Prognostic factors of idiopathic hypereosinophilic syndrome: A nationwide survey in Japan.

Idiopathic hypereosinophilic syndrome (iHES) is a condition wherein persistent hypereosinophilia associated with end-organ damage occurs without any known causes. Due to the rarity of the disease, insufficient knowledge has been accumulated. We therefore conducted a retrospective, multicentre, nationwide survey on iHES in Japan. A total of 57 patients were identified. For 43 patients who received any treatment, all cases were first treated with corticosteroids. An eosinophil percentage of less than 30% in the bone marrow and the absence of oedema were identified as factors associated with steroid dependency. The 5-year overall survival was 88.2%, and five patients died during follow-up; factors associated with worse overall survival were age >50, haemoglobin <12 g/dL, activated partial thromboplastin time >34 s, the presence of dyspnoea, the presence of thrombotic tendency and the presence of renal failure. Given the rarity of fatalities in our cohort, time-to-next-treatment (TTNT) was further analysed; the presence of renal failure, splenomegaly and lung abnormalities were associated with worse TTNT. Our nationwide study not only demonstrated clinical characteristics and the outcome of patients with iHES but also for the first time revealed clinical factors associated with steroid dependency and duration of first-line corticosteroid efficacy.

Effects of running with surgical masks on cardiopulmonary function in healthy male university students.

[Purpose] In Japan, one measure against the novel coronavirus disease-2019 infection involves the public use of surgical masks. Research indicates that exercising while wearing a mask increases the physical burden, particularly affecting young people during high-intensity exercise. This study examined the effects of wearing masks while running in male university students. [Participants and Methods] The participants were 20 healthy male university students (21.6 ± 1.6 years). The participants underwent cardiopulmonary exercise tests with the masks on and off on different days until exhaustion. The following parameters were measured: exercise duration, Borg Scale rating (respiratory or lower extremities), surface temperature around the mouth, time to sweat onset, metabolic reaction, pulmonary ventilation, and cardiovascular reaction parameters. [Results] The results showed that VO2 max remained consistent between the mask-on and mask-off conditions. However, minute ventilation, respiratory rate, and heart rate decreased in the mask-on condition, which correlated with a reduction in exercise duration. Furthermore, running with the mask significantly decreased the VE/VO2, VE/ VO2, Borg Scale rating of the lower extremities, and the time to sweat onset. [Conclusion] Running with a surgical mask affected respiratory function and decreased exercise duration in healthy male university students. However, it did not induce any changes in VO2 max.

Comparison of transplant outcomes between haploidentical transplantation and single cord blood transplantation in non-remission acute myeloid leukaemia: A nationwide retrospective study.

Allogeneic haematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for some patients with acute myeloid leukaemia (AML) who are refractory to chemotherapy. Cord blood transplantation (CBT) is a reasonable option in such cases because of its rapid availability. Recently, a growing number of human leucocyte antigen (HLA)-haploidentical related donor HSCTs (haplo-HSCTs) have been performed, although its effectiveness remains undetermined. Using the Japanese nationwide transplantation registry data, we identified 2438 patients aged ≥16 years who received CBT or haplo-HSCT as their first transplant for non-remission AML between January 2008 and December 2018. After 2:1 propensity score matching, 918 patients in the CBT group and 459 patients in the haplo-HSCT group were selected. In this matched cohort, no significant difference in overall survival (OS) was observed between the CBT and haplo-HSCT groups (hazard ratio [HR] of haplo-HSCT to CBT 1.02, 95% confidence interval [CI] 0.89-1.16). Similarly, no significant difference in the cumulative incidence of relapse (HR 1.09, 95% CI 0.93-1.28) or non-relapse mortality (HR 0.94, 95% CI 0.76-1.18). Subgroup analysis showed that CBT was significantly associated with preferable OS in patients receiving myeloablative conditioning. Our data showed comparable outcomes between haplo-HSCT and CBT recipients with non-remission AML.

Recurrent bilateral adrenal infarction with myelodysplastic/myeloproliferative neoplasm-unclassifiable (MDS/MPN-U): a case report.

