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1.
  • Bertilsson, Sara, et al. (författare)
  • Microproteinuria Predicts Organ Failure in Patients Presenting with Acute Pancreatitis
  • 2016
  • Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; 61:12, s. 3592-3601
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: The disease course of acute pancreatitis (AP) ranges from mild and self-limiting to severe inflammation, associated with significant morbidity and mortality. At present, there are no universally accepted and reliable predictors for severity. Microproteinuria has been associated with the presence of systemic inflammatory response syndrome as well as trauma, although its association with AP is not well understood. The aim of this study was to investigate the value of microproteinuria to predict development of organ failure in AP.METHODS: Consecutive AP patients were prospectively enrolled. Urine samples were collected upon admission, 12-24 h after admission, and 3 months post-discharge for calculation of urine α1-microglobulin-, albumin-, IgG-, and IgM/creatinine ratios. Data regarding AP etiology, severity, and development of organ failure were registered.RESULTS: Overall, 92 AP patients were included (14 % with organ failure; 6 % with severe AP). The α1-microglobulin-, albumin-, and IgG/creatinine ratios correlated with high-sensitivity C-reactive protein 48 h after admission (r = 0.47-0.61, p < 0.001 for all). They were also significantly higher in patients with versus without organ failure (p < 0.05 for all). The α1-microglobulin/creatinine ratio upon admission predicted organ failure [adjusted odds ratio 1.286, 95 % confidence interval (CI) 1.024-1.614] with similar accuracy (AUROC 0.81, 95 % CI 0.69-0.94) as the more complex APACHE II score (AUROC 0.86, 95 % CI 0.70-1.00).CONCLUSION: The α1-microglobulin/creatinine ratio upon presentation with AP is related to inflammation and predicts development of organ failure. Further studies are warranted to evaluate its potential usefulness in predicting outcome for AP patients.
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  • Efe, Cumali, et al. (författare)
  • Tacrolimus and Mycophenolate Mofetil as Second-Line Therapies for Pediatric Patients with Autoimmune Hepatitis
  • 2018
  • Ingår i: Digestive Diseases and Sciences. - : SPRINGER. - 0163-2116 .- 1573-2568. ; 63:5, s. 1348-1354
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied the efficacy and safety of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy in pediatric patients with autoimmune hepatitis (AIH) who were intolerant or non-responders to standard therapy (corticosteroid and azathioprine). We performed a retrospective study of data from 13 centers in Europe, USA, and Canada. Thirty-eight patients (< 18 years old) who received second-line therapy (18 MMF and 20 tacrolimus), for a median of 72 months (range 8-182) were evaluated. Patients were categorized into two groups: Group 1 (n = 17) were intolerant to corticosteroid or azathioprine, and group 2 (n = 21) were non-responders to standard therapy. Overall complete response rates were similar in patients treated with MMF and tacrolimus (55.6 vs. 65%, p = 0.552). In group 1, MMF and tacrolimus maintained a biochemical remission in 88.9 and 87.5% of patients, respectively (p = 0.929). More patients in group 2 given tacrolimus compared to MMF had a complete response, but the difference was not statistically significant (50.0 vs. 22.2%, p = 0.195). Biochemical remission was achieved in 71.1% (27/38) of patients by tacrolimus and/or MMF. Decompensated cirrhosis was more commonly seen in MMF and/or tacrolimus non-responders than in responders (45.5 vs. 7.4%, p = 0.006). Five patients who received second-line therapy (2 MMF and 3 tacrolimus) developed side effects that led to therapy withdrawal. Long-term therapy with MMF or tacrolimus was generally well tolerated by pediatric patients with AIH. Both MMF and tacrolimus had excellent efficacy in patients intolerant to corticosteroid or azathioprine. Tacrolimus might be more effective than MMF in patients failing previous therapy.
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  • Fleisher, Mark, et al. (författare)
  • Effects of Vedolizumab Therapy on Extraintestinal Manifestations in Inflammatory Bowel Disease
  • 2018
  • Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 63:4, s. 825-833
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Approximately 15–20% of ulcerative colitis patients and 20–40% of those with Crohn’s disease experience extraintestinal manifestations (EIMs) of their inflammatory bowel disease (IBD). Clinicians who treat IBD must manage EIMs affecting multiple organs that variably correlate with intestinal disease activity. Vedolizumab is a monoclonal antibody for the treatment of IBD with a gut-selective mechanism of action. Aims: This report evaluates whether vedolizumab is an effective treatment of EIMs, given its gut-specific mechanism of action. Methods: We report 8 case studies of patients with various EIMs, including pyoderma gangrenosum, peripheral arthralgia/arthritis, axial arthropathies, erythema nodosum, and uveitis, who received vedolizumab therapy. Results: Vedolizumab therapy was effective for pyoderma gangrenosum in ulcerative colitis, uveitis, erythema nodosum, polyarticular arthropathy, and ankylosing spondylitis/sacroiliitis but did not provide sustained benefit for the treatment of pyoderma gangrenosum in a patient with Crohn’s disease. Conclusions: These cases demonstrate the potential of vedolizumab as a treatment of EIMs in patients with IBD.
