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Burden and outcomes for complex perianal fistulas in Crohn's disease:Systematic review

World Journal of Gastroenterology 2018年第42期24卷 4821-4834页

作者： Julian Panes walter reinisch Ewa Rupniewska Shahnaz Khan Joan Forns Javaria Mona Khalid Daniela Bojic Haridarshan Patel Department of Gastroenterology Hospital Clínic de BarcelonaIDIBAPSCIBERehdBarcelona 08036Spain Medical University of Vienna Vienna 1090Austria RTI Health Solutions Manchester M20 2LSUnited Kingdom RTI Health Solutions Research Triangle ParkNC 27709United States RTI Health Solutions Barcelona 08028Spain Takeda DeerfieldIL 60015United States

AIM To systematically review the literature on epidemiology,disease burden, and treatment outcomes for Crohn's disease(CD) patients with complex perianal *** PubMed, Embase, and Cochrane were searched for relevant articles(published 2000-November 2016) and congress abstracts(published 2011-November 2016).RESULTS Of 535 records reviewed, 62 relevant sources were identified(mostly small observational studies). The cumulative incidence of complex perianal fistulas in CD from two referral-centre studies was 12%-14%(follow-up time, 12 years in one study; not reported in the second study). Complex perianal fistulas result in greatly diminished quality of life; up to 59% of patients are at risk of faecal incontinence. Treatments include combinations of medical and surgical interventions and expanded allogeneic adipose-derived stem cells. High proportions of patients experience lack of or inadequate response to treatment(failure and relapse rates,respectively: medical, 12%-73% and 0%-41%; surgical:0%-100% and 11%.20%; combined medical/surgical:0%-80% and 0%-50%; stem cells: 29%-47% and not reported). Few studies(1 of infliximab; 3 of surgical interventions)have been conducted in treatment-refractory patients, a population with high unmet needs. Limited data exist on the clinical value of anti-tumour necrosis factor-α dose escalation in patients with complex perianal fistulas in *** Complex perianal fistulas in CD pose substantial clinical and humanistic burden. There is a need for effective treatments, especially for patients refractory to antitumour necrosis factor-α agents, as evidenced by high failure and relapse rates.

关键词： Burden Complex perianal fistulas Crohn’s disease Epidemiology Outcomes Systematic literature review Treatment

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Resistance to activated protein C is a risk factor for fibrostenosis in Crohn’s disease

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World Journal of Gastroenterology 2006年第37期12卷 6026-6031页

作者： Gottfried Novacek Wolfgang Miehsler Julia Palkovits walter reinisch Thomas Waldhr Center of Public Health Department of Epidemiology Medical University of Vienna Vienna Austria Stylianos Kapiotis Alfred Gangl Harald Vogelsang Department of Internal Medicine Ⅳ Division of Gastroenterology andHepatology Medical University of Vienna Vienna Austria Clinical Institute of Medical and Chemical Laboratory Diagnostics Medical University of Vienna Vienna Austria

AIM: To evaluate the effect of resistance to activated protein C (aPCR), the most common known inherited thrombophilic disorder, on the risk of intestinal operation of fi brostenosis in patients with Crohn’s disease (CD). METHODS: In a previous study, we assessed the prevalence of aPCR in CD. In a retrospective case- controlled study, 8 of these CD patients with aPCR were now compared with 24 CD patients without aPCR, matched by gender, age at diagnosis and duration of disease in a 1:3 fashion. The primary end point was the occurrence of an intestinal CD-related operation with evidence of fibrostenosis in the bowel resection specimen. RESULTS: The Kaplan-Meier analysis revealed that patients with aPCR had a lower probability of remaining free of operation with f ibrostenosis than patients without aPCR (P = 0.0372; exact log-rank test) resulting in a signifi cantly shorter median time interval from diagnosis of CD to the fi rst operation with fi brostenosis (32 vs 160 mo). At 10 years, the likelihood of remaining free of operation with fi brostenosis was 25% for patients with aPCR and 57.8% for patients without aPCR. CONCLUSION: CD patients with aPCR are at higher risk to undergo intestinal operation of fi brostenosis than those without aPCR. This supports our hypothesis of aPCR being a possible risk factor for fi brostenosis in CD.

