EpiBeds: Data informed modelling of the COVID-19 hospital burden in England.

The first year of the COVID-19 pandemic put considerable strain on healthcare systems worldwide. In order to predict the effect of the local epidemic on hospital capacity in England, we used a variety of data streams to inform the construction and parameterisation of a hospital progression model, EpiBeds, which was coupled to a model of the generalised epidemic. In this model, individuals progress through different pathways (e.

Artificial-intelligence-driven discovery of catalyst genes with application to CO activation on semiconductor oxides.

Catalytic-materials design requires predictive modeling of the interaction between catalyst and reactants. This is challenging due to the complexity and diversity of structure-property relationships across the chemical space. Here, we report a strategy for a rational design of catalytic materials using the artificial intelligence approach (AI) subgroup discovery.

Typing of inflammatory lesions of the pituitary.

Inflammatory pituitary lesions account for 1.8% of all specimens from the German Pituitary Tumor Registry. They occure in 0.

Outcomes of Pregnancies With Maternal/Paternal Exposure in the Tofacitinib Safety Databases for Ulcerative Colitis.

Background: Active inflammatory bowel disease increases the risk of adverse pregnancy outcomes. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). As a small molecule, tofacitinib is likely to cross the placental barrier; however, information on the effects of tofacitinib on pregnancy outcomes is limited.

Quality of Care in Ulcerative Colitis: A Modified Delphi Panel Approach.

Objectives: To establish clinical consensus on important and relevant quality-of-care (QoC) attributes in ulcerative colitis (UC) treatment that may improve treatment outcomes and guide best practices.

Methods: Thirty-eight QoC attributes were identified in a literature review. Sixteen European-based experts were selected based on their contributions to UC guidelines, publications, and patient care.

Granulocyte/monocyte adsorptive apheresis for the treatment of therapy-refractory chronic active ulcerative colitis.

Objectives: Current options for patients with steroid-dependent, chronic-active ulcerative colitis (UC) with insufficient response/intolerance to immunosuppressants (ISs) and/or biologics are limited. The aim of this study was to assess the long-term outcome of granulocyte/monocyte adsorptive (GMA) apheresis (Adacolumn) in this population.

Materials And Methods: Ninety five adults with steroid-dependent active UC and insufficient response/intolerance to IS and/or TNF inhibitors received 5-8 aphereses in a single induction series of ≤10 weeks.

High Spatial Resolution Cardiovascular Magnetic Resonance at 7.0 Tesla in Patients with Hypertrophic Cardiomyopathy - First Experiences: Lesson Learned from 7.0 Tesla.

Background: Cardiovascular Magnetic Resonance (CMR) provides valuable information in patients with hypertrophic cardiomyopathy (HCM) based on myocardial tissue differentiation and the detection of small morphological details. CMR at 7.0T improves spatial resolution versus today's clinical protocols.

Crohn's disease.

Crohn's disease is a relapsing systemic inflammatory disease, mainly affecting the gastrointestinal tract with extraintestinal manifestations and associated immune disorders. Genome wide association studies identified susceptibility loci that--triggered by environmental factors--result in a disturbed innate (ie, disturbed intestinal barrier, Paneth cell dysfunction, endoplasmic reticulum stress, defective unfolded protein response and autophagy, impaired recognition of microbes by pattern recognition receptors, such as nucleotide binding domain and Toll like receptors on dendritic cells and macrophages) and adaptive (ie, imbalance of effector and regulatory T cells and cytokines, migration and retention of leukocytes) immune response towards a diminished diversity of commensal microbiota. We discuss the epidemiology, immunobiology, amd natural history of Crohn's disease; describe new treatment goals and risk stratification of patients; and provide an evidence based rational approach to diagnosis (ie, work-up algorithm, new imaging methods [ie, enhanced endoscopy, ultrasound, MRI and CT] and biomarkers), management, evolving therapeutic targets (ie, integrins, chemokine receptors, cell-based and stem-cell-based therapies), prevention, and surveillance.

Targeting leukocyte migration and adhesion in Crohn's disease and ulcerative colitis.

Crohn's disease and ulcerative colitis are two chronic inflammatory bowel diseases. Current biologic therapies are limited to blocking tumor necrosis factor alpha. However, some patients are primary non-responders, experience a loss of response, intolerance or side effects defining the urgent unmet need for novel treatments.

