Risk factors for thrombocytopenia and analysis of time to platelet transfusion after azacitidine treatment.

The use of azacitidine (AZA) has been known to lead to a high incidence of hematotoxic adverse events. The aims of this study were to identify the risk factors for thrombocytopenia after the administration of AZA and to analyze time to the initial platelet transfusion. Sixty-two patients with myelodysplastic syndrome (MDS), who were treated with AZA in Gifu Municipal Hospital between March 2012 and June 2020, were included in this study. The risk factors for thrombocytopenia were identified using univariate analysis of patient characteristics, disease type, and laboratory values immediately before the start of treatment. Variables with p<0.2 identified in the univariate analysis were used as independent variables in the multivariate analysis. This analysis identified "creatinine clearance (CCr) <60 mL/min" as a significant factor (odds ratio, 4.790; 95% confidence interval [CI], 1.380-16.70; p=0.014). Subsequently, time in days to the initial platelet transfusion after the initial administration of AZA was analyzed using the log-rank test. The overall median time in days to platelet transfusion was 370 days. The log-rank test was used to determine the influence of patient characteristics, disease type, and laboratory values immediately before the start of treatment. The subsequent Cox proportional hazard regression analysis using variables with p<0.2 as independent variables identified "hemoglobin (Hb) <8.0 g/dL" as a significant factor (hazard ratio, 2.143; 95% CI, 1.001-4.573; p=0.048). The results of this study led to the following clinical implications: first, patients with CCr of <60 mL/min at the start of treatment should be treated with caution due to the risk of thrombocytopenia. Second, patients with Hb of <8.0 g/dL at the start of treatment may require platelet transfusion in the early stage of treatment.

Discovery of mesoscopic nematicity wave in iron-based superconductors.

Nematicity is ubiquitous in the electronic phases of iron-based superconductors. The order parameter that characterizes the nematic phase has been investigated in momentum space, but its real-space arrangement remains largely unexplored. We use linear dichroism (LD) in a low-temperature laser­photoemission electron microscope to map out the nematic order parameter of nonmagentic FeSe and antiferromagnetic BaFe2(As0.87P0.13)2. In contrast to structural domains, which have atomic-scale domain walls, the LD patterns in both materials show peculiar sinusoidal waves of electronic nematicity with wavelengths more than 1000 times as long as the unit cell. Our findings put strong constraints on the theoretical investigation of electronic nematicity.

Penetration of MeV electrons into the mesosphere accompanying pulsating aurorae.

Pulsating aurorae (PsA) are caused by the intermittent precipitations of magnetospheric electrons (energies of a few keV to a few tens of keV) through wave-particle interactions, thereby depositing most of their energy at altitudes ~ 100 km. However, the maximum energy of precipitated electrons and its impacts on the atmosphere are unknown. Herein, we report unique observations by the European Incoherent Scatter (EISCAT) radar showing electron precipitations ranging from a few hundred keV to a few MeV during a PsA associated with a weak geomagnetic storm. Simultaneously, the Arase spacecraft has observed intense whistler-mode chorus waves at the conjugate location along magnetic field lines. A computer simulation based on the EISCAT observations shows immediate catalytic ozone depletion at the mesospheric altitudes. Since PsA occurs frequently, often in daily basis, and extends its impact over large MLT areas, we anticipate that the PsA possesses a significant forcing to the mesospheric ozone chemistry in high latitudes through high energy electron precipitations. Therefore, the generation of PsA results in the depletion of mesospheric ozone through high-energy electron precipitations caused by whistler-mode chorus waves, which are similar to the well-known effect due to solar energetic protons triggered by solar flares.

Risk factors for developing infusion reaction after rituximab administration in patients with B-cell non-Hodgkin's lymphoma.

