Browsing by Subject "inflammatory bowel disease"

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  • FINUSTE Study Grp; Sipponen, Taina; af Björkesten, Clas-Göran; Hallinen, Taru; Ilus, Tuire; Soini, Erkki; Eberl, Anja; Heikura, Mikko; Kellokumpu, Mikko; Koskela, Ritva; Nielsen, Christian; Nuutinen, Heikki; Heikkinen, Markku; Suhonen, Ulla-Maija; Tillonen, Jyrki; Wennerström, E. Christina M.; Borsi, Andras; Koivunen, Minni R. (2021)
    Background Real-world evidence to support optimal ustekinumab dosing for refractory Crohn's disease (CD) patients remains limited. Data from a retrospective nationwide chart review study was utilized to explore ustekinumab dosing dynamics and optimization, identify possible clinical predictors of dose intensification, and to evaluate ustekinumab trough concentrations (TCs) and concomitant medication use in Finland. Methods Information gathered from17 Finnish hospitals included clinical chart data from 155 adult CD patients who received intravenous ustekinumab induction during 2017-2018. Data on ustekinumab dosing and TCs, concomitant corticosteroid and immunosuppressant use, and antiustekinumab antibodies were analyzed in a two-year follow-up, subject to availability. Results Among 140 patients onustekinumab maintenance therapy, dose optimization was required in 55(39%) of the patients, and 41/47 dose-intensified patients (87%) persisted on ustekinumab. At baseline, dose-intensified patient group had significantly higher C-reactive protein (CRP) levels, and at week 16, significantly lower ustekinumab TCs than in patients without dose intensification. Irrespective of dose optimization, a statistically significant reduction in the use of corticosteroids was observed at both 16 weeks and one year, coupled with an increased proportion of patients on ustekinumab monotherapy. Antiustekinumab antibodies were undetectable in all 28 samples from 25 patients collected throughout the study period. Conclusions Nearly a third of all CD patients on ustekinumab maintenance therapy, with a history of treatment-refractory and long-standing disease, required dose intensification. These patients persisted on ustekinumab and had significant reduction of corticosteroid use. Increased baseline CRP was identified as the sole indicator of dose intensification.
  • Giaretta, Paula R.; Suchodolski, Jan S.; Jergens, Albert E.; Steiner, Jorg M.; Lidbury, Jonathan A.; Cook, Audrey K.; Hanifeh, Mohsen; Spillmann, Thomas; Kilpinen, Susanne; Syrja, Pernilla; Rech, Raquel R. (2020)
    The intestinal microbiota is believed to play a role in the pathogenesis of inflammatory bowel disease in humans and chronic inflammatory enteropathy (CIE) in dogs. While most previous studies have described the gut microbiota using sequencing methods, it is fundamental to assess the spatial distribution of the bacteria for a better understanding of their relationship with the host. The microbiota in the colonic mucosa of 22 dogs with CIE and 11 control dogs was investigated using fluorescence in situ hybridization (FISH) with a universal eubacterial probe (EUB338) and specific probes for select bacterial groups. The number of total bacteria labeled with EUB338 probe was lower within the colonic crypts of dogs with CIE compared to controls. Helicobacter spp. and Akkermansia spp. were decreased on the colonic surface and in the crypts of dogs with CIE. Dogs with CIE had increased number of Escherichia coli/Shigella spp. on the colonic surface and within the crypts compared to control dogs. In conclusion, the bacterial microbiota in the colonic mucosa differed between dogs with and without CIE, with depletion of the crypt bacteria in dogs with CIE. The crypt bacterial species that was intimately associated with the host mucosa in control dogs was composed mainly of Helicobacter spp.
