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We retrospectively evaluated the impacts of using granulocyte colony-stimulating factor (G-CSF) and its timing on posttransplant outcomes for 9766 adults with acute myeloid leukemia (AML) between 2013 and 2022 using a Japanese database. We separately evaluated three distinct cohorts based on graft type: 3248 received bone marrow transplantation (BMT), 3066 received peripheral blood stem cell transplantation (PBSCT), and 3452 received single-unit cord blood transplantation (CBT). Multivariate analysis showed that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT. However, it was associated with a higher risk of grades II-IV acute graft-versus-host disease (GVHD) across all graft types. Moreover, an increased incidence of overall chronic GVHD was observed with G-CSF administration in BMT and CBT patients, but not in PBSCT patients. G-CSF administration significantly improved overall survival (OS) and leukemia-free survival (LFS) only following CBT. Regarding the timing of G-CSF, in comparison with late initiation of G-CSF (Days 5-10), early initiation (Days 0-4) did not provide benefits for hematopoietic recovery regardless of graft type. In contrast, late initiation was significantly associated with a lower risk of grades II-IV acute GVHD and better OS and LFS in CBT patients. These data demonstrated that G-CSF administration accelerated neutrophil recovery and increased the risk of grades II-IV acute GVHD across all graft types, but significantly improved survival outcomes but only following CBT. Therefore, routine use of G-CSF should be considered for CBT in adult patients with AML., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

Ganciclovir and foscarnet are two representative anti-cytomegalovirus (CMV) agents. A previous regional study revealed a lower risk of chronic graft-versus-host disease (GVHD) in patients who received pre-emptive foscarnet. We conducted a retrospective nationwide study to confirm the results. A total of 8890 patients aged 16 or older with hematological malignancies who received foscarnet (n = 1555) or ganciclovir (n = 7335) during their first hematopoietic stem cell transplantation (HSCT) were included. The risks of chronic GVHD (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.13-1.40; P < 0.001) and extensive chronic GVHD (HR, 1.16; 95% CI, 1.01-1.33; P = 0.033) were higher with ganciclovir. Among male patients with a female donor, the incidence of extensive chronic GVHD 3 years after HSCT was clearly lower with foscarnet (13%; 95% CI, 9-16%) than with ganciclovir (27%; 95% CI, 25-29%; P < 0.001). In male patients who received HSCT from female donors, foscarnet recipients showed significantly lower incidence of extensive chronic GVHD than ganciclovir recipients, regardless of donor source or previous acute GVHD. While caution is necessary, these results indicate that foscarnet affects alloimmunization and might reduce the incidence of chronic GVHD., Competing Interests: Declarations Conflict of interest The authors declare that there are no competing financial interest to report. S. Terakura and Y.K are editors of International Journal of Hematology., (© 2024. Japanese Society of Hematology.)

We report the draft genome sequence of the Nocardia sp. strain JMUB6875, isolated from a blood culture specimen of a patient with disseminated nocardiosis. This strain appears to be a potentially novel species closely related to Nocardia concava ., Competing Interests: The authors declare no conflict of interest.

Background: De novo chronic myeloid leukemia in blastic phase (CML-BP) showing lymphoid immunophenotype mimics Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). Although upfront allogeneic hematopoietic cell transplantation (HCT) is considered in both diseases, it is not yet clear whether the transplant outcomes are also similar., Methods: Using a registry database, the transplant outcomes between de novo CML-BP and Ph-positive ALL in negative-minimal residual disease (MRD), positive MRD, and nonremission cohorts were compared, respectively. All of the included patients had received tyrosine kinase inhibitor therapy before HCT and underwent HCT between 2002 and 2021. Regarding Ph-positive ALL, patients with p210 transcripts were excluded because there was concern that this group might include patients with de novo CML-BP., Results: Although most of the outcomes were comparable, in patients with positive MRD at HCT, de novo CML-BP was significantly associated with superior disease-free survival (DFS) (hazard ratio [HR] 0.6, p = .0032), overall survival (HR 0.66, p = .027), and a lower risk of relapse (HR 0.48, p = .0051). In subgroup analyses, BCR::ABL1 mutation status had a significant interaction with the disease (p for interaction = .0027). De novo CML-BP seemed to be associated with superior disease-free survival in a BCR::ABL1 mutation-positive cohort, whereas this association was not observed in a mutation-negative cohort., Conclusions: Considering previous reports that showed inferior outcomes for de novo CML-BP compared to Ph-positive ALL, the data suggested that allogeneic HCT could overcome the poor prognosis of de novo CML-BP. These findings highlight the importance of distinguishing de novo CML-BP from Ph-positive ALL., (© 2024 American Cancer Society.)

Background/aim: In prostate cancer, robotic total prostatectomy is a popular treatment modality. However, prostate-specific antigen (PSA) recurrence after prostate cancer surgery remains a concern. Salvage radiotherapy is commonly used to treat PSA recurrence, but the recurrence rate after salvage radiotherapy is high, highlighting the need for better predictive markers. This study aimed to retrospectively evaluate the association between cribriform pattern and PSA recurrence in patients receiving radiotherapy after radical prostatectomy., Patients and Methods: Data of 50 patients who underwent radiotherapy after total prostatectomy between January 2010 and May 2020 were retrospectively evaluated. The median age was 67 years. Among these patients, two cases involved postoperative irradiation, while 48 cases involved salvage irradiation after postoperative PSA recurrence. The median time from surgery to PSA recurrence was 38.3 months. The median radiation dose was 64 Gy in 32 fractions. Three-dimensional conformal radiation therapy was administered in 38 cases and intensity-modulated radiation therapy was used in 12 cases. Combined hormone therapy was administered in 21 cases. PSA levels were measured every 3 months after treatment. Statistical analysis between groups was performed by a t-test., Results: The median follow-up period after radiotherapy was 31 months. No local recurrences were observed at the prostate bed, and no deaths related to prostate cancer were recorded during follow-up. However, 18 patients (36.0%) had PSA recurrence. The PSA recurrence rate based on the cribriform pattern was 17.6% in the none to moderate group (34 patients) and 75.0% in the severe cribriform pattern group (16 patients). The PSA recurrence rate was significantly higher in patients with a severe invasive cribriform pattern (p=0.001). No significant differences were observed in other histopathological characteristics., Conclusion: The cribriform pattern in surgical pathology specimens was found to be a useful predictor of PSA recurrence after postoperative radiotherapy., Competing Interests: The Authors declare that there are no conflicts of interest., (©2024 The Author(s). Published by the International Institute of Anticancer Research.)

Background/aim: To develop an accurate method to predict nodal pathological complete response (ypN0) in patients after neoadjuvant chemotherapy (NAC) for clinically node-positive breast cancer., Patients and Methods: We included 128 patients with clinically node-positive primary breast cancer who underwent axillary lymph node dissection after NAC., Results: Breast primary tumor clinical complete response (ycT0) was observed in 29.7% and nodal clinical complete response (ycN0) in 44.5% of cases. When ycN0 was predicted as ypN0, the negative predictive value was 77.2%, and the false-negative rate was 19.7%. Estrogen receptor status, ycT0, and ycN0 were independent predictive factors for ypN0 after NAC in patients with clinically node-positive breast cancer. These factors were used to develop a nomogram for ypN0 prediction. The following points were added: 82 in case of estrogen receptor-negative, 56 in case of ycT0, and 100 in case of ycN0. Score summation was used to prognosticate the manifestation of ypN0. Our nomogram predicted ypN0 with a negative predictive value of 92.9% and false-negative rate of 4.5%, demonstrating an approximate 15% improvement over ypN0 prediction using ycN0 alone., Conclusion: Estrogen receptor-negativity, ycT0, and ycN0 are independent predictive factors for ypN0 after NAC in clinically node-positive breast cancer. The nomogram may improve individualized axillary treatment., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Study Design: Retrospective multicenter study., Objectives: To evaluate how preoperative neck pain influences clinical outcomes following posterior decompression for cervical ossification of the posterior longitudinal ligament (OPLL)., Setting: Fourteen medical institutions in Japan., Methods: We enrolled 90 patients with cervical OPLL who underwent posterior decompression and were followed for a minimum of two years. We collected demographic data, medical history, and imaging findings. Patients were divided into two groups based on preoperative neck pain presence (Pre-op. neck pain (-) and (+) groups), and their outcomes were compared., Results: There were no significant differences in patient demographics between the Pre-op. neck pain (-) and (+) groups. Both groups showed similar distributions of ossification types and K-line positivity. Perioperative complications were comparable between the two groups. Radiographic analysis revealed no significant differences in C2-7 angles or cervical range of motion, pre- and postoperatively. Both groups demonstrated significant improvement in postoperative Japanese orthopedic association (JOA) scores, but there were no significant differences in scores or recovery rates. In the Pre-op. neck pain (-) group, factors associated with appearance of postoperative neck pain included pre- and postoperative lower JOA scores and larger C2-7 angles in neutral and extension positions., Conclusions: It emerges that lower pre- and postoperative JOA scores or larger C2-7 angles in neutral and extension positions predispose to postoperative neck pain even in those patients without preoperative neck pain. Therefore, this is worth discussing at the time of consenting patients for surgical decompression and fixation., (© 2024. The Author(s), under exclusive licence to International Spinal Cord Society.)