Rituximab (RTX), a monoclonal antibody against CD20, is known to cause fewer side effects than conventional anti-cancer drugs; however, infusion reaction (IR), which is specific to monoclonal antibody therapy, is frequently triggered by RTX. Therefore, we designed this study to identify risk factors based on clinical test values for developing IR after RTX administration. Eighty-nine patients with B-cell non-Hodgkin's lymphoma who had received RTX for the first time between February 2010 and March 2013, at the Gifu Municipal Hospital were enrolled as subjects. Analysis of data was conducted for 87 patients, after excluding patients whose data were missing. Univariate analysis showed significant differences in the number of patients exhibiting a soluble interleukin-2 receptor (sLL-2R) level > 2,000 U/L and hemoglobin (Hb) < lower standard limit (LSL) between the IR and non-IR groups. Multivariate analysis showed significant differences with respect to slL-2R > 2,000 U/L [odds ratio (OR), 4.463; 95% confidence interval (Cl), 1.262-15.779; P = 0.020], Hb < LSL [OR, 3.568; 95% CI, 1.071-11.890; P = 0.038], and steroid administration [OR, 0.284; 95% Cl, 0.094-0.852; P = 0.025]. Our findings show that sIL-2R > 2,000 U/L, Hb < LSL, and a lack of steroid premedication are risk factors for developing IR following RTX treatment.

Anisotropy of the superconducting gap in the iron-based superconductor BaFe2(As(1-x)P(x))2.

We report peculiar momentum-dependent anisotropy in the superconducting gap observed by angle-resolved photoemission spectroscopy in BaFe2(As(1-x)P(x))2 (x = 0.30, Tc = 30 K). Strongly anisotropic gap has been found only in the electron Fermi surface while the gap on the entire hole Fermi surfaces are nearly isotropic. These results are inconsistent with horizontal nodes but are consistent with modified s ± gap with nodal loops. We have shown that the complicated gap modulation can be theoretically reproduced by considering both spin and orbital fluctuations.

Disorder-induced topological change of the superconducting gap structure in iron pnictides.

In superconductors with unconventional pairing mechanisms, the energy gap in the excitation spectrum often has nodes, which allow quasiparticle excitations at low energies. In many cases, such as in d-wave cuprate superconductors, the position and topology of nodes are imposed by the symmetry, and thus the presence of gapless excitations is protected against disorder. Here we report on the observation of distinct changes in the gap structure of iron-pnictide superconductors with increasing impurity scattering. By the successive introduction of nonmagnetic point defects into BaFe2(As(1-x)P(x))(2) crystals via electron irradiation, we find from the low-temperature penetration depth measurements that the nodal state changes to a nodeless state with fully gapped excitations. Moreover, under further irradiation the gapped state evolves into another gapless state, providing bulk evidence of unconventional sign-changing s-wave superconductivity. This demonstrates that the topology of the superconducting gap can be controlled by disorder, which is a strikingly unique feature of iron pnictides.

[Congenital heart disease having left to right shunts combined with pulmonary hypertension].

A large population of patients with congenital heart disease with relevant systemic to pulmonary shunts( left to right shunts) will develop pulmonary arterial hypertension if left untreated. There are 2 different statuses of an increase in pulmonary arterial pressure. One is high resistance due to high pulmonary blood flow( high flow with high resistance), another one is low pulmonary flow due to high resistance( low flow with high resistance). Chronic large left-to-right shunt induced severe pulmonary vascular disease and pulmonary hypertension. This was then subsequence of low pulmonary blood flow with high pulmonary vascular resistance. We have to avoid this situation and have to do intervention while the pulmonary vascular reactivity has been left. Therefore accurate diagnosis, preoperative treatment for avoidance of high flow, appropriate timing of interventions and post operative various managements are important factors as aiming of low pulmonary resistance in this group. It is important to be familiar with.

Extracorporeal membrane oxygenation following pediatric cardiac surgery: development and outcomes from a single-center experience.

