Sequential Evaluation Research Articles

Adaptive support vector machine for time-variant failure probability function estimation

Time variant reliability analysis introduces additional complexity due to the inclusion of time. When the time-variant failure probability function (TFPF) of the structure is of interest, it inherently involves sequential evaluations of the failure probabilities of series systems varied with time in discretized space, posing a challenge to reliability analysis. An efficient approach for the evaluation of the TFPF, called ‘Time-dependent Adaptive Support Vector Machine combined with Monte Carlo Simulation’ (TASVM-MCS), is presented to reduce the corresponding computational cost. Based on the samples from Monte Carlo simulation (MCS), an iterative strategy is proposed to actively extract the most valuable sample points from the sample pool and iteratively update the support vector machine (SVM) model. In particular, an active learning function is proposed to take into account the diversity of samples and time simultaneously. In this way, the built SVM will be more suitable for the evaluation of TFPF other than a point-wise failure probability. The proposed TASVM-MCS method is relatively less sensitive to the dimensionality of the input variables, making it a powerful and promising approach for time-variant reliability computations. Four representative examples are given to demonstrate the significant effectiveness and efficiency of the proposed method.

How Do We Better Serve Excluded Populations When Delivering Digital Health Technology? Inclusion Evaluation of a Digital Musculoskeletal Self-Management Solution.

Digital self-management platforms have been proposed as a solution to better support people manage their musculoskeletal (MSK) condition. However, research studies often explicitly exclude people who can't access internet connected devices. An important consideration is that digital exclusion (for people without access to an internet connected device) from these new digital options will worsen already existing inequality and inequity in healthcare. To evaluate the acceptability and potential causes of digital exclusion of the South West London (SWL) MSK self-management app. (1) Explore why some patients are not using the app and any barriers they have. Explore why some clinicians are not prescribing the app. (2) Make recommendations, based on these findings, to improve digital inclusion. An explanatory sequential mixed method service evaluation that consisted of initial questionnaires to identify suitable collaborators, followed by structured interviews of patients and clinicians. Following a comprehensive data analysis, 10 sub-themes were grouped into four main themes: (1) Beliefs: Importance of understanding the role of digital; face to face consultation is still valued and needed. (2) Barriers: Lack of digital literacy; lack of physical examination/contact with a clinician. (3) Enablers: Immediate access to advice and information; perceived better control over health; ease of use; no appointment needed. (4) Solutions: Support and training; greater awareness. As digital health technology develops, strategies must change, requiring deliberate work and investments to improve inclusion. Our findings highlight how digital technology design and delivery can be adapted to address the causes of digital exclusion.

Addressing mental illness stigma in German higher education: study protocol for a mixed-methods evaluation of a psychosocial setting-based intervention

IntroductionMental illness stigma is associated with a range of negative consequences, such as reduced help-seeking for mental health problems. Since stigma affects individual, social, and structural aspects, multilevel interventions such...

Critical condition for initiation of dynamic recrystallisation in electron beam powder bed fused Ti-6Al-4 V Alloy

Despite the unique capabilities of Additive Manufacturing (AM) processes for producing Ti components with complex geometries, the desired properties are only achievable if a holistic scheme is devised, considering the synergistic role of post-processing steps. This work aimed to enhance the applicability of metal AM products by improving the process chain in the manufacturing industry. For this purpose, the current work demonstrates a comprehensive investigation into the hot deformation of Ti-6Al-4 V (Ti64) pre-forms produced via the Electron Beam Powder Bed Fusion (EB-PBF) process focusing on the determination of critical conditions for initiating Dynamic Recrystallization (DRX) in these components. Following a sequential evaluation procedure, hot deformation experiments were carried out at temperatures ranging from 1000 to 1200 °C and strain rates of 0.001–1 s−1 to determine the critical stress and strain required for initiating DRX in Ti64 pre-forms and compare them to their wrought counterparts. In addition, a specific Finite Element Model (FEM) was coupled with DRX kinetics equations to predict the volume percentage of DRX grains during the hot deformation of the pre-forms. The analysis of flow stress curves showed a significant peak stress at low strains, which is then followed by a period of flow softening and eventually transitions into a nearly steady-state flow at higher strains. In addition, compared to their wrought counterparts, the EB-PBF samples exhibited a significantly superior flow softening behavior, as evidenced by a more significant volume fraction of DRX and faster recrystallisation rates. It was also revealed that the normalised strain for DRX initiation in the EB-PBF Ti64 and wrought one was 0.55 and 0.67, respectively. FEM results closely matched the experimental finding, confirming its reliability in providing valuable insights into microstructural evolution and offering a time-efficient alternative for process design and property optimisation, lowering dependence on trial-and-error approaches. Through a combination of experiments, numerical analysis, and finite element simulations, this study sheds light on the macroscopic deformation and microstructural transformations occurring during hot working processes.

