Publications by authors named "Isao Matsumoto"

280 Publications

Specific Increase in Joint Neutrophil Extracellular Traps and Its Relation to Interleukin 6 in Autoimmune Arthritis.

Int J Mol Sci 2021 Jul 16;22(14). Epub 2021 Jul 16.

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.

Neutrophils and their extracellular traps have been shown to play an important role in the pathogenesis of rheumatoid arthritis (RA), but the detailed mechanisms in joints are still unclear, and their regulation remains to be solved. Here, we explored neutrophil extracellular trap (NET)osis in experimental models of arthritis and further investigated the effects of interleukin-6 (IL-6) inhibition in neutrophils and NETosis. In skins of peptide GPI-induced arthritis (pGIA), citrullinated protein was detected as well as citrullinated histone expression in immunized skin but this was not specific to pGIA. Citrullinated histone expression in pGIA joints was specific to pGIA and was merged with neutrophil elastase, suggesting NETosis. Neutrophils in joints tend to upregulate IL-6 receptors when compared with bone marrow neutrophils. Administration of mouse anti-IL-6 receptor antibodies in pGIA suppressed arthritis in association with a decrease in neutrophil infiltration and NETosis in joints. In the plasma of RA patients, citrullinated protein was significantly reduced after tocilizumab treatment. Our results suggest that IL-6 enhances neutrophil chemotaxis and NETosis in inflammatory joints and could be the source of citrullinated proteins.
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http://dx.doi.org/10.3390/ijms22147633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303722PMC
July 2021

Impaired function of PD-1 follicular regulatory T cells in systemic lupus erythematosus.

Clin Exp Immunol 2021 Jul 9. Epub 2021 Jul 9.

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba-city, Japan.

Aberrant autoantibody production is characteristic of systemic lupus erythematosus (SLE), but follicular regulatory T (TFR) cells can potentially suppress this abnormality. We investigate functional changes in TFR cells from SLE patients. Circulating TFR cells were collected from 19 SLE patients and 14 healthy controls (HC) to compare molecular expression and in-vitro suppressive capacity of follicular helper T (TFH) cell proliferation. To reveal the stability of forkhead box protein 3 (FoxP3) in TFR, pyrosequencing of conserved non-coding sequence (CNS) 2 at the FoxP3 gene locus was performed. We then tested interleukin (IL)-2 in SLE-TFR cells to check restoration of suppressor function. Programmed cell death 1 (PD-1) expression in SLE-TFR cells was positively correlated with anti-DNA antibody levels and disease activity. These cells had impaired suppressive function for TFH cells with decreased expression of suppression mediators FoxP3, cytotoxic T lymphocyte antigen 4 (CTLA-4) and IL-2 receptor alpha (IL-2Rα). Pyrosequencing identified hyper-methylation in CNS2 region of SLE-TFR cells comparing to HC. With in-vitro IL-2 stimulation, PD-1 expression of TFR cells significantly decreased, together with increased expression of FoxP3 and CTLA-4, especially at a low dose. Thus, SLE-TFR cells have functionally defective to TFH suppression, but low-dose IL-2 therapy might be useful to restore this ability.
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http://dx.doi.org/10.1111/cei.13643DOI Listing
July 2021

Anti-nuclear matrix protein 2 antibody-positive inflammatory myopathies represent extensive myositis without dermatomyositis-specific rash.

Rheumatology (Oxford) 2021 Jun 21. Epub 2021 Jun 21.

Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.

Objectives: Myositis-specific autoantibodies (MSAs) define distinct clinical subsets of idiopathic inflammatory myopathies (IIMs). The anti-nuclear matrix protein 2 (NXP2) antibody, a MSA detected in juvenile/adult IIMs, has been reported to be associated with a high risk of subcutaneous calcinosis, subcutaneous oedema, and internal malignancies. The study aimed to clarify the clinical features of anti-NXP2 antibody-positive IIMs in detail.

Methods: This multi-centre retrospective observational study on 76 anti-NXP2 antibody-positive patients. The antibody was detected via a serological assay using immunoprecipitation and western blotting. The patients were selected from 162 consecutive Japanese patients with IIMs.

Results: The cohort of anti-NXP2 antibody-positive IIMs included 29 juvenile patients and 47 adult patients. Twenty-seven (35.5%) patients presented with polymyositis phenotype without dermatomyositis-specific skin manifestations (heliotrope rash or Gottron sign/papules); this was more common in the adults than children (48.9% vs. 15.8%, P < 0.01). Nine (11.8%) patients had subcutaneous calcinosis, and 20 (26.3%) patients had subcutaneous oedema. In addition, the proportion of patients with muscle weakness extending to the distal limbs was high (36 patients [47.4%]) in this cohort. Adult patients had a higher prevalence of malignancy than the general population (age-standardised incidence ratio of malignancies: 22.4).

Conclusion: Anti-NXP2 antibody-positive IIMs, which include dermatomyositis sine dermatitis, are characterised by atypical skin manifestations and extensive muscular involvement.
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http://dx.doi.org/10.1093/rheumatology/keab518DOI Listing
June 2021

Chest Dynamic-Ventilatory Digital Radiography in Chronic Obstructive or Restrictive Lung Disease.

