Publications by authors named "Hisamichi Tauchi"

41 Publications

A Catheter-Related Bloodstream Infection by in a Child with Acute Myeloid Leukemia: Case Report and Literature Review.

Case Rep Pediatr 2021 9;2021:6691569. Epub 2021 Apr 9.

Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.

The most common organisms isolated from pediatric catheter-related bloodstream infections (CRBSIs) are Gram-positive cocci, such as coagulase-negative staphylococci and . There are few formal reports of infection and even fewer reports of CRBSI due to this Gram-positive rod. Here we report the first case of CRBSI due to in an 8-year-old girl with acute myeloid leukemia in Japan. The isolate exhibited decreased susceptibility to -lactam antibiotics. Antimicrobial therapy with meropenem and vancomycin, in addition to the removal of central venous catheter line, consequently led to a significant clinical improvement of the patient's symptoms. A literature review found available clinical courses in 16 cases (4 pediatric cases including our case) of infection. Our case and those in literature suggested that infection often occurs in patients with indwelling central venous catheters; the literature review further suggested that removal of central venous catheters is required in most cases. Special attention should be paid to the detection of opportunistic infections due to spp. in immunocompromized children who are using a central venous catheter.
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http://dx.doi.org/10.1155/2021/6691569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052168PMC
April 2021

Malignant Ovarian Steroid Cell Tumor, Not Otherwise Specified, Causes Virilization in a 4-Year-Old Girl: A Case Report and Literature Review.

Case Rep Oncol 2020 Jan-Apr;13(1):358-364. Epub 2020 Apr 2.

Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Japan.

We report a case of a 4-year-old girl with an ovarian steroid cell tumor, not otherwise specified (SCT-NOS). She was admitted to the hospital with progressing virilization and Cushing's syndrome, which included abnormality of the perineum, hirsutism, hypertrichosis, flushing of face, hoarseness, and weight gain. Blood testing showed a significantly increased testosterone level and slightly increased cortisol level. Computed tomography scan revealed an 8.0 × 5.0 × 5.0 cm tumor of the right ovary. The patient underwent right salpingo-oophorectomy, and pathological examination showed malignant potential. Three courses of bleomycin, etoposide, and cisplatin were administered as postoperative chemotherapy. After tumor resection, her testosterone decreased to undetectable levels. However, during the course of the treatment, the patient suffered from adrenal insufficiency resulting in the need for hydrocortisone replacement therapy. Although SCT-NOS in childhood are typically benign, pathological findings should be carefully observed for potential malignancy. In cases of cortisol-producing SCT-NOS, serum levels should be monitored, and hydrocortisone replacement therapy should be considered before resection.
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http://dx.doi.org/10.1159/000506044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184839PMC
April 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

Incidence and Antimicrobial Susceptibilities of in Pregnant Females, Ehime University Hospital.

Rinsho Biseibutshu Jinsoku Shindan Kenkyukai Shi 2020 Apr;29(2):53-58

Department of Clinical Laboratory, Ehime University Hospital. Department of Infection Control Team, Ehime University Hospital.

Objective: usually colonizes the lower urogenital tract and has been occasionally associated with pelvic inflammatory disease, postpartum fever, preterm labor in pregnant females. The aim of this study was to investigate the incidence and antimicrobial susceptibilities of isolated from the urogenital tracts of pregnant females.

Methods: Specimens were obtained from the urogenital tract of pregnant females at Department of Obstetrics and Gynecology, Ehime University Hospital, between November 2014 and December 2017. The identification of was confirmed by the polymerase chain reaction (PCR) methods. The minimum inhibitory concentrations (MICs) of antibiotics were measured using a broth microdilution assay.

Results: Of the 1074 specimens tested, 63 (5.9%) were positive for . The -positive rate was highest at 21.3% between 18 and 24 years old. The 21 (25.6%) of 82 patients with bacterial vaginosis were positive for . The 17 (40.5%) of 42 patients delivered by cesarean section that occurred infections including of intrauterine infection and pelvic abscess were positive for . They were all administered β-lactam antibiotics before and after cesarean section. All patients recovered immediately following administration of clindamycin (CLDM). β-lactam antibiotics, macrolides and fosfomycin (FOM) were all resistant against strains. In contrast, strains were susceptible to CLDM, minocycline (MINO) and quinolones.

Conclusions: Our data suggests that the prevalence of genital in pregnant females is high at younger age, bacterial vaginosis and infections after cesarean section with β-lactam antibiotics administration. CLDM, MINO and quinolones may be recommended against infection. Especially, CLDM can be used as the adequate agent for pregnant females because tetracycline and quinolones are undesirable during pregnancy and lactation.
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April 2020

Brain Abscess Associated with Polymicrobial Infection after Intraoral Laceration: A Pediatric Case Report.

