Assessment Of Response Research Articles

Computed Tomography-Based Radiomics with Machine Learning Outperforms Radiologist Assessment in Estimating Colorectal Liver Metastases Pathologic Response After Chemotherapy.

This study was designed to assess computed tomography (CT)-based radiomics of colorectal liver metastases (CRLM), extracted from posttreatment scans in estimating pathologic treatment response to neoadjuvant therapy, and to compare treatment response estimates between CT-based radiomics and radiological response assessment by using RECIST 1.1 and CT morphologic criteria. Patients who underwent resection for CRLM from January 2003-December 2012 at a single institution were included. Patients who did not receive preoperative systemic chemotherapy, or without adequate imaging, were excluded. Imaging characteristics were evaluated based on RECIST 1.1 and CT morphologic criteria. A machine-learning model was designed with radiomic features extracted from manually segmented posttreatment CT tumoral and peritumoral regions to identify pathologic responders (≥ 50% response) versus nonresponders. Statistical analysis was performed at the tumor level. Eighty-five patients (median age, 62 years; 55 women) with 95 tumors were included. None of the subjectively evaluated imaging characteristics were associated with pathologic response (p > 0.05). Inter-reader agreement was substantial for RECIST categorical response assessment (K = 0.70) and moderate for CT morphological group response (K = 0.50). In the validation cohort, the machine learning model built with radiomic features obtained an area under the curve (AUC) of 0.87 and outperformed subjective RECIST assessment (AUC = 0.53, p = 0.01) and morphologic assessment (AUC = 0.56, p = 0.02). Radiologist assessment of oligometastatic CRLM after neoadjuvant therapy using RECIST 1.1 and CT morphologic criteria was not associated with pathologic response. In contrast, a machine-learning model based on radiomic features extracted from tumoral and peritumoral regions had high diagnostic performance in assessing responders versus nonresponders.

Smeared fixed crack model for quasi-static and dynamic biaxial flexural response analysis of aluminosilicate glass plates

Glass materials are extensively used in load-bearing structures and impact-resistant components because of their distinctive physical and chemical properties. Accurate predictions and assessment of the mechanical responses of glass structures are crucial for structural design and reliability analysis. In this study, quasi-static and dynamic ball-on-ring (BOR) biaxial flexural tests are conducted on aluminosilicate glass. The smeared fixed crack model is calibrated for deformation and failure analyses. First, the model parameters are calibrated carefully, particularly for different failure criteria. Both the deformation field and fracture modes agree well with the experimental observations during the quasi-static tests. For the low-velocity impact biaxial flexural loading condition, three different numerical techniques, namely the initial scaling tensile strength criterion, non-local approach with energy criterion, and rate-dependent failure stress criterion, are implemented in the numerical models for dynamic failure analysis. Finally, the proposed smeared fixed crack model is compared with the widely used Johnson Holmquist Ⅱ (JH-2) model and demonstrates advantages for low-velocity impact response analysis of glass structures.

