Healthy first-degree relatives from multiplex families versus simplex families have a higher subclinical intestinal inflammation, a distinct fecal microbial signature, and harbor a higher risk of developing Crohn's disease.

BACKGROUND & AIMS: Unaffected first-degree relatives (FDRs) from families with two or more affected FDRs with Crohn's disease (CD, multiplex families) have a high risk of developing CD, although the underlying mechanisms driving this risk are poorly understood. We aimed to identify differences in biomarkers between FDRs from multiplex versus simplex families and to investigate the risk of future CD onset accounting for potential confounders. METHODS: We assessed the Crohn's and Colitis Canada Genetic Environmental Microbial (CCC-GEM) cohort of healthy FDRs of patients with CD. Genome-wide CD-polygenic risk scores (CD-PRS), urinary fractional excretion of lactulose-to-mannitol ratio (LMR), fecal calprotectin (FCP), and fecal 16S ribosomal RNA microbiome were measured at recruitment. Associations between CD multiplex status and baseline biomarkers were determined using generalized estimating equations models. Cox models were used to assess the risk of future CD onset. RESULTS: There were 4051 participants from simplex families and 334 from CD multiplex families. CD multiplex status was significantly associated with higher baseline FCP (p=0.026) but not with baseline CD-PRS or LMR. Three bacterial genera were found to be differentially abundant between both groups. CD multiplex status at recruitment was independently associated with an increased risk of developing CD (adjusted hazard ratio 3.65, 95% confidence interval 2.18 - 6.11, p < 0.001). CONCLUSION: Within FDRs of patients with CD, participants from multiplex families had a 3-fold increased risk of CD onset, a higher FCP, and an altered bacterial composition, but not genetic burden or altered gut permeability. These results suggest that putative environmental factors might be enriched in FDRs from multiplex families.

Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study.

HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) are recognized as distinct entities. There remains uncertainty surrounding the causal effects of smoking and alcohol on the development of these two cancer types. Here we perform multivariable Mendelian randomization (MR) to evaluate the causal effects of smoking and alcohol on the risk of HPV-positive and HPV-negative HNSCC in 3431 cases and 3469 controls. Lifetime smoking exposure, as measured by the Comprehensive Smoking Index (CSI), is associated with increased risk of both HPV-negative HNSCC (OR = 3.03, 95%CI:1.75-5.24, P = 7.00E-05) and HPV-positive HNSCC (OR = 2.73, 95%CI:1.39-5.36, P = 0.003). Drinks Per Week is also linked with increased risk of both HPV-negative HNSCC (OR = 7.72, 95%CI:3.63-16.4, P = 1.00E-07) and HPV-positive HNSCC (OR = 2.66, 95%CI:1.06-6.68, P = 0.038). Smoking and alcohol independently increase the risk of both HPV-positive and HPV-negative HNSCC. These findings have important implications for understanding the modifying risk factors between HNSCC subtypes.

Outcomes in older adults with metastatic esophageal and gastric carcinoma treated with palliative chemotherapy.