Mental health provider perspectives on a mobile health application to support remote measurement-based care: Challenges and impacts.

Measurement-based care (MBC) comprises collecting patient-reported outcomes data using validated assessments and using that information to support treatment. The Veterans Health Administration (VHA) has developed technology platforms to support MBC, including the Mental Health Checkup (MHC) mobile health application (app). Our objective was to examine VHA mental health provider perspectives on the MHC app. We completed a mixed-methods, sequential explanatory evaluation of MHC. We surveyed 284 VHA mental health providers who used MHC, then conducted semistructured telephone interviews with a purposefully selected subset of survey respondents (n = 20). Approximately half of survey respondents agreed that MHC allowed them to collect assessment data from veterans more frequently than before (51%) and that they more frequently discussed assessment results with veterans because of MHC (50%) and used those results to inform goal-setting discussions (50%) and treatment decision making (51%). Bivariate analyses indicated a positive relationship between frequency of MHC use and the aforementioned impacts on care. Interview data conveyed both advantages (e.g., increased treatment efficiency, improved treatment decision making) and challenges (e.g., limited assessment availability, difficulties engaging veterans in completing assessments through the app) to using MHC. This evaluation demonstrated how MHC supported providers working to implement MBC. The app enhanced their ability to reach and engage veterans and incorporate assessment data into clinical encounters. Still, many did not perceive that MHC was impactful on mental health care delivery; given that providers who used MHC more frequently reported more positive impressions of MHC, this may be related to how frequently they used the app. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

AI-Human Sequential Evaluation: Enhancing Performance Assessments through AI-Human Collaboration

AI-Human Sequential Evaluation: Enhancing Performance Assessments through AI-Human Collaboration

Algorithm optimization of architectural form through sequential landscape evaluation

Designing architectural and urban spaces based on continuous human spatial experience throughout a sequence may lead to architectural and urban forms not bound to conventional concepts. These forms would be made possible through the combination of a quantitative sequential landscape evaluation and morphological optimization utilizing algorithmic processes. In this study, we introduce a method for evaluating sequential landscapes, in which the configuration of buildings, trees, etc., in view changes as pedestrians move along a particular path, using a genetic algorithm optimization of architectural forms to bring them closer to the designer’s ideals. The method’s validity was tested using two case studies, assuming the design of a sequential landscape in an actual city and park. The results present a more efficient, objective, and reproducible method for designing sequences in buildings, cities, and landscapes, compared to traditional methods.

Bayesian sequential monitoring strategies for trials of digestive cancer therapeutics