7640 The first description of an MC4R variant in a patient with Kallmann syndrome and obesity

Abstract Disclosure: A.A. Aslam: None. S. Lim: None. R. Willemsen: None. K. Koysombat: None. M. Young: None. W.S. Dhillo: None. A. Abbara: None. S. Howard: None. E.F. Gevers: None. Introduction: Pathogenic MC4R gene variants result in hyperphagia and early onset obesity but puberty is not usually affected. We describe an MC4R variant in a patient with Kallmann syndrome and obesity. A 16 year old male with repaired Tetralogy of Fallot, anosmia, autism and anxiety, was referred with obesity and delayed puberty. His birth weight was 3360 g (-0.26 SDS). Height was -1.31 SDS, BMI 30.7 kg/m2. He had high arched palate, normal skin and hair colour, mild hypertelorism and upward slanting palpebral fissures. Pubertal staging was A2P1G1 5ml testes bilaterally. Results: LHRH test showed borderline low peaks (LH 5.0 U/L, FSH 2.6 U/L) and inhibin B 108 pg/mL (25-325 pg/mL). MRI brain showed hypoplastic olfactory bulbs, absent olfactory sulci and normal pituitary anatomy. CGH microarray, karyotype and the UK hypogonadism gene panel were normal. He underwent whole genome sequencing in the Genetic Factors Affecting the Timing of Puberty Study; no abnormalities in 52 known genes associated with GnRH deficiency were found but a previously described heterozygous variant was detected, MC4R c.542G>A, p.Gly181Asp, classified pathogenic and absent in control databases. Management: He was commenced on Testosterone but showed progression of testicular size to 10 mL and testosterone was stopped but required restarting. Repeat investigations off treatment, aged 22 years (height 178 cm, BMI 42 kg/m2, testes 15 mL): inhibin B 66 pg/mL, testosterone 2 nmol/L, baseline LH 2.4 U/L, stimulated peak 24.9 U/L, baseline FSH 1.2 U/L, stimulated peak 4.2 U/L. Cortisol and IGF1 were in the normal range. He also developed autoimmune hypothyroidism with raised TPO antibodies (TSH 24.7 mU/L, FT4 5.6 pmol/L). Discussion: Previous in vitro work has shown complete loss of function of MC4R p.Gly181Asp due to reduced cell surface expression and reduced binding to a-MSH. Heterozygous p.Gly181Asp variants have been described in several children/adults with obesity; but hypogonadism in heterozygous carriers has not. Homozygous MC4R p.Gly181Asp was found in a male with obesity and partial HH thought to be due to abnormal GnRH production but with normal olfactory bulbs. We are the first to describe a heterozygous MC4R p.Gly181Asp variant in a patient with partial hypogonadism and anosmia with hypoplastic bulbs in addition to obesity. Interaction between POMC-MC-leptin circuits and Kisspeptin-GnRH circuits is recognised although not completely understood. Previous work has shown that a subset of kisspeptin neurons express MC4R and that KNDy neurones receive synaptic input from POMC neurons. In addition, inhibition of MC4R/MC3R results in delayed onset of puberty in rats. Our results support a role for MC4R in GnRH secretion and potentially olfactory /GnRH neuronal migration. Assessment of spontaneous gonadotrophin production and response of gonadotrophin production to kisspeptin stimulation is currently in progress. Presentation: 6/1/2024

Resilience assessment of FPSO leakage emergency response based on quantitative FRAM

FPSO production process is prone to leakage, and failure to respond promptly and effectively will lead to accident escalation and serious consequences. However, traditional safety assessment methods cannot handle the nonlinear relationships between human, technology, and organization in emergency response process. This study proposes a quantitative FRAM to evaluate the emergency response resilience of FPSO leakage. This method establishes a resilience evaluation framework including three tiers: function, ability, and system, which can quantify system resilience based on the variability of function. First, identify basic functions according to the four stages of monitoring, response, learning and anticipation in the emergency response process, and establish the FRAM model of FPSO leakage emergency response. Then, the quantitative FRAM and Monte Carlo simulation are combined to calculate the variabilities of functions under different operating conditions. Finally, based on the simulation results, the variabilities of basic functions are aggregated and statistically analyzed to quantify system resilience. The implementation process of this method is illustrated by a case study. The influence of different factors on the system resilience is analyzed by setting various operation scenarios, and critical functions are identified by sensitivity analysis, which can provide reference for improving system resilience and ensuring FPSO safety production.

Impacts of microplastic ingestion on fish communities in Haizhou Bay, China

Microplastics are pervasive throughout aquatic ecological communities. While their negative impacts on the life history traits of aquatic species are well studied, the effects on community dynamics remain elusive. Consequently, community-level assessments of microplastic effects on marine food webs are largely lacking, creating significant knowledge gaps regarding marine ecosystem structure and dynamics in the context of microplastic contamination. Here we expand a multispecies size-spectrum model by incorporating microplastic impacts on individual life-history traits, ultimately allowing us to study microplastic-mediated structural and functional changes in fish communities. As expected, microplastic ingestion may drive species extinction, but the microplastic-to-food ratio threshold for extinction is species-specific, and not necessarily correlated with species’ asymptotic weights. Interestingly, species responses to microplastics also propagate through the community as ingestion triggers both bottom-up and top-down effects on community dynamics. Which specific type of cascading effect is dominating depends on which species is ingesting microplastics as well as its trophic role in the community. Generally, low-trophic-level species ingesting microplastics can exert large detrimental effects on community biomass. Thus, this study highlights the necessity for a comprehensive risk assessment of species-specific responses to microplastic contamination as well as an understanding of individual species’ role in their communities.

