Publications by authors named "Hiroyuki Yamashita"

141 Publications

Gastrointestinal Amyloidosis.

N Engl J Med 2021 Jun;384(22):2144

National Center for Global Health and Medicine, Tokyo, Japan

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMicm2034179DOI Listing
June 2021

Additional Tissue Sampling Trials Did Not Change Our Thyroid Practice.

Cancers (Basel) 2021 Mar 12;13(6). Epub 2021 Mar 12.

Department of Surgery, Yamashita Thyroid Hospital, Fukuoka 812-0034, Japan.

This study aimed to determine whether additional tissue sampling of encapsulated thyroid nodules would increase the frequency of follicular thyroid carcinoma (FTC) diagnoses. We examined thyroid tissue specimens from 86 patients suspected of FTC (84.9% female; mean age, 49.0 ± 17.8 years). The number of tissue blocks created for pathological assessments ranged from 3 to 20 (mean, 9.1 ± 4.1); the numbers in the previous method recommended by the Japanese General Rules for the Description of Thyroid Cancer and additional blocks ranged from 1 to 12 (mean, 6.0 ± 2.8) and from 1 to 8 (mean, 3.1 ± 2.0), respectively. The additional blocks were subsequently examined to determine whether any diagnoses changed from those based on the previous method. Five patients were diagnosed with FTC using the previous method; however, additional tissue blocks led to the diagnosis of FTC in 6 patients, as 1 diagnosis was revised from follicular adenoma to FTC. It has been reported that increasing the number of tissue blocks used for pathological assessments can increase the frequency of FTC diagnoses; however, this was not clinically significant in thyroid carcinoma, which requires completion thyroidectomy and radioactive iodine treatment. It resulted in no benefits to the patient because all minimally invasive FTCs, follicular tumors of uncertain malignant potential (FT-UMP), and follicular adenomas are treated with lobectomy alone in Japan. Additional tissue sampling only had a slight impact on our thyroid practice; therefore, we decided to cease it.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13061270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999341PMC
March 2021

Type II cryoglobulinaemic vasculitis with primary Sjögren's syndrome successfully treated with belimumab and hydroxychloroquine.

Clin Exp Rheumatol 2021 Mar 4. Epub 2021 Mar 4.

Division of Rheumatic Diseases, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
March 2021

A case of recurrence of adult-onset Still's disease in the third trimester: a case report and literature review.

BMC Pregnancy Childbirth 2021 Feb 24;21(1):163. Epub 2021 Feb 24.

Department of Obstetrics and Gynecology, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.

Background: Adult-onset Still's disease (AOSD) is a self-inflammatory disease showing macrophage and neutrophil activation by inflammatory cytokines such as TNF-α, IL-6, and IL-18. Although some cases with the flare of AOSD during pregnancy have been reported, most had flares in the first or second trimester and few had flares in the third trimester. In this report, we present the case of a patient with recurrent flare of AOSD in the third trimester and discuss the management of AOSD in the third trimester with the review of previous literatures.

Case Presentation: A 38-year-old woman in complete AOSD remission without medication presented with impaired liver function, low platelet count, mild fever, abdominal pain, splenomegaly, and elevated ferritin and IL-18 levels at 30 gestational weeks. Although the laboratory data and physical examination finding suggested HELLP syndrome or acute fatty liver of pregnancy and we considered the termination of her pregnancy, her fetus was in a reactive status. Considering her fetal status, some specific findings of AOSD, and her AOSD history, we and rheumatologists diagnosed her with AOSD recurrence and started systemic steroid therapy. In her clinical course, three flares of AOSD occurred, twice in the third trimester and once in postpartum; twice systemic steroid pulse therapies were then needed. Ultimately, a healthy infant was delivered transvaginally at 36 gestational weeks spontaneously.

Conclusions: Specific findings of the flare of AOSD such as fever, splenomegaly, elevated ferritin and IL-18 levels, and fetal status could be useful findings for differentiation from HELLP syndrome and AFLP in the third trimester. With the careful management supported by rheumatologists, patients complicated with the flare of AOSD may continue their pregnancy longer than we expected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12884-021-03648-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905546PMC
February 2021

Cricoarytenoid arthritis in rheumatoid arthritis.

Rheumatology (Oxford) 2020 Dec 25. Epub 2020 Dec 25.

1 Division of Rheumatic Diseases, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/keaa838DOI Listing
December 2020

PRIMARY HYPERPARATHYROIDISM ACCOMPANIED BY RECOVERY OF PARATHYROID BLOOD FLOW THREE MONTHS AFTER SPONTANEOUS PARATHYROID HEMORRHAGE.

