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WT1-guided pre-emptive therapy after allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia

Abstract The prognosis of patients with acute myeloid leukemia (AML) relapsing after allogeneic hematopoietic stem cell transplantation (HCT) is poor. Several studies have evaluated the significance of pre-emptive therapies using measurable residual disease (MRD) as a marker of hematological relapse. This single-center retrospective study aimed to clarify the significance of pre-emptive treatment based on Wilms’ tumor gene-1 mRNA (WT1) monitoring as an MRD in allografted patients with AML. The eligibility criteria were patients with AML who received chemotherapy for hematological relapse or WT1 increase after HCT. From January 2017 to June 2022, 30 patients with a median age of 57 (16-70) years were included and stratified into two groups: 10 in the WT1 group and 20 in the hematological relapse. The median times from HCT to WT1 increase or hematological relapse were 309 days (range: 48-985) or 242 days (range: 67-1116), respectively. Less intensive chemotherapy using azacitidine or cytarabine was selected for all patients with WT1 increase and 12 (60%) with hematological relapse. The 1-year survival and event-free survival rates for WT1 increase and hematological relapse were 70% vs. 44% (P=0.024) and 70% vs. 29% (P=0.029), respectively. These real-world data suggest that WT1-guided pre-emptive therapy may be superior to therapy after hematological relapse in allografted patients with AML.

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Assessment of diagnostic accuracy for cryptorchidism and risk factors for delayed orchidopexy.

Cryptorchidism (CO) diagnosis by palpation is challenging. Patients with suspected CO are primarily referred to pediatric urologists by general pediatricians and urologists. Currently, surgical treatment for CO is recommended earlier than in previous guidelines. In this study, we evaluated factors that lead to diagnosis discordance and delayed orchidopexy in patients referred with suspected CO in addition to timing of initial screening. In total, 731 patients (1052 testes) with suspected CO were included. Risk factors for diagnostic discrepancy in CO diagnosis by pediatric urologists and risk of delayed orchiopexy were evaluated. Herein, 659 (90%) patients were diagnosed during routine public health checkups for infants and young children, and 419 (57%) patients were referred by pediatric practitioners. Of 1052 testes, 374 (36%) were diagnosed with CO by pediatric urologists. In multivariate analysis, risk factors of diagnostic discrepancy for CO diagnosis by pediatric urologists were bilateral testis (odds ratio [OR] = 9.17, p < 0.0001), >6 months old at initial diagnosis (OR = 1.036, p < 0.0001), and pediatric referral (OR = 4.60, p < 0.0001). In total, 296 patients underwent orchiopexy for CO. In multivariate analysis, risk factors for delayed orchiopexy were presence of comorbidities (OR = 3.43, p = 0.003) and >10 months old at referral (OR = 12.62, p < 0.0001). Pediatric referral is a risk factor for discordant CO diagnostics, and late age at referral brings a risk of delayed orchiopexy. It is necessary to enlighten pediatricians, who are mainly responsible for routine health checkups, in teaching CO diagnostic techniques to ensure early referral.

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The clinical impact of comorbidities among patients with idiopathic pulmonary fibrosis undergoing anti-fibrotic treatment: A multicenter retrospective observational study.

Among patients with idiopathic pulmonary fibrosis (IPF), few studies have investigated the clinical impact of anti-fibrotic treatment (AFT) with and without comorbidities. The aim of the study was to determine whether Charlson Comorbidity Index score (CCIS) can predict the efficacy of AFT in patients with IPF. We retrospectively assessed data extracted from the medical records of IPF patients who received anti-fibrotic agents between 2009 and 2019. The collected data included age, sex, CCIS, pulmonary function test, high-resolution computed tomography (HRCT) pattern, gender/age/physiology (GAP) score, and 3-year IPF-related events defined as the first acute exacerbation or death within 3 years after starting AFT. We assessed 130 patients (median age, 74 years) who received nintedanib (n = 70) or pirfenidone (n = 60). Median duration of AFT was 425 days. Patients were categorized into high (≥ 3 points) and low (≤ 2 points) CCIS groups. There was no significant difference between the groups in terms of age, sex, duration of AFT, GAP score, or incidence of usual interstitial pneumonia pattern on HRCT except percentage predicted diffusion capacity of lung for carbon monoxide. Also, significant difference was not seen between the groups for 3-year IPF-related events (P = 0.75). Especially, in the low CCIS group but not the high CCIS group, the longer duration of AFT had better disease outcome. In the present study, we could not show any relation between CCIS and IPF disease outcomes in patients undergoing AFT, though the longer duration of AFT might be beneficial for IPF outcomes among patients with low CCIS.

