Changes In Disease Status Research Articles

Clinical profiles of leucine-rich alpha-2 glycoprotein for indicating mucosal healing in ulcerative colitis patients under administration of molecular targeted drug.

Leucine-rich alpha-2 glycoprotein (LRG) is a useful serum biomarker for monitoring disease activity during remission in ulcerative colitis (UC). Because LRG levels differ among patients, it is necessary to assess them after profiling patients, especially in patients with refractory UC undergoing treatment with molecular targeted drugs. This study aimed to analyze LRG levels that indicate mucosal healing according to clinical characteristics and molecular targeted drugs. Among 214 patients with UC treated with biologics or Janus kinase (JAK) inhibitors, this study evaluated 111 patients (174 measurements) who achieved mucosal healing based on colonoscopy performed within 2 months before and after LRG measurement and experienced no changes in disease status or treatment during the same period. We analyzed the relationship of LRG with clinical characteristics (including sex, age, body mass index, and disease type and duration) and molecular targeted drugs. Compared with men, women had significantly higher LRG levels (9.5 μg/mL vs. 11.3 μg/mL, P<0.001). In addition, LRG levels were significantly higher in older patients (12.0 μg/mL vs. 9.8 μg/mL, P<0.01). LRG levels were the highest in patients treated with vedolizumab and lower in patients treated with JAK inhibitors (vedolizumab: 12.7 μg/mL; tofacitinib: 8.9 μg/mL; upadacitinib: 8.5 μg/mL; and filgotinib: 9.1 μg/mL; P<0.0001). Among the patients who achieved mucosal healing, LRG levels were significantly higher in women and older patients. LRG levels differed according to the molecular targeted drug used, and were higher with vedolizumab and lower with JAK inhibitors.

Identify, screen and treat via electronic pathway: a semiautomated approach to retriaging a liver clinic waitlist.

Long specialist outpatient waiting lists are a source of clinical risk. Triage assignment is based on subjective assessment of referrals and fails to account for dynamic changes in disease status while patients await clinical review. To pilot an innovative triage method using a trifold approach to conduct noninvasive assessment of fibrosis and to determine the feasibility of reflex hepatitis C virus (HCV) polymerase chain reaction (PCR) testing. A total of 1006 patients awaiting an initial liver clinic appointment at a tertiary Australian hospital were sent a short message service (SMS) requesting a blood test be completed. The first 60 patients received an SMS only, and the subsequent 946 patients also received a phone call from a Liver Care Guide (LCG), a nonclinician employed to increase patient engagement. Liver fibrosis assessment through noninvasive testing was performed using an aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB4) score. Patients with an APRI ≥1, FIB4 ≥3.25 or positive HCV PCR were retriaged to Category 1. Four hundred ninety (49%) patients completed testing and 40 (4%) were triaged to Category 1. Subanalyses demonstrated increased response rates with LCG input (P = 0.012). Retriaged patients had been on the waitlist for a median of 216 days, exceeding initial category recommendations. This study successfully implemented a semiautomated strategy that prioritises patients with probable advanced liver disease or active HCV, demonstrating enhanced patient engagement with LCG support. It highlights the burden of patients referred for specialist care and the need for innovative strategies for monitoring and objective risk stratification.

Ecological patterns and processes of temporal turnover within lung infection microbiota

BackgroundChronic infection and consequent airway inflammation are the leading causes of morbidity and early mortality for people living with cystic fibrosis (CF). However, lower airway infections across a range of chronic respiratory diseases, including in CF, do not follow classical ‘one microbe, one disease’ concepts of infection pathogenesis. Instead, they are comprised of diverse and temporally dynamic lung infection microbiota. Consequently, temporal dynamics need to be considered when attempting to associate lung microbiota with changes in disease status. Set within an island biogeography framework, we aimed to determine the ecological patterns and processes of temporal turnover within the lung microbiota of 30 paediatric and adult CF patients prospectively sampled over a 3-year period. Moreover, we aimed to ascertain the contributions of constituent chronic and intermittent colonizers on turnover within the wider microbiota.ResultsThe lung microbiota within individual patients was partitioned into constituent chronic and intermittent colonizing groups using the Leeds criteria and visualised with persistence-abundance relationships. This revealed bacteria chronically infecting a patient were both persistent and common through time, whereas intermittently infecting taxa were infrequent and rare; respectively representing the resident and transient portions of the wider microbiota. It also indicated that the extent of chronic colonization was far greater than could be appreciated with microbiological culture alone. Using species-time relationships to measure temporal turnover and Vellend’s rationalized ecological processes demonstrated turnover in the resident chronic infecting groups was conserved and underpinned principally by the deterministic process of homogenizing dispersal. Conversely, intermittent colonizing groups, representing newly arrived immigrants and transient species, drove turnover in the wider microbiota and were predominately underpinned by the stochastic process of drift. For adult patients, homogenizing dispersal and drift were found to be significantly associated with lung function. Where a greater frequency of homogenizing dispersal was observed with worsening lung function and conversely drift increased with better lung function.ConclusionsOur work provides a novel ecological framework for understanding the temporal dynamics of polymicrobial infection in CF that has translational potential to guide and improve therapeutic targeting of lung microbiota in CF and across a range of chronic airway diseases.AWnQWdeG2wJZnAAmwW9_w-Video

