Publications by authors named "Hideaki Nakajima"

267 Publications

Comparison of Surgical Outcomes After Open- and Double-Door Laminoplasties for Patients with Cervical Ossification of the Posterior Longitudinal Ligament: A Prospective Multicenter Study.

Spine (Phila Pa 1976) 2021 May 6. Epub 2021 May 6.

Department of Orthopaedic Surgery, School of Medicine, Keio University, Shinjuku Ward, Tokyo, Japan Department of Orthopedic Surgery, Tokyo Medical and Dental University, Bunkyo Ward, Tokyo, Japan Department of Orthopedic Surgery, Saiseikai Kawaguchi General Hospital, Kawaguchishi, Saitama, Japan Department of Orthopedic Surgery, Kudanzaka Hospital, Chiyodaku, Japan Department of Orthopaedic Surgery, Wakayama Medical University Kihoku Hospital, Katsuragi-cho, Itogun, Wakayama, Japan Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan Department of Orthopedic Surgery, Niigata University Medicine and Dental General Hospital, Chuo Ward, Niigata, Niigata, Japan Department of Orthopedic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan Department of Orthopedics, Jichi Medical University, Shimotsuke, Tochigi, Japan Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Chuo Ward, Chiba, Japan Department of Orthopedic Surgery, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan Department of Orthopedic Surgery, Osaka Rosai Hospital, Sakaishi, Osaka, Japan Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine,, Showa Ward, Nagoya, Aichi, Japan Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan Department of Orthopaedic Surgery, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, Japan Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences University of Fukui, Eiheiji-cho, Yoshida-gun, Fukui, Japan Department of Orthopedic Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan Department of Orthopedic Surgery, Imakiire General Hospital, Kagoshimashi, Japan Department of Orthopedic Surgery, Graduate School of Medicine, Osaka University, Suita-shi, Osaka, Japan Department of Orthopaedic Surgery, Kurume University School of Medicine, Kurume-shi, Fukuoka, Japan Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan Department of Orthopedic Surgery, University of Yamanashi, Chuo Ward, Yamanashi, Japan Department of Orthopaedic Surgery, Dokkyo Medical University School of Medicine, Mibu-machi, Shimotsuga-gun, Tochigi, Japan Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan Department of Orthopedic Surgery, Surgical Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan Department of Orthopaedic Surgery, Tohoku University School of Medicine, Aoba Ward, Sendai, Miyagi, Japan Department of Orthopedic Surgery, Faculty of Medicine, University of Toyama, Toyama, Toyama, Japan Japanese Multicenter Research Organization for Ossification of the Spinal Ligament.

Study Design: A prospective multicenter study.

Objective: To evaluate and compare the surgical outcomes after open-door (OD) and double-door (DD) laminoplasties in subjects with cervical ossification of the posterior longitudinal ligament (OPLL).

Summary Of Background Data: Although previous studies compared clinical results after OD and DD laminoplasties, they were performed at a single institution with a relatively small sample size targeting mixed pathologies, including cervical spondylotic myelopathy.

Methods: This study was performed by the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament. A total of 478 patients with myelopathy caused by cervical OPLL from 28 institutions were prospectively registered from 2014 to 2017 and followed up for 2 years. Of these, 41 and 164 patients received OD and DD laminoplasties, respectively. Demographic information, medical history, and imaging findings were collected. Clinical outcomes were assessed using the cervical Japanese Orthopaedic Association (JOA), JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), and visual analog scale (VAS) scores.

Results: Age, sex, symptom duration, and comorbidities were not significantly different between the groups. Segmental ossification was the most frequent in both groups. No significant differences in K-line type, canal occupying ratio, C2-C7 angles, and range of motion (ROM) were found. Both procedures reduced the cervical ROM postoperatively. A comparable frequency of perioperative complications was observed between the groups. The cervical JOA scores showed a similar improvement at 2 years postoperatively. The reduction in VAS score for neck pain was favorable in the OD group (P = 0.02), while other pain assessments did not show any significant differences between the groups. The functional outcomes assessed using the JOACMEQ presented equivalent effective rates.

Conclusion: The results demonstrated almost comparable surgical outcomes between OD and DD laminoplasties. Laminoplasty is a valuable technique as a therapeutic option for cervical OPLL.Level of Evidence: 5.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BRS.0000000000004094DOI Listing
May 2021

PU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress.

J Exp Med 2021 Jun;218(6)

Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO.

Hematopoietic stem cells (HSCs) are capable of entering the cell cycle to replenish the blood system in response to inflammatory cues; however, excessive proliferation in response to chronic inflammation can lead to either HSC attrition or expansion. The mechanism(s) that limit HSC proliferation and expansion triggered by inflammatory signals are poorly defined. Here, we show that long-term HSCs (HSCLT) rapidly repress protein synthesis and cell cycle genes following treatment with the proinflammatory cytokine interleukin (IL)-1. This gene program is associated with activation of the transcription factor PU.1 and direct PU.1 binding at repressed target genes. Notably, PU.1 is required to repress cell cycle and protein synthesis genes, and IL-1 exposure triggers aberrant protein synthesis and cell cycle activity in PU.1-deficient HSCs. These features are associated with expansion of phenotypic PU.1-deficient HSCs. Thus, we identify a PU.1-dependent mechanism triggered by innate immune stimulation that limits HSC proliferation and pool size. These findings provide insight into how HSCs maintain homeostasis during inflammatory stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1084/jem.20201169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056754PMC
June 2021

Pathogenic variants associated with VEXAS syndrome in Japanese patients with relapsing polychondritis.

Ann Rheum Dis 2021 Mar 31. Epub 2021 Mar 31.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Objectives: To determine clinical and genetic features of individuals with relapsing polychondritis (RP) likely caused by pathogenic somatic variants in ubiquitin-like modifier activating enzyme 1 ().

Methods: Fourteen patients with RP who met the Damiani and Levine criteria were recruited (12 men, 2 women; median onset age (IQR) 72.1 years (67.1-78.0)). Sanger sequencing of was performed using genomic DNA from peripheral blood leukocytes or bone marrow tissue. Droplet digital PCR (ddPCR) and peptide nucleic acid (PNA)-clamping PCR were used to detect low-prevalence somatic variants. Clinical features of the patients were investigated retrospectively.

