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.

Impact of Early Cytomegalovirus Reactivation After Allogeneic Hematopoietic Stem Cell Transplantation on Relapse in Patients With Myelodysplastic Syndrome: A Nationwide Retrospective Study From Adult Myelodysplastic Syndrome Working Group of the JSTCT.

Cytomegalovirus (CMV) reactivation is a prominent complication associated with adverse outcomes in allogeneic hematopoietic stem cell transplantation (HSCT). However, CMV reactivation after allogeneic HSCT may be associated with a lower incidence of relapse in some hematological malignancies. This study analyzed the Japanese registry data from 1082 patients with myelodysplastic syndrome (MDS) who underwent their first allogeneic HSCT and survived for 100 days after transplantation without graft failure or disease relapse to investigate this association. Patients who received cord blood transplants, demonstrated in vivo T cell depletion, underwent prophylactic anti-CMV treatment, or diagnosed with secondary MDS were excluded. CMV reactivation measured by pp65 antigenemia within 100 days after allogeneic HSCT was observed in 57.5% of patients, with a median time of 46 days from transplant. The 5-yr overall survival and cumulative incidence of relapse (CIR) in the cohort were 60.5% and 15.6%, respectively. The 5-yr CIR showed no significant difference between patients with and without CMV reactivation (14.4% versus 17.2%; P = .185). Interestingly, CMV reactivation within 100 days was significantly associated with a lower 5-yr CIR (7.6% versus 16.4%; P = .002) in patients with <5% myeloblasts in the bone marrow (BM) just before HSCT. Furthermore, this relevancy confirmed even when excluding patients with Grade II to IV acute GVHD (Hazard ratio: 0.38; 95% confidential intervals: 0.18-0.801; P = .011). Our findings indicate a correlation between early CMV reactivation and MDS relapse, based on the proportion of myeloblasts in the BM. These results may contribute to the development of effective CMV prophylaxis post-HSCT.

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.

Short-Term Cast Immobilization of a Unilateral Lower Extremity and Physical Inactivity Induce Postural Instability during Standing in Healthy Young Men.

Previous studies have reported an increased postural sway after short-term unilateral lower limb movement restriction, even in healthy subjects. However, the associations of motion limitation have not been fully established. The question of whether short-term lower limb physical inactivity and movement restriction affect postural control in the upright position remains. One lower limb of each participant was fixed with a soft bandage and medical splint for 10 h while the participant sat on a manual wheelchair. The participants were instructed to stand still for 60 s under eyes-open (EO) and eyes-closed (EC) conditions. Using a single force plate signal, we measured the center of pressure (COP) signal in the horizontal plane and calculated the total, anterior-posterior (A-P), and medial-lateral (M-L) path lengths, sway area, and mean COP displacements in A-P and M-L directions. The COP sway increased and the COP position during the upright stance shifted from the fixed to the non-fixed side after cast removal, compared to before the cast application, under both EO and EC conditions. These findings indicated that 10 h of unilateral lower limb movement restriction induced postural instability and postural control asymmetry, suggesting the acute adverse effects of cast immobilization.

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.

External validation and extended application of the transplant conditioning intensity score in acute myeloid leukemia.

This study aimed to validate the utility of the transplant conditioning intensity (TCI) score in 1714 patients with acute myeloid leukemia (AML) undergoing allogeneic bone marrow or peripheral blood stem cell transplantation (BMT/PBSCT) and assess its applicability to 753 patients with AML undergoing umbilical cord blood transplantation (UCBT) both during first complete remission. Patients classified into a high TCI group accounted for 63% and 56% in the BMT/PBSCT and UCBT cohorts, respectively. In the BMT/PBSCT cohort, the risk of relapse was lower in patients in the high versus intermediate TCI group (P = 0.002), although non-relapse mortality (NRM) did not differ among the three TCI groups. In the UCBT cohort, both relapse and NRM did not differ among the TCI groups. Increasing cutoff points for intermediate and high TCI categories significantly improved the ability to predict relapse and NRM in the BMT/PBSCT cohort (P = 0.030 and 0.006, respectively), and relapse but not NRM in the UCBT cohort (P = 0.005 and 0.364, respectively). These findings highlight the difference in the threshold level of the TCI score for outcome discrimination between European and Japanese cohorts. The TCI scheme appears less effective for UCBT than for BMT/PBSCT.