AACE Clin Case Rep 2020 Nov-Dec;6(6):e322-e325. Epub 2020 Sep 24.

Objective: The objective of this report was to describe an unusual case of emerging primary hyperparathyroidism (PHPT) accompanied by recovery of parathyroid blood flow 3 months after spontaneous parathyroid hemorrhage.

Methods: Neck images and laboratory tests including serum calcium and parathyroid hormone (PTH) were performed to evaluate parathyroid hemorrhage. Pathologic findings after parathyroidectomy are also presented.

Results: A 58-year-old woman developed acute onset of neck pain and swelling with ecchymosis. Computed tomography showed a right paratracheal hematoma-like lesion behind the thyroid. Ultrasound (US) of the neck revealed a round, hypoechoic nodule measuring 27 × 25 × 18 mm in the right lower thyroid pole without vascular flow. Blood tests showed a corrected calcium of 9.3 mg/dL (normal, 8.7 to 10.3 mg/dL), and intact PTH of 68 pg/mL (normal, 10 to 65 pg/mL). Intact PTH measurement in fine-needle aspirate of the lesion was 339 pg/mL, confirming parathyroid origin. Repeat US after 3 months showed a remarkable decrease in lesion size with significant blood flow. Blood biochemistry showed a corrected calcium of 10.9 mg/dL, and an intact PTH of 237 pg/mL. She eventually underwent parathyroidectomy, and pathologic examination revealed parathyroid adenoma with a tiny thrombus.

Conclusion: Spontaneous remission of PHPT after parathyroid hemorrhage has been known to occur sporadically, a phenomenon referred to as autoparathyroidectomy. Although spontaneous remission with permanent improvement of PHPT may be observed, PHPT can recur in the relative short term after parathyroid hemorrhage, and so follow-up blood biochemistry surveillance is necessary. Also, evaluating parathyroid blood flow using color Doppler US might be useful in verifying the recurrence of PHPT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4158/ACCR-2020-0311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685410PMC
September 2020

Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: clinical features and prognosis.

Rheumatology (Oxford) 2021 05;60(5):2348-2354

Division of Rheumatic Diseases, National Center for Global Health and Medicine, Tokyo, Japan.

Objectives: RA-associated interstitial lung disease (RA-ILD) is commonly associated with acute exacerbations (ILD-AE). This study examined the clinical characteristics and risk factors of ILD-AE and mortality of RA-ILD.

Methods: We retrospectively collected data on 165 RA-ILD patients who visited or were admitted to our hospital between January 2007 and December 2019. We compared the clinical characteristics of patients who did and did not develop ILD-AE and identified variables significantly associated with ILD-AE. We also compared the admission characteristics of those who survived and those who died after admission for ILD-AE. ILD-AE was defined using previously proposed criteria, modified slightly for application to RA-ILD.

Results: The mean patient age was 73.6 years (s.d. 9.7) and 97 (71.9%) patients were female. Thirty (22.2%) patients developed ILD-AE, 13 (43.3%) of whom died. In univariate analyses, neither the usual interstitial pneumonia (UIP) pattern nor MTX was associated with ILD-AE. In multivariate analyses, the UIP pattern was significantly associated with ILD-AE [odds ratio (OR) 2.55 (95% CI 1.05, 6.20), P = 0.038]. In the Cox proportional hazards model, the UIP pattern [hazard ratio (HR) 4.67 (95% CI 1.02, 21.45), P = 0.048] was significantly associated with death, while MTX use [HR 0.16 (95% CI 0.04, 0.72), P = 0.016] was significantly associated with survival.

Conclusion: Our data suggest that the UIP pattern is related to ILD-AE. Furthermore, both the UIP pattern and non-use of MTX might be related to death from ILD-AE in RA-ILD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/keaa608DOI Listing
May 2021

Anti-Zo antibodies in Japanese myositis patients detected by a newly developed ELISA.

Clin Exp Rheumatol 2020 Oct 9. Epub 2020 Oct 9.

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

Objectives: The myositis-specific autoantibodies that characterise certain forms of idiopathic inflammatory myopathy (IIM) are useful for diagnosing dermatomyositis (DM) / polymyositis (PM) and predicting its prognosis. The autoantibody to phenylalanyl-tRNA synthetase (anti-Zo) has been identified as a disease marker antibody for anti-synthetase syndrome only in a UK cohort. Here we aim to establish an ELISA for the measurement of anti-Zo and to characterise the clinical features of Japanese patients who have this autoantibody.

