Soluble thrombomodulin is a promising therapeutic natural anticoagulant that is comparable to antithrombin, tissue factor pathway inhibitor and activated protein C.
We conducted a multicenter, ...double-blind, randomized, parallel-group trial to compare the efficacy and safety of recombinant human soluble thrombomodulin (ART-123) to those of low-dose heparin for the treatment of disseminated intravascular coagulation (DIC) associated with hematologic malignancy or infection.
DIC patients (n = 234) were assigned to receive ART-123 (0.06 mg kg(-1) for 30 min, once daily) or heparin sodium (8 U kg(-1) h(-1) for 24 h) for 6 days, using a double-dummy method. The primary efficacy endpoint was DIC resolution rate. The secondary endpoints included clinical course of bleeding symptoms and mortality rate at 28 days.
DIC was resolved in 66.1% of the ART-123 group, as compared with 49.9% of the heparin group difference 16.2%; 95% confidence interval (CI) 3.3-29.1. Patients in the ART-123 group also showed more marked improvement in clinical course of bleeding symptoms (P = 0.0271). The incidence of bleeding-related adverse events up to 7 days after the start of infusion was lower in the ART-123 group than in the heparin group (43.1% vs. 56.5%, P = 0.0487).
When compared with heparin therapy, ART-123 therapy more significantly improves DIC and alleviates bleeding symptoms in DIC patients.
N-doped graphite has been reported to provide enhanced catalytic properties as a support material for Pt catalysts in fuel cell applications. With use of a combined experimental and modeling ...approach, this work identifies the potential fundamental mechanisms for this enhancement effect. To ensure a well-defined experimental system, this work employs highly oriented pyrolitic graphite (HOPG) as a model analogue of the graphite support commonly used in fuel cell applications. Undoped, Ar-doped, and N-doped HOPG substrates have been investigated via electrochemical capacitance and X-ray photoelectron spectroscopy (XPS) measurements. The results indicate that doping, especially N-doping, induces significant modification to the electronic structure of the HOPG surface. A simplified model of the doping effects and band structures for the doped graphite surfaces are proposed to explain these results. When Pt nanoparticles are grown on top of these dopant-modified HOPG surfaces, the resulting Pt/surface-defect interactions significantly impact the Pt nanoparticle nucleation, growth, and catalytic activity.
Purpose
This study aimed to examine the potential benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors for patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and ...diabetes mellitus (DM) using a real-world database.
Methods
We analyzed individuals with MAFLD and DM newly initiated on SGLT2 or dipeptidyl peptidase 4 (DPP4) inhibitors from a large-scale administrative claims database. The primary outcome was the change in the fatty liver index (FLI) assessed using a linear mixed-effects model from the initiation of SGLT2 or DPP4 inhibitors. A propensity score-matching algorithm was used to compare the change in FLI among SGLT2 and DPP4 inhibitors.
Results
After propensity score matching, 6547 well-balanced pairs of SGLT2 and 6547 DPP4 inhibitor users were created. SGLT2 inhibitor use was associated with a greater decline in FLI than DPP4 inhibitor use (difference at 1-year measurement, − 3.8 95% CI − 4.7 to − 3.0). The advantage of SGLT2 inhibitor use over DPP4 inhibitor use for improvement in FLI was consistent across subgroups. The relationship between SGLT2 inhibitors and amelioration of FLI was comparable between individual SGLT2 inhibitors.
Conclusions
Our analysis using large-scale real-world data demonstrated the potential advantage of SGLT2 inhibitors over DPP4 inhibitors in patients with MAFLD and DM.
Acute promyelocytic leukemia (APL) has become a curable disease by all-trans retinoic acid (ATRA)-based induction therapy followed by two or three courses of consolidation chemotherapy. Currently ...around 90% of newly diagnosed patients with APL achieve complete remission (CR) and over 70% of patients are curable. To further increase the CR and cure rates, detection and diagnosis of this disease at its early stage is very important, hopefully before the appearance of APL-associated coagulopathy. In induction therapy, concomitant chemotherapy is indispensable, except for patients with low initial leukocyte counts. Prophylactic use of intrathecal methotrexate and cytarabine should be done, particularly for patients with hyperleukocytosis. If patients relapse hematologically or even molecularly, arsenic trioxide will be the treatment of choice under careful electrocardiogram monitoring. Am80, liposomal ATRA, gemtuzumab ozogamicin or ATRA in combination with cytotoxic drugs may be used at this stage or later. Allogeneic SCT will be the treatment of choice after patients of age <50 years have relapsed, provided that they have HLA-identical family donors or DNA-identical unrelated donors.