Int J Chron Obstruct Pulmon Dis 2021;16:1393-1399. Epub 2021 May 18.

Kanazawa University Hospital, Respiratory Medicine, Ishikawa, Japan.

Objective: The aim of this study was to identify the relationships between parameters obtained from dynamic-ventilatory digital radiography (DR) and ventilatory disorders.

Methods: This study comprised 273 participants with respiratory diseases who underwent spirometry and functional residual capacity measurements (104 with normal findings on spirometry as controls, 139 with an obstructive lung disorder, 30 with a restrictive lung disorder) were assessed by dynamic-ventilatory DR. Sequential chest radiography images of the patient's slow and maximum breathing were captured at 15 frames per second by a dynamic flat-panel imaging system. The system measured the following parameters: lung area at maximum inspiration divided by height (lung area_in/height), changes in tracheal diameter due to respiratory motions, rate of tracheal narrowing, diaphragmatic motion, and rate of change in lung area due to respiratory motion. Relationships between these parameters and ventilatory disorders were analyzed.

Results: Lung area_in/height in patients with restrictive disorders showed significant decreases. Tracheal diameter change and tracheal narrowing rate in patients with obstructive disorders were significantly increased compared to both the control participants and patients with restrictive disorders. Patients with obstructive disorders and patients with restrictive disorders showed decreased diaphragmatic motion and lung area change rate. With the restrictive disorders as references, the area under the curve (AUC), sensitivity and specificity of lung area_in/height were 0.88, 0.77, and 0.88, respectively. With the obstructive disorders as references, the AUC, sensitivity and specificity of tracheal narrowing rate were 0.67, 0.53 and 0.81, respectively.

Conclusion: Dynamic-ventilatory DR shows potential as a method for the detection and evaluation of ventilatory disorders in patients with respiratory diseases.
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http://dx.doi.org/10.2147/COPD.S309960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140888PMC
July 2021

Sjögren's syndrome-associated SNPs increase GTF2I expression in salivary gland cells to enhance inflammation development.

Int Immunol 2021 Jul;33(8):423-434

Division of Molecular Psychoimmunology, Institute for Genetic Medicine, Hokkaido University, Sapporo 0600815, Japan.

Sjögren's syndrome (SS) is an autoimmune disease characterized by inflammation with lymphoid infiltration and destruction of the salivary glands. Although many genome-wide association studies have revealed disease-associated risk alleles, the functions of the majority of these alleles are unclear. Here, we show previously unrecognized roles of GTF2I molecules by using two SS-associated single nucleotide polymorphisms (SNPs), rs73366469 and rs117026326 (GTF2I SNPs). We found that the risk alleles of GTF2I SNPs increased GTF2I expression and enhanced nuclear factor-kappa B (NF-κB) activation in human salivary gland cells via the NF-κB p65 subunit. Indeed, the knockdown of GTF2I suppressed inflammatory responses in mouse endothelial cells and in vivo. Conversely, the over-expression of GTF2I enhanced NF-κB reporter activity depending on its p65-binding N-terminal leucine zipper domain. GTF2I is highly expressed in the human salivary gland cells of SS patients expressing the risk alleles. Consistently, the risk alleles of GTF2I SNPs were strongly associated with activation of the IL-6 amplifier, which is hyperactivation machinery of the NF-κB pathway, and lymphoid infiltration in the salivary glands of SS patients. These results demonstrated that GTF2I expression in salivary glands is increased in the presence of the risk alleles of GTF2I SNPs, resulting in activation of the NF-κB pathway in salivary gland cells. They also suggest that GTF2I could be a new therapeutic target for SS.
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http://dx.doi.org/10.1093/intimm/dxab025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299718PMC
July 2021

Predicting recurrence of non-small cell lung cancer based on mean computed tomography value.

J Cardiothorac Surg 2021 May 12;16(1):128. Epub 2021 May 12.

Department of Thoracic Surgery, Kanazawa University School of Medicine, Takara-machi 13-1, Kanazawa, 920-8640, Japan.

Background: The aim of this study was to assess the ability of using mean computed tomography (mCT) values to predict non-small cell lung cancer (NSCLC) tumor recurrence.

Methods: A retrospective study was conducted on 494 patients with stage IA NSCLC. Receiver operating characteristics analysis was used to assess the ability to use mCT value, C/T ratio, tumor size, and SUV to predict tumor recurrence. Multiple logistic regression analyses were performed to determine the independent variables for the prediction of tumor recurrence.

Results: The m-CT values were - 213.7 ± 10.2 Hounsfield Units (HU) for the recurrence group and - 594.1 ± 11.6 HU for the non-recurrence group (p < 0.0001). Recurrence occurred in 45 patients (9.1%). The tumor recurrence group was strongly associated with a high CT attenuation value, high C/T ratio, large solid tumor size, and SUV. The diagnostic value of mCT value was more accurate than the C/T ratio, excluding the pure ground-glass opacity and pure solid (0 < C/T ratio < 100) groups. The SUV and mCT are independent predictive factors of tumor recurrence.