Background: Failure-free survival (FFS) rates of low-risk patients with rhabdomyosarcoma improved in Intergroup Rhabdomyosarcoma Study IV after the escalation of cyclophosphamide total dose to 26.4 g/m 2 . However, this dose may increase the risk of adverse events, including infertility, in some patients. The JRS-I LRA0401 and LRB0402 protocols aimed to reduce the cyclophosphamide dose to 9.6 g/m 2 and 17.6 g/m 2 , respectively, without decreasing the FFS rates., Methods: Subgroup-A patients received eight cycles (24 weeks) of vincristine, actinomycin D, and 1.2 g/m 2 /cycle cyclophosphamide. Subgroup-B patients received eight cycles (24 weeks) of vincristine, actinomycin D, and 2.2 g/m 2 /cycle cyclophosphamide, followed by six cycles (24 weeks) of vincristine and actinomycin D. Group II/III patients in both subgroups received radiotherapy., Results: In subgroup A (n = 12), the 3-year FFS rate was 83% (95% confidence interval [CI], 48-96), and the 3-year overall survival (OS) rate was 100%. Only one isolated local recurrence was observed (8.3%). There were no unexpected grade-4 toxicities and no deaths. In subgroup B (n = 16), the 3-year FFS and OS rates were 88% (95% CI, 59-97) and 94% (95% CI, 63-99), respectively. There were no unexpected grade 4 toxicities and no deaths., Conclusions: Shorter duration therapy using vincristine, actinomycin D, and lower dose cyclophosphamide with or without radiotherapy for patients with low-risk subgroup A rhabdomyosarcoma (JRS-I LRA0401 protocol) and moderate reduction of cyclophosphamide dose for patients with low-risk subgroup B rhabdomyosarcoma (JRS-I LRB0402 protocol) did not compromise FFS., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objectives: Heart failure may result in reduced brain perfusion, limiting the blood flow needed to achieve clinical recovery. We investigated whether plasma levels of brain natriuretic peptide (BNP), a biological marker of heart failure, were related to clinical outcomes after mechanical thrombectomy (MT)., Materials and Methods: Data were analyzed from stroke patients with internal carotid or middle cerebral artery occlusion enrolled in the SKIP trial for whom plasma level of BNP was evaluated on admission. Favorable outcome was defined as a modified Rankin scale score of 0-2 at 3 months., Results: Among 169 patients (median age, 74 years; 62% men, median National Institutes of Health Stroke Scale score, 18), 104 (62%) achieved favorable outcomes. Median plasma BNP level was lower in the favorable outcome group (124.1 pg/mL; interquartile range [IQR], 62.1-215.5 pg/mL) than in the unfavorable outcome group (198.0 pg/mL; IQR, 74.8-334.0 pg/mL; p=0.005). In multivariate regression analysis, the adjusted odds ratio for BNP for favorable outcomes was 0.971 (95% confidence interval, 0.993-0.999; p=0.048). At 3 months after onset, the favorable outcome rate was lower in the ≥186 pg/mL group (45%) than in the <186 pg/mL group (72%; p=0.001). This significant difference remained regardless of the presence of atrial fibrillation (AF), with rates of 47% and 76%, respectively, in AF patients (p=0.003) and 33% and 68%, respectively, in patients without AF (p=0.046)., Conclusion: High plasma BNP concentration appears associated with unfavorable outcomes after MT., Competing Interests: Declaration of competing interest Kazumi Kimura received lecture fees from Bristol-Myers Squibb Co. Ltd., Nippon Boehringer Ingelheim Co. Ltd., Bayer Healthcare Co. Ltd., and Daiichi Sankyo Co.; research funding from Nippon Boehringer Ingelheim Co. Ltd., Daiichi Sankyo Co., Pfizer Japan Inc., Medtronic Co. Ltd., and Teijin Pharma Ltd.; and personal funding from the 38th Mihara Cerebrovascular Disorder Research Promotion Fund Ltd. Masataka Takeuchi received lecture fees from Stryker Co. Ltd. Shigeru Fujimoto received lecture fees from Nippon Boehringer Ingelheim Co. Ltd., Daiichi Sankyo Co. Ltd., Pfizer Japan Inc., Bristol-Myers Squibb Co. Ltd., Bayer Healthcare Co. Ltd., and Takeda Pharmaceutical Co. Ltd. Teruyuki Hirano received lecture fees from Bayer Healthcare Co. Ltd., Daiichi Sankyo Co. Ltd., Nippon Boehringer Ingelheim Co. Ltd., Bristol-Myers Squibb Co. Ltd., Medtronic Co. Ltd, Sanofi Co. Ltd. Otsuka Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., CSL Behring K.K., Astellas Pharma Inc., and Pfizer Japan Inc. Yasuhiro Nishiyama received lecture fees from Daiichi Sankyo Co. Ltd. Yasuyuki Iguchi received lecture fees from Bayer Healthcare Co. Ltd., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co. Ltd., Takeda Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co. Ltd., and Daiichi Sankyo Co. Ltd.; and research funding from Sanofi Co. Ltd. Yuki Kamiya received lecture fees from Daiichi Sankyo Co. Ltd.; and research funding from Bristol-Myers Squibb Co. Ltd. Yuji Matsumaru received lecture fees from Medtronic Co. Ltd, Stryker Co. Ltd, Sanofi Co. Ltd., Daiichi Sankyo Co. Ltd., Otsuka Pharmaceutical Co. Ltd., and Biomedical solutions., (Copyright © 2024. Published by Elsevier Inc.)

The recent progress with ruxolitinib treatment might improve quality of life as well as overall survival in patients with primary myelofibrosis. Therefore, the optimal timing of allogeneic hematopoietic cell transplantation (HCT) in the ruxolitinib era remains to be elucidated. We constructed a Markov model to simulate the 5-year clinical course of transplant candidates with primary myelofibrosis and compared outcomes between those who underwent immediate HCT and those whose HCT was delayed until after ruxolitinib failure. Since older age was associated with an increased risk of mortality, we analyzed patients aged <60 and ≥60 years separately in subgroup analyses. Life expectancy was consistently longer in the groups undergoing delayed HCT after ruxolitinib failure regardless of the patients' age. Regarding quality-adjusted life years, a baseline analysis showed that immediate HCT was inferior to delayed HCT after ruxolitinib failure (2.19 vs. 2.26). In patients aged <60 years, immediate HCT was equivalent to delayed HCT after ruxolitinib failure (2.31 vs. 2.31). On the other hand, in patients aged ≥60 years, immediate HCT was inferior to delayed HCT after ruxolitinib failure (1.98 vs. 2.21). A one-way sensitivity analysis showed that the utility of being alive without chronic graft-versus-host disease after immediate HCT was the most influential parameter for quality-adjusted life years, and that a value higher than 0.836 could reverse the superiority of delayed HCT after ruxolitinib failure. As a result, delayed HCT after ruxolitinib failure is expected to be superior to immediate HCT, especially in patients aged ≥60 years, and is also a promising strategy even in those aged <60 years.

