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Aim: Crohn's anal fistula (CAF) is a complex condition, with no agreement on which patient characteristics should be routinely reported in studies. The aim of this study was to develop a core descriptor set of key patient characteristics for reporting in all CAF research.Method: Candidate descriptors were generated from published literature and stakeholder suggestions. Colorectal surgeons, gastroenterologists and specialist nurses in inflammatory bowel disease took part in three rounds of an international modified Delphi process using nine-point Likert scales to rank the importance of descriptors. Feedback was provided between rounds to allow refinement of the next ratings. Patterns in descriptor voting were assessed using principal component analysis (PCA). Resulting PCA groups were used to organize items in rounds two and three. Consensus descriptors were submitted to a patient panel for feedback. Items meeting predetermined thresholds were included in the final set and ratified at the consensus meeting.Results: One hundred and thirty three respondents from 22 countries completed round one, of whom 67.0% completed round three. Ninety seven descriptors were rated across three rounds in 11 PCA-based groups. Forty descriptors were shortlisted. The consensus meeting ratified a core descriptor set of 37 descriptors within six domains: fistula anatomy, current disease activity and phenotype, risk factors, medical interventions for CAF, surgical interventions for CAF, and patient symptoms and impact on quality of life.Conclusion: The core descriptor set proposed for all future CAF research reflects characteristics important to gastroenterologists and surgeons. This might aid transparent reporting in future studies.

Additional file 1: A supplement with additional detail about the study design (Supplemental methods) and tables comparing obeserved and expected case number for malignant tumors (Table S1), power analysis for detection of differences in cancer incidence (Table S2), analysis of association between likelihood to suffer AEs and QOL (Table S3), analysis of association of probability of suffering AEs and continued study participation (Table S4), analysis of association of apheresis number and QOL (Table S5). The supplement contains supplemental references.

The formation of Dobrogea as a modern geographical unit dates back to the late Neogene. The complex tectonic structure indicates multiphase changes in this key area that are buried under sediment or reflected in outcrops. Separate outcrops to Mesozoic sedimentary rocks and Precambrian-Paleozoic crystalline basement have been identified, while the main part of the region is characterized by Paleogene-Neogene outcrops. According to the peculiarities of the tectonic structure of Dobrogea, it is divided into the Southern, Central and Northern parts, which are separated by faults of the north-western extension and the Pre-Dobrogea depression. The main part of Dobrogea is located in Romania, within Ukraine there is the Prut ledge of the Northern Dobrogea and the Pre-Dobrogea depression, and part of the Southern Dobrogea goes within the borders of Bulgaria - the southern slope of the Dobrogea massif.The geodynamics of the joint zone determined the stages of formation, which were accompanied by platform transformations and tectonic-magmatic processes, as well as the formation of sedimentary complexes with coal, coal seams and oil and gas reservoirs. Based on the factor of destruction of Cretaceous and, possibly, Jurassic and Triassic deposits and their transformation into younger, Paleocene and Maikop deposits, it can be said that large accumulations of gas on structures in Paleogene traps are unlikely.Modern gas migration is characteristic of both the sedimentary strata of the Pre- Dobrogea Depression, ie the northern part of the study region, and the south-eastern part of Southern Dobrogea in carbonate deposits., Формування Добруджі як сучасної географічної одиниці датовано пізнім неогеном. Складна тектонічна будова вказує на багатофазні зміни цієї ключової області, які поховані під осадовим покривом і відображені у відслоненнях. Визначено окремі відслонення мезозойських осадових порід і докембрійсько-палеозойського кристалічного фундаменту, тоді як основна частина регіону характеризується палеоген-неогеновими відслоненнями. За особливостями тектонічної будови Добруджа поділяється на Південну (ПдД), Центральну (ЦД) і Північну (ПнД) частини, що розділяються розломами північно-західного простягання, та Переддобрудзький прогин. Основна частина Добруджі розміщена в Румунії, у межах України простягається Прутський виступ ПнД і Переддобрудзький прогин, а частина ПдД заходить у межі Болгарії – Південний схил масиву Добруджі.Геодинаміка зони зчленування визначала етапність формування, що супроводжувалося трансформаціями платформ і тектономагматичними процесами, а також формуванням осадових комплексів із вугільними, вуглистими пластами та нафтогазовими колекторами. Зважаючи на чинник руйнування крейдових і, можливо, юрських та тріасових покладів і переформування їх у молодших, палеоценових і майкопських відкладах, попередньо можна стверджувати, що великі скупчення газу в структурних пастках палеогену малоймовірні.Сучасна газова міграція характерна як для осадових товщ Переддобрудзького прогину, тобто північної частини регіону досліджень, так і південно-східної частини Південної Добруджі в карбонатних відкладах.

