[Ovarian hyperstimulation syndrome with controlled ovarian stimulation after induction therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia].

A 27-year-old woman with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia received induction therapy with dasatinib and prednisolone. From the time of diagnosis, oocyte storage was planned in accordance with the patient's wishes. After progesterone administration for suppression of menstruation, and blood cell recovery, ovarian stimulation was performed and a sufficient number of eggs was collected. The patient was considered at high risk for ovarian stimulation syndrome (OHSS) and received cabergoline and letrozole. However, ovarian enlargement and ascites were observed on ultrasonography 2 days after egg collection, and a diagnosis of moderate OHSS was made. Circulatory management was performed and low-molecular-weight heparin was administered. Dasatinib was discontinued due to the appearance of pleural effusion. Fluid retention improved after menstruation resumed, and the patient was able to continue consolidation with dasatinib and cord blood transplantation. Although tyrosine kinase inhibitors are expected to simplify planning of oocyte storage, the risk of complicating OHSS should be noted.

Development of split-force-controlled body weight support (SF-BWS) robot for gait rehabilitation.

This study introduces a body-weight-support (BWS) robot actuated by two pneumatic artificial muscles (PAMs). Conventional BWS devices typically use springs or a single actuator, whereas our robot has a split force-controlled BWS (SF-BWS), in which two force-controlled actuators independently support the left and right sides of the user's body. To reduce the experience of weight, vertical unweighting support forces are transferred directly to the user's left and right hips through a newly designed harness with an open space around the shoulder and upper chest area to allow freedom of movement. A motion capture evaluation with three healthy participants confirmed that the proposed harness does not impede upper-body motion during laterally identical force-controlled partial BWS walking, which is quantitatively similar to natural walking. To evaluate our SF-BWS robot, we performed a force-tracking and split-force control task using different simulated load weight setups (40, 50, and 60 kg masses). The split-force control task, providing independent force references to each PAM and conducted with a 60 kg mass and a test bench, demonstrates that our SF-BWS robot is capable of shifting human body weight in the mediolateral direction. The SF-BWS robot successfully controlled the two PAMs to generate the desired vertical support forces.

Tyrosine Kinase Inhibitors Do Not Promote a Decrease in SARS-CoV-2 Anti-Spike IgG after BNT162b2 Vaccination in Chronic Myeloid Leukemia: A Prospective Observational Study.

We performed a prospective observational study of chronic myeloid leukemia (CML) patients after anti-SARS-CoV-2 BNT162b2 vaccination (VC). In total, 32 CML patients with tyrosine kinase inhibitor (TKI) therapy, 10 CML patients with treatment-free remission, and 16 healthy subjects participated in the study. From April 2021 to September 2021, all cases (median age = 58 years) were vaccinated twice. Immunoglobulin G for SARS-CoV-2 spike protein (S-IgG) was measured at three timepoints (before the first VC, 1−5 weeks after the second VC (T1), and approximately 6 months after the second VC (T2)). S-IgG was not observed before the first VC in any participant. At T1, all cases had acquired S-IgG. There were no significant differences in S-IgG levels among groups. A paired sample comparison of median S-IgG titers between T1 and T2 in all groups showed a significant reduction in T2 S-IgG titers. There were no significant differences in S-IgG levels among groups. When all patients were analyzed, those aged ≥58 years had significantly lower S-IgG levels than those aged <58 years at T1. The BNT162b2 vaccine was highly effective in CML patients with or without TKIs, and S-IgG levels were as persistent as those in healthy individuals.

[Desquamative esophagitis associated with unrelated allogeneic peripheral blood stem cell transplantation using the FBM conditioning regimen].

Desquamative esophagitis (DE) is a rare benign condition characterized by sheet-like shedding of esophageal squamous epithelial tissue. Although cases of drug-induced DE, such as those induced by direct oral anticoagulants, have been reported, cases of DE complicated with hematopoietic stem cell transplantation (HSCT) are rare. We herein report the case of a 52-year-old woman with FLT3-ITD mutation-positive acute myeloid leukemia who presented with DE immediately after HSCT. Allogeneic peripheral blood HSCT with FBM (fludarabine 180 mg/m2, busulfan 12.8 mg/m2, and melphalan 80 mg/m2) was performed during the first remission. Tacrolimus plus short-term methotrexate was planned for graft-versus-host disease prevention. Common Terminology Criteria for Adverse Events grade 3 equivalent vomiting was observed during treatment with the conditioning regimen. On day 5 after HSCT, a white band of 10 cm in length and 1 cm in width was discharged from the oral cavity during vomiting. Upper gastrointestinal endoscopy revealed mucosal detachment in the entire esophagus and the diagnosis of DE was made. DE improved on providing conservative treatment. We concluded that the mechanical pressure that developed on the esophagus due to frequent vomiting contributed to the mucosal detachment owing to regimen-related toxicity. Even in the FBM regimen, which is widely used as a conditioning regimen, caution is required to prevent DE.

