Search

Summary There are variations in individual eltrombopag concentrations that may impact efficacy and adverse drug reactions (ADRs) in paediatric immune thrombocytopaenia (ITP). To solve this problem, we tailored the eltrombopag dosage refer to concentration, then followed up to assess concentration value in paediatric ITP. This is a single‐centre, prospective, observational study. The eltrombopag dosage was adjusted, and children were divided into three groups: the maintenance, discontinuation, and increase groups. Concentration and other data were compared to explore concentration value in guiding the individualized treatment of paediatric ITP. Thirty‐nine patients were enrolled, including 23 in the maintenance group, 3 in the discontinued group and 13 in the increase group. 3 patients discontinued eltrombopag due to ADRs, which was significantly higher than patients in the maintenance group (t = 3.606, p = 0.001). In all, 13 patients increased their dosage due to poor response, whose concentration and platelet count were significantly lower than patients in the maintenance group (t = 2.461, p = 0.019; t = 4.633, p < 0.001). Two months after the increase, the number of patients reaching CR and R respectively increased by 2 and 3, while the median platelet count was significantly raised (Z = −2.411, p = 0.016). Concentration could be used as a reference index for the individualized treatment of eltrombopag in paediatric ITP. [ABSTRACT FROM AUTHOR]

Summary: Chronic refractory primary immune thrombocytopenia (CRITP) is currently defined as refractory to multiple therapeutic of second‐line agents with or without splenectomy, faced with the threat of severe bleeding and challenging to obtain effective treatment. Although stable and effective drug therapy is needed, it is tough to find one. Daratumumab (Dara), an anti‐CD38 monoclonal antibody presented the target cloned plasma cells in multiple myeloma, has also been reported to be effective in refractory autoimmune cytopenia in some case or series reports and ongoing clinical trials for adult patients with CRITP. Here, we report the early and durable response of Dara combination with avatrombopag in three CRITP patients (2 male and 1 female aged 12, 5 and 7 years, respectively) in our centre, with a follow‐up period of more than 25 weeks. Before Dara, the duration of immune thrombocytopenia was 9, 1.4 and 4 years, respectively, a baseline platelet count of 4, 6, 9 × 109/L, the bleeding score was all above level 2 and the number of previous drugs was >3. The time to response (R: Plt ≥30 × 109/L with at least a twofold increase in the baseline count) of Dara was on Day 45, 6 and 4 and achieved complete response (CR: Plt ≥100 × 109/L) on Day 51, 6 and 8, the sustained response (SR: Plt >30 × 109/L following Dara at ≥75% of the platelet count assessment at follow‐up end‐point since the patient achieved response) was 48, 175 and 204 days with the follow‐up time of 39.1, 25.9 and 29.7 weeks. The bleeding score decreased from grade 3 to grade 0 during follow‐up. No significant treatment‐related adverse events were found during follow‐up. Dara combination with avatrombopag may be a safe and efficacious therapy for children with CRITP, but it needs to be further explored. [ABSTRACT FROM AUTHOR]