Concordance in Oncogenic Alterations Between the Primary Tumor and Advanced Disease: Insights Into the Heterogeneity of Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICCA) is characterized by significant phenotypic and clinical heterogeneities and poor response to systemic therapy, potentially related to underlying heterogeneity in oncogenic alterations. We aimed to characterize the genomic heterogeneity between primary tumors and advanced disease in patients with ICCA. Biopsy-proven CCA specimens (primary tumor and paired advanced disease [metastatic disease, progressive disease on systemic therapy, or postoperative recurrence]) from two institutions were subjected to targeted next-generation sequencing. Overall concordance (oncogenic driver mutations, copy number alterations, and fusion events) and mutational concordance (only oncogenic mutations) were compared across paired samples. A subgroup analysis was performed on the basis of exposure to systemic therapy. Patients with extrahepatic CCA (ECCA) were included as a comparison group. Sample pairs from 65 patients with ICCA (n = 54) and ECCA (n = 11) were analyzed. The median time between sample collection was 19.6 months (range, 2.7-122.9). For the entire cohort, the overall oncogenic concordance was 49% and the mutational concordance was 62% between primary and advanced disease samples. Subgroup analyses of ICCA and ECCA revealed overall/mutational concordance rates of 47%/58% and 60%/84%, respectively. Oncogenic concordance was similarly low for pairs exposed to systemic therapy between sample collections (n = 50, 53% overall, 68% mutational). In patients treated with targeted therapy for IDH1/2 alterations (n = 6) or FGFR2 fusions (n = 3), there was 100% concordance between the primary and advanced disease specimens. In two patients, FGFR2 (n = 1) and IDH1 (n = 1) alterations were detected de novo in the advanced disease specimens. The results reflect a high degree of heterogeneity in ICCA and argue for reassessment of the dominant driver mutations with change in disease status.

Building the Case for Telehealth Yoga for Minors With Arthritis and Chronic Pain: A Perspective.

Childhood arthritis has a prevalence of around 300000 US children. It has no cure, and is just one of many juvenile conditions associated with pain, fatigue, and a lifetime of medical care. Yoga has demonstrated effectiveness in improving symptoms and quality of life for adults with arthritis. Yoga can be easily adapted according to affected joints, movement limitations, and changes in disease status. It combines movement that is necessary for arthritis management and maintaining physical function, along with mental practices that help to address common psychosocial comorbidities such as depressive symptoms and affect. No research has been published on the effects of yoga in minors with arthritis and chronic pain. In-person yoga may not be feasible for this population because many patients live hours from their specialist healthcare. As telehealth becomes more acceptable, online yoga may offer an additional tool for symptom management and improved quality of life in juvenile chronic pain conditions. Clinical trials are necessary to evaluate the safety, feasibility, acceptability and effectiveness of teleyoga in the whole-person management of juvenile arthritis and chronic pain conditions.

Oncology nurse competency in chimeric antigen receptor T-cell therapy: A qualitative study

BackgroundChimeric antigen receptor (CAR) T-cell therapy is a promising therapeutic method in the field of tumor immunotherapy. An increasing number of patients are beginning to select CAR T-cell therapy in mainland China. It is characterized by a complex process, a long period of treatment, high individualization, quick disease status changes and unique side effects. Oncology nurses play a crucial role in the provision of CAR T-cell therapy. ObjectiveTo explore oncology nurses' competency in CAR T-cell therapy with guidance from the iceberg model. DesignA descriptive qualitative study. SettingsThis study was conducted with nurses on lymphoma wards in three tertiary hospitals in China. ParticipantsA total of 13 nurses and 2 nursing managers were approached, and all of them took part in this study. MethodsData were collected face-to-face or via online video using a semistructured interview guide between November 2022 and February 2023 by the first author. The study was performed and reported following the Consolidated Criteria for Reporting Qualitative Research. Content analysis was used to analyze the data. ResultsNursing competency in CAR T-cell therapy was identified as including four main categories encompassing 12 subcategories and 40 codes. The main categories were theoretical knowledge, operation skills, personality traits and motives. The subcategories were basic knowledge of chemotherapy, professional knowledge of CAR T-cell therapy, basic skills, professional skills, relevant discipline skills, communication/coordination ability, critical thinking, basic traits, professional personality, enthusiasm for the nursing profession, empathy with patients and motivation to promote professional development. ConclusionsMedical staff can develop a competency-based nurse training program to improve the professional competencies of oncology nurses in CAR T-cell therapy and meet patients' supportive needs for optimal care. Additionally, the findings may be helpful for building measurement standards to assess oncology nurses' performance.