Relevance of diffusion-weighted imaging with background body signal suppression for staging, prognosis, morphology, treatment response, and apparent diffusion coefficient in plasma-cell neoplasms: A single-center, retrospective study.

Accurate staging and evaluation of therapeutic effects are important in managing plasma-cell neoplasms. Diffusion-weighted imaging with body signal suppression magnetic resonance imaging (DWIBS-MRI) allows for acquisition of whole-body volumetric data without radiation exposure. This study aimed to investigate the usefulness of DWIBS-MRI in plasma-cell neoplasms. We retrospectively analyzed 29 and 8 Japanese patients with multiple myeloma and monoclonal gammopathy of undetermined significance, respectively, who underwent DWIBS-MRI. We conducted a histogram analysis of apparent diffusion coefficient values. The correlations between each histogram parameter and staging, cell maturation, prognosis, and treatment response were evaluated. We found that the apparent diffusion coefficient values in patients with monoclonal gammopathy of undetermined significance were lower than those in patients with multiple myeloma. Pretreatment apparent diffusion coefficient values of immature myeloma were lower than those of mature myeloma. Moreover, these values decreased in proportion to stage progression in Durie-Salmon classification system but showed no significant correlation with other staging systems or prognosis. Patients were stratified as responder, stable, and non-responder based on the International Myeloma Working Group criteria. The magnitude of changes in apparent diffusion coefficients differed significantly between responders and non-responders (0.154 ± 0.386 ×10-3 mm2/s vs. -0.307 ± 0.424 ×10-3 mm2/s, p = 0.003). Although its usefulness has yet to be established, DWIBS-MRI combined with apparent diffusion coefficient measurement allowed for excellent response evaluation in patients with multiple myeloma. Furthermore, apparent diffusion coefficient analysis using DWIBS-MRI may be useful in predicting cell maturation and total tumor volume.

Elevation of HHV-6 viral load mimicking HHV-6 reactivation after second umbilical cord blood transplantation in chromosomally integrated human herpesvirus-6.

Human herpesvirus-6 (HHV-6) reactivation is an important complication in patients receiving umbilical cord blood transplantation (CBT). Chromosomally integrated human herpesvirus-6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germline genome and is transmitted in a Mendelian manner. The influence of ciHHV-6 in recipients or donors in cases of CBT is unknown. We report the first case with ciHHV-6 that received CBT twice for acute lymphoblastic T-cell leukemia. HHV-6 DNA in peripheral blood leukocytes (PBLs) was examined over time through two CBTs. After the first CBT, the HHV-6 viral load was significantly reduced by conversion to PBLs derived from the first donor. During the second CBT, an increase in HHV-6 DNA in PBLs and plasma were observed. However, HHV-6 mRNA was not detected in either the sample before 2nd CBT or at the time of HHV-6 DNA elevation. It is considered that the HHV-6 DNA detected in PBLs and plasma samples might be the HHV-6 genome released due to tissue damage. This case suggests that physicians should be aware of HHV-6 DNA variability during allogeneic hematopoietic stem cell transplantation in ciHHV-6 patients.

Association between aphasia severity and brain network alterations after stroke assessed using the electroencephalographic phase synchrony index.

Electroencephalographic synchrony can help assess brain network status; however, its usefulness has not yet been fully proven. We developed a clinically feasible method that combines the phase synchrony index (PSI) with resting-state 19-channel electroencephalography (EEG) to evaluate post-stroke motor impairment. In this study, we investigated whether our method could be applied to aphasia, a common post-stroke cognitive impairment. This study included 31 patients with subacute aphasia and 24 healthy controls. We assessed the expressive function of patients and calculated the PSIs of three motor language-related regions: frontofrontal, left frontotemporal, and right frontotemporal. Then, we evaluated post-stroke network alterations by comparing PSIs of the patients and controls and by analyzing the correlations between PSIs and aphasia scores. The frontofrontal PSI (beta band) was lower in patients than in controls and positively correlated with aphasia scores, whereas the right frontotemporal PSI (delta band) was higher in patients than in controls and negatively correlated with aphasia scores. Evaluation of artifacts suggests that this association is attributed to true synchrony rather than spurious synchrony. These findings suggest that post-stroke aphasia is associated with alternations of two different networks and point to the usefulness of EEG PSI in understanding the pathophysiology of aphasia.

