Abdominal pain in quiescent inflammatory bowel disease.

OBJECTIVES: Inflammation is an important driver of abdominal pain in inflammatory bowel disease (IBD). However, some patients in remission still experience pain. We aimed to identify risk factors associated with abdominal pain in quiescent IBD (QP-IBD) and to characterize differences from patients with active disease experiencing pain (AP-IBD). METHODS: We performed a retrospective analysis utilizing data from our institution's IBD Natural History Registry (January 1, 2015-August 31, 2018). Endoscopic evaluation, concurrent laboratory studies, and validated surveys were completed by participants. Demographic and clinical data were also abstracted. RESULTS: We recruited 122 patients with quiescent disease (65f:57 m; 93CD:26UC:3Indeterminate) for participation in this study, 74 (60.7%) had QP-IBD. QP-IBD patients were more likely to have anxiety/depression (71.6% vs. 25.0%, p < 0.001) or to use antidepressants (47.3% vs. 22.9%, p < 0.010), opiates (18.9% vs. 2.1%, p < 0.010), other pain medications (50.0% vs. 18.8%, p < 0.010), or corticosteroids (18.9% vs. 2.1%, p < 0.010). On logistic regression analysis, corticosteroid use, anxious/depressed state, and female gender were each independently associated with QP-IBD (p < 0.050 or less). Compared with AP-IBD patients (n = 110, 59f:51 m; 69CD:38UC:3Indeterminate), QP-IBD patients were more likely to use antidepressants (45.6% vs. 26.4%, p < 0.010). Platelet, white blood cell, C-reactive protein, and sedimentation rate levels were all less likely to be elevated in QP-IBD (all p < 0.050), though 44% exhibited pathological elevation in at least one. DISCUSSION: QP-IBD was independently associated with corticosteroid use, anxiety/depression, and female gender. Compared with AP-IBD, QP-IBD patients were more likely to use antidepressants and less likely to exhibit elevated inflammatory markers. However, many QP-IBD patients still demonstrated pathological elevation of these tests, demonstrating the need to develop new noninvasive screening methods for this condition.

Abdominal Pain and Anxious or Depressed State Are Independently Associated With Weight Loss in Inflammatory Bowel Disease.

BACKGROUND: Many factors impact nutritional status in inflammatory bowel disease (IBD). We undertook this study to evaluate the potential role that abdominal pain has on weight loss and dietary behavior in IBD. METHODS: This is a retrospective cohort study utilizing data from an IBD registry at our institution between January 1, 2015 and August 31, 2018. Pain scores and nutritional outcomes were derived from validated questionnaires while key associated clinical data were derived from the medical record. RESULTS: Three hundred and three patients (154 females; 206 Crohn's disease) were included in this study. Ninety-six patients (31.7%) had experienced a 6-lb or greater weight loss in the prior month. On multivariate analysis, abdominal pain and anxious/depressed state were independently associated with weight loss, while female gender and NSAID use were inversely associated with weight loss (P < 0.05). IBD patients with abdominal pain also reported significantly poorer dietary behavior than those without this symptom. CONCLUSIONS: Abdominal pain is more likely to result in negative dietary outcomes and independently associated with weight loss in IBD. IBD providers should screen for malnutrition when patients report abdominal pain.

Over-the-scope clip management of non-acute, full-thickness gastrointestinal defects.

BACKGROUND: Endoscopic management of full-thickness gastrointestinal tract defects (FTGID) has become an attractive management strategy, as it avoids the morbidity of surgery. We have previously described the short-term outcomes of over-the-scope clip management of 22 patients with non-acute FTGID. This study updates our prior findings with a larger sample size and longer follow-up period. METHODS: A retrospective analysis of prospectively collected data was conducted. All patients undergoing over-the-scope clip management of FTGID between 2013 and 2019 were identified. Acute perforations immediately managed and FTGID requiring endoscopic suturing were excluded. Patient demographics, endoscopic adjunct therapies, number of endoscopic interventions, and need for operative management were evaluated. Success was strictly defined as complete FTGID closure. RESULTS: We identified 92 patients with 117 FTGID (65 fistulae and 52 leaks); 27.2% had more than one FTGID managed simultaneously. The OTSC device (Ovesco Endoscopy, Tubingen, Germany) was utilized in all cases. Additional closure attempts were required in 22.2% of defects. With a median follow-up period of 5.5 months, overall defect closure success rate was 66.1% (55.0% fistulae vs. 79.6% leaks, p = 0.007). There were four mortalities from causes unrelated to the FTGID. Only 14.9% of patients with FTGID underwent operative management. There were no complications related to endoscopic intervention and no patients required urgent surgical intervention. CONCLUSIONS: Over-the-scope clip management of FTGID represents a safe alternative to potentially morbid operative intervention. When strictly defining success as complete closure of all FTGID, endoscopy was successful in 64.4% of patients with only a small minority of patients ultimately requiring surgery.

Oral plasma kallikrein inhibitor BCX7353 for treatment of hereditary angioedema.

Hereditary angioedema (HAE) is rare disorder caused by a SERPING1 gene mutation that triggers severe swelling of the skin and upper airway. Treatment options for HAE with deficient and dysfunctional C1-inhibitor are expanding to include small-molecule drugs that inhibit protein interactions in the kallikrein-kinin system. Discovered by BioCryst Pharmaceuticals, BCX7353 is a synthetic, once-daily, small molecule drug that can be taken as an oral capsule to treat HAE attacks and for prophylaxis. This article will summarize recent and current BCX7353 clinical trials. Overall, results indicate BCX7353 is a promising form of therapy with a rapid 1 h onset of action, long duration of action, and acceptable tolerance.

A review of kallikrein inhibitor lanadelumab in hereditary angioedema.

