bluuebunny/crossref_metadata_2025 huggingface dataset:
127 The Epidemiology of Colorectal Cancer in Chronic Kidney Disease in the U.S.: A Population-Based Study (2014–2019)
Authors: Abureesh Mohammad , Alkhayyat Motasem , Saleh Mohannad Abou , Deeb Liliane
Published: October 2019

INTRODUCTION:

Recent studies have shown an association between chronic kidney disease (CKD) and increased risk of developing cancer. Limited data is available regarding the prevalence of colorectal cancer (CRC) in patients with CKD. Using a large database, we sought to evaluate this potential risk association.

METHODS:

We reviewed data from a commercial database (Explorys Inc, Cleveland, OH, USA) that provided electronic health records from 26 major integrated US healthcare systems. Based on the Systematized Nomenclature of Medicine—Clinical Terms (SNOMED-CT), we identified a cohort of patients with a diagnosis of CRC without CKD, from 2014–2019, which served as a control group. Similarly, we identified a cohort of patients with SNOMED-CT diagnosis of first ever with CRC after at least one year of CKD diagnosis. We performed analyses to describe distributions based on age, gender, and race, as well as to evaluate underlying risk factors.

RESULTS:

Of the 36,770,450 individuals in the database (2014–2019), 1,359,450 had the diagnosis of CKD (3.69%) and 1,438,540 (3.91%) had the diagnosis of CRC. Amongst CKD patients, 73520 (5.4%) individuals had a first ever diagnosis of CRC after at least one year of being diagnosed with CKD. When compared to individuals without a history of CKD, CKD patients were more likely to develop CRC [OR: 1.76; 95% CI 1.74–1.77, P < 0.0001]. Individuals with CKD and CRC were more likely to be males [OR: 1.21; 95% CI 1.19 to 1.23, P < 0.0001], elderly (age >65) [OR: 3.62; 95% CI 3.55 to 3.69, P < 0.0001], and African American [OR: 2.34; 95% CI 2.30 to 2.38, P < 0.0001]. They were also more likely to be smokers [OR: 1.38; 95% CI 1.36 to 1.41, P < 0.0001], diabetic [OR: 5.04; 95% CI = 4.96 to 5.11, P < 0.0001], and with history of IBD [OR: 1.32; 95% CI 1.27 to 1.38, P < 0.0001], obesity [OR: 2.55; 95% CI 2.49 to 2.56, P < 0.0001] and exposure to radiation [OR: 1.14; 95% CI 1.09 to 1.19, P < 0.0001] when compared to individuals without CKD (Figure 1).

CONCLUSION:

This population-based cohort study indicated a possible increase of 19.2% in the prevalence of CRC in patients with CKD compared to those without CKD. This may be due to either an increased utilization of the health care system by CKD patients or another unknown confounding factor or even a true association. Given the limitations of our study due to the risk of confounding bias in the database and lack of endoscopic and histological data, this association needs to be confirmed in further studies.
142 Targeting MLH-1 Gene of Colorectal Cancer Cell Line Develop From Patient of Cipto Mangunkusumo National Hospital by CRISPR CAS9 for Genome Editing
Authors: Abdullah Murdani , Syam Ari Fahrial , SImadibrata Marcellus , Meilany Sofy , Annisa Firda , Ramadhan Dimas , Makmun Dadang , Rani Abdul Aziz
Published: October 2019

INTRODUCTION:

The mismatch repair genes as MLH-1 facilitate the cells to detect and repair bases mismatch that oftenly occur during replications process. Mutations of MLH-1 genes may be inherited and increase the risk for the related person to develop severals tumors including colorectal cancer. The development of gene therapy in the recent decades arise ideas in developing experimental gene editing using CRISPR-Cas9 to the hereditary colorectal cancer patients primary cells. The objective of this study is to apply the CRISPR-Cas9 MLH-1 editing technology to primary cells of colorectal cancer primary cells from hereditary colorectal cancer patient stage 4.

METHODS:

The cells from patient biopsy with diagnosis colorectal cancer with mucinous type, the cells were extracted using Collagenase Type I and cultured in Fibroblast Growth Medium for several passages. The cells were then plated in 96-well culture plate. For genome editing we use ribonucleoprotein (RNP) consisting of Alt-R S.p. Cas9 nuclease in complex with Alt-R CRISPR-Cas9 guide RNA. We design this sg RNA targetted MLH-1 sequence using USCS genome browser. The cells then transfected with MLH-1 CRISPR-Cas9 using DMERIC reagent according to the manufacture protocols for 48 hours. After incubations, the cells were harvested. The DNA were isolated using TriZol reagent. Analysis of mutation MLH-1 were using T7E1 enzyme and primers were checked afterwards.

RESULTS:

From our study we found that efficiency of introduction of complex Alt-R S.p. Cas9 nuclease in complex with Alt-R CRISPR-Cas9 guide RNA only 40% from total cells, the analysis was performed using Tali Cytometri. For amplification and analysis of Nickase gene was using T7E1 for primary cells of colorectal cancer primary cellswe found that this gene was amplified. From this finding this methods might be alternative therapy for colorectal cancer.