  • Puolanne, Anna-Maija; Qadri, Sami; Vesterinen, Tiina; Hiltunen, Saara; Mustonen, Aaro; Kurki, Samu; Kolho, Kaija-Leena; Arola, Johanna; Färkkilä, Martti (2022)
    Background: In the inflammatory bowel diseases, chronic inflammation predisposes to dysplasia and colorectal carcinoma, leading to the need of surveillance colonoscopies. The most-used marker of colonic inflammation is faecal calprotectin. Its correlation with endoscopic and histological findings is well-documented. In this study, we evaluated the role of sequential faecal calprotectin measurements in predicting colorectal dysplasia, to identify patients with increased risk of dysplasia or colonic malignancy in ulcerative colitis. Methods: We collected the faecal calprotectin measurements and colorectal histology reports of patients with ulcerative colitis treated in Helsinki University Hospital (Helsinki, Finland) between 2007 and 2017, with a focus on IBD-associated neoplasia, inflammatory activity, and sporadic adenomas. Using the time-weighted AUC of faecal calprotectin as a marker of inflammatory burden, we tested the performance of faecal calprotectin to predict the risk for colorectal neoplasia. Results: In total, 982 patients with ulcerative colitis were included. Of them, 845 had pancolitis and 127 concomitant primary sclerosing cholangitis. Forty-one patients (4%) had IBD-associated colorectal dysplasia and seven (0.7%) developed adenocarcinoma. In patients with constantly elevated faecal calprotectin level (>500 mu g/g), colorectal neoplasia was more frequent compared to those with low (
  • Paediat IBD Porto Grp ESPGHAN; Berger, Tal David; Lee, Huey Miin; Padmanaban, Lavenya Ramasamy; Kolho, Kaija-Leena; Shamir, Raanan; Shouval, Dror S. (2022)
    Objectives: Adult studies suggest that patients with isolated colonic Crohn disease (L2 CD) exhibit unique characteristics differentiating them from patients with ileo-caecal (L1) CD and ulcerative colitis (UC). We aimed to characterize clinical features and outcomes of paediatric patients with L2. Methods: Retrospective data was collected through the Porto Inflammatory Bowel Disease group of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) on Paediatric patients with L2, L1 or UC at different time-points. Outcome measures included time to first flare, hospital admissions, initiation of anti-tumor necrosis factor-alpha (TNF alpha) drug, stricture and surgery. Results: Three hundred patients were included: 102 L1, 94 L2 and 104 UC. Rates of hematochezia at presentation were 14.7%, 44.7% and 95.2%, while rates of fever were 12.7%, 26.6% and 2.9%, for patients with L1, L2 and UC, respectively (P < 0.001 for all comparisons). Skip lesions were identified in 65% of patients with L2, and granulomas in 36%, similar to L1 patients. Rates of anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic (pANCA) positivity significantly differed between the three groups: 25.4% and 16.7% for patients with L2, compared with 55.2% and 2.3%, and 1.8% and 52.9% for patients with L1 and UC, respectively. Response rates to exclusive enteral nutrition were comparable between L1 and L2 (78.3-82.4%), as was the response to oral steroids (70.4-76.5%) in the three groups. While times to first flare and admission were similar between groups, patients with L1 were commenced on anti-TNF alpha earlier. Moreover, stricturing phenotype and need for colectomy were very rare in patients with L2. Conclusions: Significant differences are observed in the clinical presentation and outcomes of Paediatric patients with L2, compared to patients with L1 and UC.
  • Pettersen, Henrik Sahlin; Belevich, Ilya; Royset, Elin Synnove; Smistad, Erik; Simpson, Melanie Rae; Jokitalo, Eija; Reinertsen, Ingerid; Bakke, Ingunn; Pedersen, Andre (2022)
    Application of deep learning on histopathological whole slide images (WSIs) holds promise of improving diagnostic efficiency and reproducibility but is largely dependent on the ability to write computer code or purchase commercial solutions. We present a code-free pipeline utilizing free-to-use, open-source software (QuPath, DeepMIB, and FastPathology) for creating and deploying deep learning-based segmentation models for computational pathology. We demonstrate the pipeline on a use case of separating epithelium from stroma in colonic mucosa. A dataset of 251 annotated WSIs, comprising 140 hematoxylin-eosin (HE)-stained and 111 CD3 immunostained colon biopsy WSIs, were developed through active learning using the pipeline. On a hold-out test set of 36 HE and 21 CD3-stained WSIs a mean intersection over union score of 95.5 and 95.3% was achieved on epithelium segmentation. We demonstrate pathologist-level segmentation accuracy and clinical acceptable runtime performance and show that pathologists without programming experience can create near state-of-the-art segmentation solutions for histopathological WSIs using only free-to-use software. The study further demonstrates the strength of open-source solutions in its ability to create generalizable, open pipelines, of which trained models and predictions can seamlessly be exported in open formats and thereby used in external solutions. All scripts, trained models, a video tutorial, and the full dataset of 251 WSIs with ~31 k epithelium annotations are made openly available at to accelerate research in the field.
  • Jalanka, Jonna; Cheng, Jing; Hiippala, Kaisa; Ritari, Jarmo; Salojärvi, Jarkko; Ruuska, Tarja; Kalliomaki, Marko; Satokari, Reetta (2020)
    Inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), are chronic debilitating disorders of unknown etiology. Over 200 genetic risk loci are associated with IBD, highlighting a key role for immunological and epithelial barrier functions. Environmental factors account for the growing incidence of IBD, and microbiota are considered as an important contributor. Microbiota dysbiosis can lead to a loss of tolerogenic immune effects and initiate or exacerbate inflammation. We aimed to study colonic mucosal microbiota and the expression of selected host genes in pediatric UC. We used high-throughput 16S rDNA sequencing to profile microbiota in colonic biopsies of pediatric UC patients (n= 26) and non-IBD controls (n= 27). The expression of 13 genes, including five for antimicrobial peptides, in parallel biopsies was assessed with qRT-PCR. The composition of microbiota between UC and non-IBD differed significantly (PCoA,p= 0.001). UC children had a decrease in Bacteroidetes and an increase in several family-level taxa including Peptostreptococcaceae and Enterobacteriaceae, which correlated negatively with the expression of antimicrobial peptides REG3G and DEFB1, respectively. Enterobacteriaceae correlated positively with the expression siderophore binding protein LCN2 and Betaproteobacteria negatively with DEFB4A expression. The results indicate that reciprocal interaction of epithelial microbiota and defense mechanisms play a role in UC.