On application of the relative entropy concept in reliability assessment of some engineering cable structures

The main research problem studied in this work is an uncertain response and reliability assessment of the spatial cable structures due to the environmental stochasticity as well as material and geometrical imperfections. Some popular cable structures are analyzed for this purpose using the Stochastic Finite Element Method (SFEM) implemented with the use of three different techniques, namely the iterative generalized perturbation method, semi-analytical approach as well as the Monte-Carlo simulation. Uncertainty quantification delivered in this study is based on the series of FEM analyses of both static and dynamic structural problems. They enable the Least Squares Method determination of the structural polynomial responses linking extreme stresses and deformations with several uncorrelated uncertainty sources. Reliability assessment, fundamental in durability and Structural Health Monitoring, is completed using a comparison of the First Order Reliability Method (FORM) with probabilistic distance formulated by Bhattacharyya. Input uncertainties are assumed to be Gaussian according to the Maximum Entropy Principle. They have specific expected values following engineering design demands or the provisions of designing codes, whereas their standard deviations do not exceed the 10% level. The methods presented and the results obtained in this study may serve for further reliability analyses of large-scale civil engineering structures completed with both steel cables and also reinforced concrete plates like suspended bridges, for instance.

Monitoring clonal burden as an alternative to blast count for myelodysplastic neoplasm treatment response.

Accurate assessment of therapy response in myelodysplastic neoplasm (MDS) has been challenging. Directly monitoring mutational disease burden may be useful, but is not currently included in MDS response criteria, and the correlation of mutational burden and traditional response endpoints is not completely understood. Here, we used genome-wide and targeted next-generation sequencing (NGS) to monitor clonal and subclonal molecular disease burden in 452 samples from 32 patients prospectively treated in a clinical trial. Molecular responses were compared with International Working Group (IWG) 2006-defined response assessments. We found that myeloblast percentage consistently underestimates MDS molecular disease burden and that mutational clearance patterns for marrow complete remission (mCR), which depends on myeloblast assessment, was not different than stable disease or bone marrow aplasia, underscoring a major limitation of using mCR. In contrast, achieving a complete remission (CR) was associated with the highest level of mutation clearance and lowest residual mutational burden in higher-risk MDS patients. A targeted gene panel approach was inferior to genome-wide sequencing in defining subclones and their molecular responses but may be adequate for monitoring molecular disease burden when a targeted gene is present in the founding clone. Our work supports incorporating serialNGS-based monitoring into prospective MDS clinical trials.

Assessment of renal response in Tunisian patients with proliferative lupus nephritis under three different induction immunosuppressive agents: A prognostic retrospective study.

The aim of our study was to evaluate the renal response (RR) of three immunosuppressive protocols in the induction treatment of proliferative lupus nephritis (PLN) in a Tunisian population. We performed a retrospective prognostic cohort study in the Internal Medicine Department of the Habib Thameur University Hospital in Tunis from January 2000 to December 2023, and included kidney biopsy proven proliferative lupus nephritis patients. Three induction treatments were compared: High CYP regimen: glucocorticoids (GC) + IV cyclophosphamide (CYP) in monthly pulses of 0.7g/m2 for 6 months; Low CYP regimen: GC + IV CYP in biweekly pulses of 500mg for 3 months; and MMF regimen: GC + oral MMF 1.5g twice daily for 6 months. The primary endpoint was the incidence of RR (complete and partial remission) at one year post-diagnosis. The additional outcomes were end-stage kidney disease (ESKD), severe adverse events (AEs) and death. Our study included 78 PLN patients (High CYP: 17, Low CYP: 40, MMF: 21). The study found that 94.1% of patients receiving High CYP achieved the primary endpoint, RR, compared to 67.5% of those receiving Low CYP and 61.9% in the MMF group. For the additional outcomes, there were 3 cases of ESKD, all in the Low CYP group, 5 cases of death (4 in the Low CYP group and 1 in the MMF group), and 20 cases of severe AEs, all of which were severe infections (5 in the High CYP group, 12 in the Low CYP group, and 3 in the MMF group). Multivariate analysis showed that the High CYP regimen was more associated with RR than the MMF regimen, with an adjusted OR of 9.846 (95% CI: 1.087-98.210); p = 0.042. Multivariate analysis did not show statistically significant differences between the High CYP regimen and the Low CYP regimen in terms of RR. As an induction treatment for PLN, the High CYP regimen was strongly associated with a higher rate of RR than the MMF regimen. There were no statistically significant differences between the High CYP regimen and the Low CYP regimen in terms of RR.