Case Rep Pediatr 2020 9;2020:8304302. Epub 2020 Mar 9.

Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

Brain abscesses, infections within the brain parenchyma, can arise as complications of various conditions including infections, trauma, and surgery. However, brain abscesses due to polymicrobial organisms have rarely been reported in children. We herein report a case of a 9-year-old girl with unresolved congenital cyanotic heart disease (CCHD) presenting with right hemiplegia who was diagnosed with brain abscess caused by , , and after oropharyngeal injury. She was treated with intravenous antimicrobial therapy, drainage under craniotomy, and antiedema therapy with glycerol and goreisan, which led to the improvement of right hemiplegia to baseline; she was discharged following eight weeks of intravenous antimicrobial therapy. The clinical diagnosis of the brain abscess was difficult due to the nonspecific presentation, highlighting the importance of cranial imaging without haste in patients at increased risk for brain abscesses such as those with CCHD, presenting with fever in the absence of localizing symptoms or fever, accompanied with abnormal neurological findings.
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http://dx.doi.org/10.1155/2020/8304302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085370PMC
March 2020

Association between daptomycin susceptibility and teicoplanin resistance in Staphylococcus epidermidis.

Sci Rep 2019 12 6;9(1):18533. Epub 2019 Dec 6.

Department of Clinical Pharmacy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime, 790-8578, Japan.

Staphylococcus epidermidis infections are a common occurrence in hospitals, particularly in catheter-related bloodstream and surgical site infections and infective endocarditis. Higher daptomycin minimum inhibitory concentration (MIC) values may be associated with daptomycin treatment failure among patients with S. epidermidis infections. We therefore conducted a retrospective cohort study to determine the predictive value of daptomycin susceptibility. A retrospective study was undertaken in 1,337 patients with S. epidermidis infections. Data were collected from 1 January 2013 to 31 December 2016 at Ehime University Hospital, and included the following clinicopathological factors for evaluation: age, sex, resistance to vancomycin or teicoplanin, and history of antimicrobial therapy. Multiple analysis was performed using logistic regression to identify factors that independently and significantly affected the daptomycin resistance. Daptomycin-resistant S. epidermidis was identified in 38 (2.8%) patients. According to the multiple analysis, only higher MIC values (≥16 mg/L) for teicoplanin (P < 0.0001) were independently associated with an increased risk of developing daptomycin resistance. In conclusion, higher teicoplanin MIC values may predict resistance to daptomycin treatment in S. epidermidis infections.
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http://dx.doi.org/10.1038/s41598-019-55149-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898446PMC
December 2019

Mesenchymal Stem Cell Therapy Overcomes Steroid Resistance in Severe Gastrointestinal Acute Graft-Versus-Host Disease.

Case Rep Transplant 2019 21;2019:7890673. Epub 2019 May 21.

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

The authors describe the high effectiveness of human mesenchymal stem cell (hMSC) therapy to treat steroid-refractory gastrointestinal acute graft-versus-host Disease (aGVHD) in a 15-year-old boy with acute lymphoblastic leukemia (ALL). He received allogeneic hematopoietic stem cell transplantation due to high-risk hypodiploid ALL. Around the time of engraftment, he developed severe diarrhea following high-grade fever and erythema. Although methylprednisolone pulse therapy was added to tacrolimus and mycophenolate mofetil, diarrhea progressed up to 5000~6000 ml/day and brought about hypocalcemia, hypoalbuminemia, and edema. Daily fresh frozen plasma (FFP), albumin, and calcium replacements were required to maintain blood circulation. After aGVHD was confirmed by colonoscopic biopsy, MSC therapy was administered. The patient received 8 biweekly intravenous infusions of 2×10 hMSCs/kg for 4 weeks, after which additional 4 weekly infusions were performed. A few weeks after initiation, diarrhea gradually resolved, and at the eighth dose of hMSC, lab data improved without replacements. MSC therapy successfully treated steroid-refractory gastrointestinal GVHD without complications. Despite life-threatening diarrhea, the regeneration potential of children and adolescents undergoing SMC therapy successfully supports restoration of gastrointestinal damage. Even with its high treatment costs, SMC therapy should be proactively considered in cases where young patients suffer from severe gastrointestinal GVHD.
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http://dx.doi.org/10.1155/2019/7890673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556259PMC
May 2019

Early detection of the PAX3-FOXO1 fusion gene in circulating tumor-derived DNA in a case of alveolar rhabdomyosarcoma.

Genes Chromosomes Cancer 2019 08 10;58(8):521-529. Epub 2019 Feb 10.

Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

Cell-free DNA (cfDNA), which are small DNA fragments in blood derived from dead cells including tumor cells, could serve as useful biomarkers and provide valuable genetic information about the tumors. cfDNA is now used for the genetic analysis of several types of cancers, as a surrogate for tumor biopsy, designated as "liquid biopsy." Rhabdomyosarcoma (RMS), the most frequent soft tissue tumor in childhood, can arise in any part of the body, and radiological imaging is the only available method for estimating the tumor burden, because no useful specific biological markers are present in the blood. Because tumor volume is one of the determinants of treatment response and outcome, early detection at diagnosis as well as relapse is essential for improving the treatment outcome. A 15-year-old male patient was diagnosed with alveolar RMS of prostate origin with bone marrow invasion. The PAX3-FOXO1 fusion was identified in the tumor cells in the bone marrow. After the diagnosis, cfDNA was serially collected to detect the PAX3-FOXO1 fusion sequence as a tumor marker. cfDNA could be an appropriate source for detecting the fusion gene; assays using cfDNA have proved to be useful for the early detection of tumor progression/recurrence. Additionally, the fusion gene dosage estimated by quantitative polymerase chain reaction reflected the tumor volume during the course of the treatment. We suggest that for fusion gene-positive RMSs, and other soft tissue tumors, the fusion sequence should be used for monitoring the tumor burden in the body to determine the diagnosis and treatment options for the patients.
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http://dx.doi.org/10.1002/gcc.22734DOI Listing
August 2019

Exon skipping in CYBB mRNA and skewed inactivation of X chromosome cause late-onset chronic granulomatous disease.

Pediatr Hematol Oncol 2018 Aug - Sep;35(5-6):341-349. Epub 2019 Jan 11.

a Department of Pediatrics , Ehime University Graduate School of Medicine , Toon , Ehime , Japan.

Chronic granulomatous disease (CGD) is a hereditary immunodeficiency syndrome caused by a defect in the NADPH oxidase complex, which is essential for bactericidal function of phagocytes. Approximately 70% of patients with CGD have a mutation in the CYBB gene on the X chromosome, resulting in defective expression of gp91, one of the membrane-bound subunits of NADPH oxidase. Although most patients with X-linked CGD are males, owing to transmission of this disease as an X-linked recessive trait, there are female patients with X-linked CGD. Here, we report the case of a teenage girl with X-linked CGD associated with a heterozygous mutation in exon 5 of the CYBB gene (c.389G > C; R130P), which causes skipping of exon 5, resulting in a premature stop codon in exon 6 of CYBB. Accurate pro-mRNA splicing for mature mRNA formation is regulated by several splicing mechanisms that are essential for appropriate recognition of exonic sequences. The c.389G > C mutation disrupts exonic-splicing regulator sequences, thereby resulting in the aberrant skipping of exon 5 in the CYBB transcript of the patient. The patient showed an extremely skewed (≥96%) X inactivation pattern of the HUMARA locus; this inactivation is thought to be responsible for the development of CGD not only in neutrophils but also in monocytic, T-cell, and B-cell lineages and in CD34-positive immature hematopoietic cells. Our case and other reports indicate that the onset of X-linked CGD in female patients tends to occur later in life, and that the symptoms tend to be milder as compared to male patients.
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http://dx.doi.org/10.1080/08880018.2018.1522402DOI Listing
March 2019

Prolonged adrenal insufficiency after high-dose glucocorticoid in infants with leukemia.

Pediatr Hematol Oncol 2018 Aug - Sep;35(5-6):355-361. Epub 2018 Nov 20.

a Department of Pediatrics , Ehime University Graduate School of Medicine , Ehime , Japan.

Although outcomes for infant leukemia have improved recently, transient adrenal insufficiency is commonly observed during treatment, especially after glucocorticoid administration. We identified three infants with acute leukemia who suffered from prolonged adrenal insufficiency requiring long-term (from 15 to 66 months) hydrocortisone replacement. All infants showed life-threatening symptoms associated with adrenal crisis after viral infections or other stress. Severe and prolonged damage of hypothalamo-pituitary-adrenal (HPA) axis is likely to occur in early infants with leukemia, therefore routine tolerance testing to evaluate HPA axis and hydrocortisone replacement therapy are recommended for infants with leukemia to avoid life-threatening complications caused by adrenal crisis.
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http://dx.doi.org/10.1080/08880018.2018.1539148DOI Listing
March 2019

Sepsis and Pleural Empyema Caused by after Influenza A Virus Infection.

Case Rep Pediatr 2018 23;2018:4509847. Epub 2018 Sep 23.

