Termination Criterion Research Articles

A fast hybrid roundness evaluation algorithm based on computational geometry and particle swarm optimization for profiles with massive points

The advancement of measurement has led to rigorous demands for the accuracy and efficiency of roundness evaluation of minimum zone circle (MZC) for profile with massive points. Existing algorithms struggle to balance efficiency and accuracy in such cases. A fast hybrid roundness evaluation (HCGPSO) algorithm for MZC based on the computational geometry (CG) and particle swarm optimization (PSO) algorithm is proposed, which incorporates a CG-based global best (gBest) selection method into the PSO algorithm and refines the termination criterion. A comparison with the published studies demonstrated that the HCGPSO algorithm were accurate and result are displayed to 10-15 mm. The impact of target accuracy, the harmonic and the number of points contained in profile on the performance of proposed algorithm are analyzed. With sub-nanometer target evaluation precision, HCGPSO enhances efficiency by an average of 64 % for profiles containing the highest harmonics from 30 undulations per revolution (upr) to 500 upr with 1500 points. For profiles with 300 to 4000 points at 150 upr, an average efficiency enhancement of 60 % was observed. For profiles with 4000 points at 500 upr from four workpieces, the calculation time is reduced by 55 % on average compared to the PSO algorithm, with increased accuracy and stability.

Reservoir Production Management With Bayesian Optimization: Achieving Robust Results in a Fraction of the Time

Summary In well control (production) optimization, the computational cost of conducting a full-physics flow simulation on a 3D, rich grid-based model poses a significant challenge. This challenge is exacerbated in a robust optimization (RO) setting, where flow simulation must be repeated for numerous geological realizations, rendering RO impractical for many field-scale cases. In this paper, we introduce and discuss a new optimization workflow that addresses this issue by providing computational efficiency, i.e., achieving a near-global optimum of the predefined objective function with minimal forward model (flow-simulation) evaluations. In this workflow, referred to as “Bayesian optimization (BO),” the objective function for samples of decision (control) variables is first computed using a proper design experiment. Then, given the samples, a Gaussian process regression (GPR) is trained to mimic the surface of the objective function as a surrogate model. While balancing the dilemma to select the next control variable between high mean, low uncertainty (exploitation) and low mean, high uncertainty (exploration), a new control variable is selected, and flow simulation is run for this new point. Later, the GPR is updated, given the output of the flow simulation. This process continues sequentially until the termination criteria are satisfied. To validate the workflow and obtain a better insight into the detailed steps, we first optimized a 1D problem. The workflow is then implemented for a 3D synthetic reservoir model to perform RO in a realistic field scenario (8-dimensional and 45-dimensional optimization problems). The workflow is compared with two other commonly used gradient-free algorithms in the literature: particle swarm optimization (PSO) and genetic algorithm (GA). The main contributions are (1) developing a new optimization workflow to address the computational cost of flow simulation in RO, (2) demonstrating the effectiveness of the workflow on a 3D grid-based model, (3) investigating the robustness of the workflow against randomness in initiation samples and discussing the results, and (4) comparing the workflow with other optimization algorithms, showing that it achieves same near-optimal results while requiring only a fraction of the computational time.

Progressive Gaussian Decomposition of Airborne Bathymetric LiDAR Waveform for Improving Seafloor Point Extraction

Airborne bathymetric LiDAR (ABL) acquires waveform data with better accuracy and resolution and greater user control over data processing than discrete returns. The ABL waveform is a mixture of reflections from the water surface and bottom, water column backscattering, and noise, and it can be separated into individual components through waveform decomposition. Because the point density and positional accuracy of the point cloud are dependent on waveform decomposition, an effective decomposition technique is required to improve ABL measurement. In this study, a new progressive waveform decomposition technique based on Gaussian mixture models was proposed for universal applicability to various types of ABL waveforms and to maximize the observation of seafloor points. The proposed progressive Gaussian decomposition (PGD) estimates potential peaks that are not detected during the initial peak detection and progressively decomposes the waveform until the Gaussian mixture model sufficiently represents the individual waveforms. Its performance is improved by utilizing a termination criterion based on the time difference between the originally detected and estimated peaks of the approximated model. The PGD can be universally applied to various waveforms regardless of water depth or underwater environment. To evaluate the proposed approach, it was applied to the waveform data acquired from the Seahawk sensor developed in Korea. In validating the PGD through comparative evaluation with the conventional Gaussian decomposition method, the root mean square error was found to decrease by approximately 70%. In terms of point cloud extractability, the PGD extracted 14–18% more seafloor points than the Seahawk’s data processing software.