Summary: Avatrombopag (AVA) is a novel thrombopoietin receptor agonist (TPO‐RA) that has been recently approved as a second‐line therapy for immune thrombocytopenia (ITP) in adults; however, its safety and efficacy data in children are lacking. Here, we demonstrated the efficacy and safety of AVA as second‐line therapy in children with ITP. A multicentre, retrospective, observational study was conducted in children with persistent or chronic ITP who did not respond to or relapsed from previous treatment and were treated with AVA for at least 12 weeks between August 2020 and December 2022. The outcomes were the responses (defined as achieving a platelet count ≥30 × 109/L, twofold increase in platelet count from baseline and absence of bleeding), including rapid response within 4 weeks, sustained response at weeks 12 and 24, bleeding control and adverse events (AEs). Thirty‐four (18 males) patients with a mean age of 6.3 (range: 1.9–15.3) years were enrolled. The median number of previous treatment types was four (range: 1–6), and 41.2% patients switched from other TPO‐RAs. Within 4 weeks, overall response (OR) was achieved in 79.4% patients and complete response (CR, defined as a platelet count ≥100 × 109/L and the absence of bleeding) in 67.7% patients with a median response time of 7 (range: 1–27) days. At 12 weeks, OR was achieved in 88.2%, CR in 76.5% and sustained response in 44% of patients. At 24 weeks, 22/34 (64.7%) patients who achieved a response and were followed up for 24 weeks were evaluated; 12/22 (54.55%) achieved a sustained response. During AVA therapy, median platelet counts increased by week 1 and were maintained throughout the treatment period. The proportion of patients with grade 1–3 bleeding decreased from 52.95% at baseline to 2.94% at 12 weeks, while concomitant ITP medications decreased from 36.47% at baseline to 8.82% at 12 weeks, with only 9 (26.47%) patients receiving rescue therapy 23 times within 12 weeks. There were 61.8% patients with 59 AEs: 29.8% with Common Terminology Criteria for Adverse Events grade 1 and the rest with grade 2. These findings show that AVA could achieve a rapid and sustained response in children with persistent or chronic ITP as a second‐line treatment, with good clinical bleeding control and reduction of concomitant ITP therapy, without significant AEs. [ABSTRACT FROM AUTHOR]

Importance: Eltrombopag has been recommended for pediatric immune thrombocytopenia (ITP). Response and adverse drug reactions (ADRs) varied widely between individuals, even at the same dose of eltrombopag. The appropriate eltrombopag concentration in ITP has not been reported. Objective: This study aims to explore the appropriate eltrombopag concentration in pediatric ITP. Methods: This was a single‐center, prospective cohort study. Children diagnosed with refractory persistent/chronic ITP and platelet count < 30×109/L were treated with eltrombopag and followed up for at least 2 months. Concentration was detected by high‐performance liquid chromatography‐mass spectrometry at least 2 weeks after eltrombopag. The clinical characteristics‐concentration, concentration‐response, and concentration‐ADRs were analyzed. Results: A total of 30 patients were enrolled, comprising 13 males and 17 females, with a median age of 72 (45‒94) months. The median dose and concentration were 1.39 (1.09‒1.56) mg/kg and 2.70 (2.25‒4.13) mg/L, respectively. Of the enrolled patients, 14 responded to treatment, whereas 16 did not. Additionally, five experienced adverse drug reactions. No linear correlation was observed between eltrombopag concentration and clinical characteristics. The concentration was lower in the response group than in the nonresponse group, but there was no significant difference (t = 0.755, P = 0.457). Patients who experienced ADRs had a higher concentration than those without ADRs (t = 2.538, P = 0.017). The area under the receiver operating characteristic curve of ADRs was 0.78 (95% confidence interval: 0.56‒1.00). Youden's index identified the cutoff point as 4.33 mg/L, with a sensitivity of 88% and a specificity of 60%. Logistic regression analysis demonstrated that a higher platelet count before eltrombopag predicted a favorable response. Interpretation: Eltrombopag proves efficacious and well‐tolerated for treating pediatric ITP. However, prolonged and high‐dose administration may increase the likelihood of ADRs. Thus, examining the appropriate eltrombopag concentration assists in directing individualized management of pediatric ITP. [ABSTRACT FROM AUTHOR]

