Decision analysis for transplant candidates with primary myelofibrosis in the ruxolitinib era.

The recent progress with ruxolitinib treatment might improve quality-of-life as well as overall survival in patients with primary myelofibrosis (PMF). Therefore, the optimal timing of allogeneic hematopoietic cell transplantation (HCT) remains to be elucidated in the ruxolitinib era. We constructed a Markov model to simulate the 5-year clinical course of transplant candidates with PMF, and compared outcomes between immediate HCT and delayed HCT after ruxolitinib failure. Since older age was associated with an increased risk of mortality, we analyzed patients aged < 60 and ≥ 60 separately in subgroup analyses. The expected life years was consistently longer in delayed HCT after ruxolitinib failure regardless of patient age. Regarding quality-adjusted life years (QALYs), a baseline analysis showed that immediate HCT was inferior to delayed HCT after ruxolitinib failure (2.19 versus 2.26). In patients aged < 60, immediate HCT was equivalent to delayed HCT after ruxolitinib failure (2.31 versus 2.31). On the other hand, in patients aged ≥ 60, immediate HCT was inferior to delayed HCT after ruxolitinib failure (1.98 versus 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 QALYs, 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, and is also a promising strategy even in those aged < 60.

Classification and comparison of the physical characteristics and functions of various age groups of community-dwelling elderly individuals participating in the Kayoi-no-ba program.

[Purpose] To classify and compare the physical characteristics and functions of community-dwelling elderly individuals of various age groups participating in the Kayoi-no-ba program. [Participants and Methods] A total of 176 community-dwelling elderly individuals living in six cities and towns in the Niigata Prefecture who participated in the Kayoi-no-ba program between 2018 and 2020 were recruited in this study. Physical characteristics, such as strength, balance, and mobility, were assessed. [Results] Among elderly females and males who participated in the Kayoi-no-ba program, those >80 years of age showed shorter height, lighter weight, and lower body muscle mass than the other age groups. Strength, balance, and mobility functions, including grip strength, sit-to-stand test, single-leg-stand test, and timed up-and-go test, were significantly decreased, especially in patients aged >80 years. [Conclusion] Among community-dwelling elderly individuals participating in the Kayoi-no-ba program, physical characteristics and functions were affected by aging, with significant decline particularly in those aged >80 years old. These findings suggest that early intervention is necessary to maintain muscle mass, strength, balance, and mobility in the elderly.

[Successful treatment of secondary graft failure after allogeneic stem cell transplantation for aplastic anemia with eltrombopag].

Herein we report a case of successful treatment of secondary graft failure due to poor graft function (PGF) using eltrombopag. A 25-year-old woman with aplastic anemia (stage 3) underwent allogeneic bone marrow transplantation (BMT) from her HLA-matched brother. Neutrophil engraftment was achieved on day 17, but she remained dependent on platelet transfusion. Chimerism analysis showed complete donor type, but she also became dependent on red blood cell transfusion later. Eltrombopag was administered on day 253 after BMT, after which she exhibited hematopoietic recovery, resulting in the withdrawal of transfusion dependency. Blood counts continued to be stable after eltrombopag was discontinued. The use of eltrombopag enabled outpatient treatment and induced hematopoietic recovery without significant side effects. Eltrombopag may be an effective and safe option for PGF after BMT.

[Isolated central nervous system relapse of Philadelphia chromosome-positive acute lymphoblastic leukemia during ponatinib maintenance therapy].

A 65-year-old man was diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia with no initial central nervous system (CNS) involvement. Complete remission was achieved after the induction therapy. However, during consolidation therapy, he developed septic shock and pneumocystis pneumonia, leading to interruption in chemotherapy and allogeneic transplantation. Subsequently, he achieved complete molecular remission and ponatinib maintenance therapy was initiated. Two years later, he developed left leg paralysis and was diagnosed with isolated CNS relapse; however, radiation therapy improved CNS lesions and paralysis. Thus, ponatinib maintenance therapy alone is inadequate in preventing CNS relapse in patients who have not completed systemic chemotherapy for CNS relapse prevention.