关键词： Fibrostenosis Resistance to activated protein C Factor V Leiden Intestinal surgery Crohn's disease

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Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: Phenotype-genotype correlations

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World Journal of Gastroenterology 2005年第10期11卷 1489-1495页

作者： Peter Laszlo Lakatos Laszlo Lakatos Ferenc Szalay Claudia Willheim-Polli Christoph (O|¨)sterreicher Zsolt Tulassay Tamas Molnar walter reinisch Janos Papp Gyula Mozsik Hungarian IBD Study Group Peter Ferenci 1st Department of Medicine Laszlo Lakatos Department of Internal Medicine 4 2nd Department of Medicine Semmelweis University 2nd Department of MedicineSemmelweis UniversityBudapest:Laszlo PronaiAnnamaria NemethPal Miheller Erzsebet Hospital 1st Department of MedicineBudapest: Agota KovacsLaszlo Bene Szent Janos Hospital 1st Department of Medicine:Gyorgy Szekely University of Pecs 1st Department of MedicinePecs:Beata Gasztonyi University of Szeged 1st Department of MedicineSzeged:Ferenc NagyJanos Lonovics Semmelweis Hospital 1st Department of MedicineMiskolc:Laszlo Ujszaszy University of Debrecen 2nd Department of MedicineDebrecen:Istvan AltorjaiKaroly Palatka Kenezi Gy. County Hospital 2nd Department of MedicineDebrecen: Gyula G. Kiss County Hospital 2nd Department of MedicineZalaegerszeg Ferenc Tarnok Markusovszky Hospital2nd Department of MedicineSzombathely:Zoltan Dobronte Csolnoky F. County Hospital 1st Department of MedicineVeszprem:Zsuzsanna ErdelyiTunde PandurGabor Mester

AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. RESULTS: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%,P<0.0001). SNP8/R702W (10.8% vs 6%, P= 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P= 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (ORhet=1.71, 95%CI=1.12-2.6, P= 0.0001, ORtwo-risk alleles = 25.2, 95%CI =4.37- ,P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P=0.0006), ileal disease (81.9% (?) 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P= 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69,95%CI = 1.13-2.55, P= 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P= 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. CONCLUSION: These results confirm that variant NOD2/ CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.

关键词： Crohn's disease NOD2 CARD15 TLR4 Extraintestinal manifestation Phenotype

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Update on pathogenesis and predictors of response of therapeutic strategies used in inflammatory bowel disease

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World Journal of Gastroenterology 2015年第44期21卷 12519-12543页

作者： Emilio G Quetglas Zlatan Mujagic Simone Wigge Daniel Keszthelyi Sebastian Wachten Ad Masclee walter reinisch Project Strategy and Science Grünenthal GmbH Internal Medicine University of Maastricht Medical Center Translational Science Grünenthal GmbH Molecular Pharmacology Grünenthal GmbH Internal Medicine. Mc Master University

The search for biomarkers that characterize specific aspects of inflammatory bowel disease(IBD), has received substantial interest in the past years and is moving forward rapidly with the help of modern technologies. Nevertheless, there is a direct demand to identify adequate biomarkers for predicting and evaluating therapeutic response to different therapies. In this subset, pharmacogenetics deserves more attention as part of the endeavor to provide personalized medicine. The ultimate goal in this area is the adjustment of medication for a patient's specific genetic background and thereby to improve drug efficacy and safety rates. The aim of the following review is to utilize the latest knowledge on immunopathogenesis of IBD and update the findings on the field of Immunology and Genetics, to evaluate the response to the different therapies. In the present article, more than 400 publications were reviewed but finally 287 included based on design, reproducibility(or expectancy to be reproducible and translationable into humans) or already measured in humans. A few testshave shown clinical applicability. Other, i.e., genetic associations for the different therapies in IBD have not yet shown consistent or robust results. In the close future it is anticipated that this, cellular and genetic material, as well as the determination of biomarkers will be implemented in an integrated molecular diagnostic and prognostic approach to manage IBD patients.

关键词： Mucosal immunology Biomarkers Pharmacology Mode of

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Nonlinear response of a multidirectional negative-stiffness isolation system via semirecursive multibody dynamic approach

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International Journal of Mechanical System Dynamics 2024年第3期4卷 258-277页

作者： Wei Dai Biagio Carboni Giuseppe Quaranta Yongjun Pan walter Lacarbonara College of Mechanical and Vehicle Engineering Chongqing UniversityChongqingChina Department of Structural and Geotechnical Engineering Sapienza University of RomeRomeItaly

This paper investigates an innovative negative-stiffness device(NSD)that modifies the apparent stiffness of the supported structure for seismic *** NSD comprises a lower base on the bottom and a cap on the top,together with a connecting rod,vertical movable wall,and compressed elastic spring,as well as circumferentially arranged,pretensioned external ropes,and inclined shape memory *** configuration can deliver negative stiffness and energy dissipation in any direction within the horizontal plane.A numerical model of the device is developed through a two-step semirecursive method to obtain the force–displacement characteristic *** a model is first validated through comparison with the results obtained via the commercial software ***,a large parametric study is performed to assess the role and the influence of each design variable on the overall response of the proposed *** guidelines are drawn from this analysis to guide the system design and optimization.

