Examining Colorectal Cancer (CRC) Stage at Initial Diagnosis Before and During the COVID-19 Pandemic in the United States

Introduction: Colorectal Cancer (CRC) is on the rise, prompting the need for earlier screening in the United States (U.S.) population. The American Cancer Society now recommends screening for CRC in patients with average risk at the age of 45. Further complicating this picture, the COVID-19 pandemic has disrupted the routine screening process for CRC, which we hypothesize has impacted the stage at which CRC is detected. We sought to determine the extent to which the COVID-19 pandemic has affected colorectal cancer diagnosis trends at a large urban community hospital. Method(s): We performed a retrospective analysis of patients, comparing two time periods: pre-pandemic (1/1/2019-1/31/2020) and during COVID pandemic (2/1/2020-9/29/21). Data was extracted from the electronic medical record (EMR) to compile a database of patients diagnosed with CRC during these time periods. Patients included in this study had a new diagnosis of colorectal cancer and either followed with colorectal specialists at the hospital or had undergone tissue biopsy analysis by the Department of Pathology. The primary outcome was determining the stage at which CRC was detected and the modality utilized for CRC screening in that patient. Additional variables collected were as follows: age, pathological findings (grade, presence of tumor mutations, or microsatellite instability), gender, race, and insurance. Result(s): Data was collected from a total of 380 patients, which included 190 patients diagnosed with CRC within the timeframe defined as pre-pandemic and 190 diagnosed with CRC within the timeframe defined as during the pandemic. CRC diagnosis was analyzed in terms of TNM stage at time of diagnosis (Stages 0 through IV). Stage III and IV were grouped together and categorized as a late-stage diagnosis, whereas Stages 0, I, and II were grouped together and categorized as an early-stage diagnosis. Late-stage diagnosis was found in 34.7% (66/190) of patients in the pre-pandemic group. In comparison, late-stage diagnosis was found in 46.3% (88/190) of patients in the during pandemic group. Conclusion(s): Our results suggest that the COVID-19 pandemic did produce delays in care and work-up for CRC. We believe this is why CRC stage at the time of initial diagnosis was later for patients diagnosed during the pandemic than for patients diagnosed prior to the pandemic. In the future, we hope to evaluate if the impact of COVID-19 is reflected in tumor grade and genetic mutations at the time of diagnosis, and determine race and gender disparities.

Correlation between Ptt and Thromboelastography in Adult Icu Patients Requiring Bivalirudin for Ecmo

INTRODUCTION: Bivalirudin remains a viable strategy during extracorporeal membrane oxygenation (ECMO). The accuracy of activated partial thromboplastin time (aPTT) for bivalirudin intensity in ECMO may be imperfect resulting in suboptimal dosing, which may increase the risk of bleeding or thrombotic complications. The purpose of this study was to evaluate the correlation between PTT and thromboelastography (TEG) reaction (R) time in adult ECMO patients anticoagulated with bivalirudin. METHOD(S): This was a multicenter, retrospective study conducted over a 22-month period (January 2020 to October 2021. Adult ICU patients requiring ECMO and bivalirudin therapy with >=1 corresponding TEG and aPTT samples drawn <=4 hours of each other were included. The primary endpoint was to determine the correlation coefficient between the TEG R time and bivalirudin aPTT serum concentrations. Pearson's correlation coefficient was used to evaluate the correlation using a kappa measure of agreement between TEG results and bivalirudin aPTT serum concentrations. RESULT(S): A total of 104 patients consisting of 848 concurrent laboratory assessments of R time and aPTT were included. COVID-19 positive tests were confirmed in 48.1% (n=50) of included patients. A moderate correlation between TEG R time and aPTT was demonstrated in the study population (r=0.41;p< 0.001). A similar relationship between TEG R time and aPTT was observed in both COVID-19 positive (r=0.44;p< 0.0001) and negative (r=0.45;p< 0.0001). Overall, 59.2% of all concurrent TEG R time and aPTT values showed agreement on the study institution's therapeutic category (sub-, supra-, and therapeutic) of bivalirudin. 78.3% (n=277) of aPTT values were categorized as therapeutic among all discordant assessment (n=346) between TEG R time and aPTT. The discordant TEG R times with a therapeutic PTT were almost equally distributed between subtherapeutic and supratherapeutic categories. CONCLUSION(S): Moderate correlation was found between TEG R time and aPTT associated with bivalirudin during ECMO in critically ill adults. Further research is warranted to address the optimal test to guide clinical decision-making for anticoagulation dosing in ECMO patients with discordant results.