Increased SLAMF7high monocytes in myelofibrosis patients harboring JAK2V617F provide a therapeutic target of elotuzumab.

Monocyte-derived fibrocytes recently garnered attention because the novel pathogenesis of myelofibrosis (MF), and suppression of fibrocyte differentiation by serum amyloid P remarkably improved MF. We previously revealed that human fibrocytes highly expressed signaling lymphocytic activation molecule F7 (SLAMF7) compared with macrophages and that SLAMF7high monocytes in the peripheral blood (PB) of MF patients were significantly elevated relative to those in healthy controls (HCs). In this study, we evaluated SLAMF7high monocyte percentage in the PB of HCs, myeloproliferative neoplasm (MPN) patients with MF, and MPN patients without MF by using a cross-sectional approach. We found that MPN patients with MF who harbored JAK2V617F had a significantly elevated SLAMF7high monocyte percentage, which correlated positively with the JAK2V617F allele burden. In addition, the serum concentration of interleukin-1ra (IL-1ra) was significantly correlated with the SLAMF7high monocyte percentage and JAK2V617F allele burden. These findings suggest that both SLAMF7high monocytes and IL-1ra could be useful noninvasive markers of MF onset. Furthermore, the JAK2V617F allele burden of SLAMF7high monocytes was significantly higher than that of SLAMF7low monocytes and could be a potential target of elotuzumab (Elo), an anti-SLAMF7 antibody used for treating multiple myeloma. Elo independently inhibited differentiation of fibrocytes derived not only from HCs but also from MF patients in vitro. Elo also ameliorated MF and splenomegaly induced by romiplostim administration in humanized NOG mice. In conclusion, an increase of SLAMF7high monocytes with higher JAK2V617F allele burden was associated with the onset of MF in MPN patients harboring JAK2V617F, and Elo could be a therapeutic agent for MPN patients with MF who harbor JAK2V617F.

[Bendamustine and rituximab combination therapy for recurrent indolent B-cell lymphomas: a retrospective single-institution study].

This retrospective study evaluated the outcomes of patients treated with combination of bendamustine and rituximab (BR) for recurrent indolent B-cell lymphoma from January 2011 to February 2018 in our department. The cohort included 36 males and 27 females, and majority of the patients (59%) were between 51 and 70 years of age. The disease types were follicular lymphoma (FL) and mantle-cell lymphoma in 42 (67%) and 15 (24%) patients, respectively. Median progression-free survival (PFS) was not reached in patients with FL who completed BR therapy. The analysis of patients who received BR therapy revealed that the number of CD4-positive lymphocytes remained around 200/µl even five years after the end of treatment. BR therapy was a useful treatment option for recurrent indolent B-cell lymphoma, especially in patients with FL, and completion of BR therapy appeared to be important for improved PFS. Furthermore, attention should be paid for potential infections for at least five years after BR therapy because cell-mediated immunodeficiency may become apparent after treatment.

Impact of input mask signals on delay-based photonic reservoir computing with semiconductor lasers.

We experimentally investigate delay-based photonic reservoir computing using semiconductor lasers with optical feedback and injection. We apply different types of temporal mask signals, such as digital, chaos, and colored-noise mask signals, as the weights between the input signal and the virtual nodes in the reservoir. We evaluate the performance of reservoir computing by using a time-series prediction task for the different mask signals. The chaos mask signal shows superior performance than that of the digital mask signals. However, similar prediction errors can be achieved for the chaos and colored-noise mask signals. Mask signals with larger amplitudes result in better performance for all mask signals in the range of the amplitude accessible in our experiment. The performance of reservoir computing is strongly dependent on the cut-off frequency of the colored-noise mask signals, which is related to the resonance of the relaxation oscillation frequency of the laser used as the reservoir.