Conclusions: The evaluation of mCT values was useful for predicting recurrence after the limited resection of small-sized NSCLC, and may potentially contribute to the selection of suitable treatment strategies.
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http://dx.doi.org/10.1186/s13019-021-01476-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117299PMC
May 2021

[Immunoglobulin G4( IgG4)-related Fibrosing Mediastinitis Localized in the Retrosternal Area:Report of a Case].

Kyobu Geka 2021 Apr;74(4):317-320

Department of Thoracic Surgery, Kanazawa Medical Center, Kanazawa, Japan.

An 84-year-old man was referred to our out-patient clinic with an elongated mass localized to the retrosternal area that was incidentally identified by computed tomography. On 18F-fluorodeoxyglucose-positron emission tomography, this lesion showed intense tracer uptake. Thus, a surgical biopsy under thoracoscopy was performed. Histological examination revealed dense fibrous tissue associated with inflammatory cell infiltration. The immunoglobulin (Ig) G4/IgG plasma cell ratio was over 90%. Serum IgG4 levels were normal. According to the Umehara criteria for IgG4-related disease, a final diagnosis of a "possible" IgG4-related fibrosing mediastinitis was made. Oral glucocorticoid treatment with 30 mg/day prednisolone reduced the mass.
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April 2021

Assessment of pleural invasion and adhesion of lung tumors with dynamic chest radiography: A virtual clinical imaging study.

Med Phys 2021 Apr 2;48(4):1616-1623. Epub 2021 Mar 2.

Department of Diagnostic Radiology, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan.

Purpose: Accurate preoperative assessment of tumor invasion/adhesion is crucial for planning appropriate operative procedures. Recent advances in digital radiography allow a motion analysis of lung tumors with dynamic chest radiography (DCR) with total exposure dose comparable to that of conventional chest radiography. The aim of this study was to investigate the feasibility of preoperative evaluation of pleural invasion/adhesion of lung tumors with DCR through a virtual clinical imaging study, using a four-dimensional (4D) extended cardiac-torso (XCAT) computational phantom.

Methods: An XCAT phantom of an adult man (50th percentile in height and weight) with simulated respiratory and cardiac motions was generated to use as a virtual patient. To simulate lung tumors with and without pleural invasion, a 30-mm diameter tumor sphere was inserted into each lobe of the phantom. The virtual patient during respiration was virtually projected using an x-ray simulator in posteroanterior (PA) and oblique directions, and sequential bone suppression (BS) images were created. The measurement points (tumor, rib, and diaphragm) were automatically tracked on simulated images by a template matching technique. We calculated five quantitative metrics related to the movement distance and directions of the targeted tumor and evaluated whether DCR could distinguish between tumors with and without pleural invasion/adhesion.

Results: Precise tracking of the targeted tumor was achieved on the simulated BS images without undue influence of rib shadows. There was a significant difference in all five quantitative metrics between the lung tumors with and without pleural invasion both on the oblique and PA projection views (P < 0.05). Quantitative metrics related to the movement distance were effective for tumors in the middle and lower lobes, while, those related to the movement directions were effective for tumors close to the frontal chest wall on the oblique projection view. The oblique views were useful for the evaluation of the space between the chest wall and a moving tumor.

Conclusion: DCR could help distinguish between tumors with and without pleural invasion/adhesion based on the two-dimensional movement distance and direction using oblique and PA projection views. With anticipated improved image: processing to evaluate the respiratory displacement of lung tumors in the upper lobe or behind the heart, DCR holds promise for clinical assessment of tumor invasion/adhesion in the parietal pleura.
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http://dx.doi.org/10.1002/mp.14750DOI Listing
April 2021

QTc interval prolongation in patients with systemic lupus erythematosus treated with hydroxychloroquine.

Mod Rheumatol 2021 Feb 9:1-10. Epub 2021 Feb 9.

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.

Objectives: The primary objective is to reveal the effect of hydroxychloroquine (HCQ) treatment on corrected QT (QTc) interval in patients with systemic lupus erythematosus (SLE). The secondary objective is to investigate factors that affect QTc prolongation.

Methods: SLE patients who had electrocardiograms between 2015 and 2020 were recruited and assigned to two groups based on whether they were treated with HCQ (HCQ group) or not (control group). Change of QTc before and after HCQ administration in the HCQ group was measured and compared with the control group. Patients treated with HCQ were further divided into two groups based on presence or absence of QTc prolongation and the characteristics were compared.

Results: In total, 126 patients were recruited, of whom 42 were treated with HCQ. In the HCQ group, the mean QTc significantly increased ( < .001), while there was no significant difference of mean QTc in the control group. Moreover, those in the HCQ group with QTc prolongation showed a significantly higher proportion of hypertension and longer SLE duration compared to those without QTc prolongation. However, the multiple logistic regression analysis showed that there were no significant differences among them.

Conclusion: HCQ could induce QTc prolongation in SLE patients. It might be better that the possibility of QTc prolongation was taken into consideration when HCQ was administered in the patients with longer disease duration of SLE and coincidence of hypertension.
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http://dx.doi.org/10.1080/14397595.2021.1879368DOI Listing
February 2021

Clinical features of large vessel vasculitis (LVV): Elderly-onset versus young-onset.

