bluuebunny/crossref_metadata_2025_split huggingface dataset:
Refinement of the critical genomic region for hypoglycaemia in the Chromosome 9p deletion syndrome
Authors: Banerjee Indraneel , Senniappan Senthil , Laver Thomas W. , Caswell Richard , Zenker Martin , Mohnike Klaus , Cheetham Tim , Wakeling Matthew N. , Ismail Dunia , Lennerz Belinda , Splitt Miranda , Berberoğlu Merih , Empting Susann , Wabitsch Martin , Pötzsch Simone , Shah Pratik , Siklar Zeynep , Verge Charles F. , Weedon Michael N. , Ellard Sian , Hussain Khalid , Flanagan Sarah E. 
Published: October 2019

Background: Large contiguous gene deletions at the distal end of the short arm of chromosome 9 result in the complex multi-organ condition chromosome 9p deletion syndrome. A range of clinical features can result from these deletions with the most common being facial dysmorphisms and neurological impairment. Congenital hyperinsulinism is a rarely reported feature of the syndrome with the genetic mechanism for the dysregulated insulin secretion being unknown. Methods: We studied the clinical and genetic characteristics of 12 individuals with chromosome 9p deletions who had a history of neonatal hypoglycaemia. Using off-target reads generated from targeted next-generation sequencing of the genes known to cause hyperinsulinaemic hypoglycaemia (n=9), or microarray analysis (n=3), we mapped the minimal shared deleted region on chromosome 9 in this cohort. Targeted sequencing was performed in three patients to search for a recessive mutation unmasked by the deletion. Results: In 10/12 patients with hypoglycaemia, hyperinsulinism was confirmed biochemically. A range of extra-pancreatic features were also reported in these patients consistent with the diagnosis of the Chromosome 9p deletion syndrome. The minimal deleted region was mapped to 7.2 Mb, encompassing 38 protein-coding genes. In silico analysis of these genes highlighted SMARCA2 and RFX3 as potential candidates for the hypoglycaemia. Targeted sequencing performed on three of the patients did not identify a second disease-causing variant within the minimal deleted region. Conclusions: This study identifies 9p deletions as an important cause of hyperinsulinaemic hypoglycaemia and increases the number of cases reported with 9p deletions and hypoglycaemia to 15 making this a more common feature of the syndrome than previously appreciated. Whilst the precise genetic mechanism of the dysregulated insulin secretion could not be determined in these patients, mapping the deletion breakpoints highlighted potential candidate genes for hypoglycaemia within the deleted region.
SKRINING AWAL AKTIVITAS ANTIBAKTERI DAN ANTIOKSIDAN EKSTRAK SEMUT (INSECTA: FORMICIDAE) DARI GARUT - JAWA BARAT
Authors: Efendy Oscar , Fathoni Ahmad , Praptiwi Praptiwi , Royyani Mohammad Fathi , Wulansari Dewi , Agusta Andria 
Published: October 2019

Studies on the therapeutic use of insects and insect products have been neglected compared to the use of other animals or plants.This study aims to determine the antibacterial and antioxidant potential of ants extracts. Preliminary study related to antibacterial and antioxidant screeningof 17 extracts of ant colonies that belongs to 8 species were performed by Thin Layer Chromatography (TLC)-Bioautography. Antioxidant activity was measured by DPPH free radical scavenging method. The antibacterial activity was done against three pathogenic bacteria, i.e Bacillus subtilis InaCC B-1, Staphylococcus aureus InaCC B-4 and Escherichia coli InaCC B-5 were performed by non-eluted TLC-autobiography assay. The minimum inhibitory concentration (MIC) and IC50 values of DPPH radical scavenging activity of active extracts were determined by microdilution in 96-well microplate. The results showed 6 extracts active against B.subtilis, 5 extracts active against S.aureus. The lowest MIC value was 512 µg/ ml. Ten extracts had the antioxidant activity with various IC50 values. The extracts of ants might be used as bioactive resources for antibacterial and antioxidant.
5 The Prevalence and Epidemiology of Pancreatic Cancer in the USA: A Population-Based Study
Authors: Khoudari George , Saleh Mohannad Abou , Baidoun Firas , Sarmini Muhammad Talal , Vega Kenneth J. , Sanaka Madhusudhan R. 
Published: October 2019

INTRODUCTION:
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Multiple studies have reported the epidemiology of this disease with conflicting results and limited sample size. Our aim is to further investigate the epidemiology of pancreatic cancer using a large database.