Clinical Implications of CSF-Ctdna in CNS Involvement of Newly Diagnosed Diffuse Large B Cell Lymphoma: An Improvement of Diagnosis, Treatment and Evaluation

Background: CNS involvement (CNSi) is a rare and often fatal event, occurring in around 5% of patients (pts) with diffuse large B-cell lymphoma (DLBCL) during primary treatment or shortly after completion (SCNSL). Furthermore, the potential mechanisms of CNS dissemination were limited. Circulating tumor DNA from cerebrospinal fluid (CSF-ctDNA) has played an important part in the application of liquid biopsy in CNS cancers. In this study, we provided new insights into the feasibility of using CSF-ctDNA as an essential tool for CNSi diagnosis, treatment, and evaluation specifically in newly diagnosed (ND) DLBCL pts. Methods : Between December 2021 and April 2023, 168 ND DLBCL pts and 24 ND PCNSL pts have been treated in our center. One hundred DLBCL pts were enrolled in the training cohort while the other 68 pts refused to enter in our study. Another 26 ND DLBCL pts diagnosed between May 2023 and June 2023 were entered into a validation cohort. The flow of treatment and samples collections were according to the study protocol shown in Figure 1A. CSF-ctDNA positive (CSF-ctDNA(+)) criteria: (1) CSF-ctDNA detected mutations consistent with tissue; (2) Mutations detected in CSF-ctDNA were inconsistent with tissues, but were classified as grade I and grade II mutations; (3) At least one mutation was detected with an abundance >0.5%. The criteria of CNSi positive (CNSi(+)) were CSF-ctDNA(+) or/and other evidences detected by conventional methods (CM, including MRI, PET-CT, routine inspection analysis of CSF). Results: In the training cohort, 25 pts (25%) were diagnosed with CSF-ctDNA (+) while 21 pts were according to the first criteria and 4 pts were according to the second criteria. Among the 25 pts (25.0%) who were finally diagnosed with CNSi (+), only 3 pts (12.0%) have evidences of CNSi both in CM and CSF-ctDNA while similar results were shown in validation cohort ( Figure 1B). The unique mutations detected in CSF were rare compared with plasma and tissue mainly due to early detection with no clone evolution ( Figure 1C). The mean variant allele frequency was significantly higher in tumor tissue than CSF in SCNSL ( Figure 1D). The pretreatment ctDNA burden was significantly higher in CSF of PCNSL while higher in plasma of SCNSL ( Figure 1F). The distributions of gene subtypes for the 25 CNSi (+) DLBCL pts were shown in Figure 1E. Only 11 pts (44%) were MCD subtype while nearly 80% PCNSL pts were MCD subtype. There existed significant differences of gene mutation profile between SCNSL and PCNSL ( Figure 1G). We explored the association of clinical and biological factors with CNSi in ND DLBCL pts . Of note, high plasma ctDNA burden (≥2.18) were significantly related to CNSi (+) (Figure 1H). In multivariable analyses, CSF protein level ≥0.4, high plasma ctDNA burden (≥2.18) and high risk CNSi sites involvement were independent risk factors for CNSi ( Figure 1I). We use these 3 risk factors to build CNSi-IPI model which can significantly better predict CNSi than CNS-IPI ( Figure 1I). According to CNSi-IPI, pts were stratified into low-risk (0-1), intermediate-risk (2) and high-risk (3). CNSi (+) were observed in 5.0%, 48.3% and 72.7% in the training cohort and 5.9%, 50.0% and 100.0% in the validation cohort in the 3 risk groups ( Figure 1J). Pts with CARD11, JAK2, ID3, and PLCG2 mutation were more predominant with CNSi while FAT4 mutation seemed to promote tumor cells disseminating to CNS ( Figure 1K). Furthermore, the down-regulated genes of CNSi DLBCL pts significantly enriched in PI3K-AKT signaling pathway, focal adhesion, regulation of action cytoskeleton and tight junction pathways, which might be the potential mechanisms promoting CNS dissemination in ND DLBCL ( Figure 1L). The dynamic change of disease status and ctDNA burden of all the 25 CNSi (+) pts were shown in Table 1. Conclusion :In summary, our study highlighted the clinical implications of CSF-ctDNA in CNSi detection of ND DLBCL pts ( Figure 1M): (1) CSF-ctDNA exhibits higher sensitivity than CM in detecting CNSi in ND DLBCL. (2) Different genomic and clinical landscapes were observed between SCNSL and PCNSL. (3) The CNSi-IPI is a robust, highly reproducible tool that can be used to estimate the risk of CNSi in ND DLBCL. (4) Down-regulation of PI3K-AKT signaling pathway, focal adhesion, regulation of action cytoskeleton and tight junction pathways contribute to CNS dissemination in ND DLBCL. (5) Furthermore, CSF-ctDNA can be used to monitor CNS tumor burden and response to treatment.