Anti-inflammatory effects of Saccharomyces boulardii mediated by myeloid dendritic cells from patients with Crohn's disease and ulcerative colitis.

Saccharomyces boulardii (Sb) is a probiotic yeast that has demonstrated efficacy in pilot studies in patients with inflammatory bowel disease (IBD). Microbial antigen handling by dendritic cells (DC) is believed to be of critical importance for immunity and tolerance in IBD. The aim was to characterize the effects of Sb on DC from IBD patients.

Aberrant plasmacytoid dendritic cell distribution and function in patients with Crohn's disease and ulcerative colitis.

Dendritic cell (DC) function is believed to be of critical importance for the pathogenesis of inflammatory bowel disease (IBD). To date, most research in animal models and the few human data available is restricted to myeloid DC, while plasmacytoid DC (pDC) capable of controlling both innate and adaptive immune responses have not yet been investigated systematically in human Crohn's disease (CD) or ulcerative colitis (UC). CD11c(-) , CD303(+) /CD304(+) and CD123(+) pDC from peripheral blood (n = 90), mucosal tissue (n = 28) or mesenteric lymph nodes (n = 40) (MLNs) of patients with UC and CD or controls were purified and cultured.

CB-01-05-MMX, a novel oral controlled-release low molecular weight heparin for the potential treatment of ulcerative colitis.

CB-01-05-MMX (LMW Heparin MMX), being developed by Cosmo Pharmaceuticals SpA, is a novel oral parnaparin sodium formulation for the potential treatment of ulcerative colitis. At the time of publication, clinical trial data were limited and the mechanism of action had not been elucidated. However, in one phase I and one phase IIb trial in patients with left-sided ulcerative colitis, CB-01-05-MMX had an acceptable safety profile and was not associated with bleeding complications, which is a known side effect of unfractionated heparin and low molecular weight heparin compounds previously evaluated for the treatment of ulcerative colitis.

Tradition as the genealogy of truth Hippocrates and Boerhaave between assimilation, variation and deviation.

It is a matter of fact that rarely in the history of modern medicine has a physician gained such immediate and universal fame, and rarely has his contribution to medical knowledge and teaching been so promptly and almost unanimously recognized as a fundamental and, so to speak, a foundational one, as in the case of Boerhaave. In fact, the contribution he gave to provide medicine with a 'scientific' framework, and medical teaching with solid methodological bases, proved decisive. Otherwise, his appraisal of the Ancients (and especially of Hippocrates) and his will to refer to Hippocrates as a model for medical teaching were proverbial.

The physician as teacher. Epistemic function, cognitive function and the incommensurability of errors.

In many Hippocratic writings, the writers' attention is often focused on registering and discussing medical errors. Far from being sporadic and fortuitous, these discussions represent a privileged rhetorical resource in order to produce different effects. The aims of my paper will be: 1) to determine some of the most important contexts in which errors become the object of medical discourse; 2) to distinguish, per exempla, the typologies of errors made object of discourse; 3) to give an epistemological outline which may clarify which functions these discourses have and whether these functions respond coherently to a conscious plan of medical knowledge.

Prospective randomized open-label multicenter phase I/II dose escalation trial of visilizumab (HuM291) in severe steroid-refractory ulcerative colitis.

Background: Visilizumab is a humanized IgG(2) monoclonal anti-CD3 antibody. We evaluated its safety and dose response in severe intravenous steroid-refractory ulcerative colitis (UC).

Methods: In all, 104 patients were treated.

Exaggerated inflammatory response of primary human myeloid dendritic cells to lipopolysaccharide in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) results from a breakdown of tolerance towards the indigenous flora in genetically susceptible hosts. Failure of dendritic cells (DC) to interpret molecular microbial patterns appropriately when directing innate and adaptive immune responses is conceivable. Primary (conventional, non-monocyte generated) CD1c(+)CD11c(+)CD14(-)CD16(-)CD19(-) myeloid blood or mucosal dendritic cells (mDC) from 76 patients with Crohn's disease (CD) or ulcerative colitis (UC) in remission, during flare-ups (FU) and 76 healthy or non-IBD controls were analysed by fluorescence activated cell sorter (FACS) flow cytometry and real-time polymerase chain reaction.