Methods: Anti-Zo was investigated by immunoprecipitation with recombinant phenylalanyl-tRNA synthetase α/β proteins. The results were confirmed by immunoprecipitation-Western blotting with cell extract. Sera from patients with DM/PM (n=224) were screened by an ELISA with the recombinant proteins. Medical records were retrospectively reviewed to obtain detailed information on the clinical phenotypes of the anti-Zo-positive patients.

Results: Only two male patients were confirmed to have anti-Zo. Both patients had fever, myopathy, interstitial lung disease, and mechanic's hands, and these clinical features are consistent with those of anti-synthetase syndrome. Another patient's serum showed a higher level than the cut-off value for anti-phenylalanyl-tRNA synthetase α by our in-house ELISA, but was judged to be negative for anti-Zo by immunoprecipitation-Western blotting.

Conclusions: This is the first report of anti-Zo-positive IIM patients from Asia. Although Japanese patients with anti-Zo have a clinical phenotype similar to that of Caucasian patients, further large cohort studies are necessary to confirm the frequency of anti-Zo in Japanese IIM patients. Our newly developed ELISA should be validated for sensitivity and specificity in large cohorts.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2020

Comparison of F-FDG PET/CT and Ga-SPECT for the diagnosis of fever of unknown origin: a multicenter prospective study in Japan.

Ann Nucl Med 2021 Jan 9;35(1):31-46. Epub 2020 Oct 9.

Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan.

Objective: The aim of this multicenter prospective study was to compare the sensitivity of F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) with that of Ga single photon emission computed tomography (SPECT) for the identification of the site of greatest importance for the final diagnosis of the cause of fever of unknown origin (FUO).

Methods: The study participants consisted of patients with an axillary temperature ≥ 38.0 °C on ≥ 2 occasions within 1 week, with repeated episodes for ≥ 2 weeks prior to providing consent, and whose final diagnosis after undergoing specific examinations, including a chest-to-abdomen CT scan, was uncertain. All the patients underwent FDG-PET/CT imaging first, followed by Ga-SPECT imaging within 3 days. The results of the FDG-PET/CT and Ga-SPECT examinations were reviewed by the central image interpretation committee (CIIC), which was blinded to all other clinical information. The sensitivities of FDG-PET/CT and Ga-SPECT were then evaluated with regard to identifying the site of greatest importance for a final diagnosis of the cause of the fever as decided by the patient's attending physician. The clinical impacts (four grades) of FDG-PET/CT and Ga-SPECT on the final diagnosis were evaluated.

Results: A total of 149 subjects were enrolled in this study between October 2014 and September 2017. No adverse events were identified among the enrolled subjects. Twenty-one subjects were excluded from the study because of deviations from the study protocol. Among the 128 remaining subjects, a final diagnosis of the disease leading to the appearance of FUO was made for 92 (71.9%) subjects. The final diagnoses in these 92 cases were classified into four groups: noninfectious inflammatory disease (52 cases); infectious disease (31 cases), malignancy (six cases); and other (three cases). These 92 subjects were eligible for inclusion in the study's analysis, but one case did not meet the PET/CT image acquisition criteria; thus, PET/CT results were analyzed for 91 cases. According to the patient-based assessments, the sensitivity of FDG-PET/CT (45%, 95% CI 33.1-58.2%) was significantly higher than that for Ga-SPECT (25%, 95% CI 15.5-37.5%) (P = 0.0029). The clinical impact of FDG-PET/CT (91%) was also significantly higher than that for Ga-SPECT (57%, P < 0.001).

Conclusions: FDG-PET/CT showed a superior sensitivity to Ga-SPECT for the identification of the site of greatest importance for the final diagnosis of the cause of FUO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12149-020-01533-zDOI Listing
January 2021

Material-Sparing and Expedited Development of a Tablet Formulation of Carbamazepine Glutaric Acid Cocrystal- a QbD Approach.

Pharm Res 2020 Jul 23;37(8):153. Epub 2020 Jul 23.

Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 9-127B Weaver-Densford Hall 308 Harvard Street S.E., Minneapolis, Minnesota, 55455, USA.

Purpose: To efficiently develop a tablet formulation of carbamazepine using a soluble cocrystal with excess coformer to maintain phase stability during dissolution.

Methods: The carbamazepine - glutaric acid cocrystal (CBZ-GLA, 1:1) and excess glutaric acid (GLA) were mixed with suitable tablet excipients, which were selected to address powder flowability and tabletability deficiencies specifically. Tablet friability and dissolution profiles were evaluated to guide formulation optimization. Dry granules were prepared by milling simulated ribbons.