METHODS:
We used a commercial database (Explorys Inc, Cleveland, OH) which includes electronic health record data from 26 major integrated US healthcare systems. We identified all patients aged 18 and older who were diagnosed with pancreatic cancer, over the last 5 years based on Systematized Nomenclature Of Medicine – Clinical Terms (SNOMED-CT) and evaluated the prevalence of pancreatic cancer among all the patients in this database. We also performed univariate analysis to describe age-, race-, and gender-based distributions and to identify potential risk factors.

RESULTS:
Of the 36,728,450 individuals in the database, we identified 41,610 individuals with pancreatic cancer with an overall prevalence of 0.11%. Individuals with pancreatic cancer were more likely to be males, senior adults (age >65), Caucasians, (P < 0.0001 to all) compared to patients without pancreatic cancer. Similarly, patients with pancreatic cancer were more likely to have cystic fibrosis, viral hepatitis B and C, acute and chronic pancreatitis, diabetes mellitus type 1 and 2, (P < 0.0001 to all). Additionally, patients with pancreatic cancer were more likely to be smokers, drink alcohol, and take non-steroidal anti-inflammatory drugs (NSAIDs), (P < 0.0001 to all). Table 1 represents the odds ratio (OR) for all factors.

CONCLUSION:
This is one of the largest epidemiological studies investigating the prevalence and epidemiology of pancreatic cancer. Estimated prevalence rate of pancreatic cancer was 0.11%. Patients with pancreatic cancer were more likely to be males, senior adults (age >65), Caucasians, smokers, and take NSAIDs. They were also more likely to have Diabetes, Chronic pancreatitis, Hepatitis B, and Hepatitis C. Further studies are needed to confirm these findings.
8 Role of HMG CoA Reductase Inhibitors and Proton Pump Inhibitors in the Prevention of Post ERCP Pancreatitis
Authors: Muftah Mayssan , Shah Rushikesh , Cristofaro Sarah , Chawla Saurabh , Patel Vaishali , Keilin Steven , Cai Qiang , Willingham Field 
Published: October 2019

INTRODUCTION:
Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most frequent complication following ERCP. Studies have suggested that HMG CoA reductase inhibitors (statins), due to their anti-inflammatory properties, are protective against acute pancreatitis and may lessen the severity. Additionally, it has been postulated that by increasing gastric pH, proton pump inhibitors (PPIs) can prevent premature activation of pancreatic enzymes, reducing the risk of pancreatitis. The role of statins and PPIs in PEP have not been examined. The purpose of this study is to assess the impact of statin and PPI medications on PEP in native papilla ERCP in a tertiary referral center.

METHODS:
Patients who underwent ERCP in a large tertiary care referral setting were retrospectively reviewed from January 2015–December 2017. 1288 patients were screened, and 226 met inclusion criteria. Patients who had ERCP with a native papilla (index ERCP) were included. Data were extracted from chart review. Over 40 variables including demographics, clinical parameters, and procedure-related data points were collected. Variables were collected toinvestigate factors related to PEP and control for cofounders. PEP was defined using the Cotton criteria. A multivariate regression model was constructed to determine independent predictors of post-ERCP pancreatitis.

RESULTS:
226 index ERCPs were collected. Mean age was 58.2 years, 48.7% of the patients were female, and 67.1% were Caucasian. Demographics and clinical variables collected are present in Table 1. The overall rate of PEP was 5.3%. 16.7% of those with PEP were on statin therapy compared to 18.4% (P = 0.88), and 25% of patients who had PEP were on PPIs compared to 41.5% (P = 0.3). The presence of a difficult cannulation was more common in patients with PEP (36.4% vs 12.8%, P = 0.028), as was wire cannulation in the main pancreatic duct (66.7% vs 29.9%, P = 0.008). Variables with a P value < 0.1 were included in a multivariate regression model. The only significant predictors of PEP were difficult cannulation (P = 0.033) and wire cannulation of the MPD (P = 0.021). Subgroup analysis including only patients that had MPD cannulation showed that PPI use (P = 0.025) was an independent predictor of PEP.

