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Screening for colorectal cancer (CRC) is cost-effective for reducing its mortality among the average-risk population. In the US, CRC incidence and mortality differ among racial/ethnic groups, with non-Hispanic Blacks (NHB) and American Indian/Alaska Natives showing highest incidence and mortality and earlier presentation. Since 2005, some professional societies have recommended CRC screening for NHB to commence at 45 years or earlier; this was not implemented due to lack of recommendation from key groups that influence insurance payment coverage. In 2017 the highly influential U.S. Multi-Society Task Force for Colorectal Cancer recommended screening to commence at 45 years for NHB; this recommendation was supplanted by data showing an increase in early-onset CRCs in non-Hispanic Whites approaching the under-50-year rates observed for NHB. Subsequently the American Cancer Society and the USPSTF recommended that the entire average-risk population move to commence CRC screening at 45 years. Implementing screening in 45-49-year-olds has its challenges as younger groups compared with older groups participate less in preventive care. The US had made extensive progress pre-COVID-19 in closing the disparity gap for CRC screening in NHB above age 50 years; implementing screening at younger ages will take ingenuity, foresight, and creative strategy to reach a broader-aged population while preventing widening the screening disparity gap. Approaches such as navigation for non-invasive and minimally invasive CRC screening tests, removal of financial barriers such as co-pays, and complete follow up to abnormal non-invasive screening tests will need to become the norm for broad implementation and success across all racial/ethnic groups.
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Objective: To describe ischemic stroke due to floating thrombus of ascending aorta occurring as acute and subacute complication of SARS-CoV-2 infection. Material(s) and Method(s): consecutive identification in clinical practice of ischemic strokes secondary to aortic arch thrombosis and history of acute or recent Covid-19 infection. Result(s): two patients had ischemic stroke with evidence of aortic arch thrombosis. The first case had concomitant acute Covid-19 infection, the second had recent Covid-19 infection. Both patients underwent intravenous thrombolysis, and subsequent anticoagulation. One patient died due to cerebral hemorrhage. Discussion and Conclusion(s): aortic arch thrombosis can be an incidental finding in acute ischemic stroke in patients with concomitant and recent COVID-19 disease. However, the infection may lead to thrombosis in non-atherosclerotic vessels and to cerebral embolism. Our findings support active radiological search for aortic thrombosis during acute stroke in patients with acute or recent COVID-19 disease.Copyright © 2022
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The SARS-CoV-2 is constantly mutating, and the new coronavirus such as Omicron has spread to many countries around the world. Anexelekto (AXL) is a transmembrane protein with biological functions such as promoting cell growth, migration, aggregation, metastasis and adhesion, and plays an important role in cancers and coronavirus disease 2019 (COVID-19). Unlike angiotensin-converting enzyme 2 (ACE2), AXL was highly expressed in respiratory system cells. In this study, we verified the AXL expression in cancer and normal tissues and found AXL expression was strongly correlated with cancer prognosis, tumor mutation burden (TMB), the microsatellite instability (MSI) in most tumor types. Immune infiltration analysis also demonstrated that there was an inextricable link between AXL expression and immune scores in cancer patients, especially in BLCA, BRCA and CESC. The NK-cells, plasmacytoid dendritic cells, myeloid dendritic cells, as one of the important components of the tumor microenvironment, were highly expressed AXL. In addition, AXL-related tumor neoantigens were identified and might provide the novel potential targets for tumor vaccines or SARS-Cov-2 vaccines research in cancer patients.