Detection of progression and regression of genitourinary cancers by circulating tumor DNA (ctDNA).

e16508 Background: Circulating tumor DNA (ctDNA) are short DNA sequences shed by tumor cells into systemic circulation. The sensitivity and specificity of single ctDNA test to predict relapse or recurrence in solid tumor vary widely and the utility of monitoring serial ctDNA trends has not been well-described in genitourinary cancers. Methods: We conducted a retrospective study including adult patients with genitourinary cancers at the hematology-oncology clinic at William Beaumont - Royal Oak and Troy Hospitals, Michigan from, August 2021 to May 2022, who had ctDNA testing done with imaging available for comparison. We evaluated the correlation between ctDNA test, both single test as well as dynamic trends in value over time, with imaging findings. We also calculated lead time for uptrending ctDNA to detect disease progression compared to imaging. Results: 21 total ctDNA test results from eight patient were included in the study; five had renal cell cancer, two had urothelial cancer and one had prostate cancer. The median age at diagnosis was 62 years (Range: 45-82); 90% were Caucasian and 50% were female. Majority (87.5%) had Stage III or IV disease. Out of the 21 total ctDNA samples, all 16 positive ctDNA results had evidence of disease on corresponding imaging: 13 showed progression while 3 showed regression with residual disease compared to prior imaging. Of the 5 negative ctDNA test results, 2 showed no evidence of disease and 3 showed regression with residual disease on corresponding imaging. Sensitivity and specificity of a single positive ctDNA test to detect evidence of disease on imaging was 84.2% and 100%, respectively. Six patients had multiple ctDNA test results with 12 pairs of serial ctDNA values, of which 9 were up-trending, and 3 were down-trending. Both sensitivity and specificity of up-trending ctDNA values to detect progression and down-trending ctDNA values to detect regression on imaging were 100%. Uptrending ctDNA values predicted disease progression with a median lead time of 55.5 days compared to imaging. Conclusions: Given the high sensitivity and specificity of serial ctDNA monitoring to detect disease progression and regression in our study, we conclude that this may be a valid way to reliably monitor for changes in disease status in genitourinary cancers before they become evident on imaging studies. Further clinical studies are needed to prove its utility in detecting immediate changes in disease status and guide therapeutic intervention in genitourinary cancers. [Table: see text] [Table: see text]

Developing Automated Computer Algorithms to Track Periodontal Disease Change from Longitudinal Electronic Dental Records

To develop two automated computer algorithms to extract information from clinical notes, and to generate three cohorts of patients (disease improvement, disease progression, and no disease change) to track periodontal disease (PD) change over time using longitudinal electronic dental records (EDR). We conducted a retrospective study of 28,908 patients who received a comprehensive oral evaluation between 1 January 2009, and 31 December 2014, at Indiana University School of Dentistry (IUSD) clinics. We utilized various Python libraries, such as Pandas, TensorFlow, and PyTorch, and a natural language tool kit to develop and test computer algorithms. We tested the performance through a manual review process by generating a confusion matrix. We calculated precision, recall, sensitivity, specificity, and accuracy to evaluate the performances of the algorithms. Finally, we evaluated the density of longitudinal EDR data for the following follow-up times: (1) None; (2) Up to 5 years; (3) > 5 and ≤ 10 years; and (4) >10 and ≤ 15 years. Thirty-four percent (n = 9954) of the study cohort had up to five years of follow-up visits, with an average of 2.78 visits with periodontal charting information. For clinician-documented diagnoses from clinical notes, 42% of patients (n = 5562) had at least two PD diagnoses to determine their disease change. In this cohort, with clinician-documented diagnoses, 72% percent of patients (n = 3919) did not have a disease status change between their first and last visits, 669 (13%) patients' disease status progressed, and 589 (11%) patients' disease improved. This study demonstrated the feasibility of utilizing longitudinal EDR data to track disease changes over 15 years during the observation study period. We provided detailed steps and computer algorithms to clean and preprocess the EDR data and generated three cohorts of patients. This information can now be utilized for studying clinical courses using artificial intelligence and machine learning methods.

Abstract P1-05-07: Detection of progression or regression of breast cancer by circulating tumor DNA (ctDNA)

