Tokatsu Hospital

All data generated or analyzed in this study were included in the main text and are available upon reasonable request to the corresponding author.

Background: Macrocytosis commonly develops during imatinib therapy, but its relationship with cytogenetic and molecular outcomes in chronic myeloid leukemia (CML) remains unclear. We investigated whether increases in mean corpuscular volume (MCV) during imatinib treatment are associated with response depth and treatment persistence. Methods: In this retrospective study, we analyzed 101 adults with chronic-phase CML treated with a stable imatinib dose of 400 mg/day for at least 12 months. Patients with conditions that could confound MCV (hydroxyurea exposure, megaloblastic anemia, hypothyroidism, chronic liver disease, alcoholism) were excluded. Complete cytogenetic response (CCyR) and major molecular response (MMR) were assessed by conventional karyotyping and the BCR-ABL1 International Scale, respectively. Increased MCV was defined as MCV > 100 fL after six months of therapy, persisting thereafter. Associations between MCV dynamics, response, and switching to second-generation tyrosine kinase inhibitors were evaluated. Results: Twenty patients (20%) developed increased MCV. Overall, 86 patients (85%) achieved CCyR and 70 (69%) achieved MMR. All patients with increased MCV attained CCyR, compared with 66 of 81 (81%) without MCV elevation (p = 0.037), while MMR rates were 90% versus 64% (p = 0.030). During a median follow-up of 69 months, treatment modification was required in 1 of 20 (5%) patients with increased MCV versus 25 of 81 (31%) in the non-increased group (p = 0.018). Conclusions: MCV elevation during imatinib therapy is associated with deeper molecular response and reduced need for treatment modification. MCV dynamics may serve as an inexpensive pharmacodynamic marker to support risk assessment and guide monitoring in chronic-phase CML.

ABSTRACTIntroductionWhole‐exome sequencing (WES) is considered an important tool in investigating the etiology of developmental delay/intellectual disability (DD/ID) and epilepsy. Genetic diagnosis with WES has become an important tool in patients with DD/ID and epilepsy.MethodsIn this study, we present the findings of WES conducted between August 2021 and December 2024 on children with DD/ID and epilepsy. We evaluated clinically important variants identified by WES in 65 pediatric patients by retrospective analysis.ResultsSixty‐five patients with DD/ID were included in the study, 34 of whom (52.3%) were male. The most common symptom was epilepsy (45 patients, 69.2%), and the second most common symptom was DD/ID in 39 patients (60%). A total of 19 pathogenic/likely pathogenic variants (31.2%) with confirmation made in the parents and probands, 9 variants were determined to be de novo. In this study, the number of patients diagnosed was determined as 19 (31.2%). We detected a de novo likely pathogenic heterozygous c.142 T>C (p.Cys48Arg) variant in the BCL11A gene in the first reported Turkish patient with BCL11A‐related intellectual disability. Other previously unreported de novo variants identified: ASXL3 gene, NM_030632.2 c.3613G>T p.(Glu1205Ter), ANKRD11 gene, NM_001256182.2 c.4750G>T, SHANK3 gene, NM_001372044.2 c.4711_4712del.ConclusionThe cases we present contribute to the expansion of the spectrum of genetic variants in genetically heterogeneous patient groups such as DD/ID and epilepsy. These previously unreported variants advance our molecular understanding and broaden the clinical spectrum of these rare genetic disorders.

Background and Objectives: The efficacy of newly synthesized water-soluble octa-mercaptopyridine-substituted oxotitanium (IV) phthalocyanine (oxo-TiPc) and copper (II) phthalocyanine (CuPc) compounds in photodynamic therapy (PDT) was investigated using human tongue squamous cell cancer cell line (SCC-9, ATCC) cultures. Materials and Methods: A laser light source with a wavelength of 635 nm was used for this study. The cytotoxic values of the cancerous (SCC-9) and healthy (L-929) cell samples to which different Pc concentrations were applied under laser light were evaluated spectroscopically with the XTT method. Results: The oxo-TiPc compound exhibited a significantly lower IC50 value (46.8 µM) for SCC-9 cells compared to the CuPc compound (286.2 µM), indicating higher anticancer activity. This cytotoxicity may be due to decreased aggregation and enhanced reactive oxygen species (ROS) formation. Double-staining tests confirmed that oxo-TiPc-induced cell death included both apoptosis and necrosis. Conclusions: The findings show that the oxo-TiPc compound, unlike the CuPc compound, exhibited more selective toxicity to the SCC-9 cell line and has a higher phototoxic effect.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe, delayed T-cell-mediated adverse drug reaction that affects visceral organs. Typical features include fever, rash, lymphadenopathy, haematological abnormalities and various visceral organ involvements, usually appearing 2-8 weeks after drug initiation. Although commonly affected organs include the liver, kidneys and lungs, pancreatic involvement is rare. We report a rare case of acute pancreatitis associated with DRESS syndrome due to carbamazepine. To the best of our knowledge, this is the first report identifying carbamazepine as a cause of DRESS-related acute pancreatitis.

