bluuebunny/crossref_metadata_2025_split huggingface dataset:
109 Persistent Hemoconcentration After Initial Resuscitation Is Associated With Increased Need for Opiates in the ED in Patients Presenting With Acute Pancreatitis
Authors: Yang Allison L. , Jin David X. , Banks Peter A. , McNabb-Baltar Julia 
Published: October 2019

INTRODUCTION:
Opiates are commonly used in the management of abdominal pain in acute pancreatitis (AP). The factors associated with increased need for opiates during the initial management are unknown.

METHODS:
Medical records of adults presenting to the ED from 9/1/2013 to 8/31/2016 with AP were identified retrospectively. AP was diagnosed, and severity stratified using the revised Atlanta Classification (2012). Total quantity of opiates required during ED phase of care was converted to morphine equivalents (ME) and divided by number of hours in the ED to get mean ME per hour in the ED (MME). Log-linear multivariable regression analysis was performed to identify factors associated with MME. Hemoconcentration was defined as hematocrit ≥44%.

RESULTS:
318 AP patients were identified. 248 received opiates in the ED. Baseline characteristics are shown in Table 1. At ED presentation, 75 (30.65%) had at least 2 SIRS criteria and 46 (18.55%) had hemoconcentration. On the second set of labs (still within 24 hours of ED arrival), 11/46 (23.9%) remained hemoconcentrated and 2 developed hemoconcentration despite resuscitation. The distribution of mean ME per hour in the ED (MME) ranged from 0.12 mg to 24.81 mg. Mean MME was 2.15 mg (SD = 2.54). Simple linear and multivariable regression analyses are shown in Table 2. Age and first episode of AP were independently associated with less MME. After exponentiation, for every 1-year increase in age, a 1% decrease in MME was observed. Patients with the first episode of AP required 34.9% less MME compared to those with prior AP. On subgroup analysis of patients who were opiate naïve at presentation (N = 193), first episode of AP was still associated with less MME (b-coefficient −0.4024, P = 0.0025); they required 33.1% less MME compared to those with prior AP. Hemoconcentration after initial resuscitation (but within 24 hours of presentation) was associated with increased MME. Patients with hemoconcentration on the second set of labs required 95% higher MME compared to those without hemoconcentration. Increasing number of SIRS criteria was also associated with increased MME; one additional SIRS criteria was associated with a 15% increase in MME.

CONCLUSION:
Persistent or new hemoconcentration within 24 hours of presentation is associated with increased opiate requirement in the ED in patients with AP. This suggests that inadequacy of initial fluid resuscitation to correct intravascular fluid losses may lead to increased pain and need for opiate medications.
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.