Mod Rheumatol 2021 Feb 22:1-6. Epub 2021 Feb 22.

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.

Objectives: We compared large vessel vasculitis (LVV) clinical features between age groups.

Methods: We retrospectively examined clinical features and therapies in 41 LVV patients at our hospital from January 2010 to March 2020. We compared two patient groups, elderly (≥50 years) and young (<50 years).

Results: Of all patients, 29 were elderly and 12 were young. In the younger group, upper extremity symptoms ( <.05), bruits ( <.01), and cardiovascular complications ( <.01) were more common. Of the elderly group, 7 (24%) met classification criteria for giant cell arteritis while none of the younger group met these criteria; however, 10 (83%) of the younger group and 3 (10%) of the elderly group met the ACR classification criteria for Takayasu arteritis ( <.01). In the elderly group, 16 patients (66%) met no criteria ( <.01). There were no significant differences in laboratory findings but imaging showed a significantly higher incidence of head and neck artery lesions in the younger group ( <.05). The younger group was more likely to receive additional tocilizumab ( <.01) and cardiovascular complications were more likely to occur in younger patients ( < .01).

Conclusion: LVV clinical features differed between elderly- and young-age-onset groups.
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http://dx.doi.org/10.1080/14397595.2021.1878622DOI Listing
February 2021

A novel fluorescent lung-marking technique using the photodynamic diagnosis endoscope system and vitamin B2.

Interact Cardiovasc Thorac Surg 2020 12;31(6):853-859

Department of Thoracic, Cardiovascular and General Surgery, Kanazawa University, Kanazawa, Japan.

Objectives: For small pulmonary nodules that are unidentifiable by palpation or in endoscopic surgeries wherein palpation is not feasible, visualizing their location is necessary when performing pulmonary sublobar resection procedures, such as wedge resection or segmentectomy. We invented a new transbronchial lung-marking technique using the photodynamic diagnosis endoscope system and vitamin B2 and examined its feasibility and safety via porcine studies.

Methods: We established the marking procedure in pigs and examined the marking clarity and size, fluorescence intensity and duration and possible complications. In another study, sublobar resection for virtual target lesions was performed in pigs based on the fluorescent markings. The procedure duration, marking visibility, surgical margin from the lesions and technique-related complications were assessed.

Results: All 36 markings in 6 pigs were identifiable and were widely distributed over the right lung. The median diameter and fluorescence intensity at 60 min after marking were 6.0 (5.5-6.7) mm and 137.5 (122-168), respectively. All 18 markings for the 6 virtual target lesions (3 markings for each target) were clearly identified, and all target lesions were found in the resected specimens. The median duration per marking was 244 (194-255) seconds. The shortest median surgical margin from a target lesion was 11.5 (9.3-13.5) mm. No procedure-related complications were observed.

Conclusions: This novel transbronchial fluorescent lung-marking technique was useful and safe in sublobar resections for small non-palpable pulmonary lesions.
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http://dx.doi.org/10.1093/icvts/ivaa193DOI Listing
December 2020

Clinical features and prognosis of nocardiosis in patients with connective tissue diseases.

Mod Rheumatol 2021 May 2;31(3):636-642. Epub 2020 Oct 2.

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

Objectives: To investigate the clinical features and prognosis of nocardiosis complicated by connective tissue diseases (CTDs).

Methods: We examined patients with CTDs who were diagnosed with nocardiosis from October 2004 to 2019. We retrospectively investigated patient characteristics and therapeutic outcomes. We then performed a comparison between survivors and non-survivors.

Results: Fourteen patients were examined. Underlying CTDs were systemic lupus erythematosus (28.6%), vasculitis syndrome (28.6%), rheumatoid arthritis (21.4%), adult Still disease (14.3%) and dermatomyositis (7.1%). Infected organs were lung (85.7%), brain (42.9%), skin/cutaneous lesions (28.6%) and muscle (7.1%). Disseminated infections were seen in nine patients (64.3%). At the onset of nocardiosis, all patients were given prednisolone (23.2 ± 11.9 mg/day). Only two patients (14.3%) were given TMP-SMX for prophylaxis of pneumocystis pneumonia. Relapse occurred in one patient (7.1%) and four patients (28.6%) died from nocardiosis for a cumulative survival rate at 52 weeks of 76.9%. In a comparison of survivors (71.4%) and non-survivors (28.6%), cutaneous lesions were significantly more frequent in the latter (10 vs 75%,  = .04) with an odds ratio of 27.0 (95% CI: 1.7-453.4).

Conclusion: Cutaneous lesions as a result of dissemination might be a risk factor for nocardiosis mortality in patients with CTDs.
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http://dx.doi.org/10.1080/14397595.2020.1823070DOI Listing
May 2021

Transient IGF-1R inhibition combined with osimertinib eradicates AXL-low expressing EGFR mutated lung cancer.

Nat Commun 2020 09 14;11(1):4607. Epub 2020 Sep 14.

Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.