Results: was examined in 13 of the 14 patients; 73% (8/11) of the male patients had somatic variants (c.121A>C, c.121A>G or c.122T>C resulting in p.Met41Leu, p.Met41Val or p.Met41Thr, respectively). All the variant-positive patients had systemic symptoms, including a significantly high prevalence of skin lesions. ddPCR detected low prevalence (0.14%) of somatic variant (c.121A>C) in one female patient, which was subsequently confirmed by PNA-clamping PCR.

Conclusions: Genetic screening for pathogenic variants should be considered in patients with RP, especially male patients with skin lesions. The somatic variant in in the female patient is the first to be reported.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2021-220089DOI Listing
March 2021

Severity of Myelopathy is Closely Associated With Advanced Age and Signal Intensity Change in Cervical Ossification of the Posterior Longitudinal Ligament: A Prospective Nationwide Investigation.

Clin Spine Surg 2021 Mar 23. Epub 2021 Mar 23.

Department of Orthopedic Surgery, Tokyo Medical and Dental University Japanese Multicenter Research Organization for Ossification of the Spinal Ligament, Tokyo Department of Orthopedic Surgery, Saiseikai Kawaguchi General Hospital, Saitama Department of Orthopedic Surgery, Kudanzaka Hospital, Chiyadaku Department of Orthopaedic Surgery, Wakayama Medical University Kihoku Hospital, Wakayama Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine, Aomori Department of Orthopedic Surgery, Niigata University Medicine and Dental General Hospital, Niigata Department of Orthopedic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki Department of Orthopedics, Jichi Medical University, Tochigi Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Chiba Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo Department of Orthopedic Surgery, Yamaguchi University School of Medicine, Yamaguchi Department of Orthopedic Surgery, Osaka Rosai Hospital, Osaka Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Aichi Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo Department of Orthopaedic Surgery, Shiga University of Medical Science, Shiga Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui, Fukui Department of Orthopedic Surgery, Tokyo Medical University, Tokyo Department of Orthopedic Surgery, Imakiire General Hospital, Kagoshimashi Department of Orthopedic Surgery, Graduate School of Medicine, Osaka University, Osaka Department of Orthopaedic Surgery, Kurume University School of Medicine, Fukuoka Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Shizuoka Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa Department of Orthopedic Surgery, University of Yamanashi, Yamanashi Department of Orthopaedic Surgery, Dokkyo Medical University School of Medicine, Tochigi Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto Department of Orthopedic Surgery, Surgical Science, Tokai University School of Medicine, Kanagawa Department of Orthopaedic Surgery, Tohoku University School of Medicine, Miyagi Department of Orthopedic Surgery, Faculty of Medicine, University of Toyama, Toyama, Japan.

Study Design: Prospective, nationwide case series.

Objective: To identify preoperative factors associated with myelopathy and neurological impairment in patients with cervical ossification of the posterior longitudinal ligament (OPLL).

Summary Of Background Data: Various studies have reported clinical outcomes following the surgical treatment of OPLL. However, there has been no large-scale study of preoperative clinical features in patients with cervical OPLL.

Materials And Methods: Data were prospectively collected from 28 institutions nationwide in Japan. In total, 512 patients with neurological impairment caused by cervical OPLL requiring surgery were enrolled. Basic demographic and clinical data, including age, sex, diabetes status, body mass index, smoking history, and disease duration were collected. C2-7 lordotic angle, canal narrowing ratio, range of motion in flexion-extension at C2-7, and type of OPLL were evaluated on lateral radiographs to identify factors influencing the clinical features of patients with OPLL in whom surgery was planned.

Results: Complete documentation was available for 490 patients (362 male, 128 female). In total, 34 patients had the localized type, 181 had the segmental type, 64 had the continuous type, and 211 had the mixed type. Although there were no significant differences in age, body mass index, disease duration, Japanese Orthopedic Association (JOA) score, and lordotic angle at C2-7 according to the type of OPLL, significant differences were observed in a range of motion at C2-7 and the canal narrowing ratio among the 4 types. Multiple regression analysis revealed that the JOA score was significantly associated with age and signal intensity change on magnetic resonance imaging.

Conclusions: This is the first large-scale, prospective, multicenter case series study to investigate factors influencing preoperative neurological status in patients with OPLL. Age and signal intensity change on magnetic resonance images were significantly associated with JOA score in patients requiring surgery.

Level Of Evidence: Level II.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BSD.0000000000001164DOI Listing
March 2021

Comparison of Clinical Features Between Primary and Secondary Breast Diffuse Large B Cell Lymphoma: A Yokohama Cooperative Study Group for Hematology Multicenter Retrospective Study.

Indian J Hematol Blood Transfus 2021 Jan 23;37(1):60-66. Epub 2020 Jun 23.

Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine, Yokohama, Kanagawa Japan.

We performed a retrospective analysis of DLBCL with breast involvement to compare the prognosis of primary breast lymphoma (PBL) to secondary breast lymphoma (SBL; especially in limited stage cases). We retrospectively reviewed records of 25 diffuse large B-cell lymphoma (DLBCL) patients with breast involvement who received chemotherapy between January 2000 and August 2012. We compared clinical features and prognosis among patients with PBL ( = 11), limited stage SBL (LSBL;  = 6), and advanced stage SBL (ASBL,  = 8). The PBL group had significantly lesser patients with breast tumours (BTs) > 5 cm than the SBL group ( = 0.02). After a median follow-up of 71.3 months, we observed significantly better 5-year overall survival (OS) in the PBL group (90.0%) than in the LSBL (33.3%,  = 0.01) group, but not for progression-free survival (PFS). Patients with BT > 5 cm had worse OS ( = 0.01) and PFS ( = 0.04) than those with BT ≤ 5 cm. PBL had a better prognosis than SBL among limited stage DLBCL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12288-020-01307-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900317PMC
January 2021

A RUNX-CBFβ-driven enhancer directs the Irf8 dose-dependent lineage choice between DCs and monocytes.

Nat Immunol 2021 03 18;22(3):301-311. Epub 2021 Feb 18.

Department of Immunology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.