Inhalation anesthesia in the cat: Development of cuff pressure when using nitrous oxide

During inhalation anesthesia with nitrous oxide in oxygen the pressure in the cuff of the endotracheal tube may increase due to diffusion of nitrous oxide into the cuff. The aim of the study was to investigate the development of cuff pressure during nitrous oxide anesthesia under clinical conditions in feline patients and to identify possible influencing factors such as tube size and gas flow rate. The prospective study included cats scheduled for inhalation anesthesia with nitrous oxide for a minimum duration of 60 minutes at the Department for Small Animals of the University of Leipzig. Cuff pressure was adjusted with a cuff manometer and its development was recorded. In total, the cuff pressure values of 24 cats were recorded. Animals were allocated into groups by tube size (ID 4.0 mm and ID 4.5 mm) and by fresh gas flow rate: low flow rate (0.6 l/min) and high flow rate (3 l/min). During anesthesia, cuff pressure increased over time, with statistical significance occurring from 45 minutes onwards in comparison to the initial cuff pressure (p=0.005). After 60 minutes, there was a mean cuff pressure increase of 3 cmH2O. Despite this moderate mean increase, highly variable pressure values up to 48 cmH2O in individual animals were recorded. No cat reached the termination criterion of 60 cmH2O cuff pressure. Effects of tube size (p=0.63) and flow rate (p=0.334) on the cuff pressure were not evident. After a period of 45 minutes of nitrous oxide administration, a significant increase in cuff pressure occurs in the cat. However, tube size and total gas flow rate do not seem to influence the cuff pressure development. When using nitrous oxide during inhalation anesthesia, regular cuff pressure evaluation and correction are necessary and hence recommended in feline patients. As individual pressure changes may be highly variable, no fixed recommendations for optimal management are possible.

Long-Term Safety and Efficacy of SAbR for Metastatic RCC.

Metastasis-directed stereotactic ablative radiation (SAbR) in metastatic renal cell carcinoma (mRCC) has been shown to prolong time to systemic therapy start/change. However, there is a paucity of data on the durability of local control by SAbR and long-term side effects, limiting its investigation in prospective trials. Here we report the long-term local control rates of SAbR for mRCC, focusing on factors that lead to local failure where dose escalation may be beneficial. We retrospectively reviewed 354 metastatic RCC patients who received SAbR to 902 lesions between 2005 and September 2021. Acute and late adverse events and their Common Terminal Criteria for Adverse Events (CTCAE) v. 5.0 grades were collected. RECIST v. 1.1 was used to evaluate treatment response. LC was estimated using the cumulative incidence function, with death as a competing risk. Local control (LC) was calculated using the Kaplan-Meier method. Lesions were followed for a median of 16 months; 136 lesions had >36 months of follow-up. The most common radiation prescription was 36 Gy in 3 fractions, and the median biological effective dose was 72 Gy10. 3-year local control was 80% (95% CI 75, 83). 3-year LC differed according to lesion location, ranging from 65% (95% CI 52, 75) in the spine to 93% (95% CI 80, 98) in the lungs. Radiation-induced adverse events were experienced by 101 patients: 79 had an acute (≤90 days of SAbR) grade 1-2 toxicity; 20 had an acute grade 3-4 toxicity; 59 had a late grade 1-2 toxicity; 15 had a late grade 3-4 toxicity. The most common acute grade 1-2 toxicity was pain (n = 32), followed by nausea (n = 22) and fatigue (n = 16). There were 7 occurrences of acute grade 3-4 pain, 4 of nausea, and 2 fractures. The most common late grade 1-2 toxicity was fracture (n = 16), followed by pain (n = 15) and pneumonitis (n = 12). Hyperglycemia was the only late grade 3-4 toxicity that occurred more than once (n = 2). SAbR offers durable LC of mRCC lesions with an acceptable toxicity profile. LC was affected by treated lesion location, with bone (including long bones and ribs) and spine locations experiencing less durable LC, corresponding to locations that received lower-BED treatments.

Termination of Cardiopulmonary Resuscitation in Mountain Rescue: A Scoping Review and ICAR MedCom 2023 Recommendations.

