Efficacy of Ustekinumab in Crohn's Disease With and Without Concurrent Autoimmune Skin Disease.

BACKGROUND: Approximately 33% of Crohn's disease (CD) patients have associated autoimmune skin disease. The pathophysiology of the latter frequently involves interleukin-12/interleukin-23 signaling pathways that may also impact gut inflammation. Ustekinumab is an anti-IL-12/23 FDA-approved biologic for psoriasis and inflammatory bowel disease. However, its relative efficacy has never been studied in CD with autoimmune skin disease (CD-ASD) vs CD without autoimmune skin disease (CD-none). METHODS: This is a retrospective, single-center, case-control study comparing markers of disease activity between CD-ASD and CD-none. Biomarkers (fecal calprotectin [FCP], C-reactive protein [CRP]) prior to drug initiation and after at least 5 months of standard IBD dose ustekinumab therapy were extracted from the medical record. In addition, 2 blinded observers performed 5-point Likert scoring before and after endoscopic, pathologic, and imaging reports. RESULTS: In all, 395 CD patients received ustekinumab therapy (79 CD-ASD, 316 CD-none). Patients were similar in age; gender; ethnicity; CD severity, phenotype, and duration; tobacco, immunomodulator, and steroid use. Ustekinumab had greater efficacy in CD-ASD when evaluated by FCP (P = .0337) and CRP (P = .078). The CD-ASD group also showed better outcomes in Likert scores of endoscopy (P = .016), histopathology (P = .074), and imaging (P = .094). In all Likert parameters, CD-ASD had more patients with complete resolution of moderate/severe disease (P < .05). Additional subanalyses for surgeries, ulcers, abscesses, fistulas, and colitis were conducted, with colitis reaching statistical significance (P = .0011). CONCLUSIONS: Concurrent autoimmune skin disease in CD is associated with greater ustekinumab effectiveness in controlling intestinal inflammation.

Bleeding with the artificial heart: Gastrointestinal hemorrhage in CF-LVAD patients.

Continuous-flow left ventricular assist devices (CF-LVADs) have significantly improved outcomes for patients with end-stage heart failure when used as a bridge to cardiac transplantation or, more recently, as destination therapy. However, its implantations carries a risk of complications including infection, device malfunction, arrhythmias, right ventricular failure, thromboembolic disease, postoperative and nonsurgical bleeding. A significant number of left ventricular assist devices (LVAD) recipients may experience recurrent gastrointestinal hemorrhage, mainly due to combination of antiplatelet and vitamin K antagonist therapy, activation of fibrinolytic pathway, acquired von Willebrand factor deficiency, and tendency to develop small intestinal angiodysplasias due to increased rotary speed of the pump. Gastrointestinal bleeding in LVAD patients remains a source of increased morbidity including the need for blood transfusions, extended hospital stays, multiple readmissions, and overall mortality. Management of gastrointestinal bleeding in LVAD patients involves multidisciplinary approach in stabilizing the patients, addressing risk factors and performing structured endoluminal evaluation with focus on upper gastrointestinal tract including jejunum to find and eradicate culprit lesion. Medical and procedural intervention is largely successful and universal bleeding cessation occurs in transplanted patients.

A Quality Improvement Educational Intervention to Increase Knowledge of Cardiogastroenterology Amongst Medical Trainees and Nursing Staff.

Introduction: The American Society of Gastrointestinal Endoscopy recommends continuing aspirin prior to routine endoscopy. National data show that few endoscopists follow the current guidelines due to concern about bleeding and perceived minimal downside to stopping aspirin. Utilizing the Kern model, we implemented an educational quality improvement initiative aimed at increasing knowledge of antithrombotic management periendoscopy and during acute gastrointestinal (GI) bleeding. Methods: We implemented an interactive lecture incorporating a large-group discussion to help residents learn to define low- versus high-risk procedures, distinguish thrombotic risk in medical conditions, present the procedural risks associated with use of antiplatelets, and list current practice guidelines. Nursing staff received a tailored lecture with the goal of learning proper management of current antiplatelets and holding parameters for anticoagulants prior to endoscopy. Both groups received pre-and posttest questionnaires evaluating their knowledge. Results: Eighteen nurses and 75 medical trainees received this intervention. Significant score improvement was noted in both groups. The greatest change was seen in aspirin management (30.5% vs. 95.0% for group 1, 43.7% vs. 91.9% for group 2; p < .0001). For management of antiplatelets after aspirin-induced GI bleed, the medical trainees improved from 50.7% to 93.3%. Chi-square analysis showed a statistically significant difference in knowledge across all areas among medical trainees pre-and posttest (p < .001). Discussion: This quality-based educational intervention significantly increased the knowledge of nurses and medical trainees in management guidelines that directly impact patient care. Similar educational programs may be very effective in improving quality and safety.

Two design strategies for enhancement of multilayer-DNA-origami folding: underwinding for specific intercalator rescue and staple-break positioning.

Single-layer DNA origami is an efficient method for programmable self-assembly of nanostructures approximating almost any desired two-dimensional shape from ~5 MDa of DNA building material. In this method, a 7 kilobase single "scaffold" strand is assembled with hundreds of oligodeoxyribonucleotide "staple" strands to form a parallel array of double helices. Multiple layers of such DNA sheets also can be designed to assemble into a stack, enabling construction of solid three-dimensional shapes with considerably greater mechanical rigidity than two-dimensional shapes; however, the folding yield often is much lower and the required folding times are much longer. Here we introduce two strategies for designing multi-layer DNA origami that demonstrate potential for boosting assembly yield: (1) individual base pairs can be inserted between crossovers, allowing for greater bowing of helices at positions away from crossovers and therefore reduced electrostatic repulsion. At the same time, this underwinding of double helices increases a destabilizing torsional strain energy but then also increases affinity for intercalators, and binding of such intercalators can relieve this stress. We also have exploited this enhanced affinity for intercalators to PEGylate the surface of the nanostructures in a noncovalent fashion using PEG-tris-acridine. (2) Positioning of staple-strand breaks in the DNA origami such that each staple strand includes a 14 nucleotide (nt) continuous segment that binds to a complementary 14 nt continuous segment of the scaffold can greatly improve folding yields.