Search

Shosaku Nomura,1 Yoshinobu Maeda,2 Kazuyoshi Ishii,1 Yuta Katayama,3 Hideo Yagi,4 Naoto Fujishima,5 Shuichi Ota,6 Masato Moriyama,7 Takayuki Ikezoe,8 Yasuhiko Miyazaki,9 Kunio Hayashi,10 Shinya Fujita,1 Atsushi Satake,1 Tomoki Ito,1 Taiichi Kyo,3 Mitsune Tanimoto2 1First Department of Internal Medicine, Kansai Medical University, Hirakata, 2Department of Hematology and Oncology, Okayama University, Okayama, 3Division of Hematology, Hiroshima Red Cross Hospital, Hiroshima, 4Division of Hematology, Kidai Nara Hospital, Ikoma, 5Department of Hematology, Naphrology, and Rheumatology, Akita University, Akita City, 6Division of Hematology, Sapporo Hokuyu Hospital, Sapporo, 7Department of Hematology, Niigata University, Niigata, 8Department of Hematology and Respiratory Medicine, Kochi University, Nankoku, 9Division of Hematology, Oita Hospital, Oita, 10Division of Hematology, Meiwa Hospital, Nishinomiya, Japan Background: Conditioning regimens including total body irradiation (TBI) or cyclophosphamide can mobilize high-mobility group box 1 (HMGB1) to peripheral blood. Additionally, increased plasminogen activator inhibitor (PAI)-1 levels are associated with post-allogeneic hematopoietic stem cell transplantation (aHSCT). However, changes to circulating levels of HMGB1 after aHSCT are poorly understood. Materials and methods: The study cohort included 289 patients who underwent aHSCT at one of 25 institutions in Japan. We have investigated the relationship between HMGB1 and PAI-1 following aHSCT. A significant increase in HMGB1 levels occurred after conditioning treatment. Additionally, levels of HMGB1 at day 0 were significantly increased in TBI+ patients and cyclophosphamide/TBI patients. Conclusion: Our data revealed that an increased level of HMGB1 at day 0 following aHSCT correlates with increased PAI-1 after aHSCT, which is consistent with previous reports. Increased HMGB1 at day 0 after a conditioning regimen may play a role in transplantation-associated coagulopathy following aHSCT, because PAI-1 can accelerate procoagulant activity. Keywords: PAI-1, transplantation-associated coagulopathy, aHSCT, TBI, HMGB1

Background: Rituximab is widely used in patients with steroid-dependent nephrotic syndrome. However, information on the effect of long-term rituximab treatment is limited. This study examined the efficacy of rituximab during and after treatment in adult patients with steroid-dependent nephrotic syndrome., Methods: This retrospective cohort study included 30 patients with steroid-dependent nephrotic syndrome. Patients received regular single-dose rituximab (500 mg) intravenously every 6 months. Discontinuation of rituximab was considered after four to six doses if there was no recurrence of nephrotic syndrome. Glucocorticoid discontinuation with remission, first relapse after rituximab initiation, and relapse after regular rituximab treatment discontinuation were evaluated., Results: The median age was 38 (range 18-67) years. Of 30 patients, 13 and 17 were men and women, respectively. Prior to rituximab treatment, the median number of nephrotic syndrome relapses in the patients was 5 (range 2- > 20). The 1 year discontinuation rate of glucocorticoids with remission was 83%. All patients discontinued glucocorticoid treatment at least once until 3 years and 7 months. The 1 and 2 year relapse rates after initiation of rituximab treatment were 0% and 3%, respectively. 25 patients discontinued regular rituximab treatment after a median number of six (4-12) doses. Six patients relapsed after discontinuing rituximab, and the 1 and 2 year relapse rates after the last regular rituximab treatment were 9% and 25%, respectively., Conclusion: All patients with steroid-dependent nephrotic syndrome who received rituximab could discontinue glucocorticoid treatment with remission, and three-fourths of the patients remained in remission for > 2 years after discontinuing rituximab treatment., Competing Interests: Declarations Conflict of interest The authors have declared that no conflict of interest exists. Ethical approval This study was approved by the Ethics Committee of Iwate Prefectural Central Hospital and conducted in accordance with the ethical principles of the Declaration of Helsinki. Informed consent A written informed consent was not obtained from the patients because the ethical guidelines for epidemiological research in Japan do not require informed consent for a retrospective cohort study using only existing medical records., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Objectives: Diagnosis and treatment of osteoporosis are instrumental in obtaining good outcomes of hip surgery. Measuring bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA) is the gold standard for diagnosing osteoporosis. However, due to limited access to DXA, there is a need for a screening tool to identify patients at a higher risk of osteoporosis. We analyzed the potential utility of the Osteoporosis Self-assessment Tool for Asians (OSTA) as a screening tool for osteoporosis., Methods: A total of 1378 female patients who underwent hip surgery at 8 institutions were analyzed. For each patient, the BMD of the proximal femoral region was measured by DXA (DXA-BMD), and the correlation with OSTA score (as a continuous variable) was assessed. Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of OSTA score to predict osteoporosis. Lastly, the OSTA score was truncated to yield an integer (OSTA index) to clarify the percentage of patients with osteoporosis for each index., Results: DXA-BMD showed a strong correlation with OSTA (r = 0.683; P < 0.001). On ROC curve analysis, the optimal OSTA score cut-off value of -5.4 was associated with 73.8% sensitivity and 80.9% specificity for diagnosis of osteoporosis (area under the curve: 0.842). A decrease in the OSTA index by 1 unit was associated with a 7.3% increase in the probability of osteoporosis., Conclusions: OSTA is a potentially useful tool for screening osteoporosis in patients undergoing hip surgery. Our findings may help identify high-risk patients who require further investigation using DXA., Competing Interests: The authors declare no competing interests., (© 2024 The Korean Society of Osteoporosis. Publishing services by Elsevier B.V.)