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Introduction: There are no FDA-approved therapies for acquired angioedema (AAE). In AAE patients whose underlying disease process is not amenable to therapy, options are limited, sometimes requiring off-label use of medications used for hereditary angioedema (HAE). Lanadelumab with rescue use of icatibant has not been officially studied for the management of AAE but has shown efficacy in HAE patients. Case Description: A 75-year-old male with history of stage 1 colon adenocarcinoma in remission presented with angioedema initially attributed to apixaban used for treatment of post-COVID-19 pulmonary embolus. Despite discontinuing apixaban, he continued to experience monthly episodes of angioedema involving orofacial and gastrointestinal symptoms, requiring 4 hospitalizations and steroid, oral antihistamine, tranexamic acid, and fresh frozen plasma treatments. One episode involved airway compromise requiring emergency icatibant use and transient intubation. Diagnostic results showed low C4, C1 total protein, and C1 inhibitor function, with negative C1 auto-antibody. Subsequent testing revealed monoclonal gammopathy of undetermined significance (MGUS) of low to intermediate risk (IgG kappa subtype);treatment was not recommended given MGUS staging and risk of treatment. He was started on lanadelumab every 2 weeks with continued icatibant for rescue use and has had remission of AAE over the following 3 months. Discussion(s): Lanadelumab in combination with rescue icatibant is emerging as an effective regimen to reduce hospitalizations and morbidity in AAE patients, particularly in patients whose underlying etiology of disease is unknown or for which treatment is not indicated. Investigation on a larger scale is warranted to better understand this therapeutic option for patients with AAE. Copyright © 2022
ABSTRACT
The mRNA vaccine has provided a promising approach for cancer immunotherapies. However, only a few mRNA vaccines have been developed against colon adenocarcinoma (COAD). Screening potential targets for mRNA vaccines from numerous candidates is a substantial challenge. Considering the tumor heterogeneity, only a subset of patients might respond to vaccinations. This study was conducted to identify potential candidates for mRNA vaccines, and distinguish appropriate subgroups of COAD patients for vaccination. A total of five tumor antigens with prognostic values were identified, including IGF2BP3, DPCR1, HOXD10, TRIM7, and ZIC5. The COAD patients were stratified into five immune subtypes (IS1-IS5), according to consensus clustering analysis. Higher tumor mutation burden (TMB) was observed in IS1 and IS5 subtypes. The IS1 and IS5 subtypes have shown the baseline of immune-hot tumor microenvironment, while other subtypes displayed immune desert phenotype. Distinct expressions of immune checkpoints (ICPs)-related genes and immunogenic cell death (ICD) modulators were observed among five immune subtypes. Finally, the immune landscape was conducted to narrow the immune components for better personalized mRNA-based vaccination. The IFIT3, PARP9, TAP1, STAT1, and OAS2 were confirmed as hub genes, and COAD patients with higher expressions of these genes might be more appropriate for mRNA vaccination. In conclusion, the IGF2BP3, DPCR1, HOXD10, TRIM7, and ZIC5 were identified as potential candidates for developing mRNA vaccines against COAD, and patients in IS1 and IS5 subtypes might respond better to mRNA vaccination.
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SESSION TITLE: Lung Cancer Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: The outbreak of the SARS-CoV-2 virus identified a need for healthcare systems to transform in order to accommodate the large volume of patients. As a result, innovative new methods to monitor patients have emerged. One type of innovation are remote patient monitoring (RPM) devices, which allow for home vital sign (VS) measurements and telemonitoring. We present a case utilizing this technology to monitor a middle-aged male with metastatic colon cancer to the lung, who required regular debulking therapy as a means of palliation. CASE PRESENTATION: A 59 year-old male with a history of stage IV colon adenocarcinoma with metastasis to the lungs status post lung wedge resection and radiation therapy 7 years previously was found to have an enlarging left lower lobe (LLL) mass. Fiberoptic bronchoscopy revealed resurgence of his metastasis. While undergoing palliative chemotherapy, the patient became increasingly dyspneic. Serial PET CTs showed evolution of his left lung mass with left upper and lower lobe collapse due to endobronchial disease prompting