Hereditary angioedema with C1 esterase inhibitor deficiency is a rare disorder characterized by unpredictable swelling of the face, larynx and gastrointestinal tract. Kallikreins are serine proteases that cleave kininogens to produce bradykinin leading to inflammation. A new prophylactic drug is lanadelumab (DX-2930, SHP-643), a recombinant, fully human IgG1 monoclonal antibody kallikrein inhibitor. Pharmacokinetics show a half-life of 14 days with a dose-dependent effect. Completed trials for lanadelumab include two Phase III studies with updated efficacy in preventing angioedema in hereditary angioedema patients. Ongoing data show the safety of the targeted therapy along with less frequent administration requirements. Information on long-term safety is still needed, as well as, further studies on the correlation of subcutaneous administered dosing requirements and severity of side effects.

When high viscosity of pancreatic cysts precludes effective EUS-FNA: a benchtop comparison of negative pressure devices.

Background and study aims Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of pancreatic cystic lesions (PCLs) is an important diagnostic tool; however, it is often unsuccessful due to high viscosity of cystic fluid. In an effort to improve FNA, we objectively compared eight vacuum device configurations to determine the most effective method for aspirating viscous fluid collections. We also tested a high-frequency oscillation (HFO) technique that could be employed in FNA. Materials and methods Maximum gauge pressures of four vacuum devices were measured: two standard EUS-FNA syringes, a 50-cc Alliance II device, and a nonmedical hand vacuum pump. To aspirate a viscous stock solution, 19-gauge and 22-gauge needles were used and flow rates were calculated. HFO was also applied to the needle during aspiration to determine effect on aspiration rate. Results Aspiration devices generated maximum gauge pressures ranging from -21.5 to -27.5 inHg. The 19-gauge FNA needle aspirated viscous fluid 11.3 × faster on average than a 22-gauge needle. HFO increased average flow rates by 29.7 % in 19G and 124.6 % in 22G configurations. Conclusion EUS-FNA of viscous fluid can be optimized by using the lowest possible gauge needle and connecting a vacuum device capable of generating and sustaining near perfect vacuum. This can be accomplished by maximizing syringe volume. In addition, connector-tubing length between the syringe and needle should be minimized, and tubing wall should be sufficiently strong to resist collapse under vacuum. Other novel techniques to increase fluid yield include a hand vacuum pump and application of HFO to FNA.

Multimodality Imaging of the Right Ventricle.

OPINION STATEMENT: Right ventricular (RV) structure and function is clinically important in a wide range of conditions. While conventional echocardiography (echo) methods are widely used, its limitations in RV assessment due its complex geometry are well recognized. New applications of traditional echo methods as well as emerging echo techniques including 3-dimensional (3D) echo and speckle tracking strain have the potential to overcome limitations of conventional echo, though widespread clinical use remains to be seen. Volumetric methods using cardiac magnetic resonance (CMR) and computed tomography (CT) provide accurate assessment of RV function without geometric assumptions. In addition, tissue characterization imaging for myocardial scar and fat using CMR and CT provides important information regarding the RV beyond structure and function alone and has clinical applications for diagnosis and prognosis in a broad range of pathologies. Limitations also exist for these two advanced modalities including availability and patient suitability for CMR and need for contrast and radiation exposure for CT. The complementary role of each modality for the RV as well as emerging evidence for the use of each imaging method in diagnosis and management of RV pathologies is outlined in this study.

NEDE: an open-source scripting suite for developing experiments in 3D virtual environments.

BACKGROUND: As neuroscientists endeavor to understand the brain's response to ecologically valid scenarios, many are leaving behind hyper-controlled paradigms in favor of more realistic ones. This movement has made the use of 3D rendering software an increasingly compelling option. However, mastering such software and scripting rigorous experiments requires a daunting amount of time and effort. NEW METHOD: To reduce these startup costs and make virtual environment studies more accessible to researchers, we demonstrate a naturalistic experimental design environment (NEDE) that allows experimenters to present realistic virtual stimuli while still providing tight control over the subject's experience. NEDE is a suite of open-source scripts built on the widely used Unity3D game development software, giving experimenters access to powerful rendering tools while interfacing with eye tracking and EEG, randomizing stimuli, and providing custom task prompts. RESULTS: Researchers using NEDE can present a dynamic 3D virtual environment in which randomized stimulus objects can be placed, allowing subjects to explore in search of these objects. NEDE interfaces with a research-grade eye tracker in real-time to maintain precise timing records and sync with EEG or other recording modalities. COMPARISON WITH EXISTING METHODS: Python offers an alternative for experienced programmers who feel comfortable mastering and integrating the various toolboxes available. NEDE combines many of these capabilities with an easy-to-use interface and, through Unity's extensive user base, a much more substantial body of assets and tutorials. CONCLUSIONS: Our flexible, open-source experimental design system lowers the barrier to entry for neuroscientists interested in developing experiments in realistic virtual environments.

Simultaneous decomposition of multiple hyperspectral data sets: signal recovery of unknown fluorophores in the retinal pigment epithelium.

Upon excitation with different wavelengths of light, biological tissues emit distinct but related autofluorescence signals. We used non-negative matrix factorization (NMF) to simultaneously decompose co-registered hyperspectral emission data from human retinal pigment epithelium/Bruch's membrane specimens illuminated with 436 and 480 nm light. NMF analysis was initialized with Gaussian mixture model fits and constrained to provide identical abundance images for the two excitation wavelengths. Spectra recovered this way were smoother than those obtained separately; fluorophore abundances more clearly localized within tissue compartments. These studies provide evidence that leveraging multiple co-registered hyperspectral emission data sets is preferential for identifying biologically relevant fluorophore information.