Extracorporeal membrane oxygenation (ECMO) has emerged as an effective mechanical support following cardiac surgery with respiratory and cardiac failure. However, there are no clear indications for ECMO use after pediatric cardiac surgery. We retrospectively reviewed medical records of 76 pediatric patients [mean age, 10.8 months (0-86); mean weight, 5.16 kg (1.16-16.5)] with congenital heart disease who received ECMO following cardiac surgery between January 1997 and October 2010. Forty-five patients were treated with an aggressive ECMO approach (aggressive ECMO group, April 2005-October 2010) and 31 with a delayed ECMO approach (delayed ECMO group, January 1997-March 2005). Demographics, diagnosis, operative variables, ECMO indication, and duration of survivors and non-survivors were compared. Thirty-four patients (75.5%) were successfully weaned from ECMO in the aggressive ECMO group and 26 (57.7%) were discharged. Conversely, eight patients (25.8%) were successfully weaned from ECMO in the delayed ECMO group and two (6.5%) were discharged. Forty-five patients with shunted single ventricle physiology (aggressive: 29 patients, delayed: 16 patients) received ECMO, but only 15 (33.3%) survived and were discharged. The survival rate of the aggressive ECMO group was significantly better when compared with the delayed ECMO group (p<0.01). Also, ECMO duration was significantly shorter among the aggressive ECMO group survivors (96.5 ± 62.9 h, p<0.01). Thus, the aggressive ECMO approach is a superior strategy compared to the delayed ECMO approach in pediatric cardiac patients. The aggressive ECMO approach improved our outcomes of neonatal and pediatric ECMO.

Orbital-independent superconducting gaps in iron pnictides.

The origin of superconductivity in the iron pnictides has been attributed to antiferromagnetic spin ordering that occurs in close combination with a structural transition, but there are also proposals that link superconductivity to orbital ordering. We used bulk-sensitive laser angle-resolved photoemission spectroscopy on BaFe(2)(As(0.65)P(0.35))(2) and Ba(0.6)K(0.4)Fe(2)As(2) to elucidate the role of orbital degrees of freedom on the electron-pairing mechanism. In strong contrast to previous studies, an orbital-independent superconducting gap magnitude was found for the hole Fermi surfaces. Our result is not expected from the superconductivity associated with spin fluctuations and nesting, but it could be better explained invoking magnetism-induced interorbital pairing, orbital fluctuations, or a combination of orbital and spin fluctuations. Regardless of the interpretation, our results impose severe constraints on theories of iron pnictides.

Unrelated cord blood transplantation after myeloablative conditioning in adults with ALL.

We analyzed the disease-specific outcomes of adult ALL treated with cord blood transplantation (CBT) after myeloablative conditioning. Between October 2000 and November 2007, 27 adult patients with ALL were treated with unrelated CBT. All patients received four fractionated 12 Gy TBI and chemotherapy as myeloablative conditioning. The median age was 36 years, the median weight was 57 kg and the median number of nucleated cells was 2.47 x 10(7)/kg. All patients received a single and HLA-mismatched cord blood unit. The cumulative incidence of neutrophil recovery at day 30 and platelet recovery at day 200 was 92.6 and 92.3%, respectively. With a median follow-up of 47 months, the probability of EFS at 5 years was 57.2%. The 5-year cumulative incidence of TRM and relapse was 3.7 and 27.4%, respectively. These results suggest that unrelated CBT after myeloablative conditioning could be safely and effectively used for adult patients with ALL.

No occurrence of Pneumocystis jiroveci (carinii) pneumonia in 120 adults undergoing myeloablative unrelated cord blood transplantation.