International audience; Fecal microbiota transplantation (FMT) or donor feces infusion is a therapy that aims to restore a perturbed gut microbiota composition and function. FMT is effective for treatment of patients with (multiple) recurrent Clostridioides difficile infections1–3 and recommended by current guidelines.4–6 In the near future, FMT may also become an accepted treatment option for other intestinal or extra-intestinal diseases.7FMT is performed using suspensions made of donor stool from carefully selected and screened healthy individuals.1,7 Donor screening is time consuming and costly. Before the establishment of stool banks, physicians and patients had to find their own donors. This resulted in uncontrolled application of FMT, and the logistical challenge made physicians reluctant to offer FMT to their patients. To overcome these problems, stool banks have been established.8,9 The mission of those stool banks is :to produce ready-to-use donor feces suspensions for treatment of patients,to improve the quality and safety of FMT by centralization and standardization,to increase the cost effectiveness of FMT, andto facilitate research.Stool banks are built in concordance with the model of blood banks and should follow quality standards applied to other transplantation products. Most stool banks are non-profit institutions, operating at a local (institution-based), national or international level. Recently, a UEG-funded working group was initiated to define quality standards for stool banking and FMT, which will result in further standardization of this new treatment approach. The current costs to deliver a ready-to-use stool suspension are €1050–1700 in Europe.9,10 There are also commercial initiatives,11 which may aim for much higher prices.Driven by the needs of patients, stool banks have emerged as new entities in a landscape without existing regulatory boundaries. This lack of guidance and National or European legislation may become a serious threat to providing the treatment for severely ill patients. This is also illustrated by the recent safety alert in the US about the transmission of multi-drug resistant organisms through FMT,12 which underlines the need for standardization, quality assurance, and a regulatory framework supporting the activities of stool banks. Legislation requires classification of stool as a product to treat patients. We strongly believe that stool should be considered a transplant product, or be regarded equivalent in status to blood products used for transplantation or transfusion purposes. The EU Tissue and Cells Directive (2004/23/EC) is best suited to guide FMT. Currently, this Directive does not cover FMT because the mechanism of action is not mediated by human cells. An adjustment to align this directive with the new reality of fecal transplantation is thus urgently needed. Only in the case of modification to the donated feces, other than those necessary for the conservation of the microbial community, does the product made of the donated feces become comparable to a drug and is best covered within the European directive for medicinal products intended for human use (2001/83/EC).Unfortunately, the misclassification of donor feces suspensions as a drug or pharmaceutical product, although difficult to imagine, is still one of the possible outcomes of the current discussion about classification. Currently, stool has already been classified as a drug in countries such as France, Germany, and the United Kingdom. Recently, companies have formed the “Pharmabiotic Research Institute” in Europe and the “Microbiome Therapeutics Innovation Group (MTIG)” in the US. The mission of those groups is “to improve market access,” and to “enhance the regulatory, investment, and commercial environment for microbiome therapeutic drug product development.” Both groups have published statements about the classification of FMT as a drug.13,14 MTIG actively collaborates with the Food and Drug Administration for the evaluation of safety parameters related to microbiota-based therapeutic products. Concern has been raised by the MTIG that the existence and accessibility of material from stool banks limits enrollment into clinical trials for microbiome therapeutics. This illustrates how companies are active to influence the current discussion about classification and regulation of FMT. In fact, this discussion has already been troubled by commercial interest in the US some years ago.15In this regard, it is important to mention the overall major disadvantages of classification as a drug, which will result in time-consuming and costly registration processes, and a sharp and unjustified rise in costs. Most importantly, this will negatively impact availability and innovation, obstructing, for example, the future development of single-donor individualized solutions due to the requirements for standardization of active substances. We postulate that stool treatment defined as drug treatment is counterproductive. Stool is not a standardized product that is produced in a factory, but a highly diverse and donor-specific substance of human origin (SoHO) delivered by healthy, usually unpaid, volunteer donors. Therefore, stool suspensions require suitable guidance of quality and safety measures comparable to guidance of other SoHO (blood, tissues, cells and organs) within the EU.If government authorities seek affordable and quality-assured FMT, a supportive regulatory framework, in combination with appropriate funding or reimbursement, is required for stool banks. This will not only guarantee broad access and safety of FMT, but also enable the future innovation of this new treatment strategy targeting the gut microbiota. If eventually future research results in the replacement of FMT by standardized mixtures of bacteria (or another yet undiscovered stool extract that could theoretically underly the clinical effects of FMT), these should indeed be regulated as a drug or pharmaceutical product.