Summary: We have previously confirmed the efficacy and safety of eltrombopag (ELT) in children with chronic immune thrombocytopenia (cITP). However, data on both long‐term exposure and early use of TPO‐RAs are lacking, so further 'field‐practice' evidence on treatment is required. Here, we report the long‐term follow‐up results (between September 2018 and June 2023) of our previous study. The main objective of this study was to retrospectively review our large institutional experience with ITP patients previously enrolled in our paediatric cITP study. We had more than 3 years of follow‐up by June 2023 for treatment patterns and outcomes. A total of 65 patients (28 males) were enrolled, with a median age at ELT initiation of 6.34 (range 1.65, 14.13) years and a follow‐up of 47.07 (36.00, 57.00) months, with 40.36 (10.53, 56.83) months of ELT therapy at the time of analysis. In total, 29.23% (19/65) of patients discontinued ELT due to stable response, and 18.46% (12/65) of patients switched to other ITP therapies due to loss of response (LOR) after 19.13 (14.53, 26.37) months. Of the 19 patients who discontinued ELT due to a stable response, 24.62% (16/65) achieved a 12 m sustained response off‐treatment (SRoT); the last recorded platelet count ranged from 56 to 166 × 109/L (median 107 × 109/L); and 4.62% (3/65) patients relapsed at 5, 6 and 9 months after discontinuation. Of the 12 patients who LOR to ELT after 19.13 (14.53, 26.37) months of therapy, four switched to avatrombopag, three switched to hetrombopag, two switched to traditional Chinese medicine (TCM), one underwent splenectomy and two received additional prednisolone under ELT treatment. Thirty‐four patients who tapered and maintained a durable response. The patients with LOR and the patients with tapering were compared; the platelet count at the start of ELT is lower, and the time to response is longer in the patients with LOR. The platelet count at the start of ELT and the time to response may be the predictive factors for LOR during ELT treatment. We report more than 3 years of long‐term clinical data on children with cITP using ELT. These data do not raise any new safety concerns regarding the long‐term use of ELT in children with cITP. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by isolated thrombocytopenia and a haemorrhagic risk. Thrombopoietin receptor agonists (TPO‐RAs) are highly effective for ITP and are widely used to treat patients with steroid treatment failure or dependency. However, although treatment response to TPO‐RAs may differ according to the type, the potential impact of switching from eltrombopag (ELT) to avatrombopag (AVA) with respect to efficacy or tolerance in children remains unknown. This study aimed to evaluate the outcomes of switching from ELT to AVA in paediatric patients with ITP. We retrospectively evaluated children with chronic immune thrombocytopenia (cITP) switched from ELT to AVA owing to treatment failure at the Hematology‐Oncology Center of Beijing Children's Hospital between July 2021 and May 2022. Overall, 11 children (seven and four boys and girls respectively) with a median age of 8.3 (range: 3.8–15.3) years were included. The overall response and complete response (platelet [PLT] count ≥100 × 109/L) rates during AVA treatment were 81.8% (9/11) and 54.6% (6/11) respectively. The median PLT count was significantly increased from ELT to AVA (7 [range: 2–33] × 109/L vs. 74 [15–387] × 109/L; p = 0.007). The median time to PLT count ≥30 × 109/L was 18 (range: 3–120) days. Overall, 7/11 patients (63.6%) used concomitant medications, and concomitant medication use was gradually discontinued within 3–6 months after AVA initiation. In conclusion, AVA after ELT is effective in the heavily pretreated paediatric cITP population, with high response rates even in those with an inadequate response to a prior TPO‐RA. [ABSTRACT FROM AUTHOR]

Summary: Eltrombopag (ELT) is effective and safe in adult persistent/chronic immune thrombocytopenia (p/cITP); a proportion could achieve a sustained response off treatment (SRoT); however, data on children are lacking. We attempted to analyse SRoT of ELT in children with p/cITP in this study. A multicentre retrospective observational study was performed in November 2022 for children with p/cITP who used ELT alone for >2 months between January 2017 and November 2021. Clinical data of pre‐, during and post‐ELT were collected. SRoT was defined as maintaining a platelet count of ≥30 × 109/L without rescue therapy for at least 6 months off ELT. There were 143 patients enrolled; 69.2% (99/143) achieved an overall response of 43.3% and 25.9% achieved complete response (CR) and response (R). Among the 35 patients analysed from whom ELT was withdrawn, 71.4% (25/35) showed SRoT after discontinuing ELT without additional ITP therapy, with a median follow‐up of 0.94 (range, 0.53–3.8) years, equal to 17.5% (25/143) in all patients treated with ELT. Compared with the patients with relapse (n = 10), the SRoT patients (n = 25) had a higher rate of CR (80% [20/25] vs. 40% [4/10]), shorter interval time from initiation to taper (6.4 months vs. 9.4 months), longer time from taper to withdrawal (1.1 years vs. 0.3 years) and a longer duration of ELT treatment (1.6 years vs. 0.5 years) with p < 0.05. Patients who achieved CR could attain SRoT more easily (p = 0.02). ELT had a response in 69.2% of children with p/cITP and 17.5% of them attained SRoT with good tolerance. The patients who achieved CR and began ELT treatment as early as possible, with a longer treatment duration and slower tapering, had a higher probability of SRoT. [ABSTRACT FROM AUTHOR]