BackgroundNew therapeutics in oncology have presented challenges to existing paradigms and trial designs in all phases of drug development. As a motivating example, we considered an ongoing phase II trial planned to evaluate the combination of a MET inhibitor and an anti-PD-L1 immunotherapy to treat advanced oesogastric carcinoma. The objective of the paper was to exemplify the planning of an adaptive phase II trial with novel anti-cancer agents, including prolonged observation windows and joint sequential evaluation of efficacy and toxicity.MethodsWe considered various candidate designs and computed decision rules assuming correlations between efficacy and toxicity. Simulations were conducted to evaluate the operating characteristics of all designs.ResultsDesign approaches allowing continuous accrual, such as the time-to-event Bayesian Optimal Phase II design (TOP), showed good operating characteristics while ensuring a reduced trial duration. All designs were sensitive to the specification of the correlation between efficacy and toxicity during planning, but TOP can take that correlation into account more easily.ConclusionsWhile specifying design working hypotheses requires caution, Bayesian approaches such as the TOP design had desirable operating characteristics and allowed incorporating concomittant information, such as toxicity data from concomitant observations in another relevant patient population (e.g., defined by mutational status).

Is MRI ready to replace biopsy during active surveillance?

Active surveillance (AS) is a conservative management option recommended for patients diagnosed with low-risk prostate cancer (PCa) and selected cases with intermediate-risk PCa. The adoption of prostate MRI in the primary diagnostic setting has sparked interest in its application during AS. This review aims to examine the role and performance of multiparametric MRI (mpMRI) across the entire AS pathway, from initial stratification to follow-up, also relative to the utilization of the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) criteria. Given the high negative predictive value of mpMRI in detecting clinically significant PCa (csPCa), robust evidence supports its use in patient selection and risk stratification at the time of diagnosis or confirmatory biopsy. However, conflicting results have been observed when using MRI in evaluating disease progression during follow-up. Key areas requiring clarification include addressing the clinical significance of MRI-negative csPCa, optimizing MRI quality, determining the role of biparametric MRI (bpMRI) or mpMRI protocols, and integrating artificial intelligence (AI) for improved performance. CLINICAL RELEVANCE STATEMENT: MRI plays an essential role in the selection, stratification, and follow up of patients in active surveillance (AS) for prostate cancer. However, owing to existing limitations, it cannot fully replace biopsies in the context of AS. KEY POINTS: Multiparametric MRI (mpMRI) has become a crucial tool in active surveillance (AS) for prostate cancer (PCa). Conflicting results have been observed regarding multiparametric MRI efficacy in assessing disease progression. Standardizing MRI-guided protocols will be critical in addressing current limitations in active surveillance for prostate cancer.

Temporal and spatial heterogeneity of HER2 status in metastatic colorectal cancer

BackgroundHER2-targeted therapies have recently emerged as an option in the management of metastatic colorectal cancer (mCRC) overexpressing HER2. However, data regarding HER2 status in primary CRC and its corresponding liver metastases are limited, potentially influencing clinical decisions. Therefore, the aim of this study was to compare the HER2 status in primary CRC and paired liver metastases.MethodsPatients with mCRC who were operated from their primary colorectal cancer and their corresponding synchronous or metachronous liver metastases, in the digestive surgery department of Besançon University Hospital, between April 1999 and October 2021, were included. Tissue microarrays were constructed from matched primary CRC and liver metastastic tissue samples. HER2 status was assessed by immunohistochemistry and in situ hybridization according to Valtorta’s criteria.ResultsA series of 108 paired primary CRC and liver metastases, including a series of multiple liver metastases originating from the same patients (n = 24), were assessed. Among the primary CRC, 89 (82.4%), 17 (15.8%) and 2 (1.8%) cases were scored 0, 1 + and 2 + respectively. In liver metastases, 99 (91.7%), 7 (6.5%) and 2 (1.8%) were scored 0, 1 + and 2, respectively. Overall, there was a 19% discrepancy rate in HER2 status between primary CRC and metastases, which increased to 21% in cases with multiple synchronous or metachronous liver metastases in a given patient. No significant difference was found between metachronous and synchronous metastases regarding the HER2 status (p = 0.237).ConclusionsOur study highlights the temporal and spatial heterogeneity of HER2 status between primary CRC and corresponding liver metastases. These findings raise the question of a sequential evaluation of the HER2 status during disease progression, to provide the most suitable treatment strategy.

