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  • Sartelli, Massimo; Di Bella, Stefano; McFarland, Lynne V.; Khanna, Sahil; Furuya-Kanamori, Luis; Abuzeid, Nadir; Abu-Zidan, Fikri M.; Ansaloni, Luca; Augustin, Goran; Bala, Miklosh; Ben-Ishay, Offir; Biffl, Walter L.; Brecher, Stephen M.; Camacho-Ortiz, Adrian; Cainzos, Miguel A.; Chan, Shirley; Cherry-Bukowiec, Jill R.; Clanton, Jesse; Coccolini, Federico; Cocuz, Maria E.; Coimbra, Raul; Cortese, Francesco; Cui, Yunfeng; Czepiel, Jacek; Demetrashvili, Zaza; Di Carlo, Isidoro; Di Saverio, Salomone; Dumitru, Irina M.; Eckmann, Christian; Eiland, Edward H.; Forrester, Joseph D.; Fraga, Gustavo P.; Frossard, Jean L.; Fry, Donald E.; Galeiras, Rita; Ghnnam, Wagih; Gomes, Carlos A.; Griffiths, Ewen A.; Guirao, Xavier; Ahmed, Mohamed H.; Herzog, Torsten; Kim, Jae Il; Iqbal, Tariq; Isik, Arda; Itani, Kamal M. F.; Labricciosa, Francesco M.; Lee, Yeong Y.; Juang, Paul; Karamarkovic, Aleksandar; Kim, Peter K.; Kluger, Yoram; Leppäniemi, Ari; Lohsiriwat, Varut; Machain, Gustavo M.; Marwah, Sanjay; Mazuski, John E.; Metan, Gokhan; Moore, Ernest E.; Moore, Frederick A.; Ordonez, Carlos A.; Pagani, Leonardo; Petrosillo, Nicola; Portela, Francisco; Rasa, Kemal; Rems, Miran; Sakakushev, Boris E.; Segovia-Lohse, Helmut; Sganga, Gabriele; Shelat, Vishal G.; Spigaglia, Patrizia; Tattevin, Pierre; Trana, Cristian; Urbanek, Libor; Ulrych, Jan; Viale, Pierluigi; Baiocchi, Gian L.; Catena, Fausto (2019)
    In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.
  • Pediat GETAID Grp; ESPGHAN IBD Porto Grp; Madre, Chrystele; Masic, Mario; Prlenda-Touilleux, Daniela; Kolho, Kaija-Leena; Hugot, Jean-Pierre (2021)
    Objectives: Digestive perianastomotic ulcerations (DPAU) resembling Crohn disease lesions are long-term complications of intestinal resections, occurring in children and young adults. They are known to be uncommon, severe and difficult to treat. Methods: In the absence of recommendations, we performed a large European survey among the members of the ESPGHAN working group on inflammatory bowel disease (IBD) in order to collect the experience of expert pediatric gastroenterologists on DPAU. Results: Fifty-one patients (29 boys and 22 girls) were identified from 19 centers in 8 countries. Most patients were followed after necrotizing enterocolitis (n = 20) or Hirschsprung disease (n = 11). The anastomosis was performed at a median age (interquartile range) of 6 [1-23] months, and first symptoms occurred 39 [22-106] months after surgery. Anemia was the most prevalent symptom followed by diarrhea, abdominal pain, bloating, and failure to thrive. Hypoalbuminemia, elevated CRP, and fecal calprotectin were common. Deep ulcerations were found in 59% of patients usually proximally to the anastomosis (68%). During a median follow-up of 40 [19-67] months, treatments reported to be the most effective included exclusive enteral nutrition (31/35, 88%), redo anastomosis (18/22, 82%), and alternate antibiotic treatment (37/64, 58%). Conclusions: Unfortunately, persistence of symptoms, failure to thrive, and abnormal laboratory tests at last follow-up in most of patients show the burden of DPAU lacking optimal therapy and incomplete understanding of the pathophysiology.