Department of Pediatrics, Ehime University Graduate School of Medicine, Ehime, Toon, Japan.

(also referred to as group A streptococci, GAS) causes severe invasive diseases such as bacteremia, necrotizing fasciitis, pneumonia, osteomyelitis, septic arthritis, and toxic shock syndrome in children. However, there are only a few reports on pleural empyema caused by GAS in children. Here, we report the case of a 4-year-old boy who presented with pleural empyema due to GAS after influenza A virus infection. With intravenous antibiotic administration and continuous chest-tube drainage, followed by video-assisted thoracoscopic surgery, his condition improved. During the clinical course, cytokines induced in response to the influenza virus, especially IL-1 and IL-10, were elevated 1 week after influenza A infection, but these decreased as the symptoms improved. Reportedly, the IL-10 production increases during influenza virus-bacteria superinfection. These observations suggest that the immunological mechanisms induced by the influenza virus can play an important role in influencing the susceptibility to secondary bacterial infections, such as GAS, in children.
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http://dx.doi.org/10.1155/2018/4509847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174774PMC
September 2018

Therapeutic Effect of Linezolid in Children With Health Care-Associated Meningitis or Ventriculitis.

Clin Pediatr (Phila) 2018 12 27;57(14):1672-1676. Epub 2018 Sep 27.

1 Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

We evaluated the efficacy of linezolid treatment in 6 children with health care-associated meningitis or ventriculitis (HCAMV) caused by gram-positive cocci. All children were diagnosed and treated at the Ehime University Hospital between January 2010 and December 2017. Of these, 5 were treated with linezolid as an empirical therapy. In these 5 patients, vancomycin was initially used but was changed to linezolid because of cerebrospinal fluid (CSF) culture positivity (n = 3) and a high minimum inhibitory concentration of vancomycin (n = 2). The most common HCAMV pathogens were methicillin-resistant coagulase-negative staphylococci (n = 3). In 3 patients, vancomycin concentration was low in CSF but reached the target concentration in serum, while linezolid concentration was high in both CSF and serum. HCAMV treatment using antimicrobial agents with poor CSF penetration may increase the likelihood of therapy failure. Linezolid is more susceptible as the first-line treatment for HCAMV compared with vancomycin.
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http://dx.doi.org/10.1177/0009922818803399DOI Listing
December 2018

Pseudomonas oryzihabitans bacteremia in a child with peripheral T-cell lymphoma after allogeneic bone marrow transplantation.

Pediatr Int 2018 May;60(5):486-488

Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

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http://dx.doi.org/10.1111/ped.13540DOI Listing
May 2018

Usefulness of positron emission tomography-CT for diagnosis of primary bone marrow lymphoma in children.

Pediatr Hematol Oncol 2018 Mar 12;35(2):125-130. Epub 2018 Apr 12.

a Department of Pediatrics , Ehime University Graduate School of Medicine , Ehime , Japan.

Primary bone marrow lymphoma (PBML) is hard to diagnose in children, due to the difficult identification of malignant cells in bone marrow. The first case, a 5-year-old boy, showed knee swelling with an intermittent fever. The second case, a 12-year-old girl, showed fever of unknown origin without lymphadenopathy or hepatosplenomegaly. In both cases, the diagnosis was not confirmed despite the repeated bone marrow aspirations. Finally, bone marrow aspiration and biopsy at the positive site by positron emission tomography (PET)-CT contributed to definitive diagnosis of PBML. The PET-CT is useful for the accurate diagnosis of PBML in children with non-specific symptoms.
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http://dx.doi.org/10.1080/08880018.2018.1459984DOI Listing
March 2018

Combined morphological, immunohistochemical and genetic analyses of medulloepithelioma in the posterior cranial fossa.

Neuropathology 2018 Apr 3;38(2):179-184. Epub 2017 Oct 3.

Department of Neurosurgery, Ehime University School of Medicine, Toon, Japan.

Medulloepithelioma is a rare and highly malignant primitive neuroectodermal tumor that usually occurs in childhood. The diagnosis of this entity required only morphological analysis until the World Health Organization classification of central nervous system (CNS) tumors was revised, and now genetic analysis is necessary. We report a case of medulloepithelioma in the posterior cranial fossa that was diagnosed by both morphological and genetic analyses based on this classification. A 10-month-old girl was admitted to our hospital with consciousness disturbance and vomiting. Neuroimaging revealed a partially calcified mass and cyst formation in the posterior cranial fossa. Partial resection of the tumor was performed and histological findings revealed multilayered rosettes with LIN28A staining, but genetic analysis showed no amplification of the C19MC microRNA cluster at 19q14.32. Therefore, we diagnosed the tumor as medulloepithelioma belonging to other CNS embryonal tumors. The patient was immediately treated with systemic high-dose chemotherapy. Follow-up neuroimaging 10 months later showed no signs of recurrence. Medulloepitheliomas are difficult to diagnose by routine HE staining and require combined morphological, immunohistochemical and genetic analyses to provide an accurate diagnosis.
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http://dx.doi.org/10.1111/neup.12431DOI Listing
April 2018

Kluyvera ascorbata infection in a neonate.

