Publications by authors named "Kento Wada"

12 Publications

  • Page 1 of 1

Sapropterin For Phenylketonuria: A Japanese Post-Marketing Surveillance Study.

Pediatr Int 2021 Jul 31. Epub 2021 Jul 31.

Daiichi Sankyo Company Limited, 3-5-1, Nihonbashi Honcho, Chuo-ku, Tokyo, 103-8426, Japan.

Background: To assess the long-term safety and efficacy of sapropterin in a real-world setting in Japanese patients with tetrahydrobiopterin (BH4)-responsive phenylketonuria (PKU).

Methods: This post-marketing surveillance study enrolled all patients in Japan with confirmed BH4-responsive PKU who were administrated sapropterin between July 2008 and October 2017. Patients were observed at least every 3 months during follow-up, with key data collected on treatment exposure/duration, effectiveness according to physician judgement, serum phenylalanine levels, and adverse events.

Results: Of 87 enrolled patients, 85 patients (male, 42.4%; outpatients, 96.5%) were included in the safety and efficacy analysis sets. Treatment started at age <4 years in 43 (50.6%) patients and the most common starting daily dose was 5-10 mg/kg (n=41 [48.2%]) with the overall duration of treatment between 0.2 and 17.2 years. Serum phenylalanine levels according to loading tests reduced from a baseline level of 9.66 mg/dL (range 0.48-36.80 mg/dL) by >30% in 84 patients. Treatment was deemed effective in 79 of 85 patients (92.9%, 95% CI 85.3-97.4). One (1.2%) patient experienced an adverse drug reaction (alanine aminotransferase increased) 50 days after the start of administration, which resolved without complications with continued treatment.

Conclusions: Sapropterin appears well tolerated and highly effective in Japanese patients treated in a real-world setting, including those who start treatment at age <4 years and pregnant women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ped.14939DOI Listing
July 2021

Efficacy of Intratympanic Glucocorticoid Steroid Administration Therapy as an Initial Treatment for Idiopathic Sudden Sensorineural Hearing Loss During the COVID-19 Pandemic.

Ear Nose Throat J 2021 Jul 12:1455613211032534. Epub 2021 Jul 12.

Department of Otorhinolaryngology, National Hospital Organization Osaka National Hospital, Houenzaka, Osaka City, Osaka, Japan.

Objective: Systemic administration of glucocorticoid steroids is the most common initial treatment for idiopathic sudden sensorineural hearing loss (ISSNHL); however, due to the prevalence of coronavirus disease, the indications for this treatment must be carefully determined. The aim of this study was to investigate the efficacy of intratympanic steroid therapy as an initial treatment for idiopathic SSNHL.

Methods: Sixty-eight patients with idiopathic ISSNHL who were treated with intravenous or intratympanic steroids were included in this study. Patients were retrospectively evaluated regarding preoperative grade, type of additional treatment, outcome of treatment, and side effects of each treatment.

Results: In 46 cases, patients received intravenous steroid therapy as the initial treatment, while 22 patients received intratympanic steroid therapy; 10 patients underwent salvage treatment due to inadequate improvement of symptoms. Regarding additional treatment, intravenous steroid monotherapy was used in 37 patients. The outcomes were similar after both treatments; 16 (43%) and 11 (52%) patients treated exclusively with intravenous and intratympanic steroids, respectively, were completely cured. There were no significant differences in the effects between the 2 treatments, indicating that they were almost equally effective. The side effects observed in patients treated with intravenous steroid therapy were increased blood pressure, acute gastric mucosal disorder, and insomnia. None of these side effects were observed in any of the patients treated with intratympanic steroids; however, 1 case of perforation of the tympanic membrane occurred due to the procedure.

Conclusion: There were no significant differences in posttreatment outcomes between patients treated with either intratympanic or intravenous steroids. The therapeutic effects were comparable, and no severe side effects were observed; therefore, intratympanic steroid therapy may be considered useful as an initial treatment for ISSNHL in the context of widespread coronavirus disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/01455613211032534DOI Listing
July 2021

A rare case of cervical abscess caused by .