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.

Aortitis Associated with Prophylactic Short-acting Granulocyte Colony-stimulating Factor Administration: A Case Report and Review of the Literature.

We herein report an 83-year-old woman with filgrastim-associated aortitis during chemotherapy for relapsed diffuse large B-cell lymphoma. She had been treated with filgrastim as a prophylaxis for neutropenia during the fourth cycle of chemotherapy from day 9 to 18. On day 21, she developed a fever. Contrast-enhanced computed tomography revealed aortitis of the descending aorta. The fever abated with non-steroidal anti-inflammatory drug treatment. A literature review identified a small number of aortitis cases all caused by prophylactic use of granulocyte colony-stimulating factors (G-CSFs), among which short-acting filgrastim was rarely encountered. The present and previous findings imply a possible relationship between aortitis and prophylactic G-CSF usage.

[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.

Effect of Graft-versus-Host Disease on Post-Transplantation Outcomes following Single Cord Blood Transplantation Compared with Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for Adult Acute Myeloid Leukemia.

The possibility that HLA mismatches could reduce relapse after alternative HLA-mismatched allogeneic hematopoietic cell transplantation (HCT) is an attractive concept for treating acute myeloid leukemia (AML). However, it remains unclear whether the prognostic effect of graft-versus-host disease (GVHD) on survival differs between recipients of single-unit cord blood transplantation (CBT) and recipients of haploidentical HCT using post-transplantation cyclophosphamide (PTCy-haplo-HCT) for AML. The objective of this retrospective study was to compare the effect of acute GVHD and chronic GVHD on post-transplantation outcomes between recipients of CBT and recipients of PTCy-haplo-HCT. We retrospectively evaluated the effect of acute and chronic GVHD on post-transplantation outcomes following CBT and PTCy-haplo-HCT in adults with AML (n = 1981) between 2014 and 2020 using a Japanese registry database. In univariate analysis, the probability of overall survival was significantly greater in patients who developed grade I-II acute GVHD (P < .001, log-rank test) and limited chronic GVHD (P < .001, log-rank test) among CBT recipients, but these effects were not significant among PTCy-haplo-HCT recipients. In multivariate analysis, in which the development of GVHD was treated as a time-dependent covariate, the effect of grade I-II acute GVHD on reducing overall mortality differed significantly between CBT and PTCy-haplo-HCT (adjusted hazard ratio [HR] for CBT, .73, 95% confidence interval [CI], .60 to .87; adjusted HR for PTCy-haplo-HCT, 1.07; 95% CI, .70 to 1.64; P for interaction = .038). Our data demonstrate that grade I-II acute GVHD was associated with a significant improvement in overall mortality in adults with AML receiving CBT but not in recipients of PTCy-haplo-HCT.

Expansion of large granular lymphocytes after autologous hematopoietic stem cell transplantation.

Expansion of large granular lymphocytes (LGLs) is sometimes observed in allogeneic hematopoietic stem cell transplantation (HSCT) recipients, and is reported to be associated with a favorable transplant outcome. LGLs are also observed after autologous HSCT, but their clinical implications have not been well investigated. We retrospectively reviewed peripheral blood smears of consecutive autologous HSCT recipients. LGL lymphocytosis was defined as the observation of LGLs in the peripheral blood (> 20% white blood cells) in at least two consecutive blood tests. We evaluated the clinical impact of LGL lymphocytosis on autologous HSCT recipients. LGL lymphocytosis was observed in 18 of 197 patients (9.1%) who received autologous HSCT, at a median of 49 days after transplantation, with a median duration of 120.5 days. Incidence of cytomegalovirus reactivation was significantly higher in patients with LGL lymphocytosis than those without (16.7% vs. 3.3%, p = 0.038). No significant difference in survival rates was observed between groups (3 year OS 90.9% vs. 90.5%, p = 0.793 for lymphoma; 100 vs. 92.4%, p = 0.328 for myeloma). LGL lymphocytosis was observed in almost 10% of autologous HSCT recipients. In contrast to allogeneic HSCT, the duration of LGL was shorter and no significant improvement in survival was observed.

Clinical characteristics of steroid-responsive but dependent chronic graft-versus-host disease: a multicenter retrospective analysis.