The incidence of pneumonia caused by Pneumocystis carinii (PCP) (organism now renamed Pneumocystis jiroveci) during the early period after cord blood transplantation (CBT) was studied in 120 adults. Initially 89 patients (74%) received oral administration of 2 single-strength trimethoprim-sulfamethoxazole (TMP-SMZ) tablets twice daily from day -21. In 45 of 89 patients (51%), TMP-SMZ administration for a scheduled duration was completed. In the remaining 44 patients (49%), however, TMP-SMZ administration was discontinued prior to day -3 because of toxicity. Among these patients, 42 subsequently received aerosolized pentamidine (AP) on a median of day -13 (range, -20 to -6). Thirty-one patients (26%) received AP without TMP-SMZ administration on a median of day -14 (range, -21 to -9). None of the 120 patients were diagnosed with PCP within 100 days or 2 years after CBT; however, one patient who received AP before CBT but no prophylaxis after CBT developed cerebral toxoplasmosis on day +91. Pre-transplant prophylaxis against PCP did not significantly affect transplantation-related mortality or disease-free survival at 2 years after CBT. The results suggest that PCP during the early period after CBT can be effectively prevented by any pre-transplant prophylactic method.

Cardiovascular toxicity of cryopreserved cord blood cell infusion.

Although infusion of cryopreserved bone marrow or peripheral blood stem cell is associated with a variety of symptoms, there have been no reports detailing the data of infusion-related toxicities of cryopreserved cord blood (CB) units. We prospectively evaluated the incidence and significance of infusion-related toxicities in 34 adult patients undergoing unrelated CB transplantation. Cryopreserved CB units were thawed and immediately infused, unfiltered, through a central intravenous catheter without further manipulation. Heart rate, blood pressure, oxygen saturation and clinical symptoms were recorded during and after infusion. Twenty-four percent of patients experienced non-cardiovascular toxicities related to infusion. The incidence of systolic and diastolic hypertension and bradycardia was 58, 64 and 32%, respectively. Although three patients (9%) with severe systolic hypertension after the infusion required treatment with antihypertensive agents, no patients experienced life-threatening side effects or needed discontinuation of CB unit infusion. Patient or transplant characteristics had no effect on the hypertension and bradycardia related to the infusion of CB. These data suggest that infusion of cryopreserved CB without further manipulation after thawing is safe and well tolerated. However, cardiovascular toxicities including hypertension and bradycardia were frequently observed.

[Lateral tunnel versus extracardiac cavopulmonary connections].

To examine the mid term outcome of the lateral tunnel Fontan and the result is to be compared to extracardiac Fontan operation. Between March 1991 and May 2002, 72 lateral tunnel (LT) and 28 extracardiac conduit (EC) total cavopulmonary connection (TCPC) were performed. Right atrium was incised parallel to the sulcus terminalis and LT was created by using autologous right atrial wall. Lateral tunnel size was determined 1-2 mm larger than normal half pulmonary artery (PA) size according to the body weight. There were 1 early and 1 late death, both initial LT group. Supraventricular tachycardia was found in 1 patient with EC group and 4 in LT group (all heterotaxy syndrome). There were no differences in mortality and mobidity between LT and EC TCPC. Lateral tunnel TCPC is useful especially to small infants and children.

Dissociation of innate and adaptive immunity by UVB irradiation.

Increasing ultraviolet-B irradiation (UVB) resulting from diminution of stratospheric ozone is becoming a serious international problem. UVB irradiation exerts not only carcinogenic effects on animals but also causes them to become vulnerable to infections by modulating their immune responses. UVB irradiation suppresses innate immune functions of cells such as macrophages, neutrophils, Langerhans cells, dendritic cells, and the serum component, complement. UVB irradiation also causes changes in cytokine profiles, represented by the induction of a paradigm switch involving Th1/Th2 phenotypes. According to earlier studies, Th1 responses are suppressed, whereas Th2 activities are augmented by UVB irradiation. These immune modulations are caused by several pathways via cytokines and neuropeptides, and eventually may lead to increasing incidences of infection, allergy, and cancer. We have reviewed reports concerning UVB-irradiation induced immune modulation from the viewpoint of risks for human diseases and, in addition, for ecosystems and immunity of lower animals.

Establishment of a mouse thymic epithelial cell line, IT-76MHC and a brief review on cultured thymic epithelial cells.

