Publications by authors named "Masahiro Aoshima"

85 Publications

Three-dimensional histological explanation of the dermoscopy patterns in acral melanocytic lesions.

J Dermatol 2021 Apr 27. Epub 2021 Apr 27.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Dermoscopic images of pigmented lesions have distinct features on the sole where skin ridges and furrows exist. Pigmentation of benign nevus usually locates on the skin furrow, while the malignant melanoma is pigmented on the skin ridge. Correspondence between dermoscopy and pathology in the pigmented lesions on soles have been studied based on conventional vertical pathological images. However, for the full understanding of the correspondence, observation of horizontal histological images would be required, because the epidermis constructs unique horizontal structures, namely crista profunda limitans, crista profunda intermedia, and transverse ridge. In this study, we analyzed basic dermoscopic images of the representative acral melanocytic lesions (nevus, lentigo, and malignant melanoma) by horizonal histological images. We created serial horizontal pathological images by digital reconstruction of a hundred of serial vertical images. We could show that parallel furrow pattern is created by the pigmentation of crista profunda limitans, parallel ridge pattern by the pigmentation of both of crista profunda limitans and crista profunda intermediate, and lattice-like pattern by the pigmentation of transverse ridge. Our results would be useful for the intuitive histological understanding of dermoscopy.
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http://dx.doi.org/10.1111/1346-8138.15907DOI Listing
April 2021

Definitive and Indeterminate Infection in Adults with Community-Acquired Pneumonia: A Prospective Observational Study.

Ann Am Thorac Soc 2021 Feb 10. Epub 2021 Feb 10.

Institute of Tropical Medicine, Nagasaki University, Department of Clinical Medicine, Nagasaki, Nagasaki, Japan.

Rationale: Pneumonia due to (PA) is associated with high mortality and requires antipseudomonal treatment. Since PA can colonize the respiratory tract, the diagnosis of pathogenic PA involvement is challenging.

Objectives: To determine the prevalence of definitive and indeterminate PA infection in community-acquired pneumonia, to describe the clinical and microbiological profiles and to estimate the burden of unnecessary antipseudomonal drug prescriptions.

Methods: We prospectively enrolled 2,701 patients with community-acquired pneumonia. Using stringent criteria for diagnosing PA pneumonia, we generated three groups: 1) definitive PA, 2) indeterminate PA, and 3) non-PA pneumonia.

Results: The prevalence of definitive PA pneumonia was 0.9% (n = 25) and that of indeterminate PA pneumonia was 4.9% (n = 131). Considerable clinical differences were observed among the groups. Patients with definitive PA pneumonia were more likely to have a history of tuberculosis and COPD/bronchiectasis and had a higher 30-day mortality (28%) than patients with non-PA pneumonia. Patients with indeterminate PA pneumonia were more likely to have comorbidities than patients with non-PA pneumonia. More than half of the patients with indeterminate PA and 25% of the patients with non-PA pneumonia were treated with an antipseudomonal drug. No patients with definitive PA pneumonia had multidrug resistance.

Conclusions: In this population, the prevalence of community-acquired pneumonia due to PA was low. The clinical features and 30-day mortality rates of indeterminate PA pneumonia were different from those of definitive PA pneumonia. Most of the prescribed antipseudomonal drugs for patients with community-acquired pneumonia were potentially unnecessary.
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http://dx.doi.org/10.1513/AnnalsATS.201906-459OCDOI Listing
February 2021

Histologic factors associated with nintedanib efficacy in patients with idiopathic pulmonary fibrosis.

PLoS One 2021 7;16(1):e0245147. Epub 2021 Jan 7.

Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Background: Histopathologic factors predictive of nintedanib efficacy in idiopathic pulmonary fibrosis have not been studied. We aimed to describe the characteristics, focusing on histopathology, of idiopathic pulmonary fibrosis patients who did and did not respond to nintedanib.

Methods: This study retrospectively examined the clinicoradiopathologic features of 40 consecutive patients with surgical lung biopsy-confirmed idiopathic pulmonary fibrosis treated with nintedanib. Additionally, we compared the histopathologic scoring of 21 microscopic features between patients with functional or radiological progression and those with non-progression during 12 months of treatment.

Results: The histopathologic evaluation showed edematous changes in the interlobular septum as the only histologic finding observed more frequently in patients with both functional and radiological progression than in those without (58% vs. 14%, P = 0.007 and 50% vs. 0%, P = 0.003, respectively). Regarding per-year change, patients with edematous changes in the interlobular septum showed greater progression in median changes in spared area (-12%, interquartile range: [-25%--5%], vs. -3% [-7%-0%], P = 0.004) and reticular shadow (7% [3%-13%], vs. 0% [0%-5%], P = 0.041) on computed tomography. Functional and radiological progression-free survival were shorter in patients with edematous changes in the interlobular septum than in those without (6.6 months, 95% confidence interval: [5.9-25.3], vs. event <50%, [12.1-Not available], P = 0.0009, and 6.1 months, [5.2-6.6] vs. 14.5 months [7.8-not available], P<0.0001).

