Multivariate OR Research Articles

Association of Fusobacterium nucleatum with Specific T-cell Subsets in the Colorectal Carcinoma Microenvironment.

While evidence indicates that Fusobacterium nucleatum (F. nucleatum) may promote colorectal carcinogenesis through its suppressive effect on T-cell-mediated antitumor immunity, the specific T-cell subsets involved remain uncertain. We measured F. nucleatum DNA within tumor tissue by quantitative PCR on 933 cases (including 128 F. nucleatum-positive cases) among 4,465 incident colorectal carcinoma cases in two prospective cohorts. Multiplex immunofluorescence combined with digital image analysis and machine learning algorithms for CD3, CD4, CD8, CD45RO (PTPRC isoform), and FOXP3 measured various T-cell subsets. We leveraged data on Bifidobacterium, microsatellite instability (MSI), tumor whole-exome sequencing, and M1/M2-type tumor-associated macrophages [TAM; by CD68, CD86, IRF5, MAF, and MRC1 (CD206) multimarker assay]. Using the 4,465 cancer cases and inverse probability weighting method to control for selection bias due to tissue availability, multivariable-adjusted logistic regression analysis assessed the association between F. nucleatum and T-cell subsets. The amount of F. nucleatum was inversely associated with tumor stromal CD3+ lymphocytes [multivariable OR, 0.47; 95% confidence interval (CI), 0.28-0.79, for F. nucleatum-high vs. -negative category; P trend = 0.0004] and specifically stromal CD3+CD4+CD45RO+ cells (corresponding multivariable OR, 0.52; 95% CI, 0.32-0.85; P trend = 0.003). These relationships did not substantially differ by MSI status, neoantigen load, or exome-wide tumor mutational burden. F. nucleatum was not significantly associated with tumor intraepithelial T cells or with M1 or M2 TAMs. The amount of tissue F. nucleatum is associated with lower density of stromal memory helper T cells. Our findings provide evidence for the interactive pathogenic roles of microbiota and specific immune cells.

Effect of healthcare system on prostate cancer-specific mortality in African American and non-Hispanic white men.

23 Background: Disparities in prostate cancer-specific mortality (PCSM) between African American and non-Hispanic White (White) patients have been attributed to biological differences; however, recent data suggest poorer outcomes may be related to barriers to medical care from the healthcare system in which patients receive care. We sought to evaluate potential drivers of disparities by comparing outcomes between African American and White men in the Surveillance, Epidemiology and End Results (SEER) national cancer registry and a relatively equal-access healthcare system, the Veterans Health Administration (VHA). Methods: We identified African American and White patients diagnosed with prostate cancer between 2004-2015 in the SEER and VHA databases. We analyzed metastatic disease at diagnosis with multivariable logistic regression, and PCSM with cumulative incidence analysis and sequential competing-risks regression adjusting for disease and sociodemographic factors. Results: The SEER cohort included 306,609 men (57,994 [18.9%] African American and 248,615 [81.1%] White) with a median follow-up of 5.3 years (interquartile range [IQR] 2.6-8.1 years), and the VHA cohort included 90,749 men (27,412 [30.2%] African American and 63,337 [69.8%] White) with a median follow-up of 4.7 years (IQR 2.4-7.6 years). In SEER, African American men were significantly more likely to present with metastatic disease (African American 4.3% versus White 3.0%, p< 0.001; multivariable odds ratio [OR] 1.25, 95% confidence interval [CI] 1.19-1.32, p< 0.001), whereas in the VHA, African American men were not significantly more likely to present with metastatic disease (African-American 3.2% versus White 3.3%, p= 0.26; multivariable OR 1.07, 95% CI 0.98-1.17, p= 0.12). In SEER, the 8-year cumulative incidence of PCSM was significantly higher for African American compared with White men (6.9% versus 5.1%, p< 0.001), whereas in the VHA, African American compared with White men did not have a significantly higher 8-year cumulative incidence of PCSM (5.5% versus 5.4%, p= 0.93). African American race was significantly associated with an increased risk of PCSM in SEER (univariable subdistribution hazard ratio [SHR] 1.39, 95% CI 1.33-1.45, p< 0.001), but was not significantly associated with PCSM on uni- and multivariable regression in the VHA. When adjusted for disease characteristics at diagnosis in SEER, disease extent, PSA, and Gleason score contributed to 85% of the risk of PCSM for African American men (adjusted SHR 1.06, 95% CI 1.02-1.12, p= 0.008). Conclusions: Racial disparities in PCSM were present in a national cohort, SEER, but not as pronounced in a relatively equal-access healthcare system, the VHA, potentially due to differences in metastatic disease at diagnosis among African American and White men between cohorts. These findings may be attributable to reduced barriers to care in the VHA.