BACKGROUND: The incidence of esophageal and gastric carcinoma (GEC) in elderly patients is increasing, yet patients ≥75 years have historically been underrepresented in clinical trials. We sought to investigate palliative chemotherapy administration patterns and survival outcomes in older adults. MATERIALS AND METHODS: A retrospective analysis identified patients aged 65-74 (young-old) and ≥75 years (older-old) diagnosed with advanced GEC. Patient and tumor characteristics were recorded, with descriptive analysis, time-to-event data analysis using Kaplan-Meier curves and multivariate Cox proportional hazards regression analysis performed. RESULTS: One hundred and ninety-eight "young-old" and 109 'older-old' patients were identified. Patient characteristics were similar between groups except for Charlson Co-morbidity Index (CCI), with lower co-morbidities in the "young-old" compared to "older-old" cohort (P < .001; CCI = 0 in 103 (52%) "young-old" vs 31 (28%) "older-old"). The primary diagnosis in both groups was adenocarcinoma. 119 (60%) "young-old" and 25 (23%) "older-old" patients received chemotherapy (P < .001). Performance status was the primary explanation for chemotherapy non-receipt in both cohorts; age was the explanation in 21 (25%) "older-old" patients and none in the "young-old" patients. PFS for first-line systemic therapy in "young-old" patients was 6.4 (95% CI 5.9-7.6) versus 7.5 months (95% CI 5.1-11.3) in "older-old" patients (P = .69) whilst respective OS was 12.3 (95% CI 10.1-15.5) and 10.4 months (95% CI 9.0-14.6) (P = .0816). Toxicity prompted chemotherapy cessation in 17 (15%) "young-old" and 3 (13%) "older-old" patients (P = .97). Multivariate analysis identified CCI and ECOG performance status as predictive for PFS and OS, respectively. No causative relationship was identified with other variables. CONCLUSION: Our study of real-world older-adults show that significant number of "older-old" patients with GEC do not receive chemotherapy. Among "older-old" adults who do receive systemic therapy, outcomes are comparable; this underscores the importance of geriatric assessment-guided care and suggests that age alone should not be a barrier to receipt of chemotherapy in patients with advanced GEC.

Impact of an Inter-Professional Clinic on Pancreatic Cancer Outcomes: A Retrospective Cohort Study.

Background: Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in diagnosis, staging, and appropriate treatment. Furthermore, patients with PDAC often experience complex symptomatology and psychosocial implications that require multi-disciplinary and inter-professional supportive care management from health professionals. Despite these hurdles, the implementation of inter-professional clinic approaches showed promise in enhancing clinical outcomes. To assess the effectiveness of such an approach, we examined the impact of the Wallace McCain Centre for Pancreatic Cancer (WMCPC), an inter-professional clinic for patients with PDAC at the Princess Margaret Cancer Centre (PM). Methods: This retrospective cohort study included all patients diagnosed with PDAC who were seen at the PM before (July 2012-June 2014) and after (July 2014-June 2016) the establishment of the WMCPC. Standard therapies such as surgery, chemotherapy, and radiation therapy remained consistent across both time periods. The cohorts were compared in terms of survival rates, disease stage, referral patterns, time to treatment, symptoms, and the proportion of patients assessed and supported by nursing and allied health professionals. Results: A total of 993 patients were included in the review, comprising 482 patients pre-WMCPC and 511 patients post-WMCPC. In the multivariate analysis, adjusting for ECOG (Eastern Cooperative Oncology Group) and stage, it was found that post-WMCPC patients experienced longer median overall survival (mOS, HR 0.84, 95% CI 0.72-0.98, p = 0.023). Furthermore, the time from referral to initial consultation date decreased significantly from 13.4 to 8.8 days in the post-WMCPC cohort (p < 0.001), along with a reduction in the time from the first clinic appointment to biopsy (14 vs. 8 days, p = 0.022). Additionally, patient-reported well-being scores showed improvement in the post-WMCPC cohort (p = 0.02), and these patients were more frequently attended to by nursing and allied health professionals (p < 0.001). Conclusions: The implementation of an inter-professional clinic for patients diagnosed with PDAC led to improvements in overall survival, patient-reported well-being, time to initial assessment visit and pathological diagnosis, and symptom management. These findings advocate for the adoption of an inter-professional clinic model in the treatment of patients with PDAC.

Environmental Factors Associated With Risk of Crohn's Disease Development in the Crohn's and Colitis Canada - Genetic, Environmental, Microbial Project.