Pediatr Int 2017 May 12;59(5):640-641. Epub 2017 Apr 12.

Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

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http://dx.doi.org/10.1111/ped.13267DOI Listing
May 2017

Rothia mucilaginosa infection in a child with acute lymphoblastic leukemia.

Pediatr Blood Cancer 2017 01 18;64(1):205-206. Epub 2016 Jul 18.

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

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http://dx.doi.org/10.1002/pbc.26145DOI Listing
January 2017

[Homologous Analysis Using Repetitive-sequence-based PCR Typing of Exfoliative Toxin-producing Staphylococcus aureus Isolated from Our Hospital].

Kansenshogaku Zasshi 2015 May;89(3):369-74

We examined staphylococcal coagulase types and homologous analysis using the DiversiLab repetitive-sequence-based PCR system in exfoliative toxin (ET)-producing Staphylococcus aureus. Twenty-two isolates (17 methicillin-sensitive Staphylococcus aureus (MSSA) and 5 methicillin-resistant Staphylococcus aureus (MRSA) isolates) obtained in our hospital from January 2012 and December 2013 were used. Three groups were classified according to the coagulase types and serotypes of ET. The first group (4 MSSA) showed coagulase type I and ET-A, and the second group (3 MSSA and 2 MRSA) showed coagulase type I and ET-B. The third group (10 MSSA and 3 MRSA) showed coagulase type V and ET-B. An analysis by DiversiLab demonstrated that homology was high in both the first and second groups. The homogenousness was high among the third group isolates except for the ocular isolates. In our hospital, three important groups were present according to a coagulase type and an ET type, and the homology of ocular isolates could be different from other materials isolates.
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http://dx.doi.org/10.11150/kansenshogakuzasshi.89.369DOI Listing
May 2015

HMGA2 as a potential molecular target in KMT2A-AFF1-positive infant acute lymphoblastic leukaemia.

Br J Haematol 2015 Dec 25;171(5):818-29. Epub 2015 Sep 25.

Department of Paediatrics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

Acute lymphoblastic leukaemia (ALL) in infants is an intractable cancer in childhood. Although recent intensive chemotherapy progress has considerably improved ALL treatment outcome, disease cure is often accompanied by undesirable long-term side effects, and efficient, less toxic molecular targeting therapies have been anticipated. In infant ALL cells with KMT2A (MLL) fusion, the microRNA let-7b (MIRLET7B) is significantly downregulated by DNA hypermethylation of its promoter region. We show here that the expression of HMGA2, one of the oncogenes repressed by MIRLET7B, is reversely upregulated in infant ALL leukaemic cells, particularly in KMT2A-AFF1 (MLL-AF4) positive ALL. In addition to the suppression of MIRLET7B, KMT2A fusion proteins positively regulate the expression of HMGA2. HMGA2 is one of the negative regulators of CDKN2A gene, which encodes the cyclin-dependent kinase inhibitor p16(INK4A) . The HMGA2 inhibitor netropsin, when combined with demethylating agent 5-azacytidine, upregulated and sustained the expression of CDKN2A, which resulted in growth suppression of KMT2A-AFF1-expressing cell lines. This effect was more apparent compared to treatment with 5-azacytidine alone. These results indicate that the MIRLET7B-HMGA2-CDKN2A axis plays an important role in cell proliferation of leukaemic cells and could be a possible molecular target for the therapy of infant ALL with KMT2A-AFF1.
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http://dx.doi.org/10.1111/bjh.13763DOI Listing
December 2015

Tsukamurella inchonensis infection in a child with Hodgkin's lymphoma.

Pediatr Int 2015 ;57(1):e7-10

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

Tsukamurella spp. infection is a rare but important cause of bacteremia in immunocompromised patients. The organism is an aerobic, Gram-positive, weakly acid-fast bacillus that is difficult to differentiate from other aerobic Actinomycetales by standard laboratory methods. Here, we report on the case of a 14-year-old patient with Hodgkin's lymphoma who, after intensive chemotherapy, developed Tsukamurella inchonensis bacteremia, which was identified on the peripherally inserted central venous catheter (PICC) using 16S rRNA sequencing analysis. The bacteremia was successfully controlled with antimicrobial therapy and subsequent removal of the PICC. This is the first report of bacteremia by Tsukamurella inchonensis in immunocompromised children. Careful observation and prompt analysis of opportunistic infection, including Tsukamurella spp., is very important in immunocompromised children.
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http://dx.doi.org/10.1111/ped.12472DOI Listing
December 2016

Bacteriological characteristics of Arcanobacterium haemolyticum isolated from seven patients with skin and soft-tissue infections.