The transcription factor IRF8 is essential for the development of monocytes and dendritic cells (DCs), whereas it inhibits neutrophilic differentiation. It is unclear how Irf8 expression is regulated and how this single transcription factor supports the generation of both monocytes and DCs. Here, we identified a RUNX-CBFβ-driven enhancer 56 kb downstream of the Irf8 transcription start site. Deletion of this enhancer in vivo significantly decreased Irf8 expression throughout the myeloid lineage from the progenitor stages, thus resulting in loss of common DC progenitors and overproduction of Ly6C monocytes. We demonstrated that high, low or null expression of IRF8 in hematopoietic progenitor cells promotes differentiation toward type 1 conventional DCs, Ly6C monocytes or neutrophils, respectively, via epigenetic regulation of distinct sets of enhancers in cooperation with other transcription factors. Our results illustrate the mechanism through which IRF8 controls the lineage choice in a dose-dependent manner within the myeloid cell system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41590-021-00871-yDOI Listing
March 2021

Antibody titers against SARS-CoV-2 decline, but do not disappear for several months.

EClinicalMedicine 2021 Feb 11;32:100734. Epub 2021 Feb 11.

Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine, Japan.

Background: To develop an effective vaccine against a novel viral pathogen, it is important to understand the longitudinal antibody responses against its first infection. Here we performed a longitudinal study of antibody responses against SARS-CoV-2 in symptomatic patients.

Methods: Sequential blood samples were collected from 39 individuals at various timepoints between 0 and 154 days after onset. IgG or IgM titers to the receptor binding domain (RBD) of the S protein, the ectodomain of the S protein, and the N protein were determined by using an ELISA. Neutralizing antibody titers were measured by using a plaque reduction assay.

Findings: The IgG titers to the RBD of the S protein, the ectodomain of the S protein, and the N protein peaked at about 20 days after onset, gradually decreased thereafter, and were maintained for several months after onset. Extrapolation modeling analysis suggested that the IgG antibodies were maintained for this amount of time because the rate of reduction slowed after 30 days post-onset. IgM titers to the RBD decreased rapidly and disappeared in some individuals after 90 days post-onset. All patients, except one, possessed neutralizing antibodies against authentic SARS-CoV-2, which they retained at 90 days after onset. The highest antibody titers in patients with severe infections were higher than those in patients with mild or moderate infections, but the decrease in antibody titer in the severe infection cohort was more remarkable than that in the mild or moderate infection cohort.

Interpretation: Although the number of patients is limited, our results show that the antibody response against the first SARS-CoV-2 infection in symptomatic patients is typical of that observed in an acute viral infection.

Funding: The Japan Agency for Medical Research and Development and the National Institutes of Allergy and Infectious Diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2021.100734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877219PMC
February 2021

Medicine at mass gatherings: current progress of preparedness of emergency medical services and disaster medical response during 2020 Tokyo Olympic and Paralympic Games from the perspective of the Academic Consortium (AC2020).

Acute Med Surg 2021 Jan-Dec;8(1):e626. Epub 2021 Feb 2.

Japan Pediatric Society Tokyo Japan.

Mass gatherings are events characterized by "the concentration of people at a specific location for a specific purpose over a set period of time that have the potential to strain the planning and response resources of the host country or community." Previous reports showed that, as a result of the concentration of people in the limited area, injury and illness occurred due to several factors. The response plan should aim to provide timely medical care to the patients and to reduce the burden on emergency hospitals, and to maintain a daily emergency medical services system for residents of the local area. Although a mass gathering event will place a significant burden on the local health-care system, it can provide the opportunity for long-term benefits of public health-care and improvement of daily medical service systems after the end of the event. The next Olympic and Paralympic Games will be held in Tokyo, during which mass gatherings will occur on a daily basis in the context of the coronavirus disease (COVID-19) epidemic. The Academic Consortium on Emergency Medical Services and Disaster Medical Response Plan during the Tokyo Olympic and Paralympic Games in 2020 (AC2020) was launched 2016, consisting of 28 academic societies in Japan, it has released statements based on assessments of medical risk and publishing guidelines and manuals on its website. This paper outlines the issues and countermeasures for emergency and disaster medical care related to the holding of this big event, focusing on the activities of the academic consortium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ams2.626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852170PMC
February 2021

Elevated serum gasdermin D N-terminal implicates monocyte and macrophage pyroptosis in adult-onset Still's disease.

Rheumatology (Oxford) 2021 Feb 7. Epub 2021 Feb 7.

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Objectives: Elevation of serum IL-18 in adult-onset Still's disease (AOSD) and systemic JIA (sJIA) suggests the role of the inflammasome in these diseases. Gasdermin D is a pore-forming protein playing central roles in inflammasome-mediated inflammation, but its role in rheumatic disease is unknown. We aimed to elucidate the auto-inflammatory mechanisms in AOSD and sJIA.

Methods: Patients with AOSD, sJIA, hemophagocytic lymphohistiocytosis (HLH) and Behçet's disease followed at Yokohama City University (YCU), or US National Institutes of Health (NIH) were included in the study. Disease activity was evaluated by the modified Pouchot score. Ferritin and N-terminal gasdermin D levels in serum and culture supernatant were measured by ELISA. Primary monocytes (Mo) were stimulated with GM-CSF or M-CSF and differentiated into M1 macrophages (Mφ) or M2Mφ, respectively. The number of Mo/Mφ and their viability were monitored over time.

Results: Patients with active AOSD and sJIA had increased levels of serum gasdermin D N-terminal, which correlated with serum ferritin and IL-18 levels. Mo-derived Mφ from active AOSD patients showed reduced cell viability and increased cell death. The number of cultured Mφ cells on day nine was negatively correlated with the serum ferritin and gasdermin D levels. Higher ferritin and gasdermin D levels were observed in the M1Mφ culture supernatant of active AOSD patients. Gasdermin D inhibitors reduced the pyroptosis-mediated ferritin release in Mo.

Conclusion: Elevation of serum gasdermin D N-terminal provides evidence for inflammasome activation triggering gasdermin D-mediated Mo and Mφ pyroptosis in AOSD and possibly sJIA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/keaa814DOI Listing
February 2021

Initial hydroxychloroquine monotherapy in systemic lupus erythematosus: report of three cases.

Mod Rheumatol Case Rep 2021 Feb 18:1-9. Epub 2021 Feb 18.

