Publications by authors named "Takashi Iwanaga"

Background: Asthma is a heterogeneous disease with variable response to treatment. Genetic backgrounds are involved in the severity of type 2 asthma, but their effects on responses to biologics remain unknown. This study aimed to clarify the role of genetic factors in response to biologics in patients with severe asthma.

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Background: The relationship between protein intake and the long-term prognosis of elderly patients with heart failure remains poorly understood. We investigated the association between predischarge protein intake and long-term prognosis in hospitalized elderly patients with heart failure.

Methods And Results: A single-center, retrospective analysis of hospitalized patients aged ≥65 years with heart failure and reduced ejection fraction was conducted.

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  • The study aimed to explore the use of time-dependent diffusion MRI (dMRI) to differentiate between functioning and nonfunctioning pituitary adenomas (PAs).
  • It involved 54 participants, measuring the apparent diffusion coefficients (ADCs) of various types of PAs and finding that the cADC values were significantly higher in functioning PAs compared to nonfunctioning ones.
  • The results suggest that cADC is an effective diagnostic tool, particularly for distinguishing growth hormone-producing PAs from nonfunctioning PAs.
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  • * Traditional rodent models make it hard to assess the effectiveness of bisphosphonates due to high bone turnover, so models with low bone resorption are preferred for studying anti-calcifying effects in humans.
  • * Among the three bisphosphonates studied (etidronate, alendronate, and FYB-931), FYB-931 showed the strongest inhibition of calcification in both animal models tested, suggesting that mechanisms related to calcium-phosphate aggregation may be more relevant for human applications. *
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Background: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma.

Methods: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13).

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Background: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging.

Objective: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response.

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  • The study investigates how pre-biologic biomarker levels, specifically immunoglobulin E (IgE), blood eosinophil count (BEC), and fractional exhaled nitric oxide (FeNO), influence asthma treatment outcomes when patients start biologic therapy.
  • Conducted across 23 countries with over 3750 patients, the research focused on changes in exacerbation rates, symptom control, and lung function about a year after starting treatment.
  • Results showed that higher levels of BEC and FeNO were linked to significant improvements in lung function for specific biologic therapies, while IgE was not a strong predictor of treatment effectiveness.
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  • There is currently no agreed-upon definition for asthma remission in real life, and the factors that help patients achieve it after starting biologics are not well understood.
  • A study analyzed data from 23 countries to see how many adults with severe asthma reached multidomain-defined remission after beginning biologic treatment, using specific criteria for remission.
  • Results showed that less than a quarter of participants achieved full remission, with higher chances for those with fewer exacerbations, lower corticosteroid use, and better control and lung function before treatment, suggesting that early intervention is crucial for better outcomes.
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Background: Exacerbation frequency strongly influences treatment choices in patients with severe asthma.

Research Question: What is the extent of the variability of exacerbation rate across countries and its implications in disease management?

Study Design And Methods: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit.

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Background: There is little agreement on clinically useful criteria for identifying real-world responders to biologic treatments for asthma.

Objective: To investigate the impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in adults with severe asthma.

Methods: This was a longitudinal, cohort study across 22 countries participating in the International Severe Asthma Registry (https://isaregistries.

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Ectopic calcification in the cardiovascular system adversely affects life prognosis. DBA/2 mice experience calcification owing to low expression of Abcc6 as observed in pseudoxanthoma elasticum (PXE) patients; however, little is known about its characteristics as a calcification model. In this study, we explore the suitability of a DBA/2 sub-strain as a PXE-like tissue calcification model, and the effect of a bisphosphonate which prevents calcification of soft tissues in hypercalcemic models was evaluated.

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Background: This study aimed to elucidate the impact of effective diffusion time setting on apparent diffusion coefficient (ADC)-based differentiation between primary central nervous system lymphomas (PCNSLs) and glioblastomas (GBMs) and to investigate the usage of time-dependent diffusion magnetic resonance imaging (MRI) parameters.

Methods: A retrospective study was conducted involving 21 patients with PCNSLs and 66 patients with GBMs using diffusion weighted imaging (DWI) sequences with oscillating gradient spin-echo (Δ = 7.1 ms) and conventional pulsed gradient (Δ = 44.