Results: A binary blend of CBZ-GLA and GLA had poor flowability and marginal tabletability. Therefore, silica coated Avicel PH-102 (sMCC) was applied as a binder to improve the flow property and tabletability. A formulation consisting of sMCC, CBZ-GLA, and GLA exhibited good manufacturability but did not show improved dissolution because of rapid precipitation of CBZ dihydrate when CBZ-GLA came in contact with water. Dry granulation of CBZ-GLA and GLA dramatically improved dissolution profile due to the intimate contact between CBZ-GLA and GLA. Such cocrystal - coformer granules also led to much improved tablet manufacturability and dissolution.

Conclusion: The successful tablet development of CBZ-GLA, using < 3 g of the cocrystal in <3 weeks, demonstrates an efficient workflow for tablet formulation development based on material-sparing and predictive powder characterization techniques. This workflow is useful for early tablet development using enabling solid form, such as cocrystal, when only a small amount of material is available.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11095-020-02855-3DOI Listing
July 2020

Therapeutic efficacy of combined glucocorticoid, intravenous cyclophosphamide, and double-filtration plasmapheresis for skin sclerosis in diffuse systemic sclerosis.

Medicine (Baltimore) 2020 Mar;99(10):e19301

Division of Rheumatic Diseases.

We treated skin sclerosis with triple therapy consisting of a glucocorticoid, intravenous cyclophosphamide, and double-filtration plasmapheresis. The objective of this study was to analyze its effectiveness in a case series of patients who received triple therapy.We enrolled 8 patients with diffuse cutaneous systemic sclerosis (dcSSc) who received triple therapy at our hospital from 2008 to 2016. We analyzed the mean change in the modified Rodnan skin score (mRSS), percentage of the predicted forced vital capacity (%FVC), percentage of the predicted carbon monoxide diffusing capacity (%DLCO), and serum KL-6 levels from baseline to follow-up.All patients were treated with an intermediate dose of oral prednisolone (30.6 ± 2.1 mg/day) initially. The mean cumulative dose of intravenous cyclophosphamide was 1.4 ± 0.2 g. The mean mRSS decreased significantly at follow-up compared with that at baseline (27.0 ± 3.3 vs 15.8 ± 3.5; P = .03). At the end of the treatment, the mean %FVC and %DLCO were improved moderately, although the differences were not significant. The serum KL-6 levels decreased from 578.9 ± 146.5 to 205.3 ± 43.1 U/ml (P = .02). No significant correlation was found between the change in mRSS or disease duration and the initial skin score severity.Triple therapy may improve skin sclerosis, with effectiveness equal or superior to other reported treatments. This preliminary case series demonstrates the potential of triple therapy for treating dcSSc. However, prospective studies with long-term follow-up should be performed to assess its role.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000019301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478820PMC
March 2020

Serum aldolase serves as a useful marker for diagnosis and assessment of disease activity in patients with adult-onset Still's disease.

Clin Exp Rheumatol 2020 Sep-Oct;38 Suppl 127(5):119. Epub 2020 Feb 11.

Division of Rheumatic Diseases, National Centre for Global Health and Medicine, Shinjuku, Tokyo, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
February 2021

Virus-Induced Flowering by Apple Latent Spherical Virus Vector: Effective Use to Accelerate Breeding of Grapevine.

Viruses 2020 01 7;12(1). Epub 2020 Jan 7.

Faculty of Agriculture, Iwate University, Morioka 020-8550, Japan.

Apple latent spherical virus (ALSV) was successfully used in promoting flowering (virus-induced flowering, VIF) in apple and pear seedlings. In this paper, we report the use of ALSV vectors for VIF in seedlings and in vitro cultures of grapevine. After adjusting experimental conditions for biolistic inoculation of virus RNA, ALSV efficiently infected not only progeny seedlings of Vitis spp. 'Koshu,' but also in vitro cultures of V. vinifera 'Neo Muscat' without inducing viral symptoms. The grapevine seedlings and in vitro cultures inoculated with an ALSV vector expressing the 'florigen' gene (Arabidopsis , ) started to set floral buds 20-30 days after inoculation. This VIF technology was successfully used to promote flowering and produce grapes with viable seeds in in vitro cultures of F hybrids from crosses between V. ficifolia and V. vinifera and made it possible to analyze the quality of fruits within a year after germination. High-temperature (37 °C) treatment of ALSV-infected grapevine disabled virus movement to newly growing tissue to obtain ALSV-free shoots. Thus, the VIF using ALSV vectors can be used to shorten the generation time of grapevine seedlings and accelerate breeding of grapevines with desired traits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v12010070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019355PMC
January 2020

Fluorodeoxyglucose PET/CT of Arthritis in Rheumatic Diseases: A Pictorial Review.

Radiographics 2020 Jan-Feb;40(1):223-240

From the Division of Nuclear Medicine, Department of Radiology (M.H., R.M.), and Division of Rheumatic Diseases (H.K., H.Y.), National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.