bronchoscopy with argon plasma coagulation (APC) for tumor debulking within the left mainstem bronchus and dilation of the LLL airways. While the patient's symptoms improved, he became dyspneic over several months, and interval CT scans demonstrated invasion of the left mainstem bronchus with complete collapse of the left lung. Repeat dilation and APC were performed with improvement in symptoms. Due to rapid tumor growth, he was enrolled in the continuous RPM (CRPM) program for 24/7 nursing-led telemonitoring. He completed daily questionnaires on a vendor-provided digital tablet, and his VS, composed of heart rate (HR), respiratory rate (RR), SpO2, and temperature, were automatically uploaded to a network using an FDA-approved wearable device. Intermittent readings using peripheral devices to measure blood pressure and spirometry were gathered. His VS mirrored his tumor progression, indicated by elevation in his mean RR and HR while his SpO2 declined necessitating 2L of oxygen. Further evaluation showed tumor invasion into the left mainstem bronchus and began to invade his right mainstem. Successive APC and cryotherapy were performed every 2-3 months with a total of 8 debulking bronchoscopies. Once his disease progressed to obstruct his entire left mainstem, the patient unenrolled from the CRPM program and enrolled in hospice care. DISCUSSION: Several RPM devices have previously been used, but require self-reported VS rather than automated, continuous oximetry. Our CRPM program was piloted as a means to monitor COVID-19 patients following hospital discharge. However, our patient displayed benefit from his 180 day CRPM enrollment while receiving palliative tumor debulking procedures in order to fulfill his wish to maximize time at home. CONCLUSIONS: RPM devices offer a novel method of monitoring patients outside of healthcare facilities. Reference #1: Gordon WJ, Henderson D, DeSharone A, et al. Remote Patient Monitoring Program for Hospital Discharged COVID-19 Patients. Appl Clin Inform. 2020;11(05). doi:10.1055/s-0040-1721039 Reference #2: O'Carroll O, MacCann R, O'Reilly A, et al. Remote monitoring of oxygen saturation in individuals with COVID-19 pneumonia. Eur Respir J. 2020;56(2). doi:10.1183/13993003.01492-2020 Reference #3: Grutters LA, Majoor KI, Mattern ESK, Hardeman JA, van Swol CFP, Vorselaars ADM. Home telemonitoring makes early hospital discharge of COVID-19 patients possible. J Am Med Informatics Assoc. 2020;27(11). doi:10.1093/jamia/ocaa168 DISCLOSURES: No relevant relationships by Kevin Loudermilk Speaker/Speaker's Bureau relationship with Janssen Please note: $1001 - $5000 by Michael Morris, value=Honoraria Speaker/Speaker's Bureau relationship with GSK Please note: $1001 - $5000 by Michael Morris, value=Honoraria Removed 03/29/2022 by Michael Morris No relevant relationships by Michal Sobieszczyk No relevant relations ips by Robert Walter No relevant relationships by Whittney Warren
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Since 2019, the coronavirus disease (COVID-19) has caused 6,319,395 deaths worldwide. Although the COVID-19 vaccine is currently available, the latest variant of the virus, Omicron, spreads more easily than earlier strains, and its mortality rate is still high in patients with chronic diseases, especially cancer patients. So, identifying a novel compound for COVID-19 treatment could help reduce the lethal rate of the viral infection in patients with cancer. This study applied network pharmacology and systematic bioinformatics analysis to determine the possible use of curcumol for treating colon adenocarcinoma (COAD) in patients infected with COVID-19. Our results showed that COVID-19 and COAD in patients shared a cluster of genes commonly deregulated by curcumol. The clinical pathological analyses demonstrated that the expression of gamma-aminobutyric acid receptor subunit delta (GABRD) was associated with the patients' hazard ratio. More importantly, the high expression of GABRD was associated with poor survival rates and the late stages of COAD in patients. The network pharmacology result identified seven-core targets, including solute carrier family 6 member 3, gamma-aminobutyric acid receptor subunit pi, butyrylcholinesterase, cytochrome P450 3A4, 17-beta-hydroxysteroid dehydrogenase type 2, progesterone receptor, and GABRD of curcumol for treating patients with COVID-19 and COAD. The bioinformatic analysis further highlighted their importance in the biological processes and molecular functions in gland development, inflammation, retinol, and steroid metabolism. The findings of this study suggest that curcumol could be an alternative compound for treating patients with COVID-19 and COAD.