Background Aims: Pre-transplant lung dysfunction is known to be a risk factor for non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT). It is unclear which cell source gives better outcomes for patients with pulmonary dysfunction., Methods: We analyzed 3289 adult patients with standard-risk disease who had received HLA-matched allo-HCT, and compared outcomes between those who received peripheral blood stem cell (PBSC) vs. bone marrow (BM) in two cohorts based on the presence of a lung score by the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI): the Lung-scored (LS) and non-LS cohorts., Results: In the LS cohort, the 2-year overall survival (OS) in the BM group tended to be higher than that in the PBSC group (72.4% vs. 61.4%; P = 0.044). In the non-LS cohort, there was no significant difference between the two groups (71.7% vs. 73.2%; P = 0.13). Multivariate analyses confirmed that PBSC was significantly associated with inferior OS in the LS cohort (hazard ratio [HR], 1.66; 95% CI, 1.09-2.54; P = 0.019). On the other hand, the cell source did not affect OS in the non-LS cohort (HR, 0.92; 95% CI, 0.76-1.12; P = 0.41). We found that PBSC was associated with an increased risk of NRM in the LS cohort (HR, 2.17; 95% CI, 1.16-4.05; P = 0.016), while the cell source did not significantly affect NRM in the non-LS cohort. PBSC was not identified as a risk factor for relapse in either cohort., Conclusions: Our results suggest that BM might be beneficial for recipients with lung dysfunction in HLA-matched allo-HCT., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary, or financial interest in the products or companies described in this article., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Autologous hematopoietic cell transplantation (AHCT) is a commonly used treatment in multiple myeloma (MM). However, real-world global demographic and outcome data are scarce. We collected data on baseline characteristics and outcomes from 61 725 patients with newly diagnosed MM who underwent upfront AHCT between 2013 and 2017 from nine national/international registries. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM). Median OS amounted to 90.2 months (95% CI 88.2-93.6) and median PFS 36.5 months (95% CI 36.1-37.0). At 24 months, cumulative RI was 33% (95% CI 32.5%-33.4%) and NRM was 2.5% (95% CI 2.3%-2.6%). In the multivariate analysis, superior outcomes were associated with younger age, IgG subtype, complete hematological response at auto-HCT, Karnofsky score of 100%, international staging scoring (ISS) stage 1, HCT-comorbidity index (CI) 0, standard cytogenetic risk, auto-HCT in recent years, and use of lenalidomide maintenance. There were differences in the baseline characteristics and outcomes between registries. While the NRM was 1%-3% at 12 months worldwide, the OS at 36 months was 69%-84%, RI at 12 months was 12%-24% and PFS at 36 months was 43%-63%. The variability in these outcomes is attributable to differences in patient and disease characteristics as well as the use of maintenance and macroeconomic factors. In conclusion, worldwide data indicate that AHCT in MM is a safe and effective therapy with an NRM of 1%-3% with considerable regional differences in OS, PFS, RI, and patient characteristics. Maintenance treatment post-AHCT had a beneficial effect on OS., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

Venetoclax was approved for relapsed/refractory chronic lymphocytic leukemia (R/R CLL) and small lymphocytic leukemia (SLL) in Japan in September 2019; however, clinical data in Japanese patients are limited. This all-case post-marketing surveillance assessed efficacy and safety in Japanese patients with R/R CLL/SLL who started venetoclax treatment between November 2019 and August 2020. Overall, the safety and efficacy analysis sets included 129 and 114 patients, respectively. The overall response rate (ORR) was 57.0%; ORRs were higher in patients with versus without concomitant rituximab (65.4% vs. 54.7%), and in patients with 1 versus ≥ 2 prior lines of therapies (72.5% vs. 44.4%). Adverse events (AEs) were reported in 66.7% of patients (86/129); the most common AEs were neutrophil count decreased (22.5%), white blood cell count decreased (7.8%), and tumor lysis syndrome (TLS; 6.2%). AEs of special interest (TLS, myelosuppression, and infection) were manageable in clinical practice in Japan. Venetoclax is efficacious and safe for R/R CLL/SLL patients in the real-world setting in Japan. ClinicalTrials.gov ID: NCT04198415., (© 2024. The Author(s).)

Objectives: Distal anterior cerebral artery (DACA) aneurysms account for 1%-9% of all intracranial aneurysms. Microsurgical treatment is generally preferred for DACA aneurysms; however, it presents challenges owing to the anatomical complexities. Advances in neuro-interventional techniques have yielded promising results. This study aims to compare the clinical outcomes of DACA aneurysms treated with microsurgery and endovascular treatment (EVT) to elucidate the efficacy of EVT., Materials and Methods: A multicenter observational registry comprising 16 stroke centers was utilized for this study. Data was retrospectively and prospectively analyzed from 166 patients with DACA aneurysms in our database, which included 4,552 consecutive patients with ruptured or unruptured intracranial aneurysms who underwent microsurgical or endovascular treatment between January 2013 and December 2021., Results: Surgical clipping was performed in 115 patients, and 51 underwent coil embolization. The median follow-up duration was 15.3 months. No significant differences were observed in patient characteristics between the two treatment modalities. There were no differences in complication-related morbidity between the microsurgical treatment and EVT groups in either unruptured (10.5% vs. 9.1%, p=1.00) or ruptured aneurysms (5.2% vs. 6.9%, p=0.66). Coil embolization resulted in higher recurrence and retreatment rates than surgical clipping did, especially for ruptured aneurysms (2.6% vs. 27.6%, p<0.01)., Conclusions: Endovascular treatment is an alternative to microsurgery for DACA aneurysms especially in unruptured cases or the patients who have difficulty undergoing craniotomy due to their general condition, albeit with considerations for higher recurrence and retreatment rates, particularly in ruptured cases. Close follow-up is crucial for the effective management of these challenges. Further studies are needed to refine the treatment strategies for DACA aneurysms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Study Design: This was a multicenter retrospective cohort study., Objective: We investigated the incidence of postoperative shoulder imbalance (PSI) and its risk factors in patients with Lenke types 1 and 2 scoliosis corrected using vertebral coplanar alignment (VCA)., Summary of Background Data: PSI in scoliosis affects patient quality of life. While other correction methods have reported a high correction rate for the main thoracic curve (MTC) in relation to PSI, this correlation has not been confirmed for the VCA technique., Methods: We studied 176 patients with Lenke types 1 and 2 scoliosis who underwent posterior corrective fusion surgery using the VCA technique at 11 institutions. At two years postoperatively, patients were divided into two groups based on radiographic shoulder height (RSH): PSI- (RSH<2 cm) and PSI+ (RSH≧2 cm) groups. We analyzed the risk factors for PSI., Results: The overall incidence of PSI two years postoperatively was 11.4% (20/176), with 9.2% (11/119) and 15.8% (9/57) in patients with Lenke types 1 and 2, respectively. Contrary to a previous study, a high MTC correction rate did not emerge as a risk factor for PSI. Instead, preoperative left shoulder elevation and low postoperative thoracic kyphosis and greater T1 tilt and high apical vertebral body-to-rib ratio were associated with PSI in patients with Lenke type 1. Preoperative left shoulder elevation and a low postoperative proximal thoracic curve (PTC) correction rate were identified as risk factors for PSI in patients with Lenke type 2., Conclusion: Our results suggest that proper correction of the PTC, rather than compromise MTC correction, may help prevent PSI in the VCA technique. This method is particularly advantageous for addressing Lenke type 1 scoliosis and yields favorable outcomes in shoulder balance. Patients with preoperative left shoulder elevation, especially Lenke type 2, are at high risk of developing PSI., Level of Evidence: 4., Competing Interests: No conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Traditionally, ultrasound skills have been taught through a one-on-one approach, where instructors physically guide learners' hands at the bedside or in the workshop. However, this method is frequently challenged by scheduling and cost limitations. Our objective was to create a tele-education model for point-of-care ultrasound training and evaluate its effectiveness and its impact on learners' perceived workload compared to conventional education and self-directed learning methods., Methods: We conducted a 3-arm randomized trial, comparing tele-education (TE), conventional education (CE) and self-directed learning (SL) methods. All subjects underwent online didactic lectures prior to a hands-on ultrasound workshop. The TE group utilized an ultrasound machine equipped with a speakerphone, a webcam for direct visualization of learner's hand maneuvers, and an analog-to-video converter for the real-time streaming of ultrasound images. This configuration enabled remote instructors to provide immediate verbal feedback to learners. In contrast, the CE group received in-person coaching, while the SL group had no instructors present. Following the coaching session, subjects completed a scenario-based skill test and a survey on the National Aeronautics and Space Administration task load index (NASA-TLX) to measure their ultrasound competency and perceived workload, respectively., Results: Twenty-seven ultrasound novices were randomly allocated into 3 groups. The median skill test score of TE, CE, and SL was 22 [interquartile range (IQR): 18-28], 24 [IQR: 21-31], and 16 [IQR: 15-18], respectively (p < 0.01). Pairwise comparisons of median test scores of 3 groups demonstrated a statistical significance in comparisons of TE vs. SL (22 vs. 16, p = 0.01) and CE vs. SL (24 vs. 16, p < 0.01), but not in TE vs. CE (22 vs. 24, p = 0.56). There was no statistical significance observed in the median NASA-TLX scores among the 3 groups; 54 [IQR:47-61] in TE, 57 [IQR:22-64] in CE, and 66 [IQR: 66-72] in SL (p = 0.05)., Conclusions: Our tele-education model was more effective than self-directed learning. There was no statistically significant difference in effectiveness between the tele-education and the conventional education groups. Importantly, tele-education did not impose a significantly higher workload on learners compared to conventional education or self-directed learning. Tele-education has a substantial potential as an alternative to conventional ultrasound training., (© 2024. The Author(s).)