  • Rivas, Manuel A.; Graham, Daniel; Sulem, Patrick; Stevens, Christine; Desch, A. Nicole; Goyette, Philippe; Gudbjartsson, Daniel; Jonsdottir, Ingileif; Thorsteinsdottir, Unnur; Degenhardt, Frauke; Mucha, Soeren; Kurki, Mitja I.; Li, Dalin; D'Amato, Mauro; Annese, Vito; Vermeire, Severine; Weersma, Rinse K.; Halfvarson, Jonas; Paavola-Sakki, Anu Liisa Paulina; Lappalainen, Anne Maarit; Lek, Monkol; Cummings, Beryl; Tukiainen, Taru; Haritunians, Talin; Halme, Leena; Koskinen, Lotta L. E.; Ananthakrishnan, Ashwin N.; Luo, Yang; Heap, Graham A.; Visschedijk, Marijn C.; MacArthur, Daniel G.; Neale, Benjamin M.; Ahmad, Tariq; Anderson, Carl A.; Brant, Steven R.; Duerr, Richard H.; Silverberg, Mark S.; Cho, Judy H.; Palotie, Aarno; Saavalainen, Paivi; Kontula, Kimmo; Farkkila, Martti; McGovern, Dermot P. B.; Franke, Andre; Stefansson, Kari; Rioux, John D.; Xavier, Ramnik J.; Daly, Mark J. (2016)
    Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF = up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P = 6.89 x 10(-7), odds ratio = 0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain.
  • Rebane, Katariina; Tuomi, Anna-Kaisa; Kautiainen, Hannu; Peltoniemi, Suvi; Glerup, Mia; Aalto, Kristiina (2022)
    Objectives Abdominal pain (AP) is a common feature in the general population. However, in patients with juvenile idiopathic arthritis (JIA) AP has scantily been studied. Among other reasons, gastrointestinal symptoms may present as side effects due to the medical treatment of JIA. The aim of the study was to explore the frequency of AP and its relationship to disease components and health-related quality of life (HRQoL) among young adults with JIA. Methods This study included a cohort of 97 Finnish patients belonging to the population-based Nordic JIA cohort at their 17-year follow-up study visit. Mean age of the patients was 23 years. AP, functional status, fatigue, HRQoL, disease characteristics of JIA, and comorbidities were evaluated. AP was classified into three categories according to frequency: (1) never, (2) seldom (one to three times a month) and (3) frequent (at least once a week). Results About 48 (50%) young adults with JIA reported AP. Seldom AP was reported by 37 (38%), and frequent AP by 11 (11%) patients. AP was significantly associated with fatigue, female gender, functional status and arthritis-related pain. Patients having frequent AP reported lower HRQoL. AP was associated with the use of methotrexate and sulfasalazine, but not with nonsteroidal anti-inflammatory drugs (NSAIDs). Conclusion AP is an important complaint in young adults with JIA and is associated with fatigue, female gender, methotrexate and sulfasalazine use. Patients with JIA reporting frequent AP with lower functional status and higher arthritis-related pain values have lower HRQoL.
  • Chan, Yingleong; Lim, Elaine T.; Sandholm, Niina; Wang, Sophie R.; McKnight, Amy Jayne; Ripke, Stephan; Daly, Mark J.; Neale, Benjamin M.; Salem, Rany M.; Hirschhorn, Joel N.; DIAGRAM Consortium; GENIE Consortium; GIANT Consortium; IIBDGC Consortium; PGC Consortium (2014)
  • Rautava, Jaana; Gürsoy, Ulvi K.; Kullström, Adrian; Kononen, Eija; Sorsa, Timo; Tervahartiala, Taina; Gürsoy, Mervi (2020)
    The diagnostic accuracy of point-of-care (PoC) applications may be compromised in individuals with additional inflammatory conditions. This cross-sectional study examined the performance of a commercial oral rinse active matrix metalloproteinase-8 (aMMP-8) PoC immunotest in individuals with (n = 47) and without Crohn's disease (CD) (n = 41). Oral rinse collected from the participants was analyzed by the PoC immunotest. Molecular forms and fragments of salivary MMP-8 were detected by western immunoblotting. The sensitivity of the immunotest for periodontitis was 60.0% in the CD group and 90.0% in the control group. The respective specificity was 75.0% and 80.0%. In both groups, clinical diagnosis of periodontitis exhibited a significant association with the immunotest results, however, the odds ratio (OR) was more than ten-fold in controls (OR 54.3, 95% CI: 3.1-953, p = 0.006) in comparison to CD patients (OR 5.2, 95% CI: 1.3-21.6, p = 0.022). According to Western immunoblot results, the immunotest MMP-8 positivity was not related to elevated levels of molecular forms and fragments of MMP-8 in the CD group, as in the control group. The diagnostic accuracy of the aMMP-8 PoC oral rinse immunotest is reduced in CD patients, which may be related to lower levels or undetectable complexes.