Chronic graft-versus-host disease (cGVHD) is a long-term complication of allogeneic hematopoietic stem cell transplantation. The clinical importance of long-term corticosteroid dependency in steroid-responsive cGVHD is undetermined. We retrospectively reviewed the data of 120 consecutive patients who received systemic steroid therapy for cGVHD between January 2007 and December 2018 at three institutions. Among patients with steroid-responsive cGVHD, those who successfully tapered off corticosteroids within 1 year were defined as the early withdrawal group (EW-cGVHD) and others were defined as the dependent group (Dp-cGVHD). Twenty-six patients were classified as EW-cGVHD and 55 as Dp-cGVHD. The proportion of men was significantly higher and performance status was significantly better in EW-cGVHD. The 5-year overall survival and cGVHD recurrence-free survival rates were significantly higher in EW-cGVHD than Dp-cGVHD (96% vs. 68%, p = 0.017 and 84% vs. 41%, p = 0.002, respectively). While the relapse-free survival rate did not differ significantly (84% vs. 65%, p = 0.15), the proportion of patients requiring readmission, mainly due to cGVHD recurrence or infection, was significantly increased in Dp-cGVHD (38% vs. 84%, p < 0.001). In summary, steroid dependency in cGVHD for more than 1 year was significantly associated with poor transplant outcomes.

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.

Prompt Initiation of Conventional Chemotherapy to Avoid Early Death in Patients with Newly Diagnosed Acute Promyelocytic Leukemia.

Objective Compared to prospective trials, the early death rate of newly diagnosed acute promyelocytic leukemia (APL) in the real-world clinical setting is higher. However, the early death rate was heterogeneous according to the reported institutes. Thus, the therapeutic approach at each institute may be important for preventing early death. This study evaluated the management strategy for untreated APL in our institute to avoid early death. Methods We identified consecutive 21 patients with untreated APL who received induction therapy including all-trans retinoic acid (ATRA) between July 2007 and December 2021 at the University of Tokyo Hospital. Results As therapeutic approaches, 16 patients (76%) received ATRA administration on the day of admission, and the remaining 5 received ATRA within 4 days from admission. Notably, all patients received conventional chemotherapy added to ATRA at a median of 1 day from admission (range: 0-9 days). As clinical outcomes, no patient died during induction therapy for untreated APL, and all achieved complete molecular remission. Conclusion Compared to the previous nationwide survey, a higher proportion of patients at our institute received conventional chemotherapy in addition to ATRA, and it was initiated more promptly, which may have helped prevent early death.

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.

Allogeneic Hematopoietic Cell Transplantation for Patients with Relapsed Acute Promyelocytic Leukemia.

Although autologous hematopoietic cell transplantation (HCT) is an established therapy for patients with relapsed acute promyelocytic leukemia (APL) after returning to complete remission (CR), the role of allogeneic HCT remains unclear for treating relapsed APL. This study aimed to investigate allogeneic HCT outcomes in patients with relapsed APL, focusing particularly on those who underwent transplantation in non-CR and those who had relapsed after prior autologous HCT. We retrospectively analyzed Japanese nationwide transplantation registry data of patients with relapsed APL age ≥16 years who underwent allogeneic HCT between 2006 and 2020. A total of 195 patients were eligible for this analysis, including 69 who underwent transplantation in non-CR and 55 who relapsed after prior autologous HCT. The median duration of follow-up for survivors was 5.4 years. Multivariate analysis revealed that both non-CR at transplantation (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.12 to 2.71; P = .014) and prior autologous HCT (HR, 2.10; 95% CI, 1.28 to 3.44; P = .013) were associated with higher risks of overall mortality. The 5-year overall survival (OS) rates for patients who underwent transplantation in CR and non-CR were 58% and 39%, respectively (P = .085), if they did not have a history of prior autologous HCT. In the patients who had relapsed after prior autologous HCT, the 5-year OS rate was 47% for those who underwent allogeneic HCT in CR and 6% for those who did so in non-CR (P = .001). Allogeneic HCT still provides an opportunity for long-term survival for certain patients with relapsed APL for whom autologous HCT is unlikely to be effective. The dismal outcome of those with prior autologous HCT who underwent allogeneic HCT in non-CR poses a significant therapeutic challenge.