Interactions between thymocytes and thymic stromal cells are essential for thymocyte differentiation, but little evidence has been presented to directly show in vivo functions or interactions of the stromal cells. Among the stromal cells, the thymic epithelial cell has been considered to have profound effect on thymocyte differentiation and maturation. The calcium-depleted medium, originally developed for the culture of mouse epidermal cells, was applied for the culture of the mouse thymic epithelial cells, and successfully, an epithelial cell line, IT-76MHC was obtained from the mouse thymus. IT-76MHC cells were identified as distinct mouse thymic epithelial cells by 1/ mosaic-like arrangement, 2/ presence of well-developed desmosome and 3/ tonofilaments, 4/ positivity for cytokeratin, and 5/ induced expression of MHC class I and II by IFN-gamma treatment. IGF-1, IGF-2, oxytocin and vasopressin were also detected immunohistochemically in IT-76MHC cells. Furthermore, the IT-76MHC thymic epithelial cells, when injected intrathymically in the allogeneic mouse, prolonged the survival of skin graft from the same donor strain that IT-76MHC cells were derived. These results demonstrate that the thymic epithelial cell line IT-76MHC produces modest thymocyte survival factors as well as a growth suppressor, and that IT-76MHC cells have the ability to induce transplantation tolerance probably through their expression of MHC class I and II molecules. Taken altogether, the IT-76MHC thymic epithelial cells have been proved to be useful tools to better understand the in vivo functions of thymic epithelial cells, and to gain a deep insight into their involvement in the critical selection process of thymocytes which still remains obscure. Finally and additionally, literatures so far reported on thymic epithelial cells in culture, especially lines and clones, are reviewed and their identity as well as their functions are discussed.

A trimmed viral cap-independent translation enhancing sequence for rapid in vitro gene expression.

We prepared a short (29 nucleotides) 5' UTR that enhanced cap-independent translation in a wheat germ translation system by trimming the tobacco etch virus 5' UTR. The trimmed sequence, designated as TE(37-65), was obtained from a conserved region among several potyviruses. The productivities of uncapped reporter mRNAs carrying the TE(37-65) sequence were comparable to those of capped counterparts, in that 5-20 microg of proteins were synthesized per 1 mL of translation reaction mixture. The ribosome that entered onto the TE(37-65) sequence precisely initiated polypeptide synthesis at the defined initiation codon, which ensures rapid and efficient protein truncation analyses. Moreover, the TE(37-65) sequence is short enough to be involved in a PCR primer, which allows a simple method for rapid gene expression, i.e., PCR amplification of a target gene and succeeding in vitro transcription and translation. As a demonstration, the rapid in vitro expression of rice cDNAs using the TE(37-65) sequence was also performed.

Idiopathic myelofibrosis developing isolated granulocytic sarcoma with der (1;7)(q10; p10) after splenectomy and finally transforming to acute myelogenous leukemia.

A 47-year-old female with idiopathic myelofibrosis developed isolated granulocytic sarcoma with der (1; 7)(q10; p10) after splenectomy, followed by acute myelogenous leukemia. The patient had myelofibrosis since 22 years of age, received splenectomy at 47 years, and developed isolated submandibular granulocytic sarcoma, 8 months later. Although the initial tumor disappeared after irradiation, recurrent tumors selectively appeared in the areas of operative scars. She subsequently developed blastic transformation with der (1; 7)(q10; p10), and the blasts were refractory to different chemotherapy. This case is very rare in the following aspects: the onset of myelofibrosis occurred at a relatively young age; isolated granulocytic sarcoma after splenectomy preceded the transformation to acute leukemia; and the subcutaneous tumors developed in areas of operative scars.

Effect of suture closure of coronary artery fistula on aneurysmal coronary artery and myocardial ischemia.

This study indicates the importance of coronary angiography and myocardial scintigraphy on long-term follow-up of patients after surgery for coronary arterial fistula in view of the progression to coronary artery obstruction and myocardial ischemia.