  • Giaretta, Paula R; Rech, Raquel R; Guard, Blake C; Blake, Amanda B; Blick, Anna K; Steiner, Jörg M.; Lidbury, Jonathan A; Cook, Audrey K; Hanifeh, Mohsen; Spillmann, Thomas; Kilpinen, Susanne; Syrjä, Pernilla; Suchodolski, Jan (2018)
    Background Objective Intestinal absorption of bile acids is mediated by the apical sodium-dependent bile acid transporter (ASBT). Fecal bile acid dysmetabolism has been reported in dogs with chronic inflammatory enteropathy (CIE). Characterization of ASBT distribution along the intestinal tract of control dogs and comparison to dogs with CIE. Animals Methods Twenty-four dogs with CIE and 11 control dogs. The ASBT mRNA and protein expression were assessed using RNA in situ hybridization and immunohistochemistry, respectively. The concentrations of fecal bile acids were measured by gas chromatography-mass spectrometry. The fecal microbiota dysbiosis index was assessed with a quantitative polymerase chain reaction panel. Results Conclusions and Clinical Importance In control dogs, ASBT mRNA expression was observed in enterocytes in all analyzed intestinal segments, with highest expression in the ileum. The ASBT protein expression was restricted to enterocytes in the ileum, cecum, and colon. Dogs with CIE had significantly decreased expression of ASBT protein in the ileum (P = .001), which was negatively correlated with histopathological score (rho = -0.40; P-corr = .049). Additionally, dogs with CIE had a significantly increased percentage of primary bile acids in feces compared to controls (P = .04). The fecal dysbiosis index was significantly higher in dogs with CIE than in control dogs (P = .01). These findings indicate that ileal protein expression of ASBT is downregulated in dogs with CIE. This change may be linked to the inflammatory process, intestinal dysbiosis, and fecal bile acid dysmetabolism observed in these patients.
  • Koskinen, Milja (Helsingfors universitet, 2011)
    Tämä lisensiaatin tutkielma koostuu kolmesta osasta; kirjallisuuskatsauksesta, kokeellisesta osasta ja liitteistä. Iohexol on ionisoitumaton, trijodattu ja vesiliukoinen röntgenvarjoaine. Iohexolia on hyödynnetty lääketieteessä useita vuosia. Iohexolia on käytetty muun muassa angio- ja myelografiassa, lisäksi iohexolia on hyödynnetty arvioitaessa munuaiskerästen suodattumisnopeutta sekä suoliston läpäisevyyden muutoksia. Hevosen tulehduksellisessa suolistosairaudessa (Inflammatory bowel disease, IBD) suoliston rakenne ja sen läpäisevyys muuttuu; tyypillistä on tulehdussolujen kertyminen suoliston seinämään ja myös sidekudosmuodostusta saattaa esiintyä. Suolisto muutoksia saatetaan havaita sekä ohut- että paksusuolessa. IBD aiheuttaa hevoselle laihtumista, johtuen ravintoaineiden puutteellisesta imeytymisestä ja proteiinien menetyksestä suoleen suoliston häiriötilan yhteydessä. Tällä hetkellä IBD:n diagnostiikka perustuu tyypillisiin oireisiin, kliiniseen tutkimukseen, verinäytteisiin, glukoosin imeytymistestiin ja peräsuolesta otettuun koepalaan. IBD:n diagnostiikka on kuitenkin erittäin haastavaa ja tutkimusmenetelmiin liittyy lukuisia ongelmia, jotka vähentävät niiden luotettavuutta IBD:n diagnostiikassa. Tutkimuksemme tarkoituksena on kehittää hevosen IBD:n diagnostiikkaa entistä helpompaan, luotettavampaan ja turvallisempaan suuntaan. Tämän alustavan tutkimuksen tavoitteet olivat: (1) tutkia voidaanko iohexol havaita hevosen seerumissa oraalisen annostelun jälkeen ja (2) muodostaa iohexolin pitoisuuskuvaaja ajan funktiona terveillä hevosilla. Materiaalimme koostui kymmenestä terveestä hevosesta, joilla ei ollut havaittu laihtumista tai ripulia. Ennen iohexolin annostelua hevosille suoritettiin kliininen tutkimus ja verinäytteet otettiin maha-suolikanavan sairauden poissulkemiseksi. Hevosille suoritettiin myös mahalaukun tähystys. 