Successful treatment with nilotinib after bosutinib-induced pulmonary arterial hypertension recurrence following dasatinib in chronic myeloid leukemia in chronic phase.

A 52-year-old man was diagnosed with chronic myeloid leukemia in the chronic phase (CML-CP). He experienced bosutinib-induced pulmonary arterial hypertension (PAH) recurrence following dasatinib use. Symptoms and examination findings associated with PAH improved after bosutinib cessation. Although nilotinib was started because of the loss of response after bosutinib cessation, a deep molecular response without PAH recurrence was achieved 3 months after the initiation of nilotinib therapy. PAH recurrence after switching to bosutinib due to dasatinib-induced PAH should be closely monitored. In addition, nilotinib therapy might be an effective approach in PAH cases related to dasatinib and/or bosutinib in patients with CML-CP.

Prognostic impact of the dosage of methotrexate combined with tacrolimus for graft-versus-host disease prophylaxis after cord blood transplantation.

The optimal dosage of methotrexate (MTX) for graft-versus-host disease (GVHD) prophylaxis after cord blood transplantation (CBT) has not been well elucidated. Therefore, we conducted a retrospective study comparing a mini-MTX group (5 mg/m2 on day 1, 3 and 6) to a short-MTX group (10 mg/m2 on day 1 and 7 mg/m2 on day 3 and 6) after CBT. Sixty-three patients were classified as the mini-MTX group and 20 as the short-MTX group. The median time and cumulative incidence of neutrophil engraftment did not vary between the two groups. The cumulative incidence of grade 2-4 and grade 3-4 acute GVHD was similar in both groups. Overall survival in the mini-MTX group was significantly lower than in the short-MTX group (46.9% vs. 88.7% at 1 year, p < 0.01), contributing to higher non-relapse mortality (NRM) in the mini-MTX group (32.0% vs. 5.0% at 1 year, p = 0.02). In multivariate analysis, the mini-MTX regimen was the most powerful prognostic factor for OS (hazard ratio 4.11; p = 0.03). Although the reduced dosage of MTX had no effect on neutrophil engraftment, increased NRM due to higher incidence of infection, graft failure, and severe acute GVHD resulted in a lower survival rate in the mini-MTX group after CBT.

[Sarcoidosis-lymphoma syndrome showing abnormal FDG uptake in lymph nodes and muscles upon post-chemotherapy PET/CT imaging].

A 65-year-old woman was diagnosed with rheumatoid arthritis in 2010 and was treated with methotrexate (MTX). In 2012, she was diagnosed with sarcoidosis and underwent a follow-up therapy for mild peripheral neuropathy due to neurosarcoidosis. In 2018, she experienced primary splenic diffuse large B-cell lymphoma (DLBCL) and was diagnosed with sarcoidosis-lymphoma syndrome (SLS). MTX was discontinued, and six cycles of rituximab were administered combined with chemotherapy. Positron emission tomography combined with computed tomography performed 18 weeks after the last cycle of chemotherapy showed new abnormal fluoro-2-deoxy-D-glucose (FDG) uptake in the mediastinal and hilar lymph nodes and skeletal muscles. Sarcoidosis was suspected because of increased serum angiotensin-converting enzyme levels and magnetic resonance imaging findings in the lower limb muscles. However, pathological findings of DLBCL and sarcoidosis were not confirmed in the hilar lymph node biopsy. Therefore, malignant lymphoma can be distinguished from sarcoidosis using abnormal FDG uptake after chemotherapy for SLS.

Serum IgM levels independently predict immune response to influenza vaccine in long-term survivors vaccinated at >1 year after undergoing allogeneic hematopoietic stem cell transplantation.

Influenza virus infection can cause fatal complications (e.g., pneumonia) in immunodeficient long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The immune response to the vaccine improves if it is administered at >1 year after allo-HSCT, although the response may vary according to the patient's immune status. We sought to identify predictors of immune response to trivalent inactivated influenza vaccine (TIV) among patients vaccinated at >1 year after allo-HSCT. We included 27 allo-HSCT recipients, with a median interval of 4.3 years (range 1.0-10.1 years) from transplantation to vaccination. Nineteen patients achieved a response to TIV, although a low immune response to TIV was significantly associated with calcineurin inhibitor treatment, and moderate chronic graft-versus-host disease and IgM levels of <0.5 g/L at the time of vaccination. Multivariate analysis revealed that IgM levels of <0.5 g/L at the vaccination were an independent predictor of a low immune response to TIV. These results indicate that a more effective approach is needed to induce a vaccine-specific immune response among long-term survivors of allo-HSCT who have low serum IgM levels.