Compact reservoir computing with a photonic integrated circuit.

Photonic reservoir computing is a new paradigm for performing high-speed prediction and classification tasks in an efficient manner. The major challenge for the miniaturization of photonic reservoir computing is the need for the use of photonic integrated circuits. Herein, we experimentally demonstrate reservoir computing using a photonic integrated circuit with a semiconductor laser and a short external cavity. We propose a method to increase the number of virtual nodes in delayed feedback using short node intervals and outputs from multiple delay times. We perform time-series prediction and nonlinear channel equalization tasks using reservoir computing with the photonic integrated circuit. We show that the photonic integrated circuit with optical feedback outperforms the photonic integrated circuit without optical feedback for prediction tasks. To enhance the memory effect we feed past input signals in the current input data and demonstrate successful performance in an n-step-ahead prediction task.

Low urinary sodium-to-potassium ratio in the early phase following single-unit cord blood transplantation is a predictive factor for poor non-relapse mortality in adults.

Although daily higher urinary sodium (Na) and potassium (K) excretion ratio is associated with the risk of cardiovascular disease in the general population, a low Na/K ratio is associated with renal dysfunction in critically ill patients. Thus, we retrospectively analyzed the impact of daily urinary Na and K excretion and their ratio on non-relapse mortality (NRM) and overall mortality in 172 adult single-unit cord blood transplantation (CBT) patients treated at our institution between 2007 and 2020. Multivariate analysis showed that a low urinary Na/K ratio at both 14 days (hazard ratio [HR], 4.82; 95% confidence interval [CI], 1.81-12.83; P = 0.001) and 28 days (HR, 4.47; 95% CI 1.32-15.12; P = 0.015) was significantly associated with higher NRM. Furthermore, a low urinary Na/K ratio at 28 days was significantly associated with higher overall mortality (HR, 2.38; 95% CI 1.15-4.91; P = 0.018). Patients with a low urinary Na/K ratio had decreased urine volume, more weight gain, experienced more grade III-IV acute graft-versus-host disease, and required corticosteroids by 28 days after CBT. These findings indicate that a low urinary Na/K ratio early after single-unit CBT is associated with poor NRM and survival in adults.

Association of the Stanford Integrated Psychosocial Assessment for Transplant and 1-Year Outcome of Living Kidney Transplantation in Japan.

BACKGROUND: Because most kidney transplantations in Japan are performed on the basis of living donors, after-transplant outcomes should achieve optimum results, overcoming participants' possible reduced adherence. OBJECTIVE: To investigate the association between the Japanese version of the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT-J) and outcomes, 1 year after the patient's living kidney transplant (LKT). METHODS: The prospective cohort study was undertaken at Tokyo Women's Medical University Hospital from January 2020 to July 2021, with a 1-year follow-up period. The SIPAT-J assesses 18 psychosocial risk factors: (1) Patient's Readiness Level and Illness Management (SIPAT A), (2) Social Support System Level of Readiness (SIPAT B), (3) Psychological Stability and Psychopathology (SIPAT C), and (4) Lifestyle and Effect of Substance Use (SIPAT D). The evaluators, a psychiatrist and 3 clinical psychologists, conducted an independent, blinded application of the SIPAT-J using participants' medical records. The study focused on physical composite outcomes, psychiatric outcomes, and nonadherent behaviors. RESULTS: The participants were 173 LKT recipients (median age [interquartile range], 51 [38-59]); 67.1% were male and 67.1% were employed. The median (interquartile range) SIPAT scores were SIPAT A [7 (5-9)], SIPAT B [7 (5-9)], SIPAT C [2 (0-4)], SIPAT D [3 (3-4)], and SIPAT total [20 (16-23)]. The physical composite outcome was 25 (14.5%), psychiatric outcome 9 (5.2%), and nonadherent behavior 17 (9.8%). SIPAT C (odds ratio = 1.34, 95% confidence interval = 1.06-1.72, P = 0.02) was significantly associated with the psychiatric outcome. SIPAT B (odds ratio = 1.49, 95% confidence interval = 1.12-1.98, P = 0.01) and SIPAT total (odds ratio = 1.13, 95% confidence interval = 1.03-1.24, P = 0.01) were significantly associated with nonadherent behaviors. There was no significant association between the SIPAT and physical composite outcomes. CONCLUSION: This study is the first to examine the association between SIPAT and physical and psychiatric outcomes 1 year after LKT, controlling for follow-up periods and factors other than SIPAT. Comprehensive psychosocial assessment before LKT and early identification of factors that may negatively affect transplant success can allow targeted interventions to be implemented and increase the likelihood of favorable recipient outcomes.

