Antibiotic Prophylaxis for Upper Gastrointestinal Bleed in Liver Cirrhosis; Less May Be More.

INTRODUCTION: Administration of antibiotics in patients with cirrhosis and upper gastrointestinal bleeding has been shown to improve outcomes. Little is known regarding optimum duration of prophylactic antibiotics. Seven days of antibiotics are generally recommended but very few studies have compared antibiotic duration to clinical outcomes in current available scientific literature. The goal of our study was to study the effect of shorter antibiotic duration on patient outcomes. METHODS: We conducted a retrospective cohort study of patients with cirrhosis presenting with upper GI bleeding at our institute from 2010 to 2018. Patients were divided into three cohorts based on duration of antibiotic administration for prophylaxis: 1-3 days of antibiotics, 4-6 days of antibiotics and 7 days or more of antibiotics. Rates of infection diagnosis within 30 days, rebleeding, and mortality were compared between the three groups with Chi square, Fisher Exact and Kruskall-Wallace tests. Multivariable analysis was conducted to evaluate independent risk factors for infection. RESULTS: Medical charts of 980 patients with cirrhosis and upper GI bleeding during the study period were reviewed. A total of 303 with upper gastrointestinal bleeding were included in the final sample, of these 243 patients received antibiotics for prophylaxis and were included for analysis. Seventy-seven patients received antibiotic therapy for 3 days or less, 69 patients for 4-6 days, and 97 patients longer than 6 days. The three groups were well matched in demographic and clinical variables. Twenty-seven patients developed infections within 30 days of bleeding. MELD-Na score at presentation and presence of ascites were associated with infection within 30 days. Rates of infection were not statistically different between the three antibiotic groups (p = 0.78). In the thirty days following the GI bleed, pneumonia was the most diagnosed infection (eleven patients) followed by urinary tract infections (eight patients). Four patients developed spontaneous bacterial peritonitis and three were diagnosed with bacteremia. There was no difference in time to infection (Kruskall Wallace test p = 0.75), early re-bleeding (p = 0.81), late re-bleeding (p = 0.37) and in-hospital mortality (p = 0.94) in the three groups. Six patients in the cohort developed C. Difficile infection; no patient in the short antibiotic group developed C. Difficile infection. CONCLUSION: Short course of antibiotics for prophylaxis (3 days) appears safe and adequate for prophylaxis in patients with cirrhosis with upper gastrointestinal bleeding if there is no active infection.

EPR Viscometric Measurements Using a 13C-Labeled Triarylmethyl Radical in Protein-based Biotherapeutics and Human Synovial Fluids.

The viscosity measurements are of clinical significance for evaluation of the potential pathological conditions of biological lubricants such as synovial fluids of joints, and for formulation and characterization of peptide- and protein-based biotherapeutics. Due to inherent potential therapeutic activity, protein drugs have proven to be one of the most efficient therapeutic agents in treatment of several life-threatening disorders, such as diabetes and autoimmune diseases. However, home-use applications for treating chronic inflammatory diseases, such as diabetes and rheumatoid arthritis, necessitate the development of high-concentration insulin and monoclonal antibodies formulations for patient self-administration. High protein concentrations can affect viscosity of the corresponding drug solutions complicating their manufacture and administration. The measurements of the viscosity of new insulin analogs and monoclonal antibodies solutions under development is of practical importance to avoid unwanted highly viscous, and therefore, painful for injection drug formulations. Recently, we have demonstrated capability of the electron paramagnetic resonance (EPR) viscometry using viscosity-sensitive 13C-labeled trityl spin probe (13C1-dFT) to report the viscosity of human blood, and interstitial fluids measured in various organs in mice ex-vivo and in anesthetized mice, in vivo. In the present work, we demonstrate utility of the EPR viscometry using 13C1-dFT to measure microviscosity of commercial insulin samples, antibodies solution, and human synovial fluids using small microliter volume samples (5-50 µL). This viscometry analysis approach provides useful tool to control formulations and administration of new biopharmaceuticals, and for evaluation of the state of synovial fluids of importance for clinical applications.

Validation of the ENDPAC model: Identifying new-onset diabetics at risk of pancreatic cancer.