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  • Günaltay, Sezin, 1986-, et al. (författare)
  • Reduced IL-37 Production Increases Spontaneous Chemokine Expressions in Colon Epithelial Cells
  • 2017
  • Ingår i: Digestive Diseases and Sciences. - : Springer. - 0163-2116 .- 1573-2568. ; 62:5, s. 1204-1215
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aim: Microscopic colitis, comprising collagenous colitis and lymphocytic colitis, is a common cause of chronic diarrhea. Previously, we showed enhanced chemokine productions in microscopic colitis patients, indicating dysregulated immune cell chemotaxis in the immunopathogenesis. We also showed decreased mRNA of IL-37, mainly regarded as an anti-inflammatory cytokine, in the colonic mucosa of these patients, potentially an important factor for the chronicity of the colitis. Our aim in this study was to understand the possible role of IL-37 in chemokine production using a cell line model.Methods: A colon epithelial cell line, T84, was stimulated with the TLR5 ligand flagellin. IL-37 protein production was reduced 20% using the CRISPR/Cas9 system, and the changes in chemokine mRNA and protein expressions were compared to cells transfected with empty plasmid.Results: The 20% reduction in IL-37 protein levels spontaneously increased CCL5, CXCL8, CXCL10, and CXCL11 mRNA and protein expressions. CCL2 mRNA and protein levels were enhanced upon TLR5 stimulation. CCL3, CCL20, and CX3CL1 mRNA expressions were increased either spontaneously or following TLR5 stimulation, whereas CCL4 and CCL22 mRNA expressions were significantly decreased.Conclusions: Even a minor decrease in the ability of colon epithelial cells to produce IL-37 results in altered chemokine expression, mainly an increase in the production of several chemokines. Our results indicate that a decreased IL-37 expression by colon epithelial cells may be an important factor for increasing the recruitment of immune cells and subsequently developing microscopic colitis.
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  • Hagström, Hannes, et al. (författare)
  • Risk Behaviors Associated with Alcohol Consumption Predict Future Severe Liver Disease
  • 2019
  • Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 64:7, s. 2014-2023
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundExcess consumption of alcohol can lead to cirrhosis, but it is unclear whether the type of alcohol and pattern of consumption affects this risk.AimsWe aimed to investigate whether type and pattern of alcohol consumption early in life could predict development of severe liver disease.MethodsWe examined 43,242 adolescent men conscribed to military service in Sweden in 1970. Self-reported data on total amount and type of alcohol (wine, beer, and spirits) and risk behaviors associated with heavy drinking were registered. Population-based registers were used to ascertain incident cases of severe liver disease (defined as cirrhosis, decompensated liver disease, liver failure, hepatocellular carcinoma, or liver-related mortality). Cox regression models were used to estimate hazard ratios for development of severe liver disease.ResultsDuring follow-up, 392 men developed severe liver disease. In multivariable analysis, after adjustment for BMI, smoking, use of narcotics, cardiovascular fitness, cognitive ability, and total amount of alcohol, an increased risk for severe liver disease was found in men who reported drinking alcohol to alleviate a hangover (“eye-opener”; aHR 1.47, 95% CI 1.02–2.11) and men who reported having been apprehended for being drunk (aHR 2.17, 95% CI 1.63–2.90), but not for any other risk behaviors. Wine consumption was not associated with a reduced risk for severe liver disease compared to beer and spirits.ConclusionsCertain risk behaviors can identify young men with a high risk of developing severe liver disease. Wine consumption was not associated with a reduced risk for severe liver disease compared to beer and spirits.