Sex Differences in Time to Treat and Outcomes for Gliomas

BackgroundGliomas are the most common type of primary malignant brain tumor in adults, representing one third of all primary and central nervous system (CNS) tumors and 80% of malignant tumors diagnosed in the Western world. Epidemiological data indicate that the overall incidence and mortality of cancer is higher in males, while females have a better prognosis. The goal of this study is to determine whether there are sex differences in the time to treat and clinical outcomes in patients with gliomaMethodsGlioblastoma (GB) and Lower Grade Glioma (LGG) patients were defined per the Central Brain Tumor Registry of the United States (CBTRUS) from the National Cancer Database (NCDB) for diagnosis years 2004 to 2016. Associations between sex and time to treatment variables as well as associations between sex and multiple clinical outcomes were assessed using univariable and multivariable models.ResultsA total of 176,100 patients were used for analysis (124,502 GBM and 51,598 LGG). Males had a statistically significant association with >7 days to surgery (OR = 1.09, CI 1.05–1.13, p < 0.001) but this association was not observed in the multivariable model (OR = 1.05, CI 0.96–1.16, p = 0.25). After adjustment for key variables including time to treat variables, males with GB and LGG had a higher risk of death (HR = 1.11, CI 1.09–1.13, p < 0.001, HR = 1.09, CI 1.03–1.15, p < 0.001; respectfully). Sex differences in 90-day mortality for GBM were not found after adjustment (OR for males = 0.99, CI 0.91–1.08, p = 0.93). For LGG, both the univariable and multivariable logistic regression models showed no sex differences in 90-day mortality (OR for males = 1.03, CI 0.94–1.12, p = 0.45; multivariable OR for males = 0.81, CI 0.62–1.06, p = 0.13).ConclusionsBased on NCDB data, there were no statistically significant differences in time to treatment between males and females, however males had a higher proportion of GB and LGG as well as a higher risk of death compared to females.

Audit of oxygen administration to achieve a target oxygen saturation range in acutely unwell medical patients

Purpose of the studyTo evaluate documentation of a target oxygen saturation (SpO2) range and ability to achieve this range in acutely unwell inpatients.Study designIn this single-centre audit, patients with discharge...

Abstract PS8-03: Inflammation and coagulation biomarkers associated with physical resilience in older women receiving chemotherapy for early breast cancer

Abstract Background: Physical resilience, the ability to resist decline and maintain functional status despite a stressor such as chemotherapy, is a central aspect of successful aging. Understanding clinical and biological factors associated with resilience in older women receiving chemotherapy for early breast cancer may facilitate the development of targeted interventions to maintain an individual’s robustness.Methods: Women age ≥65 (N=406) with Stage I-III breast cancer who were part of a clinical study of neo/adjuvant chemotherapy in older women were recruited from 16 sites (NCT01472094, R01AG037037). The Deficit Accumulation Index (DAI), a continuous score (0-1) calculated based on 51-items from geriatric assessment data (Cohen et al Cancer 2017), was measured before and after receipt of chemotherapy. DAI was categorized as robust (0.0&amp;lt;0.2), prefrail (0.2&amp;lt;0.35) and frail (≥0.35). Baseline blood biomarkers of inflammation (interleukin-6 [IL-6], C-reactive protein [CRP]) and coagulation (D-dimer) were measured and defined as elevated if values were ≥median values in this cohort. The population of interest was older women who were robust prior to initiation of chemotherapy. The primary outcome was resilience (Yes/No); yes, defined as retaining robustness [DAI 0.0&amp;lt;0.2] before and ≤1 month after chemotherapy. Demographic, disease, and pretreatment variables associated with resilience in univariate analysis with p&amp;lt;0.1 were further adjusted using multivariable logistic regression to examine the associations between baseline biomarkers and resilience. Results: Before starting chemotherapy, 324 of 406 (80%) older women were robust. The median age was 70 (range 65-86), 61% had stage II or III disease, 29% had HER2+ disease, 22% had TNBC, 37% received an anthracycline-based regimen, 49% had planned duration of treatment &amp;gt; 12 weeks, and 74% received primary prophylaxis with WBC growth factors. Among these 324 robust older women, 253 (78%) remained robust (resilient) at the end of chemotherapy, 63 (19%) became prefrail, and 8 (3%) became frail. In univariate analyses, patients treated with anthracycline (OR=0.63, p=0.09), planned duration of treatment &amp;gt; 12 weeks (OR=0.56, p=0.04), elevated IL-6 ≥2.7 pg/ml (OR=0.59, p=0.05), elevated CRP ≥4.3 μg/ml (OR=0.57, p=0.04), elevated D-dimer ≥0.7 μg/ml (OR=0.61, p=0.07), or at least one elevated biomarker (OR=0.18, p&amp;lt;0.001) at baseline were less likely to be resilient after systemic chemotherapy. Adjusting for anthracyclines and treatment duration, patients who had one or more elevated biomarker were still significantly less likely to be resilient (OR=0.15, 95 CI 0.04-0.49, p=0.002) compared to those with no elevated biomarkers at baseline. Conclusions: In this cohort of older women with early breast cancer who were robust prior to initiation of chemotherapy, 22% became prefrail or frail at end of treatment. Resilience to chemotherapy was related to inflammatory and coagulation biomarkers. Further research is needed to examine the mechanism underlying why some older women are resilient and retain their robustness after receiving treatment, whereas others experience decline, and further explore the role of inflammation/coagulation in this phenomenon. Table 1. Multivariable associations between baseline blood biomarkers and resilienceResilient (n=253) No. %Non-resilient (n=71) No. %Multivariable OR (95%CI)P value# of elevated biomarkers*064 (25)4 (6)1.00190 (36)29 (41)0.16 (0.05-0.55)0.004255 (22)22 (31)0.14 (0.04-0.49)0.002344 (17)16 (23)0.14 (0.04-0.51)0.003No elevated biomarker64 (25)4 (6)1.00At least one elevated189 (75)67 (94)0.15 (0.04-0.49)0.002*Biomarkers were defined as elevated using the entire cohort median value as cut off points (IL-6 ≥2.7 pg/ml, CRP ≥4.3 μg/ml, and D-dimer ≥0.7 μg/ml). Combined effects of biomarkers were examined by creating a four-level categorical combination variable: 0=all three biomarkers are &amp;lt;median; 1=one of the biomarkers ≥median; 2=two of the biomarkers ≥median; and, 3=all three biomarkers ≥median. A dichotomized variable was also created comparing none (all three biomarkers are &amp;lt;median) vs at least one biomarker elevated (≥median). Citation Format: Mina S Sedrak, Canlan Sun, Hyman Muss, Rachel A. Freedman, Allison Magnuson, Cary P. Gross, William P. Tew, Heidi D. Klepin, Tanya M. Wildes, Efrat Dotan, Tracey O'Connor, Mary Ann Fenton, Ruby Sharma, Andrew Chapman, Cynthia Owusu, Selina Chow, Heeyoung Kim, Vani Katheria, Mark LaBarge, William Dale, Saro Armenian, Susan Neuhausen, Harvey J. Cohen. Inflammation and coagulation biomarkers associated with physical resilience in older women receiving chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-03.