Monitoring of Heparin Anticoagulation in Adult Patients with Severe Covid

INTRODUCTION: Severe COVID increases the risk of thrombotic complications. Therapeutic anticoagulation with unfractionated heparin (UH) is commonly utilized to prevent venous thromboembolism (VTE). Thromboelastography (TEG) provides a dynamic and global assessment of hemostasis, which may be advantageous or complimentary with standard coagulation tests like anti-Xa activity or activated partial thromboplastin time (aPTT). The purpose of this study was to evaluate the correlation between anti-Xa activity and aPTT with the TEG parameters of reaction (R) time and coagulation index (CI) in patients with severe COVID receiving UH. METHOD(S): This was a single-center, retrospective study conducted over a 15-month period (2020-2021). Adult patients with severe COVID receiving UH with >=1 corresponding TEG and anti-Xa / aPTT samples assessed <=2 hours of each other were included. The primary endpoint was the correlation between anti-Xa activity and R time. Additional associations were determined for aPTT and R time and anti-Xa activity and aPTT with CI. Pearson's coefficient was used to evaluate the correlation using a kappa measure of agreement. RESULT(S): A total of 423 assessments across 237 patients were included. R time did not correlate with anti-Xa activity (r2=0.032;p< 0.0001) nor aPTT (r2=0.007;p=0.061). CI did not correlate with anti-Xa activity (r2=0.093;p< 0.0001) nor aPTT (r2=0.017;p=0.0073). Overall, 188 (45%) R times and anti-Xa values showed agreement in terms of both demonstrating therapeutic anticoagulation, sub-therapeutic anticoagulation, or supra-therapeutic anticoagulation. Twentyeight patients (11.8%) and 21 patients (8.9%) developed a clinically relevant bleed or VTE, respectively, but all coagulation and TEG parameters were similar between those with a bleed or VTE and those without. CONCLUSION(S): The TEG parameters of R time and CI did not correlate with anti-Xa activity or aPTT for monitoring of intensity of anticoagulation with UH in patients with severe COVID-19. Using TEG in these patients to monitor UH anticoagulation offers no benefit over anti-Xa activity or aPTT. Further research is necessary to address the laboratory tests needed to help with decision-making on anticoagulation dosing in patients with severe COVID.

REDUCED SEROLOGICAL RESPONSE TO COVID-19 VACCINES IN PATIENTS WITH IBD IS FURTHER DIMINISHED BY TNF INHIBITOR THERAPY;EARLY RESULTS OF THE VARIATION STUDY (VARIABILITY IN RESPONSE IN IBD AGAINST SARS-COV2-IMMUNISATION)

Objective: Patients with inflammatory bowel disease (IBD) have attenuated responses to current vaccinations. There is a limited body of evidence suggesting patients with IBD receiving TNF antagonists have an attenuated response to vaccination against COVID-19. We sought to determine the impact of IBD and various medications for the treatment of IBD on antibody responses to vaccination against COVID-19. Design: Patients with IBD (n=270) and healthy controls (HC, n=116) were recruited prospectively and quantitative antibody responses assessed following COVID-19 vaccination. The impact of IBD and medications for treatment of IBD on vaccine response rates was investigated. Results: All HC seroconvert post complete vaccination with two vaccine doses [100%]. A small proportion of patients with IBD failed to seroconvert [2%]. Median anti-spike protein (SP) immunoglobulin (Ig)G levels post one vaccination and complete vaccination in our IBD cohort was significantly lower than HC [2,613 AU/mL versus 6,871 AU/mL, p=<0.001] [Figure 1]. A diagnosis of IBD was independently associated with lower anti-SP IgG levels [β coefficient -0.2, p = 0.001] whereas use of mRNA vaccines was independently associated with higher anti-SP IgG levels [β coefficient 0.25, p = < 0.001]. Patients with IBD receiving anti-TNF therapy had significantly lower anti-SP IgG levels [2444.6 AU/mL] than IBD patients not receiving these agents [3867.6 AU/mL] [p = < 0.001]. Patients with IBD not receiving TNF inhibitors still showed attenuated responses compared to HC receiving a similar vaccine [p = 0.001] [Figure 2]. 58 patients had an additional follow-up serology sample at a median of 12 weeks to complete vaccination to allow assessment of the durability of the response after their initial post-vaccination IgG level. There was a significant drop in IgG levels from 3952.85 AU/mL at the first timepoint checked post-complete vaccination to 921.1 AU/mL (343.1 – 2102.7) on follow-up sampling (p = <0.001). Median anti-SP IgG levels were numerically lower in our cohort receiving anti-TNF therapy (794.8 AU/mL) compared to those not receiving anti-TNF therapy (3136.9 AU/mL) on final follow-up samples (p =0.28). HC participants with previous COVID-19 infection (n= 5) had significantly higher anti-SP IgG levels post complete vaccination (20,719.6 AU/mL) compared to IBD patients (n=4) with prior infection (3,938.2 AU/mL) (p = < 0.001). Conclusions: Patients with IBD have attenuated serological responses to SARS-CoV-2 vaccination. Patients with IBD who do not seroconvert post-vaccination against COVID-19 are a particularly vulnerable cohort. Use of anti-TNF therapy negatively impacts anti-SP IgG levels. Impaired responses to vaccination in our study highlights the importance of booster vaccination programmes for patients with IBD. (Figure Presented) Differences in median IgG levels across three time points (Figure Presented) Differences in median anti-SP Levels dependent on medication for treatment of IBD.