Drug tolerance is the basis for acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) including osimertinib, through mechanisms that still remain unclear. Here, we show that while AXL-low expressing EGFR mutated lung cancer (EGFRmut-LC) cells are more sensitive to osimertinib than AXL-high expressing EGFRmut-LC cells, a small population emerge osimertinib tolerance. The tolerance is mediated by the increased expression and phosphorylation of insulin-like growth factor-1 receptor (IGF-1R), caused by the induction of its transcription factor FOXA1. IGF-1R maintains association with EGFR and adaptor proteins, including Gab1 and IRS1, in the presence of osimertinib and restores the survival signal. In AXL-low-expressing EGFRmut-LC cell-derived xenograft and patient-derived xenograft models, transient IGF-1R inhibition combined with continuous osimertinib treatment could eradicate tumors and prevent regrowth even after the cessation of osimertinib. These results indicate that optimal inhibition of tolerant signals combined with osimertinib may dramatically improve the outcome of EGFRmut-LC.
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http://dx.doi.org/10.1038/s41467-020-18442-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490421PMC
September 2020

A method to identify pulmonary intersegmental planes with intravenous vitamin B injection.

Surg Today 2021 May 14;51(5):836-843. Epub 2020 Sep 14.

Department of Thoracic, Cardiovascular and General Surgery, Kanazawa University, 13-1, Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan.

Purpose: The present study investigated whether the pulmonary intersegmental planes could be identified with the intravenous injection of vitamin B using a fluorescent camera and whether this method can be used instead of the inflation-deflation technique or the intravenous indocyanine green (ICG) method.

Methods: In experiment 1, the vitamin B was intravenously injected to visualize the pulmonary intersegmental plane and perform segmentectomy, and the visualized pulmonary intersegmental line was then compared to the inflation-deflation line in six pigs. In experiment 2, using six pigs, the fluorescent area and duration of fluorescence were compared after the intravenous injection of vitamin B and ICG in the same animals.

Results: In all animals in experiment 1, it was possible to clearly detect yellow-green fluorescence in the lung, in segments other than the one intended for resection, for at least 60 min. Moreover, the line visualized with vitamin B fluorescence matched the inflation-deflation line in all animals. In experiment 2, the area of vitamin B fluorescence corresponded to the area of ICG fluorescence in each animal.

Conclusions: The visualization of fluorescence after the intravenous injection of vitamin B using a fluorescent camera was a simple, safe, and accurate method for detecting intersegmental planes in a pig model. This method can be an alternative to the inflation-deflation technique and the intravenous ICG method.
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http://dx.doi.org/10.1007/s00595-020-02137-wDOI Listing
May 2021

Therapeutic Plasma Exchange Improved Pregnancy-associated Thrombotic Microangiopathy but not the Pregnancy Outcome in Patient with Systemic Lupus Erythematosus.

Intern Med 2020 Dec 12;59(24):3235-3238. Epub 2020 Aug 12.

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Japan.

Thrombotic microangiopathy (TMA) is a rare but life-threatening complication of systemic lupus erythematosus (SLE) and is associated with adverse pregnancy outcomes. We herein report a 30-year-old pregnant woman with SLE complicated by TMA. Because her condition was unresponsive to initial corticosteroid and fresh-frozen plasma infusion treatment, we attempted plasma exchange (PE). Although thrombocytopenia and microangiopathic hemolytic anemia gradually improved, fetal death was confirmed at 23 weeks of gestation. This case suggests that PE is an effective therapeutic option but might be insufficient to maintain pregnancy in patients with SLE complicated by TMA.
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http://dx.doi.org/10.2169/internalmedicine.4655-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807106PMC
December 2020

Comparison of dynamic flat-panel detector-based chest radiography with nuclear medicine ventilation-perfusion imaging for the evaluation of pulmonary function: A clinical validation study.

Med Phys 2020 Oct 5;47(10):4800-4809. Epub 2020 Aug 5.

Department of Radiology, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.

Purpose: Dynamic chest radiography (DCR) is a flat-panel detector (FPD)-based functional lung imaging technique capable of measuring temporal changes in radiographic lung density due to ventilation and perfusion. The aim of this study was to determine the diagnostic performance of DCR in the evaluation of pulmonary function based on changes in radiographic lung density compared to nuclear medicine lung scans.

Methods: This study included 53 patients with pulmonary disease who underwent DCR and nuclear medicine imaging at our institution. Dynamic chest radiography was conducted using a dynamic FPD system to obtain sequential chest radiographs during one breathing cycle. The maximum change in the average pixel value (Δ ) was measured, and the percentage ofΔ in each lung region, calculated relative to the sum of all lung regions (Δ %), was calculated for each factor (ventilation and perfusion). The Δ % was compared with the accumulation of radioactive agents (radioactive agents%) on ventilation and perfusion scans in each lung and lung region using correlation coefficients and scatter plots. The ratio of ventilation to perfusion Δ % was calculated and compared with nuclear medicine ventilation-perfusion (V/Q) findings in terms of sensitivity and specificity for V/Q mismatch in each lung region.