A high complete remission (CR) rate has been reported in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) following imatinib-based therapy. However, the overall ...effect of imatinib on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is undetermined. Between 2002 and 2005, 100 newly diagnosed adult patients with Ph+ALL were registered to a phase II study of imatinib-combined chemotherapy (Japan Adult Leukemia Study Group Ph+ALL202 study) and 97 patients achieved CR. We compared clinical outcomes of 51 patients who received allo-HSCT in their first CR (imatinib cohort) with those of 122 historical control patients in the pre-imatinib era (pre-imatinib cohort). The probability of overall survival at 3 years after allo-HSCT was 65% (95% confidence interval (CI), 49-78%) for the imatinib cohort and 44% (95% CI, 35-52%) for the pre-imatinib cohort. Multivariate analysis confirmed that this difference was statistically significant (adjusted hazard ratio, 0.44, P=0.005). Favorable outcomes of the imatinib cohort were also observed for disease-free survival (P=0.007) and relapse (P=0.002), but not for non-relapse mortality (P=0.265). Imatinib-based therapy is a potentially useful strategy for newly diagnosed patients with Ph+ALL, not only providing them more chance to receive allo-HSCT, but also improving the outcome of allo-HSCT.
Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human malignancy. An internal tandem duplication (ITD) of the juxtamembrane (JM) domain-coding ...sequence of the FLT3 gene (FLT3/ITD) is found in 20% of patients with acute myeloid leukemia (AML) and is strongly associated with leukocytosis and a poor prognosis. On the other hand, mutations of the c-KIT gene, which have been found in mast cell leukemia and AML, are clustered in 2 distinct regions, the JM domain and D816 within the activation loop. This study was designed to analyze the mutation of D835 of FLT3, which corresponds to D816 of c-KIT, in a large series of human hematologic malignancies. Several kinds of missense mutations were found in 30 of the 429 (7.0%) AML cases, 1 of the 29 (3.4%) myelodysplastic syndrome (MDS) cases, and 1 of the 36 (2.8%) acute lymphocytic leukemia patients. The D835Y mutation was most frequently found (22 of the 32 D835 mutations), followed by the D835V (5), and D835H (1), D835E (1), and D835N (1) mutations. Of note is that D835 mutations occurred independently of FLT3/ITD. An analysis in the 201 patients newly diagnosed with AML (excluding M3) revealed that, in contrast to the FLT3/ITD mutation (n = 46), D835 mutations (n = 8) were not significantly related to the leukocytosis, but tended to worsen disease-free survival. All D835-mutant FLT3 were constitutively tyrosine-phosphorylated and transformed 32D cells, suggesting these mutations were constitutively active. These results demonstrate that the FLT3 gene is the target most frequently mutated to become constitutively active in AML.
In this study cadmium stannate Cd2SnO4 (CTO), was sputtered onto borosilicate glass under substrate temperatures of ~25°C (room temp), 200°C, 300°C and 400°C. The CTO films were then annealed in ...contact with cadmium sulfide (CdS). This annealing process consisted of placing the CTO samples face up in a thermal furnace with a separate piece of CdS film on a borosilicate substrate face down on top of the CTO sample. This arrangement was then heated to a temperature of 600°C and annealed for one hour. The goal was to fabricate a CTO film with the highest transparency without sacrificing good electrical conductivity. The quality of CTO films, i.e. transparency and electrical conductivity can be greatly affected by processing conditions. In this paper the optical and electrical properties of CTO are investigated before and after thermal annealing to determine the affect of varying process conditions on the quality of the film. Spectroscopic ellipsometry analysis was performed on both as-deposited and annealed CTO to determine the nature of the optical response of the films over the spectral range of 0.73 to 3.34eV. The electrical properties of the films were examined using both Hall effect data and optical Drude modeling of free carrier absorption. Structural properties of the films were determined from X-ray diffraction data. The result of this investigation is a high quality CTO film with a sheet resistance of ~8Ω/□.
•Cadmium stannate (CTO) is characterized to achieve optimization as a transparent conducting oxide (TCO).•Spectroscopic ellipsometry results were substantiated with other measurements.•Specialized CTO processing yields a TCO film with low sheet resistance.
The THM growth technology for 100 mm diameter CdTe single crystals has been intensively developed. In consequence of the optimization of growth conditions, we have succeeded in controlling growth ...interface shape and growing 100 mm diameter CdTe single crystals with 300 mm in length. Concerning the behavior of Te inclusions in the grown crystal, their size and density were investigated by IR transmission microscopy. The size distribution of Te inclusions was divided into two groups, and the density of them was less than 1 times 10 5 cm -3 . Charge transport properties of the grown crystal were investigated by using the ldquomutau-modelrdquo spectral fitting method, and were found to be quite uniform all over the wafer. To investigate the homogeneity of radiation detector performances, Ohmic type and Schottky type detectors with 4 mm times 4 mm times 1 mm were fabricated from the left half and the right half of the 100 mm diameter wafer, respectively. Standard deviations of their energy resolutions for the 122 keV line from 57 Co were less than 6%. This excellent uniformity is essential for the room temperature semiconductor detectors in the major application areas, such as medical imaging, non-destructive inspection and homeland security.
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