Intervju: akademik Jakša Barbić

Over the past 20 years evidence has accumulated confirming the immunomodulatory role of the appendix in ulcerative colitis (UC). This led to the idea that appendectomy might alter the clinical course of established UC. The objective of this body of research is to evaluate the short-term and medium-term efficacy of appendectomy to maintain remission in patients with UC, and to establish the acceptability and cost-effectiveness of the intervention compared to standard treatment. These paired phase III multicenter prospective randomised studies will include patients over 18 years of age with an established diagnosis of ulcerative colitis and a disease relapse within 12 months prior to randomisation. Patients need to have been medically treated until complete clinical (Mayo score <3) and endoscopic (Mayo score 0 or 1) remission. Patients will then be randomised 1:1 to a control group (maintenance 5-ASA treatment, no appendectomy) or elective laparoscopic appendectomy plus maintenance treatment. The primary outcome measure is the one year cumulative UC relapse rate - defined both clinically and endoscopically as a total Mayo-score ≥5 with endoscopic subscore of 2 or 3. Secondary outcomes that will be assessed include the number of relapses per patient at 12 months, the time to first relapse, health related quality of life and treatment costs, and number of colectomies in each arm. The ACCURE and ACCURE-UK trials will provide evidence on the role and acceptability of appendectomy in the treatment of ulcerative colitis and the effects of appendectomy on the disease course. NTR2883 ; ISRCTN5652301

Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches

IVORY Guidelines (Instructional Videos in Otorhinolaryngology by YO-IFOS): A Consensus on Surgical Videos in Ear, Nose, and Throat

Objectives/Hypothesis: Otolaryngology instructional videos available online are often of poor quality. The objective of this article was to establish international consensus recommendations for the production of educational surgical videos in otolaryngology. Study Design: DELPHI survey. Methods: Twenty-seven international respondents participated in this study from 12 countries. Consensus was reached after three rounds of questionnaires following the Delphi methodology. The proposals having reached the 80% agreement threshold in the third round were retained. Results: The main recommendations are as follows: 1) Ethics: patients must be anonymized and unrecognizable (apart from plastic surgery if necessary). A signed authorization must be obtained if the person is recognizable. 2) Technical aspects: videos should be edited and in high-definition (HD) quality if possible. Narration or subtitles and didactic illustrations are recommended. 3) Case presentation: name of pathology and procedure must be specified; the case should be presented with relevant workup. 4) Surgery: surgical procedures should be divided into several distinct stages and include tips and pitfalls. Pathology should be shown if relevant. Key points should be detailed at the end of the procedure. 5) Organ-specific: type of approach and bilateral audiometry should be specified in otology. Coronal plane computed tomography scans should be shown in endonasal surgery. It is recommended to show pre- and postoperative videos in voice surgery and preoperative drawings and photos of scars in plastic surgery, as well as the ventilation method in airway surgery. Conclusions: International recommendations have been determined to assist in the creation and standardization of educational surgical videos in otolaryngology and head and neck surgery. Level of Evidence: 5 Laryngoscope, 2020

Expression of a colorectal antigen defined by a new monoclonal antibody, CO-TL1.

Contains fulltext : 58500.pdf (publisher's version ) (Closed access)A murine monoclonal antibody (MoAb CO-TL1, IgG1) has been raised by differential screening of hybridoma supernatants on sections of human large and small intestines, followed by screening on colon adenomas as well as on colorectal carcinomas. In both paraffin sections and cryostat sections, the antibody stained strongly all cell types in adult, neonatal and fetal human colorectal epithelium, that is, the goblet cells, the columnar cells and the endocrine cells. No staining was observed in the remaining parts of the normal gastrointestinal tract and other tissues. As revealed by immuno electron microscopy the epitope was present in the apical and basolateral cell membranes, the Golgi complex, secretory vesicles of goblet and columnar cells, and also in granules of the endocrine cells. The epitope in colorectal tissue sections was resistant to the deglycosylation enzymes neuramidase, diastase and hyaluronidase indicating its proteinaceous nature. This colorectal antigen remained expressed in 100% of colorectal adenomas (n = 39) and 86% (n = 29) of colorectal carcinomas. The expression was reduced in undifferentiated carcinomas. The CO-TL1 antibody detected also most other gastrointestinal adenocarcinomas and a few carcinomas of the ovary, uterus, breast, gallbladder and pancreas. However, it never detected carcinomas derived from the thyroid, lung, liver, bladder, kidney, prostate, testis, serous membranes of body cavities and skin. A wild-type variant protein of > 300 kDa of the colorectal antigen was identified in normal colorectal epithelium. In colorectal tumours, however, two tumour variant forms were found of 160-200 and 115-140 kDa, respectively. Our data indicate that this new MoAb CO-TL1 can be considered as a useful marker, which identifies normal colorectal epithelium and gastrointestinal tumours and especially colorectal tumours with high accuracy and excludes tumours originated from thyroid, lung, liver, bladder, kidney, prostate, testis, mesothelium and skin

Immune Modulation by Different Types of beta 2 -> 1-Fructans Is Toll-Like Receptor Dependent

<p>Introduction: beta 2 -> 1-fructans are dietary fibers. Main objectives of this study were 1) to demonstrate direct signalling of beta 2 -> 1-fructans on immune cells, 2) to study whether this is mediated by the pattern recognition receptors Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain-containing proteins (NODs), and 3) to relate the observed effects to the chain length differences in beta 2 -> 1-fructans.</p><p>Methods: Four different beta 2 -> 1-fructan formulations were characterised for their chain length profile. Human peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with beta 2 -> 1-fructans, and production of IL-1Ra, IL-1 beta, IL-6, IL-10, IL-12p70, and TNF-alpha was analysed. Reporter cells for TLRs and NODs were incubated with beta 2 -> 1-fructans and analysed for NF-kappa B/AP-1 activation.</p><p>Results: Cytokine production in human PBMCs was dose-and chain length-dependent. Strikingly, short chain enriched beta 2 -> 1-fructans induced a regulatory cytokine balance compared to long chain enriched beta 2 -> 1-fructans as measured by IL10/ IL-12 ratios. Activation of reporter cells showed that signalling was highly dependent on TLRs and their adapter, myeloid differentiation primary response protein 88 (MyD88). In human embryonic kidney reporter cells, TLR2 was prominently activated, while TLR4, 5, 7, 8, and NOD2 were mildly activated.</p><p>Conclusions: beta 2 -> 1-fructans possess direct signalling capacity on human immune cells. By activating primarily TLR2, and to a lesser extent TLR4, 5, 7, 8, and NOD2, beta 2 -> 1-fructan stimulation results in NF-kappa B/AP-1 activation. Chain length of beta 2 -> 1fructans is important for the induced activation pattern and IL-10/IL-12 ratios.</p>