Abstract Background: Circulating tumor DNA (ctDNA) are short DNA sequences shed by tumor cells into the systemic circulation. Studies have shown potential utility of the test to predict relapse or recurrence following treatment in solid tumors, but sensitivity and specificity have varied widely, ranging from 19-100% and 80-100% respectively, in breast cancer specifically. Moreover, literature describing the utility of monitoring dynamic changes in ctDNA trends is limited. We aim to evaluate the correlation between ctDNA test, both single test as well as dynamic trends in value over time, with imaging findings. Methods: We retrospectively analyzed the medical records of all adult patients diagnosed with breast cancer who underwent ctDNA testing at the hematology-oncology clinic at William Beaumont - Royal Oak and Troy Hospitals, Michigan, from August 2017 to June 2022. Patients who had ctDNA testing done but did not have imaging to correlate it with were excluded from the study. We calculated the sensitivity and specificity of a single positive ctDNA test to detect disease progression or residual disease on imaging. In patients with multiple ctDNA tests, we calculated the sensitivity and specificity of dynamic trends in ctDNA values to detect progression, regression, or absence of disease on imaging. Moreover, we calculated the lead time for positive ctDNA results to detect disease progression compared to imaging. Results: Nineteen patients were included in the study, with 34 total ctDNA test results, each utilized as a separate data point to compare with corresponding imaging findings (Table 1). Ten out of the 19 patients had multiple(>=2) ctDNA test results reported, with a total of 15 pairs of ctDNA values and each pair was analyzed separately as up trending (N=7), down trending (N=4), or persistent negative (N=4) to compare with a corresponding pair of imaging findings (Table 2). The median age at diagnosis was 55 years, and 94.7% were female. At diagnosis, majority of patients (68.4%) had either stage III or IV disease. Our primary endpoint, the correlation of single positive ctDNA result with imaging showing either progression or residual disease, showed a sensitivity and specificity of 100% and 93.3%, respectively. Secondarily, serial ctDNA trend analysis in ten patients revealed both sensitivity and specificity of 100% for up-trending ctDNA values to detect progression, down-trending to detect regression, and persistent negative results to detect absence of disease on imaging, respectively. The positive ctDNA results detected disease progression with a median lead time of 44.5 days compared to imaging. Conclusion: Given the high sensitivity and specificity to detect disease progression and regression in breast cancer patients by single ctDNA results and dynamic ctDNA trends in our study, we conclude that this may be a valid way to reliably monitor for changes in disease status before they become evident in imaging studies. Further clinical studies are required to prove the utility of ctDNA to detect changes in disease status and to guide therapeutic interventions in breast cancer. Table 1. Correlation of single ctDNA result with imaging findings. Table 2. Correlation of dynamic trends in ctDNA values with imaging findings. Citation Format: Ujjwal Karki, Bipin Ghimire, Emma Herrman, Siddhartha Yadav, Mohammad Muhsin Chisti. Detection of progression or regression of breast cancer by circulating tumor DNA (ctDNA) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-05-07.

Development and validation of an ama instrument for assessing the disease activity on the basis of constitutional features in Amavata (Rheumatoid Arthritis)

BackgroundRheumatoid Arthritis (RA), having a striking clinical resemblance to amavata in traditional Indian medicine (Ayurveda) presents an opportunity to look at disease from two different healthcare perspectives. This differential information may potentially supplement one system with the knowledge of the other for optimal application. This study is the first of its kind, where Ayurvedic concepts of amavata have been adopted to enhance the knowledge about RA where optimal care is still beyond the common reach. ObjectiveThe study was conducted to develop and validate a novel ama score based upon constitutional features of ama as depicted in ayurvedic literature as a disease activity indicator in RA. Material and methodsThe study was conducted in two parts comprising development and textual validation of the ama assessment instrument (AAI) followed by its clinical testing. AAI comprising ten items, was developed where each item was provided with a range of scores to offer the assessment close to the patient's observations. The score obtained through AAI was clinically and statistically tested on 79 RA/amavata patients randomly selected for validity and reliability. The score obtained through AAI was tested for its correlation with the DAS-28 score and ESR. ResultsAma Assessment Instrument could find a slight correlation with acute phase reactant ESR (r-value between ESR and AMA at baseline is 0.287, and at 1st, 2nd, and 3rd follow-up is 0.276, 0.276 and 0.160 respectively) and DAS-28 (The r value between DAS and AMA at baseline is 0.231, and at 1st, 2nd and 3rd follow up is 0.218, 0.201 and 0.247 respectively). It however emerged as an independent disease status marker since it could mark the changes in the study population on a time scale more precisely as compared to DAS -28 or ESR. When the ama values at different follow-ups were compared, a significant difference was observed consistent with disease activity marker catching constitutional and GI related domain of the patients. When reducing values of ama score were compared to overall improvements as reported by the patients, a similar trend was observed showing that a change in ama score is reflective of a change in disease status and the impact of the disease on the patient. ConclusionThis study provided a quantitative measure for the abstract concept of ama which could be used to mark the disease activity in amavata or RA. The change in ama based scores can be used to assess disease status and the intervention related benefits. The observations prompt for the possible inclusion of AAI in RA composite score to make it more dynamic in terms of disease activity identification in RA.

