Lactated Ringer's or Normal Saline for Initial Resuscitation in Patients Hospitalized With Acute Pancreatitis: A Retrospective Database Analysis.

OBJECTIVES: Fluid resuscitation is required in acute pancreatitis (AP) to prevent hypovolemia and organ hypoperfusion. Lactated Ringer's (LR) is a buffered crystalloid with possible advantages in AP versus normal saline (NS). We aim to assess outcomes in patients hospitalized with AP based on fluid used for resuscitation. METHODS: In this retrospective analysis, we identified hospital admissions to Veterans Affairs facilities for AP from 2011 to 2017 and grouped by initial resuscitation fluid: LR versus NS. Outcomes included major complications and mortality at 30 and 365 days. Multivariable models were used to adjust for confounding variables. RESULTS: A total of 20,049 admissions were included in the study, of which 10% received LR as initial fluid. After adjustment for all available confounders, resuscitation with LR was associated with lower 1-year mortality compared with NS (adjusted odds ratio, 0.61 [95% confidence interval, 0.50-0.76]). Major complication and early mortality were similar between groups. CONCLUSIONS: In this study, we demonstrate an association between use of LR as initial resuscitation fluid and reduced 1-year mortality in a large retrospective sample of veterans hospitalized with AP. These results support the use of LR for resuscitation for most patients hospitalized with AP.

Identification of Immunoglobulin G Autoantibody Against Malondialdehyde-Acetaldehyde Adducts as a Novel Serological Biomarker for Ulcerative Colitis.

INTRODUCTION: Inflammatory bowel disease (IBD) is associated with immune responses with oxidative stress wherein high levels of malondialdehyde result in the formation of a highly stable and immunogenic malondialdehyde-acetaldehyde adduct (MAA). Thus, this study evaluated the status of MAA and anti-MAA antibody isotypes in IBD and their potential as novel serological biomarkers for differentiating ulcerative colitis (UC) from Crohn's disease (CD). METHODS: Levels of MAA and anti-MAA antibodies were examined in patients with IBD (171), non-IBD gastrointestinal diseases (77), and controls (83) from 2 independent cohorts using immunohistochemistry and enzyme-linked immunosorbent assay. Receiver operating characteristic curves and Youden cutoff index from logistic regression were used to determine the sensitivity and specificity. RESULTS: The MAA and blood immunoglobulin G (IgG) anti-MAA antibody levels were significantly elevated in IBD compared with non-IBD patients (P = 0.0008) or controls (P = 0.02). Interestingly, patients with UC showed higher levels of IgG anti-MAA (P < 0.0001) than patients with CD including those with colonic CD (P = 0.0067). The odds ratio by logistic regression analysis predicted stronger association of IgG anti-MAA antibody with UC than CD. Subsequent analysis showed that IgG anti-MAA antibody levels could accurately identify (P = 0.0004) UC in the adult cohort with a sensitivity of 75.3% and a specificity of 71.4% and an area under the curve of 0.8072 (0.7121-0.9024). The pediatric cohort also showed an area under the curve of 0.8801 (0.7988-0.9614) and precisely distinguished (P < 0.0001) UC with sensitivity (95.8%) and specificity (72.3%). DISCUSSION: Circulating IgG anti-MAA antibody levels can serve as a novel, noninvasive, and highly sensitive test to identify patients with UC and possibly differentiate them from patients with CD.

Reversal of anti-drug antibodies against tumor necrosis factor inhibitors with addition of immunomodulators: A systematic review and meta-analysis.

BACKGROUND: The development of anti-drug antibodies (ADA) to tumor necrosis factor (TNF-α) inhibitors is a significant result contributing to the loss of clinical response in inflammatory bowel disease (IBD). AIMS: We performed a systematic review and meta-analysis to assess whether the addition of immunomodulators to TNF-α inhibitors lead to reversal of antibody formation in TNF-α inhibitor-treated IBD patients. METHODS: We conducted a comprehensive search of electronic databases from inception through October 2018 in order to identify specific studies describing clinical response in IBD patients following the addition of immunomodulators (methotrexate or thiopurines) to TNF-α inhibitors. Clinical response was expressed as an improvement of symptoms, with a noted decrease or complete elimination of ADA against TNF-α inhibitors. The meta-analysis was performed using the DerSimonian and Laird random-effect model. RESULTS: Four studies were included in our final meta-analysis, which reported outcomes in 72 patients receiving TNF-α inhibitors. Forty-nine of the seventy-two (68%) patients received either methotrexate (19) or thiopurines (30). The average follow up period was 13.5 months. The overall pooled clinical response was 73.86% (95% confidence interval [CI] = 47.36-94.38, I2 = 60.77%). CONCLUSION: In our meta-analysis, addition of immunomodulators to TNF-α inhibitors was shown to restore the clinical response in 74% of the patients by either decreasing or completely eliminating anti-drug antibody levels. Further long-term multicenter studies are needed to validate these findings.

Medical Management of Inflammatory Bowel Disease.

Inflammatory bowel disease has become a growing concern worldwide. The chronic and progressive nature of inflammatory bowel disease poses significant challenges to the treatment and management of affected patients, straining health care resources. Therapeutic options and optimal management strategies have evolved dramatically. The treat-to-target strategy has shifted focus toward identifiable and attainable treatment targets and with the ability to optimize tight control. Advancements in our understanding of the pathophysiology led to therapeutic mechanisms that have a more narrowed focus toward gut-specific targets, improving safety profiles.