BACKGROUND: Bilateral adrenal infarction is rare and only a small number of cases have been reported so far. Adrenal infarction is usually caused by thrombophilia or a hypercoagulable state, such as antiphospholipid antibody syndrome, pregnancy, and coronavirus disease 2019. However, adrenal infarction with myelodysplastic/myeloproliferative neoplasm (MDS/MPN) has not been reported. CASE PRESENTATION: An 81-year-old man with a sudden severe bilateral backache presented to our hospital. Contrast-enhanced computed tomography (CT) led to the diagnosis of bilateral adrenal infarction. Previously reported causes of adrenal infarction were all excluded and a diagnosis of MDS/MPN-unclassifiable (MDS/MPN-U) was reached, which was considered to be attributed to adrenal infarction. He developed a relapse of bilateral adrenal infarction, and aspirin administration was initiated. Partial primary adrenal insufficiency was suspected as the serum adrenocorticotropic hormone level was persistently high after the second bilateral adrenal infarction. CONCLUSION: This is the first case of bilateral adrenal infarction with MDS/MPN-U encountered. MDS/MPN has the clinical characteristics of MPN. It is reasonable to assume that MDS/MPN-U may have influenced bilateral adrenal infarction development, considering the absence of thrombosis history and a current comorbid hypercoagulable disease. This is also the first case of recurrent bilateral adrenal infarction. It is important to carefully investigate the underlying cause of adrenal infarction once adrenal infarction is diagnosed, as well as to assess adrenocortical function.

Drug approval delays in hematologic malignancies between Europe and the US and between Japan and the US: a clinical perspective.

OBJECTIVE: Since novel therapeutic agents for malignancies are developed rapidly mainly in the US, the interval of approval timing between the US and other countries is an important issue. Among them, drugs for hematologic malignancies tended to have a particularly long delays in Japan, but its characteristics have not been fully understood. This study assessed the approval delays in drugs for hematologic malignancies in Japan compared with that in Europe. METHODS: Using the public database of Europe, Japan and the US, we analyzed the differences in drug approval delays between Europe and the US and between Japan and US according to disease. New molecular entity drugs for hematologic malignancies that were already approved in the US and were approved from April 2010 to March 2022 in Europe or Japan were identified. RESULTS: The results showed the longer drug approval delays in Japan compared with that in Europe (29 vs. 9.4 months, median), presumably due to the lower proportion of participation in global clinical trials (37 vs. 94%). Notably, the participation rate in global clinical trials varied widely by disease in Japan, resulting in a greater difference in drug approval delays by disease. In contrast, when focusing on early phase trials, Japanese participation was uniformly very limited regardless of the disease. CONCLUSIONS: The current study provided data that can be used as a basis for discussion on how to improve drug approval delays in drugs for hematologic malignancies.

Toxic shock like syndrome caused by Streptococcus agalactiae bacteremia during treatment for multiple myeloma.

Toxic shock-like syndrome (TSLS) is a life-threatening hyperinflammatory complication caused by Streptococcus species infections. We reported the first case of TSLS caused by primary bacteremia of Streptococcus agalactiae during chemotherapy for multiple myeloma. A 74-year-old woman, who received combination chemotherapy of elotuzumab, pomalidomide, and dexamethasone for treatment-refractory multiple myeloma, was transported to our hospital under comatose and septic shock. Her blood culture detected Streptococcus agalactiae, and considering the progressive multiorgan failure, she was diagnosed with TSLS. Empiric antibiotic treatment with meropenem and respiratory and circulatory support were quickly initiated, resulting in an almost complete recovery of organ functions. It should be noted that with the advances of chemotherapy, the risk of infection is becoming more diverse.

[Autologous stem cell transplantation after pola-BR regimen as a salvage therapy in relapsed diffuse large B-cell lymphoma].

A 57-year-old male patient with relapsed/refractory diffuse large B-cell lymphoma received 4 courses of Pola-BR (polatuzumab vedotin-bendamustine-rituximab). After treatment, stem cell collection with G-CSF and plerixafor successfully yielded 4.2×106 cells/kg of CD34-positive cells. The patient underwent autologous peripheral hematopoietic stem cell transplantation. Neutrophil engraftment was achieved on day 12 and the patient was followed up without progression. In this case, stem cell mobilization with G-CSF and plerixafor was effective even in patients who had received chemotherapy including bendamustine, which is known to sometimes complicate stem cell collection. Although bendamustine should generally be avoided in cases where stem cell collection is planned, there are cases in which the decision to perform transplantation is made after chemotherapy including bendamustine. We have reported a case in which we were able to perform stem cell collection after pola-BR regimen.