BACKGROUND: Patients with new-onset diabetes are known to be at a higher risk of developing pancreatic cancer. The Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) model was recently developed to identify new-onset diabetics with this higher risk. Further validation is needed before the ENDPAC model is implemented as part of a screening program to identify pancreatic cancer. METHODS: A retrospective case-control study was performed; a cohort of patients with new-onset diabetes was identified using hemoglobin A1c. Patients were scored by the ENDPAC model and then divided based on whether pancreatic cancer was diagnosed after the diagnosis of diabetes. The performance of the model was assessed globally and at different cutoffs. RESULTS: There were 6254 controls and 48 cases of pancreatic cancer. Bivariate analysis showed that patients with pancreatic cancer lost weight before diagnosis while controls gained weight (-0.93 kg/m2 vs. 0.45 kg/m2, p < 0.00∗). Cases had a more significant increase in their HbA1C from one year before (1.3% vs. 0.82%, p = 0.02). Smoking and pancreatitis rates were higher in cases compared to controls (p < 0.00∗). The area under the curve (AUC) of the ENDPAC model was 0.72. A score >1 was the optimal cutoff. At this cutoff, the sensitivity was 56%, specificity was 75%, and pancreatic cancer prevalence increased from 0.78% at baseline to 1.7%. CONCLUSION: The ENDPAC model was validated in an independent cohort of patients with new-onset diabetes.

Opioid Use Is More Common in Nonalcoholic Fatty Liver Disease Patients with Cirrhosis, Higher BMI, and Psychiatric Disease.

BACKGROUND: Opioid use is a topic of growing concern among patients with nonalcoholic fatty liver disease (NAFLD). Given safety concerns of opioids, proactively identifying subgroups of patients with an increased probability of opioid use may encourage practitioners to recommend alternative therapies for pain, thus reducing the likelihood of opioid misuse. This work assessed the prevalence and patient characteristics associated with opioid use in a real-world cohort of patients with NAFLD. METHODS: TARGET-NASH, an observational study of participants at 55 academic and community sites in the United States, includes patients with NAFLD defined by pragmatic case definitions. Opioid use was defined as any documented opioid prescriptions in the year prior to enrollment. The association between patient characteristics and the odds of opioid use were modeled with stepwise multivariable logistic regression and tree ensemble methods (Classification and regression tree/Boosted Tree). RESULTS: The cohort included 3,474 adult patients with NAFLD including 18.0% with documented opioid use. Variables associated with opioid use included presence of cirrhosis (OR 1.51, 95% CI 1.16-1.98), BMI ≥32 kg/m2 (OR 1.29, 95% CI 1.05-1.59), depression (OR 1.87, 95% CI 1.50-2.33), and anxiety (OR 1.59, 95% CI 1.27-1.98). In the boosted tree analysis, history of back pain, depression, and fibromyalgia had the greatest relative importance in predicting opioid use. CONCLUSION: Prescription opioids were used in nearly 1 of 5 patients with NAFLD. Given the safety concerns of opioids in patients with NAFLD, alternative therapies including low-dose acetaminophen and nonpharmacologic treatments should be considered for these patients.

Increased DMT1 and FPN1 expression with enhanced iron absorption in ulcerative colitis human colon.

Iron deficiency anemia is a common complication of ulcerative colitis (UC) that can profoundly impact quality of life. Most iron absorption occurs in the duodenum via divalent metal transporter 1 (DMT1)-mediated uptake and ferroportin-1 (FPN1)-mediated export across the apical and basolateral membranes, respectively. However, the colon also contains iron transporters and can participate in iron absorption. Studies have shown increased duodenal DMT1 and FPN1 in patients with UC, but there is conflicting evidence about whether expression is altered in UC colon. We hypothesized that expression of colonic DMT1 and FPN1 will also increase to compensate for iron deficiency. Quantitative RT-PCR and Western blot analyses were performed on duodenal and colonic segmental (right colon, transverse colon, left colon, and rectum) biopsies obtained during colonoscopy. DMT1 mRNA and protein abundances in colonic segments were approximately equal to those in the duodenum, whereas colonic FPN1 mRNA and protein abundances of colonic segments were about one-quarter of those of the duodenum. DMT1 specific mRNA and protein abundances were increased twofold, whereas FPN1 mRNA and protein expressions were increased fivefold in UC distal colon. Immunofluorescence studies revealed enhanced expression of apical membrane- and basolateral membrane-localized DMT1 and FPN1 in UC human colon, respectively. Increased DMT1 expression was associated with enhanced 2-(3-carbamimidoylsulfanylmethyl-benzyl)-isothiourea (CISMBI, DMT1 specific inhibitor)-sensitive 59Fe uptake in UC human colon. We conclude from these results that patients with active UC have increased expression of colonic iron transporters and increased iron absorption, which may be targeted in the treatment of UC-related anemia.