HLA-haploidentical haematopoietic cell transplantation with post-transplant cyclophosphamide (PTCy-haplo) is emerging as an effective alternative due to donor availability and safety. We conducted a nationwide retrospective study comparing the outcomes of PTCy-haplo with both anti-thymocyte globulin (ATG)-free and ATG-administered matched unrelated donors (MUD) transplantation, using peripheral blood stem cells as the first transplantation for acute myeloid leukaemia (AML). Our study showed a lower and slower haematopoietic recovery and a higher incidence of infection-related deaths after PTCy-haplo than after MUD transplantation. In addition, we revealed an increased risk of acute and chronic graft-versus-host disease (GVHD) in ATG-free MUD transplantation in comparison to PTCy-haplo. For grades III-IV acute GVHD, the hazard ratio (HR) was 2.71 (95% CI, 1.46-5.01), and for extensive chronic GVHD, the HR was 3.11 (95% CI, 2.07-4.68). There was no significant difference regarding overall survival amongst the groups. In addition, GVHD-free relapse-free survival (GRFS) was lower in ATG-free MUD transplantation than in PTCy-haplo (HR, 1.46; 95% CI, 1.17-1.82). Notably, ATG-administered MUD transplantation showed no significant difference in GRFS from PTCy-haplo, negating the advantage of PTCy. Our results suggest that PTCy-haplo could be viable for AML patients without an HLA-matched related donor., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Retropharyngeal goitre extending to the oropharyngeal level is rare. We present a case of papillary thyroid carcinoma (PTC) with a retropharyngeal cystic goitre extending to the uvular level. A woman in her 50s presented with swelling of the neck and dyspnoea. CT and MRI findings showed a primary tumour in the left lobe of the thyroid gland and a retropharyngeal dumbbell-shaped cystic goitre extending to the uvular level. Total thyroidectomy, central neck dissection and tracheostomy were performed. During the surgery, we opened the retropharyngeal space, and no mass was found. The pathological findings showed that the primary PTC (pT2) was surrounded by benign lesions, including the dumbbell-shaped cystic goitre. We speculated that the dumbbell-shaped cystic goitre extended from the visceral space (VS) into the pharyngeal mucosal space (PMS) and reached the uvular level because the thyroid gland is in the VS, and the VS and PMS are continuous spaces., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Endovascular abdominal aortic repair (EVAR) has a significantly higher revision rate than open repair, primarily due to type 2 endoleak (2EL). Although 2ELs are considered benign, late open conversion (LOC) due to the expansion of the aneurysm diameter of the 2EL is a concern in the mid- and long-term. In this study, we investigated the impact of embolization of the inferior mesenteric artery (IMA) or lumbar artery (LA) at the time of the initial EVAR and its long-term outcomes., Methods: Between April 2008 and December 2021, 743 EVAR procedures for abdominal aortic aneurysms were performed at our institution. The patients were divided into 2 groups at the time of initial surgery, namely, 215 and 528 patients in the embolization (Group E) and nonembolization (Group N) groups, respectively. Branch embolization was performed in patients with an IMA diameter ≥3 mm and LA diameter ≥2 mm on preoperative computed tomography. Re-embolization with EL was performed in patients with a diameter enlargement ≥10 mm, and LOC was performed in patients with continued enlargement ≥15 mm after re-embolization. The mean follow-up period was 7.0 years., Results: The mean number of branch embolizations was 2.3 ± 1.1. Intraoperatively, the operative time, fluoroscopy time, irradiation dose, and contrast medium use were significantly higher in Group E than in Group N. There was a significant difference between the 2 groups regarding shrinkage (Group E versus Group N: 45.6% versus 37.3%; P = 0.03) and enlargement (Group E versus Group N: 9.3% vs. 19.5%; P < 0.001) of the aneurysm diameter by > 5 mm after EVAR. In the mid- and long-term, the avoidance rate of 2EL reintervention was significantly lower in Group E at 5 years (93.5% vs. 88.6%) and 10 years (87.5% vs. 76.4%; P = 0.04). LOC prevention was 5 years; Group E: 100% vs. 96.9% for Group N and 10 years; Group E: 98.8% vs. 92.5% for Group N, significantly lower in Group E (P = 0.02)., Conclusions: The impact of branch embolization at the time of the initial EVAR is believed to prevent enlargement of the aneurysmal sac and LOC. However, prolonged operation time, increased radiation exposure, and the use of contrast medium have been debated. To improve the long-term results of EVAR, embolisms of both the IMA and LA are required., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Proteinuria selectivity index (PSI) is a potential tool for histological classification and prediction of treatment response in nephrotic syndrome, but evidence is insufficient. Clinical relevance of fractional excretion of sodium (FENa) in nephrotic syndrome remains largely unexplored. This multicenter retrospective study included patients with nephrotic syndrome who underwent kidney biopsy between January 2012 and June 2022. Optimal cutoffs for predicting complete remission based on PSI and FENa were determined using receiver operating characteristic curves. Patients were divided into two groups using these cutoffs and followed until complete remission. Of the 611 patients included, 177 had minimal change disease (MCD), 52 had focal segmental glomerulosclerosis (FSGS), and 149 had membranous nephropathy (MN). Median (interquartile range) PSI were 0.14 (0.09-0.19) for MCD, 0.33 (0.23-0.40) for FSGS, and 0.20 (0.14-0.30) for MN. FENa were 0.24 (0.09-0.68), 1.03 (0.50-2.14), and 0.78 (0.41-1.28). Patients with low PSI and FENa had a higher incidence of complete remission. Cox regression analyses demonstrated that both parameters were associated with achieving complete remission (HR 2.73 [95% CI 1.97-3.81] and HR 1.93 [95% CI 1.46-2.55], respectively). PSI and FENa may be useful for histological classification and predicting remission in nephrotic syndrome., (© 2024. The Author(s).)