Cerebral toxoplasmosis complicating lymphoplasmacytic lymphoma in partial remission.

Toxoplasma gondii can develop toxoplasmic encephalitis (TE) in immunodeficient conditions such as AIDS and after organ transplantation. While some cases of TE with malignant lymphoma were reported, these cases occurred immediately after chemotherapy or when their diseases were active. Here we report the first Case of TE that occurred in patient who was in partial remission (PR) of lymphoplasmacytic lymphoma (LPL) for two years. A 76-year-old man was referred to our institute because of disturbance of consciousness, right arm weakness and paresthesia. A computed tomography (CT) scan detected multiple nodules in his brain. Magnetic resonance imaging (MRI) of the head detected multiple gadolinium-enhancing parenchymal lesions with hyperintense signals on T2-and diffusion-weighted images, located in both cerebral and cerebellar hemispheres. Blood test and cerebrospinal fluid (CSF) findings were unremarkable. His rapidly deteriorating consciousness precluded a chance of brain biopsy. Considering the limited efficacy of antimicrobials and the imaging findings that could be compatible with the diagnosis of malignant lymphoma, we suspected central nerve system (CNS) recurrence of LPL. Although chemotherapy was initiated, he died of respiratory failure just after chemotherapy. A pathological autopsy showed his cause of death was TE. To our knowledge, this is the first case of TE in long-term PR of malignant lymphoma. TE should be suspected when patients with malignant lymphoma present unexplained neurologic symptoms regardless of their treatment efficacy of lymphoma. (226/250 words).

Reduction of cycles of bendamustine plus rituximab therapy in the cases with good response for indolent B-cell lymphomas.

Bendamusutine plus rituximab (BR) regimen is one of the standard regimens for indolent B-cell lymphomas, yet the possibility of reduction of cycles of BR therapy without compromising therapeutic effects is not still uncovered. We retrospectively surveyed 57 cases including 40 follicular lymphoma cases who underwent BR regimen in our institute. The overall response (OR) rate and complete response (CR) rate were 86.0% (95% confidential interval (CI), 74.2-93.7) and 54.4% (40.7-67.6), respectively. Five-year overall survival (OS) and 5-years progression-free survival (PFS) were 76.8% and 45.7%, respectively. We then grouped the patients by the number of administered cycles of BR regimen. PFS was significantly longer in 41 cases of the later cessation group (cycle 4-6) than in 16 cases of the earlier cessation group (cycle 1-3) (p = 0.012, 5-years PFS; 46.8% vs. 35.2%, respectively), and both of OR and CR rate of the former was better than the latter (OR rate; 95.1% vs. 62.5%, p < 0.01, CR rate; 61.4% vs. 31.3%, p = 0.04). Interestingly PFS of twenty-one (36.8%) cases receiving just 4 cycles was longer than that of 20 cases who received five or 6 cycles (p < 0.01, 5-years PFS; 71.8% vs. 23.2%, respectively). Focusing on the group of four cycles, the 12 case with CR revealed longer PFS than seven cases with partial response (PR), and median PFS was not reached in CR cases and 16.9 months in the PR cases (p < 0.01). These results suggest that four cycles at least should be administered if possible, and the outcome of the patients who discontinued BR after four cycles was not inferior to that of the cases who received five or six cycles. In conclusion, discontinuation after four cycles may be permissible in some cases with complete response to BR regimen.

Risk factors for early in-hospital death in patients who developed coagulopathy during induction therapy for acute promyelocytic leukemia: a nationwide analysis in Japan.