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Glucocorticoids (GCs) use is associated with increased organ damage in systemic lupus erythematosus (SLE), and the treatment goal is to stop their use. Treatment with hydroxychloroquine (HCQ) without daily GCs may benefit patients by minimising the cumulative dose of GCs, but clinical experience with HCQ monotherapy is limited. To accumulate evidence for initial HCQ monotherapy in SLE, we retrospectively analysed three new SLE patients who visited Yokohama City University Hospital in 2015. The patients were all Japanese females with a mean age of 26.0 ± 5.3 years, high anti-dsDNA antibody titres, no major organ damage, and a mean pre-treatment Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 9.3 ± 3.1. During the mean observation period of 3.8 ± 0.8 years, none of them received daily GCs or immunosuppressants, but one of the three patients were treated with short-term oral GCs and NSAIDs for a skin rash or arthralgia flairs. SLEDAI-2K was reduced to 3.3 ± 1.2. No other new SLE symptoms emerged, and the Systemic Lupus International Collaborating Clinics Damage Index (SDI) of them were maintained at 0. None of the patients developed HCQ-related retinal toxicity. Current experience with initial HCQ monotherapy suggests that such a therapeutic strategy may be useful in managing disease activity and preserving cumulative GCs in SLE patients without organ involvements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/24725625.2021.1881215DOI Listing
February 2021

Changes in the proportion of clinical clusters contribute to the phenotypic evolution of Behçet's disease in Japan.

Arthritis Res Ther 2021 02 1;23(1):49. Epub 2021 Feb 1.

Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.

Background: We hypothesized that Behçet's disease (BD) consists of several clinical subtypes with different severity, resulting in heterogeneity of the disease. Here, we conducted a study to identify clinical clusters of BD.

Methods: A total of 657 patients registered in the Yokohama City University (YCU) regional BD registry between 1990 and 2018, as well as 6754 patients who were initially registered in the Japanese Ministry of Health, Labour and Welfare (MHLW) database between 2003 and 2014, were investigated. The YCU registry data regarding the clinical manifestations of BD, human leukocyte antigen (HLA) status, treatments, and hospitalizations were analyzed first, followed by similar analyses of the MHLW for validation. A hierarchical cluster analysis was independently performed in both patient groups.

Results: A hierarchical cluster analysis determined five independent clinical clusters in the YCU cohort. Individual counterparts of the YCU clusters were confirmed in the MHLW registry. Recent phenotypical evolutions of BD in Japan, such as increased gastrointestinal (GI) involvement, reduced complete type according to the Japan Criteria, and reduced HLA-B51 positivity were associated with chronologically changing proportions of the clinical clusters.

Conclusions: In this study, we identified independent clinical clusters among BD patients in Japan and found that the proportion of each cluster varied over time. We propose five independent clusters namely "mucocutaneous", "mucocutaneous with arthritis", "neuro", "GI", and "eye."
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13075-020-02406-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851921PMC
February 2021

Pathomechanism and prevention of further surgery after posterior decompression for lumbar spinal canal stenosis in patients with diffuse idiopathic skeletal hyperostosis.

Spine J 2021 Jan 13. Epub 2021 Jan 13.

Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences University of Fukui, 23-3 Matsuoka Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan.

Background Context: Diffuse idiopathic skeletal hyperostosis (DISH) is a risk factor for further surgery after posterior decompression without fusion for patients with lumbar spinal canal stenosis (LSS). However, a strategy to prevent revision surgery has not been described.

Purpose: The aim of this study was to review clinical and imaging findings in LSS patients with DISH extending to the lumbar segment and to propose countermeasures for prevention of revision surgery.

Study Design: A retrospective study.

Patients Sample: A total of 613 consecutive patients with LSS underwent posterior decompression without fusion at our hospital and had a minimum follow-up period of 2 years. We defined patients with DISH bridging to the lumbar segment as L-DISH cases (group D, n=111), and those without as non-L-DISH cases (group N, n=502).

Outcome Measure: Demographic data including the rate of revision surgery, neurological examination using Japanese Orthopaedic Association score, radiological studies comprised plain lumbar radiography, CT, and high-resolution MRI were assessed.

Methods: Clinical features and imaging findings were compared in patients with and without L-DISH. Revision surgery and surgical procedures (conventional laminotomy or lumbar spinous process-splitting [split] laminotomy) were examined in the two groups. No funding was received for this study.

Results: L-DISH from L2 to L4 was a risk factor for disc degeneration such as a vacuum phenomenon and for further surgical treatment. The rate of revision surgery was higher in group D than in group N (9.0% vs. 4.0%, p=.026). There was no significant difference in this rate for patients in groups D and N who underwent conventional laminotomy; however, for those who underwent split laminotomy, the rate was significantly higher in group D (16.7% vs. 2.1%, p=.0006). Furthermore, the rate of revision surgery after split laminotomy at a lower segment adjacent to L-DISH was significantly higher than that after conventional laminotomy (37.5% vs. 7.7%, p=.037).

Conclusions: A negative impact of lumbar spinous process-splitting laminotomy was found, especially with decompression at a lower segment adjacent to L-DISH. In such cases, surgery sparing the osteoligamentous structures at midline, including the spinous process and supra- and interspinous ligaments, should be selected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.spinee.2021.01.009DOI Listing
January 2021

The psychological effects of COVID-19 on hospital workers at the beginning of the outbreak with a large disease cluster on the Diamond Princess cruise ship.

PLoS One 2021 11;16(1):e0245294. Epub 2021 Jan 11.

Department of Psychiatry, Yokohama City University Hospital, Yokohama, Japan.

The aim of the present study was to investigate the psychological effects of the COVID-19 outbreak and associated factors on hospital workers at the beginning of the outbreak with a large disease cluster on the Diamond Princess cruise ship. This cross-sectional, survey-based study collected demographic data, mental health measurements, and stress-related questionnaires from workers in 2 hospitals in Yokohama, Japan, from March 23, 2020, to April 6, 2020. The prevalence rates of general psychological distress and event-related distress were assessed using the 12-item General Health Questionnaire (GHQ-12) and the 22-item Impact of Event Scale-Revised (IES-R), respectively. Exploratory factor analysis was conducted on the 26-item stress-related questionnaires. Multivariable logistic regression analysis was performed to identify factors associated with mental health outcomes for workers both at high- and low-risk for infection of COVID-19. A questionnaire was distributed to 4133 hospital workers, and 2697 (65.3%) valid questionnaires were used for analyses. Overall, 536 (20.0%) were high-risk workers, 944 (35.0%) of all hospital workers showed general distress, and 189 (7.0%) demonstrated event-related distress. Multivariable logistic regression analyses revealed that 'Feeling of being isolated and discriminated' was associated with both the general and event-related distress for both the high- and low-risk workers. In this survey, not only high-risk workers but also low-risk workers in the hospitals admitting COVID-19 patients reported experiencing psychological distress at the beginning of the outbreak.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245294PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799779PMC
January 2021

OGT Regulates Hematopoietic Stem Cell Maintenance via PINK1-Dependent Mitophagy.