  • Hetemaki, Iivo; Jarva, Hanna; Kluger, Nicolas; Baldauf, Hanna-Mari; Laakso, Sini; Bratland, Eirik; Husebye, Eystein S.; Kisand, Kai; Ranki, Annamari; Peterson, Part; Arstila, T. Petteri (2016)
    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic autoimmune disease caused by mutations in the AIRE gene. Although mainly an endocrine disease, a substantial fraction of patients have gastrointestinal manifestations. In this study, we have examined the role of anticommensal responses and their regulation. APECED patients had increased levels of Abs against Saccharomyces cerevisiae (p <0.0001) and against several species of commensal gut bacteria, but not against species predominantly associated with other locations. The anticommensal Ab levels did not correlate with gastrointestinal autoantibodies, neutralizing anti-IL-17 or -IL-22 Abs, or gastrointestinal symptoms, although scarcity of the available clinical data suggests that further study is required. However, the anti-S. cerevisiae Ab levels showed a significant inverse correlation with FOXP3 expression levels in regulatory T cells (Treg), previously shown to be dysfunctional in APECED. The correlation was strongest in the activated CD45RO(+) population (rho = 20.706; p <0.01). APECED patients also had decreased numbers of FOXP3(+) cells in gut biopsies. These results show that APECED patients develop early and sustained responses to gut microbial Ags in a pattern reminiscent of Crohn's disease. This abnormal immune recognition of gut commensals is linked to a systemic Treg defect, which is also reflected as a local decrease of gut-associated Treg. To our knowledge, these data are the first to show dysregulated responses to non-self commensal Ags in APECED and indicate that AIRE contributes to the regulation of gut homeostasis, at least indirectly. The data also raise the possibility of persistent microbial stimulation as a contributing factor in the pathogenesis of APECED.
  • Davis-Richardson, Austin G.; Ardissone, Alexandria N.; Dias, Raquel; Simell, Ville; Leonard, Michael T.; Kemppainen, Kaisa M.; Drew, Jennifer C.; Schatz, Desmond; Atkinson, Mark A.; Kolaczkowski, Bryan; Ilonen, Jorma; Knip, Mikael; Toppari, Jorma; Nurminen, Noora; Hyoty, Heikki; Veijola, Riitta; Simell, Tuula; Mykkanen, Juha; Simell, Olli; Triplett, Eric W. (2014)
  • Perazzio, Sandro F.; Allenspach, Eric J.; Eklund, Kari K.; Varjosalo, Markku; Shinohara, Michi M.; Torgerson, Troy R.; Seppänen, Mikko R. J. (2020)
    Behcet's disease (BD) is a heterogeneous multi-organ disorder in search of a unified pathophysiological theory and classification. The disease frequently has overlapping features resembling other disease clusters, such as vasculitides, spondyloarthritides and thrombophilias with similar genetic risk variants, namelyHLA-B*51,ERAP1,IL-10,IL-23R. Many of the BD manifestations, such as unprovoked recurrent episodes of inflammation and increased expression of IL-1, IL-6 and TNF alpha, overlap with those of the hereditary monogenic autoinflammatory syndromes, positioning BD at the crossroads between autoimmune and autoinflammatory syndromes. BD-like disease associates with various inborn errors of immunity, including familial Mediterranean fever, conditions related to dysregulated NF-kappa B activation (egTNFAIP3,NFKB1,OTULIN,RELA,IKBKG) and either constitutional trisomy 8 or acquired trisomy 8 in myelodysplastic syndromes. We review here the recent advances in the immunopathology of BD, BD-like diseases and the NF-kappa B pathway suggesting new elements in the elusive BD etiopathogenesis.
