Eltrombopag enables initiation and completion of pegylated interferon/ribavirin therapy in Japanese HCV-infected patients with chronic liver disease and thrombocytopenia.

To investigate the efficacy of eltrombopag for the treatment of thrombocytopenia in patients with chronic hepatitis C, a phase II, single-arm, open-label study with a 9-week pre-antiviral phase was conducted, followed by a 48-week antiviral phase and a 24-week follow-up phase. The proportion of patients who achieved a platelet count threshold, the proportion of patients who maintained a platelet count >50,000/µl, sustained virological response (SVR) rates and safety parameters were evaluated. Of the 45 enrolled patients (median age, 59 years; median platelet count, 63,000/µl; 98% with Child-Pugh class A), 43 (96%) achieved the platelet count threshold during the pre-antiviral phase. A total of 13 patients (29%) experienced ≥1 adverse event (AE), of which headache and vomiting were the most common, and 41 patients (mostly receiving eltrombopag 12.5 mg or 25 mg) entered the antiviral phase, of which 36 (88%) maintained the platelet count threshold; no patient platelet count decreased below 25,000/µl. Nine patients (22%) achieved an SVR at the 24-week follow-up. Grade ≥3 AEs occurred in 25 patients (61%). A total of 8 serious AEs occurred in five patients (12%). No mortality, thromboembolic events (TEEs), or cataract progression were reported. Eltrombopag increased the platelet count in chronic hepatitis C virus-infected patients with cirrhosis and thrombocytopenia and enabled them to initiate and complete interferon-based antiviral therapy (NCT01636778; first submitted: July 05, 2012).

Hematologic recovery induced by eltrombopag in Japanese patients with aplastic anemia refractory or intolerant to immunosuppressive therapy.

Eltrombopag, an oral thrombopoietin-receptor agonist, stimulates hematopoiesis in patients with acquired aplastic anemia (AA) and has higher exposure in patients of East Asian origin. We evaluated the pharmacokinetics, efficacy, and safety of eltrombopag in Japanese patients with AA refractory or intolerant to immunosuppressive therapy (IST). Twenty-one patients (15 with non-severe AA, six with severe AA) with platelet counts < 30,000/µL received eltrombopag in a dose-escalation fashion (25, 50, 75, or 100 mg once daily) depending on individual platelet responses; the responders continued eltrombopag treatment beyond 6 months. The primary endpoint was hematologic response at 6 months, defined as improvements in blood counts or transfusion requirements. Ten (48%) patients achieved hematologic responses in at least one lineage at 6 months. Six patients achieved tri- and/or bi-lineage responses with continuation of eltrombopag treatment, with two patients no longer requiring eltrombopag treatment. The most common adverse events were nasopharyngitis and abnormal hepatic function, with the majority being grade 1 or 2. Cytogenetic abnormalities were observed in three patients; however, no progression to myelodysplastic syndrome/other malignancy was observed. Eltrombopag can safely restore multi-lineage hematopoiesis in Japanese patients with AA refractory or intolerant to IST.Clinical Trial registration NCT02148133.

[A Case of Giant GIST Originating from the Greater Omentum].

A 60-year-old woman was admitted for abdominal distention, abdominal pain, and anorexia. Abdominal CT showed a 30×20 cm mass with contrast effect. gastrointestinal stromal tumor(GIST) of the omentum or the mesenterium was suspected. Peritoneal nodules were also recognized. We performed palliative surgery. The tumor was considered to have originatedfrom the greater omentum andinvolvedthe marginal artery of the transverse colon. We performedpartial excision of the transverse colon andresection of the tumor. Immunohistochemically, the tumor cells were c-kit(+), CD34(+), S100(-), andDOG1(-), with 1 fission image for 50 fields of view with high magnification. The patient was diagnosed with high-risk GIST originating from the greater omentum. The patient was started on imatinib administration on the 37th day but died on the 109th day.

Oral eltrombopag for up to three years is safe and well-tolerated in Japanese patients with previously treated chronic immune thrombocytopenia: an open-label, extension study.

Eltrombopag is an oral, nonpeptide, thrombopoietin receptor agonist approved for treatment of chronic immune thrombocytopenia (ITP). The safety, tolerability, and efficacy of eltrombopag for up to 3 years were evaluated in 19 Japanese patients with chronic ITP who had completed a prior 6-month study. Patients received eltrombopag once daily at the last dosage received in the prior study (12.5, 25, or 50 mg). Dose adjustments and treatment interruptions were permitted to maintain platelet counts of 50,000-200,000/µL. Primary evaluations were safety and tolerability of long-term eltrombopag treatment. The median duration of exposure was 27.5 months (range, 9.9-32.3). Adverse events were similar to those reported with short-term use of eltrombopag, and none led to treatment discontinuation. Nine serious adverse events were reported. Median platelet counts began to increase after 1 week of treatment and remained above 50,000/µL for most assessments. Bleeding episodes decreased from 63 % at baseline to 21 % after 2 weeks of treatment and remained below baseline for all assessments. Of 15 patients receiving concomitant baseline ITP medications, 10 permanently discontinued or achieved a sustained reduction of at least one treatment without requiring rescue treatment. Long-term treatment with eltrombopag was safe, well tolerated, and effective in Japanese patients with chronic ITP.

Efficacy and safety of eltrombopag in Japanese patients with chronic liver disease and thrombocytopenia: a randomized, open-label, phase II study.