BACKGROUND & AIMS: To date, it is unclear how environmental factors influence Crohn's disease (CD) risk and how they interact with biological processes. This study investigates the association between environmental exposures and CD risk and evaluates their association with pre-disease biomarkers. METHODS: We studied 4289 healthy first-degree relatives (FDRs) of patients with CD from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project. Regression models identified environmental factors associated with future CD onset and their association with pre-disease biological factors, including altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio (LMR); gut inflammation via fecal calprotectin (FCP) levels; and fecal microbiome composition through 16S rRNA sequencing. RESULTS: Over a 5.62-year median follow-up, 86 FDRs developed CD. Living with a dog between ages 5 and 15 (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.40-0.96; P = .034), and living with a large family size in the first year of life (HR, 0.43; 95% CI, 0.21-0.85; P = .016) were associated with decreased CD risk, whereas having a bird at the time of recruitment (HR, 2.78; 95% CI, 1.36-5.68; P = .005) was associated with an increased CD risk. Furthermore, living with a dog was associated with reduced LMR, altered relative abundance of multiple bacterial genera, and increased Chao1 diversity, whereas bird owners had higher FCP levels. Large family during participants' first year of life was associated with altered microbiota composition without affecting FCP or LMR. CONCLUSION: This study identifies environmental variables associated with CD risk. These variables were also associated with altered barrier function, subclinical inflammation, and gut microbiome composition shifts, suggesting potential roles in CD pathogenesis.

A latent class linear mixed model for monotonic continuous processes measured with error.

Motivated by measurement errors in radiographic diagnosis of osteoarthritis, we propose a Bayesian approach to identify latent classes in a model with continuous response subject to a monotonic, that is, non-decreasing or non-increasing, process with measurement error. A latent class linear mixed model has been introduced to consider measurement error while the monotonic process is accounted for via truncated normal distributions. The main purpose is to classify the response trajectories through the latent classes to better describe the disease progression within homogeneous subpopulations.

Association of synovial fluid and urinary C2C-HUSA levels with surgical outcomes post-total knee arthroplasty.

OBJECTIVES: After total knee arthroplasty (TKA), ∼30% of knee osteoarthritis (KOA) patients show little symptomatic improvement. Earlier studies have correlated urinary (u) type 2 collagen C terminal cleavage peptide assay (C2C-HUSA), which detects a fragment of cartilage collagen breakdown, with KOA progression. This study determines whether C2C levels in urine, synovial fluid, or their ratio, are associated with post-surgical outcomes. METHODS: From a large sample of 489 subjects, diagnosed with primary KOA undergoing TKA, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores were collected at baseline (time of surgery) and one-year post-TKA. Baseline urine (u) and synovial fluid (sf) were analysed using the IBEX-C2C-HUSA assay, with higher values indicating higher amounts of cartilage degradation. For urine, results were normalised to creatinine. Furthermore, subjects' changes in WOMAC scores were categorised based on percent reduction in pain or improvement in function, compared to baseline, such that >66.7%, >33.3 to ≤66.7%, and ≤33.3% denoted "strong", "moderate" and "mild/worse" responses, respectively. Associations of individual biofluid C2C-HUSA levels, or their ratio, with change in WOMAC pain and function scores up to one-year post-TKA, or category of change, were analysed by linear, logistic, or cumulative odds models. RESULTS: Higher baseline uC2C-HUSA levels or a lower ratio of baseline sfC2C-HUSA to uC2C-HUSA were associated with improvements in WOMAC pain by linear multivariable modelling [odds ratio -0.40 (95% confidence interval -0.76, -0.05) p = 0.03; 0.36 (0.01, 0.71), p = 0.04, respectively], while sfC2C-HUSA alone was not. However, lower ratios of sfC2C-HUSA to uC2C-HUSA were associated with improvements in WOMAC function [1.37 (0.18, 2.55), p = 0.02], while sfC2C-HUSA and uC2C-HUSA alone were not. Lower ratios of sfC2C-HUSA to uC2C-HUSA were also associated with an increased likelihood of a subject being categorised in a group where TKA was beneficial in both univariable [pain, 0.81 (0.68, 0.96), p = 0.02; function, 0.92 (0.85, 0.99), p = 0.035] and multivariable [pain, 0.81 (0.68, 0.97) p = 0.02; function, 0.92 (0.85, 1.00), p = 0.043] ordinal modelling, while sfC2C-HUSA and uC2C-HUSA alone were not. CONCLUSIONS: Overall, ratios of baseline sfC2C-HUSA to uC2C-HUSA, and baseline uC2C-HUSA, may play an important role in studying post-TKA surgical outcomes.