CONCLUSION:

Colorectal cancer result from progressive accumulation of multiple genetic and epigenetic aberrations within cells. The progression from colorectal adenoma to carcinoma is caused by three major pathways: microsatellite instability, chromosomal instability and CpG island methylator phenotype. Until now in Indonesia we still cannot define which pathway are the most common. This study we try to find out response of MLH 1 gene editing using CRISPR Cas 9. From our result we found that MLH 1 gene were able to mutated by using T7E1 assay and it was confirmed using Sanger Sekuensing.
143 ATLAS Scores Are Better Than CDSS in Predicting Any ICU Requirement and 30-Day Mortality in Patients With C. difficile Infection (CDI) >65 Years Old
Authors: Malik Umer E. , Gnanapandithan Karthik , Sharma Prabin , Mansoor Muhammad Sohail , Feuerstadt Paul
Published: October 2019

INTRODUCTION:

CDI is the most common healthcare-associated infection with significant morbidity, mortality and cost. Various scoring systems have been formulated to aide disease prognostication. Our goal was to compare the ATLAS and CDSS predictive scores, initially to validate them and subsequently establishing which score was more accurately associated with short-term mortality and colectomy.

METHODS:

We performed a retrospective cohort analysis on patients admitted to Yale-New Haven Hospital between 9/13 and 4/16. For each patient with CDI (≥3 liquid stools in a 24-hour period with a positive stool assay) we gathered various data points including demographics, diagnostics, risk factors, treatments and outcomes. The CDSS and ATLAS scoring systems were independently used to grade the severity in each patient and association with outcome (e.g., any ICU admission or 30-day mortality). Using Logistic regression (SAS 9.4), we used area under the ROCs to compare the ability of CDSS and ATLAS to predict adverse outcomes in these patients. Following initial analysis, we performed a sub-group analysis considering a cohort > 65 years old and those ≤65.

RESULTS:

488 patients were identified with CDI; 105 were excluded due to insufficient retrospective data to complete the ATLAS score. The mean age was 65.1 ± 16.1 years with females accounting for 52.7%. Mean Charlson co-morbidity score was 5.8 ± 3.1. 20.1% had prior CDI and 81.5% received antibiotics in the prior 12 weeks. Of 383 pts, 40 (10.4%) died and 122 (31.8%) required ICU admission during their stay. Both ATLAS and CDSS independently predicted adverse outcomes in these pts. In our overall cohort (all ages), there were no significant differences between the two scores in predicting 30-day mortality (Figure 1, P = 0.37), however ATLAS performed significantly better predicting ICU requirement (Figure 1, P = 0.0002). When considering only those > 65 years, ATLAS performed significantly better than CDSS for 30-day mortality (Figure 2, P < 0.05) and any ICU requirement (Figure 2, P < 0.01). For those ≤65, ATLAS was significantly more accurate at predicting ICU admission (P < 0.001) but not mortality (P = 0.92).

CONCLUSION:

CDI is associated with severe outcomes and prediction of these outcomes could help triage therapeutic decisions. ATLAS is superior to CDSS in prediction of ICU stay in our patient population with CDI and ICU/mortality in age >65. We recommend strong consideration for usage of ATLAS in clinical practice.
148 Rate of Antibiotics Prescribed for Patients With Acute Diarrheal Illness and a Positive Stool Test in Immunosuppressed Versus Non-Immunosuppressed Patients
Authors: Ziv Yonatan , Ho Tai Hang , Szymczak Wendy A. , Kwah Joann , Gendlina Inessa
Published: October 2019

INTRODUCTION:

Historically, the diagnostic yield of stool culture in patients with acute diarrheal illness (ADI) is very low. As such, the decision to administer antibiotics is usually guided by history of exposures, symptoms, and the degree of immune-competence. The advent of a gastrointestinal (GI) pathogen PCR panel offers a sensitive and rapid identification of various GI pathogens but its heuristic relevance in antibiotic stewardship for immunosuppressed patients is unknown. We aimed to compare the rate of antibiotics prescribed for ADI with positive GI pathogen PCR panel results in immunosuppressed and non-immunosuppressed patients.

METHODS:

Patients who presented to Montefiore Medical Center with an ADI with a positive GI pathogen PCR panel between April 2018 and November 2018 were identified. Data collected included patient demographics, toxic habits, and previous antibiotic and steroid use within 6 months prior to the ADI. Immunosuppressed patients were identified as having either HIV/AIDS, a history of organ transplant, active hematologic malignancy, primary immunodeficiency disease or current use of immunosuppressive medications. We excluded patients with C. difficile given its confounding effect on the rate of antibiotic administration. The primary outcome was whether antibiotics were prescribed for the ADI empirically as well as in response to a positive GI pathogen PCR panel result.

RESULTS:

Out of 472 patients, 102 patients (21.6% of the cohort) were identified as being immunosuppressed (Table 1). There was no significant difference in the rate of empiric antibiotic use between immunosuppressed and non-immunosuppressed patients with ADI (12.2% vs 10.8%, P = 0.181) (Table 2). There was also no significant difference in the rate of antibiotic use in response to a positive GI pathogen PCR panel result (49% vs 38.9%, P = 0.182).

CONCLUSION:

The ability to tailor treatment to a specific pathogen in patients with ADI does not appear to make a significant difference in the rate of antibiotic use when accounting for patients' immune-competence. As certain pathogens warranting treatment tend to be more common in immunosuppressed patients, the implications on clinical outcomes and cost effectiveness of the GI pathogen PCR panel requires further study.
169 Genetic Counseling Follow-Up Rates After Positive Lynch Syndrome Universal Tumor Screening: A Quality Assessment
Authors: Shah Ayush N. , Gampa Anuhya , Tjaden Jamie , Khan Omar , DePersia Allison
Published: October 2019

INTRODUCTION:

Lynch syndrome (LS) is the most common inherited cause of colorectal (CRC) and endometrial cancer (EC) worldwide. Universal tumor screening (UTS) for LS is recommended in all CRC/EC patients via microsatellite instability (MSI) or immunohistochemistry (IHC) testing for the absence of mismatch repair proteins. Patients with positive UTS should be referred for genetic counseling (GC) and testing. At our institution, UTS is performed for all patients with CRC or EC, and the result is reported as an addendum on pathology reports and as a separate file. The proceduralist (surgeon or gastroenterologist) is responsible for referring positive UTS patients to GC. But, many are lost to follow-up. Historically, a secondary reminder was sent to the proceduralist by the genetic counselor to encourage GC for patients with positive UTS. This workflow was not executed 6/2017–9/2018. Our quality initiative aims to evaluate how modifications in the UTS workflow (with or without a secondary reminder) affected patient follow-up and determine the best approach for future UTS follow-up.