Conclusions: Edematous changes in the interlobular septum may indicate poor nintedanib efficacy in idiopathic pulmonary fibrosis. Further studies are needed to validate these findings and address the mechanism behind ECIS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245147PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790243PMC
May 2021

Prognostic value of chest computed tomography in community-acquired pneumonia patients.

ERJ Open Res 2020 Oct 23;6(4). Epub 2020 Nov 23.

Dept of Pulmonary Medicine, Kameda Medical Center, Kamogawa, Japan.

Background: Chest computed tomography (CT) is commonly used to diagnose pneumonia in Japan, but its usability in terms of prognostic predictability is not obvious. We modified CURB-65 (confusion, urea >7 mmol·L, respiratory rate ≥30 breaths·min, blood pressure <90 mmHg (systolic) ≤60 mmHg (diastolic), age ≥65 years) and A-DROP scores with CT information and evaluated their ability to predict mortality in community-acquired pneumonia patients.

Methods: This study was conducted using a prospective registry of the Adult Pneumonia Study Group - Japan. Of the 791 registry patients, 265 hospitalised patients with chest CT were evaluated. Chest CT-modified CURB-65 scores were developed with the first 30 study patients. The 30-day mortality predictability of CT-modified, chest radiography-modified and original CURB-65 scores were validated.

Results: In score development, infiltrates over four lobes and pleural effusion on CT added extra points to CURB-65 scores. The area under the curve for CT-modified CURB-65 scores was significantly higher than that of chest radiography-modified or original CURB-65 scores (both p<0.001). The optimal cut-off CT-modified CURB-65 score was ≥4 (positive-predictive value 80.8%; negative-predictive value 78.6%, for 30-day mortality). For sensitivity analyses, chest CT-modified A-DROP scores also demonstrated better prognostic value than did chest radiography-modified and original A-DROP scores. Poor physical status, chronic heart failure and multiple infiltration hampered chest radiography evaluation.

Conclusion: Chest CT modification of CURB-65 or A-DROP scores improved the prognostic predictability relative to the unmodified scores. In particular, in patients with poor physical status or chronic heart failure, CT findings have a significant advantage. Therefore, CT can be used to enhance prognosis prediction.
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http://dx.doi.org/10.1183/23120541.00079-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680909PMC
October 2020

Automated computed tomography quantification of fibrosis predicts prognosis in combined pulmonary fibrosis and emphysema in a real-world setting: a single-centre, retrospective study.

Respir Res 2020 Oct 20;21(1):275. Epub 2020 Oct 20.

Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.

Background: Combined pulmonary fibrosis and emphysema (CPFE) is a heterogeneous clinico-radiological syndrome without a consensus definition. There are limited data on the relation between the amount of parenchymal fibrosis and prognosis. In this study, we assessed the prognostic implications of the extent of fibrosis assessed by an automated quantitative computed tomography (CT) technique and the radiological and functional change over time in patients with a broad spectrum of fibrotic interstitial lung diseases (ILDs) encountered in a real-world setting.

Methods: We conducted a single-centre, retrospective study of 228 consecutive patients with CPFE, encountered from 2007 to 2015 at Kameda Medical Center, Chiba, Japan. We investigated the prognostic value of automated CT fibrosis quantification and the subsequent course of CPFE.

Results: Among 228 patients with CPFE, 89 had fibrosis affecting < 5% of their lungs, 54 had 5 to < 10% fibrosis, and 85 had ≥ 10% fibrosis at the time of diagnosis. Lower volume of fibrosis correlated with lower rates of mortality and acute exacerbation (p < 0.001). In particular, among those with < 5% fibrosis, only 4.5% died and none experienced acute exacerbation during follow-up, whereas 57.6% and 29.4% of those with ≥ 10% fibrosis experienced death and acute exacerbation, respectively. Although, the ≥ 10% fibrosis group had the poorest overall survival as well as the highest incidence of acute exacerbation, the incidence of decline in pulmonary function tests, change per year in total lung volume, and progression of fibrosis on chest CT was highest in the 5 to < 10% fibrosis group. The Cox proportional hazard model for CPFE progression (defined by composite criteria of death, acute exacerbation, and decline in forced vital capacity or diffusing capacity) showed fibrosis proportion was a risk factor independent of age, sex, smoking pack-years, the Charlson Comorbidity Index, lung cancer, connective tissue disease, and idiopathic pulmonary fibrosis.

Conclusions: Less severe (< 5%) fibrosis at baseline was associated with disease stability and better prognosis compared to more severe fibrosis in CPFE occurring with fibrotic ILDs. Further studies including a validation cohort will be needed. Trial Registration Retrospectively registered.
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http://dx.doi.org/10.1186/s12931-020-01545-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576807PMC
October 2020

The utility of transbronchial rebiopsy for peripheral pulmonary lesions in patients with advanced non-squamous non-small cell lung cancer.

BMC Pulm Med 2020 Sep 9;20(1):238. Epub 2020 Sep 9.

Department of Endoscopy, Respiratory Endoscopy Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan.