The South Balkan extensional system consists of normal faults and associated sedimentary basins within southern Bulgaria, Macedonia, eastern Albania, northern Greece, and northwestern Turkey. Extensional tectonism began during the final convergence across the Vardar, Intra-Pontide, and Izmir-Ankara suture zones, where oceanic regions closed between continental Europe and continental fragments that make up the Pelagonian, Sakar, and western Anatolian tectonic units. Earliest extension of latest Cretaceous-middle Eocene age appears to have occurred within a regional convergent tectonic setting and may be related to an increase in gravitation potential energy within a thickening continental lithosphere. Following diachronous closure across the suture zone, from the middle Eocene to late Oligocene, the transition from a regionally convergent to a regionally extensional tectonic setting occurred and was associated with abundant magmatism and formation of sedimentary basins. Extension was associated with lithospheric thinning probably related to changes in geometry of the subducted slab, dynamics of the mantle wedge, and beginning of slab rollback along the Hellenic subduction zone. A short period of local and diachronous (?) shortening (during latest Oligocene-early Miocene time) occurred in the Thrace basin of northwestern Turkey and in some basins in western Bulgaria and eastern Macedonia. Regional extension began in middle Miocene time and was related to the regional extensional tectonic setting that has dominated the Aegean extensional region to the present. Trench rollback was the dominant dynamic process, but during late Miocene time it was modified by the formation of the western part of the North Anatolian fault zone that partially decoupled the South Balkan extensional system from the Aegean extensional region. During late Cenozoic time, east-west-striking normal faults and associated sedimentary basins in the eastern part of the South Balkan extensional system propagated westward in tandem with westward migration of north-south-striking normal faults and sedimentary basins from western Bulgaria into eastern Albania. This migration was caused by evolution of the Hellenic subduction zone as it increased its curvature during trench rollback and clockwise and counterclockwise rotation of crustal fragments in the west and east, respectively. After formation of the western part of the North Anatolian fault zone, extension within the eastern part of the South Balkan extensional system was related to southward movement of its lithosphere at a slower rate than the extension within the Aegean extensional region. Active extension and basin formation show two provinces of extension that are nearly at right angles to one another and their overlap in the central South Balkan extensional system: east-west extension in central Albania to eastern Macedonia and north-south extension from northwestern Greece and eastern Macedonia to eastern Bulgaria and northwestern Turkey. © 2008 Geological Society of America.

http://www.uni-tuebingen.de/geo/met-map/index.html

Background: Acid suppressing drugs (ASD) are generally used in acute pancreatitis (AP); however, large cohorts are not available to understand their efficiency and safety. Therefore, our aims were to evaluate the association between the administration of ASDs, the outcome of AP, the frequency of gastrointestinal (GI) bleeding and GI infection in patients with AP. Methods: We initiated an international survey and performed retrospective data analysis on AP patients hospitalized between January 2013 and December 2018. Results: Data of 17,422 adult patients with AP were collected from 59 centers of 23 countries. We found that 23.3% of patients received ASDs before and 86.6% during the course of AP. ASDs were prescribed to 57.6% of patients at discharge. ASD administration was associated with more severe AP and higher mortality. GI bleeding was reported in 4.7% of patients, and it was associated with pancreatitis severity, mortality and ASD therapy. Stool culture test was performed in 6.3% of the patients with 28.4% positive results. Clostridium difficile was the cause of GI infection in 60.5% of cases. Among the patients with GI infections, 28.9% received ASDs, whereas 24.1% were without any acid suppression treatment. GI infection was associated with more severe pancreatitis and higher mortality. Conclusions: Although ASD therapy is widely used, it is unlikely to have beneficial effects either on the outcome of AP or on the prevention of GI bleeding during AP. Therefore, ASD therapy should be substantially decreased in the therapeutic management of AP. (C) 2020 IAP and EPC. Published by Elsevier B.V.