  • Pfaller, Birgit; Yepes-Nuñez, Juan José; Agache, Ioana; Akdis, Cezmi A.; Alsalamah, Mohammad; Bavbek, Sevim; Bossios, Apostolos; Boyman, Onur; Chaker, Adam; Chan, Susan; Chatzipetrou, Alexia; du Toit, George; Jutel, Marek; Kauppi, Paula; Kolios, Antonios; Li, Carmen; Matucci, Andrea; Marson, Alanna; Bendien, Sarah; Palomares, Oscar; Rogala, Barbara; Szepfalusi, Zsolt; Untersmayr, Eva; Vultaggio, Alessandra; Eiwegger, Thomas (2021)
    Abstract Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scare and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, pre-conception counseling, and health care provider education is crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.
  • UK IBD Genetics Consortium; Natl Inst Diabet Digestive Kidney; Gettler, Kyle; Levantovsky, Rachel; Moscati, Arden; Daly, Mark J.; Cho, Judy H. (2021)
    BACKGROUND AND AIMS: Polygenic risk scores (PRS) may soon be used to predict inflammatory bowel disease (IBD) risk in prevention efforts. We leveraged exome-sequence and single nucleotide polymorphism (SNP) array data from 29,358 individuals in the multiethnic, randomly ascertained health system-based BioMe biobank to define effects of common and rare IBD variants on disease prediction and pathophysiology. METHODS: PRS were calculated from European, African American, and Ashkenazi Jewish (AJ) reference case-control studies, and a meta-GWAS run using all three association datasets. PRS were then combined using regression to assess which combination of scores best predicted IBD status in European, AJ, Hispanic, and African American cohorts in BioMe. Additionally, rare variants were assessed in genes associated with very early-onset IBD (VEO-IBD), by estimating genetic penetrance in each BioMe population. RESULTS: Combining risk scores based on association data from distinct ancestral populations improved IBD prediction for every population in BioMe and significantly improved prediction among European ancestry UK Biobank individuals. Lower predictive power for non-Europeans was observed, reflecting in part substantially lower African IBD case-control reference sizes. We replicated associations for two VEO-IBD genes, ADAM17 and LRBA, with high dominant model penetrance in BioMe. Autosomal recessive LRBA risk alleles are associated with severe, early-onset autoimmunity; we show that heterozygous carriage of an African-predominant LRBA protein-altering allele is associated with significantly decreased LRBA and CTLA-4 expression with T-cell activation. CONCLUSIONS: Greater genetic diversity in African populations improves prediction across populations, and generalizes some VEO-IBD genes. Increasing African American IBD case-collections should be prioritized to reduce health disparities and enhance pathophysiological insight.
  • Toresson, L.; Steiner, J. M.; Razdan, P.; Spodsberg, E.; Olmedal, G.; Suchodolski, J. S.; Spillmann, T. (2018)
    The aim of this study was to compare the efficacies of parenteral and oral cobalamin supplementation protocols in dogs with chronic enteropathies and low cobalamin concentrations. It was hypothesised that both treatments would increase serum cobalamin concentrations significantly. Fifty-three dogs with chronic enteropathies and serum cobalamin concentrations <285 ng/L (reference interval 244-959 ng/L) were enrolled. Dogs were randomised to treatment with either daily oral cobalamin tablets (0.25-1.0 mg cyanocobalamin daily according to body weight) or parenteral cobalamin (0.4-1.2 mg hydroxycobalamin according to body weight). Serum cobalamin concentrations were analysed 28 +/- 5 days and 90 +/- 15 days after initiation of supplementation. After 28 days, all dogs had serum cobalamin concentrations within the reference interval or above. In the parenteral group (n = 26), median (range) cobalamin concentrations were 228 (150-285) ng/L at inclusion, 2107 (725-10,009) ng/L after 28 days and 877 (188-1267) ng/L after 90 days. In the oral group (n = 27), median (range) serum cobalamin concentrations were 245 (150-285) ng/L at inclusion, 975 (564-2385) ng/L after 28 days and 1244 (738-4999) ng/L after 90 days. In both groups, there were significant differences in serum cobalamin concentrations between baseline and 28 days, and between 28 days and 90 days (P <0.001). In conclusion, both parenteral and oral cobalamin supplementation effectively increase serum cobalamin concentrations in dogs with chronic enteropathies and low cobalamin concentrations. (C) 2017 Elsevier Ltd. All rights reserved.