BACKGROUND: Eltrombopag is an oral thrombopoietin receptor agonist that stimulates thrombopoiesis and shows higher exposure in East Asian patients than in non-Asian patients. We evaluated the pharmacokinetics, efficacy, and safety of eltrombopag in Japanese patients with thrombocytopenia associated with chronic liver disease (CLD). METHODS: Thirty-eight patients with CLD and thrombocytopenia (platelets <50,000/µL) were enrolled in this phase II, open-label, dose-ranging study that consisted of 2 parts. In the first part, 12 patients received 12.5 mg of eltrombopag once daily for 2 weeks. After the evaluation of safety, 26 patients were randomly assigned to receive either 25 or 37.5 mg of eltrombopag once daily for 2 weeks in the second part. RESULTS: Pharmacokinetics showed that the geometric means of the maximum plasma concentration (C(max)) and the area under the curve (AUC) in the 12.5 mg group were 3,413 ng/mL and 65,236 ng h/mL, respectively. At week 2, the mean increases from baseline in platelet counts were 24,800, 54,000, and 60,000/µL in the 12.5, 25, and 37.5 mg groups, respectively. The median platelet counts increased within 2 weeks of the beginning of administration in all groups, and remained at the same level throughout the 2-week post-treatment period in the 12.5 mg group, whereas the platelet counts peaked a week after the last treatment in both the 25 and 37.5 mg groups. Most adverse events reported were grade 1 or 2; 2 patients in the 37.5 mg group had drug-related serious adverse events. CONCLUSIONS: Eltrombopag ameliorated thrombocytopenia in Japanese patients with CLD and thrombocytopenia. The recommended dose for these patients is 25 mg daily for 2 weeks.

The effects of a lower irrigation system on pollutant removal and on the microflora of a biofilter.

Moisture control is one the most important parameters in biofilters for air pollution control. Biofilters tend to experience drying at the air inlet port, which causes decreased pollutant removal over time. In this study, the installation of an irrigation system within the lower part of the biofilter bed was proposed, and its effect was quantified in a laboratory scale biofilter operated side by side with a control biofilter. The removal of toluene vapours at short gas residence time (13.5 s) served as a model system. The results showed that the rate of toluene elimination in the biofilter with the lower irrigation system was 1.2-1.7 times greater than the rate of toluene elimination in the control biofilter. At the completion of the two-month experiment, a detailed examination was conducted of the packing materials with the immobilized pollutant-degrading culture. The results highlighted the effects of bed drying on cell viability in the control biofilter. They also revealed that the bottom segment of the biofilter with the lower irrigation system had a higher moisture content, a higher biomass density and a larger fraction of active biomass than the corresponding segment in the conventional biofilter. These detailed examinations explained why an increased toluene removal was observed in the system equipped with a lower irrigation system. Overall, this study demonstrates enhanced pollutant removal in biofilters equipped with a lower irrigation system through a better control of moisture.

Removal of ammonia from contaminated air in a biotrickling filter - denitrifying bioreactor combination system.

The removal of gaseous ammonia in a system consisting of a biotrickling filter, a denitrification reactor and a polishing bioreactor for the trickling liquid was investigated. The system allowed sustained treatment of ammonia while preventing biological inhibition by accumulating nitrate and nitrite and avoiding generation of contaminated water. All bioreactors were packed with cattle bone composite ceramics, a porous support with a large interfacial area. Excellent removal of ammonia gas was obtained. The critical loading ranged from 60 to 120 gm(-3)h(-1) depending on the conditions, and loadings below 56 gm(-3)h(-1) resulted in essentially complete removal of ammonia. In addition, concentrations of ammonia, nitrite, nitrate and COD in the recycle liquid of the inlet and outlet of each reactor were measured to determine the fate of nitrogen in the reactor, close nitrogen balances and calculate nitrogen to COD ratios. Ammonia absorption and nitrification occurred in the biotrickling filter; nitrate and nitrite were biologically removed in the denitrification reactor and excess dissolved COD and ammonia were treated in the polishing bioreactor. Overall, ammonia gas was very successfully removed in the bioreactor system and steady state operation with respect to nitrogen species was achieved.

Comparison of different packing materials for the biofiltration of air toxics.

Four different biofilter packing materials (two porous ceramics, perlite, and open pore polyurethane foam) were compared for the removal of toluene vapors. The focus was on evaluating performance at relatively short gas retention time (13.5 and 27 sec). The reactors were initially operated as biotrickling filters with continuous feeding and trickling of a nutrient solution. After significant plugging of the biotrickling filter beds with biomass was observed, the operation mode was switched to biofiltration with only periodic supply of mineral nutrients. This resulted in stable conditions, which allowed detailed investigations over > 6 months. The reactor packed with cattle bone Porcelite (CBP), a ceramic material containing some macronutrients and micronutrients, exhibited the highest performance. The critical load (i.e., load at which 95% removal occurred) was 29 g m(-3) hr(-1) at a gas retention time of 13.5 sec and 66 g m(-3) hr(-1) at a gas retention time of 27 sec. After the long-term experiment, the packing materials were taken from the reactors and examined. The reactors were divided into three sections, top, middle, and bottom, to determine whether spatial differentiation of biomass occurred. The assays included a double-staining technique to count total and live microorganisms and determination of moisture, protein, and dry weight contents. Microbial community analysis was also conducted by denaturing gradient gel electrophoresis. The results showed that most reactors had a significant fraction of inactive biomass. Comparatively, the CBP biofilter held significantly higher densities of active biomass, which may be the reason for the higher toluene removal performance. The analyses suggest that favorable material properties and the nutrients slowly released by the CBP provided better environmental conditions for the process culture.