Involvement of transfusion unit staff in the informed consent process.

BACKGROUND AND OBJECTIVES: Obtaining informed consent (IC) for a blood transfusion is an absolute requirement. In this study, we compared the depth of understanding of blood transfusion among patients with or without an explanation by the transfusion unit staff and evaluated the usefulness of this intervention in obtaining IC. MATERIALS AND METHODS: Expert staff from the transfusion unit started to provide patients with a basic explanation of blood transfusion (intervention group, n = 129). The efficacy of this strategy was assessed by comparison with explanation given by the primary doctors only (conventional group, n = 31). We performed a questionnaire survey to analyze the length of time spent providing information of blood transfusion and the depth of understanding of blood transfusion in the two groups. RESULTS: The median time in providing information in the conventional and intervention groups was 6 and 20 minutes, respectively (P < 0.0001). Patients in the intervention group had a better understanding of several key points on blood transfusion than those in the conventional group. CONCLUSION: Our results show that expert staff from the transfusion unit should be involved in obtaining IC for a blood transfusion. Patients who were provided information by transfusion unit staff were more likely to have a better understanding of the risks and benefits of transfusion.

Evaluation of the in-hospital hemovigilance by introduction of the information technology-based system.

BACKGROUND: Hemovigilance is an important aspect of transfusion medicine. However, the frequency of the adverse reactions often varies using different reporters. Recently, we have employed a new information technology (IT)-based in-hospital hemovigilance system. Here, we evaluated changes in practice after implementation of an IT-based reporting system. STUDY DESIGN AND METHODS: We compared the rate of frequency and details of blood transfusion-related adverse reactions 3 years before and after introduction of the IT-based reporting system. Contents and severity of the adverse reactions were reported in a paper-based reporting system, but input by selecting items in an IT-based reporting system. The details of adverse reactions are immediately sent to the blood transfusion unit online. RESULTS: After we introduced the IT-based reporting system, the reported rate of transfusion-related adverse reactions increased approximately 10-fold from 0.20% to 2.18% (p < 0.001), and frequencies of urticaria, pruritus, rash, fever (p < 0.001), hypertension (p = 0.001), tachycardia (p = 0.003), and nausea and vomiting (p = 0.010) increased significantly. Although there was no error report in the paper-based reporting, incorrect reports were observed in 90 cases (0.52%) in the IT-based reporting (p < 0.001). CONCLUSION: The advantages of IT-based reporting were: 1) a significant increase in the frequency of adverse reaction reporting and 2) a significant decrease in underreporting, although the true frequency has yet to be clarified. The disadvantage of the IT-based reporting was an increased incidence of incorrect inputs, all of which was unnoticed by the reporters. Our results showed several important points in need of monitoring after introduction of an IT-based reporting system.

[Management directed at preventing misidentifications by introduction of the computed identification system and blood sampling by the transfusion unit; aim for good partnership between a transfusion unit and bedsides].

The initial step of blood transfusion therapy is blood type grouping. ABO-mismatch blood transfusion results in serious adverse effects. Several incidents in the process of blood sampling had been experienced in our hospital since 2006 to 2008. Therefore, we have introduced the computed identification system, and the transfusion unit has taken a part of blood sampling. Just after we introduced it in July 2010, only 7% of the doctors and the nurses used the system in blood sampling. Repeated training programs for doctors and nurses on blood sampling procedure improved the utilization to 95%. We realized the importance of our management in face of its introduction. We have to make continuous efforts on the safety of transfusion therapy, because new type of incidents can appear.

Increased arterial stiffness in female-to-male transsexuals treated with androgen.