Lugnet, Viktor, Miles McDonough, Les Gordon, Mercedes Galindez, Nicolas Mena Reyes, Alison Sheets, Ken Zafren, and Peter Paal. Termination of cardiopulmonary resuscitation in mountain rescue: a scoping review and ICAR MedCom 2023 recommendations. High Alt Med Biol. 24:274-286, 2023. Background: In 2012, the International Commission for Mountain Emergency Medicine (ICAR MedCom) published recommendations for termination of cardiopulmonary resuscitation (CPR) in mountain rescue. New developments have necessitated an update. This is the 2023 update for termination of CPR in mountain rescue. Methods: For this scoping review, we searched the PubMed and Cochrane libraries, updated the recommendations, and obtained consensus approval within the writing group and the ICAR MedCom. Results: We screened a total of 9,102 articles, of which 120 articles met the inclusion criteria. We developed 17 recommendations graded according to the strength of recommendation and level of evidence. Conclusions: Most of the recommendations from 2012 are still valid. We made minor changes regarding the safety of rescuers and responses to primary or traumatic cardiac arrest. The criteria for termination of CPR remain unchanged. The principal changes include updated recommendations for mechanical chest compression, point of care ultrasound (POCUS), extracorporeal life support (ECLS) for hypothermia, the effects of water temperature in drowning, and the use of burial times in avalanche rescue.

A short-term prediction-based efficient optimization power control strategy for heavy-duty hybrid electric vehicle

This study proposes a short-term prediction-based power control strategy using the modified iteration sequential clustering quadratic programming (MISCQP) algorithm for heavy-duty series hybrid electric vehicles (SHEVs). In this strategy, a power preconditioning method is established on the basis of demand power prediction which guarantees the stable power output under transient high-power condition. Through the prediction sequence, MISCQP algorithm is proposed to solve receding horizon problem and achieve real-time control by improving the iteration efficiency. For this purpose, the clustering algorithm is designed to skip the unnecessary short step in the iteration which is too few to obtain sufficient descent. The iteration points in various iteration domains are clustered and the corresponding cluster centers are obtained. Next, the aforementioned clustering results are introduced to improve the termination criterion. The updated criterion turns to skip the short step when the distance of cluster centers of various iteration domains varies within the set threshold. Finally, the performance of the proposed strategy is validated both in simulation and hardware-in-loop tests. The results reveal that the proposed strategy achieves 5.00 %, 5.86 %, 6.27 % less fuel consumption while maintaining stable power output under all the driving cycles. And the average iteration number of proposed strategy is decreased by 10.36 %, 8.47 %, 9.21 %, respectively.

Belief propagation list decoding for polar codes: Performance analysis and software implementation on GPU

Belief propagation (BP) decoding outputs soft information and can be naturally used in iterative receivers. BP list (BPL) decoding provides comparable error-correction performance to the successive cancellation list (SCL) decoding. In this paper, we firstly introduce an enhanced code construction scheme for BPL decoding to improve its error-correction capability. Then, a GPU-based BPL decoder with adoption of the new code construction is presented. Finally, the proposed BPL decoder is tested on NVIDIA RTX3070 and GTX1060. Experimental results show that the presented BPL decoder with early termination criterion achieves above 1 Gbps throughput on RTX3070 for the code (1024, 512) with 32 lists under good channel conditions.

SIMULATION OF STEEPNESS-LIMITED BREAKING WAVES IN A FULLY NONLINEAR POTENTIAL FLOW MODEL

Steepness-limited wave breaking is simulated in a fully nonlinear potential flow model and validated with laboratory data. Breaking onset is based on the ratio of horizontal particle velocity at the crest, relative to the crest velocity reaching a threshold value. A breaking dissipation model, where the non-dimensional breaking strength parameter is predicted based on the linear wave steepness is used. A new time-dependent dissipation is tested, and the breaking termination criterion is studied.