METHODS TO DERIVE A CROHN'S DISEASE ACTIVITY INDEX FROM ELECTRONIC HEALTH RECORDS DATA

Abstract BACKGROUND The Crohn’s Disease Activity Index (CDAI) is currently the gold-standard for measuring disease activity in Crohn’s disease (CD) patients. It is the most commonly used outcome measure in clinical trials, however, due to the burden of completion, it is infrequently used in routine care. Real world data, including electronic health records (EHR), are useful for studying longitudinal disease and treatment outcomes in the real world, but most EHR databases do not include CDAI. Building off the methods presented by Rudrapatna et al. 2021, we calculated a derived CDAI using data elements available in EHRs. METHODS Data were derived from the OM1 PremiOM UC Dataset (OM1, Boston, MA), a multisource real-world database with linked healthcare claims and EHR data on US patients with CD (2013-present). Weight, body temperature and hematocrit were sourced from structured vital signs and laboratory data. Ideal body weight was calculated from height and gender using the Devine formula. Extraintestinal manifestations/complications were evaluated based on the presence or absence of ICD diagnosis codes for each condition. Abdominal mass was abstracted from clinical notes. Number of stools in the past 7 days, average daily abdominal pain, and general well being were extrapolated from single-day measures extracted from clinical notes rather than based on 7-day diaries. Each component value was multiplied by the weights outlined in Best et al. 1976. Components recorded within 4 months were added to calculate a derived CDAI. Multiple CDAIs could be calculated for each patient over time, but each component was allowed to contribute to only one CDAI score. RESULTS Among 13,159 CD patients, only 12 had a CDAI recorded in their notes. After applying the algorithm, we were able to calculate a derived CDAI for 1,378 patients. 489 patients had > 1 score derived. Figure 1 shows the distribution of derived CDAIs. Patients with a derived CDAI were younger and a higher proportion were treated with biologics and corticosteroids than those who could not have a CDAI calculated (Table 1). CONCLUSIONS A derived CDAI can be calculated from data that may be routinely recorded in EHRs. Efforts to standardize the collection of CDAI components in EHRs would further increase the availability of derived CDAIs. Further work to validate these derived scores against a gold standard and to replicate the findings in other real-world datasets should be considered. Validation was not feasible in this dataset due to the lack of recorded CDAIs. Derived CDAIs could potentially be used to study longitudinal changes in disease status and treatment effectiveness in settings where observed CDAIs are unavailable.

Population pharmacokinetic modelling of tremelimumab in patients with advanced solid tumours and the impact of disease status on time-varying clearance.

Tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 human monoclonal antibody of the immunoglobulin G2 κ isotype, has been studied in oncology clinical trials as both monotherapy and in combination with durvalumab. This study characterized the pharmacokinetics of tremelimumab as monotherapy and in combination with durvalumab and evaluated the impact of patient covariates on pharmacokinetics. A pooled-analysis population pharmacokinetics model was built using NONMEM methodology. Pharmacokinetic data from 5 studies spanning different tumour types and therapy regimens were pooled for model development (956 patients). A dataset pooled from 4 additional studies was used for external validation (554 patients). Demographic and relevant clinical covariates were explored during model development. Tremelimumab exhibited linear pharmacokinetics, well described by a 2-compartment model, with time-varying clearance (0.276 L/day at baseline) associated primarily with therapy regimen and linked with changes in disease status. As monotherapy and combination therapy, tremelimumab clearance over 1 year increased by ~16% and decreased by ~17%, respectively. Pharmacokinetic behaviour was consistent across patient demographics and cancer subtypes. Patients with higher bodyweight and lower albumin levels at baseline had significantly higher clearance; however, no dosage adjustments are warranted. A flat dose (75 mg) was projected to provide comparable exposure to weight-based dosing (1mg/kg) in adults. Tremelimumab exhibited linear pharmacokinetics but consistently opposite trends of time-varying clearance as monotherapy and in combination with durvalumab. Baseline bodyweight and albumin were significant covariates, but conversion from weight-based dosing at 1mg/kg to flat dosing at 75 mg had no clinically relevant impact.

Evaluation of Patient and Physician Assessments of Gastrointestinal Disease Activity in Systemic Sclerosis.

To assess whether patient and physician global assessment of gastrointestinal tract (GIT) disease in systemic sclerosis (SSc) are associated with a meaningful change in disease status. One hundred forty-three participants from the Australian Scleroderma Cohort Study were recruited to this study. Using logistic regression analysis, we evaluated the relationship between patient-reported and physician-assessed GIT disease status and symptoms, measures of health-related quality of life (36-item Short Form Health Survey [SF-36]) and GIT disease severity, measured by the Scleroderma Clinical Trials Consortium UCLA Gastrointestinal Tract 2.0 (GIT 2.0) score. Patient-reported worsening of GIT symptoms in the month preceding assessment was significantly associated with more severe GIT disease (odds ratio [OR] 6.14, P < 0.01) and progressive worsening GIT disease severity as measured by the GIT 2.0 score (OR 45.98, P < 0.01). The new onset of reflux was the only specific symptom associated with patient-reported GIT disease activity (OR 2.98, P = 0.04). Physician-assessed GIT disease activity was not significantly associated with higher GIT 2.0 scores or increasing severity of disease. Patient-reported and physician-assessed GIT activity was not associated with SF-36 scores. In the absence of objective measures of GIT disease activity in SSc, patient-reported symptoms of GIT disease could be used to indicate disease activity and should merit consideration for inclusion in a multisystem disease activity index.