Issues des transferts cumulés d’embryons frais et congelés en fécondation in vitro chez les femmes infectées par le virus de l’hépatite B

ObjectiveTo assess the impact of hepatitis B virus (HBV) infection in women on in vitro fertilization (IVF) outcomes. MethodsAn observational monocentric case-control cohort study conducted between 2012 and 2019 compared the outcomes of the first cycle of IVF between 64 woman infected with HBV and 128 seronegative controls. Frozen embryos transfers made within 18 months of the puncture were included. The exclusion criteria were severe infections, viral co-infection in women, any viral infection in their spouse, or lack of fresh embryo transfer. The matching was performed according to age, primary infertility or secondary, conventional or intracytoplasmic injection IVF technique and date of attempt. The main analysis focused on cumulative live births rates (LBR). ResultsThe clinical and ovarian stimulation characteristics were comparable except for a longer period of infertility in the HBV group. The LBR in the HBV group, when compared to controls, was not different after transfer of fresh (14.06 vs. 25.00% P=0.08) or frozen embryos (4.17 vs. 18.92% P=0.08), but significantly decreased in cumulative analysis (15.63 vs. 35.94% P=0.003). HBV infection was negatively associated with LBR in multivariate analysis OR=0.38 (95% CI 0.14–0.92) P<0.05. The implantation rate was lower in the HBV group versus controls, in fresh (14.89 vs. 27.72% P=0.02) and frozen (3.03 vs. 21.65% P=0.01) embryo transfers. ConclusionThis study suggests a negative impact of HBV infection in women on the cumulative LBR after IVF.

Elevated Faecal Calprotectin in Patients with a Normal Colonoscopy: Does It Matter in Clinical Practice? A Retrospective Observational Study

Introduction: Faecal calprotectin (FC) is commonly used as a diagnostic tool for patients with gastrointestinal (GI) symptoms. However, there is uncertainty in daily clinical practice how to interpret an elevated FC in patients with a normal colonoscopy. We investigated if patients with a normal colonoscopy but with an elevated FC more often were diagnosed with a GI disease in a 3-year follow-up period. Methods: Patients referred for colonoscopy (n = 1,263) to the Umeå University Hospital endoscopy unit between 2007 and 2013 performed a FC test (CALPRO^®) on the day before bowel preparation. A medical chart review was performed on all patients who had normal findings on their colonoscopy (n = 585, median age 64 years). Results: Thirty-four percent of the patients (n = 202) with normal colonoscopy had elevated FC (>50 μg/g), and these patients were more frequently diagnosed with upper GI disease during the follow-up period than patients with normal FC levels (9.9 vs. 4.7%; p = 0.015). The upper GI diseases were mainly benign (i.e., gastritis). In a binary logistic regression analysis controlling for age, gender, nonsteroid anti-inflammatory drug use, and proton-pump inhibitor use, there was no difference for a new diagnosis of upper GI disease in the follow-up period (multivariate OR 1.70; 95% CI: 0.77–3.74). There was no difference in a new diagnosis of lower GI disease (6.4 vs. 5.2%; p = 0.545) or cardiovascular disease/death (multivariate OR 1.68; 95% CI: 0.83–3.42) in the follow-up period between patients with elevated versus normal FC levels. Conclusions: In patients with a normal colonoscopy, a simultaneously measured increased FC level was not associated with an increased risk for significant GI disease during a follow-up period of 3 years.