16 tunnin paaston jälkeen 1 ml/kg Iohexolia annosteltiin 10 % -liuoksena nenämahaletkulla suoraan mahaan ja verinäytteet otettiin 0, 30, 60, 120, 180, 240, 300 ja 360 minuuttia annostelun jälkeen. Iohexolin pitoisuus määritettiin käyttämällä korkean erotuskyvyn nestekromatografiaa. Iohexolin pitoisuuksista tietyillä ajanhetkillä muodostettiin kuvaaja. Hevosilla ei havaittu maha-suolikanavan sairauksia. Kaikki hevoset olivat hyvässä kuntoluokassa ja mahalaukun tähystyksessä ei havaittu merkittäviä muutoksia. Verinäytteiden tulokset olivat viiterajoissa. Kaikki hevoset sietivät iohexolia hyvin ja haittavaikutuksia ei havaittu. Iohexol oli havaittavissa seerumissa 60 minuutin kuluttua annostelusta. Kuvaajassa voitiin havaita kaksi huippua. Statistiset menetelmät tukivat löydöksiä. Iohexol testi oli yksinkertainen suorittaa ja siihen ei liittynyt haittavaikutuksia. Annos 1ml/kg oli havaittavissa seerumissa. Iohexolin pitoisuuskuvaaja muodosti kaksi huippua, ja tämänkaltainen ilmiö on kuvattu kirjallisuudessa aikaisemmin useiden lääkkeiden tapauksessa. Hevosella ilmiö liittyy todennäköisesti maha-suolikanavan rakenteellisiin ja fysiologisiin eroavaisuuksiin ja lisätutkimuksia ilmiön varmistamiseksi tarvitaan. Iohexol näyttää olevan potentiaalinen merkkiaine suoliston läpäisevyyden arviointiin ja lisätutkimuksia IBD:tä sairastavien hevosten seerumin iohexolin pitoisuuksista verrattuna terveiden hevosten seerumin iohexolin pitoisuuksiin on suunnitteilla.
  • Haisma, Sjoukje-Marije; Weersma, Rinse K.; Joosse, Maria E.; de Koning, Barbara A. E.; de Meij, Tim; Koot, Bart G. P.; Wolters, Victorien; Norbruis, Obbe; Daly, Mark J.; Stevens, Christine; Xavier, Ramnik J.; Koskela, Jukka; Rivas, Manuel A.; Visschedijk, Marijn C.; Verkade, Henkjan J.; Barbieri, Ruggero; Jansen, Dianne B. H.; Festen, Eleonora A. M.; van Rheenen, Patrick F.; van Diemen, Cleo C. (2021)
    BACKGROUND & AIMS Primary sclerosing cholangitis (PSC) is a rare bile duct disease strongly associated with inflammatory bowel disease (IBD). Whole-exome sequencing (WES) has contributed to understanding the molecular basis of very early-onset IBD, but rare protein-altering genetic variants have not been identified for early-onset PSC. We performed WES in patients diagnosed with PSC METHODS In this multicentre study, WES was performed on 87 DNA samples from 29 patient-parent trios with early-onset PSC. We selected rare (minor allele frequency <2%) coding and splice-site variants that matched recessive (homozygous and compound heterozygous variants) and dominant (de novo) inheritance in the index patients. Variant pathogenicity was predicted by an in-house developed algorithm (GAVIN), and PSC-relevant variants were selected using gene expression data and gene function. RESULTS In 22 of 29 trios we identified at least 1 possibly pathogenic variant. We prioritized 36 genes, harbouring a total of 54 variants with predicted pathogenic effects. In 18 genes, we identified 36 compound heterozygous variants, whereas in the other 18 genes we identified 18 de novo variants. Twelve of 36 candidate risk genes are known to play a role in transmembrane transport, adaptive and innate immunity, and epithelial barrier function. CONCLUSIONS The 36 candidate genes for early-onset PSC need further verification in other patient cohorts and evaluation of gene function before a causal role can be attributed to its variants.