Cell Rep 2021 Jan;34(1):108579

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address:

O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is a unique enzyme introducing O-GlcNAc moiety on target proteins, and it critically regulates various cellular processes in diverse cell types. However, its roles in hematopoietic stem and progenitor cells (HSPCs) remain elusive. Here, using Ogt conditional knockout mice, we show that OGT is essential for HSPCs. Ogt is highly expressed in HSPCs, and its disruption induces rapid loss of HSPCs with increased reactive oxygen species and apoptosis. In particular, Ogt-deficient hematopoietic stem cells (HSCs) lose quiescence, cannot be maintained in vivo, and become vulnerable to regenerative and competitive stress. Interestingly, Ogt-deficient HSCs accumulate defective mitochondria due to impaired mitophagy with decreased key mitophagy regulator, Pink1, through dysregulation of H3K4me3. Furthermore, overexpression of PINK1 restores mitophagy and the number of Ogt-deficient HSCs. Collectively, our results reveal that OGT critically regulates maintenance and stress response of HSCs by ensuring mitochondrial quality through PINK1-dependent mitophagy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2020.108579DOI Listing
January 2021

Establishment of a High-risk MDS/AML Cell Line YCU-AML1 and its Xenograft Model Harboring t(3;3) and Monosomy 7.

Hemasphere 2020 Oct 17;4(5):e469. Epub 2020 Sep 17.

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan.

Acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) with both inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and monosomy 7 defines an extremely aggressive myeloid cancer whose molecular pathogenesis and optimal therapeutic strategy still remain unclear. We established a new MDS/AML cell line, YCU-AML1, and its patient-derived xenograft (PDX) model from a high-risk MDS patient who later transformed into AML harboring both t(3;3)(q21;q26.2) and monosomy 7. YCU-AML1 cells propagated in co-culture system with stromal cells in granulocyte macrophage colony-stimulating factor (GM-CSF)-dependent manner. CD34 bone marrow cells derived from our PDX model showed high and low expression. Moreover, mutational profile of our MDS/AML model was consistent with recently published mutational spectrum of myeloid malignancies with inv(3)/t(3;3). These data suggest that YCU-AML1 cells and its MDS/AML model strongly mimics a high-risk human myeloid cancer with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and monosomy 7 in terms of both clinical phenotype and molecular basis. We believe our model can be used as a feasible tool to further explore molecular pathogenesis and novel treatment strategy of high-risk MDS/AML with t(3;3)(q21;q26.2) and monosomy 7.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HS9.0000000000000469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643909PMC
October 2020

Detection of residual disease in chronic myeloid leukemia utilizing genomic next generation sequencing reveals persistence of differentiated Ph B cells but not bone marrow stem/progenitors.

Leuk Lymphoma 2021 03 26;62(3):679-687. Epub 2020 Oct 26.

Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.

Persistence of leukemic stem cells (LSCs) results in the recurrence of chronic myeloid leukemia (CML) after the administration of tyrosine kinase inhibitors (TKIs). Thus, the detection of minimal residual disease (MRD) with LSC potential can improve prognosis. Here, we analyzed 115 CML patients and found that CD25 was preferentially expressed on the phenotypic stem and progenitor cells (SPCs), and TKI therapy decreased the number of CD25-positive cells in the SPC fraction. To detect MRD harboring fusion DNA, we developed a highly-sensitive method using patient-specific primers and next-generation sequencing. By using this method, we identified that in patients who achieved molecular remission, almost all residual CD25-positive SPCs were -negative. Moreover, in some patients was detectable in peripheral B cells but not in SPCs. We conclude that CD25 marks LSCs at diagnosis but does not mark MRD following TKI treatment and that analysis of peripheral B cells can allow sensitive detection of MRD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2020.1837366DOI Listing
March 2021

Refractory optic perineuritis related to granulomatosis with polyangiitis treated with intensive immunosuppressive therapy combined with plasma exchange.

Mod Rheumatol Case Rep 2020 01 8;4(1):84-89. Epub 2019 Aug 8.

Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine, Yokohama, Japan.

Optic perineuritis (OPN), which is an inflammatory disorder affecting the optic nerve sheath, is one of the rare complications in granulomatosis with polyangiitis (GPA). Although several groups have reported that immunosuppressive therapies are generally effective against GPA-associated OPN, so far, there is little information as to other options for refractory cases. Here we demonstrate a case of GPA-associated OPN, which is refractory to potent immunosuppressive therapy including high-dose glucocorticoid, intravenous cyclophosphamide and rituximab therapy, and effective application of therapeutic plasma exchange. We also report here that CSF IL-6 levels may serve as a new biomarker for GPA-associated OPN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/24725625.2019.1649857DOI Listing
January 2020

Risk Factor for Poor Patient Satisfaction After Lumbar Spine Surgery in Elderly Patients Aged Over 80 years.

Clin Spine Surg 2021 May;34(4):E223-E228

Department of Orthopaedic Surgery, Shinshu University, Nagano.

Study Design: Retrospective cohort study.

Objective: To clarify the poor patient satisfaction after lumbar spinal surgery in elderly patients.

Summary Of Background Data: As the global population continues to age, it is important to consider the surgical outcome and patient satisfaction in the elderly. No studies have assessed patient satisfaction in elderly patients undergoing surgical treatment and risk factors for poor satisfaction in elderly patients after lumbar spinal surgery.

Materials And Methods: A retrospective multicenter survey was performed in 169 patients aged above 80 years who underwent lumbar spinal surgery. Patients were followed up for at least 1 year after surgery. We assessed patient satisfaction from the results of surgery by using a newly developed patient questionnaire. Patients were assessed by demographic data, surgical procedures, complications, reoperation rate, pain improvement, and risk factors for poor patient satisfaction with surgery for lumbar spinal disease.