SAGE Open Med Case Rep 2021 11;9:2050313X211024505. Epub 2021 Jun 11.

Department of Otorhinolaryngology, National Hospital Organization Osaka National Hospital, Osaka City, Japan.

Cervical abscesses develop in the tissue spaces between the cervical fascia. The rapid expansion of these abscesses can lead to fatal outcomes. We describe a case of a deep cervical abscess caused by . He was referred to our department with complaints of sore throat and neck pain. Ultrasonography revealed a hypoechoic area in the cervical interfascicular space. An ultrasound-guided puncture was performed to collect pus for bacteriological examination. Subsequently, a contrast-enhanced computed tomography scan revealed a multi-focal abscess extending from the left mandible to the left side of the neck, without any mediastinal abscess. An emergency drainage and antibacterial therapies were performed, and the patient progressed well. , a gram-positive anaerobic bacterium, was detected in the pus collected before incision, and appropriate antibiotics were immediately administered. The collection of pus prior to incision and drainage aids accurate identification of the causative organism and appropriate treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2050313X211024505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202303PMC
June 2021

Myeloproliferative neoplasm-driving Calr frameshift promotes the development of pulmonary hypertension in mice.

J Hematol Oncol 2021 03 30;14(1):52. Epub 2021 Mar 30.

Department of Blood Transfusion and Transplantation Immunology, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.

Frameshifts in the Calreticulin (CALR) exon 9 provide a recurrent driver mutation of essential thrombocythemia (ET) and primary myelofibrosis among myeloproliferative neoplasms (MPNs). Here, we generated knock-in mice with murine Calr exon 9 mimicking the human CALR mutations, using the CRISPR-Cas9 method. Knock-in mice with del10 [Calr mice] exhibited an ET phenotype with increases of peripheral blood (PB) platelets and leukocytes, and accumulation of megakaryocytes in bone marrow (BM), while those with ins2 (Calr mice) showed a slight splenic enlargement. Phosphorylated STAT3 (pSTAT3) was upregulated in BM cells of both knock-in mice. In BM transplantation (BMT) recipients from Calr mice, although PB cell counts were not different from those in BMT recipients from Calr mice, Calr BM-derived macrophages exhibited elevations of pSTAT3 and Endothelin-1 levels. Strikingly, BMT recipients from Calr mice developed more severe pulmonary hypertension (PH)-which often arises as a comorbidity in patients with MPNs-than BMT recipients from Calr mice, with pulmonary arterial remodeling accompanied by an accumulation of donor-derived macrophages in response to chronic hypoxia. In conclusion, our murine model with the frameshifted murine Calr presented an ET phenotype analogous to human MPNs in molecular mechanisms and cardiovascular complications such as PH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13045-021-01064-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011226PMC
March 2021

A Case of Cochlear Implant Replacement Requiring Full-Thickness Skin Grafting.

Ear Nose Throat J 2021 Mar 23:145561321996837. Epub 2021 Mar 23.

Department of Otorhinolaryngology, 13707National Hospital Organization Osaka, Osaka City, Japan.

Cochlear implants improve the quality of life of patients with bilateral severe sensorineural hearing loss. Normally, patients with cochlear implants can continue to use the devices for years without any complications. However, equipment failure or infection at the implant site could develop in some patients, and this might often necessitate implant replacement. Although cochlear implant replacement surgery itself is not a major risk in most cases, extensive tissue resection will be required in cases involving infection, and the insertion site of the temporal bone implant will need to be changed. We encountered a case of skin necrosis at the temporal bone implant site caused by constant external irritation from the temple of an eyeglass frame. The patient underwent cochlear implant replacement surgery involving full-thickness skin grafting from the abdomen. Thereafter, the patient's condition improved. Full-thickness skin grafting can be useful in cases of extensive skin defects encountered during cochlear implant replacement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0145561321996837DOI Listing
March 2021

Crucial role of hematopoietic V617F in the development of aortic aneurysms.

Haematologica 2021 07 1;106(7):1910-1922. Epub 2021 Jul 1.

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima.