To prevent early death, management of coagulopathy is important in patients with untreated acute promyelocytic leukemia (APL). This study aimed to clarify factors associated with in-hospital death in patients with coagulopathy during induction therapy for APL. We retrospectively identified patients with newly diagnosed APL who received induction therapy including all-trans retinoic acid (ATRA) and developed coagulopathy, using a nationwide inpatient database in Japan. Of 1115 eligible patients, 175 (15%) died at a median of 13 days (interquartile range, 7-30) after admission. In the multivariable analysis, compared with younger patients (aged < 40 years), the occurrence of in-hospital death was significantly more common among older patients (aged ≥ 40 and < 60 years: odds ratio = 2.58 [95% confidence interval: 1.29-5.19]; aged ≥ 60 and < 80 years: 7.66 [3.89-15.10]; aged ≥ 80 years: 16.83 [7.41-38.21]). Delayed initiation of ATRA and no conventional chemotherapy were significantly associated with in-hospital death (1.79 [1.16-2.76] and 2.40 [1.47-3.92], respectively). A total of 699 patients (63%) received anticoagulant therapies, but none of these was significantly associated with lower mortality. Although the present study was constrained by a lack of laboratory findings because of database limitations, the results showed that untreated patients with APL, especially the elderly, had a poor prognosis. Immediate administration of ATRA may reduce in-hospital mortality.

Difference of preventing effects of G-CSF according to age in patients with malignant lymphoma: A nation-wide analysis in Japan.

INTRODUCTION: There has been no comprehensive analysis of the age-specific efficacy of G-CSF to prevent febrile neutropenia (FN). We evaluated factors associated with FN occurrence according to patient age in rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP) treatment. METHODS: We retrospectively reviewed diffuse large B-cell lymphoma (DLBCL) patients aged ≥50 years, who underwent the first R-CHOP cycle between July 2010 and March 2017, using a Japanese inpatient database. Multivariable logistic regression analysis was performed to identify the factors associated with FN. RESULTS: A total of 16,399 patients with untreated DLBCL were identified. Primary prophylaxis with pegfilgrastim was significantly associated with the lower occurrence of FN (odds ratio: 0.71 [95% confidence interval: 0.51-0.99]). Subgroup analysis according to age was then performed. Although there was no significance, primary prophylaxis with pegfilgrastim tended to have a lower odds ratio for the occurrence of FN in patients aged 50-60 years (0.86 [0.39-1.89]) and 61-70 years (0.64 [0.36-1.13]). In patients aged 71-80 years, primary prophylaxis with pegfilgrastim was significantly associated with reduced FN occurrence (0.46 [0.26-0.80]). Notably, in patients aged >80 years, the use of pegfilgrastim tended to be associated with a rather higher occurrence of FN (1.55 [0.84-2.87]). CONCLUSIONS: Preventing effect of G-CSF may be limited in patients aged >80 years.

Effects of short-term immobilization of the upper limb on the somatosensory pathway: a study of short-latency somatosensory evoked potentials.

[Purpose] Previous studies have reported that the nervous system is influenced during short-term cast immobilization. However, the effects of short-term inactivity on somatosensory information processing systems are not well understood. This study investigated the effect of 10 h of upper limb immobilization on the somatosensory pathway using short-latency somatosensory evoked potentials. [Participants and Methods] Twenty right-handed healthy participants (mean age 21.7 years) were enrolled in this study. The participants' left hands and forearms were wrapped in a soft bandage at a 90° elbow flexed position. The participants were instructed not to move their left hand for 10 h. To obtain short-latency somatosensory evoked potentials, we used a multimodal evoked potential system. The left median nerve was electrically stimulated at a rate of 5 Hz for a duration of 0.2 ms. The intensity of the stimulus was adjusted to induce mild twitches of the thumb. The amplitudes and latencies of the short-latency somatosensory evoked potential components (N9, N13, and N20) were measured before and after immobilization. [Results] The amplitude of the N9 component significantly increased after immobilization. [Conclusion] Our results indicated that the changes in the excitability of the peripheral somatosensory nerve were due to 10 h of inactivity.

A path analysis of the interdependent relationships between life space assessment scores and relevant factors in an elderly Japanese community.

[Purpose] This study aimed to examine the direct and indirect effects of factors influencing the risk of life space assessment using path analysis. [Participants and Methods] A sample of 212 elderly residents (at least 65 years old) with no clear indications of cognitive dysfunction, visual impairment, and physical dysfunction were recruited for the study. Data on these factors were collected from the participants at a community gathering using measures of life space assessment, skeletal muscle mass, lower extremity muscle strength, mobility, cognitive function, and fear of falling. Correlational and path analyses were used to investigate the relationships between these variables. [Results] The final path model satisfied the requisite statistical criteria, and subsequently, the relationships between the physiological and psychological factors associated with life space assessment were structured and represented visually. Age, skeletal muscle mass, fear of falling, and mobility had a direct effect on life space assessment, whereas lower extremity muscle strength and cognitive function affected it indirectly. [Conclusion] In this study, direct and indirect effects of physiological and psychological factors related to risk of life space assessment of the elderly were clarified using path analysis.