COVID-19 infection masquerading as inflammatory bowel disease

Introduction: Although COVID-19 infection has been associated with GI manifestations like nausea, vomiting, diarrhea, and even transaminitis, there is no known association between this virus and inflammatory bowel disease (IBD). Here we present the case of COVID-19 infection masquerading as IBD. We describe the instance of a COVID-19 patient with hematochezia, found to have histological changes similar to IBD on colon biopsy. Case Description/Methods: A 70 year-old female with PMH of HTN, DM, CAD, COPD, and recently diagnosed poorly differentiated colonic adenocarcinoma with signet ring features (statuspost hemicolectomy and chemotherapy), presented to the ED with hypotension in the setting of nausea, vomiting, and diarrhea for 5 days. Patient had been started on chemotherapy two weeks prior and was found to have a blood pressure of 76/53, but was afebrile with no signs of tachycardia or hypoxia. Labs were significant for a white blood cell count of 0.67 (absolute neutrophil count 247), platelets of 115, lactate of 0.9, potassium of 6.2, BUN/creatinine of 88/5.6, and CRP of 20.78. COVID- 19 PCR was positive. Abdominal CT identified non-specific ileitis, and GI was consulted due to concern for neutropenic enteritis and ileus. During the hospital stay, she developed hematochezia with a drop in hemoglobin. C. diff and GI PCR were negative. A colonoscopy was performed which showed patchy areas of edema, erythema, and ulceration (Figure 1B). Colon biopsies revealed crypt abscesses, consistent with IBD (Figure 1C). However, prior colonoscopy 4 months ago, which identified colon cancer, did not find any evidence of IBD (Figure 1A). Patient clinically declined, ultimately dying of acute hypoxic respiratory failure. Discussion: Given this patient's age and the fact that she had previously had a colonoscopy that did not show evidence of crypt abscesses, it is unlikely she developed a new diagnosis of inflammatory bowel disease in the interim. It is more likely that the crypt abscesses noted on colon biopsy were due to COVID-19 infection. One study found that of 651 patients with COVID-19, 11.4% exhibited GI symptoms, most often developing acute gastritis or enteritis. We present this case to raise awareness of an unprecedented phenomenon in COVID-19 infection .

Pillcam eso capsule: An alternative diagnostic tool during the covid-19 pandemic. first irish experience

Introduction: The Covid-19 pandemic has led to unprecedented endoscopy practice. At the peak of the pandemic in Ireland, many routine and surveillance endoscopies were deferred, with only urgent procedures prioritised. To allow safe and effective upper gastrointestinal investigations continue, alternative modalities were explored. HSE national guidance document for safe endoscopy in pandemic conditions recommends that alternative non-invasive investigation be considered for all non-urgent referrals for endoscopy. The PillCam ESO® (Given Imaging Ltd., Yoqneam, Israel) offers such an alternative for evaluation of the UGI tract. We conducted a prospective analysis of PillCam ESO® as an alternative diagnostic tool during the Covid-19 pandemic to help tackle the increasing waiting list for gastroscopy at our unit. Aims & Methods: The Aim was to assess if the PillCam ESO can identify important anatomical landmarks as stated in the British Society of Gastroenterology quality standards for upper gastrointestinal endoscopy and if it can effectively identify pathology in the Upper GI Tract. Methods: Patients who fitted our inclusion criteria were prospectively invited to participate into our trial. The three main indications were: 1. Patients with dyspepsia less than 40 years of age with no red flag symptoms, 2. Known cirrhosis to screen for varices, 3. UGI bleeds with a low Blatchford score (≤2). A local protocol for ingestion and series of positional guidelines was developed for the procedure. Ethical approval was granted for this study. Capsule transit time, endoscopic landmarks, and pathology detection were evaluated by two independent endoscopists. Results: 66 exams have been successfully performed in the GI Lab from June 2020 to date without complications. The two frequent indications were dyspepsia (66%) and abdominal pain (24%). IM Metoclopramide was administered in 52% of cases. Complete visualisation of the following major anatomical landmarks was achieved in 100% of cases: Oesophagus, Oesophageal-gastro junction, and Gastric. A full view of the cardia, fundus, greater curve, lesser curve, incisura angularis, antrum, pylorus, and second part of Duodenum was obtained in 99%, 94%, 99%, 97%, 97%, 92%, 91%, and 80% of cases, respectively. D2 intubation was achieved in 80% of cases. The mean capsule transit times was 62 mins (SD 28). A normal exam was reported in 41% of cases. Reflux oesophagitis and gastritis were the most common pathology detected. Adenocarcinoma of the OG junction was detected in 1 case. Conclusion: The PillCam ESO achieves excellent views of the upper GI tract. In selective cases, it is a safe alternative to gastroscopy which may help reduce gastroscopy waiting times.

