ASKA Pharmaceutical (Japan)

Widespread use of BCR::ABL1 tyrosine kinase inhibitors (TKIs) has transformed the clinical landscape of chronic myeloid leukemia (CML). However, BCR::ABL1 mutation-driven treatment resistance challenges optimal care and outcomes. The purpose of this study was to ascertain real-world practices concerning such mutational profiling in US hematology and oncology practices, which were mainly community-based. This is the first chart review of BCR::ABL1 kinase domain mutational profiling in the US. In this study of the Cardinal Health Oncology Provider Extended Network (OPEN), 13 hematologists and/or oncologists selected charts of adults with chronic-phase CML for approximately equal numbers of patients who underwent such testing (Cohort 1; n=26) or did not (Cohort 2; n=25). Across most time points, failure and warning signs by molecular testing were not significantly more frequent in patients who did or did not undergo BCR::ABL1 mutational profiling. Conversely, similar frequencies of optimal milestones were observed in patients with or without testing. Patients who underwent BCR::ABL1 mutational profiling were more likely to have splenomegaly (p=0.0069) versus those who did not. There were few significant differences in failure and warning signs by molecular testing in patients who did or did not undergo mutational profiling. Patients who underwent BCR::ABL1 mutational profiling were significantly more likely to have splenomegaly, which is not included in consensus guidelines as a reason to conduct such testing. Taken together, these findings raise potential concerns about consensus guideline adherence as a means to optimize CML management for TKI resistance.

In atopic dermatitis (AD), scratching sustains inflammation and impairs the skin barrier. Beyond scratching driven by itch, affected individuals may engage in habitual scratching, defined as repetitive, unconscious scratching that occurs without itch. The extent and clinical significance of habitual scratching in Japanese patients remain unclear. This study aimed to assess the frequency of habitual scratching and its association with AD severity in the Japanese population. This cross-sectional study was conducted in Japan using data from anonymized health insurance claims and a nationwide app-based questionnaire administered in October 2022. Included individuals were adults (aged 19-74years) and children (aged ≤ 18years) with a self-reported diagnosis of AD and either symptoms or treatment within the previous 6months. Habitual scratching was assessed using two yes/no questions. Disease severity was measured using the Patient-Oriented Eczema Measure (POEM), and associations were tested using the Cochran-Armitage trend test. A total of 1507 adults and 525 children were included. Among adults, 44.5% reported scratching without feeling itchy, and 30.0% reported only noticing scratching when it was pointed out; among children, these proportions were 57.5% and 53.3%, respectively. The proportion of patients exhibiting both behaviors increased significantly with POEM severity. For scratching without itch, rates ranged from 35.1% to 62.9% in adults and from 44.5% to 82.6% in children (p < 0.001 for both). For unnoticed scratching, rates ranged from 19.0% to 50.3% in adults and from 41.2% to 69.6% in children (p < 0.001 for both). Habitual scratching was commonly reported across all severity levels of AD in Japan and was associated with greater disease severity. These findings highlight the importance of recognizing/noticing and actively managing unconscious scratching behaviors as part of comprehensive AD care.

Metal binder jet additive manufacturing has attracted industrial attention due to its low production costs. However, the green part strength is low and easily damaged by handling and depowdering. In addition, there are many issues in terms of the binder, such as the residual carbon from the binder in the debinder process, which inhibits powder sintering and has adverse effects on the properties of dissolved carbon in the sintering part. In this study, we investigated the binder that is cured by a thermal polymerization reaction using a thermosetting low molecular weight prepolymer. It can increase the amount of bonding components in the binder, and the green part strength is improved by thermal polymerization of the prepolymer to be high molecular weight. In addition, we designed the binder with less carbon residue by controlling the thermal curing and depolymerization temperature.

Early identification and treatment optimization for the patients with primary aldosteronism are crucial to minimizing the enhanced cardiovascular risks.However, the natural course of primary aldosteronism development remains unclear.An 18-year-old man visited our outpatient clinic for hypertension.At baseline, confirmatory testing ruled out primary aldosteronism, and computed tomography showed normal adrenal glands.During subsequent outpatient follow-up, his blood pressure gradually increased despite treatment with multiple antihypertensive medications.At his 7 th -year visit, he eventually presented severe hypokalemia with a right adrenal tumor.Endocrinological evaluation revealed hyperaldosteronism along with suppressed renin activity, suggesting primary aldosteronism.Subsequent diagnostic procedures, including the captopril challenge test and adrenal venous sampling, confirmed the diagnosis of primary aldosteronism due to the right adrenal tumor.The patient underwent left adrenalectomy, leading to remission of primary aldosteronism.Histopathological analysis confirmed the resected adrenal tumor as a KCNJ5-mutated aldosterone-producing adenoma.Notably, plasma steroid profiling retrospectively revealed elevated peripheral 18-oxocortisol levels, a biomarker of KCNJ5mutated aldosterone-producing adenomas, before the diagnosis of primary aldosteronism.This case clearly demonstrated a natural course of unilateral primary aldosteronism and highlights the potential utility of steroid profiling as part of the diagnostic strategy for primary aldosteronism.