Background: Patients treated for non-squamous (non-Sq) non-small cell lung cancer (NSCLC) often require repeat biopsies to determine the optimal subsequent treatment. However, the differences between rebiopsy and initial biopsy in terms of their diagnostic yields and their ability to test the molecular profiles using bronchoscopy with radial endobronchial ultrasound guidance in patients with advanced NSCLC remain unclear. Hence, we aimed to compare the diagnostic yields and ability for molecular analyses of rebiopsies with those of initial biopsies.

Methods: We investigated 301 patients with advanced non-Sq NSCLC who underwent radial endobronchial ultrasound-guided transbronchial biopsy (TBB) for peripheral pulmonary lesions (PPLs) between August 2014 and July 2017. Patients were divided into the rebiopsy and initial biopsy groups: the latter referred to the biopsy that determined the definitive diagnosis. The diagnostic yields and ability for molecular analyses were compared between the two groups, and the factors affecting the TBB diagnostic yield were identified using univariate and multivariate analyses.

Results: The diagnostic yields of the rebiopsy and initial biopsy groups were comparable (86.8 and 90.8%, respectively; p = 0.287). Furthermore, 93.0 and 94.0% of the patients in the rebiopsy and initial biopsy groups, respectively, had adequate specimens for gene profiling and mutational analysis (p = 0.765). The factors that increased the diagnostic yield were a positive bronchus sign (p < 0.001) and tumour location within the internal two-thirds of the lungs (p = 0.026).

Conclusions: The PPL diagnostic yield of the rebiopsy group was as high as that of the initial biopsy group. Hence, TBB for PPLs is feasible for patients requiring rebiopsy as well as for those with initial diagnoses. Adequate, high-quality biopsy specimens can be obtained by transbronchial rebiopsy for molecular testing.
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http://dx.doi.org/10.1186/s12890-020-01277-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487475PMC
September 2020

Suprabasin-null mice retain skin barrier function and show high contact hypersensitivity to nickel upon oral nickel loading.

Sci Rep 2020 09 3;10(1):14559. Epub 2020 Sep 3.

Department of Dermatology, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-Ku, Hamamatsu, 431-3192, Japan.

Suprabasin (SBSN) is expressed not only in epidermis but also in epithelial cells of the upper digestive tract where metals such as nickel are absorbed. We have recently shown that SBSN level is decreased in the stratum corneum and serum of atopic dermatitis (AD) patients, especially in intrinsic AD, which is characterized by metal allergy. By using SBSN-null (Sbsn) mice, this study was conducted to investigate the outcome of SBSN deficiency in relation to AD. Sbsn mice exhibited skin barrier dysfunction on embryonic day 16.5, but after birth, their barrier function was not perturbed despite the presence of ultrastructural changes in stratum corneum and keratohyalin granules. Sbsn mice showed a comparable ovalbumin-specific skin immune response to wild type (WT) mice and rather lower contact hypersensitivity (CHS) responses to haptens than did WT mice. The blood nickel level after oral feeding of nickel was significantly higher in Sbsn mice than in WT mice, and CHS to nickel was elevated in Sbsn mice under nickel-loading condition. Our study suggests that the completely SBSN deficient mice retain normal barrier function, but harbor abnormal upper digestive tract epithelium that promotes nickel absorption and high CHS to nickel, sharing the features of intrinsic AD.
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http://dx.doi.org/10.1038/s41598-020-71536-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471289PMC
September 2020

Pulmonary Sarcoidosis Presenting with Acute Respiratory Failure: A Report of a Case Diagnosed by Endobronchial Ultrasound-guided Transbronchial Needle Aspiration on Ventilation after Intubation.

Intern Med 2020 Sep 15;59(18):2291-2295. Epub 2020 Jun 15.

Department of Pulmonology, Kameda Medical Center, Japan.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology and is pathologically characterized by non-caseating granulomas in the organs involved. We herein report a case of sarcoidosis in a Japanese woman with acute respiratory failure, diagnosed using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) on the ventilator after intubation. Only a few cases of previously undiagnosed sarcoidosis presenting acute respiratory failure have been reported. It is important to be aware that undiagnosed sarcoidosis may present with acute respiratory failure. Therefore, EBUS-TBNA under mechanical ventilation may be useful for the immediate diagnosis of patients.
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http://dx.doi.org/10.2169/internalmedicine.4624-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578599PMC
September 2020

Safety of the anterior approach versus the lateral approach for chest tube insertion by residents treating spontaneous pneumothorax: a propensity score weighted analysis.

Gen Thorac Cardiovasc Surg 2020 Dec 9;68(12):1425-1431. Epub 2020 Jun 9.

Department of Pulmonology, Kameda Medical Center, 929 Higashi-cho, Kamogawa, Chiba, 296-8602, Japan.

Objective: To compare the risk of chest tube malposition, the most common complication during chest tube insertion, with the anterior or lateral approach for thoracostomy performed for patients with spontaneous pneumothorax by junior and senior residents.