A Simple Simulation System for Quantifying Buttock Loads Caused by Daily Activities of Wheelchair Users.

The purpose of this study is to quantify the load generated on the buttocks during wheelchair operation in order to clarify the cause of pressure injuries on the buttocks of wheelchair users. In the case of repeated measurements, pressure injuries may occur by conducting experiments with people with actual disabilities. In this study, we proposed a method of dynamic simulation using a humanoid model in order to carry out buttock load safely due to exercise. In addition, the load on the buttocks is quantified by reproducing a simulated cushion that reproduces the actual physical properties on the simulator. When we conducted an evaluation experiment of the developed simulation to quantify the buttock load, we confirmed the validity of this simulator in the front-back direction. On the other hand, the correlation with the actual data is low in the left-right direction, and it is considered necessary to improve the humanoid model in order to improve the accuracy.

Characterization of the stanford integrated psychosocial assessment for transplant for heart, liver, and kidney transplant candidates in Japan.

BACKGROUND: The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a comprehensive psychosocial assessment proven useful for predicting the outcomes of organ transplantation that is expected to be useful in Japan. However, the characteristics of organ-specific SIPAT scores for organ transplant recipient candidates in Japan are unclear and, to date, the SIPAT has not been properly utilized in clinical practice. The purpose of this study was to present basic data that can be used to establish the relation between SIPAT scores and post-transplantation psychosocial outcomes as well as organ-specific outcomes. METHODS: This study included 167 transplant recipient candidates (25 heart, 71 liver, and 71 kidney) who completed a semi-structured interview based on the Japanese version of SIPAT (SIPAT-J) prior to transplantation. The differences between organs in terms of SIPAT scores and differences in SIPAT scores based on demographic data were comparatively analyzed. RESULTS: The total SIPAT scores were higher for liver recipient candidates than for heart recipient candidates (P = .019). Regarding the subscales, SIPAT B (social support system) scores were higher for liver and kidney recipient candidates than for heart recipient candidates (P = .021), whereas SIPAT C (psychological stability and psychopathology) scores were higher for liver recipient candidates than for kidney recipient candidates (P = .002). Recipient candidates with a history of psychiatric treatment and those who were unemployed had higher SIPAT scores, regardless of the transplant organ, than recipient candidates without a history of psychiatric treatment and those who were employed (P < .001, P = .016, respectively). CONCLUSIONS: There were notable differences in the total SIPAT-J and subscale scores among the liver, heart, and kidney recipient candidates. Each organ was associated with specific psychosocial issues that should be addressed before transplantation. Interventions such as information provision and patient education based on SIPAT assessment results for each organ may improve recipient post-transplant outcomes.

Clinical implications of augmented renal clearance after unrelated single cord blood transplantation in adults.