First impressions: A prospective evaluation of patient-physician concordance and satisfaction following the initial medical oncology consultation.

BACKGROUND: An especially significant event in the patient-oncologist relationship is the initial consultation, where many complex topics-diagnosis, treatment intent, and often, prognosis-are discussed in a relatively short period of time. This study aimed to measure patients' understanding of the information discussed during their first medical oncology visit and their satisfaction with the communication from medical oncologists. METHODS: Between January and August 2021, patients without prior systemic treatment of their gastrointestinal malignancy (GI) attending the Princess Margaret Cancer Centre (PMCC) were approached within 24 h of their initial consultation to complete a paper-based questionnaire assessing understanding of their disease (diagnosis, treatment plan/intent, and prognosis) and satisfaction with the consultation. Medical oncology physicians simultaneously completed a similar questionnaire about the information discussed at the initial visit. Matched patient-physician responses were compared to assess the degree of concordance. RESULTS: A total of 184 matched patient-physician surveys were completed. The concordance rates for understanding of diagnosis, treatment plan, treatment intent, and prognosis were 92.9%, 59.2%, 66.8%, and 59.8%, respectively. After adjusting for patient and physician variables, patients who reported treatment intent to be unclear at the time of the consultation were independently associated with lower satisfaction scores (global p = 0.014). There was no statistically significant association between patient satisfaction and whether prognosis was disclosed (p = 0.08). CONCLUSION: An in-depth conversation as to what treatment intent and prognosis means is reasonable during the initial medical oncology consultation to ensure patients and caregivers have a better understanding about their cancer.

Characterization of direct and/or indirect genetic associations for multiple traits in longitudinal studies of disease progression.

When quantitative longitudinal traits are risk factors for disease progression and subject to random biological variation, joint model analysis of time-to-event and longitudinal traits can effectively identify direct and/or indirect genetic association of single nucleotide polymorphisms (SNPs) with time-to-event. We present a joint model that integrates: (1) a multivariate linear mixed model describing trajectories of multiple longitudinal traits as a function of time, SNP effects, and subject-specific random effects and (2) a frailty Cox survival model that depends on SNPs, longitudinal trajectory effects, and subject-specific frailty accounting for dependence among multiple time-to-event traits. Motivated by complex genetic architecture of type 1 diabetes complications (T1DC) observed in the Diabetes Control and Complications Trial (DCCT), we implement a 2-stage approach to inference with bootstrap joint covariance estimation and develop a hypothesis testing procedure to classify direct and/or indirect SNP association with each time-to-event trait. By realistic simulation study, we show that joint modeling of 2 time-to-T1DC (retinopathy and nephropathy) and 2 longitudinal risk factors (HbA1c and systolic blood pressure) reduces estimation bias in genetic effects and improves classification accuracy of direct and/or indirect SNP associations, compared to methods that ignore within-subject risk factor variability and dependence among longitudinal and time-to-event traits. Through DCCT data analysis, we demonstrate feasibility for candidate SNP modeling and quantify effects of sample size and Winner's curse bias on classification for 2 SNPs identified as having indirect associations with time-to-T1DC traits. Joint analysis of multiple longitudinal and multiple time-to-event traits provides insight into complex traits architecture.

Gut Microbiome Composition Is Associated With Future Onset of Crohn's Disease in Healthy First-Degree Relatives.