Associated factors with negative health perception and quality of life of Brazilian older adults

The purpose of this study was to analyze the factors associated with negative Health Perception and Quality of Life (QoL) of older adults. This was a cross-sectional study composed of 224 older adults with a median age of 70.58±6.43 years old. A questionnaire was designed to incorporate ABEP (socioeconomic questionnaire), WHOQOL-BREF, IPAQ, and Senior Fitness Test (SFT). Binary logistic regression with p>0.05, organized in univariate and multivariate models in SPSS version 22. Variables upper extremities poor flexibility OR = 2.43 (1.37 – 4.31) and lower extremities poor flexibility OR = 2.69 (1.54 – 4.69) were significantly associated with negative health perception. Being not financial responsible OR= 0.33 (0.12 – 0.85) presented lower odds of negative QoL perception. The variable Lower extremities poor flexibility univariate OR= 2.52 (1.45 – 4.39) and multivariate model OR= 2.42 (1.38 – 4.24) showed almost three times higher probabilities of negative QoL perception.

SARS-CoV-2 seroprevalence and transmission risk factors among high-risk close contacts: a retrospective cohort study

BackgroundThe proportion of asymptomatic carriers and transmission risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among household and non-household contacts remains unclear. In Singapore, extensive contact tracing by the Ministry of Health for every diagnosed COVID-19 case, and legally enforced quarantine and intensive health surveillance of close contacts provided a rare opportunity to determine asymptomatic attack rates and SARS-CoV-2 transmission risk factors among community close contacts of patients with COVID-19.MethodsThis retrospective cohort study involved all close contacts of confirmed COVID-19 cases in Singapore, identified between Jan 23 and April 3, 2020. Household contacts were defined as individuals who shared a residence with the index COVID-19 case. Non-household close contacts were defined as those who had contact for at least 30 min within 2 m of the index case. All patients with COVID-19 in Singapore received inpatient treatment, with access restricted to health-care staff. All close contacts were quarantined for 14 days with thrice-daily symptom monitoring via telephone. Symptomatic contacts underwent PCR testing for SARS-CoV-2. Secondary clinical attack rates were derived from the prevalence of PCR-confirmed SARS-CoV-2 among close contacts. Consenting contacts underwent serology testing and detailed exposure risk assessment. Bayesian modelling was used to estimate the prevalence of missed diagnoses and asymptomatic SARS-CoV-2-positive cases. Univariable and multivariable logistic regression models were used to determine SARS-CoV-2 transmission risk factors.FindingsBetween Jan 23 and April 3, 2020, 7770 close contacts (1863 household contacts, 2319 work contacts, and 3588 social contacts) linked to 1114 PCR-confirmed index cases were identified. Symptom-based PCR testing detected 188 COVID-19 cases, and 7582 close contacts completed quarantine without a positive SARS-CoV-2 PCR test. Among 7518 (96·8%) of the 7770 close contacts with complete data, the secondary clinical attack rate was 5·9% (95% CI 4·9–7·1) for 1779 household contacts, 1·3% (0·9–1·9) for 2231 work contacts, and 1·3% (1·0–1·7) for 3508 social contacts. Bayesian analysis of serology and symptom data obtained from 1150 close contacts (524 household contacts, 207 work contacts, and 419 social contacts) estimated that a symptom-based PCR-testing strategy missed 62% (95% credible interval 55–69) of COVID-19 diagnoses, and 36% (27–45) of individuals with SARS-CoV-2 infection were asymptomatic. Sharing a bedroom (multivariable odds ratio [OR] 5·38 [95% CI 1·82–15·84]; p=0·0023) and being spoken to by an index case for 30 min or longer (7·86 [3·86–16·02]; p<0·0001) were associated with SARS-CoV-2 transmission among household contacts. Among non-household contacts, exposure to more than one case (multivariable OR 3·92 [95% CI 2·07–7·40], p<0·0001), being spoken to by an index case for 30 min or longer (2·67 [1·21–5·88]; p=0·015), and sharing a vehicle with an index case (3·07 [1·55–6·08]; p=0·0013) were associated with SARS-CoV-2 transmission. Among both household and non-household contacts, indirect contact, meal sharing, and lavatory co-usage were not independently associated with SARS-CoV-2 transmission.InterpretationTargeted community measures should include physical distancing and minimising verbal interactions. Testing of all household contacts, including asymptomatic individuals, is warranted.FundingMinistry of Health of Singapore, National Research Foundation of Singapore, and National Natural Science Foundation of China.

Chronic Baseline Prostate Inflammation is Associated with Lower Tumor Grade in Men with Prostate Cancer on Repeat Biopsy: Results from the REDUCE Study.

