Ultrasound Assessment of Kidney Volume in Patients with Acute Decompensated Heart Failure: A Predictor of Diuretic Resistance

［Background］Diuretics are essential for treating acute decompensated heart failure (ADHF), but the response is inconsistent. This study aimed to clarify whether kidney volume as assessed by ultrasound (US) predicts diuretic resistance in patients with ADHF. ［Methods］We enrolled 29 patients with ADHF and 32 controls. Height-adjusted kidney volume was assessed by US. We divided patients into two groups based on the median value of total daily use of furosemide (intravenous dose plus 0.5 × oral dose of furosemide equivalents) during 3 days from admission. ［Results］Patients with ADHF had a significantly smaller left kidney volume than did control subjects (27.7 ± 10.0 vs. 32.8 ± 8.8 mL/m, P < 0.05). Patients in the highdose furosemide group (? 51.7 mg/d) had a significantly lower estimated glomerular filtration rate (eGFR) and a significantly smaller kidney volume than did those in the low-dose furosemide group (eGFR: 43.9 ± 20.4 vs. 60.8± 21.6 mL/min/1.73 m2, left kidney volume: 23.2 ± 5.2vs. 32.6 ± 11.0 mL/m, right kidney volume: 26.5 ± 7.5vs. 32.6 ± 7.9 mL/m, all P < 0.05). Multivariate logistic analysis showed that left kidney volume, but not eGFR,was independently associated with the requirement of high-dose furosemide (odds ratio: 0.856, 95% confidence interval: 0.735?0.997, P < 0.05). ［Conclusion］Kidney volume as assessed by US is a useful predictor of diuretic resistance in patients with ADHF

The first Japanese biobank of patient‐derived pediatric acute lymphoblastic leukemia xenograft models

A lack of practical resources in Japan has limited preclinical discovery and testing of therapies for pediatric relapsed and refractory acute lymphoblastic leukemia (ALL), which has poor outcomes. Here, we established 57 patient-derived xenografts (PDXs) in NOD.Cg-Prkdcscidll2rgtm1Sug/ShiJic (NOG) mice and created a biobank by preserving PDX cells including three extramedullary relapsed ALL PDXs. We demonstrated that our PDX mice and PDX cells mimicked the biological features of relapsed ALL and that PDX models reproduced treatment-mediated clonal selection. Our PDX biobank is a useful scientific resource for capturing drug sensitivity features of pediatric patients with ALL, providing an essential tool for the development of targeted therapies

Programmed Self-Assembly Systems of Amphiphilic Random Copolymers into Size-Controlled and Thermoresponsive Micelles in Water

We report programmed self-assembly systems of amphiphilic random copolymers bearing hydrophilic poly­(ethylene glycol) (PEG) and hydrophobic alkyl pendants into size-controlled and thermoresponsive micelles in water. This system affords simultaneous and precise control of the size, aggregation numbers, and cloud point (Cp) of micelles in water by primary structure (pendant alkyl groups, composition, and chain length) that is programmed in the copolymers. Typically, random copolymers bearing PEG and alkyl pendants (butyl, octyl, dodecyl, and octadecyl groups) universally induce intermolecular self-assembly in water to produce uniform size micelles (<10 nm). The size is just determined by the content and alkyl pendant length of the hydrophobic monomers, independent of main chain length (below critical length for self-folding): The size increased with increasing the content and the pendant length. Design of hydrophobic alkyl groups with tuning composition allow us to widely control the size (molecular weight: 20K–1350K) and cloud point (from 45 to 85 °C) of the polymer micelles. We can thus tailor-make various micelles with identical size yet different Cp or those with identical Cp yet different size. Thanks to such dual controllability, self-sorting and stepwise thermoresponsive micelle systems were also created with blends of different copolymers; binary copolymers induced orthogonal self-assembly in water to provide discrete micelles with different size and cloud point

Incidence of skeletal‐related events in patients with Ewing sarcoma: An observational retrospective study in Japan

Abstract Background Skeletal‐related events (SREs), including the pathological fracture, surgical treatment or radiation of bone lesions, malignant spinal cord compression, hypercalcemia, are important considerations when managing metastatic bone tumors; however, owing to their rarity, the incidence of SREs in patients with Ewing sarcoma remains unknown. Methods We retrospectively reviewed the clinical data from 146 patients with Ewing sarcoma treated at a single institution from 2005 to 2019. The median age at diagnosis was 22.7 years. Fifty patients (34.2%) had metastatic disease at diagnosis. The primary outcome was the SRE‐free rate among patients with Ewing sarcoma. Moreover, we identified the risk factors for SREs using univariate or multivariate analyses. Results During the observational period (median, 2.6 years), SREs occurred in 23 patients. Radiation to the bone, malignant spinal cord compression, and hypercalcemia were documented as the initial SREs in 12 patients (52.2%), 10 patients (43.5%), and one patient (4.3%), respectively. The SRE‐free rate was 94.2 ± 2.0, 87.3 ± 3.0, and 79.6 ± 3.8% at 1, 2, and 3 years after the initial visit, respectively. Multivariate analysis revealed bone metastasis at diagnosis (hazard ratio [HR] = 4.41, p = 0.007), bone marrow invasion (HR = 34.08, p < 0.001), and local progression or recurrence after definitive treatment (HR = 3.98, p = 0.012) as independent risk factors for SREs. Conclusions SREs are non‐rare events that can occur during the treatment course for Ewing sarcoma, with an especially high incidence of malignant spinal cord compression. Patients with metastatic disease at diagnosis, especially in the bone or bone marrow, or with local progression or recurrence after definitive treatment, should be carefully monitored for the occurrence of SREs. The most effective methods to monitor the occurrence of SREs and new preventative therapies for SREs should be investigated in the future

Phase I clinical study of oral olaparib in pediatric patients with refractory solid tumors: study protocol

Abstract Background There is no established standard chemotherapy for recurrent pediatric solid tumors such as neuroblastoma and sarcoma. Since some of these tumor cells show dysfunctions in homologous recombination repair, the goal is to conduct a phase I study of olaparib, a poly(ADP-ribose) polymerase inhibitor. In this clinical trial, the aims are to evaluate the safety, tolerability, and efficacy of olaparib in pediatric patients with refractory solid tumors and to recommend a dose for phase II trials. Methods In this open-label, multicenter study, olaparib tablets (62.5, 125, and 187.5 mg/m2 b.i.d.) will be administered orally in a standard 3 + 3 dose escalation design. Patients aged 3 to 18 years with recurrent pediatric solid tumors are eligible. Pharmacokinetic and pharmacodynamic analyses will also be performed. Discussion This study aims to extend the indications for olaparib by assessing its safety and efficacy in pediatric refractory solid tumor patients. Trial registration UMIN-CTR (UMIN000025521); Registered on January 4, 2017