COVID-related anxiety is prevalent and accurately reflects serious COVID risks in breast cancer patients

Background: A current cancer diagnosis is a risk factor for serious COVID-19 complications (CDC). In addition, the pandemic has caused major disruptions in medical care and support networks, resulting in treatment delays, limited access to doctors, worsening health disparities, social isolation;and driving higher utilization of telemedicine and online resources. Breastcancer.org has experienced a sustained surge of new and repeat users seeking urgent information and support. To better understand these unmet needs, we conducted a survey of the Breastcancer.org Community. Methods:Members of the Breastcancer.org Community were invited to complete a survey on the effects of the COVID-19 pandemic on their breast cancer care, including questions on demographics, comorbidities (including lung, heart, liver and kidney disease, asthma, diabetes, obesity, and other chronic health conditions);care delays, anxiety due to COVIDrelated care delays, use of telemedicine, and satisfaction with care during COVID. The survey was conducted between 4/27/2020-6/1/2020 using Survey Monkey. Results were tabulated and compared by chi square test. A p-value of 0.05 is considered significant. Data were analyzed using Stata 16.0 (Stata Corp., Inc, College Station, TX). Results: Our analysis included 568 breast cancer patients of whom 44% had ≥1 other comorbidities associated with serious COVID-19 complications (per CDC) and 37% had moderate to extreme anxiety about contracting COVID. This anxiety increased with the number of comorbidities (p=0.021), age (p=0.040), and with a current breast cancer diagnosis (p=0.011) (see table). Anxiety was significantly higher in those currently diagnosed, ≥65, or with ≥3 other comorbidities, compared to those diagnosed in the past, age <44, or without other comorbidities. Conclusions: Our survey reveals that COVID-related anxiety is prevalent at any age regardless of overall health status, but it increased with the number of other comorbidities, older age, and a current breast cancer diagnosis. Thus, reported anxiety is proportional to the risk of developing serious complications from COVID. Current breast cancer patients of all ages-especially with other comorbidities-require emotional support, safe access to their providers, and prioritization for vaccination. (Table Presented).

The impact of sars-cov-2 on the irish national colorectal cancer screening programme: A report from two high-volume endoscopy centres

Aims The Irish National BowelScreen programme paused activities in March 2020 to prioritise the emergency response tothe SARS-CoV-2 pandemic. As a result, patients with positive fecal immunochemical test (FIT) results that had already beenreturned, experienced delays in time to colonoscopy. The standard lead time in BowelScreen is 20 working days. The aim ofthis study was to examine the impact of this delay on time to colonoscopy for index FIT positive cases in two tertiaryendoscopy units. Methods Index cases affected by the pause which were subsequently completed (up to July 2020) were analyzed andcompared to the same period in 2019. All colonoscopy's were performed by a BowelScreen accredited consultantendoscopist. Endoscopy and histology data was obtained from the BowelScreen database and patient records. Results In total, 111 colonoscopies were performed during the study period. During the same period in 2019, 226 indexcolonoscopies were completed. The median lead time in 2020 was 38 working days, or almost double the recommendedlead time. The median age in 2020 was 66.5 years (IQR 60-70) and in 2019 63 years (IQR 60-70). Men accounted for 55 %of patients in 2020 and 66 % in 2019. A total of 191 polyps were detected in the 2020 group, 16 % of which were advanced adenomas (adenoma ≥ 10mm). There were 394 polyps identified in the 2019 group, 16 % of which were advancedadenomas. The majority of these advanced adenomas (77 % in 2020 and 90 % in 2019) were left sided. High gradedysplasia was detected in one polyp in 2020 and in five in 2019. There were 3 cancers detected in 2020 and 11 in 2019. Conclusions There was a significant delay in lead time to index colonoscopy for FIT positive patients in BowelScreen.Despite this, the two groups had comparable advanced adenoma and cancer pathology detection rates.