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  • Kolb, Jennifer M., et al. (författare)
  • Locations and Mucosal Lesions Responsible for Major Gastrointestinal Bleeding in Patients on Warfarin or Dabigatran
  • 2018
  • Ingår i: Digestive Diseases and Sciences. - : SPRINGER. - 0163-2116 .- 1573-2568. ; 63:7, s. 1878-1889
  • Tidskriftsartikel (refereegranskat)abstract
    • Different oral anticoagulants may be associated with gastrointestinal bleeding (GIB) from different locations or mucosal lesions. We aimed to test this hypothesis. Two blinded gastroenterologists independently analyzed source documents from the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial of dabigatran 150 mg BID (D150), dabigatran 110 mg BID (D110) versus warfarin in non-valvular atrial fibrillation (NVAF). Major GIB events (total n = 546) and life-threatening GIB events (n = 258) were more common with D150 versus warfarin (RR 1.57 [1.28-1.92] and RR 1.62 [1.20-2.18], respectively) and similar for D110 compared to warfarin (RR 1.11 [0.89-1.38] and RR 1.16 [0.84-1.61], respectively). Fatal bleeding was similarly rare across treatment groups. Lower GI major bleeding and life-threatening bleeding were more common with D150 compared to warfarin (RR 2.23 [1.47, 3.38] and RR 2.64 [1.36, 5.13], respectively) and with D110 compared to warfarin (RR 1.78 [1.16, 2.75] and RR 2.00 [1.00, 4.00], respectively). MGIB from colonic angiodysplasia was increased with dabigatran versus warfarin (P < 0.01 for both dose comparisons). Subacute and chronic MGIB events were more common with D150 than with warfarin (RR 1.72 [1.06, 2.78] and RR 1.66 [1.12, 2.45], respectively), as were hematochezia or melena (RR 1.67 [1.18, 2.36] and RR 1.72 [1.20, 2.47], respectively). In a chronic NVAF population, D150 but not D110 is associated with increased major and life-threatening GI bleeding in comparison with warfarin. At both dabigatran doses, increased bleeding from the colorectum, in particular from angiodysplasia, is seen.
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  • Koulaouzidis, Anastasios, et al. (författare)
  • Association Between Fecal Calprotectin Levels and Small-bowel Inflammation Score in Capsule Endoscopy : A Multicenter Retrospective Study
  • 2016
  • Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; 61:7, s. 2033-2040
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Accurate inflammation reporting in capsule endoscopy (CE) is important for diagnosis and monitoring of treatment of inflammatory bowel disease (IBD). Fecal calprotectin (FC) is a highly specific biomarker of gut inflammation. Lewis score (LS) was developed to standardize quantification of inflammation in small-bowel (SB) CE images.GOALS: Multicenter retrospective study aiming to investigate correlation between LS and FC in a large group of patients undergoing CE for suspected or known small-bowel IBD, and to develop a model for prediction of CE results (LS) based on FC levels.STUDY: Five academic centers and a district general hospital offering CE in UK, Finland, Sweden, Canada, and Israel. In total, 333 patients were recruited. They had small-bowel CE and FC done within 3 months.RESULTS: Overall, correlation between FC and LS was weak (r s: 0.232, P < 0.001). When two clinically significant FC thresholds (100 and 250 μg/g) were examined, the r s between FC and LS was 0.247 (weak) and 0.337 (moderate), respectively (P = 0.307). For clinically significant (LS ≥ 135) or negative (LS < 135) for SB inflammation, ROC curves gave an optimum cutoff point of FC 76 μg/g with sensitivity 0.59 and specificity 0.41.LIMITATIONS: Retrospective design.CONCLUSIONS: LS appears to show low correlation with FC as well as other serology markers of inflammation. FC does not appear to be a reliable biomarker for significant small-bowel inflammation. Nevertheless, FC level ≥ 76 μg/g may be associated with appreciable visual inflammation on small-bowel CE in patients with negative prior diagnostic workup.