Dynamic response and vibration suitability analysis of the large-span double-connected structure under coupled wind and pedestrian loads

Modern buildings increasingly utilize lightweight, high-strength materials and feature high-rise, large-span structural designs. These structures often exhibit low natural frequencies and are susceptible to resonance from low-frequency dynamic loads such as wind and pedestrian loads. This paper focuses on a large-span double-connected structure and analyzes its dynamic response under the combined effects of wind and pedestrian loads. First, a finite element model of the structure was created using ANSYS, and model validity verification and modal analysis were performed. Second, a Fourier-based pedestrian model was used to simulate pedestrian loads and generate time-range data. The pulsating wind speed was generated from the Davenport spectrum using the harmonic superposition method. Wind load time-range data were calculated for different heights using Bernoulli’s theorem. Finally, the solution yields information about the dynamic response of the structure. The study revealed maximum vertical comfort ratings in the connecting corridor were achieved when crowd density did not exceed 0.3 persons/m2. The connecting corridor’s most unfavorable horizontal comfort level was evaluated as a medium, except for the 0-degree wind angle condition. This paper provides experience in studying the dynamic response and vibration suitability assessment of the large-span double-connected structure under wind and pedestrian loads.

B-342 Teclistamab interference in serum protein electrophoresis and serum immunofixation electrophoresis in patients with recurrent or relapsed multiple myeloma

Abstract Background Serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (IFE) analyses are mainstays in the initial diagnosis, risk stratification, and evaluating treatment response in patients with multiple myeloma (MM) in accordance with the International Myeloma Working Group criteria. Published reports have demonstrated that therapeutic monoclonal antibodies (mAbs) used to treat MM (e.g. anti-CD38 IgG-kappa) are detectable by SPEP and IFE, which may interfere with accurate evaluation of complete response. Recently, Teclistamab (Tecvayli®; Janssen Biotech, Horsham Township, PA), a humanized bispecific IgG-lambda mAb targeting B-cell maturation antigen (BCMA) and CD3 on T cells was approved for treating patients with penta-refractory MM. In contrast with other IgG-kappa therapeutic mAbs, the degree to which Teclistamab may interfere with detection and quantification of monoclonal proteins is unknown. Therefore, we sought to assess the interference of Teclistamab therapy on routine SPEP and IFE analysis. Methods Patients treated with Teclistamab were identified by retrospective review of electronic medical records. Teclistamab (90 mg/mL) was spiked into a remnant patient sample with IgG lambda MM at a final concentration of 10 μg/mL, which corresponds to ½Cmax values in patients infused with Teclistamab. SPEP and IFE were performed using the Helena SPIFE Touch instrument. Computer-assisted densitometry was used to quantify monoclonal proteins in the gamma region of SPEP gels. Results In several patients with refractory MM treated with Teclistamab, IFE analysis revealed IgG lambda or lambda light chain monoclonal proteins, which were inconsistent with previously-identified monoclonal proteins (e.g. IgG kappa). In one patient diagnosed with IgG lambda MM, spiking 10 μg/mL Teclistamab increased M-spike abundance by approximately 0.15 g/dL when quantified by SPEP. Conclusions In patients with relapsed or refractory MM, treatment with Teclistamab may confound accurate clinical assessment of complete response by SPEP and IFE methods. Increased awareness of this preanalytical interference is necessary to guide clinical decision making.

B-165 The EXENT System reliably distinguishes daratumumab from endogenous monoclonal immunoglobulins in multiple myeloma patients