Results: There was a high correlation between Δ % and radioactive agents% for each lung (Ventilation: r = 0.81, perfusion: r = 0.87). However, correlation coefficients were lower (0.37 to 0.80) when comparing individual lung regions, with the upper lung regions showing the lowest correlation coefficients. The sensitivity and specificity of DCR for V/Q mismatch were 63.3% (19/30) and 60.1% (173/288), respectively. Motion artifacts occasionally increased Δ %, resulting in false negatives.

Conclusions: Ventilation and perfusion Δ % correlated reasonably with radioactive agents% on ventilation and perfusion scans. Although the regional correlations were lower and the detection performance for V/Q mismatch was not enough for clinical use at the moment, these results suggest the potential for DCR to be used as a functional imaging modality that can be performed without the use of radioactive contrast agents. Further technical improvement is required for the implementation of DCR-based V/Q studies.
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http://dx.doi.org/10.1002/mp.14407DOI Listing
October 2020

Case report: uniportal video-assisted thoracoscopic resection of a solitary fibrous tumor preoperatively predicted visceral pleura origin using dynamic chest radiography.

J Cardiothorac Surg 2020 Jul 8;15(1):166. Epub 2020 Jul 8.

Department of Thoracic, Cardiovascular and General Surgery, Kanazawa University, Takara-machi 13-1, Kanazawa, 920-8640, Japan.

Background: Dynamic chest radiography (DCR) is a flat-panel detector (FPD)-based functional X-ray imaging, which is performed as an additional examination in chest radiography. DCR provides objective and quantifiable information, such as diaphragm movement, pulmonary ventilation and circulation, and is reasonable for detecting tumor invasion or adhesion.

Case Presentation: We present a case of Solitary Fibrous Tumor of Pleura (SFTP), preoperatively predicted visceral pleura origin using Dynamic chest radiography (DCR) and surgically resected through single-access (uniportal) video-assisted thoracoscopic surgery (UVATS).

Conclusions: UVATS may be a suitable surgical option for pedunculated SFTPs. Dynamic chest radiography provides information, such as tumor invasion or adhesion and helpful for predicting origin of the tumor.
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http://dx.doi.org/10.1186/s13019-020-01212-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346465PMC
July 2020

M3 muscarinic acetylcholine receptor-reactive Th17 cells in primary Sjögren's syndrome.

JCI Insight 2020 08 6;5(15). Epub 2020 Aug 6.

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.

M3 muscarinic acetylcholine receptor (M3R) is one of the autoantigens associated with Sjögren's syndrome (SS) and is localized in exocrine glands where disease-specific inflammation occurs. The inflammatory lesion is characterized by infiltration of CD4+ T cells, including clonally expanded Th17 cells. We undertook this study to identify circulating M3R-specific Th17 cells and to determine functional properties of those cells. Using the enzyme-linked immunospot assay (ELISpot) method, we identified M3R-reactive Th17 cells in the peripheral blood of patients with primary SS (pSS). Among 10 examined pSS patients, 10 healthy subjects (HS), and 5 IgG4-related disease (IgG4-RD) patients, M3R-reactive IL-17 secreting cells were significantly increased in 5 pSS patients specifically. The most common T cell epitope, which was analyzed and confirmed by coculture of isolated CD4+ T cells with antigen presenting cells plus M3R peptides in vitro, was peptide 83-95 of M3R. Peptide recognition was partly in an HLA-DR-restricted manner, confirmed by blocking assay. M3R-reactive Th17 cells positivity correlated with higher titers of anti-M3R antibodies, whose systemic disease activity score tended to be higher. Our studies highlight the role of tissue-specific autoantigen-derived circulating Th17 cells in pSS, for which further work might lead to antigen-specific targeted therapy.
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http://dx.doi.org/10.1172/jci.insight.135982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455086PMC
August 2020

T follicular helper cell subsets: a potential key player in autoimmunity.

Immunol Med 2021 Mar 17;44(1):1-9. Epub 2020 Jun 17.

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Follicular helper T (Tfh) cells are one of CD4+ helper T subsets which promote B cell maturation, activation and antigen-specific antibody production. Autoantibodies are hallmarks of autoimmune diseases, and crucial contributions of Tfh cells in development of these diseases are now evident. Deregulation of Tfh activities can contribute to a pathogenic autoantibody production and can play an important role in the promotion of autoimmune diseases. These days multiple researchers reported three subpopulations which has distinct effector functions in Tfh cells: Tfh1, Tfh2 and Tfh17 cells. In this review, we summarize the observed alterations in whole Tfh cells and subset distribution during autoimmune diseases.
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http://dx.doi.org/10.1080/25785826.2020.1776079DOI Listing
March 2021

Semi-comprehensive analysis of gene amplification in thymic malignant tumors using multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.

Int J Clin Exp Pathol 2020 1;13(5):1035-1044. Epub 2020 May 1.

Department of Molecular and Cellular Pathology, Graduate School of Medical Science, Kanazawa University Ishikawa, Japan.