A Novel Response Factor-Based Method for In Situ Measurement of Wall Thermal Resistance

The heat flow meter method (HFM) is one of the most-used methods for the in situ measurement of wall thermal resistance. However, the standard HFM method has some issues: it is challenging to balance simplicity and accuracy in data analysis and the measurement period needs to be shorter. In this paper, a new dynamic data analysis method for the in situ measurement of wall thermal resistance is introduced, which is based on a truncated form of the infinite response factors for a wall heat conduction process and has a theoretically deducted convergence criteria for the automatic termination of an in situ measurement. The efficacy of the proposed method is validated by a theoretical analysis and by experiments from one simulation dataset and one measurement dataset. Preliminary experimental results show that the proposed method can reduce the measurement time by about one-third on average while maintaining the same accuracy as the standard average method. Due to the advantages of a clear physical meaning, a simple principle, and a short measurement period, the proposed method contributes to the quick and accurate estimation of the wall thermal resistance in buildings.

The prognosis of neonatal respiratory status within three years after birth in chronic abruption-oligohydramnios sequence.

Chronic abruption-oligohydramnios sequence (CAOS), which is characterized by vaginal bleeding and oligohydramnios, adversely affects the lungs of fetuses due to bloody amniotic fluid and oligohydramnios. The criteria for termination of pregnancy remain controversial. This study aimed to examine respiratory function in infants within 3 years after birth and risk factors for respiratory prognosis, and to clarify the management of CAOS. This study is a case series of patients with CAOS managed at our institution between 2010 and 2020. The clinical data of the patients and their infants within 3 years after birth were reviewed. The amniotic fluid volume was measured using the maximum vertical pocket (MVP). Six of 17 neonates (35.3%) used inhaled nitric oxide (iNO) to improve oxygenation. Women with longer periods of MVP <1 cm delivered more neonates using iNO; however, periods of MVP <2 cm were not associated with iNO use. Almost half of the infants required home oxygen therapy when discharged, regardless of amniotic fluid volume. At 18 months corrected age, only one child needed respiratory support, and the others discontinued. Two neonates, both born at 23 weeks of gestational age, died within 1 month after birth because of extremely preterm birth. The amniotic fluid volume could predict the use of iNO in neonates, but it did not affect the child's respiratory function after the newborn period. Almost all children born to women with CAOS can improve their respiratory function as they grow up.

A nationwide cross-sectional study using a web-based questionnaire survey of the duration of isolation of COVID-19 inpatients with cancer at Japanese cancer centers

There is no clear consensus regarding the optimal isolation duration for immunocompromised patients with coronavirus disease 2019 (COVID-19). Therefore, we conducted a questionnaire survey at eight Japanese cancer centers to investigate the practices of infectious disease specialists regarding the duration of isolation for COVID-19 inpatients with cancer. For asymptomatic to severely ill COVID-19 inpatients without severe immunodeficiency, four centers reported at least 10 days of isolation without testing, and two reported at least 20 days. Two centers incorporated polymerase chain reaction (PCR) as a criterion for terminating the isolation of inpatients without severe immunodeficiency. For severely immunocompromised COVID-19 inpatients, at least 20 days of isolation were required in seven facilities, regardless of illness severity. Additionally, seven centers had implemented Ct or antigen quantification test values as criteria for de-isolating severely immunocompromised inpatients. No cases caused nosocomial outbreaks after isolation was terminated based on each facility's criteria for isolation termination. Thus, cancer patients required longer isolation periods than the general population in most facilities, and for those with severe immunodeficiency, the isolation periods were longer and more tightly controlled with tests.

Enhanced Multi-Objective Power Flow Optimization for IEEE-118 Bus Test System using Advanced Grey Wolf Optimization Algorithm

This research article thoroughly examines the implementation of an enhanced Grey Wolf Optimization (GWO) method for Multi-Objective Power Flow Optimization (MO-PFO) in the IEEE-118 bus test system. Given the growing complexity and uncertainty in modern power systems, power flow optimization presents a crucial challenge. The suggested enhanced GWO algorithm improves the performance of the traditional GWO for MO-PFO issues while addressing its inherent flaws.&#x0D; The goal of this study is to obtain optimal solutions concurrently for multiple objectives, including the reduction of power losses, voltage variations, and the enhancement of system stability. In the Related Works section, I review the research on power flow optimization in the literature, which also showcases the improvements achieved by applying various optimization techniques and discusses the benefits and drawbacks of traditional optimization methods and their effectiveness in dealing with MO-PFO issues.&#x0D; The improved GWO algorithm, designed specifically for MO-PFO, is described in detail in the Methodology section. I explain the adjustments made to the regular GWO algorithm and introduce a cutting-edge method for handling multiple objectives. In the IEEE-118 bus test system, I present the mathematical model of the MO-PFO problem and develop fitness functions for each objective.&#x0D; Furthermore, I describe the implementation of the enhanced GWO algorithm, including parameter settings and termination criteria. The proposed algorithm demonstrates its capability to effectively handle the multi-objective nature of power flow optimization, thereby paving the way for future power system operations that are more dependable and sustainable