JAK2V617F is the most frequent driver mutation in myeloproliferative neoplasms (MPNs) and is associated with vascular complications. However, the impact of hematopoietic JAK2V617F on the aortic aneurysms (AAs) remains unknown. Our cross-sectional study indicated that 9 (23%) out of 39 MPN patients with JAK2V617F exhibited the presence of AAs. Next, to clarify whether the hematopoietic JAK2V617F contributes to the AAs, we applied a bone marrow transplantation (BMT) with the donor cells from Jak2V617F transgenic (JAK2V617F) mice or control wild-type (WT) mice into lethally irradiated apolipoprotein E-deficient mice. Five weeks after BMT, the JAK2V617F-BMT mice and WT-BMT mice were subjected to continuous angiotensin II infusion to induce AA formation. Four weeks after angiotensin II infusion, the abdominal aorta diameter in JAK2V617F-BMT mice was significantly enlarged compared to that in the WT-BMT mice. Additionally, the abdominal AA-free survival rate was significantly lower in the JAK2V617F-BMT mice. Hematopoietic JAK2V617F accelerated aortic elastic lamina degradation as well as activation of matrix metalloproteinase (MMP)-2 and MMP-9 in the abdominal aorta. The numbers of infiltrated macrophages were significantly upregulated in the abdominal aorta of the JAK2V617F-BMT mice accompanied by STAT3 phosphorylation. The accumulation of BM-derived hematopoietic cells carrying JAK2V617F in the abdominal aorta was confirmed by use of reporter GFP-transgene. BM-derived macrophages carrying JAK2V617F showed increases in mRNA expression levels of Mmp2, Mmp9, and Mmp13. Ruxolitinib decreased the abdominal aorta diameter and the incidence of abdominal AA in the JAK2V617F-BMT mice. Our findings provide a novel feature of vascular complications of AAs in MPNs with JAK2V617F.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3324/haematol.2020.264085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252954PMC
July 2021

A Rare Case of Prostate Carcinoma Metastasis in the Orbital Apex.

Ear Nose Throat J 2020 Nov 20:145561320973783. Epub 2020 Nov 20.

Department of Otorhinolaryngology, National Hospital Organization Osaka National Hospital, Osaka City, Osaka, Japan.

Prostate cancer (PC) is prone to bone metastases, but very rarely it can spread to soft tissues. In the head and neck region, PC can metastasize to the orbital soft tissue, causing various symptoms such as vision loss. In this report, we describe the case of a 79-year-old man with PC metastasis in the orbital apex. He presented to an ophthalmologist at our hospital with progressively worsening vision in his left eye over 3 to 4 months. He complained of a drooping eyelid in the same eye; thus, intracranial disease was suspected. Closer inspection with head computed tomography revealed a space-occupying lesion from the orbit to the posterior ethmoid sinus, and he was referred to our department. He had a history of PC, and we performed endoscopic sinus surgery for the diagnosis of malignancy, including metastasis of PC. As a result, the mass was diagnosed as PC metastasis by pathological examination. The patient began androgen blockade therapy and 3 months postoperatively, magnetic resonance imaging revealed that the extraconal orbital mass had decreased significantly. It is important to determine the metastases of PC in the paranasal region when the patient has a preexisting medical history.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0145561320973783DOI Listing
November 2020

A Case of Ceruminous Adenocarcinoma Not Otherwise Specified (NOS) in the External Auditory Canal.

Ear Nose Throat J 2020 Aug 30:145561320954128. Epub 2020 Aug 30.

Department of Otorhinolaryngology, 13707National Hospital Organization Osaka National Hospital, Osaka City, Osaka, Japan.

External auditory canal cancer is a rare disease which can be treated by surgery or chemoradiation. The most common histological type is squamous cell carcinoma, but rare types such as adenocarcinoma have been reported and are thought to be derived from the ceruminous glands. Here, we present a case of ceruminous adenocarcinoma, not otherwise specified (NOS) in the external auditory canal. A 72-year-old woman was referred to our department with discomfort due to a mass in the external ear canal. No typical symptoms of malignancy, such as pain or bleeding, were noted at the initial examination. The patient underwent a total excision under local anesthesia as a diagnostic treatment. She was diagnosed with ceruminous adenocarcinoma, NOS based on the results of immunostaining of the excised specimen, and is currently being followed up as an outpatient. Adenocarcinoma is thought to originate from the cerumen glands of the ear canal and the lack of specific symptoms may make it difficult to differentiate it from benign tumors. Although adenocarcinoma, NOS has been reported in the head and neck region, there have been no reported cases occurring in the external ear canal, and to the best of our knowledge, this is the first report.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0145561320954128DOI Listing
August 2020

Clinical impact of sleep-disordered breathing on very short-term blood pressure variability determined by pulse transit time.