Methods: We retrospectively included patients aged ≥ 20 years who exhibited primary or secondary spontaneous pneumothorax without pleural adhesion and underwent chest tube drainage performed by junior or senior residents at tertiary care hospital. The study exposure involved insertion of the chest tube in the midclavicular line (anterior approach) or the anterior or midaxillary line (lateral approach). The primary outcome was the number of chest tube malpositions. Multiple imputation was used for missing data. The inverse probability of treatment weighting method was used to adjust for baseline confounders.

Results: We identified 34 and 219 patients who underwent thoracostomy using the midclavicular and lateral approaches, respectively. The number of chest tube malpositions was 4 (11.8%) in the anterior approach and 34 (15.5%) in the lateral approach. The inverse probability of treatment weighting analysis revealed that the estimated odds ratio for chest tube malposition in the anterior approach group versus the lateral approach group was 0.61 (95% confidence interval, 0.17-2.11). The duration of chest tube drainage and the number of operations for persistent air leaks were not significantly different between the groups.

Conclusions: The current study revealed that the risk of chest tube malposition in thoracostomies with the midclavicular approach was not different from that with the lateral approach.
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http://dx.doi.org/10.1007/s11748-020-01403-5DOI Listing
December 2020

Protective role of Galectin-7 for skin barrier impairment in atopic dermatitis.

Clin Exp Allergy 2020 08 14;50(8):922-931. Epub 2020 Jun 14.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Background: Atopic dermatitis (AD) patients have a barrier disorder in association with Th2 dominant skin inflammation. Galectin-7 (Gal-7), a soluble unglycosylated lectin, is highly expressed in the stratum corneum of AD patients. However, the biological significance of increased Gal-7 expression in AD skin lesions remains unclear.

Objective: We aimed to investigate the production mechanism and functional role of Gal-7 in AD patients and IL-4/IL-13-stimulated epidermal keratinocytes.

Methods: We assessed the Gal-7 expression levels in skin lesions and sera from AD patients. Gal-7 levels were also measured in monolayered normal human epidermal keratinocytes (NHEKs) and 3-dimensional (3D)-reconstructed epidermis in the presence or absence of IL-4/IL-13 with or without Stat3, Stat6 or Gal-7 gene silencing.

Results: Gal-7 was highly expressed in the stratum corneum or intercellular space of AD lesional epidermis as assessed by the stratum corneum proteome analysis and immunohistochemistry. A positive correlation was noted between serum Gal-7 level and transepidermal water loss in patients with AD. These clinical findings were corroborated by our in vitro data, which showed that IL-4/IL-13 facilitated the extracellular release of endogenous Gal-7 in both monolayered NHEKs and 3D-reconstructed epidermis. This machinery was caused by IL-4/IL-13-induced cell damage and inhibited by knockdown of Stat6 but not Stat3 in NHEKs. Moreover, we performed Gal-7 knockdown experiment on 3D-reconstructed epidermis and the result suggested that endogenous Gal-7 serves as a protector from IL-4/IL-13-induced disruption of cell-to-cell adhesion and/or cell-to-extracellular matrix adhesion.

Conclusion And Clinical Relevance: Our study unveils the characteristic of Gal-7 and its possible role as an alarmin that reflects the IL-4/IL-13-induced skin barrier impairment in AD.
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http://dx.doi.org/10.1111/cea.13672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496409PMC
August 2020

Corrigendum to "Impact of the pediatric 13-valent pneumococcal conjugate vaccine on serotype distribution and clinical characteristics of pneumococcal pneumonia in adults: The Japan Pneumococcal Vaccine Effectiveness Study (J-PAVE)" [Vaccine 37 (2019) 2687-2693].

Vaccine 2020 Apr 19;38(17):3404. Epub 2020 Mar 19.

Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; Department of Clinical Tropical Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.vaccine.2020.03.031DOI Listing
April 2020

Skin Infiltration of Pathogenic Migratory and Resident T Cells Is Decreased by Secukinumab Treatment in Psoriasis.

J Invest Dermatol 2020 10 19;140(10):2073-2076.e6. Epub 2020 Mar 19.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

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http://dx.doi.org/10.1016/j.jid.2020.02.024DOI Listing
October 2020

Thrombomodulin Alfa for Acute Exacerbation of Idiopathic Pulmonary Fibrosis. A Randomized, Double-Blind Placebo-controlled Trial.

Am J Respir Crit Care Med 2020 05;201(9):1110-1119

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Aichi, Japan.