BACKGROUND & AIMS: The cause of Crohn's disease (CD) is unknown, but the current hypothesis is that microbial or environmental factors induce gut inflammation in genetically susceptible individuals, leading to chronic intestinal inflammation. Case-control studies of patients with CD have cataloged alterations in the gut microbiome composition; however, these studies fail to distinguish whether the altered gut microbiome composition is associated with initiation of CD or is the result of inflammation or drug treatment. METHODS: In this prospective cohort study, 3483 healthy first-degree relatives (FDRs) of patients with CD were recruited to identify the gut microbiome composition that precedes the onset of CD and to what extent this composition predicts the risk of developing CD. We applied a machine learning approach to the analysis of the gut microbiome composition (based on 16S ribosomal RNA sequencing) to define a microbial signature that associates with future development of CD. The performance of the model was assessed in an independent validation cohort. RESULTS: In the validation cohort, the microbiome risk score (MRS) model yielded a hazard ratio of 2.24 (95% confidence interval, 1.03-4.84; P = .04), using the median of the MRS from the discovery cohort as the threshold. The MRS demonstrated a temporal validity by capturing individuals that developed CD up to 5 years before disease onset (area under the curve > 0.65). The 5 most important taxa contributing to the MRS included Ruminococcus torques, Blautia, Colidextribacter, an uncultured genus-level group from Oscillospiraceae, and Roseburia. CONCLUSION: This study is the first to demonstrate that gut microbiome composition is associated with future onset of CD and suggests that gut microbiome is a contributor in the pathogenesis of CD.

Multimodal immunogenomic biomarker analysis of tumors from pediatric patients enrolled to a phase 1-2 study of single-agent atezolizumab.

We report herein an exploratory biomarker analysis of refractory tumors collected from pediatric patients before atezolizumab therapy (iMATRIX-atezolizumab, NCT02541604 ). Elevated levels of CD8+ T cells and PD-L1 were associated with progression-free survival and a diverse baseline infiltrating T-cell receptor repertoire was prognostic. Differential gene expression analysis revealed elevated expression of CALCA (preprocalcitonin) and CCDC183 (highly expressed in testes) in patients who experienced clinical activity, suggesting that tumor neoantigens from these genes may contribute to immune response. In patients who experienced partial response or stable disease, elevated Igα2 expression correlated with T- and B-cell infiltration, suggesting that tertiary lymphoid structures existed in these patients' tumors. Consensus gene co-expression network analysis identified core cellular pathways that may play a role in antitumor immunity. Our study uncovers features associated with response to immune-checkpoint inhibition in pediatric patients with cancer and provides biological and translational insights to guide prospective biomarker profiling in future clinical trials.

Nodal Yield <15 Is Associated With Reduced Survival in Esophagectomy and Is a Quality Metric.

BACKGROUND: Surgical resection after neoadjuvant therapy remains the cornerstone of curative management of esophageal adenocarcinoma and is frequently used for squamous cell carcinoma. The optimal extent of lymphadenectomy and whether increasing lymph node yields confer a survival benefit remains unclear. Guidelines suggest resecting and examining a minimum of 15 lymph nodes at esophagectomy. This study assessed the impact of lymph node yield and lymph node ratio (LNR) on survival, identifying factors influencing nodal yield and radicality of resection. METHODS: All patients undergoing esophagectomy with curative intent at a single institution (stage 1-4 inclusive) from January 1, 2010, to December 31, 2020, were reviewed. Clinical and pathologic variables were interrogated. LNR was calculated by dividing positive lymph nodes by the total nodes resected. RESULTS: Esophagectomy was performed in 397 patients, with 288 undergoing minimally invasive esophagectomy (MIE). Margin status (hazard ratio [HR], 1.80; 95% CI, 1.15-2.83; P < .01), nodal yield <15 (HR, 1.98; 95% CI, 1.29-3.04; P = .002), and elevated LNR (HR, 8.16; 95% CI, 2.89-23.06; P < .001) predicted survival. MIE had higher nodal yields compared with open procedures (30.7 vs 25.3, P < .001). Patients undergoing neoadjuvant chemoradiotherapy had lower nodal yields compared with those with no neoadjuvant therapy and those with neoadjuvant chemotherapy (26.4 vs 30.6 vs 36.8, respectively; P < .001). Regression analysis determined a LNR of <0.05 was associated with a survival benefit. CONCLUSIONS: Textbook lymphadenectomy is associated with improved survival. Low lymph node yield and a high LNR are associated with reduced overall survival. A LNR of <0.05 is associated with significant survival benefit. A minimum nodal yield of 15 should remain the standard of care.