Abstract Background The use of therapeutic monoclonal antibodies (t-mAbs) in the treatment of multiple myeloma (MM) has created challenges in the clinical laboratory. Co-migration of t-mAbs (predominantly IgGK) and the endogenous M-protein during serum protein electrophoresis can result in inability to distinguish between a patient’s M protein and the t-mAb. This can hinder accurate assessment of therapeutic responses or may lead to extensive workup with immunofixation electrophoresis and gel-shift assays for accurate confirmation of a complete response, or to exclude the emergence of a new clone. There is a need for an analytically specific routine method to identify t-mAb interference. MALDI-TOF mass spectrometry is an especially promising tool, as due to its ability to identify M proteins’ molecular mass, it has the potential to recognize any t-mAbs with known amino acid composition. We have used the EXENT® Immunoglobulin Isotypes (GAM) Assay for the EXENT Analyzer (The Binding Site, part of Thermo Fisher Scientific) to assess the reproducibility of daratumumab (anti-CD38, IgGK) detection in an analytical study, and assessed the EXENT System’s ability to detect daratumumab in a cohort of MM patients. Methods The expected mass to charge ratio (m/z) of the +2-charge state of daratumumab’s kappa light chain was calculated based on published information. Daratumumab was spiked into normal human serum at 1.0 g/L, and this material was tested in 5 replicates a day over 5 days. In addition, 109 samples from 34 MM patients receiving daratumumab, carfilzomib, lenalidomide and dexamethasone (Dara-KRd) treatment were also tested. Samples were obtained after 14 or 28 days following daratumumab administration in various treatment cycles, ranging from cycle 4 to end-of-treatment. Results The expected m/z for the +2-charge state of daratumumab’s kappa light chain was calculated as 11,691.01 to 11,693.1. In the reproducibility experiment, the median m/z was 11691.3, within the expected range. The difference between the lowest and highest m/z was 1.3 across the 25 replicates. Daratumumab was detected in 103 out of 109 samples (97.3%): 51/57 (89.5%) in IgGK samples, and in all IgGL (23) and IgA (29) samples. In two IgGK patients, where daratumumab was not detected in 2 out of 4 samples and in 1 out of 3 samples, respectively, the patients’ own M proteins were in the proximity (24.8 and 27.1 m/z) of daratumumab’s m/z. In the other three cases where daratumumab was not modeled by the algorithm, the daratumumab peak overlapped with the endogenous M-protein's adduct peak (estimated m/z 11,688) in one sample; it was masked by the shoulder of a large (8.42 g/L) IgGK M-protein in another sample; and no obvious reason was identified in the third sample. There was no difference in the detection rate between 14 days and 28 days post administration. Conclusions The EXENT Immunoglobulin Isotypes (GAM) Assay has successfully identified the presence of daratumumab in approximately 90% of IgGK patient samples in addition to all other (non-IgGK) MM samples. These results demonstrate the potential of the EXENT Immunoglobulin Isotypes (GAM) Assay for recognizing known t-mAb interference.

A-306 High Sensitivity Capability of an Anti-müllerian Hormone Assay on the Beckman Coulter DxI 9000 Immunoassay Analyzer*, a Next Step Toward Enabling Ovarian Failure Staging?

Abstract Background Measurement of anti-müllerian hormone (AMH) has proven value in the evaluation of ovarian reserve using assays such as the Beckman Coulter Access AMH assay. If improved sensitivity of AMH measurement can be achieved, enhanced clinical utility during the assessment of reproductive aging and ovarian response to enable staging of ovarian failure is possible (Practice Committee of the American Society of Reproductive Medicine 2020, Cappola et al. 2023). The Beckman Coulter DxI 9000 Immunoassay Analyzer* has been designed with new technology that can be leveraged to improve assay sensitivity. Such technological advancements include the new Lumi-Phos PRO chemiluminescent substrate which yields markedly increased signal-to-noise, a new luminometer with increased dynamic range, and improved low-volume pipetting capabilities. Data herein summarize results from analytical verification studies of the Access AMH assay on the DxI 9000 Immunoassay Analyzer. Results demonstrate an example of DxI 9000 technologies enabling sensitivity claims that are up to 20-fold improved. * The official name is DxI 9000 Access Immunoassay Analyzer. Methods A method comparison study was performed based on CLSI guideline EP09c, 3rd ed. to compare results for the Access AMH assay on DxI 9000 to the predicate device, the Access AMH assay on the Access 2 Immunoassay System. Within-laboratory precision was also evaluated following CLSI EP05-A3. Finally, performance at low analyte levels was evaluated following CLSI EP17-A2, and linearity was evaluated following CLSI EP06-Ed2. Results Method comparison of the Access AMH assay on DxI 9000 compared to the Access AMH assay on the Access 2 yielded excellent agreement with a Passing-Bablok slope of 1.02 for N=126 samples. Further, bias estimates for a number of key medical decision points suggest minimal bias (≤ 2%) across the assay range, and minimal non-linearity was observed. 20-day imprecision studies yielded CV’s between 2 and 5% across a broad range of concentrations evaluated. Sensitivity studies yielded estimates of limit of quantitation (LoQ) between 0.001 and 0.003 ng/mL. This represents an approximately 10- to 20-fold improvement in sensitivity claims compared to the AMH assay on the Access 2 and other commercially available automated immunoassay analyzers. Conclusions The data herein present performance data for the Access AMH assay on the DxI 9000 Immunoassay Analyzer. The assay demonstrates excellent accuracy relative to the predicate device, while showing good linearity and imprecision. Of note, the Access AMH assay exhibits exceptional low-end performance on the DxI 9000 analyzer as demonstrated by the ability to enable sensitivity claims that are up to 20-fold improved in comparison to existing immunoassays for the measurement of AMH. The sensitivity capabilities of the Access AMH assay on DxI 9000 suggest an opportunity for the addition of further intended uses for scenarios where extremely low AMH measurements can provide additional value of clinical significance. Further studies are needed to fully understand additional clinical utilities of the Access AMH assay with high sensitivity capability on DxI 9000, including the assessment of reproductive aging for menopause diagnosis or ovarian response for fertility treatment.