J Med Microbiol 2015 Apr 9;64(Pt 4):369-374. Epub 2015 Feb 9.

Department of Clinical Laboratory, Ehime University Hospital, Toon, Japan.

Bacteriological examinations were conducted for seven Arcanobacterium haemolyticum strains isolated from elderly patients with skin and soft-tissue infections, such as cellulitis and skin ulcers. Streptococcus dysgalactiae or Gram-positive cocci were isolated together with A. haemolyticum from all patients. The strains were identified as A. haemolyticum based on their being catalase negative, reverse Christie, Atkins and Munch-Petersen (CAMP) positive and phospholipase D gene positive in respective tests. Moreover, API Coryne and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry confirmed the identification of A. haemolyticum. All strains showed good susceptibility to minocycline, vancomycin and β-lactam antibiotics, but several strains were resistant to gentamicin and levofloxacin.
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http://dx.doi.org/10.1099/jmm.0.000038DOI Listing
April 2015

Procalcitonin as a marker of respiratory disorder in neonates.

Pediatr Int 2015 Apr 11;57(2):263-8. Epub 2014 Dec 11.

Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

Background: Serum procalcitonin (PCT) increases in various respiratory disorders such as acute respiratory distress syndrome. Elevated PCT is also observed in healthy neonates. In this study, we investigated whether PCT is a good marker of respiratory disorder in neonates.

Methods: A total of 155 neonates with or without respiratory disorder, were eligible for the study. PCT was measured on electrochemiluminescence immunoassay. Each neonate was allocated to the non-respiratory disorder (control) group (n = 95), or a respiratory disorder group (n = 60). PCT was compared between the groups, and association with other markers, including C-reactive protein (CRP) and white blood cell (WBC) count, was analyzed.

Results: Of the 60 neonates in the respiratory disorder group, 39, 10, five, one, two, two, and one neonates had transient tachypnea of the newborn, respiratory distress syndrome, air leak syndrome, meconium aspiration syndrome, 18-trisomy, neonatal asphyxia, and congenital diaphragmatic hernia, respectively. Mean PCT, CRP and WBC count in the respiratory disorder group were 9.01 ng/mL, 0.26 mg/dL, and 16,100 cells/μL, respectively. The area under the curve obtained for PCT in distinguishing between the respiratory disorder and control groups was 0.85 (sensitivity, 66.7%; specificity, 93.0%; optimum cut-off, 3.73 ng/mL), that for CRP was 0.72 (sensitivity, 75.0%; specificity, 64.6%; optimum cut-off, 0.14 mg/dL), and for WBC it was 0.44 (sensitivity, 60.0%; specificity, 29.6%; optimum cut-off, 15,000 cells/μL).

Conclusions: PCT is more susceptible, as a diagnostic parameter of infection, to the effect of respiratory disturbance than CRP and WBC.
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http://dx.doi.org/10.1111/ped.12505DOI Listing
April 2015

Salvage allogeneic stem cell transplantation in patients with pediatric myelodysplastic syndrome and myeloproliferative neoplasms.

Pediatr Blood Cancer 2014 Oct 29;61(10):1860-6. Epub 2014 Jun 29.

Department of Pediatrics, The University of Tokyo, Tokyo, Japan; Department of Cell Therapy and Transplantation Medicine, The University of Tokyo, Tokyo, Japan; Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curable approach for myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN); however, the event-free survival rate of patients with pediatric MDS and MPN is still only approximately 60%. Although salvage HSCT is the only curative approach for patients with the failure of previous HSCT, its safety and efficacy have yet to be determined.

Procedures: We retrospectively analyzed 51 pediatric MDS or MPN who received salvage HSCT for relapse or graft failure following HSCT using registry data of the Japan Society for Hematopoietic Cell Transplantation. The indications used for salvage HSCT were relapse in 22 patients and graft failure in 29 patients.

Results: The overall survival (OS) rate for salvage HSCT in relapsed patients was 49.0 ± 10.8% at 3 years. The cumulative incidence of relapse following salvage HSCT was 29.8 ± 10.7% at 3 years, whereas the incidence of non-relapse mortality (NRM) was 28.6 ± 10.2%. No significant differences were observed in the OS after salvage HSCT between disease types. Twenty-four of 29 patients who received salvage HSCT for graft failure achieved engraftment, resulting in an engraftment probability of 81.5 ± 8.0% on day 100. The OS rate after salvage HSCT for graft failure was 56.8 ± 9.6% at 3 years.