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Limited efficacy of low-dose dexamethasone for the treatment of severe COVID-19 pneumonia: A retrospective study

BackgroundCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. Its symptoms range from mild to severe, with the latter often being life-threatening. This study aims to assess the effects of low-dose dexamethasone (DEX) in mild-to-severe COVID-19 pneumonia and examine the final clinical outcomes to identify the optimal therapeutic dose. MethodsClinical data from 132 patients hospitalized for COVID-19 pneumonia between January and October 2021 at Yamato Municipal Hospital were retrospectively analyzed. Based on the ratio of peripheral arterial oxygen saturation (SpO2) to inspired fraction of oxygen (FiO2), patients were categorized into the mild (>450, n = 65), moderate (315–450, n = 55), and severe (<315, n = 12) pneumonia groups. The event of interest was defined as the worsening of the patient's condition during treatment (need to increase FiO2 > 0.1). Patients were treated with low-dose DEX (6.6 mg/day) for 10 days. ResultsThe event-free survival rate decreased significantly in patients with severe pneumonia compared with in those with mild and moderate pneumonia (Bonferroni-adjusted p < 0.02). A total of 16 patients were treated with high-dose corticosteroids because of severe hypoxia. Recovery was observed in all discharged patients with respiratory condition improvement. Low SpO2/FiO2 at admission was significantly associated with serum C-reactive protein levels. ConclusionsFor Japanese patients with COVID-19, severe pneumonia, and SpO2/FiO2 of <315, it may be necessary to administer a dose of corticosteroids of >6.6 mg DEX.

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Pediatric allergies in Japan: Coronavirus disease pandemic-related risk factors.

The coronavirus disease 2019 (COVID-19) pandemic impacted various parts of society, including Japanese children with allergies. This study investigated risk factors for pediatric allergic diseases associated with the state of emergency owing to the COVID-19 pandemic in Japan, including during school closures. Parents of pediatric patients (0-15 years) with allergies were enrolled and queried regarding the impact of school closure on pediatric allergies compared to that before the COVID-19 pandemic. A valid response was obtained from 2302 parents; 1740 of them had children with food allergies. Approximately 4% (62/1740) of the parents reported accidental food allergen ingestion was increased compared to that before the COVID-19 pandemic. Accidental ingestion during school closures was associated with increased contact with meals containing allergens meant for siblings or other members of the family at home. The exacerbation rate during the pandemic was highest for atopic dermatitis at 13% (127/976), followed by allergic rhinitis at 8% (58/697), and bronchial asthma at 4% (27/757). The main risk factors for worsening atopic dermatitis, allergic rhinitis, and bronchial asthma were contact dermatitis of the mask area (34/120 total comments); home allergens, such as mites, dogs, and cats (15/51 total comments); and seasonal changes (6/25 total comments), respectively. The main factors affecting allergic diseases were likely related to increased time at home, preventive measures against COVID-19, and refraining from doctor visits. Children with allergies were affected by changes in social conditions; however, some factors, such as preventing accidental ingestion and the management of allergens at home, were similar to those before the COVID-19 pandemic. Patients who had received instructions on allergen avoidance at home before the pandemic were able to manage their disease better even when their social conditions changed.

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Development and multi-institutional evaluation of a new phantom for verifying beam-positioning errors at off-isocenter positions

PurposeSingle-isocenter stereotactic radiotherapy for multiple brain metastases requires highly accurate treatment delivery at off-isocenter positions (off-iso). This study aimed to verify the beam-positioning errors at off-iso using a newly developed phantom tested at multiple institutions. MethodsThe off-iso phantom comprised five stainless-steel balls with a 3-mm diameter placed at the center and at four peripheral positions on a diagonal line. Each ball was placed 3.5 cm apart along each of the three axes. Two patterns of the phantom setup were defined as 0° and 90° phantom rotations to evaluate the beam-positioning error, which is the distance between the center of the ball and the irradiated field on the electronic portal imaging device. Furthermore, the reproducibility of the beam-positioning errors was verified by evaluating their standard deviation (SD) at a single institution, which included five measurements for two treatment machines. The errors were evaluated at multiple institutions using eight treatment machines. ResultsThe measurement time from setup to image acquisition was approximately 20 min for two patterns. The SD of the beam-positioning errors in the reproducibility tests was 0.41 mm. In the multi-institutional evaluation, the beam-positioning error at the isocenter position was within 1.00 mm of the AAPM-RSS tolerance, with the exception of two linacs. The largest beam-positioning error (1.36 mm) was observed 7.5 cm away from the isocenter in three directions at a gantry angle of 180°. ConclusionsThe developed phantom can be applied as a new tool for establishing beam-positioning errors in single-isocenter stereotactic radiotherapy at off-isocenter positions.

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Sarcopenia in patients following stroke: Prevalence and associated factors

BackgroundThis study aimed to investigate the prevalence and associated factors of sarcopenia in patients following stroke during acute hospitalisation. MethodsThis single-centre prospective observational cohort study assessed skeletal muscle mass using bioelectrical impedance analysis and muscle strength of patients with acute stroke at hospital discharge. Sarcopenia was diagnosed according to the AWGS-2019 criteria. Multiple logistic regression analyses were performed to identify associated factors of post stroke sarcopenia. ResultsA total of 286 participants (32% female; median age, 72 years) were included in this study. The prevalence of post-stroke sarcopenia was 32.5% (n = 93). In multiple logistic regression analysis, age (adjusted odds ratio [aOR]: 1.10; 95% confidence interval [CI]: 1.05–1.05), National Institute of Health Stroke Scale (aOR: 1.15; 95% CI: 1.04–1.27), body mass index (BMI) (aOR: 0.73; 95% CI: 0.64–0.84) and Functional Oral Intake Scale (aOR: 0.67; 95% CI: 0.51–0.89) were independently associated with post-stroke sarcopenia during acute hospitalisation. ConclusionApproximately one-third of acute stroke patients were diagnosed with sarcopenia at hospital discharge, and older age, severe stroke, low BMI, and poor swallowing function are associated with sarcopenia following stroke during acute hospitalisation.

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