METHODS:

Cases reviewed 6/24/17–9/12/18 that underwent UTS for CRC/EC. These patients did not have a secondary GC reminder. UTS positive patient charts were analyzed to see: 1. if a GC referral was placed or recommended in the progress note, 2. if GC follow-up was completed and 3. if genetic testing was completed. Rates of patients with appropriate referrals and genetic testing were calculated. These were compared to historical results 2010–2017 when the UTS workflow included secondary reminders.

RESULTS:

Of the 239 patients with CRC/EC without a secondary reminder, 63 (26.4%) screened positive. Of the 63 patients, 29 (46%) had a referral ordered, 9 (14.3%) had GC recommended by the provider in the progress note, 27 (43.9%) had both a referral and documentation in a progress note. 40 (63.5%) of the 63 patients had one or both modes of GC referrals. 21 (33.3%) of the 63 followed up with GC. Of the 21, 20 (95.2%) had genetic testing. The historical rate of presentation to GC following positive UTS when a secondary reminder was part of the workflow was 89/192 (46.4%).

CONCLUSION:

33% of CRC/EC patients with positive UTS followed up with GC during the current UTS workflow compared to 46% when a secondary reminder was sent to the proceduralist by the genetic counselor. Implementing a standardized approach for follow-up of patients with positive UTS that includes genetic counselor reminders improves GC rates for LS in CRC/EC patients.
180 Association of Helicobacter pylori (HP) Infection With Advanced Adenomas of the Colon
Authors: Peysin Konstantin , Chaudhury Samiran Roy , Choudhry Mohammad K. , Debesai Meron , Haghi Masoud , Ekeledo Baron , Holloway Jamila , Bernstein Michael
Published: October 2019

INTRODUCTION:

HP has long been recognized as a carcinogen due to its association with gastric neoplasia. Recently, the link between HP and colonic dysplasia has been studied with results suggesting an association between the two entities. Despite the steady fall of colon cancer rates with the routine utilization of colonoscopy, rates of advanced disease diagnosed before age 50 are increasing. This leaves room for additional tools to help identify patients at risk for colonic dysplasia. We aim to further investigate the association of colonic dysplasia and HP.

METHODS:

IRB approved, single center, retrospective chart review of patients who underwent a colonoscopy, within one year of an esophagogastroduodenoscopy (EGD) with gastric biopsy, between January 2010 and December 2018 at Coney Island Hospital. Exclusions included age < 18, incomplete colonoscopy, inflammatory bowel disease, polyposis syndromes, personal history of colon cancer, prior polypectomy or HP eradication prior to the study window. For each patient, we noted age, sex, BMI, HP status, total number of polyps, adenomas, advanced adenomas, serrated polyps, colorectal cancer, smoking, diabetes, and alcohol history. Advanced adenomas were defined as >1 cm and/or containing a villous component and/or containing high grade dysplasia.

RESULTS:

A total of 3175 patients had a colonoscopy within one year of an EGD during the study window. Of these, 1786 were included after chart review. 471 (26%) patients were < 50 years old. There were 654 (37%) HP positive patients. Groups were well matched for BMI, diabetes, alcohol abuse and smoking history (Figure 1). Patients with HP infection were found to have a statistically significant difference in rates of advanced adenomas (6.4% in HP-positive patients vs. 3.5% in HP-negative patients, P = 0.004). There were no statistically significant differences between the two groups for all polyps (33% vs 31%, P = 0.22), all adenomas (25% vs 23%, P = 0.21) and adenocarcinoma (1.2% vs 1.3%, P = 0.52). Patients <50 years old showed a trend towards more advanced adenomas (2.7% vs 1.4%, P = 0.102).

CONCLUSION:

Patients with HP infection were twice as likely to have an advanced adenoma on index colonoscopy. This trend continued in patients <50 years old without reaching statistical significance. Advanced adenomas are a significant risk factor for adenocarcinoma. This data makes a case for including HP status as a risk factor for colorectal carcinoma and may suggest the need for earlier screening in affected patients.
181 Long Noncoding RNAs (lncRNAs) Are Different in Polyps of Obese and Lean Suggesting Different Pathophysiology
Authors: Sethi Sajiv , Edwards Jade , Warman Anmol , Duffoo Carla , Patel Niketa , Vidyarthi Gitanjali
Published: October 2019

INTRODUCTION:

Colorectal cancer is the third most cancer diagnosed in USA. Long noncoding RNAs (lncRNAs) are important orchestrators of essential biological networks and regulate cell growth, apoptosis, epigenetics transcription and translation. Multiple lines of evidence link regulatory lncRNAs to diseases.
1,2

METHODS:

The project determined the expression of lncRNAs in samples from normal and highly aggressive colorectal cancer. Using paraffin imbedded samples, the epithelial layer was demarcated under the microscope and isolated with a scalpel. Total RNA was isolated and cDNA was used in the LncProfiler qPCR Array (SBI).