Pillcam ESO capsule, an alternative diagnostic tool during the COVID-19 pandemic. firstirish experience

Aims At the peak of the Covid-19 pandemic in Ireland, many routine and surveillance endoscopies were deferred, with onlyurgent procedures prioritised. The PillCam ESO (Given Imaging Ltd., Yoqneam, Israel) is a non-invasive investigation, whichoffers an alternative method of evaluating the UGI tract for non-urgent referrals for endoscopy. A prospective study to assess if the PillCam ESO can identify important anatomical landmarks stated in the British Societyof Gastroenterology quality standards for upper gastrointestinal endoscopy and pathology in the Upper GI Tract. Methods Patients who fitted our inclusion criteria were prospectively invited to participate into our trial. The three main indications were 1;patients with dyspepsia less than 40 years of age with no red flag symptoms, 2;knowncirrhosis to screen for varices, 3;UGI bleeds with a low Blatchford score (≤2). A local protocol for ingestion and series of positional guidelines was developed for the procedure. Endoscopic landmarks, and pathology detection were evaluated by two independent endoscopists. Results 32 exams have been successfully performed from June 2020 to date without complications. The two frequentindications were dyspepsia (66 %) and abdominal pain (19 %). Metoclopramide was administered in 66 % of cases. Visualisation of the following major anatomical landmarks was achieved in 100 % of cases: Oesophagus, oesophageal-gastro junction, greater curve, pylorus. A full view of the cardia, fundus, lesser curve, incisura angularis and antrum was obtained in 97 %, 87 %, 93 %, 97 % and97 % of cases, respectively. D2 intubation was achieved in 90 % of cases. A normal exam was reported in 34 % of cases.Reflux oesophagitis and gastritis were the most common pathology detected. Adenocarcinoma of the OG junction wasdetected in 1 case. Conclusions The PillCam ESO achieves excellent views of the upper GI tract. In selective cases, it is a safe alternative togastroscopy which may help reduce gastroscopy waiting times.

Air on the side of caution: A case of gastric emphysema

INTRODUCTION: Gastric pneumatosis, the presence of intramural gas in the stomach, is a rare but alarming radiographic finding. Gastric emphysema (GE) and emphysematous gastritis remain the two most important differential diagnoses of gastric pneumatosis, both differing vastly in their management and prognosis. Due to these differences, it is essential to reach an accurate clinical diagnosis early. Here we describe the case of a young male with GE due to severe gastroparesis from uncontrolled diabetes. CASE DESCRIPTION/METHODS: A 36 year-old COVID-19 positive male with a history of uncontrolled Type 1 Diabetes, Hepatitis C, and Hirschsprung disease presented with generalized weakness, fatigue, polyuria, and polydipsia for two days. Laboratory work revealed diabetic ketoacidosis which improved with intravenous (IV) fluids and insulin. However, his course was complicated by persistent nausea, inability to tolerate oral diet, abdominal distension, and worsening leukocytosis. Computed Tomography (CT) of the abdomen demonstrated a markedly distended stomach containing air and undigested food, air in the gastric wall, gas and thrombus in the left portal vein, and pancolitis. He remained afebrile, hemodynamically stable with negative blood cultures and was initially treated conservatively with fluconazole and piperacillin-tazobactam, nasogastric suction and supportive care. Repeat CT of the abdomen two days later showed improvement in gastric pneumatosis and portal venous gas. Subsequent EGD revealed retained gastric contents, an open pylorus, and large necroticappearing ulcerations extending most of the lesser curvature and fundus of the stomach. These findings were consistent with GE, likely a chronic issue from longstanding gastroparesis. However microvascular thrombi related to COVID remain on the differential as there is a known propensity for a procoagulable state in these patients. DISCUSSION: GE can be due to an increase in intraluminal pressure or mucosal injury that leads to intramural gas formation. In our patient, we suspect his GE was due to uncontrolled diabetes, causing severe gastroparesis and gastric wall distention. GE is benign and managed with observation and conservative treatment. Comparatively emphysematous gastritis is often associated with systemic toxicity, is potentially fatal, and often requires more aggressive therapy including surgery. As in the majority of GE cases, our patient's symptoms improved with conservative treatment and follow-up imaging revealed interval improvement.