Stress Screening and Social Intervention in Radiation Oncology Consultation: A Demonstration of Need

<h3>Purpose/Objective(s)</h3> Cancer-related stress is a common and under-treated condition. The NCCN recommends distress screening with the distress thermometer (DT) scale of 0-10 for all cancer patients at all stages of disease in all settings, emphasizing screening at initial visits and after changes in disease status. Distressed patients should be clinically evaluated and referred to social work (SW), mental health professionals, or chaplain care. This study assesses the rate of distress screening and receipt of appropriate SW care at a high-volume academic healthcare network. <h3>Materials/Methods</h3> All patients seen for Radiation Medicine consultation between 7/1/21-12/31/21 were reviewed. Rates of DT documentation, patient distress, and SW intervention (SW referral or consultation) within 14 days were assessed. Chi-square test was used to test if binary variables (curative vs noncurative consult and community vs central tertiary location) were associated with rates of DT screening and SW intervention. Binary logistic regression was used to test the relationship between age and distress. <h3>Results</h3> 2214 patients were seen for radiation oncology consult, and 784 (35%) had DT screening documented. 411 (52%) screened patients were distressed (DT ≥ 4), and 194 (25%) patients were severely distressed (DT ≥ 7). Median age was 67 years. Median distress level was 4 (SD = 3.2, R: 1-6). A total of 306 (14%) patients received SW intervention. Higher rates of SW intervention were present in screened patients vs unscreened patients (30% vs 5%, X²=265.9, p<0.001). Screened patients were more likely to get SW support if they were distressed vs not distressed (48% vs 10%, X²=140, p<0.001). 116 (60%) severely distressed patients received SW intervention. Each additional year of age was associated with a lower rate of reported distress (OR=0.983, p<0.001). Curative, noncurative, and benign consultations composed 58%, 39%, and 3% of the cohort respectively. Rates of distress (52% vs 56%, X²=0.791, p=0.34) and rates of distressed patients receiving SW intervention (51% vs 48%, X²= 0.179, p=0.672) were similar between curative vs noncurative consultations. More patients were seen at community campuses (58%) vs the central tertiary location (42%). Screenings were more frequently documented at community locations vs the central location (40% vs 29%, X²= 28.5, p<0.001). Distressed patients received higher rates of SW intervention at community locations vs the central location (55% vs 36%, X²=14, p<0.001). <h3>Conclusion</h3> Current rates of distress screening at radiation consultation are low. Since 52% of screened patients report distress and unscreened patients are less likely to receive SW support, these results underscore a large unmet need in the care of cancer-related stress. Differences in implementation at the central vs community location indicate unique program initiatives can improve screening and psychosocial support utilization.

S333 How Reliable Is Circulating Tumor DNA in Detecting Disease Progression or Regression of Non-Colorectal Gastrointestinal Cancers

Introduction: Circulating tumor DNA are short DNA sequences of tumor cells shed into the systemic circulation. Post-operative ctDNA positivity has been studied as a potential marker for disease recurrence, however, dynamic changes in its level and immediate correlation with imaging have not been well described. Methods: We conducted a retrospective study including adult patients with non-colorectal gastrointestinal (GI) cancer. We evaluated the correlation of ctDNA with imaging studies to detect disease progression or regression. Eighteen patients, with 33 ctDNA samples were included. Results: Out of the 18 patients, five had pancreatic, three each had hepatocellular and cholangiocarcinoma, two each had anal cancer and neuroendocrine tumor, and one each had gastric, small bowel, and GI malignancy of unknown primary. Among the patients, 50% were male, and the median age at diagnosis was 64 years. 72.2% of the patients had advanced disease (stage III/IV), and only 22.2% had a predisposing condition leading to malignancy. Our primary endpoint, the correlation of single positive ctDNA results with imaging showing either progression or residual disease, showed a sensitivity of 60% and specificity of 100%. Secondarily, serial ctDNA was analyzed in ten patients with at least two ctDNA test results. This revealed a sensitivity of 80% and specificity of 100% for up-trending ctDNA values to detect progression, down-trending to detect regression, and persistent negative results to detect the absence of disease. This calculated sensitivity was lower than our separate analysis of colorectal cancer, where the sensitivity of single and serial ctDNA was 84.8% and 92.9%, respectively. The specificity, however, was 100% in both cancer groups. The positive ctDNA results detected disease progression with a median lead-time of 44 days compared to imaging. Conclusion: Colorectal cancer is the most studied malignancy in regards to the use of circulating tumor DNA as a marker of tumor recurrence. Similar studies in non-colorectal GI cancers are lacking. However, limited studies have shown some promising results for the use of post-operative ctDNA. The test’s sensitivity in our study was inferior compared to colorectal cancer, but given high specificity and improvement in sensitivity with serial analysis, ctDNA can be a valid way to monitor disease progression or regression in non-colorectal GI cancers. Further clinical studies are required to prove its utility in the reliable detection of immediate changes in disease status.