  • Guo, Michael H.; Nandakumar, Satish K.; Ulirsch, Jacob C.; Zekavat, Seyedeh M.; Buenrostro, Jason D.; Natarajan, Pradeep; Salem, Rany M.; Chiarle, Roberto; Mitt, Mario; Kals, Mart; Pärn, Kalle; Fischer, Krista; Milani, Lili; Magi, Reedik; Palta, Priit; Gabriel, Stacey B.; Metspalu, Andres; Lander, Eric S.; Kathiresan, Sekar; Hirschhorn, Joel N.; Esko, Tonu; Sankaran, Vijay G. (2017)
    Genetic variants affecting hematopoiesis can influence commonly measured blood cell traits. To identify factors that affect hematopoiesis, we performed association studies for blood cell traits in the population-based Estonian Biobank using high-coverage whole-genome sequencing (WGS) in 2,284 samples and SNP genotyping in an additional 14,904 samples. Using up to 7,134 samples with available phenotype data, our analyses identified 17 associations across 14 blood cell traits. Integration of WGS-based fine-mapping and complementary epigenomic datasets provided evidence for causal mechanisms at several loci, including at a previously undiscovered basophil count-associated locus near the master hematopoietic transcription factor CEBPA. The fine-mapped variant at this basophil count association near CEBPA overlapped an enhancer active in common myeloid progenitors and influenced its activity. In situ perturbation of this enhancer by CRISPR/Cas9 mutagenesis in hematopoietic stem and progenitor cells demonstrated that it is necessary for and specifically regulates CEBPA expression during basophil differentiation. We additionally identified basophil count-associated variation at another more pleiotropic myeloid enhancer near GATA2, highlighting regulatory mechanisms for ordered expression of master hematopoietic regulators during lineage specification. Our study illustrates how population-based genetic studies can provide key insights into poorly understood cell differentiation processes of considerable physiologic relevance.
  • Kolho, Kaija-Leena; Alfthan, Henrik (2020)
    Objectives Fecal calprotectin is a valued surrogate marker for intestinal inflammation. It has been argued that calprotectin levels are higher in early age than in later life hampering the use of calprotectin in young children. Subjects and methods To study age-related variation, we used data from our laboratory information system on consecutive, unselected fecal calprotectin measurements from 2014 to 2017 in all children aged 0 to 18 years. From each individual, the first measurement was included and repeated measurements were excluded. Fecal calprotectin was quantitated in the major clinical laboratory in southern Finland, HUSLAB with an ELISA kit from Calpro AS (Calpro/Calprolab, Oslo, Norway). Currently, the assay is performed on two automatic pipetting analysers (Dynex DS2, Chantilly, USA) according to the instructions of the manufacturer. Results There were altogether 11,255 fecal calprotectin results from as many children. The median level of fecal calprotectin was 51 mg/kg in infants <1 year of age (95(th)percentile 648 mg/kg;n = 239). This was 3-4-fold higher when compared to yearly age groups from 1 to 10 years (total number of children included 5,691). Across yearly age groups from 11 to 18, the median values varied from 11 to 19 mg/kg (total number of included children 5,325). The proportion of samples above the routine cut-off for an elevated concentration >100 mg/kg increased with increasing age. Conclusions Fecal calprotectin values in children beyond the first year of life are in general low and comparable in children and adolescents.
  • Int PSC Study Grp; Ponsioen, Cyriel Y.; Assis, David N.; Boberg, Kirsten M.; Färkkilä, Martti; Hübscher, Stefan G. (2021)
  • Nieminen, Janne K.; Niemi, Mirja; Sipponen, Taina; Salo, Harri M.; Klemetti, Paula; Färkkilä, Martti Antero; Vakkila, Jukka; Vaarala, Outi (2013)
  • Jongsma, Maria M. E.; Vuijk, Stephanie A.; Cozijnsen, Martinus A.; van Pieterson, Merel; Norbruis, Obbe F.; Groeneweg, Michael; Wolters, Victorien M.; van Wering, Herbert M.; Hojsak, Iva; Kolho, Kaija-Leena; van Wijk, Michiel P.; Teklenburg-Roord, Sarah T. A.; de Meij, Tim G. J.; Escher, Johanna C.; de Ridder, Lissy (2022)
    To induce remission in luminal paediatric Crohn's disease (CD), the ESPGHAN/ECCO guideline recommends treatment with exclusive enteral nutrition (EEN) or oral corticosteroids. In newly diagnosed moderate-to-severe paediatric CD patients, we determined the proportion of patients in which EEN or corticosteroids induced remission and maintained remission on azathioprine monotherapy. We included patients from the "TISKids" study assigned to the conventional treatment arm. Patients were aged 3-17 years and had new-onset, untreated luminal CD with weighted paediatric CD activity index (wPCDAI)> 40. Induction treatment consisted of EEN or oral corticosteroids; all received azathioprine maintenance treatment from start of treatment. The primary outcome of this study was endoscopic remission defined as a SES-CD score Conclusion: In children with moderate-to-severe newly diagnosed CD, induction treatment with EEN or CS regularly is insufficient to achieve endoscopic remission without treatment escalation at week 10.