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Purpose/Background: Early onset CRC (EO CRC), patients <50yo, is increasing in incidence. Diagnosis is driven by symptoms as the patients are ineligible for screening. Where patients access the health system is unclear. Hypothesis/Aim: We hypothesize that non-white patients with EO CRC present at disproportionate rates to the Emergency Department (ED). Methods/Interventions: Our institutional tumor board registry was reviewed for patients who were presented from August 2020-August 2021. Clinical chart review for race, sex, age, hospital presentation, site of malignancy, and access to health system: primary care, emergency department, outside referral, were extracted. Access to the health system was determined by who ordered the diagnostic colonoscopy or imaging study. Results/Outcome(s): One-hundred ninety-seven patients with colon and rectal adenocarcinoma were discussed at tumor board between August 2020-August 2021 (Table 1). Fifty-seven were EO and 140/197 were age >50. The sex distribution was approximately equal across ages. Of those <50 the median age was 45, and non-white patients were disproportionally represented with 47% Hispanic, 17.5% Black, 10.5% Asian patients. Non-white EO patients were more likely to present through the ED (16/34) relative to white EO patients (1/13). Of all EO patients 17 presented through the Emergency Department, 24 through primary care providers, 11 were referred in from an outside facility, and 2 diagnosed internationally (Figure). Limitations: This is an exploratory, retrospective single institution review of patients discussed at multidisciplinary tumor board over a single year. The population includes a safety-net institution and may not reflect presentation patterns at other hospitals. The cohort size is underpowered for meaningful statistical comparison. The cohort was generated during the COVID-19 pandemic. Conclusions/Discussion: Patients with early onset colorectal cancer are referred for colonoscopic or imaging diagnostics through their primary care doctors, followed by the Emergency Department. Non-white patients, compared to other groups, access the healthcare system through the ED. However, whether this observation is due to the absence of a PCP access, due to restricted screening/diagnostic guidelines, or due to colonoscopic provider availability is unclear. Hispanic patients are disproportionately represented in our early onset cohort relative to the demographics of the hospital referral base. While the study is underpowered, it is provocative for requiring further investigation. Resources to heighten the suspicion for malignancy in patients presenting to our emergency departments and primary care offices, especially in young, non-white populations, may expedite access to diagnosis and definitive therapy for these patients. (Figure Presented).
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 29 million people and has caused more than 900,000 deaths worldwide as of September 14, 2020. The SARS-CoV-2 human cell receptor ACE2 has recently received extensive attention for its role in SARS-CoV-2 infection. Many studies have also explored the association between ACE2 and cancer. However, a systemic investigation into associations between ACE2 and oncogenic pathways, tumor progression, and clinical outcomes in pan-cancer remains lacking. Using cancer genomics datasets from the Cancer Genome Atlas (TCGA) program, we performed computational analyses of associations between ACE2 expression and antitumor immunity, immunotherapy response, oncogenic pathways, tumor progression phenotypes, and clinical outcomes in 13 cancer cohorts. We found that ACE2 upregulation was associated with increased antitumor immune signatures and PD-L1 expression, and favorable anti-PD-1/PD-L1/CTLA-4 immunotherapy response. ACE2 expression levels inversely correlated with the activity of cell cycle, mismatch repair, TGF-ß, Wnt, VEGF, and Notch signaling pathways. Moreover, ACE2 expression levels had significant inverse correlations with tumor proliferation, stemness, and epithelial-mesenchymal transition. ACE2 upregulation was associated with favorable survival in pan-cancer and in multiple individual cancer types. These results suggest that ACE2 is a potential protective factor for cancer progression. Our data may provide potential clinical implications for treating cancer patients infected with SARS-CoV-2.