Conclusions: Second HSCT should be considered as a valuable option for the patients with relapse and graft failure in patients with pediatric MDS or MPN after HSCT, but high NRM is an important issue that needs to be addressed.
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http://dx.doi.org/10.1002/pbc.25121DOI Listing
October 2014

Infantile generalized pustular psoriasis: successful disease control with intermittent etretinate.

J Dermatol 2014 May;41(5):403-6

Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan.

Infantile generalized pustular psoriasis is a rare form of psoriasis and the best treatment is controversial. We experienced a 2-year-old female with erythema on her neck and axilla starting at 3 months of age. She presented with recurrent annular and geographic scaly erythema with a few pustules on the neck, precordium and axilla, but no fever. The histopathology revealed subcorneal neutrophilic infiltration and microabscesses without Kogoj's spongiform pustules. The initial diagnosis was subcorneal pustular dermatosis. However, she developed widespread geographic erythema and numerous pustules over her entire body with a fever when she got a cold. A second skin biopsy revealed monolocular pustules and Kogoj's spongiform pustules in the subcorneal layer. Etretinate was administrated after a diagnosis of pustular psoriasis was made and her condition improved gradually. The choice of treatment depends on patient age, general condition and the disease severity.
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http://dx.doi.org/10.1111/1346-8138.12481DOI Listing
May 2014

Lineage-dependent skewing of loss of heterozygosity (LOH) of KRAS gene in a case of juvenile myelomonocytic leukemia.

Eur J Haematol 2015 Feb 17;94(2):177-81. Epub 2014 May 17.

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

Juvenile myelomonocytic leukemia (JMML) is a clonal disease arising from abnormal hematopoietic stem cells, although the involvement of lymphoid lineage differs among reported cases. Here, we present a case of JMML with a KRAS G13D mutation. The mutation was detected in various hematopoietic lineages, including T and B lymphocytes and also in lineage(-) CD34(+) CD38(-) hematopoietic stem cells, showing a different percentage of affected cells in each lineage. Single cell-based analysis of hematopoietic cells revealed the loss of wild-type KRAS in a significant proportion of G13D-harboring cells. The percentage of loss of heterozygosity (LOH)/non-LOH cells showed lineage-dependent skewing in hematopoietic cells. The loss of the wild-type KRAS allele may be a common secondary genetic change in KRAS-related JMML and may affect the differentiation behavior of early JMML progenitors.
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http://dx.doi.org/10.1111/ejh.12355DOI Listing
February 2015

Pediatric subcutaneous panniculitis-like T-cell lymphoma with favorable result by immunosuppressive therapy: a report of two cases.

Pediatr Hematol Oncol 2014 Sep 31;31(6):528-33. Epub 2014 Mar 31.

Department of Hematology and Oncology, Shikoku Medical Center for Children and Adults , Kagawa , Japan.

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a rare type of skin lymphoma. Histopathology mimicking a lobular panniculitis makes it difficult to distinguish SPTL from benign autoimmune disease. We present cases of a 10-year-old female and an 11-year-old male with SPTL showing recurrent panniculitis and systemic manifestations. Initially, antibiotics and steroids were administered to treat infectious disease and benign panniculitis. However, they experienced recurrent fever and erythema nodosum. Additional immunohistochemistry and T-cell receptor (TCR) gene rearrangement analyses were performed, enabling the establishment of an SPTL diagnosis. The affected patients were given immunosuppressive therapy with favorable results.
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http://dx.doi.org/10.3109/08880018.2014.896062DOI Listing
September 2014

CLTC-ALK fusion as a primary event in congenital blastic plasmacytoid dendritic cell neoplasm.

Genes Chromosomes Cancer 2014 Jan 21;53(1):78-89. Epub 2013 Oct 21.

Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a subtype of acute myeloid leukemia, affecting mainly the elderly. It is thought to be derived from plasmacytoid dendritic cell precursors, which frequently present as cutaneous lesions. We have made a detailed analysis of an infant with BPDCN, who manifested with hemophagocytic lymphohistiocytosis. The peripheral blood leukocytes revealed the t(2;17;8)(p23;q23;p23) translocation and a CLTC-ALK fusion gene, which have never been reported in BPDCN or in any myeloid malignancies thus far. Neonatal blood spots on the patient's Guthrie card were analyzed for the presence of the CLTC-ALK fusion gene, identifying the in utero origin of the leukemic cell. Although the leukemic cells were positive for CD4, CD56, CD123, and CD303, indicating a plasmacytoid dendritic cell phenotype, detailed analysis of the lineage distribution of CLTC-ALK revealed that part of monocytes, neutrophils, and T cells possessed the fusion gene and were involved in the leukemic clone. These results indicated that leukemic cells with CLTC-ALK originated in a multipotent hematopoietic progenitor in utero. This is the first report of the CLTC-ALK fusion gene being associated with a myeloid malignancy, which may give us an important clue to the origin of this rare neoplasm.
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http://dx.doi.org/10.1002/gcc.22119DOI Listing
January 2014

Treatment with linezolid in a neonate with meningitis caused by methicillin-resistant Staphylococcus epidermidis.

Eur J Pediatr 2013 Oct 26;172(10):1419-21. Epub 2013 Feb 26.

Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.

Unlabelled: Recent findings have focused on the possible role of linezolid (LZD) as a suitable candidate for the treatment of central nervous system infections. LZD treatment for meningitis has been sporadically reported in adults, but there are no reports in neonates or infants. We report a case of meningitis caused by methicillin-resistant Staphylococcus epidermidis (MRSE) in a neonatal girl. The patient had intraventricular hemorrhage on postnatal day 1 and was treated with ventricular drainage. Twenty-two days after drainage, the patient developed a fever and seizure. Although ampicillin and ceftriaxone were given empirically for meningitis, an increased cell count and protein were observed in cerebrospinal fluid (CSF). Vancomycin (VCM) was administered intravenously because MRSE was detected from CSF 2 days after the administration of ampicillin and ceftriaxone. However, intravenous administration of VCM did not show any effect. Subsequent treatment of LZD successfully reduced the cell count and protein in CSF.

Conclusion: LZD may be a treatment option for neonates and infants for drain-associated meningitis caused by MRSE.
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http://dx.doi.org/10.1007/s00431-013-1978-7DOI Listing
October 2013

Infantile inflammatory pseudotumor of the facial nerve as a complication of epidermal nevus syndrome with cholesteatoma.

Auris Nasus Larynx 2013 Dec 19;40(6):569-72. Epub 2013 Feb 19.

Department of Otolaryngology, Ehime University School of Medicine, Ehime, Japan.

The first reported case of facial paralysis due to an inflammatory pseudotumor (IPT) of the facial nerve as a complication of epidermal nevus syndrome (ENS) is herein presented. A 10-month-old female patient was diagnosed with ENS at 3 months of age. She was referred to us because of moderate left facial paralysis. Epidermal nevi of her left auricle extended deep into the external ear canal. Otoscopy revealed polypous nevi and cholesteatoma debris filling the left ear. Computed tomography showed a soft mass filling the ear canal, including the middle ear, and an enormously enlarged facial nerve. Surgical exploration revealed numerous polypous nevi, external ear cholesteatoma, and tumorous swelling of the facial nerve. The middle ear ossicles were completely lost. The facial paralysis was improved after decompression surgery, but recurred 5 months later. A second operation was conducted 10 months after the first. During this operation, facial nerve decompression was completed from the geniculate ganglion to near the stylomastoid foramen. Histological diagnosis of the facial nerve tumor was IPT probably caused by chronic external ear inflammation induced by epidermal nevi. The facial paralysis gradually improved to House-Blackmann grade III 5 years after the second operation.
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http://dx.doi.org/10.1016/j.anl.2012.11.016DOI Listing
December 2013

Neonatal iliopsoas abscess.

Pediatr Int 2012 Oct;54(5):712-4

Departments of Surgery, Division of Gastrointestinal Surgery and Surgical Oncology, Ehime University School of Medicine, Ehime, Japan.

Iliopsoas abscess (IPA) is rare in children, particularly in neonates. A male neonate was born at 38 weeks of gestation with a weight of 2915 g. On day 22 after birth, his family noticed that his right thigh was swollen. Abdominal computed tomography showed a mass extending to the right iliopsoas from the right thigh with thick septa. Puncture to the right groin yielded purulent fluid, and so a diagnosis of abscess was made. The puncture was followed by surgical drainage through a small inguinal incision, and the abscess cavity was irrigated thoroughly using normal saline. Culture of abscess fluid was positive for Streptococcus pneumoniae, so intravenous ABPC infusion was continued. The postoperative magnetic resonance imaging indicate that the IPA was derived from arthritis of the hip, and the patients received Riemenbügel for the incomplete hip dislocation. He is doing well at 2 years of age.
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http://dx.doi.org/10.1111/j.1442-200X.2012.03593.xDOI Listing
October 2012