Acute exacerbation during the course of idiopathic pulmonary fibrosis causes a poor prognosis. Coagulation abnormalities and endothelial damage are involved in its pathogenesis. Thrombomodulin alfa, a recombinant human soluble thrombomodulin, has anticoagulant and antiinflammatory effects. Several clinical studies have shown that thrombomodulin alfa may improve survival of acute exacerbation. To determine the efficacy and safety of thrombomodulin alfa compared with placebo in acute exacerbation of idiopathic pulmonary fibrosis. This randomized, double-blind placebo-controlled phase 3 study conducted at 27 sites in Japan involved patients with an acute exacerbation of idiopathic pulmonary fibrosis. Subjects were randomized 1:1 to receive placebo or thrombomodulin alfa (380 U/kg/d for 14 d by intravenous drip infusion). All subjects were treated with high-dose corticosteroid therapy. The primary endpoint was the survival proportion on Day 90. Of the 82 randomized subjects, 77 completed the study and were included in the full analysis set (thrombomodulin alfa,  = 40; placebo,  = 37). The survival proportions on Day 90 were 72.5% (29 of 40) in the thrombomodulin alfa group and 89.2% (33 of 37) in the placebo group, a difference of -16.7 percentage points (95% confidence interval, -33.8 to 0.4%;  = 0.0863). In the safety population ( = 80), bleeding adverse events occurred in the thrombomodulin alfa group (10 of 42; 23.8%) and the placebo group (4 of 38; 10.5%). Thrombomodulin alfa did not improve the 90-day survival proportion. The present results suggest that the use of thrombomodulin alfa for the treatment of acute exacerbation of idiopathic pulmonary fibrosis not be recommended.Clinical trial registered with www.clinicaltrials.gov (NCT02739165).
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http://dx.doi.org/10.1164/rccm.201909-1818OCDOI Listing
May 2020

An intuitive explanation of dermoscopic structures by digitally reconstructed pathological horizontal top-down view images.

Sci Rep 2019 12 27;9(1):19875. Epub 2019 Dec 27.

Department of Dermatology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-Ku, Hamamatsu, 431-3192, Japan.

Dermoscopy is a convenient tool to diagnose melanocytic lesions, especially nevus and melanoma. Various pigmented structures, including pigment network, dots and globules, and streaks, are observed in dermoscopy. Usually, 2D vertical images are used to explain the correlation of dermoscopy and histopathology. However, because the image of dermoscopy is horizontal, it is difficult for the horizontal view of dermoscopy to refer to the vertical view of histopathology. In our study, we digitally reconstructed 2D horizontal top-down view images and 3D aerial images from 50-100 serial 2D vertical sections by using high-speed scanner and 3D software in 6 cases of melanocytic lesion. Our new technology intuitively explained the histopathological structures corresponding to the dermoscopic structures. This technique could be used as a good educational tool for beginners.
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http://dx.doi.org/10.1038/s41598-019-56522-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934765PMC
December 2019

Severe acute respiratory failure due to Sai-rei-to-induced lung injury successfully treated by multi-modal therapy including immunosuppressive therapy, plasma exchange, and intravenous immunoglobulin: A case report.

Respir Med Case Rep 2019 16;28:100955. Epub 2019 Oct 16.

Department of Pulmonology, Kameda Medical Center, 929 Higashi-cho, Kamogawa-shi, Chiba, 296-8602, Japan.

Corticosteroid therapy may not be enough to control pneumonitis in some cases of severe drug-induced lung injury (DLI); however, an advanced treatment strategy for such cases is lacking. Here, we report the case of an 88-year-old man who presented with severe DLI, caused by Sai-rei-to. The patient visited our hospital complaining of progressive dyspnea. High-resolution computed tomography of the chest demonstrated bilateral patchy ground-glass opacities and infiltrative shadows. Nasal high-flow oxygen therapy was initiated because of severe hypoxemia. Bronchoalveolar lavage on admission revealed diffuse alveolar hemorrhage. Further, as the patient had started taking Sai-rei-to a month earlier, DLI caused by Sai-rei-to was the most likely diagnosis. Therefore, Sai-rei-to was stopped and steroid pulse therapy was initiated. However, he still required high-flow oxygen therapy. We considered an alternative diagnosis of Goodpasture syndrome or anti-neutrophil cytoplasmic antibody (ANCA) related vasculitis. We initiated the administration of cyclosporin A and therapeutic plasma exchange (TPE), but his respiratory condition did not improve satisfactorily. Therefore, we also initiated intravenous immunoglobulin (IVIG) therapy for the treatment of potential vasculitis. Subsequently, his respiratory status began to improve. Further, tests for anti-glomerular basement membrane antibody, myeloperoxidase-ANCA, and proteinase 3-ANCA revealed negative results. Drug-induced lymphocyte stimulation test performed six months after withdrawing methylprednisolone was positive for Sai-rei-to. Thus, the final diagnosis was DLI due to Sai-rei-to. Our findings demonstrate that in cases of severe acute respiratory failure due to DLI, the multi-modal therapy with plasma exchange and IVIG in addition to conventional treatment with prednisolone and immunosuppressant may be beneficial.
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http://dx.doi.org/10.1016/j.rmcr.2019.100955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831833PMC
October 2019

Laparoscopic surgery in patients with interstitial lung disease: A single-center retrospective observational cohort study.

Asian J Endosc Surg 2020 Jul 5;13(3):279-286. Epub 2019 Nov 5.

Department of Gastroenterological Surgery, Kameda Medical Center, Kamogawa, Japan.

Introduction: Laparoscopic surgery requiring longer operative times and artificial pneumoperitoneum may affect pulmonary function; its feasibility in patients with interstitial lung disease remains unknown. Therefore, we examined the feasibility of laparoscopic surgery in patients with interstitial lung disease.

Methods: We conducted a retrospective observational cohort study and examined the clinical data of patients with interstitial lung disease who had undergone abdominal surgery under general anesthesia. The primary end-point was the incidence of pulmonary complications. The secondary end-points were non-pulmonary complications and in-hospital mortality.