Assessment of Bayesian guidance strategy to develop bake-hardening ferritic steel

ABSTRACT Developing alloys with optimal properties involves tuning several compositional and processing parameters. As the parametric space is often high-dimensional, doing so may require a prohibitively large number of experiments, which demand ample time and physical resources. In this study, we examine whether the method of Bayesian optimisation, which involves a sequential function evaluation scheme, applies to designing metallic alloys. We consider the example of bake-hardening ferritic steel and aim to maximise the extent of bake-hardening by tuning more than a dozen parameters while reducing the number of experimental fabrications and measurements. To this end, an existing dataset has been used to create a regression model, which acts as a surrogate for experimental measurements. The Bayesian optimiser has been implemented with three different covariance functions and two acquisition functions. Our results suggest that a design strategy guided by Bayesian optimisation has the potential to substantially reduce the time and cost of developing alloys through experimental routes.

Sequential MRI Evaluation of Lymphatic Abnormalities over the Course of Fontan Completion.

Purpose To evaluate lymphatic abnormalities before and after Fontan completion using noncontrast lymphatic imaging and relate findings with postoperative outcomes. Materials and Methods This study is a retrospective review of noncontrast T2-weighted lymphatic imaging performed at The Children's Hospital of Philadelphia from June 2012 to February 2023 in patients with single ventricle physiology. All individuals with imaging at both pre-Fontan and Fontan stages were eligible. Lymphatic abnormalities were classified into four types based on severity and location of lymphatic vessels. Classifications were compared between images and related to clinical outcomes such as postoperative drainage and hospitalization, lymphatic complications, heart transplant, and death. Results Forty-three patients (median age, 10 years [IQR, 8-11]; 20 [47%] boys, 23 [53%] girls) were included in the study. Lymphatic abnormalities progressed in 19 individuals after Fontan completion (distribution of lymphatic classifications: type 1, 23; type 2, 11; type 3, 6; type 4, 3 vs type 1, 10; type 2, 18; type 3, 10; type 4, 5; P = .04). Compared with individuals showing no progression of lymphatic abnormalities, those progressing to a high-grade lymphatic classification had longer postoperative drainage (median time, 9 days [IQR, 6-14] vs 17 days [IQR, 10-23]; P = .04) and hospitalization (median time, 13 days [IQR, 9-25] vs 26 days [IQR, 18-30]; P = .03) after Fontan completion and were more likely to develop chylothorax (12% [three of 24] vs 75% [six of eight]; P < .01) and/or protein-losing enteropathy (0% [0 of 24] vs 38% [three of eight]; P < .01) during a median follow-up of 8 years (IQR, 5-9). Progression to any type was not associated with an increased risk of adverse events. Conclusion The study demonstrated that lymphatic structural abnormalities may progress in select individuals with single ventricle physiology after Fontan completion, and progression of abnormalities to a high-grade classification was associated with worse postoperative outcomes. Keywords: Congenital Heart Disease, Glenn, Fontan, Lymphatic Imaging, Cardiovascular MRI Supplemental material is available for this article. Published under a CC BY 4.0 license.

The physician oncology referral process and its effect on tumor board outcomes.