Convergence analysis of Lattice Boltzmann method for Stokes flow in digital rock characterization

The absolute permeability is a key parameter for characterization of reservoir rocks. It can be estimated numerically by combining digital rocks and Stokes flow simulation using Lattice Boltzmann Method (LBM). In previous research, the LBM is usually implemented as an iterative process, which continues until the changes in estimates of the parameters between two consecutive iterations reach below a certain threshold level. We remark that this termination criterion is not appropriate and may lead to low accuracy in the simulation results. Here we analyze the convergence of LBM in various tests including the Poiseuille flow between two parallel plates, and several types of digital rocks (dune sand, sandstone and carbonates). The logarithm of relative error of each estimate compared with the estimate at infinite time (as stable state) is found to have a linear relation with regard to the number of iterations, indicating an exponential rate of convergence. If the difference of errors between two consecutive iterations is used as the termination condition, the result could be far from a stable state. Instead, we recommend using the decay trend of the error difference in the LBM simulation to provide an accurate termination criterion, which serves as a practical and more adequate way for characterization of reservoir rocks. We also provided the theoretical explanation of convergence rate, which is related to the spectral radius of iterative matrix in linear algebra.

Discrepancy between predicted and measured exercise intensity for eliciting the maximal rate of lipid oxidation

Background and aimsEctopic lipid storage is implicated in type 2 diabetes pathogenesis; hence, exercise to deplete stores (i.e., at the intensity that allows for maximal rate of lipid oxidation; MLO) might be optimal for restoring metabolic health. This intensity (“Fatmax”) is estimated during incremental exercise (“Fatmax test”). However, in “the field” general recommendations exist regarding a range of percentages of maximal heart rate (HR) to elicit MLO. The degree to which this range is aligned with measured Fatmax has not been investigated. We compared measured HR at Fatmax, with maximal HR percentages within the typically recommended range in a sample of 26 individuals (Female: n = 11, European ancestry: n = 17). Methods and resultsSubjects completed a modified Fatmax test with a 5-min warmup, followed by incremental stages starting at 15 W with work rate increased by 15 W every 5 min until termination criteria were reached. Pulmonary gas exchange was recorded and average values for V˙ o2 and V˙ co2 for the final minute of each stage were used to estimate substrate-oxidation rates. We modeled lipid-oxidation kinetics using a sinusoidal model and expressed MLO relative to peak V˙ o2 and HR. Bland-Altman analysis demonstrated lack of concordance between HR at Fatmax and at 50%, 70%, and 80% of age-predicted maximum with a mean difference of 23 b·min−1. ConclusionOur results indicate that estimated “fat-burning” heart rate zones are inappropriate for prescribing exercise to elicit MLO and we recommend direct individual exercise lipid oxidation measurements to elicit these values.

Hierarchical K-means clustering method for accelerated Lorentzian estimation (KALE) in chemical exchange saturation transfer-magnetic resonance imaging quantification.

