Jong-Ho Won

Acute promyelocytic leukemia (APL) has been treated for decades with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO), which achieve excellent survival but remain limited by induction mortality, ATO-related toxicities, and relapse in some patients. Src family kinases (SFKs) regulate proliferation and survival of myeloid lineage cells, and SFK inhibition has been reported to enhance retinoic acid (RA)-induced differentiation. We investigated whether clinically available SFK inhibitors can augment ATRA-induced differentiation of APL-derived NB4 cells more effectively than the ATRA plus ATO standard regimen. NB4 cells were treated with PP2, bosutinib, or dasatinib with or without ATRA. Differentiation was assessed by CD11b expression using flow cytometry and by nitroblue tetrazolium reduction. SFK phosphorylation and retinoic acid receptor (RAR) target gene expression were evaluated by immunoblotting. Apoptosis was analyzed to distinguish differentiation from cytotoxic effects. ATRA plus ATO modestly increased CD11b-positive cells (17.4%±1.7), whereas ATRA combined with PP2, bosutinib, or dasatinib yielded 49.5%±5.3, 31.4%±2.1, and 53.2%±2.3 CD11b-positive cells, respectively, all significantly higher than ATRA plus ATO (p<0.05). Enhanced granulocytic differentiation was confirmed by nitroblue tetrazolium reduction and was not accompanied by increased apoptosis. SFK inhibitors reduced SFK phosphorylation and increased RAR target protein expression in parallel with augmented differentiation. Clinically available SFK inhibitors, particularly dasatinib, synergistically enhance ATRA-induced myeloid differentiation of NB4 APL cells and are more effective than the conventional ATRA plus ATO combination in this in vitro model. These findings support further preclinical and clinical evaluation of SFK inhibitor plus ATRA combinations as differentiation-oriented strategies and potential alternatives or complements to ATO-containing regimens in APL.

The neutrophil-to-lymphocyte ratio (NLR), a simple marker of systemic inflammation, may assist in differentiating polycythemia vera (PV) from secondary polycythemia (SP), especially when access to JAK2 mutation testing is limited due to cost or delayed turnaround. We retrospectively analyzed 655 patients with erythrocytosis who underwent JAK2 mutation testing between 2007 and 2024 across three South Korean tertiary hospitals. PV and SP were diagnosed per 2016 WHO criteria. NLR was calculated from complete blood counts and compared to serum erythropoietin (EPO) using receiver operating characteristic (ROC) analysis. The mean NLR was significantly higher in PV than SP (6.92 vs. 2.24, p < 0.001). NLR outperformed EPO in distinguishing PV (AUC 0.919 vs. 0.835, p < 0.001), and the combination further improved diagnostic accuracy (AUC 0.955). Notably, 98.8% (159/161) of patients with NLR < 1.5 had SP, suggesting these patients may safely undergo delayed JAK2 testing while secondary causes are prioritized. NLR may serve as a cost-effective triage marker to identify patients at low risk for PV, potentially reducing unnecessary molecular testing and expediting appropriate diagnostic pathways in erythrocytosis.

Junseo Lee, B.D., Seryeong Kim, B.D., Sun Young Jeong, M.D., Seug Yun Yoon, M.D., Namsu Lee, M.D., Ph.D., Jong-Ho Won, M.D., Ph.D., Jeong Won Shin, M.D., Ph.D., Soon Hyo Kwon, M.D., Ph.D., Min-Young Lee, M.D. Ph.D., and Kyoung Ha Kim, M.D. Ph.D.. Ann Lab Med -0001;0:. https://doi.org/10.3343/alm.2023.0355

Seug Yun Yoon, Jong-Ho Won. Blood Res 2023;58:S83-9. https://doi.org/10.5045/br.2023.2023013