RESULTS:

Results show an increase in lncRNAs DISC2, HAR1A, HAR1B, HULC, NEAT1, NRON, PRINS and RNCR3 in the cancer samples compared to the normal. We further sought to evaluate whether an obese environment could promote the normal colon cells into cancer-like phenotype. To evaluate this, we used exosomes derived from adipose stem cells (ASC) obtained from lean or normal individuals to mimic the obese environment. Colon epithelial cells were cultured and either treated with lean ASC exosomes or obese exosomes for 24 hours. Total RNA was isolated and cDNA was used in the LncProfiler qPCR Array. Amongst the detected lncRNAs, our results showed an increase in DISC-2, NEAT1, NRON, PRINS and RNCR3 lncRNAs which were observed to be increased in the colon cancer samples. Simultaneously, using real time qPCR we saw an increase in pro-survival genes Bcl2, Bcl-xL and caspase 9b in cells treated with exosomes from obese ASC.

CONCLUSION:

The results suggest that obesity may lead to increased incidence of colon cancer. We have known it for years for obesity to increase the risk od colorectal cancers slightly and now we have some insights into the pathophysiology.
184 Cost-Effective Analysis of Prophylactic Oral Vancomycin Use to Prevent Recurrent Clostridium difficile Infections in Hospitalized Patients
Authors: Namn Yunseok , Penmetcha Akhil , Desai Deepak
Published: October 2019

INTRODUCTION:

Clostridium difficile infections (CDI) is the single largest cause of morbidity and mortality among hospital acquired infections and is characterized by frequent recurrence. In the hospital setting, CDI tends to occur in patients with predisposing risk factors such as advanced age, prolonged stay, and exposure to systemic antibiotics. Although antimicrobial agents are major risk factors for CDI, their use in patients is often necessary and inevitable. There is an emerging practice of giving prophylactic oral vancomycin as secondary prophylaxis to prevent recurrent CDI. Prior published retrospective cohort studies suggest patients on systemic antimicrobial therapy who received prophylactic oral vancomycin had significantly lower rates of recurrent CDI compared to patients who did not receive the prophylaxis. However, the cost effectiveness of oral vancomycin used as secondary prophylaxis to prevent recurrent CDI is unknown.

METHODS:

We programmed a Markov Chain Monte Carlo simulation analytic model using published literature and national databases. For each scenario, 500 patients were simulated. The base case was modeled as a hypothetic cohort of hospitalized patients with a history of CDI, currently receiving systemic antimicrobial therapy, who either received or did not receive secondary prophylactic oral vancomycin. Projected outcomes included cost (US dollars). 2-way sensitivity analyses were conducted. A P-value less than 0.05 was considered significant.

RESULTS:

Across 500 simulations, prophylactic oral vancomycin resulted in a greater cost compared to no oral vancomycin at $12,045.67, 95% CI = [11880.80–12210.53] and $8,135.48, 95% CI = [8,047.37–8,223.58], respectively (Figure 1). The difference was statistically significant (P value <1 × 10−6). The treatment arm with oral vancomycin also resulted in approximately a 2.45 increased risk of mortality compared to patients who did not receive vancomycin.

CONCLUSION:

Our findings suggest that prophylactic oral vancomycin may not be a cost-effective strategy in reducing the incidence of CDI recurrence and may, in fact, be associated with an increased risk of mortality in hospitalized patients receiving high dose systemic antimicrobial therapy. These findings appear to be largely driven by the risk of developing vancomycin resistant enterococcus (VRE) infections, namely VRE bacteremia which is associated with high economic burden and increased mortality.
191 Decreasing Hospital Clostridium difficile Infections: Impact of an Educational Module
Authors: Jarodiya Vijay , Singh Tejveer , Khan Zarak H.
Published: October 2019

INTRODUCTION:

Clostridium difficile is a leading cause of healthcare associated infections in the United States accounting for approximately 12% of infections acquired in healthcare settings. Currently there is no primary prevention through immunization to prevent Clostridium difficile infections. Therefore hospital staff should be knowledgeable about evidence-based infection-control guidelines to decrease transmission of Clostridium difficile and decrease risk of infection in the hospital. We created an educational module that focused on Clostridium difficile education.

METHODS:

We developed an educational module that focuses on general information about Clostridium difficile including the pathogenesis of infection and ways to decrease or prevent transmission. A module was created which consisted of a pre-test to determine the level of knowledge prior to our intervention as well as an educational module which consisted of PowerPoint slides going over information about Clostridium difficile as well as strategies to decrease and prevent transmission and answering frequently asked questions. This is followed up with a post-test which was meant to test retained information provided during the module. Our initial study was conducted with physicians, nurses and nursing assistants. Our second cycle was conducted from January to June 2018 and expanded to include hospital staff that may not be involved with medical management but also would interact with patients, which included case managers, social workers, patient transportation staff, janitorial staff, food services and other staff.

RESULTS:

Our PDSA cycle revealed a pre-test score of 70.63% with an increase to 96.93% post-test (P < 0.001). The Standardized Infection Ratio in the months prior to the intervention was 1.967 (P = 0.0139) and post-intervention it was 0.746 (P = 0.4187).