Systemic inflammatory prognostic scores in advanced pancreatic adenocarcinoma.

BACKGROUND: Systemic inflammatory scores may aid prognostication and patient selection for trials. We compared five scores in advanced pancreatic adenocarcinoma (PDAC). METHODS: Unresectable/metastatic PDAC patients enrolled in the Comprehensive Molecular Characterisation of Advanced Pancreatic Ductal Adenocarcinoma for Better Treatment Selection trial (NCT02750657) were included. Patients had pre-treatment biopsies for whole genome and RNA sequencing. CD8 immunohistochemistry was available in a subset. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, Prognostic Nutritional Index, Gustave Roussy Immune Score (GRIm-S), and Memorial Sloan Kettering Prognostic Score (MPS) were calculated. Overall survival (OS) was estimated using Kaplan-Meier methods. Associations between inflammatory scores, clinical/genomic characteristics, and OS were analysed. RESULTS: We analysed 263 patients. High-risk NLR, GRIm-S and MPS were poorly prognostic. The GRIm-S had the highest predictive ability: median OS 6.4 vs. 10 months for high risk vs. low-risk (P < 0.001); HR 2.26 (P < 0.001). ECOG ≥ 1, the basal-like subtype, and low-HRDetect were additional poor prognostic factors (P < 0.01). Inflammatory scores did not associate with RNA-based classifiers or homologous recombination repair deficiency genotypes. High-risk MPS (P = 0.04) and GRIm-S (P = 0.02) patients had lower median CD8 + tumour-infiltrating lymphocytes. CONCLUSIONS: Inflammatory scores incorporating NLR have prognostic value in advanced PDAC. Understanding immunophenotypes of poor-risk patients and using these scores in trials will advance the field.

Analysis of Real-Time Face-Verification Methods for Surveillance Applications.

In the last decade, face-recognition and -verification methods based on deep learning have increasingly used deeper and more complex architectures to obtain state-of-the-art (SOTA) accuracy. Hence, these architectures are limited to powerful devices that can handle heavy computational resources. Conversely, lightweight and efficient methods have recently been proposed to achieve real-time performance on limited devices and embedded systems. However, real-time face-verification methods struggle with problems usually solved by their heavy counterparts-for example, illumination changes, occlusions, face rotation, and distance to the subject. These challenges are strongly related to surveillance applications that deal with low-resolution face images under unconstrained conditions. Therefore, this paper compares three SOTA real-time face-verification methods for coping with specific problems in surveillance applications. To this end, we created an evaluation subset from two available datasets consisting of 3000 face images presenting face rotation and low-resolution problems. We defined five groups of face rotation with five levels of resolutions that can appear in common surveillance scenarios. With our evaluation subset, we methodically evaluated the face-verification accuracy of MobileFaceNet, EfficientNet-B0, and GhostNet. Furthermore, we also evaluated them with conventional datasets, such as Cross-Pose LFW and QMUL-SurvFace. When examining the experimental results of the three mentioned datasets, we found that EfficientNet-B0 could deal with both surveillance problems, but MobileFaceNet was better at handling extreme face rotation over 80 degrees.

Immune response and barrier dysfunction-related proteomic signatures in preclinical phase of Crohn's disease highlight earliest events of pathogenesis.