Saccharomyces boulardii inhibits lipopolysaccharide-induced activation of human dendritic cells and T cell proliferation.

Saccharomyces boulardii (Sb) is a probiotic yeast preparation that has demonstrated efficacy in inflammatory and infectious disorders of the gastrointestinal tract in controlled clinical trials. Although patients clearly benefit from treatment with Sb, little is known on how Sb unfolds its anti-inflammatory properties in humans. Dendritic cells (DC) balance tolerance and immunity and are involved critically in the control of T cell activation.

Management of severe abdominal infections.

Abdominal infections are associated with significant morbidity and mortality. Nearly all bacteria causing abdominal infections are derived from the endogenous flora of the alimentary tract. The resulting infection is typically polymicrobial and comprised of both aerobic and anaerobic microbes.

What's new in inflammatory bowel disease in 2008?

Ulcerative colitis and Crohn's disease represent the two major forms of inflammatory bowel disease. In this highlight topic series of articles we cover the latest developments in genetics and epidemiology, intestinal physiology, mucosal immunology, mechanisms of epithelial cell injury and restitution, current medical therapy, modern surgical management, important extra-intestinal complications such as primary sclerosing cholangitis, cholangiocellular carcinoma and autoimmune hepatitis as well as endoscopic and molecular screening, detection and prevention of small bowel and colorectal cancer.

Inflammatory bowel disease: clinical aspects and established and evolving therapies.

Crohn's disease and ulcerative colitis are two idiopathic inflammatory bowel disorders. In this paper we discuss the current diagnostic approach, their pathology, natural course, and common complications, the assessment of disease activity, extraintestinal manifestations, and medical and surgical management, and provide diagnostic and therapeutic algorithms. We critically review the evidence for established (5-aminosalicylic acid compounds, corticosteroids, immunomodulators, calcineurin inhibitors) and emerging novel therapies--including biological therapies--directed at cytokines (eg, infliximab, adalimumab, certolizumab pegol) and receptors (eg, visilizumab, abatacept) involved in T-cell activation, selective adhesion molecule blockers (eg, natalizumab, MLN-02, alicaforsen), anti-inflammatory cytokines (eg, interleukin 10), modulation of the intestinal flora (eg, antibiotics, prebiotics, probiotics), leucocyte apheresis and many more monoclonal antibodies, small molecules, recombinant growth factors, and MAP kinase inhibitors targeting various inflammatory cells and pathways.

Inflammatory bowel disease: cause and immunobiology.

Crohn's disease and ulcerative colitis are idiopathic inflammatory bowel disorders. In this paper, we discuss how environmental factors (eg, geography, cigarette smoking, sanitation and hygiene), infectious microbes, ethnic origin, genetic susceptibility, and a dysregulated immune system can result in mucosal inflammation. After describing the symbiotic interaction of the commensal microbiota with the host, oral tolerance, epithelial barrier function, antigen recognition, and immunoregulation by the innate and adaptive immune system, we examine the initiating and perpetuating events of mucosal inflammation.

Tacrolimus is safe and effective in patients with severe steroid-refractory or steroid-dependent inflammatory bowel disease--a long-term follow-up.

Objective: We and others have reported the use of tacrolimus in refractory inflammatory bowel disease (IBD). Little is known about its long-term efficacy and safety.

Methods: In this retrospective, observational single center study the charts of 53 adult patients with steroid-dependent (n = 18) or steroid-refractory (n = 35) IBD, Crohn's disease (CD) (n = 11), ulcerative colitis (UC) (n = 40), or pouchitis (PC) (n = 2) were reviewed.

Mesalamine promotes intestinal epithelial wound healing in vitro through a TGF-beta-independent mechanism.

Objective: Treatment with 5-aminosalicylic acid (5-ASA) derivatives is one of the main principles in the therapy of uncomplicated mild to moderate inflammatory bowel diseases (IBD). The beneficial effect of 5-ASA in the treatment of IBD is attributed to its anti-inflammatory and anti-oxidant properties within the inflamed gut. The aim of this study was to investigate whether 5-ASA also modulates intestinal epithelial wound repair in vitro.