  • Huoponen, Saara; Eberl, Anja; Räsänen, Pirjo; Roine, Risto P.; Sipponen, Taina; Arkkila, Perttu; Blom, Marja (2020)
    Effectiveness, efficacy and safety of biosimilar infliximab (CT-P13) in inflammatory bowel disease (IBD) patients has been shown in previous studies. Limited data exist on health-related quality of life (HRQoL) of switching originator to biosimilar infliximab (IFX) in IBD patients. The objective of this study was to evaluate impact of switching originator to biosimilar IFX on HRQoL, disease activity, and health care costs in IBD maintenance treatment. In this single-center prospective observational study, all IBD patients receiving maintenance IFX therapy were switched to biosimilar IFX. HRQoL was measured using the generic 15D health-related quality of life instrument (15D) utility measurement and the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ). Crohn Disease Activity Index (CDAI) or Partial Mayo Score (pMayo), and fecal calprotectin (FC) served for evaluation of disease activity. Data were collected at time of switching and 3 and 12 months after switching. Patients' characteristics, clinical background information and costs were collected from patient records and the hospital's electronic database. Fifty-four patients were included in the analysis. No statistically significant changes were observed in 15D, CDAI, pMayo, and FC during 1-year follow-up. IBDQ scores were higher (P = .018) in Crohn disease 3 months after switching than at time of switching. Costs of biosimilar IFX were one-third of costs of originator one. Total costs related to secondary health care (excluding costs of IFX), were similar before and after the onset of biosimilar IFX. HRQoL and disease activity were after switching from originator to biosimilar IFX comparable, but the costs of biosimilar IFX were only one-third of those of the originator one.
  • Molander, Pauliina; Ylänne, Karoliina (2019)
    Introduction: The Ulcerative Colitis (UC) Narrative is a global initiative to engage patients with UC, in order to help identify the impact of UC on patients' lives. The aim of the UC Narrative extension survey in Finland was to identify and describe the unmet needs in quality care. Methods: Seventeen Finnish physicians were surveyed in the original UC Narrative survey between 7 December 2017 and 24 January 2018. In the extension phase, Finnish UC patients, recruited through the Finnish patient association, were surveyed from 15 November to 3 December 2018, covering questions on disease characteristics, impact on life, most common challenges in communication with health care professionals (HCPs) and access to care. Results: Five hundred and eight patients with self-reported UC diagnosis participated (137 male [27.0%]). Diagnostic delay was, on average, 2.3 (SD 5.5) years; 14.4% had waited five years or more for diagnosis. Most patients (396; 78.0%) considered themselves to be in remission and rated their overall state of health as 'excellent' or 'good' (303; 59.7%). Most patients (79.6%) were satisfied with the communication with their HCPs, and the majority (74.2%) felt comfortable raising concerns and fears with HCPs. However, the satisfaction in discussing mental and emotional health impacts of UC was lower (44.3%). A relatively large number of patients (38.5%) felt that they would be a more successful person without UC. Conclusions: The UC Narrative survey highlighted the diagnostic delay in UC, challenges in communication with HCPs and the impact of UC on life from the patients' perspective.
  • Guard, Blake C.; Honneffer, Julia B.; Jergens, Albert E.; Jonika, Michelle M.; Toresson, Linda; Lawrence, Yuri A.; Webb, Craig B.; Hill, Steve; Lidbury, Jonathan A.; Steiner, Joerg M.; Suchodolski, Jan S. (2019)
    Abstract Background Mounting evidence from human studies suggests that bile acid dysmetabolism might play a role in various human chronic gastrointestinal diseases. It is unknown whether fecal bile acid dysmetabolism occurs in dogs with chronic inflammatory enteropathy (CE). Objective To assess microbial dysbiosis, fecal unconjugated bile acids (fUBA), and disease activity in dogs with steroid-responsive CE. Animals Twenty-four healthy control dogs and 23 dogs with steroid-responsive CE. Methods In this retrospective study, fUBA were measured and analyzed. Fecal microbiota were assessed using a dysbiosis index. The canine inflammatory bowel disease activity index was used to evaluate remission of clinical signs. This was a multi-institutional study where dogs with steroid-responsive CE were evaluated over time. Results The dysbiosis index was increased in dogs with CE (median, 2.5; range, ?6.2 to 6.5) at baseline compared with healthy dogs (median, ?4.5; range, ?6.5 to ?2.6; P?=?.002) but did not change in dogs with CE over time. Secondary fUBA were decreased in dogs with CE (median, 29%; range, 1%-99%) compared with healthy dogs (median, 88%; 4%-96%; P?=?.049). The percent of secondary fUBA in dogs with CE increased from baseline values (median, 28%; range, 1%-99%) after 2-3?months of treatment (median, 94%; range, 1%-99%; P?=?0.0183). Conclusions and Clinical Importance These findings suggest that corticosteroids regulate fecal bile acids in dogs with CE. Additionally, resolution of clinical activity index in dogs with therapeutically managed CE and bile acid dysmetabolism are likely correlated. However, subclinical disease (i.e., microbial dysbiosis) can persist in dogs with steroid-responsive CE.