Development of machine learning support for reading whole body diffusion-weighted MRI (WB-MRI) in myeloma for the detection and quantification of the extent of disease before and after treatment (MALIMAR): protocol for a cross-sectional diagnostic test accuracy study

IntroductionWhole-body MRI (WB-MRI) is recommended by the National Institute of Clinical Excellence as the first-line imaging tool for diagnosis of multiple myeloma. Reporting WB-MRI scans requires expertise to interpret and...

HE4 and CA125 serum biomarker monitoring in women with epithelial ovarian cancer.

CA125 is the gold standard serum biomarker for monitoring patients with epithelial ovarian cancer (EOC). Human epididymal protein 4 (HE4) is a novel serum biomarker for EOC patients. The objective of this trial was to examine the utility of measuring serum HE4 levels for monitoring EOC patients and to compare HE4 performance parameters to serum CA125. A retrospective trial using residual longitudinal serum samples drawn during treatment and monitoring from EOC patients. Serum CA125 and HE4 levels were analyzed at each time point, and a velocity of change was calculated and correlated with clinical status. The null hypothesis was that HE4 is inferior to CA125, and this was tested using concordance and two-sided Fisher's exact testing. McNemar's test was used to assess the overall agreement of the two assays with the clinical status. A total of 129 patients with 272 separate clinical periods and 1739 events (serum samples) were evaluated. Using a 25% change in serum biomarker levels to indicate change in disease status, the accuracy and NPV determined for HE4 versus CA125 were 81.8% versus 82.6% (p = 0.846) and 87.4% versus 89.7% (p = 0.082), respectively. Concordance comparison of HE4 accuracy / CA125 accuracy was 0.990, indicating HE4 was not inferior to CA125 (McNemar's test p-value = 0.522). Performing a velocity of change analysis, the accuracy and NPV determined for HE4 versus CA125 were 78.3% versus 78.6% (p = 0.995) and 74.9% versus 76.3% (p = 0.815), respectively. Concordance comparison of HE4 velocity accuracy / CA125 velocity accuracy was 0.996, again indicating HE4 was not inferior to CA125 (McNemar's test p-value = 0.884). The combination of HE4 and CA125 velocity changes showed a similar accuracy of 81.3% (p = 0.797 compared to HE4 and CA125 alone) and NPV of 81.1% (p≥0.172 compared to HE4 and CA125 alone), and an increased sensitivity of 70.5% (p≤0.070 compared to HE4 and CA125 alone). HE4 is equivalent to CA125 for monitoring of EOC patients. The combination of CA125 and HE4 velocities is superior to either marker alone.

Evaluation of safety and efficacy of Unani Add-on regimen in preventing the progression of severity of the disease in hospitalized SARS-CoV2 tested positive asymptomatic /mild to moderate symptomatic COVID-19 cases- A Randomised Controlled Clinical Trial

Objectives: The study aimed to establish the effectiveness of Unani add-on regimen by comparing theduration required for change in disease status from COVID-19 positive asymptomatic / mildto moderate symptomatic patients to asymptomatic negative. Methods: This single-centric, randomized, twin arm, controlled, clinical trial was carried out on a totalnumber of 62 RT-PCR confirmed COVID-19 patients. The Intervention group (IG) receivedUnani Regimen (Khameera Marwareed and Unani Joshanda) in addition to the conventional management, while the Control group (CG) received only conventional management. Results: It was observed that 16 (51.6%) patients in Intervention Group and 3 (9.4%) patients incontrol group became negative for COVID-19 at day 7 and remaining 13 out of 15 (93.5%) patients in Intervention Group and 20 out of 28 (74.1%) patients in control group becamenegative for COVID-19 at day 14 .This effect of the Unani Regimen in comparison to thecontrol group was statistically significant (p =0.003). Conclusions: It can be concluded that the change of COVID-19 positive asymptomatic / mild to moderate symptomatic patients to RT-PCR negative was much earlier in the add-on Unani regimen group as compared to control group. Bangladesh Journal of Medical Science Vol. 21 No. 04 October’22 Page : 901-911

Longitudinal Monitoring of Progressive Supranuclear Palsy using Body-Worn Movement Sensors.

We have previously shown that wearable technology and machine learning techniques can accurately discriminate between progressive supranuclear palsy (PSP), Parkinson's disease, and healthy controls. To date these techniques have not been applied in longitudinal studies of disease progression in PSP. We aimed to establish whether data collected by a body-worn inertial measurement unit (IMU) network could predict clinical rating scale scores in PSP and whether it could be used to track disease progression. We studied gait and postural stability in 17 participants with PSP over five visits at 3-month intervals. Participants performed a 2-minute walk and an assessment of postural stability by standing for 30seconds with their eyes closed, while wearing an array of six IMUs. Thirty-two gait and posture features were identified, which progressed significantly with time. A simple linear regression model incorporating the three features with the clearest progression pattern was able to detect statistically significant progression 3 months in advance of the clinical scores. A more complex linear regression and a random forest approach did not improve on this. The reduced variability of the models, in comparison to clinical rating scales, allows a significant change in disease status from baseline to be observed at an earlier stage. The current study sheds light on the individual features that are important in tracking disease progression. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.