Augmented renal clearance (ARC) is a phenomenon characterized by increased renal functionality, which can impact the pharmacokinetics and pharmacodynamics of antimicrobial drugs eliminated by the kidneys. It is a potential concern for infection treatment. Cord blood transplantation (CBT) is primarily impeded by delayed neutrophil recovery and immune reconstitution, thereby increasing susceptibility to infection. However, the clinical implications of ARC following CBT remain unexplored. We retrospectively assessed the influence of ARC on post-transplant outcomes at various time points in 194 adult recipients of single-unit unrelated CBT between 2007 and 2022 at our institution. ARC was observed in 52.9% of patients at 1 day, 39.8% at 15 days, and 26.5% at 29 days post-CBT. ARC was not significantly associated with bloodstream infection, acute graft-versus-host disease, or veno-occlusive disease/sinusoidal obstruction syndrome at any time point. ARC at 1 day, 15 days, and 29 days post-CBT was not significantly associated  with overall survival, non-relapse mortality, or relapse rates. These findings suggest that ARC is common in adults during the early stages of CBT, but does not discernibly influence clinical outcomes or post-CBT complications.

Family functioning before kidney transplantation from living-related donors: Perspectives of donors and recipients in Japan.

INTRODUCTION: In Japan, approximately 90% of kidney transplantations involve living donors who are relatives. Selection of a living donor from potential family member donors could affect the entire family. However, reports focusing on preliving-related kidney transplant (LRKT) family functioning are lacking. Family functioning comprises ways that family members communicate and cooperate with each other. The Family Assessment Device (FAD) was used to measure family functioning from the perspective of donors and recipients just prior to LRKT. METHOD: A total of 122 donor-recipient pairs (244 participants in total) who planned to have LRKT were recruited consecutively from July 2020 to July 2021 and included in the analysis. RESULTS: There was no significant difference in FAD scores between donors and recipients, with approximately 20% of both groups reporting poor family functioning. Differences in family functioning according to types of relatives were shown in recipients. The rate of poor family functioning was significantly lower in the spouse group than in the parent-to-child group (recipient: 6.6%, 29.3%; donor: 8.2%, 34.1%, respectively). However, agreement regarding good or poor family functioning assessment was high in the parent-to-child pairs and low in the spouse pairs. DISCUSSION: Most LRKT donors and recipients reported good family functioning; however, some perceived poor family functioning. Evaluations by donors did not always align with that of recipients, especially among spouse pairs. It is important to treat them as independent entities. Preoperative assessment to connect them with appropriate support can enhance recovery after LRKT. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Quartz crystal microbalance sensor using ionophore for ammonium ion detection.

Ionophore-based quartz crystal microbalance (QCM) ammonium ion sensors with a detection limit for ammonium ion concentrations as low as 2.2 microM were fabricated. Ionophores are molecules, which selectively bind a particular ion. In this study, one of the known ionophores for ammonium, nonactin, was used to detect ammonium ions for environmental in-situ monitoring of aquarium water for the first time. To fabricate the sensing films, poly(vinyl chloride) was used as the matrix for the immobilization of nonactin. Furthermore, the anionic additive, tetrakis (4-chlorophenyl) borate potassium salt and the plasticizer dioctyl sebacate were used to enhance the sensor properties. The sensor allowed detecting ammonium ions not only in static solution, but also in flowing water. The sensor showed a nearly linear response with the increase of the ammonium ion concentration. The QCM resonance frequency increased with the increase of ammonium ion concentration, suggesting a decreasing weight of the sensing film. The detailed response mechanism could not be verified yet. However, from the results obtained when using a different plasticizer, nitrophenyl octyl ether, it is considered that this effect is caused by the release of water molecules. Consequently, the newly fabricated sensor detects ammonium ions by discharge of water. It shows high selectivity over potassium and sodium ions. We conclude that the newly fabricated sensor can be applied for detecting ammonium ions in aquarium water, since it allows measuring low ammonium ion concentrations. This sensor will be usable for water quality monitoring and controlling.

Optimal time and threshold of absolute lymphocyte count recovery as a prognostic factor after single-unit cord blood transplantation in adults.