Effects of the combination therapy of tilt sensor functional electrical stimulation and integrated volitional control electrical stimulation on brain activity during the subacute phase following stroke: a feasibility study.

[Purpose] The aim of this study was to investigate whether the combination of integrated volitional control functional electrical stimulation and tilt sensor functional electrical stimulation training affected brain activation during the subacute phase following a stroke. [Participant and Methods] The patient was a 60-year-old male with right hemiparesis, secondary to stroke in the left thalamus. Conventional intervention was performed for 60 minutes per day during the first two weeks of treatment (the control condition). Functional electrical stimulation intervention, including integrated volitional control functional electrical stimulation and tilt sensor functional electrical stimulation training, was then performed for 60 minutes per day for two weeks (the experimental condition). These sessions were repeated four times. Brain activity was measured during voluntary right ankle dorsiflexion in both sessions, using functional magnetic resonance imaging. Brain activity measurements were obtained a total of eight times every two weeks (34, 48, 62, 76, 90, 104, 118, and 132 days following the stroke). [Results] There was a significantly higher level of activation in the bilateral cerebellum and the left side of the supplementary motor area in the experimental condition than in the control condition. [Conclusion] The present study demonstrates that the combination of integrated volitional control functional.

A therapeutic benefit of daptomycin against glycopeptide-resistant gram-positive cocci bloodstream infections under neutropenia.

Antibiotic-resistant infections remain to be a major issue for all over the world. Although appropriate diagnosis and rapid treatment initiation are crucially important particularly in immunocompromised patients, selection of antibiotics without identification of causative bacteria is often challenging. A 44-year-old woman with acute myeloid leukemia (AML) under myelosuppression suffered from teicoplanin-resistant gram-positive cocci bacteremia. Taking severe neutropenia due to chemotherapy and glycopeptide-resistance into account, teicoplanin was empirically substituted with daptomycin, which led to prompt defervescence. This microorganism later turned out to be Leuconostoc lactis (L. Lactis), and daptmycin was continued to use based on antimicrobial susceptibility tests. As a result, empiric use of daptomycin successfully controlled glycopeptide-resistant gram-positive cocci bacteremia under neutropenia. This is the first report of daptomycin treatment for L. lactis bacteremia in a patient with AML under neutropenia. Our findings suggest that daptomycin would be a suitable treatment option for glycopeptide-resistant gram-positive cocci bloodstream infections, especially in myelosuppressive patients.

Factors influencing executive function by physical activity level among young adults: a near-infrared spectroscopy study.

[Purpose] Prevention of dementia requires early intervention against it. To ensure that early interventions are effective it is crucial to study the cognitive functions related to dementia in young adulthood. Moreover, it is needed not only to verify the cognitive function test but also to elucidate the actual brain activity and the influence of related factors on the brain activity. To investigate the factors influencing cognitive function among young adults and examine the differences in executive function by physical activity level. [Subjects and Methods] Forty healthy university students (mean age, 20.4 years) were classified into two groups by cognitive function score (HIGH and LOW), determined according to Trail Making Test performance and Stroop task processing time. We then assessed what factors were related to cognitive function by logistic regression analysis. Executive function was determined by brain blood flow using near-infrared spectroscopy during the Stroop task, and was then compared by physical activity levels (determined according to number of steps per hour). [Results] Full-scale Intelligence Quotient according to the 3rd Wechsler Adult Intelligent Scale and number of steps per hour influenced cognitive function score, with odds ratios of 1.104 and 1.012, respectively. Oxy-hemoglobin concentrations in areas related to executive function during the Stroop task were significantly higher among those in the high physical activity group than among those in the low physical activity group. [Conclusion] The study revealed that Full-scale Intelligence Quotient and a number of steps per hour are factors associated with the cognitive functions in young adulthood. In addition, activity in execution function related area was found to be significantly higher in the high physical activity group than in the low physical activity group, suggesting the importance of physical activity for enhancing young adulthood cognitive functions.