AIM: Female-to-male (FTM) transsexuals are treated with long-term and high-dose androgen. Although androgen is known to affect the cardiovascular system, vascular function in FTM transsexuals has not been fully elucidated. The aim of this study was to evaluate the arterial stiffness in FTM transsexuals treated with androgen. METHODS: We evaluated the arterial stiffness in 111 FTM transsexuals (63 untreated FTM transsexuals and 48 FTM transsexuals treated with androgen) using a volume-plethysmographic apparatus equipped with a multi-element applanation tonometry sensor. RESULTS: There were no significant differences in age, body mass index and heart rate between the untreated FTM transsexuals and those treated with androgen. The systolic and diastolic blood pressures in FTM transsexuals treated with androgen were significantly higher than those in untreated FTM transsexuals. The level of brachial-ankle pulse wave velocity in FTM transsexuals treated with androgen (1202.8+/-138.2 cm/s) was significantly higher than that in untreated FTM transsexuals (1080.2+/-113.7 cm/s) while there was no significant difference in the carotid augmentation index between untreated FTM transsexuals and those treated with androgen. CONCLUSIONS: Long-term and high-dose administration of androgen is likely to cause increased arterial stiffness in FTM transsexuals. To prevent atherosclerosis and cardiovascular events, a periodic checkup and pharmacological therapies for hypertension should be tailored on an individual basis.

Properties of Orange-Pupa-Inducing Factor (OPIF) in the swallowtail butterfly, Papilio xuthus L.

Diapause pupae of the swallowtail butterfly Papilio xuthus L. exhibit diapause-green, orange and brownish-orange color polymorphism. Development of orange pupae involves a neuroendocrine factor inducing orange pupa (Orange-Pupa-Inducing Factor, OPIF), which is secreted from the head-thoracic region during late pharate pupal stages, in particular from the ganglia of short-day animals located posteriorly from the second thoracic ganglion2 (TG2). This report describes certain properties of OPIF using bioassays involving ligated abdomens of short-day pharate pupae. Localization of OPIF in the central nervous system of short-day larvae indicated that it was present predominantly in TG2, thoracic ganglion3 (TG3) and abdominal ganglion1 (AG1) complexes. OPIF activity in TG(2,3)-AG1 complexes was over two times higher than in the more posteriorely located ganglia. The developmental profile of OPIF in last instar short-day larvae revealed that OPIF activity in larval ganglia posterior to TG2 became gradually higher as larval growth proceeded, suggesting that OPIF might be accumulated in TG(2,3)-AG(1-7) complexes as larvae prepare for pupal molting. Furthermore, ligated abdomens of short-day larvae developed into pupae of an orange type when a 2% NaCl extract containing OPIF prepared from TG(2,3)-AG(1-7) complexes of long-day larvae was injected into ligated abdomens of short-day pharate pupae, indicating that OPIF is also present in long-day larvae. Additionally, a biochemical investigation using gel filtration chromatography showed that the molecular weight of OPIF was about 10 kDa.

Hormonal control of the orange coloration of diapause pupae in the swallowtail butterfly, Papilio xuthus L. (Lepidoptera: Papilionidae).

Diapause pupae of Papilio xuthus show color polymorphism, represented by diapause-green, orange, and brownish-orange types that are each associated with specific pupation sites. We investigated the role of the site of pupation on the induction of the development of orange types (or brownish-orange types), and the endocrine mechanism underlying the control of color polymorphism in short-day pupae. All short-day larvae of the wandering stage developed into orange or brownish-orange type pupae when they were placed in rough-surfaced containers after gut-purge. Utilizing a pharate pupal ligation between the thorax and abdomen, the endocrine mechanism underlying the control of color polymorphism was shown to involve a head-thorax factor (Orange-Pupa-Inducing Factor: OPIF) that induced orange types in short-day pupae. OPIF was bioassayed using the ligated abdomens of short-day pharate pupae. OPIF was extractable with 2% NaCl solution from 5th-instar larval ganglia complexes following the mesothoracic complex (TG(2,3)-AG(1-7)), but it could not be extracted with either acetone or 80% ethanol solution. OPIF may not exist in the brains of day-0 pupae or in brain-subesophageal ganglion and prothoracic ganglion complexes of 5th-instar larvae. The short-day pharate pupae responded to OPIF in a dose-dependent manner.