We investigated whether baseline acute or chronic prostate inflammation among men with initial negative biopsies for prostate cancer was associated with cancer grade in 2-year repeat biopsies. Retrospective analyses were conducted of 889 men aged 50 to 75 years old with negative baseline prostate biopsy and 2-year repeat biopsy positive for prostate cancer in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study. Acute and chronic prostate inflammation and cancer grade were determined by central pathology during the REDUCE study. The association of inflammation in baseline and 2-year repeat biopsy and prostate cancer grade in 2-year repeat biopsy was evaluated with Student's t-test, chi-squared test and multivariable logistic regression. Chronic, acute inflammation and both were detected in 533 (60%), 12 (1%) and 85 (10%) baseline biopsies, respectively. Presence of acute and chronic inflammation were significantly associated with each other (p <0.001). Both types of inflammation were unrelated to race, body mass index, prostate specific antigen or digital rectal exam. At the 2-year biopsy, 621 (70%) tumors were low grade (Gleason scores 2-6) and 268 (30%) were high grade (Gleason scores 7-10). In univariable and multivariable analyses, men with baseline chronic inflammation had significantly fewer high grade tumors (univariable OR 0.64, 95% CI 0.47-0.87, p=0.004; multivariable OR=0.68, 95% CI0.50-0.93, p=0.016) than those without baseline chronic inflammation. Baseline acute inflammation was not associated with tumor grade (univariable OR 0.74, 95% CI 0.45-1.20, p=0.22; multivariable OR 0.78, 95% CI 0.48-1.29, p=0.34). Chronic inflammation in a negative biopsy was associated with lower prostate cancer grade among men with cancer on follow-up 2-year biopsy.

Epidemiology of Cranial Cruciate Ligament Rupture and Patellar Luxation in Dogs from the Province of Buenos Aires, Argentina.

The aim of this study was to investigate the prevalence of cranial cruciate ligament rupture and patellar luxation and the associated risk factors in dogs. A total of 13,072 clinical records of dogs were reviewed from School Hospital (Faculty of Veterinary Sciences, National University of La Plata). Data of age, breed, sex, body weight, patellar luxation and cranial cruciate ligament rupture condition were registered. Chi-squared and Fisher's exact tests were used to compare the prevalence of cranial cruciate ligament rupture and patellar luxation with the variables and then univariable logistic regression was used to evaluate the risk of having cranial cruciate ligament rupture and patellar luxation. Multivariable logistic regression was used including all variables to assess the odds of having patellar luxation and cranial cruciate ligament rupture. Of 13,072 patients treated, 72 and 51 had cranial cruciate ligament rupture and patellar luxation respectively. Sex was not a major risk factor for either condition. Adult (odds ratio [OR] = 8.2) and senior (OR = 4.3) patients had increased risk of having cranial cruciate ligament rupture, while for patellar luxation age was not a risk factor. Groups 2, 3 and 8 were more likely to have cranial cruciate ligament rupture (OR = 5.5, OR = 9.1 and OR = 2.6), and group 11 had lower risk of having patellar luxation (OR = 0.08). Maxi (OR = 2.4) and giant (OR = 6.0) breeds had higher risk of having cranial cruciate ligament rupture, and medium and maxi breeds had higher risk of patellar luxation (OR = 0.05 and OR = 0.3). Multivariate OR test confirmed that age (adult), body size (giant and maxi) and breed group (Group 3) were significantly associated with having cranial cruciate ligament rupture, and age was associated with having patellar luxation. This is the first epidemiological study of cranial cruciate ligament rupture and patellar luxation in dogs from School Hospital (Faculty of Veterinary Sciences, National University of La Plata). Giant and large adult dogs from the Molossoid and Terrier breeds were more likely to have cranial cruciate ligament rupture, while mixed and large dog breeds showed the lowest risk of having patellar luxation.

Abstract PO-063: Impact of cancer history on outcomes among hospitalized COVID-19 patients: A case-control analysis

Abstract Background: Early reports suggest a possible increased risk of serious complications and death in COVID-19 patients with cancer. However, rigorous comparisons with non-cancer control patients with COVID-19 are lacking. Methods: We systematically identified all patients with a history of cancer admitted to two major academic medical centers in Boston with symptomatic COVID-19 infections between 03/13/2020 and 05/10/2020. 162 cases were identified, and matched 1:2 by age, gender, race, and admission date with systematically identified controls without a cancer history. Sociodemographics, comorbidities, presenting symptoms, hospital course, and COVID-19 outcomes were extracted from medical records for all patients. Cancer history and treatments were documented for cases. Clinical characteristics and outcomes were compared between cases and controls using conditional logistic regression. Among cancer patients, logistic regression models were fit to identify predictors of death/discharge to hospice. Results: As of 06/05/2020, among 162 cancer patients (median time since diagnosis, 35.6 [range 0.39-435] months; 80% with solid tumor, 20%, hematologic diagnosis), 27.8% died or were discharged to hospice and 4.3% were still hospitalized. Among the 324 controls, 25.6% died or were discharged to hospice, and 3.1% were still hospitalized. Median duration of hospitalization was 9 days for both cases and controls. The proportion of controls who were intubated (36.1%) was higher than cases (27.2%). The odds of mortality/discharge to hospice (vs. discharge to home/facility) were similar between cancer cases and matched controls (univariable OR: 1.15, 95% CI: 0.73-1.82; multivariable OR: 1.54, 95% CI: 0.90-2.65). In multivariable analyses, cancer patients were more likely to be immunosuppressed (OR: 4.21, 95% CI: 2.42-7.34), to have presented at hospital admission with fatigue (OR: 1.71, 95% CI: 1.05-2.78), and were less likely to have a premorbid neurologic condition (OR: 0.37, 95% CI: 0.16-0.82). Among cancer cases, patients with metastatic disease or who had received cancer-directed therapy in the last 6 months (n=74, 46%) did not have higher odds of death/discharge to hospice following their hospital course (univariable OR: 1.37, 95% CI: 0.68-2.75; multivariable OR: 1.77, 95% CI: 0.80-3.93) compared to patients with no evidence of disease and no treatment within 6 months. Conclusions: Patients with a history of cancer hospitalized for COVID-19 had similar hospital course and mortality to matched hospitalized COVID-19+ controls without cancer. Additionally, we did not find an association between having metastatic disease or recent cancer treatment and experiencing an adverse outcome. During the onset and surge peak of the COVID-19 crisis in Boston, people with a history of cancer admitted to two large teaching hospitals for COVID-19 infection fared no worse than those without a history of cancer. Citation Format: Isaac Klein, Shoshana Rosenberg, Camille Kotton, Kerry Reynolds, Leyre Zubiri, Rachel Gaither, Hannah Freeman, Greg Kirkner, Chanu Rhee, Michael Klompas, Meghan Baker, Martha Wadleigh, Eric Winer, Ann Partridge. Impact of cancer history on outcomes among hospitalized COVID-19 patients: A case-control analysis [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-063.