Quantification of in vivo chemical exchange saturation transfer (CEST) magnetic resonance signals is challenging due to contamination from coexisting effects, including the direct water effect and asymmetric magnetization transfer. Fitting-based analysis allows the calculation of multiple types of signals from the line shape of Z-spectra. However, the conventional voxelwise method has several drawbacks, including its long computation time and its susceptibility to image noise and Z-spectra oscillations, and it is difficult to determine the initial fitting parameters. Herein, we propose a K-means clustering method for accelerated Lorentzian estimation (KALE) in CEST quantification. Briefly, voxels in CEST images are clustered into K groups according to their Z-spectra characteristics. A 'groupwise' fitting process is then performed with preset initial values, yielding a set of fitted spectra and fitted parameters for each group. With the updated initial values, each group is further clustered into subgroups, and groupwise fitting is performed again. This hierarchical K-means clustering and parameter updating process continues until the pixel number or intensity error meets the termination criteria. Voxelwise fitting could be further conducted to improve the quantification images (termed voxel-K) by utilizing the previous groupwise KALE results as the initial values (termed group-K). Incorporated with Lorentzian difference (LD) quantification, KALE was first optimized and evaluated on 5 healthy human brain datasets at 3 Tesla. Compared with traditional voxel-by-voxel LD quantification, the computation times of group-K and voxel-K were significantly reduced by ~85% and ~70%, respectively (P<0.001). Furthermore, the group-K images exhibited better denoising performance than traditional LD and voxel-K. KALE was further validated on six ischemic rat brains acquired at 7 Tesla, with both LD_group-K and LD_voxel-K displaying almost identical contrast maps with traditional voxelwise maps. When incorporated with the five-pool Lorentzian fitting (LF), KALE exhibited an improved contrast-to-noise ratio (CNR) for amplitude maps of each pool [P=0.003, 0.015, 0.047, and 0.047 for amide, nuclear Overhauser effect (NOE), magnetic transfer (MT) and guanidine amine, respectively] and improved fitting goodness (P=0.033). KALE quantification provides comparable or even superior contrast maps to traditional voxelwise fitting, with significantly reduced computation time. The 'smart' and hierarchical voxel-clustering and parameter updating process of KALE may facilitate more preclinical and clinical CEST applications.

Applying multidimensional computerized adaptive testing to the MSQOL-54: a simulation study

BackgroundThe Multiple Sclerosis Quality of Life-54 (MSQOL-54) is one of the most commonly-used MS-specific health-related quality of life (HRQOL) measures. It is a multidimensional, MS-specific HRQOL inventory, which includes the generic SF-36 core items, supplemented with 18 MS-targeted items. Availability of an adaptive short version providing immediate item scoring may improve instrument usability and validity. However, multidimensional computerized adaptive testing (MCAT) has not been previously applied to MSQOL-54 items. We thus aimed to apply MCAT to the MSQOL-54 and assess its performance.MethodsResponses from a large international sample of 3669 MS patients were assessed. We calibrated 52 (of the 54) items using bifactor graded response model (10 group factors and one general HRQOL factor). Then, eight simulations were run with different termination criteria: standard errors (SE) for the general factor and group factors set to different values, and change in factor estimates from one item to the next set at < 0.01 for both the general and the group factors. Performance of the MCAT was assessed by the number of administered items, root mean square difference (RMSD), and correlation.ResultsEight items were removed due to local dependency. The simulation with SE set to 0.32 (general factor), and no SE thresholds (group factors) provided satisfactory performance: the median number of administered items was 24, RMSD was 0.32, and correlation was 0.94.ConclusionsCompared to the full-length MSQOL-54, the simulated MCAT required fewer items without losing precision for the general HRQOL factor. Further work is needed to add/integrate/revise MSQOL-54 items in order to make the calibration and MCAT performance efficient also on group factors, so that the MCAT version may be used in clinical practice and research.

A fixed-point iteration method for high frequency vector wave equations

For numerically solving the high frequency vector wave equations, we present a simple approach based on fixed point iterations, where the problem is transferred into a fixed-point problem related to an exponential operator. The associated functional evaluations are achieved by unconditionally stable operator-splitting based pseudospectral schemes such that large step sizes are allowed to reach the approximated fixed point efficiently for prescribed termination criteria. For the sub-operator that is related to non-constant relative permeability, the Krylov subspace method or Taylor expansion is adapted for approximating its exponential. Furthermore, the Anderson acceleration is incorporated to accelerate the convergence of the fixed-point iterations. Numerical experiments are presented to demonstrate the accuracy and efficiency of the method.

A randomized, double-blind, phase 3 study of jaktinib versus hydroxyurea (HU) in patients (pts) with intermediate-2 or high-risk myelofibrosis (MF).