CONCLUSION:

Our study shows that an educational module is an effective way to help combat Clostridium difficile infection rates. We had a statistically significant improvement in test scores which correlated with a decrease in Clostridium difficile infections. While the post-intervention SIR was not statistically significant, it was clinically significant and there was a statistically significant improvement from pre to post-intervention. Some concerns include the possibility of a decay effect from a passive intervention such as a module.
205 Benefit of the Polyp Size-Based Resect and Discard Strategy for Polyp Smaller Than 10 mm in Screening Colonoscopy
Authors: Vanduangden Kunvadee , Sritunyarat Yingluk , Kongtab Natanong , Aniwan Satimai , Rerknimitr Rungsun
Published: October 2019

INTRODUCTION:

The routine histological assessment of all polyps is costly. A resect and discard small polyp has yet to be used widely in practice. Practically, a 10-year surveillance interval is recommended. Without histological confirmation for these polyps, the surveillance interval may be too long in those with a high-risk adenoma (HRA) since the guidelines recommend the 3-year interval for HRA whereas the 10-year interval for a low-risk adenoma (LRA) and no adenoma. Therefore, we aimed to determine the benefit of this strategy and the risk of hidden HRA and cancer based on only polyp size assessment.

METHODS:

The electronic database of 7612 screening colonoscopy between January 2007 and February 2019 was retrospectively reviewed. All polyps sized <10 mm were resected and enrolled. In our practice, all identified polyps were resected and sent to a pathologist except diminutive polyps (polyp size <6 mm) at the recto-sigmoid colon would have left. The size of each polyp was estimated by using opened biopsy forceps, which was 7-mm diameter. The location of polyp was classified as the proximal and distal colon. The proximal colon was defined as the region between cecum and the splenic flexure. A HRA was defined as adenoma with high-grade dysplasia, or villous adenoma. A LRA was defined as tubular adenoma. Stratification with polyp size of <6 mm and 6–9 mm, the NPV for diagnosis of a HRA, and number needed for histological assessment (NNH) to detect one HRA were calculated.

RESULTS:

A total of 5064 polyps <10 mm detected in 4419 subjects were included (Table 1). Of those, size <6 mm was 4211 (83%) and size 6–9 mm was 853 (17%). Histology showed LRA in 3492 (69%) polyps, and HRA in 102 (2%) polyps (Table 1). None had cancer. The prevalence of HRA between proximal polyps and distal polyps was not different (1.7% vs. 2.3%, P = 0.16). Using only polyp size of <6 mm and 6–9 mm, the NPV for diagnosis of HRA were 96.4% and 98.3%, respectively. The NNHs to detect one HRA were 60 in polyp size <6 mm and 28 in polyp size 6–9 mm (Table 2). At $50 per specimen, the polyp size-based resect and discard strategy could save $57,298 for each 1000 subjects with at least one polyp <10 mm.

CONCLUSION:

In a country with financial constrain, resecting polyp <10 mm without histological assessment is recommended because there was no risk for missing cancer and this strategy achieved the Preservation and Incorporation of Valuable Endoscopic Innovation (PIVI) threshold with NPV at 96% for the HRA.
206 Oral Vancomycin Prophylaxis for the Primary and Secondary Prevention of Clostridium difficile Infection: A Systematic Review and Meta-Analysis
Authors: El Kurdi Bara , El Iskandarani Mahmoud , Babar Sumbal , Haddad Ibrahim , Alomari Mohammad , Al Momani Laith , Young Mark
Published: October 2019

INTRODUCTION:

Clostridium difficile infection (CDI) is the leading cause of infectious healthcare-associated diarrhea. It is a major cause of in-hospital morbidity and increased healthcare costs. Past research has identified populations at high risk of CDI. However, there is no current consensus on CDI prophylaxis. Oral vancomycin prophylaxis (OVP) has been suggested for the primary and secondary prevention of CDI. Therefore, we have conducted a comprehensive systematic review and meta-analysis to investigate the role of OVP in CDI prevention in published literature.

METHODS:

A computerized search of MEDLINE, EMBASE and Cochrane databases from inception to March 2019 for publications investigating OVP for CDI prevention. Results were screened for relevance and eligibility criteria. Relevant data was extracted and analyzed using Comprehensive Meta Analysis software. Publication bias was assessed for using Egger's test. P < 0.05 was considered significant.

RESULTS:

Six retrospective cohort studies with total of 1263 patients published between 2016–2019 were included. OVP use was associated with lower CDI (OR 0.175, CI 0.06–0.52) with considerable heterogeneity (I2 67%). OVP use was associated with lower CDI in immunocompromised (OR 0.072 CI 0.01–0.92) (I2 30.8%) as well as immunocompetent (OR 0.22, CI 0.07–0.69) (I2 71%) patients. The reduction in CDI was noted when OVP was used for primary (OR 0.04, CI 0.01–0.27) (I2 0%) as well as secondary (OR 0.27, CI 0.10–0.76) (I2 64%) prevention. Meta regression analysis showed that total daily dose of OVP was correlated to OR of CDI and was able to explain 100% of heterogeneity noted between studies. Only two studies evaluated the risk of VRE emergence in treated populations and found no significant increase. No publication bias was found using Egger's test.

CONCLUSION:

Our results suggest that the use of OVP was associated with lower CDI rates in at-risk populations. Higher daily doses of OVP were associated with higher rates of CDI suggesting that a lower OVP dose might be more effective for CDI prevention. While it might be prudent for physicians to prescribe OVP for high risk patients, the total daily dose, duration of treatment and long term side-effects are yet to be determined. These questions should be further evaluated with randomized controlled trials.
210 Clostridioides (Clostridium) difficile PCR Amplification Cycle Threshold: More Than Just a Number?
Authors: Tung William , Hunold Thomas , Poulter Melinda D. , Warren Cirle , Wu Martin , Hays R. Ann
Published: October 2019

INTRODUCTION:

The optimal diagnostic approach for C. difficile infection (CDI) is controversial. Infectious Disease Society of America currently recommends a high sensitivity test such as a nucleic acid amplification test (NAAT) PCR, followed by a stool toxin enzyme immunoassay to confirm clinical suspicion of CDI. C. difficile PCR cycle threshold (Ct) is the number of cycles required for a signal to exceed background fluorescence with low numbers reflecting a larger C. difficile nucleic acid burden. Recent reports correlate Ct in symptomatic patients with disease severity and mortality. Data regarding the predictive value of PCR Ct in recurrence of CDI is preliminary. We aim to determine the association between Ct and recurrence of CDI.