Cardiopulmonary Exercise Testing Versus Frailty, Measured by the Clinical Frailty Score, in Predicting Morbidity in Patients Undergoing Major Abdominal Cancer Surgery

The primary outcome of this study is to investigate the association between the cardiopulmonary exercise testing (CPET) variables: anaerobic threshold (AT), peak oxygen uptake (VO2 peak), peak work rate (WR), ventilatory equivalence of CO2 (VE/VCO2) at the anaerobic threshold (AT) with frailty, measured by the clinical frailty scale (CFS) in patients planned to undergo major abdominal cancer surgery. The secondary outcome is to compare the CPET variables (VO2 peak, peak WR, VE/VCO2 at AT) with frailty measured by the CFS in predicting postoperative surgical morbidity in patients following major abdominal cancer surgery. This study was a single-centre prospective cohort analysis of consecutive adult patients undergoing CPET and CFS scoring as part of their pre-operative work-up for major abdominal cancer surgery. A total of n = 317 patients underwent CPET and CFS assessment ahead of planned abdominal oncological surgery. Negative correlations were observed between the CPET variables: AT - 0.42 p < 0.01; VO2 peak - 0.53 p < 0.01; peak WR - 0.54 p < 0.01 with CFS scores and a positive correlation betweenCFS scoresand VE/VCO2 0.29 p < 0.01. Only CFS remained statistically significant in a multivariate model OR 2.11 (1.42-3.15) 95% CI associated with Clavien-Dindo (CD) ≥ 1 defined morbidity including the significant univariate variables (VO2 peak, peak WR and CFS scores). No variables were associated with CD ≥ 3 morbidity. In patients scheduled to have major abdominal cancer surgery there was a weak association between poor performance on CPET and increasing frailty measured by the CFS. The CFS score unlike CPET was associated with all post-operative morbidity, but not major complications alone, in these patients. This suggests that CFS may be used as a less expensive alternative to CPET for predicting any postoperative morbidity in major abdominal cancer surgery.

Statins Use and Outcome of Acute Ischemic Stroke Patients after Systemic Thrombolysis

Aim: The aim of this was to study the effects of statins and their intensity on symptomatic intracranial hemorrhage (sICH) and outcome after IV thrombolysis (IVT) for acute ischemic stroke (AIS). Methods: We retrospectively reviewed the medical records and cerebrovascular images of all the patients treated with IVT for AIS in our center in a 10-year period. Patients were further characterized as any statin users versus non-users on admission to the emergency department. Statins were categorized in high intensity or low intensity statin based on its propensity to reduce lower low-density cholesterol by ≥45% or <45%, respectively. Safety and discharge modified Rankin Score were compared between statin users versus non-users and also between high-intensity versus low-intensity groups. Results: A total of 834 patients received IVT for AIS in our center during a 10-year period. Multivariate models were adjusted for age, NIH Stroke Scale at admission, INR, and history of DM and atrial fibrillation. There was no association between odds of sICH and any statin use (OR = 0.52 [0.26–1.03], p = 0.06). In multivariate model, any statin use was not associated with odds of poor outcome (Table 4: OR = 1.01 [0.79–1.55], p = 0.57). There was no significant association between odds of sICH among patients on high-intensity statin compared to low intensity statin (multivariate model OR = 0.39 [0.11–1.40], p = 0.15). There was 47% reduced odds of poor outcome among patients on high-intensity statin as compared to low-intensity statin (OR = 0.53[0.32–0.88] p = 0.01). However, this significant association was lost in the multivariate model (OR = 0.60 [0.35–1.05], p = 0.07). Conclusion: Our study does not show any significant association between risk of sICH and poor outcome after IVT for patients on prior statin therapy. We also did not find significant association between the risk of sICH and poor outcome after IVT and the intensity of the stain used.

Clinical features and predictors of remission in children under the age of 7 years with Graves' disease.