关键词： multibody system negative stiffness semirecursive approach seismic protection vibration isolation

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The Paris 2024 Olympic and Paralympic Games

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Journal of Sport and Health Science 2024年第6期13卷 717-718页

作者： walter Herzog Human Performance Laboratory Faculty of KinesiologyUniversity of CalgaryCalgaryAB T2N 1N4Canada

The first modern Olympic Games took place in Athens in *** in those early days of the Olympics only amateur and gentleman athletes were allowed to participate,today Olympic athletes are highly trained professionals often dedicating decades of preparation for the chance to compete in the Olympic *** sharp contrast to these highly trained athletes,the world’s population becomes less physically active on average,resulting in an obesity epidemic with associated metabolic syndrome and increased mortality through non-communicable diseases(e.g.,Collins et al.^(1)).

关键词： Olympic allowed sharp

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Intraocular pressure before and after capsulorhexis using two viscoelastic substances and two surgical approaches in enucleated porcine eyes

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1156-1160页

作者： Chiraz Ben Abdallah walter Sekundo Markus SLadewig Daniel M.Handzel Augenzentrum Osthessen Fulda 36037Germany University Eye Hospital Philipps-University Marburg 35043Germany University Eye Hospital Philipps-University Campus FuldaFulda 36043Germany

AIM:To investigate the influence of ophthalmic viscoelastic devices(OVDs)and different surgical approaches on the intraocular pressure(IOP)before and after creation of the curvilinear circular capsulorhexis(CCC)as a measure for anterior chamber stability during this ***:Prospective experimental WetLab study carried out on enucleated porcine *** was measured before and after CCC with the iCare Rebound tonometer(iCare ic200;iCare Finland Oy,Vantaa,Finland).The OVDs used were a cohesive one[Z-Hyalin,Carl Zeiss Meditec AG,Germany;hyaluronic acid(HA)]and a dispersive[Z-Celcoat,Carl Zeiss Meditec AG,Germany;hydroxy propylmethylcellulosis(HPMC)].The CCC was created using Utrata forceps or 23 g microforceps in different combinations with the ***:Using the Utrata forceps the IOP dropped from 63.65±6.44 to 11.25±3.63 mm Hg during the *** use of different OVDs made no *** the 23 g microforceps the IOP dropped from 65.35±8.15 to 36.55±6.09 mm *** difference between IOP drop using either Utrata forceps or 23 g microforceps was highly significant regardless of the OVD ***:Using the sideport for the creation of the capsulorhexis leads to a lesser drop in IOP during this maneuver compared to the main incision in enucleated porcine *** use of different OVD has no significant influence on IOP drop.

关键词： cataract surgery ophthalmosurgical viscoelastic device intraocular pressure capsulorhexis enucleated porcine eye

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A simple laboratory method for the generation of mixed brominated-chlorinated paraffin single chain mixtures

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Emerging Contaminants 2024年第2期10卷 90-97页

作者： walter Vetter Clara Hägele Karin Herrmann Tobias Schulz Sina Schweizer University of Hohenheim Institute of Food Chemistry(170b)Garbenstr.2870599StuttgartGermany

Brominated-chlorinated paraffins(Br-CPs)are a comparably new compound class that features both Cl and Br atoms on one or several alkane *** to legal restrictions in the use of conventional chlorinated paraffins(CPs),Br-CPs have the potential to become emerging ***,their determination is hampered by the lack of suitable reference ***,we present a simple synthesis procedure with single chain alkanes that leads to Br-CPs with∼4–8 chlorine and 1 to 4 bromine substituents according to gas chromatography with electron capture negative ion mass spectrometry(GC/ECNI-MS).The single-chain Br-CP mixtures were obtained by the shared chlorination and bromination of eight single-chain alkanes(C10 to C17)at two reaction times,*** carbon content of the 16 single-chain Br-CP products,determined by elemental analysis(EA),ranged from 30.8 to 43.8%.The typical hump peak known from CPs was detected with GC with flame ionization detection(GC/FID),electron capture detection(GC/ECD)and GC/*** complexity indicated that low-resolution mass spectrometry is not sufficient for an adequate analysis of Br-CPs.A mathematical formula was developed which allows to calculate all possible combinations of Br and Cl that are in line with the carbon *** proton magnetic resonance spectroscopy(1H NMR)spectra showed similarities to the ones of CPs with one chemical shift range for protons on nonhalogenated carbons and one for protons with one halogen on the same carbon.