Results: Twenty-nine patients who had undergone abdominal surgery were diagnosed with interstitial lung disease after a review of their clinical and imaging records. Laparoscopic surgery and open surgery were performed in 11 and 18 patients, respectively. Acute exacerbation occurred in one (9%) patient in the laparoscopic group and three patients (17%) in the open group; all had undergone emergency surgery. Postoperative pneumonia did not occur in any patients. Non-pulmonary complications occurred in one patient (9%) in the laparoscopic group and two patients (11%) in the open group. One patient in each group died of acute exacerbation during hospitalization.

Conclusion: Neither acute exacerbation nor pulmonary complications occurred after elective laparoscopic or open surgery in patients with interstitial lung disease. The risk of acute exacerbation after elective laparoscopic surgery may not be as high as that after elective thoracic surgery.
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http://dx.doi.org/10.1111/ases.12762DOI Listing
July 2020

Decreased expression of suprabasin induces aberrant differentiation and apoptosis of epidermal keratinocytes: Possible role for atopic dermatitis.

J Dermatol Sci 2019 Sep 27;95(3):107-112. Epub 2019 Jul 27.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address:

Background: Suprabasin (SBSN), a secreted protein, is expressed in various epithelial tissues. The role of SBSN in epidermal differentiation and atopic dermatitis (AD) pathology remains largely unknown.

Objective: To evaluate the effects of SBSN on epidermal keratinocytes and its role in AD.

Methods: We examined the SBSN expression levels in the stratum corneum and the epidermis by proteome analysis and immunohistochemistry, respectively. The serum SBSN concentration was measured by ELISA. These values were compared between AD and healthy control. Morphological changes in the epidermis were investigated in SBSN-knockdown three-dimensional human living skin equivalent (LSE) model with or without IL-4/IL-13.

Results: Epidermal SBSN expression was decreased in AD lesional skin compared to healthy skin, as assessed by the stratum corneum proteome analysis and immunohistochemistry. The SBSN serum levels were significantly lower in AD patients than in normal subjects (P<0.05). The SBSN-deficient LSE exhibited compact stratum corneum, immature stratum granulosum, and increased keratinocyte apoptosis. Th2 cytokines, IL-4 and IL-13, did not affect SBSN expression in LSE. There were no differentiation-associated makers that were affected by the SBSN knockdown. SBSN deficiency-induced apoptosis of keratinocytes was exaggerated by IL-4/IL-13, and accordingly, the addition of recombinant SBSN induced significant keratinocyte proliferation (P<0.05).

Conclusion: Our data demonstrated that SBSN regulates normal epidermal barrier. Th2 cytokines unaffect SBSN expression in keratinocytes, but promote SBSN deficiency-induced apoptosis. It is suggested that SBSN has an anti-apoptotic activity, and its deficiency is involved in the pathogenesis of AD.
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http://dx.doi.org/10.1016/j.jdermsci.2019.07.009DOI Listing
September 2019

A case of protein-losing gastroenteropathy caused by systemic AA amyloidosis secondary to undifferentiated carcinoma of unknown primary origin.

Oxf Med Case Reports 2019 Aug;2019(8)

Department of Pulmonology, Kameda Medical Center, 929 Higashi-cho, Kamogawa 296-8602, Chiba Prefecture, Japan.

We report the case of a 61-year-old woman with Kartagener syndrome who presented with a 3-month history of chronic watery diarrhoea and severe hypoalbuminaemia. Histopathological examination of duodenum and large intestine biopsies showed amyloid A (AA) amyloid deposition. Scintigraphy and alpha-1 anti-trypsin clearance evaluations revealed protein-losing gastroenteropathy. Computed tomography with contrast and positron emission tomography showed a pelvic mass with multiple para-aortic lymph node enlargement. We suspected protein-losing gastroenteropathy secondary to AA amyloid produced related to malignant tumours. Following tumour resection, histopathological examination of the lesion revealed undifferentiated carcinoma of unknown origin. Postoperatively, the patient's nutritional condition improved. There has been no recurrence of protein-losing gastroenteropathy 6 months postoperatively. This is the first report of protein-losing gastroenteropathy and AA amyloidosis secondary to undifferentiated carcinoma. Early recognition and intervention could increase the likelihood of amyloidosis remission.
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http://dx.doi.org/10.1093/omcr/omz074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688888PMC
August 2019

Trichophyton tonsurans-induced kerion celsi with decreased defensin expression and paradoxically increased interleukin-17A production.