Rheumatic diseases are various painful conditions that affect joints, bones, cartilage, tendons, ligaments, and muscles. Arthritis is a typical condition of rheumatic disease. Although rheumatoid arthritis is a representative rheumatic disease, various diseases other than rheumatoid arthritis can also affect joints, and differential diagnosis of rheumatic diseases is often difficult owing to the similar clinical manifestations. However, accurate diagnosis is crucial for an appropriate treatment strategy. The utility of fluorine 18 fluorodeoxyglucose (FDG) PET/CT has been established, and it is widely used for assessing malignancies. In addition to accumulating in tumor cells, FDG also accumulates in inflammatory tissue, allowing FDG PET/CT to demonstrate arthritis. PET/CT allows evaluation of whole-body articular and extra-articular lesions in one examination, representing a key advantage over US and MRI, which allow assessment of only a few regions because of their limited field of view. Although FDG PET/CT is sensitive for detecting inflammatory lesions, the uptake itself is nonspecific; therefore, knowledge of characteristic uptake patterns is necessary to narrow the differential diagnosis in rheumatic disease. Furthermore, pathognomonic extra-articular findings such as vasculitis, skin lesions, lymphadenopathy, and chondritis play an important role in achieving accurate diagnosis. The authors present the FDG PET/CT appearances of rheumatoid arthritis and allied disorders (polymyalgia rheumatica, remitting seronegative symmetrical synovitis with pitting edema, adult-onset Still disease), spondyloarthritis (ankylosing spondylitis, psoriatic arthritis, reactive arthritis, inflammatory bowel disease arthritis, SAPHO [ynovitis, cne, ustulosis, yperostosis, and steitis] syndrome, chronic recurrent multifocal osteomyelitis), and miscellaneous systemic disorders with arthropathy (relapsing polychondritis, multicentric reticulohistiocytosis, amyloidosis, sarcoidosis, hemophilia). RSNA, 2020.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/rg.2020190047DOI Listing
February 2021

Polyarteritis Nodosa With Reversible FDG Accumulation in Vessels and Kidneys.

Clin Nucl Med 2019 Nov;44(11):889-891

From the Division of Rheumatic Diseases, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655 Japan.

A 59-year-old man presented with fever and lower extremity myalgia. Laboratory studies revealed elevated C-reactive protein. F-FDG PET/CT demonstrated FDG uptake not only in the brachial arteries, femoral arteries, and their main ramifications, which were equivalent to small- to medium-sized arteries but also in the kidneys. Angiography revealed a renal aneurysm, confirming the diagnosis of polyarteritis nodosa. The increased FDG uptake in the vessels and kidneys resolved after 6 months of glucocorticoid treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/RLU.0000000000002784DOI Listing
November 2019

Classifications of scleroderma renal crisis and reconsideration of its pathophysiology.

Rheumatology (Oxford) 2019 12;58(12):2099-2106

Division of Rheumatic Diseases, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan.

Categorization of scleroderma renal crisis (SRC) as hypertensive or normotensive can potentially overlook the underlying pathophysiology that might be unique in each patient, as they often exhibit a mixture of distinct pathological characteristics of narrowly defined SRC (nd-SRC) and systemic sclerosis associated thrombocytic micro-angiopathy (SSc-TMA). In this review, we provide evidence suggesting that better categorization of patients presenting with certain clinical features of both nd-SRC and TMA will improve treatment approaches. Based on our clinical experience and literature review, distinguishing between nd-SRC and SSc-TMA is important because the association of SSc-TMA with prior steroid administration and poor prognosis was stronger than that of nd-SRC. Although the two pathological entities cannot be easily distinguished based on blood pressure, we suggest that the detailed clinical course is helpful. Typically, nd-SRC exhibits prominently elevated blood pressure and worsening of renal function initially, followed by mild thrombocytopenia. Conversely, SSc-TMA presents first with severe thrombocytopenia, followed by elevated blood pressure and renal function deterioration. The degree of involvement in each pathological condition should be considered for determination of appropriate therapeutic interventions and prognostic prediction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/kez435DOI Listing
December 2019

Impact of adding tacrolimus to initial treatment of interstitial pneumonitis in polymyositis/dermatomyositis: a single-arm clinical trial.

Rheumatology (Oxford) 2020 05;59(5):1084-1093

Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Objective: Interstitial pneumonia is common and has high short-term mortality in patients with PM and DM despite glucocorticoid (GC) treatment. Retrospective studies suggested that the early use of immunosuppressive drugs with GCs might improve its short-term mortality.