关键词： NMR) mixtures alkanes

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Pumping-induced Well Hydraulics and Groundwater Budget in a Leaky Aquifer System with Vertical Heterogeneity in Aquitard Hydraulic Properties

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Acta Geologica Sinica(English Edition) 2024年第2期98卷 477-490页

作者： ZHUANG Chao LÜChenyang YAN Long LI Yabing ZHOU Zhifang WANG Jinguo DOU Zhi walter A.ILLMAN School of Earth Sciences and Engineering Hohai UniversityNanjing 211100China School of Geography Earth and Environmental SciencesUniversity of BirminghamBirmingham B152TTU.K. Department of Modern Mechanics University of Science and Technology of ChinaHefei 230027China Department of Earth and Environmental Sciences University of WaterlooOntario N2L 3G1Canada

In groundwater hydrology,aquitard heterogeneity is often less considered compared to aquifers,despite its significant impact on groundwater hydraulics and groundwater resources evaluation.A semi-analytical solution is derived for pumping-induced well hydraulics and groundwater budget with consideration of vertical heterogeneity in aquitard hydraulic conductivity(K)and specific storage(S_(s)).The proposed new solution is innovative in its partitioning of the aquitard into multiple homogeneous sub-layers to enable consideration of various forms of vertically heterogeneous K or S_(s).Two scenarios of analytical investigations are explored:one is the presence of aquitard interlayers with distinct K or S_(s) values,a common field-scale occurrence;another is an exponentially depth-decaying aquitard S_(s),a regional-scale phenomenon supported by statistical *** investigations reveal that a low-K interlayer can significantly increase aquifer drawdown and enhance aquifer/aquitard depletion;a high-S_(s) interlayer can noticeably reduce aquifer drawdown and increase aquitard *** of low-K or high-S_(s) interlayers also significantly impact well hydraulics and groundwater *** the context of an exponentially depth-decaying aquitard S_(s),a larger decay exponent can enhance aquifer *** using current models with a vertically homogeneous aquitard,half the sum of the geometric and harmonic means of exponentially depth-decaying aquitard S_(s) should be used to calculate aquitard depletion and unconfined aquifer leakage.

关键词： hydrogeology aquitard vertical heterogeneity semi-analytical solution well hydraulics groundwater budget

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Plant community on a volcano mountaintop reveals unique high-altitude vegetation in southeastern Brazil

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Journal of Mountain Science 2024年第9期21卷 3018-3030页

作者： Igor Musauer KESSOUS Ruy JoséValka ALVES Nílber Gonçalves da SILVA Amilcar walter SAPORETTI JUNIOR Biodiversity Laboratory Federal Institute of EducationScience and Technology of Southern Minas Gerais(IFSULDEMINAS)Av.Dirce Pereira Rosa300-Jardim Esperança37713-100Poços de CaldasMGBrazil Department of Botany National MuseumFederal University of Rio de JaneiroQuinta da Boa Vista s.n.São Cristóvão20949-040Rio de JaneiroRJBrazil Gothenburg Global Biodiversity Centre Carl Skottsbergs Gata 22BSE 41319GothenburgSweden

Mountains exhibit a high degree of endemism and diversity,however,quantifying their biodiversity can be *** to islands,species isolation in mountainous regions results in comparable patterns of evolution and extinction,rendering their biodiversity unique and highly susceptible to anthropogenic *** topographic relief in mountains plays a crucial role in creating habitat complexity,which in turn contribute to high plant ***,we investigated plant diversity in the volcano mountaintop vegetation on the Poços de Caldas Plateau,a region situated in the ecotone between the Atlantic Forest and Cerrado,characterized by natural radiation and significant anthropogenic *** employed an automated approach through the filtering of georeferenced and non-georeferenced data to obtain a list of plant species in the ***,we statistically investigated the similarity among different high-altitude vegetations belonging to the campos de altitude from the Atlantic Forest and campos rupestres from the *** plateau exhibits high plant diversity,including 1,659 specific and infraspecific taxa,especially belonging to Asteraceae and *** analyses suggest that geographical distance is a strong predictor of dissimilarity and that the Poços de Caldas Plateau is more floristically related to the campos rupestres,despite being associated with campos de *** region possesses a unique set of biodiversity,indicating that it may be a distinct ***,we hypothesize that Pleistocene events likely influenced the conformation of the current floristic composition in the region through species interchange between the Cerrado and Atlantic *** study also highlights the few taxa assessed for conservation status and anthropogenic threats that this habitat is facing.

关键词： Atlantic Forest Biogeography Cerrado Community ecology Grassland

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