Impact of Holding Immunosuppressive Therapy in Patients with Inflammatory Bowel Disease Around mRNA COVID-19 Vaccine Administration on Humoral Immune Response and Development of COVID-19 Infection

BACKGROUND AND AIMS: The BNT162b2 and mRNA-1273 COVID-19 vaccines are efficacious in patients with inflammatory bowel disease; but there is a lack of data examining if holding immunosuppressive therapy around vaccination improves immune response. We studied the effect of holding IBD medications around the time of vaccination on antibody response and breakthrough COVID-19 infection. METHODS: Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID is a prospective cohort of individuals with IBD receiving COVID-19 vaccination. Quantitative measurement of anti-receptor binding domain IgG antibodies to SARS-CoV-2 was performed 8 weeks after completing a vaccination series. RESULTS: A total of 1854 patients were included; 59% were on anti-tumour necrosis factor [TNF] [10% of these on combination therapy], 11% on vedolizumab, and 14% on ustekinumab; 11% of participants held therapy before or after vaccine administration for at least 2 weeks. Antibody levels were similar in participants continuing versus holding anti-TNF monotherapy before or after the second vaccine [BNT162b2: 10 μg/mL vs 8.9 μg/mL; mRNA-1273: 17.5 μg/mL vs 14.5 μg/mL]. Comparable results were seen in those on combination therapy. Antibody titres in those on ustekinumab or vedolizumab were higher compared with anti-TNF users, but there was no significant difference if the drug was held or continued [BNT162b2: 22.5 μg/mL vs 23 μg/mL; mRNA-1273: 88 μg/mL vs 51 μg/mL]. Holding therapy was not associated with decreased rate of COVID-19 infection compared with those not holding therapy [BNT162b2: 28% vs 29%; mRNA-1273: 19% vs 31%]. CONCLUSION: We recommend continuing IBD medications while receiving mRNA COVID-19 vaccination without interruption

Pearling and Pinching: Propagation of Rayleigh Instabilities

A new category of front propagation problems is proposed in which a spreading instability evolves through a singular configuration before saturating. We examine the nature of this front for the viscous Rayleigh instability of a column of one fluid immersed in another, using the marginal stability criterion to estimate the front velocity, front width, and the selected wavelength in terms of the surface tension and viscosity contrast. Experiments are suggested on systems that may display this phenomenon, including droplets elongated in extensional flows, capillary bridges, liquid crystal tethers, and viscoelastic fluids. The related problem of propagation in Rayleigh-like systems that do not fission is also considered.Comment: Revtex, 7 pages, 4 ps figs, PR

Dietary patterns are not associated with disease activity among patients with inflammatory conditions of the pouch in a prospective cohort

BACKGROUND: Evidence-based recommendations regarding the influence of diet on inflammatory conditions of the pouch after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) are limited. METHODS: We analyzed dietary patterns at enrollment in a prospective registry of patients with 1 of 4 inflammatory conditions of the pouch (acute pouchitis, chronic antibiotic-dependent pouchitis, chronic antibiotic refractory pouchitis, and Crohn\u27s disease of the pouch). We analyzed dietary intake by disease activity at enrollment and then compared dietary patterns among patients who remained in remission throughout the 12-month follow-up to those patients who experienced a disease relapse. We also compared dietary patterns among patients with inflammatory conditions of the pouch to the United States Department of Agriculture (USDA) recommended daily goals. RESULTS: Among 308 patients, there were no differences in dietary patterns among patients with 1 of the 4 disease states at enrollment. Additionally, among the 102 patients in remission at baseline, there were no significant differences noted among patients who went on to experience a disease flare in the 12 months after enrollment compared to those patients who remained in remission. However, patients with inflammatory conditions of the pouch demonstrated decreased intake of several food groups and macronutrients including dairy, fruits, vegetables, whole grains, and fiber when compared to USDA recommendations. CONCLUSIONS: In a prospective cohort, we demonstrated no impact of dietary patterns on disease activity. The relative deficiencies in several food groups and macronutrients among patients after IPAA indicate the potential role of targeted nutritional counseling in this population

Unraveling the Link between Periodontitis and Inflammatory Bowel Disease: Challenges and Outlook

Periodontitis and Inflammatory Bowel Disease (IBD) are chronic inflammatory conditions, characterized by microbial dysbiosis and hyper-immunoinflammatory responses. Growing evidence suggest an interconnection between periodontitis and IBD, implying a shift from the traditional concept of independent diseases to a complex, reciprocal cycle. This review outlines the evidence supporting an Oral-Gut axis, marked by a higher prevalence of periodontitis in IBD patients and vice versa. The specific mechanisms linking periodontitis and IBD remain to be fully elucidated, but emerging evidence points to the ectopic colonization of the gut by oral bacteria, which promote intestinal inflammation by activating host immune responses. This review presents an in-depth examination of the interconnection between periodontitis and IBD, highlighting the shared microbiological and immunological pathways, and proposing a multi-hit hypothesis in the pathogenesis of periodontitis-mediated intestinal inflammation. Furthermore, the review underscores the critical need for a collaborative approach between dentists and gastroenterologists to provide holistic oral-systemic healthcare.Comment: Total Words: 7,016 Figures: 3 Tables: 2 Reference: 34