  • af Björkesten, Clas-Göran; Ilus, Tuire; Hallinen, Taru; Soini, Erkki; Eberl, Anja; Hakala, Kalle; Heikura, Mikko; Jussila, Airi; Koskela, Ritva; Koskinen, Inka; Moilanen, Veikko; Nielsen, Christian; Nieminen, Urpo; Nuutinen, Heikki; Heikkinen, Markku; Suhonen, Ulla-Maija; Tillonen, Jyrki; Utriainen, Karri; Vihriälä, Ilkka; Wennerström, Christina; Borsi, Andras; Nissinen, Riikka; Koivunen, Minni R.; Sipponen, Taina (2020)
    Objective Long-term evidence on ustekinumab treatment response and persistence in patients with Crohn's disease in a real-world setting is scarce. We performed a retrospective nationwide chart review study of long-term clinical outcomes in Crohn's disease patients treated with ustekinumab. Methods The study was conducted in 17 Finnish hospitals and included adult Crohn's disease patients who received an initial intravenous dose of ustekinumab during 2017-2018. Disease activity data were collected at baseline, 16 weeks, and 1 year from health records. Results The study included 155 patients. The disease was stricturing or penetrating in 69 and 59% had prior Crohn's disease-related surgeries, and 97% had a treatment history of at least one biologic agent. Of 93 patients with >= 1 year of follow-up, 77 (83%) were still on ustekinumab at 1 year. In patients with data available, from baseline to the 1-year follow-up the simple endoscopic score for Crohn's disease (SES-CD) decreased from 10 to 3 (P = 0.033), C-reactive protein from 7 to 5 mg/L, (P 0.001) and faecal calprotectin from 776 to 305 mu g/g (P 0.001). Conclusions Ustekinumab treatment in patients with highly refractory Crohn's disease resulted in high long-term treatment persistence and significantly reduced disease activity, assessed with objective markers for intestinal inflammatory activity.
  • Haaramo, Anu; Alapulli, Heikki; Aine, Liisa; Tuokkola, Jetta; Saarnisto, Ulla; Roine, Risto P.; Pitkäranta, Anne; Kolho, Kaija-Leena (2019)
    Background: Up to 50% of pediatric patients with Crohn's disease (CD) report oral manifestations, but less is known about their oral health when they become adults. Goals: Our aim was to provide detailed descriptions of the presence of oral and otorhinolaryngological manifestations in patients with pediatric onset CD once they reached adulthood, to look for predisposing factors and to compare the findings to matched controls. Study: Adult patients diagnosed with CD in childhood at the Children's Hospital, University of Helsinki, Finland, after 2000 were invited for a follow-up appointment in 2016 and 24 were examined by a dentist and otorhinolaryngologist. They were compared with 22 matched controls from the Population Register Centre. The participants completed questionnaires about their general health, any special diets, and their health-related quality of life. Their nutrition was evaluated from food records. Results: Patients with CD had minor oral manifestations at a median of 9 years after their childhood diagnosis and the most common was angular cheilitis, which affected 6 patients and 1 control, but was not statistically significant (P=0.0984). CD with perianal abscessing disease correlated to orofacial findings (P=0.0312). Most of the patients had normal otorhinolaryngological findings. Subjects with oral lesions had lower mean health-related quality of life scores than subjects without oral findings and the differences were clinically but not statistically significant. Oral manifestations were not associated with differences in energy intake. Conclusions: Oral manifestations in adult patients with pediatric onset CD were mild and were not associated with otorhinolaryngological pathology.
  • Drobin, Kimi; Assadi, Ghazaleh; Hong, Mun-Gwan; Andersson, Eni; Fredolini, Claudia; Forsstrom, Bjorn; Reznichenko, Anna; Akhter, Tahmina; Ek, Weronica E.; Bonfiglio, Ferdinando; Hansen, Mark Berner; Sandberg, Kristian; Greco, Dario; Repsilber, Dirk; Schwenk, Jochen M.; D'Amato, Mauro; Halfvarson, Jonas (2019)
    Few studies have investigated the blood proteome of inflammatory bowel disease (IBD). We characterized the serum abundance of proteins encoded at 163 known IBD risk loci and tested these proteins for their biomarker discovery potential. Based on the Human Protein Atlas (HPA) antibody availability, 218 proteins from genes mapping at 163 IBD risk loci were selected. Targeted serum protein profiles from 49 Crohns disease (CD) patients, 51 ulcerative colitis (UC) patients, and 50 sex- and age-matched healthy individuals were obtained using multiplexed antibody suspension bead array assays. Differences in relative serum abundance levels between disease groups and controls were examined. Replication was attempted for CD-UC comparisons (including disease subtypes) by including 64 additional patients (33 CD and 31 UC). Antibodies targeting a potentially novel risk protein were validated by paired antibodies, Western blot, immuno-capture mass spectrometry, and epitope mapping. By univariate analysis, 13 proteins mostly related to neutrophil, T-cell, and B-cell activation and function were differentially expressed in IBD patients vs healthy controls, 3 in CD patients vs healthy controls and 2 in UC patients vs healthy controls (q <0.01). Multivariate analyses further differentiated disease groups from healthy controls and CD subtypes from UC (P <0.05). Extended characterization of an antibody targeting a novel, discriminative serum marker, the laccase (multicopper oxidoreductase) domain containing 1 (LACC1) protein, provided evidence for antibody on-target specificity. Using affinity proteomics, we identified a set of IBD-associated serum proteins encoded at IBD risk loci. These candidate proteins hold the potential to be exploited as diagnostic biomarkers of IBD.