ImportanceGraves’ disease (GD) is rare in children under the age of 7 years. Children with this disease exhibit greater thyrotoxicity at diagnosis and require a longer course of medical therapy, compared with pubertal and postpubertal children and adults.ObjectiveTo investigate the clinical features and identify predictors of remission in children under the age of 7 years with GD.MethodsThis retrospective study included 77 children who were diagnosed with GD under the age of 7 years and were treated in the Department of Endocrinology, Beijing Children’s Hospital from 2010 to 2018. Clinical manifestations, laboratory data, and follow‐up records were collected for all patients. Children who achieved remission of treatment with methimazole were compared with those who had persistent disease to identify which variables were associated with remission; multiple logistic regression and Cox regression analyses were used to evaluate interactions among predictive variables.ResultsSixty‐three boys and 14 girls were included; the median age at diagnosis was 4.2 years (interquartile range: 3.2–5.3 years). Forty‐six (56.7%) patients had no family history of thyroid disease, 17 patients had family history of thyroid disease and 14 patients with unknown family history. Of the 77 patients, 18 (23.4%) patients achieved remission of treatment with methimazole and 59 patients did not; moreover, 51 (66.2%) had Graves’ ophthalmopathy. Univariate analyses revealed no significant differences between the remission group and non‐remission group in terms of age at diagnosis, sex, initial goiter size, or initial thyroid hormone concentration. However, there were a trend of correlation between the initial level of thyroid peroxidase antibody (TPOAb) and remission status (univariate analysis OR 1.002, P = 0.038; multivariate analysis OR 1.004, P = 0.019). Similar results were observed in univariate analysis of the initial thyrotropin receptor antibody (TRAb) level, but this association was not significant in multivariate analysis. Cox regression analyses revealed that children with high TRAb level required longer duration of remission, compared with low TRAb level (OR 0.950, 95% CI 0.904–0.997, P = 0.037).InterpretationInitial TRAb level was an independent predictor of remission outcome in young children under the age of 7 years with GD. Initial TRAb level may predict the likelihood of remission in patients with young‐age‐of‐onset GD.

Association between consumption frequency of honey and non-alcoholic fatty liver disease: results from a cross-sectional analysis based on the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) Cohort Study

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Recent evidence has suggested the protective effects of honey consumption against the metabolic syndrome, but the association between honey intake and NAFLD is still unclear. We investigated how the consumption frequency of honey was associated with NAFLD in the general population. This was a cross-sectional study of 21979 adults aged 20-90 years. NAFLD was diagnosed based on the ultrasound-diagnosed fatty liver without significant alcohol intake and other liver diseases. Diet information, including consumption frequency of honey, was assessed by a validated 100-item FFQ. OR with 95 % CI were calculated by the binary logistic regression model, adjusting for confounding factors identified by the directed acyclic graph. Overall, 6513 adults (29·6 %) had NAFLD. Compared with participants consuming ≤1 time/week of honey, the multivariable OR of NAFLD were 0·86 (95 % CI 0·77, 0·97) for 2-6 times/week and 1·10 (95 % CI 0·95, 1·27) for ≥1 times/d (Pfor trend = 0·90). The results were generally similar in subgroups of BMI at a cut-point of 24·0 kg/m2 (Pfor interaction = 0·10). In this large-scale study, consuming honey 2-6 times/week was inversely associated with NAFLD, whereas consuming honey ≥1 times/d had no association with NAFLD. These results need replication in other large-scale prospective studies.

Abstract 2353: A two-tiered targeted proteomics approach to identify biomarkers of colorectal cancer risk

Abstract Colorectal cancer (CRC) mortality is highly dependent on stage at diagnosis, and measures to increase the likelihood of early detection are urgently needed. Many countries have ongoing screening programs, but the addition of blood-based pre-screening biomarkers for risk stratification could reduce costs and increase compliance. In this study, we used prospectively collected plasma samples from the population-based Northern Sweden Health and Disease Study (NSHDS) to evaluate panels of protein biomarkers in relation to CRC risk. Using a two-tiered approach, we first included a unique set of 58 CRC cases and 58 matched controls with time-matched, repeated, prediagnostic samples (10 years apart, with the second sample collected three months to five years before diagnosis). Relative plasma concentrations of 161 proteins were analyzed by multiplex immunoassay (Olink proteomics, inflammation panel and oncology II panel). In the second tier, 15 of these proteins were selected for further analysis, together with six promising early detection protein markers from the literature. The second sample set included prediagnostic samples from 450 CRC cases and 450 matched controls, of which 33 case/control pairs had repeated samples. Conditional logistic regression and linear mixed models were used to estimate odds ratios for CRC risk. In the second-tier analyses, Lasso regression was used to develop multi-marker models, and the resulting protein combinations were tested using ROC analysis. Of the 15 proteins showing promise as predictive biomarkers in the first phase, none retained statistical significance in the second phase. The most promising marker candidate was FGF-21 (multivariable OR: 1.14 95% CI: 0.99-1.30), a metabolic hormone involved in stimulation of glucose uptake that has been associated with body mass index. FGF-21 was also the only protein consistently selected by the Lasso algorithm. Sensitivity analysis for FGF-21 in subgroups based on tumor site, stage and molecular subtypes including BRAF and KRAS mutations did not reach statistical significance. Our findings highlight the challenge of identifying cancer biomarkers that can be used in the prediagnostic window of opportunity for early detection. For early risk stratification, with the vision of achieving effective precision screening, single biomarkers or small marker panels may not be sufficient. Large studies using prospectively collected samples and machine learning to identify biomarker risk patterns may be a more promising approach. Citation Format: Sophia Harlid, Justin Harbs, Robin Myte, Carl Brunius, Marc Gunter, Xijia Liu, Richard Palmqvist, Bethany Van Guelpen. A two-tiered targeted proteomics approach to identify biomarkers of colorectal cancer risk [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2353.