In this study, we construct a Cu@ZrO2 heterogenous structure as a new catalyst that achieves a large NH3 yield of 15.4 mg h−1 mg−1cat. and a high faradaic efficiency of 67.6% at −0.7 V vs. RHE in 0.1 M PBS with 0.1 M NaNO3, and it also shows excellent electrochemical durability and structural stability. Theoretical calculations reveal an extremely low adsorption energy of −1.54 eV at Cu surfaces and Cu can significantly reduce the applied overpotential and correspondingly promote the catalytic activity. [ABSTRACT FROM AUTHOR]

Electrochemical synthesis of ammonia via nitrogen reduction reaction is a rational route to save energy and relieve pollution compared to the traditional Haber‐Bosch process. In this report, ZrO2 nanosphere derived from thermolysis of Zr‐based biphenyl‐4,4′‐dicarboxylic acid MOFs (ZrO2/C) as a non‐noble metal catalyst with large specific surface area and porous structure is proposed to fix nitrogen to ammonia at ambient conditions. Such catalyst achieves Faradaic efficiency of 11.86 % and a NH3 yield rate of 10.72 μg h−1 mg−1cat. at −0.6 V vs. the reversible hydrogen electrode in 0.1 M Na2SO4. First‐principles calculations confirm the alternating reaction at the catalyst surface. [ABSTRACT FROM AUTHOR]

A method to design the metasurface‐based splitter with dual beams which have different power distributions, polarizations, and radiated angles is proposed. The presented metasurface is ultrathin which is only 0.12λ and the whole unit cell is mainly composed of receiving antenna with single‐polarization, power divider, dual‐channel phase shifter with independent control and transmitting antenna with dual‐polarization. According to the functional requirements of the beam splitter, the main components which are power divider and phase shifter can be artificially tailored correspondingly. And the fixed design of receiving and transmitting antennas can receive the incident electromagnetic (EM) wave with single‐polarization and transmit the EM wave with dual‐polarization, respectively. Comparing with conventional cascaded transmitarray and bulk lens, the design logic of proposed whole splitter is very clear that scanning and optimizing massive parameters of unit cells for satisfying the demands of polarization, transmission phase, and power distribution simultaneously is not needed. The good consistent results of experiment and simulation can verify the validity of our design. [ABSTRACT FROM AUTHOR]

High‐performance earth‐abundant electrocatalysts for oxygen evolution reaction (OER) are highly desirable. In this report, we successfully synthesized amorphous Fe−P shell electrodeposited on Co(OH)F nanowire arrays supported on titanium mesh (Fe−P@Co(OH)F/TM) as an efficient catalyst for OER. Such catalyst exhibits excellent OER activity with a low overpotential of 267 mV to reach the geometrical current density of 10 mA cm−2 in 1.0 M KOH. In addition, it has good electrochemical durability to maintain its activity for at least 20 h. [ABSTRACT FROM AUTHOR]

A benign thermal stress in solid oxide fuel cell is of great importance for its stability and the interfaces between different components suffer from unexpected risks of instability such as electrode delamination and crack due to varying thermal expansion coefficients. Besides, chromium poisoning cathode materials leads to phase changes, which possibly induces thermal stresses at the interface of electrolyte and cathode. A three dimensional model at the microscale level is thus developed to unravel the effect of thermal stress on the interface. The model is constructed by governing equations including heat, species, momentum, ion and electronic transportation. The contact modes between the active cathode and electrolyte are studied to reveal the cell performance and thermal stresses, which are strongly related to the number of contact sites and the contact area. Moreover, chromium poisoning the contact causes the disordered distribution of thermal stresses with the increase of the contact sites, worsening the cell current density and durability. The resulting conclusions are expected to offer a solution to avoid possible fatal mechanical failure due to unfavorable interface design and chromium attack. [ABSTRACT FROM AUTHOR]