METHODS:

This was an IRB approved, single-center retrospective chart review cohort of 76 randomly chosen patients ≥18 y.o., with completely unformed stools that were C.difficile NAAT positive. 10 patients were excluded due to lack of Ct values. Recurrence defined as any positive test for C. difficile within 3 months after treatment for CDI. Severe CDI defined as WBC >15,000 or creatinine ≥1.5 md/dL and fulminant disease as refractory hypotension, ileus or megacolon. Poor clinical outcome defined as severe or fulminant CDI, or death within 30 days of diagnosis. A t-test or Mann Whitney U test was performed on populations with or without a normal distribution, respectively. A scatterplot was generated with Ct values for patients with initial vs recurrent episodes of CDI.

RESULTS:

Of 66 patients, mean Ct values of 8 patients with recurrent CDI (12.1%) and 58 without recurrence were 25.71 and 26.15 respectively (P = 0.79). Recurrence rates after the initial episode of CDI (n = 4), 1st recurrence (n = 1), and 2nd/subsequent recurrence (n = 3) were 9.1%, 12.5% and 21.2%, respectively. Mean Ct values trended lower for patients with poor outcomes (25.40 vs 26.42, P = 0.37).

CONCLUSION:

In our single center study, Ct values did not associate with a recurrence of CDI. Our findings suggest that Ct cannot be used to predict which patients will be at risk for recurrent CDI. The trend of lower Ct values associating with worse outcomes is worth a prospective study. Interestingly, there was no association with Ct values and common risk factors for CDI such as prior antibiotic use, suggesting that Ct values may not clarify current controversies in testing for CDI.
223 Does “Prior Appendectomy” Affect the Outcomes of Clostridium difficile Infection in Hospitalized Patients? A Retrospective Review and Analysis
Authors: Shaikh Danial , Patel Harish , Mehershahi Shehriyar , Pirzada Usman , Alemam Ahmed , Sun Haozhe , Nawaz Iqra , Naher Kamrun , Islam M. Rizwanul , Hanumanthu Siddarth , Nayudu Suresh
Published: October 2019

INTRODUCTION:

Clostridium difficile infection (CDI) is prevalent in hospitalized patients and accounts for significant morbidity and mortality. Management and outcomes of these patients depend on the severity of CDI. Current classification of severity of CDI includes parameters that depict its inflammatory response. We attempted to study the influence of prior appendectomy on severity and outcomes of CDI.

METHODS:

We conducted a retrospective chart review of 1248 patients admitted to our institute between 2008 and 2016, whose stool tested positive for Clostridium difficile toxin. Baseline characteristics, comorbidities, and lab values were extracted from the EMR. Information regarding prior appendectomy was obtained from medical documentation and abdominal imaging, whichever was available. Patients were grouped into those with prior appendectomy (group A) and those without (group B). In-hospital Mortality was defined as death during the same hospital admission as CDI. Severity was defined as per the Infectious Diseases Society of America guidelines. The primary outcomes were to 1) assess all-cause in-patient mortality and 2) severity of CDI, attributable to prior appendectomy.

RESULTS:

There were a total of 1248 patients of which 13.5% (n = 175) had a history of prior appendectomy. The mean age was similar in both groups (57 years), and baseline characteristics were comparable. There was a female preponderance (60.06%) in group A. The dominant patient race was African American (36.6% in group A and 39.8% in group B). All lab parameters were similar in both groups, except WBC counts, which were higher amongst patients with appendectomy (13 vs. 11, ±8) (P 0.013). Group A patients were more likely to have a severe presentation of CDI (40%, n = 68), whereas group B had mostly mild CDI (45.9%, n = 492). Prior appendectomy did affect the severity status, although statistical significance was not achieved (P 0.057). There was no statistical difference in mortality either, with 25 deaths in group A (14.3%) and 169 in group B (15.8%) (P 0.62). Regression analysis performed to ascertain independent predictors of all-cause mortality in CDI did not identify prior appendectomy as a risk factor.

CONCLUSION:

Prior appendectomy status may affect the severity of CDI and hence the need for colectomy. However, we did not observe a difference in mortality associated with prior appendectomy. Since the prevalence of prior appendectomy was low in our study, larger population studies are needed to establish significant outcomes.
229 Assessing Varying Techniques of Colonic Endoscopic Mucosal Resection and Subsequent Residual Adenoma at 6-Month Follow-Up
Authors: Groff Andrew , Lester Courtney , Levenick John M.
Published: October 2019

INTRODUCTION:

Local recurrence at colonic endoscopic mucosal resection (EMR) sites of medium to large polyps is common at first follow-up (∼10–30%). Extended edge resection has not shown a benefit of reducing this rate; however, edge ablation with snare tip soft coagulation has shown reduced local recurrence. Hybrid argon plasma coagulation (APC) is a novel technique, which can be used to treat microscopic residual disease to prevent local recurrence at follow-up surveillance colonoscopy. This study aims to evaluate if treating both the edges and base of an EMR site with a novel technique, hybrid APC, can reduce the rate of local recurrence at 6-month follow-up versus standard EMR assessing a single endoscopist.