e13752 Background: Oncology settings are known for their hierarchical structure, with distinct status demarcations among professional occupational specialties. The physician oncology referral process, a critical aspect of cancer management, reflects this hierarchical nature. This process, initiated upon suspicion of cancer, entails sequential clinical evaluation and treatment by physicians in the following order: surgeons, medical oncologists, specialty physicians, and referral physicians like interventional radiologists and radiation oncologists. Those at the top of the hierarchy wield considerable influence over the oncology referral process, directing subsequent patient care. While several studies have criticized the effectiveness of cancer management teams, little attention has been given to the potential role of the referral process in reinforcing hierarchical structures within tumor boards, possibly undermining their intended goals. Methods: This qualitative, ethnographic study investigated the interplay between the physician oncology referral process and tumor board outcomes in oncology settings. Data spanning three years were collected from seven research hospitals in the United States and the United Kingdom, encompassing observations from 44 tumor boards and eighteen semi- and unstructured interviews. The principal investigator conducted an analysis and synthesis of the gathered data. Results: The ethnographic study revealed that the hierarchies observed in tumor boards align with and are influenced by the traditional oncology referral process. Group interactions and treatment deliberation outcomes were significantly affected by the social dynamics of hierarchy mirrored in the referral process, ultimately compromising the intended objectives of tumor boards. Surgeons and medical oncologists, who traditionally lead the referral process, tended to dominate tumor board meetings. In contrast, sub-specialties like interventional radiologists and radiation oncologists, positioned at the end of the referral process, were less engaged in deliberations and often overlooked for treatment referrals. The higher the position in the hierarchy and referral process, the more pronounced the tacit authority and ability to direct patient treatment. Conclusions: This study highlights the alignment of traditional oncology referral processes with tumor board dynamics, showcasing similar social and clinical impacts. Despite potential resentment cultivated by reinforced hierarchy in the referral process, tumor board members tend to acquiesce, accepting decisions even when they may not align with optimal patient care.

The frequency of sepsis-associated delirium in intensive care unit and its effect on nurse workload.

To determine the frequency of sepsis-associated delirium (SAD) in the intensive care unit and its effect on nurse workload. A cross-sectional and correlational design was used. The study was conducted with 158 patients in the adult intensive care unit of a hospital between October 28 and July 28, 2022. Data analysis included frequency, chi-squared/fisher's exact test, independent samples t-test, correlation analysis, simple and multiple linear regression analyses. The study adhered to the STROBE guidelines. Sepsis was detected in 12.7% of the patients, delirium in 39.9%, and SAD in 10.1%. SAD was more common in males (19%) and 56.3% of the patients were admitted to the unit from the emergency department. Patients developing SAD had significantly higher age and mean sequential organ failure evaluation, acute physiology and chronic health evaluation II, and C-reactive protein and lactate scores, but their Glasgow Coma Scale scores were significantly low. There was a moderate positive relationship between the patients' Sequential Organ Failure Assessment score and the presence of SAD. The most common source of infection in patients diagnosed with SAD was bloodstream infection (44.4%). SAD significantly increased nurse workload and average care time (1.8 h) and it explained 22.8% of the total variance in nurse workload. Additionally, the use of antibiotics, vasopressors and invasive mechanical ventilation significantly increased nurse workload. In the study, in patients who developed SAD increased nurse workload and average care time significantly. Preventive nursing approaches and effective management of SAD can reduce the rate of development of SAD and nurse workload. It is important to work with routine screening, prevention and patient-nurse ratio appropriate to the workload for SAD.

A formative mixed methods evaluation of a new Ross program: why context matters

BackgroundThe Ross procedure is a technically complex operation to address the pathology of the aortic valve. Prior attempts at widespread implementation have been plagued with variations in effectiveness. We report our initial programmatic outcomes using dissemination and implementation (D&I) science frameworks, with an aim to define both programmatic efficacy and effectiveness. The study design was a single center, explanatory sequential mixed methods evaluation of a Ross surgery program from June 2020 to April 2023. Quantitative measures for baseline patient characteristics and postoperative outcomes were summarized. Qualitative measures were obtained using semi-structured interviews and characterized using implementation science frameworks.ResultsA total of 71 patients underwent the Ross procedure at a single academic center. Mean age was 40 years (± 13). There were no perioperative deaths or valve-related reinterventions (0%). During the follow-up period, 2 (2.8%) patients required re-operation and 2 (2.8%) required balloon dilation of the pulmonary homograft. Qualitative measures noted communication and prospective self-audit facilitated measures of effectiveness, as dichotomy within expected vs. observed outcomes led to program modifications. Collaboration across hospital systems promoted adoption and implementation, which led to the incorporation of the Ross procedure into accepted organizational practice.ConclusionsIn this formative evaluation, limited-efficacy outcomes demonstrated similar programmatic success to data from other established centers. With the prerequisite center volume and case selection, the Ross procedure is a safe and efficacious treatment for aortic valvular disease. Implementation science can be used both in real-time and retrospectively to guide organizational efforts to improve outcomes and to improve the translation of results across centers.