Research on the amplification of oncogenes in thymic malignant tumor is limited. In this study, we aimed to determine the gene amplification status of receptor tyrosine kinases and other cell regulator genes in thymic malignant tumors, with a view toward the future introduction of molecular targeted therapy. In addition, we examined the usefulness of multiplex, ligation-dependent probe amplification (MLPA) in the semi-comprehensive detection of these gene amplifications. The participants of this study were nine patients with thymic carcinoma and one patient with atypical carcinoid who underwent resection at our department from 1999 to 2016. Twenty-four oncogenes () were analyzed for amplification by MLPA. In cases where amplification by MLPA was suspected, confirmation was performed by fluorescence in situ hybridization (FISH). Immunostaining for detected oncoproteins and p53 were performed in cases with confirmed oncogene amplification. (2/10, 20%) and (1/10, 10%) amplifications were detected using MLPA and FISH. Immunostaining in both cases was positive. The -amplified tumor relapsed and spread rapidly after operation despite the use of post-operative chemo-radiotherapy. amplification may be involved in the carcinogenesis of thymic malignant tumors. In addition, amplification may be a concern in the increased malignancy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270679PMC
May 2020

[Thymoma Presenting Synchronously with a Mycosis Fungoides;Report of a Case].

Kyobu Geka 2020 Jun;73(6):466-470

Department of Thoracic Surgery, Kanazawa Medical Center, Kanazawa, Japan.

A 65-year-old woman presented with mycosis fungoides and an anterior mediastinal tumor. Stage Ⅱa mycosis fungoides was treated with bath psoralen plus ultraviolet A, topical corticosteroids, and oral bexarotene. One month later, a surgical resection was performed for the anterior mediastinal tumor, which was a stage Ⅱ thymoma with membrane invasion. Furthermore, adjuvant radiotherapy was performed for anterior mediastinum. The mycosis fungoides lesion exacerbated after 3 months;thus, chemotherapies were performed. The patient died of respiratory insufficiency due to multiple pulmonary metastases of mycosis fungoides 1 year after the operation.
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June 2020

[Surgical Treatment of Pectus Excavatum in Patients with Marfan Syndrome Associated with Vertebral or Cardiovascular Disease].

Kyobu Geka 2020 Mar;73(3):163-168

Department of General, Thoracic and Cardiovascular Surgery, Kanazawa University, Kanazawa, Japan.

Surgical treatment is often required in patients with Marfan syndrome presenting with scoliosis or cardioaortic disease. If these patients present with pectus excavatum, surgery for spinal deformity correction or chest wall closure during cardioaortic surgery can cause thoracic organ compression secondary to narrowing of the thorax resulting in hemodynamic and respiratory compromise. Cardiovascular complications serve as prognostic factors in patients with Marfan syndrome, and surgical treatment is often required in these cases. In our case series involving 4 patients, 2 patients with pectus excavatum and scoliosis underwent a Nuss procedure followed by safe and successful spinal correction surgery 6 months later. A Nuss procedure was also performed in a patient complicated with sinus of Valsalva dilatation, and thoracotomy was performed before cardioaortic surgery. Another patient with a complication of pectus excavatum and acute deterioration of cardiac status underwent concomitant repair with sternal elevation using an AO plate and cardioaortic surgery. In patients with Marfan syndrome presenting with pectus excavatum complicated by scoliosis or cardioaortic disease, it is necessary to consider concomitant or staged repair depending on the disease condition.
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March 2020

Dynamic-Ventilatory Digital Radiography in Air Flow Limitation: A Change in Lung Area Reflects Air Trapping.

Respiration 2020;99(5):382-388. Epub 2020 Apr 29.

College of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan.

Objective: The aim of this study was to determine the utility of dynamic-ventilatory digital radiography (DR) for pulmonary function assessment in patients with airflow limitation.

Methods: One hundred and eighteen patients with airflow limitation (72 patients with lung cancer before surgery, 35 patients with chronic obstructive pulmonary disease [COPD], 6 patients with asthma, and 5 patients with asthma-COPD overlap syndrome) were assessed with dynamic-ventilatory DR. The patients were instructed to inhale and exhale slowly and maximally. Sequential chest X-ray images were captured in 15 frames per second using a dynamic flat-panel imaging system. The relationship between the lung area and the rate of change in the lung area due to respiratory motion with respect to pulmonary function was analyzed.

Results: The rate of change in the lung area from maximum inspiration to maximum expiration (Rs ratio) was associated with the RV/TLC ratio (r = 0.48, p < 0.01) and the percentage of the predicted FEV1 (r = -0.33, p < 0.01) in patients with airflow limitations. The Rs ratio also decreased in an FEV1-dependent manner.

Conclusion: The rate of change in the lung area due to respiratory motion evaluated with dynamic DR reflects air trapping. Dynamic DR is a potential tool for the comprehensive assessment of pulmonary function in patients with COPD.
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http://dx.doi.org/10.1159/000506881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845443PMC
April 2021

Dynamic chest radiography: Novel and less-invasive imaging approach for preoperative assessments of pleural invasion and adhesion.

Radiol Case Rep 2020 Jun 6;15(6):702-704. Epub 2020 Apr 6.

Department of Thoracic, Cardiovascular and General Surgery, Kanazawa University, Kanazawa, Japan.