J Dermatol 2019 Sep 11;46(9):794-797. Epub 2019 Jul 11.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

We report a case of kerion celsi due to Trichophyton tonsurans. An 18-year-old male student judo practitioner had alopecic patches, black dots and subcutaneous abscesses on the right temporal region. The damaged hair represented endothrix infection with T. tonsurans, as assessed by mycological examinations. He was treated with oral itraconazole without any therapeutic effect, followed by terbinafine with good effect. A skin biopsy showed neutrophil, lymphocyte and histiocyte infiltration into the dermis and subcutaneous tissue with abscesses around a number of dilated hair follicles. Immunostaining showed that the expression level of human β-defensin 2 (HBD-2) was decreased in the epidermis of the alopecic and adjacent skin. Because interleukin (IL)-17A generally induces HBD-2 production by epidermal keratinocytes, we also immunohistochemically investigated IL-17A expression. Unexpectedly, many IL-17A-bearing cells were found around destructed hair follicles, indicating that IL-17A expression was not attenuated, but rather increased in the skin lesion. Our case suggests that IL-17A-upregulated antimicrobial peptide expression is disordered in kerion celsi, and severe inflammation with IL-17A may cause tissue damage and resultant scar.
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http://dx.doi.org/10.1111/1346-8138.15008DOI Listing
September 2019

Hepatitis B Virus-associated Vasculitis: Multiple Cavitary Masses in the Lung Mimicking Granulomatous Polyangiitis.

Intern Med 2019 Oct 27;58(20):3013-3017. Epub 2019 Jun 27.

Department of Pulmonary Medicine, Kameda Medical Center, Japan.

Hepatitis B virus (HBV) is one of the main causes of polyarteritis nodosa (PAN). We herein report a rare case of HBV-associated vasculitis presenting with multiple pulmonary nodules, mimicking granulomatous polyangiitis (GPA), with no abnormalities of the ear, nose, or kidney. A surgical lung biopsy revealed geographic necrosis surrounded by palisading granuloma and capillaritis. Because the HBV surface antigen was positive with a serum HBV-DNA level of 2.9 log10 copies/mL, we first treated the patient with entecavir and 2 weeks of prednisone 50 mg/day. The pulmonary nodules resolved, and seroconversion was observed after one month.
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http://dx.doi.org/10.2169/internalmedicine.3012-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859398PMC
October 2019

Sarcoid-like reaction and vitiligo occurring after nivolumab therapy in a patient with metastatic melanoma.

J Dermatol 2019 10 15;46(10):e359-e360. Epub 2019 Apr 15.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

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http://dx.doi.org/10.1111/1346-8138.14887DOI Listing
October 2019

Impact of the pediatric 13-valent pneumococcal conjugate vaccine on serotype distribution and clinical characteristics of pneumococcal pneumonia in adults: The Japan Pneumococcal Vaccine Effectiveness Study (J-PAVE).

Vaccine 2019 05 8;37(20):2687-2693. Epub 2019 Apr 8.

Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; Department of Clinical Tropical Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. Electronic address:

Background: The pediatric 13-valent pneumococcal conjugate vaccine (PCV13) was included in the pediatric immunization programme in Japan in late 2013. The impact of vaccination on the serotype distribution and clinical characteristics of pneumococcal pneumonia has not been described.

Methods: The first phase of this multicentre prospective study was conducted at community-based hospitals in Japan from 2011 to 2014. The second phase was conducted from 2016 to 2017. Pneumococcal isolates and clinical data were collected from patients with community-acquired pneumonia who were ≥15 years of age. Patients were classified by pneumococcal serotype to PCV13 serotype, 23-valent pneumococcal polysaccharide vaccine (PPV23) non-PCV13 serotype, and non-vaccine serotype.

Results: A total of 484 patients were enrolled, 241 in the first phase and 243 in the second. The proportion of PCV13 serotypes decreased from 53% to 33% (p < 0.001), whereas PPV23 non-PCV13 serotypes did not change (p = 0.754). PCV13 serotypes were associated with increased risk of elevated blood urea nitrogen (adjusted odds ratio 2.49; 95% confidence interval: 1.49-4.16) and hospitalization (adjusted odds ratio 1.74; 95% confidence interval: 1.02-2.95). These associations were not observed in patients with PPV23 non-PCV13 serotypes.

Conclusions: The occurrence of pneumococcal pneumonia caused by vaccine-covered serotypes dramatically decreased following the introduction of pediatric PCV13. The PCV13 serotypes were associated with pneumonia severity.
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http://dx.doi.org/10.1016/j.vaccine.2019.04.009DOI Listing
May 2019

Voriconazole-photoinduced polyomavirus-negative Merkel cell carcinoma.

J Dermatol 2019 08 12;46(8):e287-e288. Epub 2019 Mar 12.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

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http://dx.doi.org/10.1111/1346-8138.14849DOI Listing
August 2019

Unknown primary Merkel cell carcinoma responding well to first-line treatment with avelumab.

J Dermatol 2019 08 25;46(8):e273-e275. Epub 2019 Feb 25.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

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http://dx.doi.org/10.1111/1346-8138.14827DOI Listing
August 2019

Pulmonary Tumor Thrombotic Microangiopathy Mimicking Inhalation Lung Injury.

Intern Med 2019 May 10;58(9):1311-1314. Epub 2019 Jan 10.