We retrospectively evaluated the optimal time and threshold of absolute lymphocyte count (ALC) recovery as a prognostic factor in 174 adult patients who received single-unit cord blood transplantation (CBT) at our institute. We analyzed the impact of ALC ≥300, ≥600, and ≥900/µl by 30 and 60 days on transplant outcomes. Multivariate analysis showed that only ALC ≥300/µl at 60 days was significantly associated with overall mortality (hazard ratio, 0.24; p = 0.001) following CBT. The optimal time point to use ALC recovery as a prognostic tool following CBT could be later than those following adult donor transplantation.

Psychosocial Assessment of Transplant Candidates: Inter-rater Reliability and Concurrent Validity of the Japanese Version of the Stanford Integrated Psychosocial Assessment for Transplantation.

BACKGROUND: The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a comprehensive instrument developed to provide a standardized, objective, and evidence-based psychosocial evaluation of the main pretransplant psychosocial risk factors that may influence transplant outcomes. OBJECTIVE: Because established assessment procedures or standardized tools designed to perform pre-solid organ transplant psychosocial evaluation are currently unavailable in Japan, the present study aimed to develop and preliminarily validate the Japanese version of the SIPAT. METHODS: First, the Japanese version of the SIPAT was developed using standard forward-back-translation procedures. Then, the Japanese versions of the SIPAT and the Japanese version of Psychosocial Assessment of Candidates for Transplant were retrospectively and blindly applied to 107 transplant cases by 4 independent raters. RESULTS: The interrater reliability of the scores obtained with the Japanese version of the SIPAT was excellent (Pearson's correlation coefficient = 0.86). The concurrent validity of the SIPAT to the Psychosocial Assessment of Candidates for Transplant for each examiner was substantial (Spearman's rank correlation coefficient = -0.66). CONCLUSION: These findings suggest that the Japanese version of the SIPAT is a promising and reliable instrument. Further research is required to test the predictive validity of the Japanese version of the SIPAT.

Jellyfish vision starts with cAMP signaling mediated by opsin-G(s) cascade.

Light sensing starts with phototransduction in photoreceptor cells. The phototransduction cascade has diverged in different species, such as those mediated by transducin in vertebrate rods and cones, by G(q)-type G protein in insect and molluscan rhabdomeric-type visual cells and vertebrate photosensitive retinal ganglion cells, and by G(o)-type G protein in scallop ciliary-type visual cells. Here, we investigated the phototransduction cascade of a prebilaterian box jellyfish, the most basal animal having eyes containing lens and ciliary-type visual cells similar to vertebrate eyes, to examine the similarity at the molecular level and to obtain an implication of the origin of the vertebrate phototransduction cascade. We showed that the opsin-based pigment functions as a green-sensitive visual pigment and triggers the G(s)-type G protein-mediated phototransduction cascade in the ciliary-type visual cells of the box jellyfish lens eyes. We also demonstrated the light-dependent cAMP increase in the jellyfish visual cells and HEK293S cells expressing the jellyfish opsin. The first identified prebilaterian cascade was distinct from known phototransduction cascades but exhibited significant partial similarity with those in vertebrate and molluscan ciliary-type visual cells, because all involved cyclic nucleotide signaling. These similarities imply a monophyletic origin of ciliary phototransduction cascades distributed from prebilaterian to vertebrate.

Characterization of novel zebrafish MHC class I U lineage genes and their haplotype.

Major histocompatibility complex (MHC) genes are essential for distinguishing between individuals in all jawed vertebrates. Although MHC class I (mhc1) genes in zebrafish comprise distinct haplotypes, not all members of the mhc1 gene family have been fully characterized. In this study, we report the identification of two novel U lineage genes isolated from the WIK strain of zebrafish. These new mhc1 genes, named una and uoa, are located in tandem on chromosome 19 with >70% homology to previously isolated U genes. Sequencing of their neighboring genes revealed that una and uoa form a unique haplotype different from the previously known U lineage haplotypes. Additionally, we determined the expression profiles of U, Z, and L genes in three different tissues. These findings collectively suggest that mhc1 U lineage genes and their haplotypes in zebrafish are more divergent than previously considered, and their expression patterns vary significantly among different tissues.