PET/CT Response Assessment in Pediatric Hodgkin Lymphoma: Does Deauville Score 3 Reflect Negativity?

FDG PET is required for the staging and response evaluation of pediatric Hodgkin lymphoma. This study aimed to evaluate the outcomes of pediatric patients with Hodgkin's lymphoma based on interim PET CT assessments of early response following second-cycle chemotherapy using the Deauville score (DS). It also determines whether DS-3 is providing an adequate or inadequate response. We conducted a retrospective cohort study including 504 pediatric patients with classic Hodgkin lymphoma who were treated with chemotherapy based on the Euro-Net protocol at the Children Cancer Hospital Egypt from March 2019 till the end of October 2022. Patients with adequate response DS 1/2 and DS 3 showed nearly the same 3-year event-free survival (EFS) of 91.9% and 91.5%, respectively, compared with those patients with inadequate response DS 4/5, who showed an EFS of 80.4% ( P =0.001). Patients with a DS 3 at interim PET evaluation were considered negative as DS 1/2. Patients of DS 3 group who did not receive radiotherapy had a much worse 3-year EFS by the existence of positive B symptoms, an ESR>30, or an advanced stage. Radiation therapy did not improve the 3-year EFS in patients with an inadequate response (DS4/5) and poor prognostic characteristics. They still need more advanced treatment. DS 1/2 and DS 3 had about the same 3-year EFS, which is better than the 3-year EFS of patients with DS 4/5. Therefore, we can classify DS 3 as having negative FDG PET CT uptake.

Pathologic Validation of Deauville Score-Based Disease on F-18 FDG PET/CT after First-Line Treatment in Patients with Lymphoma.

PET/CT-based Deauville scoring (DS) is routinely used for lymphoma response assessment. However, pathological correlation of DS is not yet precisely documented. In the present study we aimed to pathological confirm the PET/CT-based Deauville scoring (DS) in lymphoma after first-line chemotherapy. Participants undergoing PET/CT for response assessment following first-line treatment were recruited prospectively. DS ≥ 4 lesions were interpreted as PET-positive, while DS ≤ 3 as PET-negative. Participants with a PET-positive lesion or suspicious of inadequate response (DS ≤ 3) were recruited for metabolic core-needle biopsy. True-negative and benign histopathology were kept on follow-up for three months. Histopathological, clinical and imaging findings were assessed for diagnostic performance. Procedure-related complications were also noted. In all, 148/480 participants were PET-positive, and 332/480 were PET-negative. 138/148 PET-positive and 12/332 PET-negative lesions were recruited for biopsy. Biopsy was performed in 147/150 participants (PET-positive 135; PET-negative 12). Three patients with inaccessible lesions were excluded. The diagnostic yield of the procedure was 97.3% (143/147). Histology revealed lymphoma in 106 participants (including 70% of total DS-4, 100% of DS-5a and 73.9% of DS-5b lesions), with three false-negative lesions. DS ≤ 3 lesions were true-negative except one diagnosed with lymphoma (8.3%) on follow-up. Non-lymphomatous malignancies (n = 5), granulomas (n = 12), non-specific inflammation (n = 9) and no residual disease (n = 11) were diagnosed in the rest. No major procedure-related adverse event was noted. A DS-5a lesion suggests residual disease; hence, a biopsy can be prevented unless Richter's transformation is suspected. DS-4 and DS-5b lesions require a biopsy before changing the treatment plan, as a certain number of participants had non-lymphomatous F-18 FDG-avid lesions.