CONCLUSION:
Use of statins was not found to be different between PEP groups. In patients that had MPD cannulation, PPI was a predictor of PEP. Further prospective studies are needed to determine the clinical significance of statin and PPI use in relation to PEP.
17 Cholangiocarcinoma: Incidence, Prevalence and Descriptive Analysis in the VA Caribbean Healthcare System in Puerto Rico
Authors: Estremera-Marcial Rodolfo , Marzan-Loyola Adriana , Martin-Ortiz Jose , Toro-Lugo Doris 
Published: October 2019

INTRODUCTION:
Cholangiocarcinoma (CCA) is a rare cancer that arises from the epithelial cells of the bile ducts. Although uncommon, it is highly lethal, since usually it is advanced at the time of presentation. According to the Global Burden of Disease Study there were 139,500 deaths from biliary tract cancers in 2013, which is a 22% increase from the estimated 115,400 deaths in 1990. The incidence and prevalence of CCA at the VA Caribbean Healthcare System (VACHS) in San Juan, Puerto Rico, has not been statistically determined. The aim of this study is to determine the incidence and prevalence of CCA and to provide a descriptive analysis of the veteran population at the VACHS.

METHODS:
Veteran male subjects ≥21 years old with a diagnosis of CCA as documented in ICD-9/ICD-10 were included in this study from 2001–2017. The data was collected from the electronic medical record at the VACHS.

RESULTS:
A total of fifty-seven patients were diagnosed with CCA by the ICD 9-10 criteria. Fifty-four confirmed by biopsy. The mean age of the subjects was 75 years old. The overall estimate prevalence of CCA is 88/100,000 population. According to the data collected, 63%, 30%, 5% and 2% patients with CCA served in the Korean, Vietnam, WWII and Persian Gulf wars, respectively. The most common comorbidities in the biopsy-proven subjects were diabetes mellitus type II (50%), cirrhosis (26.4%), cholelithiasis (21.8%) and obesity (10.5%). Among the patients who had underlying cirrhosis, 29% had HCV. A total of 29 patients (54%) had a positive history of tobacco use and 15% of ethanolism. The most common clinical presentations identified were painless jaundice (44.4%), weight loss (29.6%), RUQ pain (27.8%) and incidental finding on imaging (18.5%). Most of the cases (85%) presented with a cholestatic pattern on routine laboratories. A total of 59.6% of the CCAs were intrahepatic and 26.9% were located distally. At the time of diagnosis, more than half (51.2%) had distant metastasis.

CONCLUSION:
This clinical study, although limited by a small population size and the absence of a control group for comparison, describes the most common clinical and social characteristics related to CCA and its overall prevalence and incidence per year at the VACHS from 2001–2017. Although, the overall estimate prevalence of CCA in our population is low, the rarity of this tumor, along with its asymptomatic presentation and poor prognosis, supports the claim that further research is needed to achieve early detection and better outcomes.
23 Serially Molecular Testing of Pancreatic Cyst Fluid Over Time: Progression and Regression
Authors: Toney Nicole A. , Jackson Sara A. , Narick Christina M. , Finkelstein Sydney D. 
Published: October 2019

INTRODUCTION:
Currently, guideline recommended surveillance of pancreatic cysts is based on low quality evidence, as the natural history of such lesions is not well understood. Our study aimed to review pancreatic cystic lesions serially tested by an integrated molecular pathology (IMP) to better understand their natural history and their resulting risk classifications over time.

METHODS:
We conducted retrospective data review of patients that underwent ≥2 endoscopic ultrasound-guided fine needle aspirations (EUS-FNAs) of their pancreatic cyst, each of which had IMP testing as part of standard of care (PancraGenTM, Interpace Diagnostics) between April 2012–March 2019. The four category IMP result classifies pancreatic cysts as either low risk (Benign and Statistically Indolent [SI]), moderate risk (Statistically High Risk [SHR]) or high risk (Aggressive).

RESULTS:
2,167 pancreatic cysts underwent serial IMP testing. The median number of serial tests performed was 2. The majority of cysts serially tested had time intervals between <1 year and 1–2 years (66%, 1,442/2,167), with 10% (208/2,167) having testing with a >4 year time interval (Table 1). Among cases serially tested, 86% initially had a low risk IMP result of which 92% remained low risk at follow-up EUS-FNA while 8% progressed to a moderate/high risk IMP classification. 99% of diagnostic progression was only to moderate risk IMP. Conversely, among cases serially tested, 14% initially had moderate/high risk IMP results of which 21% remained moderate/high risk at follow-up while 79% regressed to low risk IMP classification. >99% of diagnostic regression was from moderate risk IMP.