Effect of Neurofeedback Facilitation on Poststroke Gait and Balance Recovery: A Randomized Controlled Trial.

OBJECTIVE: To test the hypothesis that supplementary motor area (SMA) facilitation with functional near-infrared spectroscopy-mediated neurofeedback (fNIRS-NFB) augments poststroke gait and balance recovery, we conducted a 2-center, double-blind, randomized controlled trial involving 54 Japanese patients using the 3-meter Timed Up and Go (TUG) test. METHODS: Patients with subcortical stroke-induced mild to moderate gait disturbance more than 12 weeks from onset underwent 6 sessions of SMA neurofeedback facilitation during gait- and balance-related motor imagery using fNIRS-NFB. Participants were randomly allocated to intervention (28 patients) or placebo (sham: 26 patients). In the intervention group, the fNIRS signal contained participants' cortical activation information. The primary outcome was TUG improvement 4 weeks postintervention. RESULTS: The intervention group showed greater improvement in the TUG test (12.84 ± 15.07 seconds, 95% confidence interval 7.00-18.68) than the sham group (5.51 ± 7.64 seconds, 95% confidence interval 2.43-8.60; group difference 7.33 seconds, 95% CI 0.83-13.83; p = 0.028), even after adjusting for covariates (group × time interaction; F 1.23,61.69 = 4.50, p = 0.030, partial η2 = 0.083). Only the intervention group showed significantly increased imagery-related SMA activation and enhancement of resting-state connectivity between SMA and ventrolateral premotor area. Adverse effects associated with fNIRS-mediated neurofeedback intervention were absent. CONCLUSION: SMA facilitation during motor imagery using fNIRS neurofeedback may augment poststroke gait and balance recovery by modulating the SMA and its related network. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with gait disturbance from subcortical stroke, SMA neurofeedback facilitation improves TUG time (UMIN000010723 at UMIN-CTR; umin.ac.jp/english/).

Epstein-Barr virus-associated post-transplant lymphoproliferative disease during dasatinib treatment occurred 10 years after umbilical cord blood transplantation.

Post-transplant lymphoproliferative disease (PTLD) is defined as a lymphoma that occurs after solid-organ or hematopoietic stem-cell transplantation (HSCT), caused by immunosuppression and Epstein-Barr virus (EBV) reactivation. It is an important post-transplant complication that can be fatal. After HSCT, most PTLD occurs within 2 years. Recent evidence suggests that tyrosine kinase inhibitors (TKIs) are expected to be effective maintenance therapy after HSCT for Philadelphia chromosome-positive leukemia. However, it is unclear whether the use of TKIs might pose a risk of developing PTLD after HSCT. We present the first case of late-onset PTLD during dasatinib treatment, which occurred 10 years after umbilical cord blood transplantation (CBT). A 59-year-old man who received CBT for chronic myeloid leukemia blast phase needed long-term dasatinib therapy for molecular relapse. Ten years after CBT, he developed diffuse-large B-cell lymphoma (DLBCL). We observed chimerism of the DLBCL sample, which indicated complete donor type and EBV-DNA, and the patient was diagnosed with PTLD. Because of treatment resistance, he died 6 months after PTLD onset. Although he received no long-term administration of immunosuppressive agents, he received long-term dasatinib treatment, which suggests that prolonged dasatinib use after CBT caused EBV reactivation and led to PTLD. Our case suggests that the potential contribution of molecular-targeted agents after HSCT to the development of PTLD should be carefully considered.

Successful cord blood transplantation for myelodysplastic syndrome complicated by Mycobacterium kansasii pneumonia.