Immunotherapy response and resistance in patients with advanced uveal melanoma: a retrospective cohort study.

Metastatic uveal melanoma (mUM) is associated with poor prognosis. Ipilimumab/nivolumab has shown antitumor efficacy in phase II studies. Tebentafusp resulted in longer overall survival (OS) compared to investigator`s choice in a phase III study. We sought to describe the radiological response patterns of mUM patients treated with immunotherapy. Patients with mUM treated with ipilimumab/nivolumab and tebentafusp between July 2018 and December 2022, with available radiological assessment per RECISTv1.1 and/or imPERCIST5, were retrospectively identified and included. Progression-free survival (PFS) and OS rates, liver-specific response and pathological assessment in available liver biopsies were evaluated. In the ipilimumab/nivolumab group, median PFS (mPFS) was 2.9 months (95% CI 2.2-28.6) and mOS 28.9 months (95% CI 12.7-NR). Complete (CMR) and partial (PMR) metabolic response per imPERCIST5, and partial response (PR) per RECISTv1.1 were associated with longer PFS and OS by trend, compared to morphologically and metabolically stable or progressive disease. In the tebentafusp group, mPFS was 2.7 months (95% CI 2.2-3) and mOS 18.6 months (95% CI 11.5-NR). PMR and PR were associated with longer PFS by trend. In both treatments, the overall treatment response was associated with the radiological response at the liver site. In available liver tumor biopsies, differences in pathological and radiological responses were noted. ImPERCIST5 and RECIST v1.1 are valuable tools in the radiological response assessment, but both methods display limitations. Accurate biomarkers to stratify patients at risk for disease progression and future translational studies to investigate mechanisms of response and resistance are required.

Assessment of bronchodilator responsiveness using low-frequency impedance in type 2–high uncontrolled severe asthma

Assessment of bronchodilator responsiveness using low-frequency impedance in type 2–high uncontrolled severe asthma

Defining Echocardiographic Degrees of Right Heart Size and Function in Pulmonary Vascular Disease From the PVDOMICS Study

BACKGROUND: Defining qualitative grades of echocardiographic metrics of right heart chamber size and function is critical for screening, clinical assessment, and measurement of therapeutic response in individuals with pulmonary vascular disease (PVD). In a population enriched for PVD, we sought to establish qualitative grades and prognostic value of right heart chamber size and function. METHODS: We investigated 1053 study participants in PVDOMICS (Redefining Pulmonary Hypertension Through the PVD Phenomics Program) to determine clinical and echocardiographic differences associated with increasing pulmonary vascular resistance severity. Right heart chamber size and function were qualitatively assessed using a percentile-based approach above the median values to create a clinical grading system for right heart adaptation. The relationship between echocardiographic categories and all-cause mortality was examined using survival analyses adjusted for potential confounders. RESULTS: A stepwise increase in adverse right heart remodeling was observed with a concomitant decrease in functional parameters by pulmonary vascular resistance strata ( P <0.001 for all). Mild, moderate, and severe categories of right heart chamber size and dysfunction were defined using a percentile-based approach across the spectrum of PVD. During a median follow-up of 2.07 years (interquartile range, 1.23–3.01 years), 130 participants died (11.4%). Progressive pulmonary vascular resistance increase and 2DE evidence of right heart dysfunction inclusive of fractional area change, and right ventricular global longitudinal strain were independently associated with increased all-cause mortality risk in multivariate analysis adjusted for age, disease duration, and male sex. CONCLUSIONS: In this well-characterized sample of adults with diverse etiologies and varying PVD severity, we define categories of abnormal right heart chamber size and function. Further, we demonstrate a stepwise relationship between these categories of abnormal morphology and function and all-cause mortality. Defining grades of right ventricular dysfunction in individuals with known PVD has important clinical implications for monitoring disease progression and response to therapies.