Here, we report a case of lung cancer with preoperatively predicted invasion to the parietal pleura on dynamic chest radiography (DCR). An 82-year-old patient was referred for staging of a right lung tumor. Preoperative DCR revealed invasion or adhesion of the tumor to the chest wall, and intraoperative findings revealed invasion of the tumor to the parietal pleura. DCR provides objective and quantifiable information, including diaphragmatic movement, pulmonary ventilation, and circulation, as well as tumor invasion or adhesion and is less invasive compared to 3-dimensional chest computed tomography or cine magnetic resonance imaging. This study was our initial attempt at performing a quantitative assessment using DCR.
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http://dx.doi.org/10.1016/j.radcr.2020.02.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138928PMC
June 2020

Vitamin B2 lung-marking method using black light irradiation.

J Thorac Dis 2020 Mar;12(3):651-658

Department of Thoracic, Cardiovascular and General Surgery, Kanazawa University, Kanazawa, Japan.

Background: Various approaches and markers for marking the lungs prior to lung tumor resection have been reported. In clinical practice, the hook wire localization method is often used owing to the simplicity of the technique. However, although rare, this method is associated with air embolism, which can be lethal. Because vitamin B2 is harmless to the body and fluorescent, it was applied to various methods for thoracic surgery. Using a pig model, we aimed to examine whether a lung-marking method involving the injection of vitamin B2 to peripheral small lung lesions and observing them under black light irradiation could replace the hook wire localization method.

Methods: We used a pig model to perform hook wire localization of the lungs and at the same time injected 1 mL of a vitamin B2 aqueous solution to the lung parenchyma at the hook wire puncture site under the visceral pleura. Subsequently, we measured the length of the fluorescent marked area and fluorescence intensity over time. Black light was used to assess the fluorescent marked area, and fluorescence intensity was quantified using image analysis software.

Results: Lung-marking was successful in all five pigs and we visualized the vitamin B2-marked area under black light irradiation. Measurements were taken immediately after thoracotomy (0 min) and 60 and 120 min thereafter. No changes in the length of the marked area (1.3±0.3/1.2±0.3/1.1±0.3 cm, 0/60/120 min, P=0.21) and fluorescence intensity (162.8±55.1/157.2±63.1/165.2±62.2, 0/60/120 min, P=0.96) were observed over time. Compared to the non-marked area (normal lungs), the marked area showed significantly higher fluorescence intensity (P=0.01/0.01/0.01, 0/60/120 min).

Conclusions: Vitamin B2 lung-marking was performed safely and accurately using the pig model, providing good visibility of the marked area. This approach may replace the hook wire localization method. In the near future, we plan to conduct clinical trials to evaluate the applicability of this method in humans.
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http://dx.doi.org/10.21037/jtd.2020.01.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139060PMC
March 2020

IgG4-related pleural disease with aortitis and submandibular glands involvement successfully treated with corticosteroid: case-based review.

Rheumatol Int 2020 Oct 23;40(10):1725-1732. Epub 2020 Mar 23.

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition characterized by increased serum IgG4 level, infiltration of lymphocytes and IgG4-positive (IgG4) plasma cells and fibrosis. It can occur in almost all organs, commonly affecting the pancreas, biliary tract, salivary and lacrimal glands and kidneys. However, reports of IgG4-RD accompanied by pathologically confirmed, IgG4-related pleural disease are scarce. Here, we present a case of a 64-year-old man with suspected malignant pleural mesothelioma based on imaging findings but finally diagnosed with IgG4-RD (including pleuritis, periaortitis and bilateral submandibular gland enlargement) based on a high serum IgG4 level and pleural histopathological findings such as lymphoplasmacytic infiltration including IgG4 plasma cells and fibrosis. Systemic corticosteroid therapy was effective at reducing serum IgG4, improving bilateral submandibular gland enlargement, and regressing pleural thickening and periaortic soft tissue. We also discuss clinical characteristics and pleural pathological features of previously reported cases with IgG4-related pleural disease based on a comprehensive literature review. Our case of IgG4-RD with pleura, aorta and submandibular gland involvement, pathologically confirmed by pleural specimen might be unique and very rare.
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http://dx.doi.org/10.1007/s00296-020-04555-yDOI Listing
October 2020

Aortic Arch Aneurysm in Behçet Disease Successfully Treated with Infliximab.

Intern Med 2020 Apr 9;59(8):1087-1091. Epub 2020 Jan 9.

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Japan.

Aortic arch aneurysm (AAA) is a rare involvement in Behçet disease (BD). It is often life-threatening, yet few reports related to the treatment of AAA have been published. We herein report a 27-year-old woman with AAA caused by vascular BD. She was initially treated with prednisolone 1 mg/kg/d. However, the inflammation had not subsided after three weeks, so infliximab (IFX) was added for relief. After IFX administration, the C-reactive protein level normalized, and computed tomography at three months after therapeutic intervention revealed that the aneurysm had disappeared. This case suggests that early induction of IFX might be effective for aortic aneurysm in BD.
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http://dx.doi.org/10.2169/internalmedicine.3946-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205534PMC
April 2020
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