Reduced risk of post ERCP pancreatitis in statin users.

BACKGROUND: One of the most feared complications of endoscopic retrograde cholangiopancreatography (ERCP), with an incidence of 3.5 to 15%, is post ERCP pancreatitis (PEP). Given the role of statins in the reduction of systemic and pancreatic intraluminal inflammation, we hypothesized that the use of statins may lower the risk of PEP. METHODS: A retrospective cohort study of all patients undergoing ERCP at West Virginia University during the years 2016 and 2017 was performed. Possible association of collected variables with PEP was assessed with Univariate tests and multivariable logistic regression analyses. RESULTS: A total of 1162 ERCPs were included. Mean age was 60.12 years (SD: 17.5). 51.3% of the participants were female. Two hundred and sixty-three participants underwent more than one ERCP during the study period. Seven hundred and ninety-nine ERCPs (78.8%) were conducted in participants who were not taking a statin medication at the time of ERCP, while 363 participants were on statin medications at the time of ERCP; 118 and 245 participants were taking high dose statins (atorvastatin 40-80 mg or rosuvastatin 20 mg), and low/medium dose statins (all other statin regimens) at the time of the procedure, respectively. The overall incidence of PEP in the cohort was 7.3%. In the non-statin and statin groups, 9.5 and 3.4% of participants developed PEP, respectively. On univariate analysis, young age, no statin use, history of PEP, and endoscopic sphincterotomy were found to be significantly associated with the development of PEP. In a binary logistic regression model, young age (P = 0.033), history of PEP (P = 0.0001, OR 2.41, 95% CI: 1.05-5.51) and endoscopic sphincterotomy (P = 0.038, OR 2.85, 95% CI: 1.7-4.78) were found to be associated with increased risk of PEP. Statin usage was found to be protective against PEP, (OR 0.35, 95% CI: 0.18-0.69). CONCLUSION: Chronic statin usage is protective against post ERCP pancreatitis, and our findings suggest a potential role of these drugs as prophylactic agents. Randomized controlled trials are needed to establish any potential clinical application.

Independent association of obstructive sleep apnea with Barrett's esophagus.

BACKGROUND AND AIM: Current guidelines suggest screening at-risk groups of patients for Barrett's esophagus (BE), a precursor to esophageal cancer. Although BE and obstructive sleep apnea (OSA) have common risk factors, including elevated body mass index and gastroesophageal reflux disease (GERD), the relationship between these two conditions has not been well established. METHODS: Retrospectively, all patients who had undergone a polysomnography and esophagogastroduodenoscopy at West Virginia University Hospital from 2013 to 2018 were identified and divided into groups on the basis of the presence or absence of OSA. Clinical course and procedure reports were reviewed to identify relevant variables. RESULTS: One thousand ninety-one patients met inclusion criteria; 60.9% were female, and mean age of participants was 53.5 years. Univariate analysis revealed that male gender, age, diagnosis of OSA, severity of OSA, and a clinical diagnosis of GERD were associated with BE (P values < 0.05). Multiple logistic regression incorporating age, sex, clinical diagnosis of GERD, smoking history, body mass index, Helicobacter pylori status, and presence of hiatal hernia was utilized. Patients with OSA had an increased risk of BE than had those without OSA (P < 0.001, odds ratio 3.26 [1.72-6.85]). The risk increased with increasing severity of OSA, categorized in apnea-hypopnea index increments of 10. CONCLUSION: Obstructive sleep apnea is associated with BE, a relationship that is independent of other known risk factors. Additionally, this risk increases with increasing severity of OSA. Future efforts should determine if patients with severe OSA need to be screened for BE due to its potential for causing esophageal cancer.