Treatment patterns and standardized outcome assessments among patients with inflammatory conditions of the pouch in a prospective multicenter registry

BACKGROUND: Much of our understanding about the natural history of pouch-related disorders has been generated from selected populations. We designed a geographically diverse, prospective registry to study the disease course among patients with 1 of 4 inflammatory conditions of the pouch. The primary objectives in this study were to demonstrate the feasibility of a prospective pouch registry and to evaluate the predominant treatment patterns for pouch-related disorders. METHODS: We used standardized diagnostic criteria to prospectively enroll patients with acute pouchitis, chronic antibiotic-dependent pouchitis (CADP), chronic antibiotic refractory pouchitis (CARP), or Crohn\u27s disease (CD) of the pouch. We obtained detailed clinical and demographic data at the time of enrollment, along with patient-reported outcome (PRO) measures. RESULTS: We enrolled 318 patients (10% acute pouchitis, 27% CADP, 12% CARP, and 51% CD of the pouch). Among all patients, 55% were on a biologic or small molecule therapy. Patients with CD of the pouch were more likely to use several classes of therapy ( CONCLUSIONS: In a population where most patients had refractory inflammatory conditions of the pouch, we established a framework to evaluate PROs and clinical effectiveness. This infrastructure will be valuable for long-term studies of real-world effectiveness for pouch-related disorders

The Shapes of Flux Domains in the Intermediate State of Type-I Superconductors

In the intermediate state of a thin type-I superconductor magnetic flux penetrates in a disordered set of highly branched and fingered macroscopic domains. To understand these shapes, we study in detail a recently proposed "current-loop" (CL) model that models the intermediate state as a collection of tense current ribbons flowing along the superconducting-normal interfaces and subject to the constraint of global flux conservation. The validity of this model is tested through a detailed reanalysis of Landau's original conformal mapping treatment of the laminar state, in which the superconductor-normal interfaces are flared within the slab, and of a closely-related straight-lamina model. A simplified dynamical model is described that elucidates the nature of possible shape instabilities of flux stripes and stripe arrays, and numerical studies of the highly nonlinear regime of those instabilities demonstrate patterns like those seen experimentally. Of particular interest is the buckling instability commonly seen in the intermediate state. The free-boundary approach further allows for a calculation of the elastic properties of the laminar state, which closely resembles that of smectic liquid crystals. We suggest several new experiments to explore of flux domain shape instabilities, including an Eckhaus instability induced by changing the out-of-plane magnetic field, and an analog of the Helfrich-Hurault instability of smectics induced by an in-plane field.Comment: 23 pages, 22 bitmapped postscript figures, RevTex 3.0, submitted to Phys. Rev. B. Higher resolution figures may be obtained by contacting the author

Twirling and Whirling: Viscous Dynamics of Rotating Elastica

Motivated by diverse phenomena in cellular biophysics, including bacterial flagellar motion and DNA transcription and replication, we study the overdamped nonlinear dynamics of a rotationally forced filament with twist and bend elasticity. Competition between twist injection, twist diffusion, and writhing instabilities is described by a novel pair of coupled PDEs for twist and bend evolution. Analytical and numerical methods elucidate the twist/bend coupling and reveal two dynamical regimes separated by a Hopf bifurcation: (i) diffusion-dominated axial rotation, or twirling, and (ii) steady-state crankshafting motion, or whirling. The consequences of these phenomena for self-propulsion are investigated, and experimental tests proposed.Comment: To be published in Physical Review Letter

IBD LIVE Case Series—Case 6: Persistent Skin Lesions in a Patient with Crohn's Disease: You Hear Hoof Beats and Discover a Zebra

LEARNING OBJECTIVES After completing this IBD LIVE-CME activity, physicians should be better able to: 1. Explain the side effects of medications used to treat IBD, particularly anti-TNFs. 2. Recognize the various types of skin lesions that may occur in IBD patients, focusing on those that arise among patients on immunosuppressants. 3. Be cognizant of the presentation and treatment of pyoderma gangrenosum in IBD patients. 4. Describe the various types of mycobacterial infections that may occur among IBD patients, especially those that are on anti-TNFs. 5. Describe the risk factors for developing a Mycobacterial marinum infection and how it may present dermatologically. 6. Explain how to diagnose and treat a Mycobacterial marinum infection