Results: In total, 131 patients (77.5%, G-group) were satisfied and 38 patients (22.5%, P-group) were dissatisfied with surgery. The 2 groups did not differ significantly in baseline characteristics and surgical data. Postoperative visual analog scale score for low back pain and leg pain were significantly higher in the P-group than in the G-group (low back pain: G-group, 1.7±1.9 vs. P-group, 5.2±2.5, P<0.001; leg pain: G-group, 1.4±2.0 vs. P-group, 5.5±2.6, P<0.001). Multivariate regression analysis revealed that postoperative vertebral fracture (P=0.049; odds ratio, 3.096; 95% confidence interval, 1.004-9.547) and reoperation (P=0.025; odds ratio, 5.692; 95% confidence interval, 1.250-25.913) were significantly associated with the patient satisfaction after lumbar spinal surgery.

Conclusions: Postoperative vertebral fracture and reoperation were found to be risk factors for poor patient satisfaction after lumbar spinal surgery in elderly patients, which suggests a need for careful treatment of osteoporosis in addition to careful determination of surgical indication and procedure in elderly patients.

Level Of Evidence: Level III.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BSD.0000000000001101DOI Listing
May 2021

TET2: A cornerstone in normal and malignant hematopoiesis.

Cancer Sci 2021 Jan 18;112(1):31-40. Epub 2020 Nov 18.

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Regulation of genome-wide DNA methylation is fundamental for a variety of biological processes such as mammalian development, stem cell function, cellular proliferation/differentiation, and oncogenesis. Among the regulators of DNA methylation, ten-eleven translocation 2 (TET2) is one of the most frequently mutated genes in clonal hematopoiesis of indeterminate potential and in various hematological malignancies, underscoring a pivotal role for TET2 in blood homeostasis and hematopoietic transformation. TET2 oxidizes methylated cytosines to further modify cytosines, which behave as intermediates in active/passive DNA demethylation processes. TET2 itself associates with histone modifiers, thereby regulating histone modifications and expression of target genes. A number of studies have reported pleiotropic effects of TET2 on hematopoietic stem cell self-renewal, hematopoietic differentiation, genome instability and inflammatory response. Recent single-cell genomics studies have identified gene promoters as well as transcription factor binding sites as TET2-targeted genetic loci in which disruption of DNA methylation can fundamentally modify hematopoietic differentiation and promote leukemogenesis. TET2 mutations show convergent cooperativity with other disease alleles in signaling molecules, epigenetic modifiers, and spliceosome factors in hematopoietic transformation. Future studies focusing on the molecular basis of stem cell and immune regulation by TET2 loss will further deepen our understanding of the entire landscape of pathophysiology and molecular vulnerabilities of TET2-mutated hematological malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.14688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780023PMC
January 2021

Clonal hematopoiesis: Molecular basis and clinical relevance.

Leuk Res 2020 11 23;98:106457. Epub 2020 Sep 23.

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku Yokohama, Japan. Electronic address:

Recent genomics studies have revealed that clonal hematopoietic expansion due to recurrent somatic mutations in hematopoietic cells are common in older people without evidence of hematological malignancies. This phenomenon, termed clonal hematopoiesis of indeterminate potential (CHIP), is associated with greater risk for hematological malignancy and cardiovascular diseases, leading to decreased overall survival of the affected individuals. The most frequently mutated genes in CHIP cases include genes associated with epigenetic modification, cell signaling, DNA damage response and RNA splicing, which are all recurrently mutated in myeloid malignancies. Recent findings suggest that these genetic alleles exert pleiotropic effects on hematopoietic stem cell (HSC) functions, transcriptional regulations, DNA damage responses and resistance to cellular stresses. Recent studies have uncovered the clinical relevance of CHIP in various settings during the management of hematological malignancies. Elucidating overall picture of clonal evolution based on CHIP will help developing preventive measures and novel treatments for hematological malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.leukres.2020.106457DOI Listing
November 2020

Efficacy and safety of apremilast for 3 months in Behçet's disease: A prospective observational study.

Mod Rheumatol 2020 Oct 16:1-6. Epub 2020 Oct 16.

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Objective: To determine the real-world short-term efficacy and safety of apremilast for Behçet's disease (BD).

Methods: The study included patients who received apremilast for refractory oral ulcers in addition to meeting International Study Group criteria for BD or the revised International Criteria for Behçet's Disease. To assess the efficacy of apremilast, Behçet's disease current activity form (BDCAF) and patients' self-perception of their disease activity were monitored for three months. The disease phenotypes, laboratory data, concomitant medication use, and adverse events were also investigated.

Results: Fourteen BD patients were included in the study. Concomitant drug use were as follows: colchicine 92.9%, prednisolone 21.4%, immunosuppressants 28.6%, and tumor-necrosis inhibitor 14.3%. Oral ulcers and BDCAF scores at 3 months showed significant improvement compared to baseline. Adverse events during the study were diarrhea ( = 3, 21.4%), nausea ( = 3, 21.4%), music hallucination ( = 1, 7.1%), and branch retinal vein occlusion ( = 1, 7.1%). Apremilast was discontinued in 1 patient (7.1%) due to nausea.

Conclusion: Significant improvement in oral ulcer and BDCAF with apremilast was confirmed in real-world BD patients after 3 months. The combination of colchicine and apremilast appears to be well tolerated in BD in the short-term.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14397595.2020.1830504DOI Listing
October 2020

Primary intradural extramedullary Ewing sarcoma: A case report and literature review.

Oncol Lett 2020 Sep 26;20(3):2347-2355. Epub 2020 Jun 26.

Department of Orthopaedics and Rehabilitation Medicine, University of Fukui Faculty of Medical Sciences, Eiheiji, Fukui 910-1193, Japan.