Non-tuberculous mycobacterial (NTM) disease is a rare cause of neutropenic fever in patients with hematological malignancies. There are few studies on the optimal management for such patients with NTM. We report a case of myelodysplastic syndrome (MDS) treated by umbilical cord blood transplantation (CBT) after Mycobacterium kansasii (M kansasii) pneumonia. A 38-year-old man diagnosed with MDS developed severe pneumonia during induction chemotherapy. Repeated sputum culture uncovered mycobacterium infection. Then, by the polymerase chain reaction of the bronchial lavage fluid, M kansasii infection was proven. After 140 days of anti-NTM therapy, CBT was successfully carried out and the patient recovered without recurrence of NTM infection. This case provides valuable evidence that hematopoietic stem cell transplantation is feasible after a reliable diagnosis and continuous anti-NTM therapy.

[Persistent malnutrition caused by Nihonkaiense diphyllobothriasis diagnosed during treatment of malignant lymphoma].

A 72-year-old man with ileocecal lymphadenopathy was found to have Epstein-Barr virus-positive diffuse large B-cell lymphoma using open biopsy, and an ileostoma was created. R-CHOP-like chemotherapy was initiated, but his malnutrition did not improve. After 3 cycles of chemotherapy, a 2-m-long Cestoda was removed from the stoma and was identified as Diphyllobothrium nihonkaiense using mitochondria cytochrome c oxidase subunit 1 targeted polymerase chain reaction analysis. Although D. nihonkaiense infections are asymptomatic, the ileostomy was thought to have exacerbated the malabsorption in this patient. Parasitic infections are rare; however, they should be added to the differential diagnosis of malnutrition of unknown cause during chemotherapy for hematological malignancies.

Electroencephalographic Phase Synchrony Index as a Biomarker of Poststroke Motor Impairment and Recovery.

Background. Motor recovery after stroke is of great clinical interest. Besides magnetic resonance imaging functional connectivity, electroencephalographic synchrony is also an available biomarker. However, the clinical relevance of electroencephalographic synchrony in hemiparesis has not been fully understood. Objective. We aimed to demonstrate the usefulness of the phase synchrony index (PSI) by showing associations between the PSI and poststroke outcome in patients with hemiparesis. Methods. This observational study included 40 participants with cortical ischemic stroke (aged 69.8 ± 13.8 years) and 22 healthy controls (aged 66.9 ± 6.5 years). Nineteen-channel electroencephalography was recorded at 36.9 ± 11.8 days poststroke. Upper extremity Fugl-Meyer scores were assessed at the time of admission/before discharge (FM-UE1/FM-UE2; 32.6 ± 12.3/121.0 ± 44.7 days poststroke). Then, correlations between the PSIs and FM-UE1 as well as impairment reduction after rehabilitation (FM-UEgain) were analyzed. Results. The interhemispheric PSI (alpha band) between the primary motor areas (M1s) was lower in patients than in controls and was selectively correlated with FM-UE1 (P = .001). In contrast, the PSI (theta band) centered on the contralesional M1 was higher in patients than in controls and was selectively correlated with FM-UEgain (P = .003). These correlations remained significant after adjusting for confounding factors (age, time poststroke, National Institute of Health Stroke Scale, and lesion volume). Furthermore, the latter correlation was significant in severely impaired patients (FM-UE1 ≤ 10). Conclusions. This study showed that the PSIs were selectively correlated with motor impairment and recovery. Therefore, the PSIs may be potential biomarkers in persons with a hemispheric infarction.

Downregulation of extracellular vesicle microRNA-101 derived from bone marrow mesenchymal stromal cells in myelodysplastic syndrome with disease progression.

To evaluate the mechanism underlying the communication between myeloid malignant and bone marrow (BM) microenvironment cells in disease progression, the current study established BM mesenchymal stromal cells (MSCs) and assessed extracellular vesicle (EV) microRNA (miR) expression in 22 patients with myelodysplastic syndrome (MDS) and 7 patients with acute myeloid leukemia and myelodysplasia-related changes (AML/MRC). Patients with MDS were separated into two categories based on the revised International Prognostic Scoring System (IPSS-R), and EV-miR expression in BM-MSCs was evaluated using a TaqMan low-density array. The selected miRs were evaluated using reverse transcription-quantitative PCR. The current study demonstrated that the expression of BM-MSC-derived EV-miR was heterogenous and based on MDS severity, the expression of EV-miR-101 was lower in high-risk group and patients with AML/MRC compared with the control and low-risk groups. This reversibly correlated with BM blast percentage, with which the cellular miR-101 from BM-MSCs or serum EV-miR-101 expression exhibited no association. Database analyses indicated that miR-101 negatively regulated cell proliferation and epigenetic gene expression. The downregulation of BM-MSC-derived EV-miR-101 may be associated with cell-to-cell communication and may accelerate the malignant process in MDS cells.