Outcomes of SARS-CoV-2 infection in patients with celiac disease: a multicenter research network study.

Background: Celiac disease (CD) is associated with an increased risk for respiratory infections and severe outcomes. No data have been reported in the scientific literature regarding the outcomes of COVID-19 in this population. The aim of this study was to report matched clinical outcomes in a large cohort of 930 patients with COVID-19 in the setting of known CD. Methods: Analysis of a multicenter research network TriNETX was performed, including COVID-19 patients aged more than 16 years. Outcomes of COVID-19-positive patients with concurrent CD were compared with a propensity-matched cohort of patients without CD. Results: A total of 341,499 patients with SARS-CoV-2 infection were identified on the research network: 930 (0.27%) with CD and 340,569 (99.73%) without CD. In the 30- and 60-day periods post SARS-CoV-2 infection, 12 (1.29%) and 13 (1.40%) deaths, respectively, were reported in the CD group. Fewer patients in the CD group reached the composite outcome of either mechanical ventilation or mortality at 60 days (risk ratio 0.58, 95% confidence interval 0.36-0.95). After propensity matching, no difference in clinical outcomes was observed. Conclusion: Our data suggest that patients with CD are not at increased risk of COVID-19-related morbidity or mortality.

Incidence, outcomes, and impact of COVID-19 on inflammatory bowel disease: propensity matched research network analysis.

BACKGROUND: Accurate estimates for the risk of COVID-19 in IBD, and an understanding of the impact of COVID-19 on IBD course and the risk of incident post-infectious IBD are needed. AIMS: To estimate the risk of COVID-19 in IBD and study its impact on IBD course and the risk of incident post-infectious IBD. METHODS: A retrospective propensity score matched cohort study utilising multi-institutional research network TriNetX. COVID-19 patients with and without IBD were identified to quantify the risk of COVID-19 in patients with IBD, COVID-19 outcomes in patients with IBD and the impact of COVID-19 on IBD disease course. The risk of incident post-infectious IBD in COVID-19 patients was compared to the population not infected with COVID-19 during a similar time period. RESULTS: Incidence rate ratio for COVID-19 was lower in IBD patients compared to the non-IBD population (0.79, 95% CI: 0.72-0.86). COVID-19-infected patients with IBD were at increased risk for requiring hospitalisation compared to non-IBD population (RR: 1.17, 95% CI: 1.02-1.34) with no differences in need for mechanical ventilation or mortality. Patients with IBD on steroids were at an increased risk for critical care need (RR: 2.22, 95% CI: 1.29-3.82). Up to 7% of patients with IBD infected with COVID-19 suffered an IBD flare 3-months post-infection. Risk for incident IBD post-COVID was lower than that seen in the non-COVID population (RR: 0.64, 95% CI: 0.54-0.65). CONCLUSION: We observed no increase in risk for COVID-19 amongst patients with IBD or risk for de novo IBD after COVID-19 infection. We confirmed prior observations regarding the impact of steroid use on COVID-19 severity in patients with IBD.

Recurrent hematochezia secondary to gastrointestinal stromal tumors (GISTs) in neurofibromatosis type one.

BACKGROUND: Patients with neurofibromatosis type 1 (NF1) suffer from cutaneous, neurological and intestinal complications due to the mutation of the neurofibromin gene and abnormal protein product. Gastrointestinal stromal tumors (GISTs) are relatively rare primary tumors of the stomach and small intestine. Patients with NF1 are prone to developing GISTs. We present a case of recurrent gastrointestinal (GI) bleeding from multiple GISTs in a patient with NF1. CASE: A 42 year-old male with NF1 presented with significant GI bleeding; endoscopies failed to identify the source. Multiple lesions involving the small bowel were seen on laparotomy; he underwent reparative small bowel resection. Pathology showed a well circumscribed spindle cell proliferation with minimal atypia and rare mitoses; immunostaining was positive for CD117 (KIT) and CD34; KIT mutations in exons 9, 11, 13 and 17 were negative. DISCUSSION: Up to 25% of patients with NF1 develop GISTs with non-specific presentations; however they may be a source of significant GI bleeding. The pathology, course and molecular composition of these tumors are different from sporadic GISTs. In NF1, GISTs are usually multiple, located in the small bowel (as opposed to the stomach as in sporadic cases) and occur at a younger age. Their clinical scenario is not unlike other hereditary tumor syndromes-multiple tumors with a 10-20% malignant potential. NF1-associated GISTs almost uniformly do not exhibit gain-of-function activation of KIT or PDGFA (pathogenesis is suggested to be from the loss of heterozygosity of the NF1 gene) and are not likely to respond to imatinib. Multiple means of localizing GISTs exist and capsule endoscopy should be recommended to all NF1 patients as it provides a non-invasive approach to localizing the tumors for further surgical management.