METHODS:

This is a single center retrospective case series of all colonic EMRs with 6-month surveillance performed by a single endoscopist at a tertiary care center using both standard EMR and hybrid APC assisted EMR from May 2018 to May 2019. The main outcome measure was recurrence of precancerous polyp at prior EMR site at 6-month surveillance colonoscopy. Secondary outcome measures were the rate of procedure associated complications, including post-polypectomy bleeding and post-polypectomy syndrome.

RESULTS:

A total of 84 EMRs, 38 utilized hAPC, were performed from in the study period. 25 patients (mean age: 65.4 years, 48% men) with 30 polyps were included who completed surveillance colonoscopy after 6 months to evaluate for recurrence (Table 1). The average resected polyp size was 32 mm. Residual polyp recurrence occurred at 4 prior EMR sites (13.3%), with all of the recurrences occurring in patients who underwent standard EMR (100%). There was no recurrence of residual polyps in patients treated with hAPC assisted EMR. Further, 4 patients (15.4%) experienced post-polypectomy bleeding complications within 6 months, with all complications associated with patients treated with standard EMR (Table 2). There was a statistically non-significant trend toward higher recurrence and complication rate in patients treated with standard EMR compared to hAPC assisted EMR.

CONCLUSION:

In this retrospective study of colonic EMRs, the use of hAPC at initial EMR was associated with decreased local recurrence rate of precancerous tissue at EMR sites and rate of early complications. The findings of this early retrospective study warrant further studies to determine the efficacy of hAPC in reducing the recurrence rate after 6 months and how it compares to standard EMR procedure with snare tip soft coagulation.
230 Dosing Strategy for Itacitinib, a Selective JAK1 Inhibitor, for the Treatment of Ulcerative Colitis
Authors: Barbour April , Zhang Yan , Punwani Naresh , Diamond Sharon , Chen Xuejun , Yeleswaram Swamy
Published: October 2019

INTRODUCTION:

Itacitinib is a JAK1 inhibitor currently under development for oncologic and auto-immune diseases. Itacitinib is delivered as a sustained release formulation with 27.1% of the dose eliminated as unchanged itacitinib in the feces. A clinical and an ex vivo study were conducted to understand colonic disposition, important for ulcerative colitis (UC).

METHODS:

Clinical study: Itacitinib concentrations in plasma and feces (colonic surrogate) were determined following a single 25 mg oral dose. Itacitinib concentrations in plasma following a single 100 mg dose were also determined in a separate study. Ex vivo study: Colon tissue samples from healthy and UC subjects (2/group) were mounted on a vertical Ussing diffusion chamber. 14C-Itacitnib was applied to the apical side of the chamber at 100 and 1000 nM and incubated for 1 h. Samples were collected from the donor and receiver sides for determination of itacitinib concentration. The colonic tissue was snap frozen for quantitative autoradiography.

RESULTS:

Following a single 25 mg dose of itacitinib, 8/12 patients had fecal concentrations that exceeded the in vitro IC50 for JAK1 inhibition. Systemic concentrations were below the IC50 for JAK1 inhibition in whole blood at both doses evaluated, mean (SD) Cmax = 18.9 (7.46) nM for 25 mg and 84.4 (45.8) nM for 100 mg. Ex vivo, no itacitinib related radioactivity was detected from the receiver side. Itacitinib penetrated into the mucosal layer and, to a lesser extent, submucosal layer in a concentration dependent manner.

CONCLUSION:

A dose range of 25 mg BID to 100 mg QD is recommended for study in UC patients to maximize colonic exposure while minimizing the potential for systemic exposure.
232 Numerous Non-Advanced Adenomas Are Not Associated With Metachronous Advanced Neoplasia
Authors: Rouphael Carol , Lopez Rocio , McMichael John , Burke Carol A.
Published: October 2019

INTRODUCTION:

Studies using standard definition colonoscopes in the early 2000s demonstrated the risk of metachronous advanced neoplasia (MAN) was doubled in patients with >3 vs 1–2 small tubular adenomas. In the last decade, attention to the importance of adenoma detection rate and the use of high definition (HD) colonoscopes, increases small adenoma detection. We analyzed the association between baseline adenoma features, particularly multiplicity of non-advanced adenomas, on the risk of MAN in patients undergoing HD colonoscopy.

METHODS:

Patients undergoing first colonoscopy at age ≥50 in the era of HD colonoscopes (≥2006) and follow-up colonoscopy >24 months from baseline exam were identified from the electronic medical record. Exclusions included inflammatory bowel disease, history of colorectal cancer or colon surgery, incomplete colonoscopy, and inadequate bowel preparation. High risk adenoma (HRA) patients included those with an advanced adenoma (≥10 mm in size, adenoma with villous features/high-grade dysplasia) or ≥3 adenomas. Low risk adenoma (LRA) patients included those with 1–2, <10 mm tubular adenomas. The risk of MAN was calculated according to baseline adenoma features. Multivariable analysis compared the risk of MAN between individuals with LRA vs HRA on baseline HD colonoscopy adjusted for interval between first and follow-up colonoscopies.

RESULTS:

159,273 patients underwent colonoscopy at age ≥50 in 2006 or later. After exclusions, 3,383 were included. Mean age was 60.5 ± 7.8 and 54.6% were females. The median time interval between the first and follow-up colonoscopy was 59.9 (42.5–66.7) months for the LRA group and 41.8 (36.3–52.2) months for the HRA group. The risk of MAN was 3.8% in individuals with no baseline adenomas; 4% with LRA; and 9.2% with HRA. The risk of MAN in individuals with >3 non-advanced adenomas was 6.3%; 6.1% with 3–4 and 7.4% with >5 non-advanced adenomas (Table 1). On multivariable analysis, the risk of MAN was not different between HRA and LRA based upon the number of non-advanced adenomas: >3 [OR 1.6, (0.7, 3.9)]; 3–4 [OR 1.6, (0.61, 4.0)] and >5 non-advanced adenomas [OR 2.2, (0.27, 17.0)] (Table 2).