7015 Background: Ruxolitinib and HU are recommended by Chinese MF guideline for splenomegaly. There is an unmet need for new treatments. Jaktinib, a novel JAK and AVCR1 inhibitor, showed promising activity on splenomegaly, anemia, and MF symptoms in a phase 2 study (NCT03886415). Here we present the interim results of a phase 3 study, which assessed the efficacy and safety of jaktinib compared to HU. Methods: Pts aged ≥ 18 with primary or post-ET/PV MF, DIPSS Int-2 or high risk, and no prior or ≤10 days’ treatment with a JAK inhibitor were enrolled and randomly assigned (2:1) to receive jaktinib 100 mg bid plus HU placebo or HU 0.5g bid plus jaktinib placebo, stratified by DIPSS risk status (Int-2 or high risk). One interim analysis was pre-specified to be conducted when 70 pts completed the week (wk) 24 visit or met the criteria for treatment termination before wk 24. The primary endpoint was the proportion of pts with a spleen volume reduction of ≥ 35% from baseline (SVR35) at wk 24, measured by MRI/CT images and assessed centrally. Secondary endpoints included the best spleen response rate (defined as achieving SVR35 at any time), the proportion of pts with a ≥ 50% reduction in Total Symptom Score (TSS50), improvement of anemia, safety, etc. Results: This interim analysis (cut-off: April 8, 2022) included 47 pts receiving jaktinib and 23 receiving HU. 66.0% (jaktinib) and 69.6% (HU) had a baseline hemoglobin (Hb) &lt; 100 g/L. 59.6% (jaktinib) and 69.6% (HU) were JAK2V617F positive. The SVR35 rates at wk 24 were 72.3% for jaktinib vs. 17.4% for HU ( p≤0.0001). The best spleen response rates were 80.9% of jaktinib-treat pts vs. 26.1% of HU-treated pts ( p≤0.0001). The median maximum percentage change from baseline in spleen volume were -46.59% vs. -18.50%. The TSS50 rates at wk 24 were 63.8% for jaktinib vs. 43.5% for HU ( p = 0.1163). 5 of 7 jaktinib-treated and two of 5 HU-treated pts who required RBC transfusion at baseline achieved a ≥50% decrease in RBC transfusion by wk 24. In transfusion-independent pts with baseline Hb ≤100 g/L, 39.3% for jaktinib and 15.4% for HU had a ≥20 g/L Hb increase. The most common grade ≥3 hematological treatment emergent adverse events (TEAEs) (jaktinib vs. HU) were anemia (25.5% vs. 43.5%), thrombocytopenia (17.0% vs. 39.1%), leukopenia (2.1% vs. 21.7%), neutropenia (2.1% vs. 21.7%) and decreased lymphocyte count (2.1% vs. 13.0%). Most common non-hematological TEAEs were upper respiratory tract infection (21.3% vs. 21.7%), elevated bilirubin (12.8% vs. 26.1%), fever (12.8% vs. 21.7%) and diarrhea (10.6% vs. 21.7%), predominantly of grade 1 or 2. TEAEs leading to treatment discontinuation occurred in 8.5% of jaktinib and 17.4% of HU. Conclusions: Jaktinib demonstrated significant clinical benefits over HU in MF pts for spleen response with improved symptom response and less cytopenias. Jaktinib may be a new treatment option for MF pts, especially for those with anemia. Clinical trial information: NCT04617028 .

Termination of trastuzumab in HER2-positive metastatic breast cancer patients who received trastuzumab beyond progression

The purpose of the study was to assess the prognosis of HER2-positive metastatic breast cancer patients who received trastuzumab beyond progression and investigate the predictors of complete response. HER2-positive metastatic breast cancer patients who received long-term trastuzumab were included in the study. Predictors of complete response were analyzed with binary regression analysis. The prognosis of patients who had their trastuzumab-based treatment terminated was assessed. Eighty patients were involved in the study. The patients were received with trastuzumab for a median of 62 months (12–191). A complete response was observed in 60 (75%) patients. The median duration to development of complete response was found as 14.8 months (2.4–55). In logistic regression analysis: using endocrine therapy with trastuzumab (p = 0.04), menopausal status (p = 0.03), and the number of metastatic sites (p = 0.01) were found to be statistically significant factors for a complete response. Trastuzumab-based therapy of fifteen patients was terminated, six (40%) patients continued to receive an aromatase inhibitor, and nine (60%) patients were followed up without treatment. After termination of trastuzumab, at a median follow-up of 32 months (11–66), recurrence was detected in two (13.3%) patients. We detected that menopausal status, the number of metastatic sites, and using endocrine therapy with trastuzumab were predictors of complete response in HER2-positive metastatic breast cancer patients who received long-term trastuzumab-based therapy. We observed that HER2-positive metastatic breast cancer patients may be completely cured with trastuzumab-based therapy. There are no defined criteria for termination of trastuzumab treatment in this selected patient group. It is necessary to confirm our data with multicenter studies involving a large number of patients.