The efficacy of a computed tomography (CT)-based navigation system to accurately position the stem for intended alignment is unclear. In addition, the influence of stem design on the accuracy of insertion is unknown. We therefore retrospectively compared the accuracy and precision for the intended alignment of two different designs of femoral stem which were implanted with or without the navigation system. Forty-nine total hip arthroplasties (THAs) using a tapered wedge stem and 91 THAs using an anatomic stem were evaluated for the navigation group. Thirty-three THAs using the tapered wedge stem and 15 THAs using the anatomic stem were controls for the non-navigation group. Differences between postoperative measurement and preoperative planning were compared among the groups. In the navigation groups, accuracy (mean absolute difference) and precision (95% limits of agreement) of stem anteversion were 4.3° and ± 10.1° in the tapered wedge stem and 3.1° and ± 6.9° in the anatomic stem. In the non-navigation groups, these were 6.0° and ± 15.2° and 4.8° and ± 12.4°, respectively. The accuracy and precision in the navigation groups were significantly superior to those in the non-navigation group, and those in the anatomic stem group were significantly superior to those in the tapered wedge group. Using the CT-based navigation system, the accuracy and precision for intended stem anteversion were improved. When compared under guidance of navigation system, the accuracy and precision for intended stem anteversion in the anatomic stem were superior to those in the tapered wedge stem.

The lipidome of mammalian cells not only contain sphingomyelin (SM) but also, as a minor component, dihydrosphongomyelin (DHSM), in which the double bond at C4-C5 in the sphingosine base is reduced to a single-bond linkage. It has been indicated that DHSM forms ordered domains more effectively than SM due to its greater potential to induce intermolecular hydrogen bonds. However, direct information on partition and dynamic behaviors of DHSM in raft-like liquid-ordered (L o ) and non-raft-like liquid-disordered (L d ) phase-segregated membranes has been lacking. In the present study, we prepared fluorescent derivatives of DHSM and compared their behaviors to those of fluorescent SM and phosphatidylcholine (PC) derivatives. Fluorescence microscopy showed that DHSM is more preferentially localized to the L o domains in the L o /L d phase-segregated giant unilamellar vesicles than SM and PC. Most importantly, diffusion coefficient measurements indicated that DHSM molecules form DHSM-condensed assembly inside the SM-rich L o domain of the SM/dioleoylphosphatidylcholine/cholesterol system even when DHSM accounts for 1-3.3 mol% of total lipids. Such heterogeneous distribution of DHSM in the SM-rich L o domains was further confirmed by inter-lipid FRET experiments. This study provides new insights into the biological functions and significance of minor component DHSM in lipid rafts.

A computed tomography (CT)-based navigation system is one of the support tools to place implant with appropriate alignment and position in total hip arthroplasty (THA). To determine whether the higher performance of the navigation would further improve the accuracy of implant placement in the clinical setting, we retrospectively compared the navigation accuracy of two different versions of a navigation system. The newer version of the navigation system had an upgraded optical sensor with superior positional accuracy. Navigation accuracy, defined as differences between postoperative measurements on CT images and intraoperative records on the navigation system, of 49 THAs performed with the newer version of the navigation system was compared with that of 49 THAs performed with the older version. With the newer version, the mean absolute accuracy (95% limits of agreement) of implant alignment was 1.2° (± 3.3°) for cup inclination, 1.0° (± 2.4°) for cup anteversion, 2.0° (± 4.9°) for stem anteversion, and 1.1° (± 2.4°) for stem valgus angle. The accuracy of the implant position was 1.5 mm (± 3.1 mm), 1.3 mm (± 3.0 mm), and 1.5 mm (± 3.1 mm) for cup x-, y-, and z-axes, respectively, 1.6 mm (± 3.2 mm), 1.4 mm (± 2.9 mm), and 1.5 mm (± 2.7 mm) for stem x-, y-, and z-axes, respectively, and 2.4 mm (± 4.5 mm) for leg length discrepancy. The values for the newer version were significantly more accurate with less variation compared to those of the older version. With upgraded navigation performance, more accurate implant placement was demonstrated in the clinical setting.

In this ongoing Phase 1/2 study (NCT01667133), we evaluated ponatinib and assessed its recommended dose in Japanese patients with chronic myeloid leukemia (CML) resistant/intolerant to dasatinib or nilotinib, or with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) resistant/intolerant to ≥1 tyrosine kinase inhibitor (TKI). The primary endpoints were safety of the recommended dose (Phase 1) and major cytogenetic response (MCyR) by 12 months in chronic-phase CML (CP-CML) patients or major hematologic response (MaHR) by 6 months in patients with advanced phase disease (Phase 2). MCyR was achieved/maintained by 12 months in 65% of CP-CML patients; MaHR was achieved by 6 months in 61% of patients with advanced phase disease. The most common nonhematologic grade 3/4 treatment-emergent adverse event (AE) was hypertension (37%); common hematologic grade 3/4 AEs were thrombocytopenia (57%), neutropenia (34%), and leukopenia (26%). Overall, five (14%) patients experienced arterial occlusive events (AOEs); no grade 5 AOEs were reported. The steady-state accumulation ratio of ponatinib (based on area under the curve) ranged from 2.6 (15 mg/day) to 1.3 (45 mg/day). In summary, ponatinib demonstrated efficacy in Japanese patients with CML and Ph + ALL resistant/intolerant to prior TKI treatment; safety data support a recommended starting dose of 45 mg/day in these patients.