A Macromolecular Janus Kinase (JAK) Inhibitor Prodrug Effectively Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice.

BACKGROUND: Tofacitinib (Tofa) has been approved for moderately to severely active ulcerative colitis (UC). To improve its therapeutic efficacy and limit dose-dependent toxicity, we developed a macromolecular prodrug of Tofa (P-Tofa). If the prodrug design improves the potency and duration of Tofa therapy, it would widen its therapeutic window, potentially leading to improved safety and better clinical management of UC. METHODS: P-Tofa was synthesized by conjugating Tofa to N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer via a cleavable carbamate linker. DSS-induced UC mouse model were treated with Tofa (daily oral gavage, from day 8), P-Tofa (single intravenous administration on day 8, dose equivalent to Tofa treatment) and saline. Healthy mice were used as a positive control. The therapeutic efficacy was evaluated using disease activity index (DAI), endoscopic score and end-point histology. The optical imaging, immunohistochemistry and flow cytometry were used to understand P-Tofa's working mechanism. RESULTS: DAI results suggested that a single dose P-Tofa treatment was more efficacious than dose equivalent daily Tofa treatment. Endoscopic evaluation and histology analyses confirmed that while both P-Tofa and Tofa protected the colon, P-Tofa treated group was observed with better colon integrity with less tissue damage. Optical imaging, flow cytometry and immunohistochemistry results showed that P-Tofa passively targeted the inflamed colon and being retained via cellular sequestration. CONCLUSIONS: Single intravenous administration of P-Tofa was more effective than dose equivalent daily oral Tofa gavage in ameliorating DSS-induced colitis. This observed superior therapeutic efficacy may be attributed to P-Tofa's passive targeting to and retention by the inflamed colon.

Needle-Knife Fistulotomy for the Rescue: An Unusual Cause of Iatrogenic Extrahepatic Biliary Obstruction.

A 71-year-old male presented to our institution with cholestatic hepatitis after having recently undergone upper endoscopy for treatment of gastrointestinal bleeding. Further investigation with endoscopic retrograde cholangiopancreatography revealed a hemostatic clip on the ampulla of Vater. After initial attempts at cannulation of the common bile duct were unsuccessful, biliary decompression was achieved by use of needle-knife fistulotomy. A common bile duct stent was placed and the liver function tests improved prior to discharge.

Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis.

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are complex diseases that result from the chronic dysregulated immune response in the gastrointestinal tract. The exact etiology is not fully understood, but it is accepted that it occurs when an inappropriate aggressive inflammatory response in a genetically susceptible host due to inciting environmental factors occurs. To investigate the pathogenesis and etiology of human IBD, various animal models of IBD have been developed that provided indispensable insights into the histopathological and morphological changes as well as factors associated with the pathogenesis of IBD and evaluation of therapeutic options in the last few decades. The most widely used experimental model employs dextran sodium sulfate (DSS) to induce epithelial damage. The DSS colitis model in IBD research has advantages over other various chemically induced experimental models due to its rapidity, simplicity, reproducibility and controllability. In this manuscript, we review the newer publicized advances of research in murine colitis models that focus upon the disruption of the barrier function of the intestine, effects of mucin on the development of colitis, alterations found in microbial balance and resultant changes in the metabolome specifically in the DSS colitis murine model and its relation to the pathogenesis of IBD.

Hemoperitoneum Secondary to Spontaneous Rupture of a Retroperitoneal Varix.

Hemoperitoneum due to a ruptured retroperitoneal varix is an exceedingly rare condition and a poor prognostic sign with catastrophic and life-threatening complication of portal hypertension. We present a unique case of a 56-year-old female with cirrhosis secondary to primary sclerosing cholangitis who presented with acute abdominal pain and hypovolemic shock prior to a cardiac arrest following a ruptured retroperitoneal varix without prior esophageal varices and a newly identified intrahepatic cholangiocarcinoma. The clinical presentation with abdominal pain and hemorrhagic shock is consistently reported in the relevant literature. Early recognition affords appropriate management and urgent surgical intervention leading to survival.

Spontaneous intramural duodenal hematoma in type 2B von Willebrand disease.

Intramural duodenal hematoma is a rare cause of a proximal gastrointestinal tract obstruction. Presentation of intramural duodenal hematoma most often occurs following blunt abdominal trauma in children, but spontaneous non-traumatic cases have been linked to anticoagulant therapy, pancreatitis, malignancy, vasculitis and endoscopy. We report an unusual case of spontaneous intramural duodenal hematoma presenting as an intestinal obstruction associated with acute pancreatitis in a patient with established von Willebrand disease, type 2B. The patient presented with abrupt onset of abdominal pain, nausea, and vomiting. Computed tomography imaging identified an intramural duodenal mass consistent with blood measuring 4.7 cm × 8.7 cm in the second portion of the duodenum abutting on the head of the pancreas. Serum lipase was 3828 units/L. Patient was managed conservatively with bowel rest, continuous nasogastric decompression, total parenteral nutrition, recombinant factor VIII (humateP) and transfusion. Symptoms resolved over the course of the hospitalization. This case highlights an important complication of an inherited coagulopathy.