Functional dipeptides carnosine and anserine are abundant in muscle. We determined the effect of short-term dietary histidine (His) content on muscle carnosine and anserine contents and meat quality of broilers. Three groups of 28-day-old female broilers were fed diets with His contents of 67%, 100%, or 150% of requirement for 10days before market (His contents 0.21%, 0.32%, and 0.48%, respectively). The carnosine and anserine contents of 0-h aged muscle significantly increased with dietary His content; in particular, the carnosine content was 162% higher in the His 0.48% group than in the His 0.32% group. The contents of both peptides also increased with dietary His content in 48-h aged muscle, but carnosine was not detected in 0- and 48-h aged muscle of the His 0.21% group. The drip loss, cooking loss, shear force, and pH of meat were not affected by the dietary His content. The 2-thiobarbituric acid-reactive substances contents of 24- and 48-h aged muscles were lower in the His 0.48% group than in the other groups, and the a* and b* values were lower in the His 0.21% group. These results suggest that short-term dietary His content affects imidazole dipeptide contents, antioxidative capacity, and color of broiler meat.

Hepatic encephalopathy (HE) is the neuropsychiatric complication of liver cirrhosis (LC). The influence of gut microbiota on HE pathogenesis has been suggested but not precisely elucidated. Here, we investigate how the gut microbial profile changed in patients with HE to clarify the functional gut microbial species associated with HE. We focused on their responses to rifaximin (RFX), a nonabsorbable antibiotic used in HE therapy. Feces samples were collected from patients with decompensated LC (all HE), patients with compensated LC, and healthy controls, and fecal gut microbial profiles were compared using 16S ribosomal RNA gene amplicon and metagenomic sequencing. The linear discriminant analysis effect size was used to identify specific species. Urease‐positive Streptococcus salivarius, which can produce ammonia, was identified as the most significantly abundant gut microbiota in the HE group, and its ability to elevate the levels of blood ammonia as well as brain glutamine was experimentally verified in mice. Urease‐negative Ruminococcus gnavus was also identified as a significantly abundant species in patients with RFX‐nonresponsive HE after RFX administration. Interestingly, R. gnavus enhanced urease activity of recombinant urease itself, implying that R. gnavus could amplify ammonia production of surrounding urease‐positive microbiota. Furthermore, the sensitivity of S. salivarius and R. gnavus to RFX depended on conjugated secondary bile acid levels, suggesting a therapeutic potential of the combined use of secondary bile acid levels with RFX for enhancing the efficacy of RFX. This study identified specific gut bacterial species abundant in patients with HE and verified their functions linked to HE pathophysiology. Targeting these bacteria could be a potentially effective strategy to treat HE.

Hyaluronan (HA) possesses radical scavenging properties. The low molecular weight HA (LHA)-containing drink (PL) is a dietary supplement that consists of several antioxidants in addition to LHA. The aim of this study is to characterize the hydroxyl radical scavenging activity of LHA through the interactions between the components of PL in in vitro assays. Moreover, the efficacy of LHA toward oxidative stresses (ultraviolet C irradiation, oxidative DNA damage) was evaluated. LHA revealed the following hydroxyl radical-scavenging properties: 1) LHA directly scavenges hydroxyl radicals, 2) LHA activity is enhanced in the presence of other PL components, thereby enabling protection against oxidative damage to DNA, and 3) exposure to UVC-radiation temporarily attenuated the antioxidant activity of PL, which is recovered in an LHA-dependent process. These results suggest that LHA is an excellent material because its antioxidative activity is enhanced in the presence of other antioxidants, which ultimately increases resistance to oxidative stress.

Background and AimBecause covert hepatic encephalopathy (CHE) has been shown to affect the prognosis of cirrhotic patients, early diagnosis of hepatic encephalopathy (HE) is a prerequisite for the preservation of patients' quality of life and for prophylaxis of overt HE. The aim of this study was to identify a clinical parameter to predict impairment of cognitive function in cirrhotic patients with early‐stage HE.MethodsWe investigated the data from 172 patients with cirrhotic or idiopathic portosystemic shunt (PSS) in phase II/III trials of rifaximin in Japan. Classification and regression trees (CARTs) were constructed to identify clinical profiles related to cognitive dysfunction as indicated by the prolongation of time required for the Number Connection Test (NCT‐B).ResultsCART analysis detected age 65 years as the variable for the initial split, and serum albumin level was selected as the variable for the second split among patients aged ≤65 years. In 27 cirrhotic patients aged ≤65 years without PSS, receiver operating characteristic curve analysis revealed that the optimal albumin level cutoff point was 3.05 g/dL, and the area under the curve was 0.80 for the prolongation of NCT‐B time, which was higher than that of the branched‐chain amino acids‐to‐tyrosine ratio (0.46), the prothrombin time–international normalized ratio (PT‐INR) (0.68), serum ammonia (0.61), and total bilirubin (0.69).ConclusionsLower serum albumin level as a clinical biomarker associated with impaired cognitive function may be available as a screening examination for early‐stage HE in cirrhotic patients aged ≤65 years without PSS before undergoing neuropsychological tests.