CONCLUSION:
Examining molecular progression and regression of pancreatic cysts over time can lead to a better understanding of their natural history, which can help guide surveillance intervals. The majority of cases (92%) that initially had low risk IMP results remained low risk overtime, supporting less frequent surveillance intervals. Of those that progressed, 99% were only to moderate risk levels where diagnostic regression most often occurs.
26 Outcomes of Acute Pancreatitis in Liver Transplant Patients. A Nationwide Readmission Database Analysis
Authors: Gad Mohamed , Simons-Linares Roberto , Saad Anas , Saleh Mohannad Abou , Chahal Prabhleen 
Published: October 2019

INTRODUCTION:
Acute pancreatitis (AP) is a well-recognized and generally serious complication following liver transplantation. We sought to assess AP following adult liver transplantation to describe the risk factors, natural history of the disease and outcomes.

METHODS:
Data from Nationwide Readmission database from 2010 to 2015 was analyzed. All adult patients who were hospitalized for a primary diagnosis of acute pancreatitis were identified and patients who had a history of liver transplantation were compared to patients with no transplantation, using the appropriate ICD 9 codes. Continuous variables were expressed as means ± standard deviation or median (IQR), and categorical variables were expressed as percentages. All statistical tests were two-sided.

RESULTS:
1,575,148 AP patients were included, and out of those 1581 patients (0.1%) had a history of liver transplantation. Patients with a history of transplantation had higher rates of hypertension 59.1% vs. 53.8%, P-value < 0.001, uncomplicated diabetes mellitus, 32.6% vs. 22.9%, P-value < 0.001, diabetes mellitus with chronic complications, 5.8% vs. 3.8%, P-value < 0.001, chronic pancreatitis, 18.2% vs. 16.1%, P-value = 0.02, chronic renal failure 39.6% vs. 7.9%, P-value < 0.001. Transplant patients had higher rates of in-hospital AP complications: acute kidney injury 20.3% vs. 8.3%, P-value < 0.001, transfusion requirement 7.2% vs. 3.0%, P-value < 0.001. No significant difference in the rates of systemic inflammatory response syndrome (SIRS), 2.1% vs. 2.1%, P-value = 0.929, or ileus, 4.0% vs. 3.7%, P-value = 0.595. Transplant patients had lower rates of acute respiratory distress syndrome and/or ventilation need, 0.6% vs. 2.3%, P-value < 0.001, and sepsis 0.5% vs. 1.6%, P-value < 0.001. In-hospital mortality was higher in patients with history of liver transplantation 0.8%vs. 0.3%, P-value = 0.053. Median length of stay was not significantly different 3.00 (2–6) days vs. 3.00 (2–5), P-value = 0.17. Charges of hospitalization were significantly higher in the transplantation group 23,615 USD vs. 21,020 USD, P-value < 0.001.

CONCLUSION:
Post-liver transplant AP carries significant morbidity and mortality. The extensive nature of the anatomical dissection around the pancreas, the type of biliary reconstruction and anastomosis, chronic immunosuppression medications, associated comorbidities, could be contributing factors. Our study highlights possible areas for further investigation in the liver transplant population.
32 Outcomes of Pancreatic Cancer Surveillance in High Risk Individuals
Authors: Kwon RIchard , Dust Henry , McCarthy Sean , Hosmer Amy , Carulli Alexis , Scheiman James , Koeppe Erika , Anderson Michelle , Stoffel Elena 
Published: October 2019

INTRODUCTION:
Consensus guidelines recommend surveillance for pancreatic cancer (PC) for individuals who meet specific high-risk criteria, however outcome data are lacking. We report findings of pancreatic surveillance in individuals at high risk for PC.

METHODS:
Subjects at high risk for PC were identified through the Cancer Genetics Registry at the University of Michigan. High risk individuals (HRI) included the following: 1) familial pancreatic cancer (FPC) defined as ≥3 relatives, or 2 first degree relatives with PC, 2) pathogenic germline variant in BRCA1/BRCA2, PALB2, ATM or Lynch Syndrome (LS) DNA Mismatch repair genes (LS) with ≥1 relative affected with PC or 3) pathogenic germline variant in CDKN2A, STK11, or PRSS1. Results of pancreatic imaging tests were ascertained through chart review.