Objectives: To advance robotic radical prostatectomy, we developed a novel anterior approach that uses a peritoneal incision created between the umbilical ligaments to develop the Retzius space and thus spares vessels that surround the bladder and prostate, with the space being closed after prostatectomy and vesicourethral anastomosis. This approach may improve continence recovery. We investigated continence recovery following the novel anterior approach compared to after the conventional anterior approach., Methods: We retrospectively reviewed 516 patients who underwent robotic radical prostatectomy from January 2019 to July 2023. We compared continence recovery following our novel anterior approach (N = 282) to that after conventional anterior approach (N = 234), and we compared the oncological outcomes and safety profiles of the two groups., Results: Patient demographics did not differ significantly between the two groups. Continence recovery in patients undergoing the novel anterior approach was significantly better than that of patients treated via the conventional approach (hazard ratio: 1.651, 95% confidence interval: 1.325-2.057, p < 0.0001). Use of the novel anterior approach in addition to nerve sparing and preservation of the detrusor apron independently predicted continence, and the mixture of these three techniques afforded excellent continence recovery (1- and 2-year total continence rate of 81.1% and 93.7%). Neither the biochemical recurrence-free survival nor the complication rate differed significantly between the two groups., Conclusion: Our novel anterior approach may improve continence recovery compared to the conventional anterior approach, without compromising the oncological outcomes. Prospective comparative studies are necessary to confirm the benefits of this approach., (© 2024 The Japanese Urological Association.)

The fludarabine/intravenous busulfan 12.8 mg/kg (FB4) regimen is an effective conditioning regimen in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome (MDS); however, limited data is available on the prognostic impact of FB4 with low-dose anti-thymoglobulin (ATG ≤ 5 mg/kg) or low-dose total body irradiation (TBI ≤ 4 Gy). Therefore, we retrospectively evaluated the outcomes in 280 adults with de novo MDS who underwent their first transplantation from an unrelated donor between 2009 and 2018. Median age was 61 years (range, 16 to 70 years). In the FB4 alone (FB4), FB4 plus ATG (FB4-ATG), and FB4 plus TBI (FB4-TBI) groups, 3-years overall survival (OS) rates were 39.9%, 64.8%, and 43.7%; 3-years nonrelapse mortality (NRM) were 32.1%, 22.1%, and 27.1%; and 3-years relapse incidences were 34.7%, 21.2%, and 28.9%, respectively. The multivariate analyses showed that FB4-ATG group significantly correlated with better OS (hazard Ratio [HR], 0.51; 95% confidence interval [CI], 0.27 to 0.95; P = .032) than FB4 group. FB4-ATG group tended to correlate with lower NRM (HR, 0.36; 95% CI, 0.13 to 1.06; P = .063) than FB4 group. In comparison with FB4-TBI group, FB4-ATG group showed better OS (HR 0.52, 95% CI 0.27 to 0.99, P = .049) and NRM (HR 0.034, 95% CI 0.11 to 0.92, P = .034). No significant differences were observed in OS and NRM between the FB4-TBI and FB4 groups. The present study demonstrated that the FB4 plus low-dose ATG regimen improved OS and NRM, but FB4 plus low-dose TBI regimen had no clear benefit over FB4 alone, in MDS patients who used unrelated donors., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Allogeneic hematopoietic stem cell transplantation from a female donor to a male recipient (female-to-male allo-HCT) is a well-established risk factor for chronic graft-versus-host disease (GVHD) and non-relapse mortality (NRM). The inferior outcomes of female-to-male allo-HCT are considered to be due to allo-immunity against H-Y antigens. However, the influence of minor histocompatibility antigens in haplo-identical allo-HCT remains to be elucidated. We investigated the impact of female-to-male allo-HCT according to the haplo-HCT subtype. In the post-transplant cyclophosphamide (PTCY) cohort (n = 660), a female-to-male sex-mismatch was significantly associated with a decreased risk of relapse (HR: 0.70 [95% CI: 0.49-0.99], P = 0.045), but not with overall survival (OS) or NRM (HR: OS 0.89 [95% CI: 0.68-1.16], P = 0.40; NRM 0.98 [95% CI: 0.68-1.41], P = 0.90). On the other hand, in the non-PTCY cohort (n = 219), a female-to-male sex-mismatch was associated with inferior risks of OS and NRM, but was not associated with relapse. These results suggested that the survival impact of the haplo-HCT subtype differed according to the presence of a sex-mismatch. PTCY might be feasible for overcoming the inferiority of female-to-male allo-HCT and might preserve a GVL effect against H-Y antigens., Competing Interests: Declaration of competing interest M.Tamaki received honoraria from Astella Pharma. H.Nakasone. received subsidies from JCR Pharmaceuticals, Kyowa Kirin, Terumo, Santen Pharmaceutical, Taiho Pharma, and honoraria from Takeda Pharmaceutical, Otsuka Pharmaceutical, Bristol-Myers Squibb, Pfizer, Novartis, Janssen Pharmaceutical, Eisai, Chugai Pharmaceutical, Meiji Seika Pharma, and Nippon Shinyaku., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Despite advances in techniques for olfactory neuroblastoma (ONB), such as unilateral cranial resection, preserving the patient’s sense of smell remains a challenge. This study aimed to examine the effectiveness of post-operative olfactory training in patients who underwent unilateral resection of ONB., Methods: This retrospective cohort study assessed the effect of post-operative olfactory training on olfactory preservation in patients with ONB undergoing unilateral cranial resection. Patients were divided into training intervention (n = 5) and non-intervention (n = 6) groups. Olfactory tests were conducted pre-operatively and at multiple post-operative intervals., Results: Partial olfactory function was preserved in all cases in the training intervention group, whereas only 17% of cases in the non-intervention group maintained partial olfactory function. Significant improvements in olfactory test scores were observed in the training intervention group compared with the non-intervention group., Conclusions: Our findings suggest that post-operative olfactory training could aid in olfactory preservation for patients with ONB after unilateral cranial resection. However, these results should be interpreted with caution, and further research with larger cohorts and extended follow-up periods is needed to confirm these observations.

The number of very elderly patients with acute coronary syndrome (ACS) is increasing. Therefore, owing to the need for evidence-based treatment decisions in this population, this study aimed to examine the clinical outcomes during 1 year after percutaneous coronary intervention (PCI) in very elderly patients with ACS. This prospective multicenter observational study comprised 1337 patients with ACS treated with PCI, classified into the following four groups according to age: under 60, <60 years; sexagenarian, ≥60 and <69 years; septuagenarian, ≥70 and <80 years; and very elderly, ≥80 years. The primary endpoint was a composite of the first occurrence of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and bleeding within 1 year after PCI. We used the sexagenarian group as a reference and compared outcomes with those of the other groups. The incidence of the primary endpoint was significantly higher in the very elderly group than in the sexagenarian group (36 [12.7%] vs. 24 [6.9%], respectively; hazard ratio, 1.94; 95% confidence interval: 1.16-3.26; p = 0.012). The higher incidence of the primary endpoint was primarily driven by a higher incidence of all-cause death. When the multivariable analysis was used to adjust for patient characteristics and comorbidities, no difference was observed in the primary endpoint between the very elderly and sexagenarian groups (p = 0.96). The incidence of adverse events after PCI, particularly all-cause death, in very elderly patients with ACS was high. However, if several confounders are adjusted, comparable outcomes may be expected within 1 year after PCI among this population., (© 2024. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Purpose: Given that left upper lobe and right upper and middle lobes share a similar anatomy, segmentectomy, such as upper division and lingulectomy, should yield identical oncological clearance to left upper lobectomy. We compared the prognosis of segmentectomy with that of lobectomy for early stage non-small-cell lung cancer (NSCLC) in the left upper lobe., Methods: We retrospectively examined 2115 patients who underwent segmentectomy or lobectomy for c-stage I (TNM 8th edition) NSCLC in the left upper lobe in 2010. We compared the oncological outcomes of segmentectomy (n = 483) and lobectomy (n = 483) using a propensity score matching analysis., Results: The 5-year recurrence-free and overall survival rates in the segmentectomy and lobectomy groups were comparable, irrespective of c-stage IA or IB. Subset analyses according to radiological tumor findings showed that segmentectomy yielded oncological outcomes comparable to those of lobectomy for non-pure solid tumors. In cases where the solid tumor exceeded 20 mm, segmentectomy showed a recurrence-free survival inferior to that of lobectomy (p = 0.028), despite an equivalent overall survival (p = 0.38)., Conclusion: Segmentectomy may be an acceptable alternative to lobectomy with regard to the overall survival of patients with c-stage I NSCLC in the left upper lobe., (© 2024. The Author(s).)