Department of Pulmonology, Kameda Medical Center, Japan.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a complication characterized by dyspnea, pulmonary hypertension, and occasionally sudden death. We encountered a man who developed PTTM and had an inhalation history of chemical herbicides and abnormal findings on chest computed tomography, mimicking chemical inhalation lung injury. He was diagnosed with PTTM with adenocarcinoma by a transbronchial lung biopsy and received chemotherapy and anticoagulant therapy. He survived for one month. An autopsy revealed primary gastric cancer with PTTM that can have a presentation similar to diffuse pulmonary diseases, including chemical inhalation lung injury. The examination of a biopsy specimen is crucial in such patients.
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http://dx.doi.org/10.2169/internalmedicine.1796-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543225PMC
May 2019

Refractory diffuse alveolar hemorrhage caused by eosinophilic granulomatosis with polyangiitis in the absence of elevated biomarkers treated successfully by rituximab and mepolizumab: A case report.

Respir Med Case Rep 2019 15;26:112-114. Epub 2018 Dec 15.

Department of Pulmonology, Kameda Medical Center, Kamogawa, Chiba, Japan.

Here we report on a 61-year-old man with refractory eosinophilic granulomatosis with polyangiitis (EGPA) who presented with dyspnea. Despite treatment with glucocorticoids, intravenous cyclophosphamide, and plasma exchange, his symptoms worsened despite his eosinophil count and myeloperoxidase antineutrophil cytoplasmic antibody titer trending downwards. EGPA with diffuse alveolar hemorrhage was diagnosed on analysis of bronchoalveolar lavage fluid. The patient was treated with rituximab and methylprednisolone pulse therapy and a remission was achieved. He has been receiving mepolizumab since then and remains in remission. It should be recognized that refractory diffuse alveolar hemorrhage can occur in patients with EGPA without elevation of biomarkers if they are receiving systemic corticosteroids.
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http://dx.doi.org/10.1016/j.rmcr.2018.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302118PMC
December 2018

A diver with immersion pulmonary oedema and prolonged respiratory symptoms.

Diving Hyperb Med 2018 Dec;48(4):259-261

Department of Pulmonary Medicine, Kameda Medical Centre, Kamogawa, Chiba, Japan.

Immersion pulmonary oedema (IPE) is particularly associated with an excessive reaction to exercise and/or cold stress. IPE usually resolves without recompression therapy within a day or two. Herein we report a diver diagnosed with IPE, in whom symptoms persisted for five days. A 58-year-old man presented with sudden onset of dyspnoea, cough and haemoptysis after surfacing. He was an experienced diving instructor with a history of moderate mitral valve regurgitation. While IPE was diagnosed and oxygen administered, respiratory symptoms deteriorated, and serum C-reactive protein elevated. No evidence of infection was seen. Three hyperbaric oxygen treatments were given on the basis of suspected decompression sickness, and symptoms subsequently resolved. The recently diagnosed mitral valve regurgitation and inflammatory response were considered to have contributed to the prolongation of symptoms.
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http://dx.doi.org/10.28920/dhm48.4.259-261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355313PMC
December 2018

Disseminated varicella-zoster virus infection with abdominal pain possibly caused by pirfenidone: A case report.

Respir Med Case Rep 2018 26;25:330-332. Epub 2018 Oct 26.

Department of Pulmonary Medicine, Kameda Medical Center, 929 Higashi-cho, Kamogawa, Chiba 296-8602, Japan.

We report a case of chronic hypersensitivity pneumonitis treated with pirfenidone in a 76-year-old woman who complained of acute-onset abdominal pain and rashes. The patient was diagnosed with disseminated varicella-zoster virus (VZV) infection, and pirfenidone was discontinued. Her condition improved in one month. Pirfenidone may induce disseminated VZV infection.
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http://dx.doi.org/10.1016/j.rmcr.2018.10.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214882PMC
October 2018

Combined radiotherapy with nivolumab for extracranial metastatic malignant melanoma.

Jpn J Radiol 2018 Dec 11;36(12):712-718. Epub 2018 Sep 11.

Department of Radiation Oncology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, Japan.

Purpose: We retrospectively evaluated the tumor regression after radiotherapy in combination with the immune checkpoint inhibitor nivolumab for metastatic melanoma.

Materials And Methods: We evaluated the extracranial metastatic melanoma lesions to which concomitant radiotherapy with nivolumab was administered from June 2015 to February 2017. Tumor volume and maximum diameter were measured at the time of pre-radiotherapy and best response, and the tumor reduction rate was assessed in two ways that our hospital adopts: tumor volume and diameter.

Results: Seven lesions in five patients were evaluated. The median time from the start of nivolumab treatment to the start of radiotherapy was 5 months (range 0-22 months). The objective response rate was 85.7% in the evaluation by tumor volume and 42.9% by maximum diameter of the tumor. The objective complete response rate was 28.6% in evaluation by tumor volume and 14.3% by maximum dia. The 1-year tumor control rate was 62.5%. The 1- and 2-year overall survival rate after nivolumab treatment were 75% and 50%, respectively. Two patients who obtained a complete response had presented with vitiligo.

Conclusion: The combination of radiotherapy and nivolumab treatment produced favorable responses. Vitiligo may be correlated with a good response to concomitant radiotherapy with nivolumab.
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http://dx.doi.org/10.1007/s11604-018-0774-8DOI Listing
December 2018
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