Tumors of the spinal cord and cauda equina show a wide spectrum of histology and require careful diagnosis and treatment. Primary intradural extramedullary Ewing sarcoma (IEES) is extremely rare, and initial imaging and clinical findings for this tumor mimic those of benign intradural spinal tumors. The present report describes a case of a 35-year-old woman who presented with IEES with meningeal seeding, and the literature on the management and clinical course of these tumors was reviewed. An examination revealed right-side leg dominant rapidly progressive hypoesthesia and motor deficits. MRI identified intradural tumors at the T12-L1 and L4-5 levels. Growth and an increase in the number of intradural tumors occurred over 3 weeks. Gadolinium-contrast T1-weighted MRI revealed diffusely enhanced signals for tumorous lesions with meningeal seeding in the cervical and thoracic spinal cord. Excision of a tumor at T12-L1 was performed to alleviate the symptoms and to make a histologic diagnosis. Microscopically, the tumor consisted of dense sheets of small round cells. Immunohistochemically, tumor cells showed intense and diffuse positive staining for CD99, ETS transcription factor ERG and Fli-1 proto-oncogene, ETS transcription factor (FLI1). The sequence analysis revealed the EWS RNA binding protein 1-FLI1 fusion transcript. The lesion was diagnosed as primary intradural ES. Adjuvant chemotherapy following radiotherapy for the whole spine was performed; however, multiple brain metastases were found at 10 months after diagnosis and the patient died of diffusely disseminated disease limited to the central nervous system without evidence of distant metastases at 16 months after the initial diagnosis. In a literature review of IEES cases, the 1- and 5-year overall survival rates were 79.8 and 26.6%, respectively, and the 1-, 2- and 5-year progression-free survival rates were 61.0, 52.3 and 10.9%, respectively. Therefore, primary IEES has a poor prognosis compared with ES of bone, and novel agents and treatment strategies are required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2020.11786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401003PMC
September 2020

Expression Analysis of Susceptibility Genes for Ossification of the Posterior Longitudinal Ligament of the Cervical Spine in Human OPLL-related Tissues and a Spinal Hyperostotic Mouse (ttw/ttw).

Spine (Phila Pa 1976) 2020 Nov;45(22):E1460-E1468

Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences University of Fukui, Eiheiji-cho, Yoshida-gun, Fukui, Japan.

Study Design: Immunohistochemical and real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis.

Objective: The aim of this study was to analyze the expression of five susceptibility genes (RSPO2, HAO1, CCDC91, RHPH9, and STK38L) for human ossification of the posterior longitudinal ligaments (OPLL) identified in a genome-wide association study.

Summary Of Background Data: Detailed expression and functional studies for the five susceptibility genes are needed to aid in clarification of the etiology and pathogenesis of OPLL.

Methods: Immunostaining, cell culture, and real-time RT-PCR were performed on ossified ligament samples collected during anterior cervical decompression for symptomatic OPLL (n = 39 patients) and on control non-OPLL samples (n = 8 patients). Immunohistochemical analysis in spinal hyperostotic mice (ttw/ttw) (n = 25) was also performed. The sample sections were stained for RSPO2, HAO1, CCDC91, RHPH9, STK38L, Runx2, Sox9, and CD90. The mRNA expression levels of the five susceptibility genes were also analyzed in cultured human OPLL and non-OPLL cells subjected to cyclic tensile strain.

Results: Immunoreactivity for RSPO2 and Sox9 was evident in proliferating chondrocytes in human OPLL tissues and ttw/ttw mice. Application of cyclic tensile strain to cultured human OPLL cells resulted in increases in mRNA levels for RSPO2, HAO1, and CCDC91. However, individual differences in expression in human OPLL-related samples were seen. HAO1-positive cells were detected only in 3- to 6-week-old ttw/ttw mice that did not simultaneously express RSPO2-positive samples.

Conclusion: Among the five susceptibility genes, RSPO2, HAO1, and CCDC91 might be contributory factors in progression of OPLL. RSPO2 may be involved in endochondral ossification, especially in mixed or continuous type OPLL, HAO1 may be an initiation factor for OPLL that is rarely seen in mature human OPLL samples, and CCDC91 may be associated with progression of ossification caused by mechanical stress. These findings provide important insights into the pathogenesis and therapeutic targets for OPLL.

Level Of Evidence: N/A.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BRS.0000000000003648DOI Listing
November 2020

Distribution and polarization of microglia and macrophages at injured sites and the lumbar enlargement after spinal cord injury.

Neurosci Lett 2020 10 9;737:135152. Epub 2020 Jun 9.

Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan.

Spinal cord injury (SCI) causes loss of locomotor function and chronic neuropathic pain (NeP). Hematogenous macrophages and activated microglia are key monocytic lineage cell types in the response to SCI, and each has M1- and M2-phenotypes. To understand the roles of these cells in neuronal regeneration and chronic NeP after SCI, differences in distribution and phenotypes of activated microglia and infiltrated macrophages after SCI were examined at the injured site and the lumbar enlargement, as a remote region. Chimeric mice were used for differentiating activated microglia from hematogenous macrophages. The prevalences of activated microglia and infiltrating macrophages increased at day 14 after SCI, at the time of most severe pain hypersensitivity, with mainly M1-type hematogenous macrophages at the injured site and M2-type activated microglia at the lumbar enlargement. Peak expression of TNF-α, an M1-induced cytokine, occurred on day 4 post-SCI at the injured site, but not until day 14 at the lumbar enlargement. Expression of IL-4, a M2-induced cytokine, peaked at 4 days after SCI at both sites. These results suggest different roles of activated microglia and hematogenous macrophages, including both phenotypes of each cell, in neuronal regeneration and chronic NeP after SCI at the injured site and lumbar enlargement. The prevalence of the M1 over the M2 phenotype at the injured site until the subacute phase after SCI may be partially responsible for the lack of functional recovery and chronic NeP after SCI. Activation of M2-type microglia at the lumbar enlargement in response to inflammatory cytokines from the injured site might be important in chronic below-level pain. These findings are useful for establishment of a therapeutic target for prevention of motor deterioration and NeP in the time-dependent response to SCI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neulet.2020.135152DOI Listing
October 2020

Differences in clinical and radiological features of thoracic disc herniation presenting with acute progressive myelopathy.

Eur Spine J 2021 Apr 7;30(4):829-836. Epub 2020 Jun 7.

Department of Orthopaedics and Rehabilitation Medicine, University of Fukui Faculty of Medical Sciences, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan.

Purpose: Symptomatic thoracic disc herniation (TDH) is relatively rare, but patients with progressive myelopathy require surgical treatment without delay in diagnosis. The aim of this study was to review clinical and radiological features in patients with TDH presenting with myelopathy.

Methods: A total of 28 consecutive patients with thoracic myelopathy (Frankel grade C or worse) due to TDH who underwent surgery were divided into 3 groups based on the time for development of myelopathy (acute (< 72 h), subacute (within a few weeks), and chronic [gradually over > 1 month)] and their data were analyzed.

Results: The patients in the acute group were significantly younger and had a higher body mass index (BMI) compared to those in the subacute and chronic groups. Most cases of acute myelopathy were affected in the upper thoracic level, whereas all patients with subacute and chronic myelopathy had lesions in the lower thoracic level below T8-9. Interestingly, the affected thoracic level in patients with acute myelopathy matched the upper line of the sternum. The rate of acquired walking ability without assistance was only 50.0% in the acute group.