Introduction: To verify the value of the pathological criteria for additional treatment in locally resected pT1 colorectal carcinoma (CRC) which have been used in the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines since 2009., Methods: We enrolled 4,667 patients with pT1 CRC treated at 27 institutions between July 2009 and December 2016 (1,257 patients with local resection alone [group A], 1,512 patients with additional surgery after local resection [group B], and 1,898 patients with surgery alone [group C]). All 5 factors of the JSCCR guidelines (submucosal resection margin, tumor histologic grade, submucosal invasion depth, lymphovascular invasion, and tumor budding) for lymph node metastasis (LNM) had been diagnosed prospectively., Results: Any of the risk factors were present in 3,751 patients. The LNM incidence was 10.4% (95% confidence interval 9.4-11.5) in group B/C patients with risk factors, whereas it was 1.8% (95% confidence interval 0.4-5.3) in those without risk factors ( P < 0.01). In group A, the incidence of recurrence was 3.6% in patients with risk factors, but it was only 0.4% in patients without risk factors ( P < 0.01). The disease-free survival rate of group A patients classified as risk positive was significantly worse than those of groups B and C patients. However, the 5-year disease-free survival rate in group A patients with no risk was 99.6%., Discussion: Our large-scale real-world multicenter study demonstrated the validity of the JSCCR criteria for pT1 CRC after local resection, especially regarding favorable outcomes in patients with low risk of LNM., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Systemic corticosteroid therapy is a well-established first-line treatment for grades II-IV acute graft-versus-host disease (aGVHD). Recently, several developments have occurred, including the introduction of transplantation from human leukocyte antigen (HLA) haploidentical donors using post-transplant cyclophosphamide (PTCY-Haplo), and improvements in prognosis after cord blood transplantation (CBT) in Japan. This study aimed to analyze the association between donor sources and outcomes in patients with aGVHD. Our study included 2732 patients who developed grades II-IV aGVHD, and were treated with systemic corticosteroids. We compared HLA-matched related donors (MRD), HLA-matched unrelated donors (MUD), PTCY-Haplo, and CBT. We set endpoint as response rate, 1-year cumulative incidence of non-relapse mortality (NRM), and overall survival (OS). The adjusted odds ratios for a complete response (CR) were 0.99 (95% confidence interval [CI]: 0.74-1.31, P = 0.925) for MUD, 2.08 (95% CI: 1.35-3.25, P = 0.001) for PTCY-Haplo, and 1.08 (95% CI: 0.83-1.41, P = 0.550) for CBT compared with MRD. A significant increase in response rates for PTCY were only found in a single-organ involvement. No significant association was observed between the donor source and NRM or OS. In conclusion, PTCY-Haplo is associated with a high response rate in patients with a single-organ aGVHD; however, MUD and CBT were not associated with treatment response., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Adult T-cell leukemia/lymphoma (ATL) develops from the infection of T cells with human T lymphotropic virus type 1 (HTLV-1). There are an estimated 5-20 million HTLV-1 carriers worldwide and the patients are frequently observed in subtropical Africa, the Caribbean, Middle East, South America, and South West Japan. The prognosis of ATL remains dismal due to rapid acquired resistance to treatment with cytotoxic chemotherapeutic agents. In particular, the development of novel therapies for relapsed or refractory (R/R) ATL is an unmet need. Previous clinical trials revealed that bendamustine (BDM) was effective as the first-line treatment for indolent lymphoma and R/R cases of diffuse large B-cell lymphoma. Its major advantage is that it has few side effects such as hair loss and peripheral neuropathy, and does not impair the quality of life. However, its efficacy has not been verified for ATL in pre-clinical or clinical studies. In this study, we have shown the cytotoxicity of BDM alone and in combination with novel agents including the histone deacetylase (HDAC) inhibitor tucidinostat, the enhancer of zeste homolog 1/2 (EZH1/2) dual inhibitor valemetostat, and the Bcl2 family inhibitor ABT-737. The combined in vitro effects of BDM and tucidinostat were reproduced in a murine model without any obvious hematological toxicity. Our present results suggest that the combination of tucidinostat and BDM could additively prolong the survival of patients with R/R progressive ATL. The efficacy and safety of this combination are thus worthy of investigation in clinical settings., Competing Interests: Yusuke Furukawa received research funding from SymBio Pharmaceuticals Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Other authors have no conflict of interest., (Copyright: © 2024 Osada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: The PEComa family of tumours is defined by spindle/epithelioid cells with myomelanocytic differentiation. A small subset harbours TFE3 fusion; however, YAP1::TEE3 has not been reported. Clear cell stromal tumour of the lung (CCST-L) is an emerging entity characterized by spindle to epithelioid cells with focal cytoplasmic clearing, inflammatory infiltrates, no myomelanocytic differentiation, and YAP1::TFE3 fusion. Herein, we report two cases of lung tumours with myomelanocytic differentiation that showed inflammatory spindle cell histology, focal epithelioid clear cells, as well as YAP1::TFE3 fusion., Methods and Results: The patients were both men, aged 61 and 68 years. The tumours in both cases presented as well-circumscribed solid masses involving the lung hilum. After lobectomy, no recurrence was observed at 7 and 32 months. Both tumours shared storiform to short fascicular growth of long spindle cells, with a minor component of epithelioid cells showing clear cytoplasm in the background of substantial intratumoral chronic inflammation and dilated blood vessels. One tumour showed focal melanin deposition. Both tumours were immunohistochemically positive for HMB45, Melan A, and h-caldesmon. Fluorescence in situ hybridization assays indicated the presence of YAP1::TFE3 fusions, which was confirmed by RNA sequencing in one case tested, and by immunohistochemical TFE3 expression and loss of YAP1 C-terminus staining., Conclusion: We present two cases of inflammatory spindle to epithelioid cell tumours of the lungs with myomelanocytic differentiation and YAP1::TFE3 fusion. This unique morphology and gene fusion suggest that these tumours may constitute a distinct subset of lung PEComa. Furthermore, morphological and molecular overlap with CCST-L gives rise to a hypothesis of a potential inherent relationship between PEComa and CCST-L., (© 2024 John Wiley & Sons Ltd.)