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  • Previous studies on how comorbidities affect the effectiveness of biologic agents in asthma were limited in size and duration, lacking comparisons between different biologic classes.
  • This cohort study analyzed data from the International Severe Asthma Registry across 21 countries to assess changes in asthma outcomes after starting biologic therapy in patients with type 2-related comorbidities.
  • Results showed that patients with chronic rhinosinusitis (CRS) and nasal polyps (NPs) experienced significantly better outcomes, including fewer exacerbations and improved asthma control, while allergic rhinitis and atopic dermatitis did not influence therapy effectiveness.
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Background: Obstructive sleep apnea (OSA) is one of the major co-morbidities and aggravating factors of asthma. In OSA-complicated asthma, obesity, visceral fat, and systemic inflammation are associated with its severity, but the role of bronchial hyperresponsiveness (BHR) is unclear. We investigated the involvement of BHR and mediastinal fat width, as a measure of visceral fat, with OSA severity in patients with OSA and asthma-like symptoms.

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Aim: The International Severe Asthma Registry (ISAR; http://isaregistries.org/) uses standardised variables to enable multi-country and adequately powered research in severe asthma. This study aims to look at the data countries within ISAR and non-ISAR countries reported collecting that enable global research that support individual country interests.

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  • The study aimed to evaluate the prevalence and impact of comorbidities in adults with severe asthma, as their presence can complicate asthma management practices.* -
  • Data was analyzed from the International Severe Asthma Registry, identifying 30 comorbidities linked to asthma, with findings indicating a significant percentage of patients experience multiple comorbidities that affect their asthma outcomes.* -
  • Results showed that patients with specific comorbidities like allergic rhinitis and nasal polyposis had higher rates of asthma exacerbations and were more likely to require long-term oral corticosteroids, highlighting the need for effective management strategies.*
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Background: This study was designed to investigate the use of time-dependent diffusion magnetic resonance imaging (MRI) parameters in distinguishing between glioblastomas and brain metastases.

Methods: A retrospective study was conducted involving 65 patients with glioblastomas and 27 patients with metastases using a diffusion-weighted imaging sequence with oscillating gradient spin-echo (OGSE, 50 Hz) and a conventional pulsed gradient spin-echo (PGSE, 0 Hz) sequence. In addition to apparent diffusion coefficient (ADC) maps from two sequences (ADC and ADC), we generated maps of the ADC change (cADC): ADC - ADC and the relative ADC change (rcADC): (ADC - ADC)/ ADC × 100 (%).

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Background: Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS) nor been compared with effectiveness of continuing with HOCS alone.

Objective: To examine the effectiveness of initiating biologics in a large, real-world cohort of adult patients with severe asthma and HOCS.

Methods: This was a propensity score-matched, prospective cohort study using data from the International Severe Asthma Registry.

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Purpose: Treatment patterns and patient characteristics are not well elucidated among Japanese patients with severe uncontrolled asthma who currently have various treatment options, including biologics. We analyzed baseline characteristics of patients who did/did not initiate biologic treatment in PROSPECT, a 24-month observational study.

Patients And Methods: Patients with severe uncontrolled asthma were prospectively enrolled at 34 sites in Japan from December 2019 to September 2021.

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Background: Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life.

Methods: This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R.

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Uricosuric agents lower serum uric acid levels by increasing urinary excretion via inhibition of urate transporter 1 (URAT1), urate reabsorption transporter in the renal proximal tubules. Probenecid and benzbromarone have been used as uricosurics, but these drugs inhibit organic anion transporters (OATs) in addition to URAT1. In this study, we investigated whether uricosuric agents interacted with adefovir, known as a substrate for OAT1, using Sprague-Dawley (SD) rats.

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Article Synopsis
  • Many severe asthma patients with high oral corticosteroid exposure (HOCS) are eligible for biologic treatments but often do not start them; this study compares those that do and don’t initiate biologics.
  • The study analyzed data from 1,412 patients worldwide between 2015 and 2021, finding that 70.5% initiated a biologic, with differences in patient characteristics influencing this decision, such as higher blood eosinophil counts and more health complications in those who did start treatment.
  • Despite similar rates of asthma exacerbations, one-third of severe HOCS patients did not receive biologics, indicating a gap in treatment that may depend on specific disease features rather than just exacerbation frequency. *
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