OBJECTIVE: The measure of serum proteome in the preclinical state of Crohn's disease (CD) may provide insight into biological pathways involved in CD pathogenesis. We aimed to assess associations of serum proteins with future CD onset and with other biomarkers predicting CD risk in a healthy at-risk cohort. DESIGN: In a nested case-control study within the Crohn's and Colitis Canada Genetics Environment Microbial Project (CCC-GEM) cohort, which prospectively follows healthy first-degree relatives (FDRs), subjects who developed CD (n=71) were matched with four FDRs remaining healthy (n=284). Using samples at recruitment, serum protein profiles using the Olink Proximity Extension Assay platform was assessed for association with future development of CD and with other baseline biomarkers as follows: serum antimicrobial antibodies (AS: positive antibody sum) (Prometheus); faecal calprotectin (FCP); gut barrier function using the fractional excretion of lactulose-to-mannitol ratio (LMR) assay. RESULTS: We identified 25 of 446 serum proteins significantly associated with future development of CD. C-X-C motif chemokine 9 (CXCL9) had the highest OR with future risk of CD (OR=2.07 per SD, 95% CI 1.58 to 2.73, q=7.9e-5), whereas matrix extracellular phosphoglycoprotein had the lowest OR (OR 0.44, 95% CI 0.29 to 0.66, q=0.02). Notably, CXCL9 was the only analyte significantly associated with all other CD-risk biomarkers with consistent direction of effect (FCP: OR=2.21; LMR: OR=1.67; AS: OR=1.59) (q<0.05 for all). CONCLUSION: We identified serum proteomic signatures associated with future CD development, reflecting potential early biological processes of immune and barrier dysfunction.

Prospective evaluation of Gadoxetate-enhanced magnetic resonance imaging and computed tomography for hepatocellular carcinoma detection and transplant eligibility assessment with explant histopathology correlation.

BACKGROUND: We aimed to prospectively compare the diagnostic performance of gadoxetic acid-enhanced MRI (EOB-MRI) and contrast-enhanced Computed Tomography (CECT) for hepatocellular carcinoma (HCC) detection and liver transplant (LT) eligibility assessment in cirrhotic patients with explant histopathology correlation. METHODS: In this prospective, single-institution ethics-approved study, 101 cirrhotic patients were enrolled consecutively from the pre-LT clinic with written informed consent. Patients underwent CECT and EOB-MRI alternately every 3 months until LT or study exclusion. Two blinded radiologists independently scored hepatic lesions on CECT and EOB-MRI utilizing the liver imaging reporting and data system (LI-RADS) version 2018. Liver explant histopathology was the reference standard. Pre-LT eligibility accuracies with EOB-MRI and CECT as per Milan criteria (MC) were assessed in reference to post-LT explant histopathology. Lesion-level and patient-level statistical analyses were performed. RESULTS: Sixty patients (49 men; age 33-72 years) underwent LT successfully. One hundred four non-treated HCC and 42 viable HCC in previously treated HCC were identified at explant histopathology. For LR-4/5 category lesions, EOB-MRI had a higher pooled sensitivity (86.7% versus 75.3%, p <  0.001) but lower specificity (84.6% versus 100%, p <  0.001) compared to CECT. EOB-MRI had a sensitivity twice that of CECT (65.9% versus 32.2%, p <  0.001) when all HCC identified at explant histopathology were included in the analysis instead of imaging visible lesions only. Disregarding the hepatobiliary phase resulted in a significant drop in EOB-MRI performance (86.7 to 72.8%, p <  0.001). EOB-MRI had significantly lower pooled sensitivity and specificity versus CECT in the LR5 category with lesion size < 2 cm (50% versus 79%, p = 0.002 and 88.9% versus 100%, p = 0.002). EOB-MRI had higher sensitivity (84.8% versus 75%, p <  0.037) compared to CECT for detecting < 2 cm viable HCC in treated lesions. Accuracies of LT eligibility assessment were comparable between EOB-MRI (90-91.7%, p = 0.156) and CECT (90-95%, p = 0.158). CONCLUSION: EOB-MRI had superior sensitivity for HCC detection; however, with lower specificity compared to CECT in LR4/5 category lesions while it was inferior to CECT in the LR5 category under 2 cm. The accuracy for LT eligibility assessment based on MC was not significantly different between EOB-MRI and CECT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03342677 , Registered: November 17, 2017.