Neutrophil to lymphocyte ratio and breast cancer risk: analysis by subtype and potential interactions

Multiple studies have found the neutrophil to lymphocyte ratio (NLR) to be associated with adverse breast cancer (BC) prognosis and survival. Very limited data exist on the role of NLR and risk of BC. The BREOGAN study is a population-based case–control study conducted in Galicia, Spain. We examined the WBC- and NLR-BC relationships. The risk of BC increased with increasing levels of neutrophils percentage (NE%) (multivariable OR for the highest category (95% CI) = 2.14 (1.39–3.32), P-trend < 0.001) and of the NLR (multivariable OR for the highest category (95% CI) = 1.93 (1.26–2.97), P-trend < 0.001). Lymphocytes absolute (L#) and percentage (L%) were associated with a decreased risk of BC (multivariable OR for the highest category (95% CI) = 0.54 (0.35–0.83), and 0.51 (0.33–0.79), P-trend = 0.001 and < 0.001, respectively). The NLR-BC association was more pronounced among Luminal A BC (multivariable OR for the highest category (95% CI) = 2.00 (1.17–3.45), P-trend < 0.001), HER2-negative BC (multivariable OR for the highest category (95% CI) = 1.87 (1.16–3.02), P-trend < 0.001), and those with high total cholesterol and low H2O2 levels.

Dietary sodium:potassium ratio and CVD risk factors among Japanese adults: a retrospective cross-sectional study of pooled data from the National Health and Nutrition Survey, 2003-2017.

Few studies have reported associations between the Na:K ratio and risk factors related to CVD among the general population in Asian countries. This study aimed to investigate the dietary Na:K ratio association with CVD risk factors among Japanese adults. This retrospective cross-sectional study included 48800 Japanese participants (19386 men and 29414 women) aged ≥20 years, registered in the 2003-2017 National Health and Nutrition Survey. Multivariate OR and 95 % CI for risk of hypertension, high glycated HbA1c levels, hypercholesterolaemia, low serum levels of HDL-cholesterol and high non-HDL-cholesterol levels according to the Na:K ratio were estimated using logistic regression models. Dietary Na:K ratio decreased for both men and women from 2003 to 2017. Higher Na:K ratio and higher hypertension prevalence were observed (multivariate OR (fifth v. first quintiles) 1·27, 95 % CI 1·15, 1·40; Pfor trend < 0·001 for men and 1·12, 95 % CI 1·01, 1·23; Pfor trend = 0·007 for women). Higher Na:K ratio was associated with higher prevalence of high HbA1c levels in men (multivariate OR 1·56, 95 % CI 1·24, 1·96). Prevalence of low HDL-cholesterol levels was increased with higher Na:K ratio (Pfor trend =0·002 for men and <0·001 for women). No significant associations were found between Na:K ratio and hypercholesterolaemia in men or high non-HDL-cholesterol levels in both men and women. Our findings suggest that dietary Na:K ratio is associated with several CVD risk factors among Japanese adults.

Clinical features and outcomes of PComA aneurysms originating from fetal posterior communicating arteries in a single institution

BackgroundThe aim of this study was to retrospectively analyze our experience with the patients who underwent surgical treatment of posterior communicating artery (PComA) aneurysms originating from fetal posterior cerebral artery (fPCA) and analyze the risk factors for the postoperative radiological infarction and outcome.MethodsFrom 2011 to 2020, we retrospectively reviewed 74 PComA aneurysms originating from fPCA in terms of the clinical and radiological features and obtained the follow-up data from the Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University. The relationships between these features and follow-up data were assessed with the univariate and multivariate analysis.ResultsIn this series, 74 aneurysms were occurring at the origin of fPCAs. All the patients showed complete obliteration of their aneurysms. Full fPCA type tends to be a predictive factor for radiological infarction (univariate χ2 = 5.873, P = 0.027; multivariate OR = 0.264, P = 0.060). Postoperative radiological infarction (univariate χ2 = 12.611, P = 0.001; multivariate OR = 6.033, P = 0.043), rupture (univariate χ2 = 4.514, P = 0.047; multivariate OR = 57.966, P = 0.044), and hypertension (univariate χ2 = 5.301, P = 0.024; multivariate OR = 24.462, P = 0.029) tend to be the independent predictive factors for poor prognosis at 3 months after discharge.ConclusionsIn conclusion, we report a series of patients harboring aneurysms originating from the fPCA. Surgical clipping is a reliable strategy. Full fPCA type is related to postsurgical infarction. Postoperative radiological infarction, rupture, and hypertension tend to be the independent predictive factor for poor prognosis at 3 months after discharge.