  • Lehto, Markku; Groop, Per-Henrik (2018)
    Diabetic kidney disease (DKD) is a devastating condition associated with increased morbidity and premature mortality. The etiology of DKD is still largely unknown. However, the risk of DKD development and progression is most likely modulated by a combination of genetic and environmental factors. Patients with autoimmune diseases, like type 1 diabetes, inflammatory bowel disease, and celiac disease, share some genetic background. Furthermore, gastrointestinal disorders are associated with an increased risk of kidney disease, although the true mechanisms have still to be elucidated. Therefore, the principal aim of this review is to evaluate the impact of disturbances in the gastrointestinal tract on the development of renal disorders.
  • Haapamaki, Johanna; Heikkinen, Erjastiina; Sipponen, Taina; Roine, Risto P.; Arkkila, Perttu (2018)
    Background: Inflammatory bowel disease (IBD) has a substantial impact on patients health-related quality of life (HRQoL). In this study, we examined the impact of adaptation courses on HRQoL, psychological well-being, depression and number of sick-leave days of IBD patients.Methods: The study recruited 142 IBD patients attending an adaptation course of 5-12 days. The courses were specially designed for IBD patients and included multidisciplinary information about IBD, peer support, group activities and encouragement for adequate physical exercise. The participants completed the study questionnaire at the beginning and the end of the course and after six and 12 months of follow-up. HRQoL was assessed with the generic 15-dimensional (15D) tool and depression with Beck's Depression Inventory (BDI). Utilization of health care services and work absenteeism was also assessed. Visual analog scales were used for assessing psychological functioning.Results: 15D, BDI scores and scores describing psychological well-being were significantly better at the end of the course when compared to baseline (15D 0.82 vs. 0.84, p
  • Karvonen, Marianna (Helsingfors universitet, 2013)
    Maha-suolistokanavan tähystystä ja kudosnäytteiden histopatologista tutkimusta käytetään maha-suolistokanavan sairauksien diagnostiikassa erityisesti taudin vakavuuden ja esiintymislaajuuden määrittämiseen. Limakalvossa näkyvien vaurioiden, kliinisten oireiden, histopatologisten löydösten ja hoidon välisen yhteyden määrittäminen on kuitenkin haastavaa. Tämä tutkielma tarjoaa ajantasaista tietoa koirien maha-suolistokanavan sairauksien diagnosoinnin laadusta Suomessa. Maha-suolistokanavan sairaudet ovat yleinen ongelma Yliopistolliseen Pieneläinsairaalaan tuotavilla potilailla. Joskus näiden potilaiden tutkiminen vaatii maha-suolistokanavan tähystystä ja histopatologista tutkimusta diagnoosin selvittämiseksi. Toistaiseksi koirapotilaiden maha-suolistokanavan tähystyksessä raportoitujen löydösten ja histopatologisten tulosten välistä tilastollista riippuvuutta ei ole tutkittu Suomessa. Tämän lisensiaatin tutkielman tavoitteena on selvittää limakalvomuutosten ja histologisten löydösten keskinäisen korrelaation vahvuus. Aineisto on kerätty Yliopistollisen Pieneläinsairaalan potilaista, joille on tehty ruuansulatuskanavan tähystystutkimus vuosien 2007 ja 2010 välisenä aikana. Toimenpiteitä on tehty 271 kappaletta yhteensä 243 potilaalle. Yliopistollisessa Pieneläinsairaalassa ei ole käytössä yhtenäistä menetelmää tähystyksessä havaittujen löydösten raportoimiseksi. Tutkielmani toinen tavoite on osoittaa yhtenäisen raportointimenetelmän käytön hyödyt raportoinnin laadun parantamiseksi. Tutkielma on kuvaileva, takautuva tutkimus. Tutkimuksessa keskitytään pääasiassa mahalaukun, ohutsuolen ja paksusuolen löydöksiin. Saatuja tuloksia ei voida soveltaa suoraan koskemaan kaikkia Suomessa koirille tehtäviä ruuansulatuskanavan tähystyksiä ja histopatologisia tutkimuksia, sillä potilasmateriaalina on käytetty ainoastaan Yliopistollisen Pieneläinsairaalan potilaita. Tähystyksessä ja histologisessa tutkimuksessa havaittujen löydösten voimakkuuden välinen tilastollinen riippuvuus vaihteli suuresti. Mahalaukussa löydösten välinen korrelaatio oli 0,33 ja ohutsuolessa 0,31. Paksusuolessa korrelaatio oli voimakkaampi: 0,72. Kaikki arvot ovat tilastollisesti merkitseviä >99 % luottamustasolla. Samanlaisia tuloksia on saatu myös muualla, sillä useissa tutkimuksissa on epäonnistuttu määrittelemään yhteys histologisesti havaittujen vaurioiden ja koiran suolistossa näkyvien muutosten, oireiden vakavuuden tai hoitovasteen välillä. Tähystyksistä kirjoitetuissa toimenpidekertomuksissa ohutsuolen löydöksistä 13,1 %, mahalaukun löydöksistä 16,3 % ja paksusuolen löydöksistä 18,8 % oli sellaisia, että niiden arvioiminen jälkikäteen oli mahdotonta. Yhtenäisen raportointimenetelmän käyttö koirien ruuansulatuskanavan tähystyslöydösten arvioimisessa olisi mitä todennäköisimmin pienentänyt epäselvien löydösten määrää.