Methods: A multicentre, single-arm, 52-week-long clinical trial was performed to test whether the initial combination treatment with tacrolimus (0.075 mg/kg/day, adjusted for the target whole-blood trough levels between 5 and 10 ng/ml) and GCs (0.6-1.0 mg/kg/day of prednisolone followed by a slow taper) improves short-term mortality of PM/DM-interstitial pneumonia patients. The primary outcome was overall survival. We originally intended to compare, by using propensity-score matching, the outcome data of clinical trial patients with that of historical control patients who were initially treated with GCs alone.

Results: The 52-week survival rate with the combination treatment (N = 26) was 88.0% (95% CI, 67.3, 96.0). Safety profiles of the combination treatment were consistent with those known for tacrolimus and high-dose GCs individually. Serious adverse events occurred in 11 patients (44.0%), which included four opportunistic infections. Only 16 patients, including only 1 deceased patient, were registered as historical controls, which precluded meaningful comparative analysis against the clinical trial patients.

Conclusion: Our study provided findings which suggest that initial treatment with tacrolimus and GCs may improve short-term mortality of PM/DM-interstitial pneumonia patients with manageable safety profiles. This was the first prospective clinical investigation conducted according to the Good Clinical Practice Guideline of the International Conference on Harmonization for the treatment of this potentially life-threatening disease.

Trial Registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT00504348.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/kez394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850120PMC
May 2020

Clinical characteristics and prognosis of polymyositis and dermatomyositis associated with malignancy: a 25-year retrospective study.

Rheumatol Int 2019 Oct 23;39(10):1733-1739. Epub 2019 Aug 23.

Division of Rheumatic Diseases, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku, Tokyo, 162-8655, Japan.

The objective of this study was to identify factors predictive of malignancy in patients with polymyositis (PM) and dermatomyositis (DM) in Japan. We conducted a retrospective study of PM and DM patients who were admitted to our hospital between January 1992 and September 2017. Among 134 patients, 29 (21.6%) were diagnosed with cancer in the 3 years prior to and 3 years after the initial diagnosis of PM or DM. According to multivariate analyses, male sex [odds ratio (OR) = 3.65, p = 0.03], old age (OR = 1.05, p = 0.02), and a past history of diabetes mellitus (OR = 10.4, p = 0.005) were associated with an increased risk of malignancy. The absence of interstitial lung disease (ILD) (OR = 0.25, p = 0.03) was also associated with an increased risk of malignancy. Diabetes mellitus was observed in 28.6% of PM and DM patients with malignancy, but in only 7.3% of those with malignancy. Survival was significantly lower in patients with malignancy than in those without malignancy (p < 0.001). Independent factors associated with malignancies in patients with PM or DM were male sex, old age, the absence of ILD, and, especially, a past history of diabetes mellitus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00296-019-04428-zDOI Listing
October 2019

Expedited Tablet Formulation Development of a Highly Soluble Carbamazepine Cocrystal Enabled by Precipitation Inhibition in Diffusion Layer.

Pharm Res 2019 Apr 23;36(6):90. Epub 2019 Apr 23.

Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 9-127B Weaver-Densford Hall, 308 Harvard Street S.E., Minneapolis, MN, 55455, USA.

Purpose: To address the problem of precipitation of a poorly soluble drug during dissolution of highly soluble cocrystals by preparing granules intimately mixed with a water-soluble polymer.

Methods: Effectiveness of polymers as precipitation inhibitors during the dissolution of carbamazepine-nicotinamide (CBZ-NCT) cocrystal was assessed based on induction time of crystallization from a supersaturated solution in presence of different polymers at two concentrations. Dissolution was evaluated by both intrinsic dissolution rate (IDR) and USP dissolution method. Powder manufacturability was assessed using a shear cell and compaction simulator to assess flowability and tabletability, respectively.

Results: Hydroxypropyl methylcellulose acetate succinate (HPMCAS) was the most effective polymer against precipitation of CBZ and the IDR of a 1:1 (w/w) CBZ-NCT/HPMCAS mixture was the highest. The final formulation of 1:1 CBZ-NCT/HPMCAS granule exhibited excellent flowability, good tabletability, and significantly improved drug release rate than cocrystal formulations without HPMCAS or the CBZ formulation.

Conclusion: The particle engineering strategy of modifying the diffusion layer on the surface of highly soluble cocrystal with a polymer is effective for inhibiting premature precipitation of CBZ. Assisted with predictive tools for characterizing powder flowability and tabletability, the design of high quality tablet product with improved drug release rate and manufacturability can be achieved in an efficient manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11095-019-2622-7DOI Listing
April 2019

[Bone and calcium metabolism associated with malignancy. Paraneoplastic rheumatologic musculoskeletal manifestations.]