J Hypertens 2020 09;38(9):1703-1711

Department of Cardiovascular Medicine.

Background: Sleep-disordered breathing (SDB) and blood pressure variability (BPV) are strongly associated with cardiovascular diseases. Recently, pulse transit time (PTT) has enabled the monitoring of beat-to-beat BP; however, little is known about its clinical utility. The present study aimed to clarify the impact of SDB on very short-term BPV determined by PTT-based BP monitoring (PTT-BP).

Methods: We analyzed 242 patients with suspected SDB. PTT-BP was continuously recorded overnight together with a portable sleep monitor. PTT index was defined as the average number of transient rises in PTT-BP (≥12 mmHg) within 30 s/h. We compared PTT-BP values with each SDB parameter, and examined the association between BPV and subclinical organ damage.

Results: Standard deviation (SD) of systolic, mean or diastolic PTT-BP, which indicates very short-term BPV, was significantly correlated with apnea--hypopnea index (AHI) and oxygen desaturation index (ODI). PTT index was positively associated with AHI, ODI, and minimal SpO2. Regression analyses showed that AHI and ODI were significant variables to determine systolic, mean, or diastolic PTT-BP SD and PTT index. Logistic regression analyses demonstrated that diastolic PTT-BP SD significantly influenced the presence of chronic kidney disease and left ventricular hypertrophy.

Conclusion: SDB severity was closely associated with very short-term BP variability, and diastolic PTT-BP SD might be an important factor linked to subclinical organ damage. PTT-BP measurement may be useful to evaluate very short-term BPV during the night.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000002445DOI Listing
September 2020

Novel Parameter to Predict Left Ventricular Filling Pressure: Product of Log B-Type Natriuretic Peptide and Ratio of Mitral Inflow Early and Late Diastolic Filling Velocities.

J Card Fail 2018 01 12;24(1):29-32. Epub 2017 Oct 12.

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.

Background: Several echocardiographic parameters are currently used to evaluate left ventricular (LV) filling pressure. However, these parameters are not always consistent in the clinical setting. We aimed to determine a novel parameter by multiplying log B-type natriuretic peptide (lnBNP) and the ratio of mitral inflow early and late diastolic filling velocities (E/A) for the prediction of pulmonary capillary wedge pressure (PCWP).

Methods And Results: One hundred ninety-eight patients suspected of chronic heart failure were analyzed. The product of lnBNP and E/A (BNP × E/A) showed the highest correlation coefficient with mean PCWP (R = 0.7326) compared with E/A (R = 0.7010) and E/e' (R = 0.3922). Multivariate logistic regression analysis revealed that BNP × E/A was associated with elevated PCWP (odds ratio 1.640, 95% confidence interval 1.312-2.197; P <.01). In the receiver operating characteristic curve analysis for detecting elevated PCWP, BNP × E/A showed the largest area under the curve (AUC) compared with E/A and E/e' (0.880 vs 0.827 and 0.788, respectively; P <.05). BNP × E/A still showed large AUC (0.842) for detection of elevated PCWP in patients with normal LV ejection fraction.

Conclusion: BNP × E/A is a useful parameter for detecting elevated PCWP regardless of the LV ejection fraction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cardfail.2017.10.008DOI Listing
January 2018

Simultaneous cardiac imaging to detect inflammation and scar tissue with (18)F-fluorodeoxyglucose PET/MRI in cardiac sarcoidosis.

J Nucl Cardiol 2016 Oct 1;23(5):1180-1182. Epub 2015 Dec 1.

Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12350-015-0348-4DOI Listing
October 2016
-->