Sequential Evaluation of Hematology Markers as a Prognostic Factor in Glioblastoma Patients.

In our study, we investigated the prognostic significance of hematological markers-NLR (Neutrophil-to-Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio), and RDW-CV (Red Blood Cell Distribution Width-Coefficient of Variation)-in 117 glioblastoma patients. The data collected from January 2016 to December 2018 included demographics, clinical scores, and treatment regimens. Unlike previous research, which often examined these markers solely before surgery, our unique approach analyzed them at multiple stages: preoperative, postoperative, and before adjuvant therapies. We correlated these markers with the overall survival (OS) and progression-free survival (PFS) using statistical tools, including ANOVA, Cox regression, and Kaplan-Meier survival analyses, employing SPSS version 29.0. Our findings revealed notable variations in the NLR, PLR, and RDW-CV across different treatment stages. The NLR and PLR decreased after surgery, with some stabilization post-STUPP phase (NLR: p = 0.007, η2p = 0.06; PLR: p = 0.001, η2p = 0.23), while the RDW-CV increased post-surgery and during subsequent treatments (RDW-CV: p < 0.001, η2p = 0.67). Importantly, we observed significant differences between the preoperative phase and other treatment phases. Additionally, a higher NLR and RDW-CV at the second-line treatment and disease progression were associated with an increased risk of death (NLR at 2nd line: HR = 1.03, p = 0.029; RDW-CV at progression: HR = 1.14, p = 0.004). We proposed specific marker cut-offs that demonstrated significant associations with survival outcomes when applied to Kaplan-Meier survival curves (NLR at 2nd line < 5: p < 0.017; RDW-CV at progression < 15: p = 0.007). An elevated NLR and RDW-CV at later treatment stages correlated with poorer OS and PFS. No significant preoperative differences were detected. These biomarkers may serve as non-invasive tools for glioblastoma management.

Veteran Experiences With an mHealth App to Support Measurement-Based Mental Health Care: Results From a Mixed Methods Evaluation.

Mental health conditions are highly prevalent among US veterans. The Veterans Health Administration (VHA) is committed to enhancing mental health care through the integration of measurement-based care (MBC) practices, guided by its Collect-Share-Act model. Incorporating the use of remote mobile apps may further support the implementation of MBC for mental health care. This study aims to evaluate veteran experiences with Mental Health Checkup (MHC), a VHA mobile app to support remote MBC for mental health. Our mixed methods sequential explanatory evaluation encompassed mailed surveys with veterans who used MHC and follow-up semistructured interviews with a subset of survey respondents. We analyzed survey data using descriptive statistics. We then compared responses between veterans who indicated having used MHC for ≥3 versus <3 months using χ2 tests. We analyzed interview data using thematic analysis. We received 533 surveys (533/2631, for a 20% response rate) and completed 20 interviews. Findings from these data supported one another and highlighted 4 key themes. (1) The MHC app had positive impacts on care processes for veterans: a majority of MHC users overall, and a greater proportion who had used MHC for ≥3 months (versus <3 months), agreed or strongly agreed that using MHC helped them be more engaged in their health and health care (169/262, 65%), make decisions about their treatment (157/262, 60%), and set goals related to their health and health care (156/262, 60%). Similarly, interviewees described that visualizing progress through graphs of their assessment data over time motivated them to continue therapy and increased self-awareness. (2) A majority of respondents overall, and a greater proportion who had used MHC for ≥3 months (versus <3 months), agreed/strongly agreed that using MHC enhanced their communication (112/164, 68% versus 51/98, 52%; P=.009) and rapport (95/164, 58% versus 42/98, 43%; P=.02) with their VHA providers. Likewise, interviewees described how MHC helped focus therapy time and facilitated trust. (3) However, veterans also endorsed some challenges using MHC. Among respondents overall, these included difficulty understanding graphs of their assessment data (102/245, 42%), not receiving enough training on the app (73/259, 28%), and not being able to change responses to assessment questions (72/256, 28%). (4) Interviewees offered suggestions for improving the app (eg, facilitating ease of log-in, offering additional reminder features) and for increasing adoption (eg, marketing the app and its potential advantages for veterans receiving mental health care). Although experiences with the MHC app varied, veterans were positive overall about its use. Veterans described associations between the use of MHC and engagement in their own care, self-management, and interactions with their VHA mental health providers. Findings support the potential of MHC as a technology capable of supporting the VHA's Collect-Share-Act model of MBC.