A novel non-invasive monitoring assay of 5-azacitidine efficacy using global DNA methylation of peripheral blood in myelodysplastic syndrome.

Purpose: Monitoring response and resistance to 5-azacitidine (AZA) is essential when treating patients with myelodysplastic syndrome (MDS). To quantify methylated DNA not only in the promoter region but also in the gene body, we established a single-molecule methylation assay (SMMA). Patients and methods: We first investigated the methylation extent (expressed as methylation index [MI]) by SMMA among 28 MDS and 6 post-MDS acute myeloid leukemia patients. We then analyzed the MI in 13 AZA-treated patients. Results: Whole-blood DNA from all 34 patients had low MI values compared with healthy volunteers (P<0.0001). DNA hypomethylation in MDS patients was more evident in neutrophils (P=0.0008) than in peripheral mononuclear cells (P=0.0713). No consistent pattern of genome-wide DNA hypomethylation was found among MDS subtypes or revised International Prognostic Scoring System (IPSS-R) categories; however, we found that the MI was significantly increased for patients at very high risk who were separated by the new cytogenetic scoring system for IPSS-R (P=0.0398). There was no significant difference in MI before AZA, regardless of the response to AZA (P=0.8689); however, sequential measurement of MI in peripheral blood demonstrated that AZA non-responders did not have normalized MI at the time of next course of AZA (P=0.0352). Conclusion: Our results suggest that sequential SMMA of peripheral blood after AZA may represent a non-invasive monitoring marker for AZA efficacy in MDS patients.

Involvement of cortical dysfunction in frequent falls in patients with Parkinson's disease.

INTRODUCTION: Gait and balance disorders are common clinical features of Parkinson's disease (PD). Although falls significantly affect the activities of daily living (ADL) and quality of life (QOL) of patients with PD, the underlying neural mechanisms associated with frequent falls in PD patients are still unclear. METHODS: Hypothesizing that the cerebral cortex would contribute to frequent falls in PD, we obtained 3D T1-weighted images from 91 non-dementia patients with PD and performed voxel-based morphometric analysis (VBM). Gray matter volume was compared between patients with and without frequent falls to investigate the structural basis for frequent falls in PD. As an ancillary analysis, we also performed resting-state functional magnetic resonance analysis using data from 58 patients. RESULTS: Among the 91 patients, 36 had experienced frequent falls. Gray matter volume in the right superior temporal gyrus (STG) and the right inferior parietal lobule (IPL) of these patients was significantly lower than that of the non-frequent fallers. There was also a significant correlation between fall frequency and gray matter volume in these two regions. Additionally, resting-state functional analysis revealed lower connectivity in the right posterior perisylvian region, including in the IPL and STG, in frequent fallers than in non-frequent fallers. CONCLUSION: Frequent falls in PD are associated with structural and functional abnormality of the cerebral cortex including the right IPL and STG.

BIM deletion polymorphism accounts for lack of favorable outcome in Japanese females with follicular lymphoma.

Deletion polymorphism of BCL-2-like protein 11 (BIM) is specifically found in East Asia. To explain some epidemiological discrepancies between Asian and Western countries, we analyzed a silent single nucleotide polymorphism (SNP) in exon 5 (c465C > T) and a deletion site (2903 bp) in intron 2 in 77 patients with follicular lymphoma by the Q-invader method using PCR. In females, 5-year progression-free survivals (PFS) were 20.0% in the BIM deletion group, 66.7% in the SNP group and 81.5% in the wild-type (WT) group (p = .0012). In the WT group, 5-year PFS was 40.4% in males (p = .0448 vs. female PFS). This tendency was strengthened in patients receiving rituximab (26.9% vs. 84.2%, p = .006). Superior PFS in the WT females in Japan was comparable with the results of cohort studies in the United States and Sweden. Favorable prognosis in Japanese females may be masked by the BIM deletion polymorphism.

Cardiac biopsy with intracardiac echocardiographic guidance for successful diagnosis of cardiac lymphoma.

The diagnosis and appropriate treatment of cardiac lymphoma are often delayed by the difficulty in obtaining heart tissue biopsies. Intracardiac echocardiography-guided biopsy can improve the prognosis of cardiac lymphoma by decreasing postbiopsy complications and increasing biopsy quality, allowing collection of sufficient material for multilateral analysis.