Staff Experiences With Remote Work in a Comprehensive Cancer Center During the COVID-19 Pandemic and Recommendations for Long-Term Adoption.

BACKGROUND: The COVID-19 pandemic led to the rapid implementation of remote work, but few studies have examined the impact. We evaluated clinical staff experience with working remotely at a large, urban comprehensive cancer center in Toronto, Canada. METHODS: An electronic survey was disseminated between June 2021, and August 2021, via e-mail to staff who had completed at least some remote work during the COVID-19 pandemic. Factors associated with a negative experience were examined with binary logistic regression. Barriers were derived from a thematic analysis of open-text fields. RESULTS: Most respondents (N = 333; response rate, 33.2%) were age 40-69 years (46.2%), female (61.3%), and physicians (24.6%). Although the majority of respondents wished to continue remote work (85.6%), relative to administrative staff (admin), physicians (odds ratio [OR], 16.6; 95% CI, 1.45 to 190.14) and pharmacists (OR, 12.6; 95% CI, 1.0 to 158.9) were more likely to want to return on-site. Physicians were approximately eight times more likely to report dissatisfaction with remote work (OR, 8.4; 95% CI, 1.4 to 51.6) and 24 times more likely to report that remote work negatively affected efficiency (OR, 24.0; 95% CI, 2.7 to 213.0); nurses were approximately seven times more likely to report the need for additional resources (OR, 6.5; 95% CI, 1.71 to 24.48) and/or training (OR, 7.02; 95% CI, 1.78 to 27.62). The most common barriers were the absence of fair processes for allocation of remote work, poor integration of digital applications and connectivity, and poor role clarity. CONCLUSION: Although overall satisfaction with working remotely was high, work is needed to overcome barriers to implementation of remote and hybrid work models in the health care setting.

Comparison of Four Clinical Prognostic Scores in Patients with Advanced Gastric and Esophageal Cancer.

BACKGROUND: Prognostic scores that can identify patients at risk for early death are needed to aid treatment decision-making and patient selection for clinical trials. We compared the accuracy of four scores to predict early death (within 90 days) and overall survival (OS) in patients with metastatic gastric and esophageal (GE) cancer. METHODS: Advanced GE cancer patients receiving first-line systemic therapy were included. Prognostic risks were calculated using: Royal Marsden Hospital (RMH), MD Anderson Cancer Centre (MDACC), Gustave Roussy Immune (GRIm-Score), and MD Anderson Immune Checkpoint Inhibitor (MDA-ICI) scores. Overall survival (OS) was estimated using the Kaplan-Meier method. Cox proportional hazards models were used to analyze associations between prognostic scores and OS. The predictive discrimination was estimated using Harrell's c-index. Predictive ability for early death was measured using time-dependent AUCs. RESULTS: In total, 451 patients with metastatic GE cancer were included. High risk patients had shorter OS for all scores (RMH high- vs. low-risk median OS 7.9 vs. 12.2 months, P < .001; MDACC 6.8 vs. 11.9 months P < .001; GRIm-Score 5.3 vs. 13 months, P < .001; MDA-ICI 8.2 vs. 12.2 months, P < .001). On multivariable analysis, each prognostic score was significantly associated with OS. The GRIm-Score had the highest predictive discrimination and predictive ability for early death. CONCLUSIONS: The GRIm-Score had the highest accuracy in predicting early death and OS. Clinicians may use this score to identify patients at higher risk of early death to guide treatment decisions including clinical trial enrolment. This score could also be used as a stratification factor in future clinical trial designs.