Noninvasive Models Screen New-Onset Diabetics at Low Risk of Early-Onset Pancreatic Cancer.

OBJECTIVES: Several noninvasive models have been developed to identify new-onset diabetics at higher risk of developing pancreatic ductal adenocarcinoma (PDAC). However, they need external validation before implementation. METHODS: This study validated one such model (Boursi model) among a cohort of new-onset diabetics. A bivariate analysis of the model's components was done between patients who developed PDAC and type 2 diabetics. The model performance was assessed through receiver-operative characteristic curve analysis. RESULTS: Patients with PDAC had significantly lower total cholesterol and alkaline phosphatase at diagnosis of diabetes (P < 0.01). They were observed losing body mass index (BMI) preceding diagnosis (ΔBMI = -0.42 kg/m2, P < 0.01). The model's area under the curve was 0.83 (95% confidence interval, 0.79-0.88). The cutoff that maximized the Youden index was at 0.8%. At this cutoff, the sensitivity was 75%, specificity was 80%, and the prevalence of pancreatic cancer increased from 0.19% at baseline to 0.69%. CONCLUSIONS: Boursi model enriches the prevalence of PDAC among new-onset diabetics.

Superimposed Infectious Colitis in Crohn's Disease.

The differential diagnosis for an acute Crohn's flare should include enteric infection, a challenging yet critical distinction to make when determining appropriate therapy. Since both present similarly, identification of an enteric infection should be performed with comprehensive stool microbial testing. In the setting of moderate-to-severe disease, patients on biologic therapy may be more prone to infectious complications. We present a patient with chronic Crohn's disease with an unusual, previously undetected enteric infection due to Plesiomonas shigelloides. Once identified, appropriate antibiotic treatment led to resolution of the patient's acute symptomatology. This is the first reported case of P. shigelloides infection in Crohn's disease.

Not so Goody's powder.

Over-the-counter analgesic medications are widely used amongst American adults and are also available in powder forms. Their adverse effects have been well documented in literature. Gastrocolic fistulas as a complication of peptic ulcer disease from analgesic powder usage have been previously unreported. Here, we report a patient with upper gastrointestinal bleeding and acute anaemia secondary to peptic ulcer complicated by gastrocolic fistula in a patient using analgesic powder.

Outcomes of SARS-CoV-2 infection in patients with pulmonary sarcoidosis: A multicenter retrospective research network study.

BACKGROUND: Analyses of COVID-19 infection outcomes in patients with preexisting pulmonary sarcoidosis are lacking and are limited to case reports or small case series with the largest study reporting outcomes of 37 patients. RESEARCH QUESTION: Retrospective cohort study to assess clinical outcomes of 945 patients with pulmonary sarcoidosis, presenting with COVID 19, compared to a propensity matched cohort of patients without sarcoidosis. STUDY DESIGN AND METHODS: Analysis of a multi-center research network TriNETX was performed including patients more than 16 years of age diagnosed with COVID-19. Outcomes in COVID-19 positive patients with concurrent pulmonary sarcoidosis were compared with a propensity score matched cohort of patients without pulmonary sarcoidosis. RESULTS: A total of 278,271 patients with COVID-19 on the research network were identified, 954 patients (0.34 %) carried a diagnosis of pulmonary sarcoidosis. Mean age of patients with sarcoidosis was 56.3 ± 13.2 years, with female predominance (n = 619, 64.89 %). 49.69 % of the participants were African American (n = 474). Co-morbidities including hypertension, chronic lower respiratory diseases, diabetes mellitus, ischemic heart disease, nicotine dependence, and chronic kidney disease were more common in patients with pulmonary sarcoidosis when compared to the non-pulmonary sarcoidosis cohort (all p values < 0.01). In unmatched analysis, pulmonary sarcoidosis group had higher mortality, increased risk for hospitalization, intubation and need for renal replacement therapy. After propensity score matching, no difference in any of the outcome measures was observed. INTERPRETATION: Crude COVID-19 mortality and other clinical outcome measures are poor in pulmonary sarcoidosis cohort; however, propensity-matched analyses revealed no difference in outcomes, showing that higher mortality is driven by higher burden of comorbidities.