The feasibility of sequential remote motor evaluations of people with possible Parkinson’s disease and related conditions

The feasibility of sequential remote motor evaluations of people with possible Parkinson’s disease and related conditions

A systematic approach for screening green entrainers combining the environmental-health-safety indexes and separation performance

Here we propose a new approach for extractive distillation (ED) process design, integrating environmental-health-safety (EHS) indexes as early as during the entrainer screening phase. Typically, safety and environmental factors are addressed later in the design process, often during optimization or in a sequential evaluation after cost-based optimization. However, in this study, we propose for the early incorporation of EHS considerations during the entrainer screening phase. This involves assessing the entrainer suitability using traditional metrics alongside additional EHS criteria, such as lethal dose (LD50) and flash point. Two azeotropic mixtures, i.e., tetrahydrofuran (THF)/ethanol (EtOH) and THF/methanol (MeOH), are chosen to exemplify our proposed methodology. Among the 1432 screened entrainers, the top 10 entrainers were identified based on separation index. These candidates were then subjected to further evaluation based on EHS criteria. Ethylenediamine (EDA) emerged as the optimal choice for the separation of THF/MeOH and THF/EtOH mixtures, demonstrating commendable EHS performance. Both separation processes were successfully simulated using Aspen Plus, which confirms the validity and suitability of the screened entrainer.

Sequential RAS mutations evaluation in cell-free DNA of patients with tissue RAS wild-type metastatic colorectal cancer: the PERSEIDA (Cohort 2) study

PurposeRAS (KRAS/NRAS) mutational status on a tumor biopsy is mandatory to guide the best treatment in metastatic colorectal cancer (mCRC). Determining the RAS mutational status by tumor-tissue biopsy is essential in guiding the optimal treatment decision for mCRC. RAS mutations are negative predictive factors for the use of EGFR monoclonal antibodies. Cell-free DNA (cfDNA) analysis enables minimally invasive monitoring of tumor evolution.Methods/patientsPERSEIDA was an observational, prospective study assessing cfDNA RAS, BRAF and EGFR mutations (using Idylla™) in first-line mCRC, RAS wild-type (baseline tumor-tissue biopsy) patients (cohort 2). Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression.Results117 patients were included (103 received panitumumab + chemotherapy as first-line treatment). At baseline, 7 (6.8%) patients had RAS mutations, 4 (3.9%) BRAF mutations and no EGFR mutations were detected (cfDNA, panitumumab + chemotherapy subpopulation [panitumumab + Ch]). The baseline RAS mutational status concordance between tissue and liquid biopsies was 94.0% (93.2%, panitumumab + Ch). At 20 weeks, only one patient in the study (included in the panitumumab + Ch) had an emerging cfDNA RAS mutation. No emerging BRAF or EGFR mutations were reported. At disease progression, 6 patients had emergent mutations not present at baseline (RAS conversion rate: 13.3% [6/45]; 15.0% [6/40], panitumumab + Ch).ConclusionsThe concordance rate between liquid and solid biopsies at baseline was very high, as previously reported, while our results suggest a considerable emergence of RAS mutations during disease progression. Thus, the dynamics of the genomic landscape in ctDNA may provide relevant information for the management of mCRC patients.