  • Koninckx, Carmen Ribes; Donat, Ester; Benninga, Marc A.; Broekaert, Ilse J.; Gottrand, Frederic; Kolho, Kaija-Leena; Lionetti, Paolo; Miele, Erasmo; Orel, Rok; Papadopoulou, Alexandra; Pienar, Corina; Schappi, Michela G.; Wilschanski, Michael; Thapar, Nikhil (2021)
    Objectives: The aim of the study was to review the evidence regarding the clinical use and value of fecal calprotectin (FC) measurements in different gastrointestinal disorders in children. Methods: A literature search was conducted in the PubMed, MEDLINE, EMBASE, and Cochrane databases until October 31, 2019. Subtopics were identified and each assigned to individual authors. Results: A total of 28 recommendations were voted on using the nominal voting technique. Recommendations are given related to sampling, measurement methods, and results interpretation. The 14 authors anonymously voted on each recommendation using a 9-point scale (1 strongly disagree to 9 fully agree). Consensus was considered achieved if at least 75% of the authors voted 6, 7, 8, or 9. Conclusions: Consensus was reached for all recommendations. Limitations for the use of FC in clinical practice include variability in extraction methodology, performance of test kits as well as the need to establish local reference ranges because of the influence of individual factors, such as age, diet, microbiota, and drugs. The main utility of FC measurement at present is in the diagnosis and monitoring of inflammatory bowel disease (IBD) as well as to differentiate it from functional gastrointestinal disorders (FAPDs). FC, however, has neither utility in the diagnosis of infantile colic nor to differentiate between functional and organic constipation. A rise in FC concentration, may alert to the risk of developing necrotizing enterocolitis and help identifying gastrointestinal involvement in children with Henoch-Schonlein purpura. FC measurement is of little value in Cow's Milk Protein Allergy, coeliac disease (CD), and cystic fibrosis. FC does neither help to distinguish bacterial from viral acute gastroenteritis (AGE), nor to diagnose Helicobacter Pylori infection, small intestinal bacterial overgrowth (SIBO), acute appendicitis (AA), or intestinal polyps.
  • Global UC Narrative Survey Panel; Dubinsky, Marla C.; Watanabe, Kenji; Molander, Pauliina; Connor, Susan (2021)
    Background: The Ulcerative Colitis (UC) Narrative is a global patient and physician survey aimed at identifying the impact of UC and comparing and contrasting perceptions of UC burden and management approaches. Methods: Surveys of patients with UC (self-reported diagnosis; n = 2100) and physicians (n = 1254) were completed across 10 countries by The Harris Poll between August 2017 and February 2018. Questionnaires covered multiple aspects of UC, including diagnosis, treatment, and impact on patient quality of life, in addition to standard demographic information. Descriptive statistics are reported. Results:The majority of patients (82%) had moderate to severe UC (based on medication history; those who had only ever taken 5-a minosalicylates were excluded); 67% described their UC as controlled with few to no symptoms. On average, patients experienced 4.3 flares (standard deviation, 7.4) in the past year. Diagnostic delay was on average 2.0 years (standard deviation, 5.4); 42% of patients waited >= 1 year. Most patients (65%) felt that UC controlled their life rather than them controlling their disease. Because of the fear of repercussions, many patients had not disclosed their UC to their employer. Discussion of the emotional impact of UC during routine appointments was less of a priority for physicians, compared with patients. Conclusions: The data from this global survey highlight that patients with UC experience diagnostic delay, poor disease control, and adverse impact on their quality of life. Patients report UC to be a mentally exhausting condition; however, emotional and mental health issues are infrequently discussed at routine appointments.