Comparison of RECIST 1.1, mRECIST and PERCIST for assessment of peptide receptor radionuclide therapy treatment response in metastatic neuroendocrine tumors

PurposeTo compare RECIST 1.1, modified RECIST (mRECIST) and PERCIST for assessment of Peptide Receptor Radionuclide Therapy (PRRT) treatment response in metastatic neuroendocrine tumors. MaterialsIn this IRB-approved, HIPAA compliant retrospective study, patients treated with PRRT between July 2019 and Dec 2022 were identified. Inclusion criteria were presence of at least one pre-and one post-treatment imaging (CT, MRI, Ga 68 or Cu64 DOTATATE PET/CT) within one year of the start and end of PRRT respectively. The imaging was reviewed independently by two radiologists using RECIST 1.1, modified RECIST (mRECIST) and PERCIST criteria. Response of first post treatment scan and presence of disease progression during follow-up were recorded along with the date of best response and disease progression. Statistical analysis was performed to determine inter-reader agreement and agreement between the various response criteria using kappa statistics. ResultsBest response by RECIST 1.1 was recorded in 26 patients (PR-7, SD- 13, PD- 6), by mRECIST in 22 patients (PR-7, SD- 10, PD- 5), by PERCIST in 14 patients (PR-4, SD- 3, PD- 7). Inter-reader agreement was highest for PERCIST (weighted kappa 0.921, standard error 0.078 95% CI 0.769 to 1.000) followed by RECIST 1.1 (weighted kappa 0.897, standard error 0.071 95% CI 0.758 to 1.000) and mRECIST (weighted kappa 0.883, standard error 0.079 95% CI 0.727 to 1.000).

Exploring the Protein Signature of Endometrial Cancer: A Comprehensive Review Through Diverse Samples and Mass Spectrometry-Based Proteomics

Endometrial cancer (EC) is increasing incidence in among women, and it constitutes a health problem for women globally. An important aspect of EC management involves the use of protein biomarkers for early detection and monitoring. Protein biomarkers allow the identification of high-risk patients, detecting the disease in its early stages, and the assessment of treatment responses. Mass spectrometry (MS)-based proteomics offers robust analytical techniques and a comprehensive understanding of proteins. Proteomics methods allow scientists to investigate both the quantities and function of proteins. Thus, it provides valuable insights into how proteins are altered under different conditions. This review summarizes recent advances in MS-based proteomic biomarker discovery for EC, focusing on different sample types and MS-based techniques used in clinical studies. The review emphasized in detail the most commonly used key sources such as blood, urine, vaginal fluids and tissue. Furthermore, MS-based proteomics techniques such as untargeted, targeted, sequential window acquisition of all theoretical mass spectra (SWATH-MS) and mass spectrometry imaging used in discovery and validation/validation phases were evaluated. This review highlights the importance of biomarker discovery and clinical translation to improve diagnostic and therapeutic outcomes in EC. It aims to provide a comprehensive overview of MS-based proteomics in EC, guiding future research and clinical applications.

Concordance of whole slide imaging and conventional light microscopy for assessment of pathologic response following neoadjuvant therapy for lung cancer

Pathologic response is an endpoint in many ongoing clinical trials for neoadjuvant regimens, including immune checkpoint blockade and chemotherapy. Whole slide scanning of glass slides generates high resolution digital images and allows for remote review and potential measurement with image analysis tools, but concordance of pathologic response assessment on digital scans compared to glass slides has yet to be evaluated. Such a validation goes beyond previous concordance studies which focused on establishing surgical pathology diagnoses, as it requires quantitative assessment of tumor, necrosis, and regression. Further, as pathologic response assessment is being used as an endpoint, such concordance studies have regulatory implications. The purpose of this study was two fold: firstly, to determine the concordance between pathologic response assessed on glass slides and on digital scans; and secondly, to determine if pathologists benefited from using measurement tools when determining pathologic response. To that end, H&E-stained glass slides from 64 non-small cell lung carcinoma specimens were visually assessed for percent residual viable tumor (%RVT). The sensitivity and specificity for digital vs. glass reads of complete pathologic response (pCR, 0% RVT) and major pathologic response (MPR, ≤10% RVT) were all >95%. When %RVT was considered as a continuous variable, intraclass correlation coefficient of digital vs. glass reads was 0.94. The visual assessments of pathologic response were supported by pathologist annotations of residual tumor and tumor bed areas. In a separate subset of H&E-stained glass slides, several measurement approaches to quantifying %RVT were performed. Pathologist estimates strongly reflected measured %RVT. This study demonstrates the high level of concordance between glass slides evaluated using light microscopy and digital whole slide images for pathologic response assessments. Pathologists did not require measurement tools to generate robust %RVT values from slide annotations. These findings have broad implications for improving clinical workflows and multisite clinical trials.