RESULTS:
121 patients (65 FPC, 20 CDKN2A, 13 LS, 10 ATM, 6 STK11, 4 BRCA, 2 PALB2,1 PRSS1) underwent ≥1 pancreatic imaging tests. Mean age at first screening was 56 ± 10 y with mean of 4 exams per subject (range 1–16). 53 (44%) subjects had abnormalities noted on exam, including parenchymal abnormalities in 28 (53%), cystic lesions in 20 (38%) and ductal abnormalities in 3 (6%). 29 (24%) patients had worrisome findings associated with increased risk for PC (multiple cysts (21), possible solid mass (5), dilated main pancreatic duct (3), cyst >3cm (2)). Of these, there were 13 patients (23%) with a germline mutation (5 CDKN2A, 3 ATM, 2 LS, 2 STK11, 1 PRSS1) versus 16 FPC pts (24%) (P = NS). Seven (24%) patients underwent surgical resection after median 1.9 y (range 0.6–8.6 y) surveillance (indication = mass (2), main duct involvement (3), cyst >3 cm (2)) (Table 1). Pathology revealed PC (1), main duct IPMN with high grade dysplasia (1), neuroendocrine tumors (2, both with IPMN), IPMN with low grade dysplasia (2), and chronic pancreatitis (1). In our cohort, there was one other patient (LS) with PC (a 2cm mass found on initial imaging (MRI); pt now undergoing treatment). The remaining 21 pts are cancer-free with mean 4.3 ± 3.8y follow up.

CONCLUSION:
One in 4 high risk individuals have worrisome pancreatic lesions. The presence of a mass, main duct dilation, and cyst size appear to be the most important findings. Further studies are necessary to better stratify patients and imaging findings at highest risk for progression to PC.
38 Does Cannabis Consumption Impact Chronic Pancreatitis Related Complications?
Authors: Mbachi Chimezie , Wang Yuchen , Barkin Jodie A. , Demetria Melchor V. , Barkin Jamie S. , Kroner Paul T. , Simons-Linares Roberto 
Published: October 2019

INTRODUCTION:
Chronic pancreatitis (CP) does not currently have a cure and it leads to multiple complications (pain, exocrine pancreatic insufficiency, steatorrhea, bone disease), its management is still a challenge. There is evidence that stimulating the endocannabinoid system may reduce inflammation and fibrosis in pancreatic stellate cells. Cannabis is the most frequently used recreational drug in the US and in recent years its legalization has increased. There are currently multiple States in the US that have approved medical cannabis for CP. We investigate the prevalence and outcomes of CP-related complications amongst cannabis-exposed (CE) and non-cannabis-exposed (non-CE) CP patients.

METHODS:
The National Inpatient Sample (NIS) database from 2005 to 2014 was queried for all patients with a primary or secondary discharge diagnosis of chronic pancreatitis as per the International Classification of Diseases 9th revision (ICD-9) code 577.1 and a complication related to chronic pancreatitis. Active exposure to cannabis was ascertained based on ICD-9 code 304.3X and 305.2X. We compared CE vs. non-CE patients. Outcomes included pancreatic cancer diagnosis, biliary stricture, pancreatic duct stricture, cholangitis, endoscopic retrograde cholangiopancreatography (ERCP) use for either diagnostic or therapeutic purpose. Propensity match analysis for age, gender, race, median income quartile, hospital characteristics and Elixhauser comorbidity index and multivariable logistic regression models were performed using SAS software (STATA 14).

RESULTS:
109,326 patients with CP were analyzed (Figure 1). Prevalence of CE was 2.2% (2360 patients). The mean age of CP patients was 49. When comparing CE vs. non-CE, the CP-related complications amongst matched cohorts were as follows chronic abdominal pain 5.2% vs 0.3% (P < 0.001), steatorrhea/diarrhea 1.2% vs 13.5% (P < 0.001), biliary stricture 0.3% vs. 7.1% (P < 0.001), pancreatic cancer 0.4% vs. 11.8% (P < 0.001), cholangitis (0.1% vs 2.6%; P < 0.001), pancreatic cancer (0.4 vs 11.8; P < 0.001). Cannabis users also required less diagnostic ERCP (1.4% vs 5.5%; P < 0.001) and therapeutic ERCP (3.5% vs 9.3%; P < 0.001) (Figure 2).

CONCLUSION:
In CP patients admitted to the hospital, CE patients had lower rates of CP-related complications and importantly pancreatic cancer. These effects could possibly be through the effect of cannabis in the endocannabinoid system as previously shown in mice studies in Germany. More studies are needed to corroborate our findings.