Pain from arteriovenous fistula puncture significantly affects the quality of life of patients undergoing hemodialysis. AT-04 was designed to alleviate this pain using magnetic stimulation, which is anticipated to be beneficial for managing pain across different conditions. However, limited research exists on the effectiveness of AT-04 in diminishing the pain related to arteriovenous fistula puncture in hemodialysis patients. Between July and August 2024, we enrolled 14 outpatient maintenance hemodialysis patients at Tokyu Hospital who had given informed consent. AT-04 was administered before arteriovenous fistula puncture. We assessed the pain intensity of the puncture using the Visual Analog Scale (VAS) before the application of AT-04, as well as at one and four weeks afterward. We observed changes in puncture pain levels before and after the AT-04 application. The participants had an average age of 80years (IQR, 74-85) and a mean dialysis duration of 5.8years (IQR, 1.0-8.9). Lidocaine tape was utilized by 71.4% of participants, painkillers by 7.1%, and 28.6% used sleeping pills, with none taking antidepressants. The median VAS score before starting AT-04 was 40.5 (IQR, 23.5-55.5). One week after starting AT-04, the median VAS score dropped to 27.0 (IQR, 4.5-32.8), and four weeks later, it further decreased to 16.5 (IQR, 5.0-38.8). These decreases were statistically significant compared to the pre-treatment VAS score (one week after p = 0.0057, four weeks after p = 0.0076). The AT-04 device, which uses alternating magnetic field therapy, significantly alleviated pain from arteriovenous fistula puncture in hemodialysis patients.

Background: Transabdominal ultrasound is used to detect fecal impaction, but the rectum is difficult to visualize without bladder urine or with gastrointestinal gas. Objective: We developed a transgluteal cleft approach that is unaffected by these factors and sought to determine if our ultrasound method could detect and classify fecal matter in the lower rectum using this approach. Methods: We classified ultrasound images from hospitalized patients into four groups: Group 1 (bowed and rock-like echogenic areas), Group 2 (irregular and cotton candy-like hyperechoic areas), Group 3 (flat and mousse-like hyperechoic areas), and Group 4 (linear echogenic areas in the lumen). Stool characteristics were classified as hard, normal, and muddy/watery. Sensitivity and specificity were determined based on fecal impaction and stool classification accuracy. Results: We obtained 129 ultrasound images of 23 patients. The sensitivity and specificity for fecal retention in the rectum were both 100.0%. The recall rates were 71.8% for Group 1, 93.1% for Group 2, 100.0% for Group 3, and 100.0% for Group 4. The precision rates were 96.6% for Group 1, 71.1% for Group 2, 88.9% for Group 3, and 100.0% for Group 4. Our method was 89.9% accurate overall. Conclusion: Transgluteal cleft approach ultrasound scanning can detect and classify fecal properties with high accuracy.

AimWe conducted a 1‐year retrospective mirror‐image study to investigate the effect of aripiprazole once monthly (AOM) on rehospitalization for bipolar disorder.MethodsParticipants were recruited from psychiatric emergency and acute care hospitals in western Japan. We included 39 participants with bipolar disorder who had been administered AOM for at least 1 year with no missing medical records during the observational period. The primary outcomes were rehospitalization rate, number of rehospitalizations, total hospitalization days, and time to rehospitalization in the context of overall psychiatric readmissions. The significance level was set at p < 0.05.ResultsAOM significantly reduced the rehospitalization rate from 23/39 (59%) to 7/39 (18%) (p = 0.001). The number of rehospitalizations decreased significantly from a mean of 0.85 per person‐year to 0.41 per person‐year (p = 0.048). The total hospitalization days significantly decreased from a mean of 34.9 days to 14.4 days (p = 0.008). AOM significantly prolonged the time to rehospitalization (p < 0.001).ConclusionThis study found that AOM reduces overall psychiatric rehospitalization for bipolar disorder based on data from 1 year before and after AOM administration in the real‐world setting. Future studies should examine the robustness and persistence of the rehospitalization preventive effect of AOM with larger sample sizes and longer observation periods beyond 1 year.