Conclusions: This study suggests that TDH presenting with acute myelopathy may have different clinical and radiological features compared to those of TDH with subacute and chronic myelopathy. Upper TDH should be suspected in cases of acute myelopathy that develops with sudden-onset back pain after certain triggers in younger and higher BMI people. These affected thoracic level matched with the upper line of the sternum in each case.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00586-020-06485-6DOI Listing
April 2021

Computed tomography-defined sarcopenia: prognostic predictor of nonrelapse mortality after allogeneic hematopoietic stem cell transplantation: a multicenter retrospective study.

Int J Hematol 2020 Jul 25;112(1):46-56. Epub 2020 May 25.

Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine, Yokohama, Japan.

We analyzed clinical cutoffs for defining computed tomography (CT) methods for sarcopenia and examined the prognostic value of CT for allogeneic hematopoietic stem cell transplantation (allo-HCST) outcomes of patients with myeloid malignancy. One hundred twenty-five adult patients with acute myeloid leukemia and myelodysplastic syndrome who underwent first allo-HSCT between 2000 and 2017 were included. Sarcopenia was assessed using CT-based skeletal muscle index (SMI) and mean muscle attenuation at L3. A statistical difference in SMI was confirmed between sarcopenia (n = 52) and nonsarcopenia (n = 73) patients. There were no significant correlations of muscularity with age, performance status, or other characteristics of HSCT. After 2 years, overall survival (OS) was 43.5% and 70.1%, disease-free survival was 52.9% and 68.6%, nonrelapse mortality (NRM) was 20.8% and 8.4%, incidence of acute GVHD (≥ grade 2) was 38.8% and 39.1%, that of chronic GVHD was 53.2% and 37.3%, and median duration of hospitalization was 88 days and 74 days (P = 0.026), respectively, in the sarcopenia and nonsarcopenia groups. Multivariate analysis showed that presence of sarcopenia is a novel adverse factor for high NRM and poor OS. Pretransplant CT-defined sarcopenia is correlated with decreased OS, increased NRM, and prolonged hospitalization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-020-02870-5DOI Listing
July 2020

Idiopathic pneumoperitoneum without gastrointestinal perforation in a low-birth weight infant: A rare type of air leak syndrome.

Radiol Case Rep 2020 Jul 7;15(7):926-928. Epub 2020 May 7.

Department of Pediatric Surgery, Shizuoka Children's Hospital, 860 Urushiyama, Aoi-ku, Shizuoka 420-8660, Shizuoka, Japan.

Neonatal free air on X-ray images is generally due to intestinal perforation, and requires surgical intervention. However, some cases without intestinal perforation show free air on X-ray images. Pneumoperitoneum without perforation is caused by an air leak syndrome. We present here the case of a low-birth-weight infant with free air on X-ray images, who had no evidence of intestinal perforation intraoperatively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radcr.2020.04.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215104PMC
July 2020

Clinical course of 2019 novel coronavirus disease (COVID-19) in individuals present during the outbreak on the Diamond Princess cruise ship.

J Infect Chemother 2020 Aug 13;26(8):865-869. Epub 2020 May 13.

Department of Respiratory Internal Medicine, St. Marianna University School of Medicine, Yokohama City Seibu Hospital, Japan.

We investigated the clinical course of individuals with 2019 novel coronavirus disease (COVID-19) who were transferred from the Diamond Princess cruise ship to 12 local hospitals. The conditions and clinical courses of patients with pneumonia were compared with those of patients without pneumonia. Among 70 patients (median age: 67 years) analyzed, the major symptoms were fever (64.3%), cough (54.3%), and general fatigue (24.3%). Forty-three patients (61.4%) had pneumonia. Higher body temperature, heart rate, and respiratory rate as well as higher of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels and lower serum albumin level and lymphocyte count were associated with the presence of pneumonia. Ground-glass opacity was found in 97.7% of the patients with pneumonia. Patients were administered neuraminidase inhibitors (20%), lopinavir/ritonavir (32.9%), and ciclesonide inhalation (11.4%). Mechanical ventilation and veno-venous extracorporeal membrane oxygenation was performed on 14 (20%) and 2 (2.9%) patients, respectively; two patients died. The median duration of intubation was 12 days. The patients with COVID-19 transferred to local hospitals during the outbreak had severe conditions and needed close monitoring. The severity of COVID-19 depends on the presence of pneumonia. High serum LDH, AST and CRP levels and low serum albumin level and lymphocyte count were found to be predictors of pneumonia. It was challenging for local hospitals to admit and treat these patients during the outbreak of COVID-19. Assessment of severity was crucial to manage a large number of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jiac.2020.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218347PMC
August 2020

Cyclic tensile strain facilitates ossification of the cervical posterior longitudinal ligament via increased Indian hedgehog signaling.

Sci Rep 2020 04 29;10(1):7231. Epub 2020 Apr 29.

Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences University of Fukui, 23-3 Matsuoka Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan.

The pathomechanisms of initiation and progression of ossification of the posterior longitudinal ligament (OPLL) are unclear. Indian hedgehog (Ihh) and related signaling molecules are key factors in normal enchondral ossification. The purpose of this study is to investigate the contribution of mechanical strain to OPLL and the relationship of Ihh with OPLL. Sections of the posterior longitudinal ligament (PLL) were obtained from 49 patients with OPLL and from 7 patients without OPLL. Cultured PLL cells were subjected to 24 hours of cyclic tensile strain. To identify differentially expressed genes associated with cyclic tensile strain, microarray analysis was performed. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified upregulation of various genes, particularly of the Hedgehog signaling pathway; Ihh and related genes had increased expression compared with controls after 24-hour cyclic tensile strain. In immunoblotting analysis, Ihh, Runx2, Sox9, Gli2, Gli3, and smoothened (SMO) had significantly increased expression after 6- or 12-hour cyclic tensile strain. OPLL samples were strongly immunopositive for Ihh, Sox9, Runx2, Gli2, Gli3, and SMO in the ossification front of OPLL. These results suggest that cyclic tensile strain induces abnormal activation of Ihh and related signaling molecules, and this might be important in the ossification process in OPLL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-64304-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190672PMC
April 2020