CONCLUSION:

In the contemporary era of HD colonoscopy, compared to LRA patients, patients with ≥3 non-advanced adenomas are not at increased risk of MAN including patients with 3–4 and ≥5 non-advanced adenomas. These data support a longer colonoscopy interval (>5 years) in these individuals.
243  An Interim Analysis of a Patient Navigation Program (PNP) to Improve Colonoscopy Access After Abnormal FIT
Authors: Idos Gregory , Herman David , Haghighat Shida , Gainey Christina , Shen Stacy , Mulgaonkar Ashwini , Dea Stanley
Published: October 2019

INTRODUCTION:

Colorectal cancer (CRC) is a leading cause of cancer mortality despite being largely preventable. The fecal immunochemical test (FIT) is a recommended screening method, but timely evaluation of abnormal results is critical to the effectiveness of CRC screening. Recent studies indicate low rates of follow up colonoscopy after abnormal FIT within safety net health systems. A patient navigator program (PNP) is an evidence based strategy that has been shown to improve colonoscopy completion. The aim of this study was to evaluate the effectiveness of a PNP to encourage follow up colonoscopy after abnormal FIT within a large safety net hospital system.

METHODS:

We established an enterprise-wide PNP at five tertiary care hospitals within the Los Angeles County Department of Health Services (LAC-DHS) system. Patients 50–75 years of age with an abnormal FIT result were assisted by the PNP to complete their follow up colonoscopy within 6 months. Here we perform an interim analysis of a prospective cohort of patients from June 1, 2018 to December 31, 2018 assisted by the PNP. We compare the effectiveness of the PNP intervention by comparing colonoscopy rates to a period prior to the intervention. We also summarize the endoscopic findings of patients undergoing colonoscopy.

RESULTS:

Among 1217 patients with abnormal FIT results, 43% (n = 546) were men with a mean age of 60.3 ± 6.2 years. From a previous baseline of 167 days (SD 118), the mean time from abnormal FIT to colonoscopy improved to 117 days (SD 53) with navigation. The frequency of colonoscopy completion increased in patients who received navigation (53%, n = 642) as compared to patients who did not receive navigation (40.5%, 492/1213). Among PNP patients undergoing colonoscopy (N = 642), 50.2% (n = 322) had adenomatous polyps, 24% (n = 156) had “high risk” adenomas, and 2% (n = 12) had CRC.

CONCLUSION:

After the introduction of a patient navigator program, there was an overall increase in patients undergoing follow-up colonoscopy after abnormal FIT within a shorter time interval. Over half of the patients undergoing colonoscopy were found to have clinically significant findings including high risk adenomas and CRC. In this interim analysis, we demonstrate that the integration of a patient navigator program for CRC screening may be instrumental in increasing adherence to recommended screening guidelines across a large safety net health system.
244 Exogenous Insulin Therapy Increases the Risk of Advanced Colorectal Adenoma Among Patients With Type 2 Diabetes Mellitus
Authors: Lam Robert , Chennareddy Sumanth , Brahmbhatt Mihir , Glassman Caroline , Yang Yu-Xiao
Published: October 2019

INTRODUCTION:

Endogenous hyperinsulinemia increases the risk of colorectal cancer (CRC) among patients with type 2 diabetes mellitus (T2DM). Exogenous insulin therapy, used by 30% of T2DM patients, further increases systemic levels of insulin and has been shown to increase the risk of CRC in animal models. We sought to evaluate the effect of exogenous insulin therapy on the incidence of advanced adenoma in T2DM patients.

METHODS:

We conducted a retrospective cohort study among patients with T2DM aged 40–80 at a tertiary healthcare center. Among other inclusion/exclusion criteria (Figure 1), eligible patients must have undergone 2 rounds of colonoscopy examinations – a baseline colonoscopy and a follow-up (index) colonoscopy ≥1 year later. Primary outcome was incident advanced adenomas at index colonoscopy. Primary exposure was long-term (≥1 year) insulin therapy before index colonoscopy. Assuming α = 0.05, background advanced adenoma incidence of 5%, and prevalence of insulin therapy among T2DM of 20%, a cohort size of 865 would be required to have 90% power to detect a 7.5 percentage point increase in advanced adenoma incidence among long-term insulin users. Multivariable logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI).

RESULTS:

Among patients with ≥1 diagnostic code for DM and ≥2 colonoscopy procedure codes, we randomly selected 1,900 patients for chart review and identified 867 eligible patients (Figure 1). Except for BMI, baseline characteristics between short-term/non-insulin users versus long-term insulin users were not significantly different (Table 1). Characteristics of the baseline and index colonoscopies were similar between the two groups (Table 1). Incidence of advanced adenoma at index colonoscopy was higher among the long-term insulin users versus short-term/non-insulin users (20% versus 4.7%, chi2
P < 0.001). Multivariable adjusted OR for advanced adenoma risk associated with long-term insulin use was 6.2 (95% CI: 3.4–11.3). Long-term insulin use was also associated with increased risk of having ≥3 adenomas (adjusted OR 2.8, 95% CI 1.4–5.4) and having ≥1 right-sided advanced adenoma (adjusted OR 6.9, 95% CI 3.5–13.8) at index colonoscopy.

CONCLUSION:

Chronic insulin therapy was associated with increased risk of advanced adenoma occurrence in T2DM patients. This novel observation is important for developing a risk-tailored approach to the use of colonoscopy in CRC screening/surveillance in patients with T2DM.