Outcomes of COVID-19 in Solid Organ Transplant Recipients: A Propensity-matched Analysis of a Large Research Network.

BACKGROUND: Organ transplant recipients comprise an immunocompromised and vulnerable cohort. Outcomes of coronavirus disease 2019 (COVID-19) in solid organ transplant (SOT) recipients remain understudied. METHODS: We used a multicenter federated research network to compare clinical outcomes of COVID-19 in patients with SOT to a propensity--matched cohort of patients without SOT. RESULTS: We identified 2307 SOT recipients and 231 047 nontransplant patients with COVID-19. Transplant patients were more likely to be male individuals, older, have a body mass index >30 kg/m2, and have comorbid hypertension, diabetes, nicotine dependence, heart failure, and ischemic heart disease compared with the nontransplant group (P < 0.05). One-to-one matching was performed for diabetes, hypertension, chronic lung diseases, race, nicotine dependence, heart failure, ischemic heart disease, and gender. There was no difference in the composite outcome of intubation or mechanical ventilation at 30 days (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.86-1.26) or 60 days (RR, 1.03; 95% CI, 0.86-1.24) between the 2 groups. Hospitalization rate was higher in the transplant cohort (30.97% versus 25.47%; RR, 1.22; 95% CI, 1.11-1.34). There was no difference in mortality at 30 days (6.45% versus 5.29%; RR, 1.22; 95% CI, 0.88-1.68) or 60 days postdiagnosis (RR, 1.05; 95% CI, 0.83-1.32). More patients in the SOT group developed acute renal injury compared with non-SOT cohort (24.73% versus 14.29%; RR, 1.73; 95% CI, 1.53-1.96). CONCLUSIONS: Patients with SOT have high COVID-19-related mortality; however, propensity-matched analyses reveal that this increased risk is secondary to higher burden of comorbidities. SOT status independently increases risk of hospital admission and acute kidney injury.

Are We Overradiating Patients with Irritable Bowel Syndrome?

INTRODUCTION: Protracted exposures to small doses of radiation, even cumulative effective doses (CED) as low as 50-100 mSv, may increase the risk for malignancy. Medical radiation exposure has not been rigorously examined for patients with irritable bowel syndrome (IBS). We examined medical radiation exposure in patients with IBS at a tertiary care center in the USA. METHODS: Patients diagnosed with IBS at our institute from 2009 to 2018 were included in a retrospective cohort study. Medical charts were examined to calculate total and annual CED. RESULTS: 221 patients were included; mean CED was 40.32 mSv (SD: 54.36). Fifty-nine participants (26.7%) received >50 mSv of CED with 27 participants (12.2%) exceeding 100 mSv. Conventional imaging, nuclear medicine, and fluoroscopy accounted for 74.08, 12.93, and 12.98% of total CED, respectively. CT scans contributed to 66.61% of total CED. Outpatient orders accounted for 37.96% of total CED, while 31.4% of total CED was ordered in the emergency department. Population-specific high total CED was calculated as 105.65 mSv. Multivariable binomial logistic regression model found that comorbid anxiety, chronic pain medication use, and diarrhea-predominant IBS were independently positively associated with population-specific high CED exposure. No significant temporal trend in peri-diagnostic mean CED was found. CONCLUSION: Patients with IBS receive high amounts of medical radiation, with 1 in 4 patients reaching at-risk levels of 50 mSv or more. Usage of pain medication at home, comorbid anxiety, and IBS-D are independently linked to an increased risk of high CED.