and TBL1XR1-ROS1) in 3 of 16 patients (18%) who lacked canonical RAS pathway mutations. Crizotinib, an ALK/ROS1 inhibitor, markedly suppressed ALK/ROS1 fusion-positive JMML cell proliferation in vitro. Therefore, we administered crizotinib to a chemotherapy-resistant patient with the RANBP2-ALK fusion who subsequently achieved complete molecular remission. In addition, crizotinib also suppressed proliferation of JMML cells with canonical RAS pathway mutations. Genome-wide methylation analysis identified a hypermethylation profile resembling that of acute myeloid leukemia (AML), which correlated significantly with genetic markers with poor outcomes such as PTPN11/NF1 gene mutations, 2 or more genetic mutations, an AML-type expression profile, and LIN28B expression. In summary, we identified recurrent activated ALK/ROS1 fusions in JMML patients without canonical RAS pathway gene mutations and revealed the relationships among biomarkers for JMML. Crizotinib is a promising candidate drug for the treatment of JMML, particularly in patients with ALK/ROS1 fusions.

Investigation of perioperative safety and clinical results of one-stage bilateral total knee arthroplasty in selected low-risk patients.

BACKGROUND: An increased perioperative complication rate has been a concern with one-stage bilateral total knee arthroplasty (TKA). The purpose of this study was to retrospectively investigate the perioperative safety and clinical results of one-stage bilateral TKA in selected low-risk patients. METHODS: Sixty-seven patients who received one-stage bilateral TKAs for osteoarthritis who were American Society of Anesthesiology (ASA) class 1 or 2 were included in this study. Perioperative complications, blood loss, transfusion rate, blood laboratory results, and clinical results were evaluated up to 1 year after surgery. RESULTS: No major complications (deep infection, pulmonary embolism, cerebrovascular accident, myocardial infarction, death, or removal or revision of the implants) were observed. The average total blood loss was 1139.5 ml. The transfusion rate was 95.5%. Postoperative hemoglobin level and C-reactive protein level gradually improved up to postoperative day 21 (P < 0.01). Bilateral knee extension knee angles and clinical scores improved postoperatively as compared with preoperative values (P < 0.01). CONCLUSIONS: Although total blood loss and transfusion rate can be high, this preliminary case series suggested that the one-stage bilateral TKA in ASA class 1 or 2 patients can have high perioperative safety levels, and good clinical results can be obtained up to 1 year after surgery. If low-risk patients are selected for bilateral TKA, a one-stage procedure can be beneficial for patients, with a minimal increase in the risk of complications.

Factors influencing period from surgery to discharge in patients with femoral trochanteric fractures.

[Purpose] The purpose of this study was to investigate factors influencing the period from surgery to discharge in patients with femoral trochanteric fractures. [Subjects and Methods] Sixty patients with femoral trochanteric fractures were investigated retrospectively. Based on the mean period from surgery to discharge (85.6 ± 26.6 days), the patients were divided into two groups: an under-85-day group (range, 29-78 days) and an over-85-day group (87-128 days). Age, gender, fracture type, presence of lesser trochanteric displacement, discharge destination, and walking ability were investigated. The relationship between these factors and the period from surgery to discharge was analyzed with logistic regression analysis. [Results] Age and lesser trochanteric displacement were significantly higher in the over-85-day group, and walking ability before fracture and at discharge were significantly lower in the over-85-day group. Logistic regression analysis showed that lesser trochanteric displacement and age were predictors of the length from surgery to discharge. Lesser trochanteric displacement were observed in 87.5% of these. Immediate displacement after surgery occurred in 57.8% of lesser trochanteric fractures, while 26.3% displaced 1 to 3 weeks after surgery. [Conclusion] This study revealed that lesser trochanteric displacement, higher age, and lower walking ability before fracture and at discharge were associated with longer hospitalizations in patients with femoral trochanteric fractures. Lesser trochanteric displacement were observed in 87.5% of lesser trochanteric fractures. These displacements occurred within 3 weeks after surgery in 84.1% of cases.