Iron deficiency anemia (IDA) is the most prevalent and common nutritional deficiency worldwide and is a global health problem with significant risk, particularly among women of reproductive age. Oral iron supplementation is the most widely used and cost-effective treatment for iron deficiency and IDA. However, there are limitations regarding side effects such as enteritis, treatment compliance, and bioavailability. Intestinal microbiome characteristic research has been recently conducted to overcome these issues, but more is needed. Against this background, a metagenomics study on the 16S gene in the feces of young women vulnerable to IDA was conducted. As a result of analyzing 16 normal subjects and 15 IDA patients, significant differences in bacterial community distribution were identified. In particular, a significant decrease in Faecalibacterium was characteristic in IDA patients compared with normal subjects. Furthermore, in the case of patients who recovered from IDA following iron supplementation treatment, it was confirmed that Faecalibacterium significantly recovered to normal levels. However, no significance in beta diversity was seen compared with before treatment. There were also no differences in the beta diversity results between the recovered and normal subjects. Therefore, intestinal dysbiosis during the disease state was considered to be restored as IDA improved. Although the results were derived from a limited number of subjects and additional research is needed, the results of this study are expected to be the basis for developing treatment and prevention strategies based on host–microbiome crosstalk in IDA.

Purpose High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard management for relapsed or high-risk non-Hodgkin’s lymphoma (NHL). We reported the busulfan, melphalan, and etoposide (BuME) conditioning regimen was effective in patients with relapsed or high-risk NHL. Moreover, the busulfan, cyclophosphamide, and etoposide (BuCE) conditioning regimen has been used widely in ASCT for NHL. Therefore, based on these encouraging results, this randomized phase II multicenter trial compared the outcomes of BuME and BuCE as conditioning therapies for ASCT in patients with NHL.Materials and Methods Patients were randomly assigned to receive either BuME (n=36) or BuCE (n=39). The BuME regimen was comprised of busulfan (3.2 mg/kg/day, intravenously) administered on days –7, –6, and –5, etoposide (400 mg/m2 intravenously) on days –5 and –4, and melphalan (50 mg/m2/day intravenously) on days –3 and –2. The BuCE regimen was comprised of busulfan (3.2 mg/kg/day intravenously) on days –7, –6, and –5, etoposide (400 mg/m2/day intravenously) on days –5 and –4, and cyclophosphamide (50 mg/kg/day intravenously) on days –3 and –2. The primary endpoint was 2-year progression-free survival (PFS).Results Seventy-five patients were enrolled. Eleven patients (30.5%) in the BuME group and 13 patients (33.3%) in the BuCE group had disease progression or died. The 2-year PFS rate was 65.4% in the BuME group and 60.6% in the BuCE group (p=0.746). There were no non-relapse mortalities within 100 days after transplantation.Conclusion There were no significant differences in PFS between the two groups. Therefore, busulfan-based conditioning regimens, BuME and BuCE, may be important treatment substitutes for the BCNU-containing regimens.

Ji YS, et al. Yonsei Med J. 2023 Jan;64:e14. https://doi.org/10.3349/ymj.2022.0331

BACKGROUND: The aims of this study were to evaluate the long-term effects of hearing-aid use on auditory spectral discrimination, temporal envelope sensitivity, and speech perception ability and to determine whether hearing performance changes with the duration of hearing-aid use. METHODS: The study included 13 elderly participants (64.15 ± 9.87 years) who had used hearing-aids for 12 months in everyday life. We compared the auditory performance without hearing-aids at the time of pre-fitting with the auditory performance with hearing-aids at 1 month and 12 months after fitting. Three different psychoacoustic measurements were made at their most comfortable levels to exclude the effect of amplification: (1) spectral-ripple discrimination, (2) temporal modulation detection, and (3) speech recognition in white noise. RESULTS: Repeated-measures analysis of variance demonstrated that the duration of hearing-aid use significantly affected spectral-ripple discrimination thresholds and 100 Hz temporal modulation detection threshold (P < .05). Post hoc tests revealed that the improvements in spectral discrimination in the early post-fitting stage (1 month) did not seem to increase over the period of hearing-aid use, whereas the temporal envelope sensitivity improved continuously over time (up to 12 months). CONCLUSION: These results imply that hearing-aid users adapt to hearing-aid processing for spectral discrimination immediately, whereas they need time to adapt to hearing-aid processing for temporal envelope sensitivity. Alternatively, long-term hearing-aid use could induce positive plastic changes exclusively in terms of temporal envelope sensitivity. Cite this article as: An Y, Sub Lee E, Hyun Kim D, Sik Oh H, Ho Won J, Joon Shim H. Long-term effects of hearing aid use on auditory spectral discrimination and temporal envelope sensitivity and speech perception in noise. J Int Adv Otol. 2022;18(1):43-50.