Clin Calcium 2018;28(11):1479-1484

Division of Rheumatic Diseases, National Center for Global Health and Medicine, Tokyo, Japan.

Patients with malignant tumors may present with joint pain or arthritis(paraneoplastic arthritis). It needs to be carefully determined whether these symptoms are related to the malignant tumor, due to a concomitant rheumatoid disease, due to an adverse reaction to treatment, or due to a relapse. It can be relatively easy to diagnose paraneoplastic syndrome when there is clearly a malignant tumor present or typical symptoms are exhibited. However, clinicians should be aware that these paraneoplastic syndrome phenomena can occur before the malignant tumor is diagnosed. An occult malignancy should be suspected when a patient is elderly and exhibits atypical clinical symptoms of a rheumatic disease;is poorly responsive to usual treatment;or has general symptoms such as weight loss or exhibits suggestive physical findings. In particular, hematological malignancies require careful observations as they do not surface quickly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/CliCa181114791484DOI Listing
June 2019

Cohort study exploring the effect of lenvatinib on differentiated thyroid cancer.

Endocr J 2018 Nov 24;65(11):1071-1074. Epub 2018 Oct 24.

National Hospital Organization, Higashinagoya National Hospital, Nagoya, Aichi 465-8620, Japan.

Lenvatinib is a molecular-targeting agent that was recently approved in Japan for treatment of curatively unresectable, radioactive iodine-refractory, progressive differentiated thyroid cancer (DTC). Because only a few Japanese patients have received lenvatinib in clinical trials, there are limited domestic data on its safety and efficacy or prognostic factors. Therefore, a prospective observational study has been designed to collect safety and efficacy data in at least 300 patients with curatively unresectable DTC receiving lenvatinib therapy (24 mg/day), in order to find predictors of antitumor activity and survival. Patients with progressive curatively unresectable DTC refractory to radioiodine therapy will be enrolled and the primary endpoint will be overall survival. This study is designed to estimate the 95% confidence intervals of the 1-year and 2-year survival rates with a two-sided width of less than 10%. Secondary endpoints will be the time to treatment failure, time to strategy failure, progression-free survival time with clinical progressive disease, response rate, quality of life, safety, and patient reports. The ultimate goal is to obtain information for developing evidence-based guidelines for treatment of DTC, including recommendations on patient selection, dosages, and duration of treatment. This study has been registered with the UMIN Clinical Trials Registry (UMIN000022243).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1507/endocrj.EJ18-0261DOI Listing
November 2018

FDG PET/CT Findings in TAFRO Syndrome.

Clin Nucl Med 2018 Nov;43(11):828-829

Division of Rheumatic Diseases, National Center for Global Health and Medicine, Tokyo, Japan.

A 67-year-old woman with prolonged fever, thrombocytopenia, and renal dysfunction underwent FDG PET/CT to evaluate underlying causes, including malignancy. PET/CT showed FDG uptake in ascites, subcutaneous edema, lymph nodes, spleen, and bone marrow. Subsequent bone marrow biopsy revealed myelofibrosis, and laboratory testing showed elevated concentrations of interleukin 6 in serum and ascites. These findings led to the diagnosis of TAFRO syndrome, a variant of multicentric Castleman disease, characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, and organomegaly. Because TAFRO syndrome is potentially fatal, accurate diagnosis is crucial. Characteristic FDG PET/CT findings facilitate the diagnosis of TAFRO syndrome, which is generally challenging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/RLU.0000000000002278DOI Listing
November 2018

Thrombotic Microangiopathy with Polymyositis/Dermatomyositis: Three Case Reports and a Literature Review.

Intern Med 2018 1;57(15):2259-2265. Epub 2018 Aug 1.

Division of Rheumatic Diseases, National Center for Global Health and Medicine, Japan.

Thrombotic microangiopathies (TMAs) rarely accompany polymyositis/dermatomyositis. We treated three patients with dermatomyositis combined with TMA. A literature review identified 13 previously reported cases. Exacerbation of myositis at the time of the TMA onset was observed in 62.5% of all patients, suggesting that the TMA onset may be associated with autoantibody production. We also found that cases of TMA with polymyositis/dermatomyositis often had a poor treatment response rate (37.5%). Furthermore, even if treatment was effective, the mortality rate associated with subsequent complications was high, and the survival rate was low (18.8%). Therefore, careful attention should be paid to patient management after TMA treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2169/internalmedicine.0512-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120848PMC
November 2018

Successful treatment of a patient with both systemic lupus erythematosus and progressive hepatitis C using immunosuppressive therapy and interferon beta.