Rationale: Thromboembolism is a serious complication of endovascular treatment for ruptured cerebral aneurysms. The administration of antiplatelet agents before endovascular treatment for ruptured cerebral aneurysms may reduce the risk of thromboembolic complications., Aim: This study aimed to assess the safety and efficacy of preoperative aspirin administration in endovascular treatment for ruptured cerebral aneurysms., Sample Size Estimates: Assuming a 15% incidence rate of both intraoperative thromboembolic morbidity and symptomatic ischemic lesions on magnetic resonance imaging diffusion-weighted imaging scans assessed by an Independent Review Committee, a sample size of 484 will be required to detect a 10% improvement with aspirin administration with 90% power using the Pearson's chi-square test at a two-sided significance level of 2.5% for each primary outcome, after accounting for a 5% dropout rate., Methods and Design: ASTOP is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 484 patients with ruptured cerebral aneurysms receiving coil embolization within 72 h of onset will be randomly assigned 1:1 to receive 200 mg of aspirin or placebo before the procedure., Study Outcomes: The primary outcomes will be the incidence rates of intraoperative thromboembolic complications and symptomatic ischemic lesions on magnetic resonance imaging diffusion-weighted imaging scans evaluated by the Independent Review Committee. The secondary outcomes will be the incidence rate of cerebral ischemic events and all bleeding events within 14 days of enrollment and functional outcomes defined by the modified Rankin Scale score at 90 days., Discussion: This trial will provide valuable data on the role of antiplatelet agents during endovascular treatment for ruptured cerebral aneurysms., Trial Registration: Registration: Japan Registry of Clinical Trials, Identifier: jRCTs031210421., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hirai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for relapsed or refractory non-Hodgkin lymphoma (R/R NHL). Allo-HSCT using post-transplant cyclophosphamide (PTCY-haplo) and umbilical cord blood transplantation (uCBT) are important donor options in the absence of matched related siblings. However, the data comparing these two donor sources in R/R NHL are limited. Using the Japanese nationwide transplantation registry data, we identified 857 patients with R/R NHL, including 169 patients who received PTCY-haplo and 688 who received uCBT for their first allo-HSCT between January 2013 and December 2021; 514 patients (60%) had B-cell lymphoma. More PTCY-haplo recipients received allo-HSCT using a reduced-intensity conditioning regimen in recent years. The 3-year overall survival (OS), progression-free survival (PFS), and graft-versus-host disease (GVHD)-free/relapse-free survival (GRFS) rates in the PTCY-haplo and uCBT groups were 44% versus 39% (P = 0.326), 34% versus 33% (P = 0.660), and 19% versus 23% (P = 0.910), respectively; the adjusted hazard ratios for OS, PFS, and GRFS were 0.89 (95% confidence interval: 0.69-1.15, P = 0.373), 0.98 (0.78-1.22, P = 0.852), and 0.92 (0.83-1.21, P = 0.920), respectively. The PTCY-haplo group showed faster neutrophil and platelet engraftment and a lower incidence of grade III-IV acute GVHD. Thus, PTCY-haplo and uCBT could serve as alternative donor sources in patients with R/R NHL., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Reported postoperative complications of mediastinal goitre include recurrent laryngeal nerve palsy, hypoparathyroidism and tracheomalacia. Voice and swallowing symptoms after thyroid surgery have been associated with laryngopharyngeal reflux, but it is unclear whether the retrograde flow of gastric contents into the oesophagus, larynx and pharynx worsens after thyroid surgery. We present the case of a man in his 40s with gastro-oesophageal reflux disease (GERD) who developed heartburn and laryngeal granuloma after total thyroidectomy for mediastinal goitre. Vonoprazan therapy effectively controlled these symptoms. Although the exact cause remains unclear, we suggest that changes in pressure dynamics after thyroidectomy may worsen the retrograde flow of gastric contents into the oesophagus, larynx and pharynx, contributing to GERD symptoms and laryngeal granuloma. This case highlights the need to consider the management of retrograde flow of gastric contents into the oesophagus, larynx and pharynx in the postoperative care of mediastinal goitre resections., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Japanese Society of Hypertension have established a blood pressure (BP) target of 130/80 mmHg for patients with coronary artery disease (CAD). We evaluated the data of 8793 CAD patients in the Clinical Deep Data Accumulation System database who underwent cardiac catheterization at six university hospitals and the National Cerebral and Cardiovascular Center (average age 70 ± 11 years, 78% male, 43% with acute coronary syndrome [ACS]). Patients were divided into two groups based on whether or not they achieved the guideline-recommended BP of <130/80 mmHg. We analyzed the relationship between BP classification and major adverse cardiac and cerebral event (MACCE) separately in two groups: those with ACS and those with chronic coronary syndrome (CCS). During an average follow-up period of 33 months, 710 MACCEs occurred. A BP below 130/80 mmHg was associated with fewer MACCEs in both the overall (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.70-1.00, p = 0.048) and the ACS group (HR 0.67, 95%CI 0.51-0.88, p = 0.003). In particular, stroke events were also lower among those with a BP below 130/80 mmHg in both the overall (HR 0.69, 95%CI 0.53-0.90, p = 0.006) and ACS groups (HR 0.44, 95%CI 0.30-0.67, p < 0.001). In conclusion, the achievement of BP guidelines was associated with improved outcomes in CAD patients, particularly in reducing stroke risk among those with ACS., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Competing Interests: Conflicts of interest The authors declare no conflicts of interest.

Aim: This study aimed to assess the impact of a physician-led intervention on advance care planning (ACP) introduction among older outpatients using a model discussion video., Methods: This prospective interventional study included Japanese general practice outpatients aged ≥65 years. All participants received an ACP leaflet. Co-researchers were trained using a model discussion video based on the "Serious Illness Conversation Guide," and provided ACP introduction explanations to the intervention group to ensure intervention content consistency. The control group received the ACP leaflet only, with no standardized explanations. The primary outcome was ACP discussion occurrence. Secondary outcomes included ACP engagement (assessed through the 4-item ACP Engagement Survey), engagement score for advance directives acquisition and score for surrogate decision-maker identification, and anxiety incidence (assessed through Generalized Anxiety Disorder-7)., Results: This study included 48 participants: 25 (52.1%) in the intervention group and 23 (47.9%) in the control group. Regarding primary outcome, the intervention group had significantly more ACP discussions compared with the control group (92.0% vs 26.1%, adjusted odds ratio 50.2, P = 0.0012). Regarding secondary outcomes, the intervention group showed greater readiness (mean scores for the 4-item Engagement Survey [P = 0.0001], engagement score for advance directives acquisition [P = 0.01] and score for surrogate decision-maker determination [P = 0.03]) than the control group, without increasing anxiety., Conclusions: This physician-led ACP introduction for older patients in a Japanese general practice setting enhanced ACP readiness and stimulated discussions, without increasing anxiety. The model discussion video for ACP introduction might effectively train physicians in general practice settings. Geriatr Gerontol Int 2024; 24: 859-866., (© 2024 Japan Geriatrics Society.)

The impact of letermovir (LTV)-an anti-cytomegalovirus (CMV) drug-on human herpesvirus-6 (HHV-6) encephalitis is unclear. We hypothesized that LTV prophylaxis may increase the incidence of HHV-6 encephalitis by reducing anti-CMV therapies after allogeneic hematopoietic stem cell transplantation (HSCT). To evaluate the association between HHV-6 encephalitis and antiviral prophylaxis, 7985 adult patients from a nationwide registry who underwent their first HSCT between January 2019 and December 2021 were analyzed. The incidence of HHV-6 encephalitis on day 100 after HSCT was 3.6%; 11.5% for the broad-spectrum antiviral group (foscarnet, ganciclovir, or valganciclovir); 2.8% for the LTV group, and 3.8% for the other antiviral group (p < 0.001). These differences persisted when cord blood transplantation (CBT) was analyzed separately (14.1%, 5.9%, and 7.4%, p < 0.001). In the multivariate analysis, CBT (hazard ratio [HR]: 2.90), broad-spectrum antiviral prophylaxis (HR: 1.91), and grade II-IV acute graft-versus-host disease requiring systemic corticosteroids (HR: 2.42) were independent risk factors for encephalitis (all p < 0.001). The findings of this large modern database study indicate that broad-spectrum antiviral prophylaxis, rather than LTV prophylaxis, is paradoxically associated with HHV-6 encephalitis in the LTV era. This paradoxical finding needs to be further explored in future studies., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Purpose: The ryanodine receptor 2 (RyR2) is present in both the heart and kidneys, and plays a crucial role in maintaining intracellular Ca 2+ homeostasis in cells in these organs. This study aimed to investigate the impact of M201-A on RyR2, as well as studying its effects on cardiac and renal functions in preclinical and clinical studies., Experimental Approach: Following the administration of M201-A (1,4-benzothiazepine-1-oxide derivative), we monitored diastolic Ca 2+ leak via RyR2 and intracellular Ca 2+ concentration in isolated rat cardiomyocytes and in cardiac and renal function in animals. In a clinical study, M201-A was administered intravenously at doses of 0.2 and 0.4 mg·kg -1 once daily for 20 min for four consecutive days in healthy males, with the assessment of haemodynamic responses., Key Results: In rat heart cells, M201-A effectively inhibited spontaneous diastolic Ca 2+ leakage through RyR2 and exhibited positive lusi-inotropic effects on the rat heart. Additionally, it enhanced natriuresis and improved renal function in dogs. In human clinical studies, when administered intravenously, M201-A demonstrated an increase in natriuresis, glomerular filtration rate and creatinine clearance, while maintaining acceptable levels of drug safety and tolerability., Conclusions and Implications: The novel drug M201-A inhibited diastolic Ca 2+ leak via RyR2, improved cardiac lusi-inotropic effects in rats, and enhanced natriuresis and renal function in humans. These findings suggest that this drug may offer a potential new treatment option for chronic kidney disease and heart failure., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Reduced-intensity conditioning regimens are commonly used in allogeneic haematopoietic cell transplantation for non-Hodgkin lymphoma (NHL); however, the optimal regimen remains unknown. In this study, the outcomes of adult patients with NHL who received fludarabine plus reduced-dose busulfan (6.4 mg/kg; Flu/Bu2) (n = 286) and fludarabine plus low-dose melphalan (80 or 100 mg/m 2 ; Flu/Mel80-100) (n = 283) between January 2009 and December 2020 were compared using Japanese registry data. The primary end-point was the 5-year overall survival (OS). The 5-year OS was 53.8% (95% CI, 47.6-59.6) and 42.4% (95% CI, 35.6-49.0) in the Flu/Bu2 and Flu/Mel80-100 groups respectively (p = 0.030). After inverse probability of treatment weighting adjustment, the adjusted HR of Flu/Bu2 compared with Flu/Mel80-100 group for 5-year OS was 0.77 (95% CI, 0.60-0.99, p = 0.046), 0.97 (95% CI, 0.78-1.21, p = 0.798) for 5-year progression-free survival, 0.65 (95% CI, 0.45-0.94, p = 0.022) for 5-year cumulative risk of non-relapse mortality and 1.25 (95% CI, 0.95-1.64, p = 0.115) for 5-year cumulative risk of relapse. In this study, patients with NHL who received Flu/Bu2 were associated with better OS and lower non-relapse mortality than those who received Flu/Mel80-100., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