Bone Regeneration and Remodeling within a Unidirectional Porous Hydroxyapatite Bone Substitute at a Cortical Bone Defect Site: Histological Analysis at One and Two Years after Implantation.

Unidirectional porous hydroxyapatite (UDPHAp) is an artificial bone substitute with a unique microstructure consisting of 100-300-µm oval pores that present the material unidirectionally. UDPHAp has a compression strength of 14 MPa and a porosity of 75%, which promotes cell migration and capillary formation within the material. Despite these advantageous properties, bone remodeling and bone formation with UDPHAp remain unclear. To examine long-term remodeling and differences in bone formation based on the defect site, trapezoidal prism-shaped UDPHAp blocks were implanted into rectangular-shaped cortical bone defects in the proximal tibia of Japanese white rabbits. Histological analysis performed at 52 and 104 weeks after implantation revealed that bone and capillaries had formed within the implanted UDPHAp material. Bone formed within the UDPHAp implanted in the cortical defect of rabbit tibia and remodel up to two years. The percentage of new bone area within UDPHAp was larger in cortical lesions than that in medullary lesions. These findings suggest that UDPHAp is a promising material for the repair of non-critical-sized cortical bone defects.

Outcome of TCF3-PBX1 positive pediatric acute lymphoblastic leukemia patients in Japan: a collaborative study of Japan Association of Childhood Leukemia Study (JACLS) and Children's Cancer and Leukemia Study Group (CCLSG).

This study reviewed the clinical characteristics of 112 pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients with TCF3-PBX1 fusion treated according to the Japan Association of Childhood Leukemia Study (JACLS) ALL02 protocol (n = 82) and Children's Cancer and Leukemia Study Group (CCLSG) ALL 2004 protocol (n = 30). The 3-year event-free survival (EFS) and overall survival (OS) rates were 85.4 ± 3.9% and 89.0 ± 3.5% in JACLS cohort, and the 5-year EFS and OS were 82.8 ± 7.0% and 86.3 ± 6.4% in CCLSG cohort, respectively, which are comparable to those reported in western countries. Conventional prognostic factors such as age at onset, initial white blood cell count, and National Cancer Institute risk have also no impact on OS in both cohorts. Surprisingly, the pattern of relapse in JACLS cohort, 9 of 82 patients, was unique: eight of nine patients relapsed during the maintenance phase and one patient had primary induction failure. However, bone marrow status and assessment of minimal residual disease on days 15 and 33 did not identify those patients. Interestingly, the two patients with IKZF1 deletion eventually relapsed in JACLS cohort, as did one patient in CCLSG cohort. International collaborative study of larger cohort is warranted to clarify the impact of the IKZF1 deletion on the poor outcome of TCF3-PBX1 positive BCP-ALL.

Assessment of corticosteroid-induced osteonecrosis in children undergoing chemotherapy for acute lymphoblastic leukemia: a report from the Japanese Childhood Cancer and Leukemia Study Group.

Steroid-induced osteonecrosis (ON) is a challenging complication encountered during modern chemotherapy for childhood acute lymphoblastic leukemia (ALL). We retrospectively assessed the incidence of ON and its risk factors in a total of 1095 patients enrolled in 3 consecutive Japanese Children's Cancer and Leukemia Study Group ALL studies (ALL941 [1994 to 2000], n=464; ALL2000 [2000 to 2004], n=305; and ALL2004 [2004 to 2010], n=326). ON was diagnosed in 16 patients, of whom 15 were symptomatic. The cumulative incidence of ON was 0.76% in ALL941, 0.35% in ALL2000, and 3.6% in ALL2004. The incidence of ON in ALL941/2000, in which only prednisolone was administered as a steroid, was significantly lower than that in ALL2004, in which dexamethasone was used as a partial substitute for prednisolone (P<0.01). In ALL2004, sex and age were significantly correlated with the incidence of ON (1.3% in boys vs. 6.7% in girls, P=0.0132; 0.42% for age <10 y vs. 15.6% for age ≥10 y, P<0.0001), suggesting that girls aged 10 years and above are at a greater risk of ON onset. These results indicate that the risk of ON should be considered when administering dexamethasone as part of ALL protocol treatment in girls aged 10 years and above.