Clin Exp Rheumatol 2018 Jul-Aug;36(4):686. Epub 2018 May 8.

Division of Rheumatic Diseases, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
September 2018

A case of giant cell arteritis mimicking vertebral dissection on contrast-enhanced magnetic resonance angiography.

Clin Exp Rheumatol 2018 Mar-Apr;36 Suppl 111(2):178-179. Epub 2018 Apr 19.

Division of Rheumatic Diseases, National Centre for Global Health and Medicine, Shinjuku, Tokyo, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
July 2018

Improving Dissolution Rate of Carbamazepine-Glutaric Acid Cocrystal Through Solubilization by Excess Coformer.

Pharm Res 2017 12 29;35(1). Epub 2017 Dec 29.

Pharmaceutical Materials Science and Engineering Laboratory Department of Pharmaceutics College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, 55455, U.S.A..

Purpose: The use of soluble cocrystals is a promising strategy for delivering poorly soluble drugs. However, precipitation of poorly soluble crystal form during dissolution hinders the successful tablet development of cocrystals. This work was aimed to understand the mechanisms for improving dissolution performance of a soluble cocrystals by using excess coformer.

Methods: A highly soluble carbamazepine (CBZ) cocrystal with- glutaric acid (GLA) was studied. Impact of excess GLA on solubility and intrinsic dissolution rate (IDR) was assessed. Viscosity of GLA solutions was also measured. Solid form of powders and pellets was examined using powder X-ray diffractometry. IDRs of cocrystal and GLA mixtures in different ratios were measured to identify a suitable formulation for maintaining high dissolution rate of CBZ-GLA in an aqueous environment.

Results: IDR of CBZ-GLA in a pH 1.2 HCl solution was improved when GLA was present in the solution. Precipitation of CBZ·2HO was eliminated when GLA concentration was ≥100 mg/mL. The improved IDR was accompanied by higher solubility of CBZ in GLA solution and increased solution viscosity. The trend in IDR profile matched well with the solubility profile normalized by solution viscosity. Mixture of cocrystal and GLA led to improved IDR in simulated intestinal fluid.

Conclusions: The excess GLA increased the aqueous solubility of CBZ·2HO and, thereby, reduced the propensity to precipitation of CBZ·2HO during dissolution by lowering the degree of supersaturation. This strategy allowed development of a CBZ-GLA formulation with a significantly enhanced dissolution rate than CBZ-GLA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11095-017-2309-xDOI Listing
December 2017

A Case of Clinically Amyopathic Dermatomyositis With Hoarseness Due to Vocal Cord Necrosis.

J Clin Rheumatol 2018 Jan;24(1):50-51

Division of Rheumatic Diseases, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/RHU.0000000000000575DOI Listing
January 2018

Tuberculosis screening prior to anti-tumor necrosis factor therapy among patients with immune-mediated inflammatory diseases in Japan: a longitudinal study using a large-scale health insurance claims database.

Int J Rheum Dis 2017 Nov 26;20(11):1674-1683. Epub 2017 Oct 26.

Department of Clinical Epidemiology and Health Economics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Aim: Tuberculosis screening is recommended for patients with immune-mediated inflammatory diseases (IMIDs) prior to anti-tumor necrosis factor (TNF) therapy. However, adherence to the recommended practice is unknown in the current clinical setting in Japan.

Methods: We used a large-scale health insurance claims database in Japan to conduct a longitudinal observational study. Of more than two million beneficiaries in the database between 2013 and 2014, we enrolled those with IMIDs aged 15-69 years who had initiated anti-TNF therapy. We defined tuberculosis screening primarily as tuberculin skin test and/or interferon-gamma release assay (TST/IGRA) within 2 months before commencing anti-TNF therapy. We analyzed the proportions of the patients who had undergone tuberculosis screening and the associations with primary disease, type of anti-TNF agent, methotrexate prescription prior to anti-TNF therapy, and treatment for latent tuberculosis infection (LTBI).

Results: Of 385 patients presumed to have initiated anti-TNF therapy, 252 (66%) had undergone tuberculosis screening by TST/IGRA (22% TST, 56% IGRA, and 12% both TST and IGRA), and 231 (60%) had undergone TST/IGRA and radiography. Patients with psoriasis tended to be more likely to undergo tuberculosis screening than those with other diseases; however, this association was not statistically significant. Treatment for LTBI was provided to 43 (11%) patients; 123 (32%) received neither TST/IGRA nor LTBI treatment.

Conclusions: Tuberculosis screening was often not performed prior to anti-TNF therapy despite the guidelines' recommendations; thus, patients could be put at unnecessary risk of reactivation of tuberculosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1756-185X.13190DOI Listing
November 2017