To investigate the safety of total body irradiation-based myeloablative conditioning (TBI-MAC) in adolescent and young adult (AYA) Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) patients treated with pediatric protocols, treatment outcomes of 106 AYA patients aged 16-39 years old undergoing allogeneic stem cell transplant (allo-SCT) with TBI-MAC in the first remission were compared according to chemotherapy types before transplant. Pediatric and adult protocols were used in 56 and 50 of the patients, respectively. The cumulative incidence (CI) of non-relapse mortality (NRM) and the overall survival (OS) rates were not significantly different between the pediatric-protocol and adult-protocol group (NRM: 4 % vs. 14 % at five years post-transplant, respectively, p = 0.26; OS: 81 % vs. 66 %, respectively, p = 0.14). Multivariate analysis for NRM revealed that a performance status >0 (hazard ratio [HR] = 4.8) and transplant due to chemotherapy toxicities (HR = 3.5) were independent risk factors, but a pediatric protocol was not (HR = 0.48). The CI of NRM and the OS rates were also similar among patients aged over 24 years old. These findings suggested that conventional allo-SCT with TBI-MAC can be performed without increasing NRM in AYA patients with Ph-negative ALL even after pediatric protocols., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Maturity-Onset Diabetes of the Young (MODY) is a diabetes mellitus subtype caused by a single gene. The detection rate of the responsible gene is 27% in the United Kingdom, indicating that the causative gene remains unknown in the majority of clinically diagnosed MODY cases. To improve the detection rate, we applied comprehensive genetic testing using whole exome sequencing (WES) followed by Multiplex Ligation-dependent Probe Amplification (MLPA) and functional analyses. Twenty-one unrelated Japanese participants with MODY were enrolled in the study. To detect copy number variations (CNVs), WES was performed first, followed by MLPA analysis for participants who were negative on the basis of WES. Undetermined variants were analyzed according to their functional properties. WES identified 7 pathogenic and 3 novel likely pathogenic variants in the 21 participants. Functional analyses revealed that 1 in 3 variants was pathogenic. MLPA analysis applied to the remaining 13 undetermined samples identified 4 cases with pathogenic CNVs: 3 in HNF4A and 1 in HNF1B. Pathogenic variants were identified in 12 participants (12/21, 57.1%) - relatively high rate reported to date. Notably, one-third of the participants had CNVs in HNF4A or HNF1B, indicating a limitation of WES-only screening., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The prognosis in patients with breast cancer with isolated locoregional recurrence (ILRR) without simultaneous distant metastases after immediate breast reconstruction (IBR) remains unknown. We aimed to investigate the prognosis in this patient population., Methods: This multi-institutional retrospective observational study evaluated 3295 patients with primary breast cancer who underwent IBR at 12 Japanese medical facilities between January 1, 2008 and December 31, 2016. The outcome measures were the prognostic factors for ILRR after IBR, 5-year distant metastasis-free interval (DMFI), and 5-year overall survival (OS)., Results: Mastectomy or skin-sparing mastectomy was performed in 3295 patients. ILRR occurred in 70 patients, and the median observation period from ILRR diagnosis was 39.3 months. Of the 70 patients, 9 (12.9%) had axillary lymph node recurrence (ALNR) at the time of ILRR diagnosis. The 5-year DMFI and OS rates after ILRR were 92.4% and 91.2%, respectively. Pathological lymph node metastasis at primary surgery (P = 0.041) and ALNR (P = 0.022) at ILRR were significantly associated with DMFI in the univariate analysis. ALNR was the only independent prognostic factor in the multivariate analysis (P = 0.041). Post-mastectomy radiation therapy (PMRT; P = 0.022) and ALNR (P = 0.043) were significantly associated with OS in the univariate analysis, and both PMRT (P = 0.010) and ALNR (P = 0.028) were independent prognostic factors in the multivariate analysis for OS., Conclusions: Although patients with breast cancer who had ILRR after IBR have favorable prognosis, ALNR may lead to poor prognosis. To the best of our knowledge, this study is the first to report the prognosis of these patients., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Seronegative human immunodeficiency virus (HIV) infection, where an HIV-specific antibody response is lacking even in chronic or late-stage HIV infections, is extremely rare. Here, we report the case of a 50-year-old Japanese man presenting with Pneumocystis pneumonia who did not produce antibodies against HIV-1 until the initiation of antiretroviral therapy (ART). Fourth-generation antigen-antibody testing temporarily reverted from weakly positive to negative soon after initiating ART, likely due to a reduction in viral load (assessed by p24 antigen levels). His HIV-1 antibody titers remained low or indeterminate even after four years of ART. A literature review suggested that the absence of HIV-1-specific antibody production may be associated with unimpeded HIV replication and rapid CD4 + T cell decline. Seronegative HIV infection can lead to deferred diagnosis and treatment, thereby increasing the risk of transmitting the virus to others or developing opportunistic illnesses. It is important to combine multiple tests for diagnosis, depending on the medical condition. Further studies are required to investigate the host factors involved in the production of HIV-1-specific antibodies., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objective: In recent years, the clinical efficacy of medications for adenoid hypertrophy has been demonstrated. Topical nasal steroids have effects to shrink hypertrophic adenoids and improve symptoms of associated diseases. However, the mechanism which topical steroid administrations cause adenoid shrinkage remains unclear, herein, sensitivity for topical steroids in the mucosal epithelium of adenoids was evaluated histologically by comparing with tonsils., Methods: Histological analysis was performed on adenoids and tonsils removed from 32 pediatric patients with adenoid hypertrophy. In hematoxylin-eosin-stained specimens, the morphology of the mucosal epithelium and eosinophil infiltration were evaluated. The expression of the glucocorticoid receptor (GR), interleukin (IL)-4, and IL-25 in the mucosal epithelium was evaluated, and the staining intensity was scored as 0 (none), 1 (weak), and 2 (strong). The number of eosinophils and expression scores of GR, IL-4, and IL-25 were statistically compared between adenoids and tonsils and analyzed correlations with adenoids sizes., Results: Adenoids were covered with ciliated epithelium, and eosinophils in the mucosal epithelium and submucosal area was higher than tonsils (p < 0.05). GR expression in the most superficial layer of the mucosal epithelium was observed in adenoids, and the expression intensity score was higher than that in tonsils (p < 0.05). IL-4 and IL-25 were more widely expressed in the mucosal epithelium of adenoids than in tonsils, and their expression intensity scores were also higher than in tonsils (p < 0.05). A correlation was found between adenoid size and the intensity of IL-25 expression in the adenoid epithelium (p < 0.05)., Conclusion: Eosinophilic inflammations in adenoids mucosal epithelium could be one of etiology of adenoid hypertrophy, and the GR and eosinophilic inflammation in the adenoids mucosal epithelium might be target of topical nasal steroids to shrink hypertrophic adenoids., Competing Interests: Declaration of competing interest All authors have no financial conflicts of interest disclose concerning this study and article., (Copyright © 2024 Elsevier B.V. All rights reserved.)