  • Wacklin, Pirjo; Tuimala, Jarno; Nikkila, Janne; Tims, Sebastian; Makivuokko, Harri; Alakulppi, Noora; Laine, Pia; Rajilic-Stojanovic, Mirjana; Paulin, Lars; de Vos, Willem M.; Matto, Jaana (2014)
  • Aalto, Kristiina; Lahdenne, Pekka; Kolho, Kaija-Leena (2017)
    Background: Patients with juvenile idiopathic arthritis (JIA) on non-steroidal anti- inflammatory drugs (NSAIDs) may experience abdominal pain. In adults, NSAID use has been linked to an increase in fecal calprotectin (FC) levels, a surrogate marker for gut inflammation. In JIA, data on gut inflammation related to drug use is scarce. Methods: JIA patients followed up at the outpatient pediatric rheumatology clinic in Children's Hospital, Helsinki University Hospital, Helsinki, Finland were routinely assessed for FC if they complained about abdominal pain, had an elevated erythrocyte sedimentation rate (ESR) or used NSAIDs on a daily basis. The FC levels were related to the presence of abdominal pain, to ESR, and to the presence of HLA-B27. Results: Of the total group of 90 patients (median age 9.1 years; 45 JIA patients with disease modifying antirheumatic drugs (DMARDs), 25 without DMARD medication, and 20 arthralgia patients as controls), approximately 50% used NSAIDs, of whom 40% complained about abdominal pain. In patients with abdominal pain, one-third had elevated FC values (>100 mu g/g). The FC values, for the most part, declined along with the discontinuation or reduction of NSAIDs and after intensifying the DMARD medication, where after the pain disappeared. In patients with an elevated ESR, the FC values and ESR normalized in parallel. The presence of HLA-B27 was not associated with FC levels. Conclusion: In patients with JIA and abdominal pain, it may be useful to determine the FC when evaluating the need for further gastrointestinal examinations.
  • Hukkinen, Maria; Pakarinen, Mikko Petteri; Merras-Salmio, Laura; Koivusalo, Antti; Rintala, Risto; Kolho, Kaija-Leena (2016)
    Background: Fecal calprotectin (FC) correlates with endoscopic recurrence of Crohn's disease (CD) in adults but has not been studied among children postoperatively. We aimed to analyze whether FC relates with postoperative CD recurrence in children. Methods: Altogether 51 postoperative endoscopies and FC measurements from 22 patients having undergone surgery for CD at age Results: Ileocecal resection (n = 15), small bowel resection (n = 6), or left hemicolectomy (n = 1) was performed at median age of 15.1 (interquartile range 14.4-17.6) years. Following surgery, FC decreased significantly (659 vs. 103 mu g/g, p = 0.001). During median follow-up of 5.7 (4.2-7.7) years, either endoscopic or histological recurrence occurred in 17 patients (77%). FC > 139 mu g/g at time of endoscopy or FC increase of 79 mu g/g compared to first postoperative value was suggestive of endoscopic recurrence (Rutgeerts score i2-i4), while FC > 101 mu g/g or increase of 21 mu g/g indicated histological recurrence. Best accuracy for prediction of recurrence was obtained by combining FC at endoscopy and the postoperative increase of FC. The corresponding AUROC values were 0.74 (95% 0.58-0.89) for endoscopic recurrence whereas 0.81 (95% CI 0.67-0.95) for histological recurrence. Conclusion: FC is a useful surrogate marker of postoperative recurrence also in pediatric CD patients. (C) 2016 Elsevier Inc. All rights reserved.