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  • Noren, Elisabeth, et al. (författare)
  • Genetic Variation and Gene Expression Levels of Tight Junction Genes Indicates Relationships Between PTEN as well as MAGI1 and Microscopic Colitis
  • 2018
  • Ingår i: Digestive Diseases and Sciences. - : SPRINGER. - 0163-2116 .- 1573-2568. ; 63:1, s. 105-112
  • Tidskriftsartikel (refereegranskat)abstract
    • Microscopic colitis (MC) has been associated with increased paracellular permeability. Therefore, we aimed to investigate potential associations between MC and several genes encoding tight junction (TJ) proteins reported to interact with each other. The association between MC and single nucleotide polymorphisms (SNP; n = 63) within TJ genes (F11R, MAGI1, MAGI2, MAGI3, PARD3, PTEN, and TJP1) were investigated in a case-control study (n (MC patients) = 104 and n (controls) = 423). The genes that exhibited an association with MC were further investigated for gene expression related to genotype, MC phenotype, and gender using colonic biopsies from MC patients (n = 25) and controls (n = 58). Based on the number of investigated genes and after correction for multiple testing, an association was detected between a SNP marker in PTEN (rs1234224) and both MC overall (OR = 1.70, 95% CI 1.23-2.34, p = 0.001) and collagenous colitis (CC; OR = 1.79, 95% CI 1.22-2.62, p = 0.003). Further, SNP markers in MAGI1 (rs17417230) and F11R (rs790055) were associated with MC overall (OR = 1.58, 95% CI 1.14-2.19, p = 0.006) and with CC (OR = 2.58, 95% CI 1.27-5.25, p = 0.007), respectively. However, none of the associated SNPs contributed markedly to the expression of the respective genes. Nonetheless, decreased MAGI1 (p = 3.47 x 10(-4)) and PTEN (p = 0.004) expression was associated with lymphocytic colitis (LC) and CC, respectively, compared to controls. Decreased expression of PTEN and MAGI1 in the colonic mucosa might contribute to the pathogenesis of MC and its sub-phenotypes. Furthermore, our study indicates that genetic variants of TJ components are predisposing factors in the etiology of MC. Finally, F11R, MAGI1, and PTEN are new candidate genes that exhibit an association with MC.
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  • Saberi, Samaneh, et al. (författare)
  • Helicobacter pylori Strains from Duodenal Ulcer Patients Exhibit Mixed babA/B Genotypes with Low Levels of BabA Adhesin and Lewis b Binding
  • 2016
  • Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 61:10, s. 2868-2877
  • Tidskriftsartikel (refereegranskat)abstract
    • BabA is a Helicobacter pylori cell surface adhesin, which binds to the ABO/Le(b) histo-blood group antigens (Le(b)) and serves as a virulence factor. H. pylori single colonies were isolated from 156 [non-ulcer dyspepsia (NUD) = 97, duodenal ulcer (DU) = 34, gastric cancer (GC) = 25)] patients. babA and babB genes were evaluated by gene/locus-specific PCR. BabA protein expression and Le(b) binding activity were determined by immunoblotting and ELISA, respectively. The combined categorization of H. pylori strains based on high, low or no levels of BabA expression and Le(b) binding, produced 4 groups: (I) BabA-high/Le(b)-high (36 %), (II) BabA-low/Le(b)-low (26 %), (III) BabA-neg/Le(b)-low (30 %) and (IV) BabA-neg/Le(b)-neg (8 %) strains. The majority (63 %) of the BabA-low/Le(b)-low strains exhibited mixed babA/B genotypes as compared to merely 18 % of the BabA-high/Le(b)-high, 15 % of the BabA-neg/Le(b)-neg and 11 % of the BabA-neg/Le(b)-low (P = 0.0001) strains. In contrast to NUD strains, the great majority (70 %) of DU strains were BabA-low/Le(b)-low (11 %, P = 0.0001), which compared to NUD strains, enhanced the risk of DU by 18.8-fold. In parallel, infection with babA/B mixed genotype strains amplified the risk of DU by 3.6-fold (vs. babA-positive: P = 0.01) to 6.9-fold (vs. babA-negative: P = 0.007). Here, we show higher prevalence of mixed babA/B genotypes among BabA-low/Le(b)-low clinical strains. Recombination of babA and babB genes across their loci may yield lower BabA expression and lower Le(b) binding activity. We conclude that H. pylori strains with lower Le(b) binding activity are better adapted for colonization of the gastric metaplastic patches in the duodenum and enhance the risk of duodenal ulcers.
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  • Sargenti, Konstantina, et al. (författare)
  • Dysfunction of Circulating Polymorphonuclear Leukocytes and Monocytes in Ambulatory Cirrhotics Predicts Patient Outcome
  • 2016
  • Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 61:8, s. 2294-2302
  • Tidskriftsartikel (refereegranskat)abstract
    • Cirrhosis represents a state of functional immune paresis with increased infection risk. To investigate polymorphonuclear (PMN) leukocyte and monocyte function in ambulatory cirrhotics, and their potential relation with cirrhosis etiology or patient outcome. Consecutive ambulatory cirrhotics without current or recent (< 1 month) infection or acute decompensation were prospectively enrolled in 2013 and followed for a median time of 20 months until death, transplant or end of 2014. Oxidative burst and phagocytosis of circulating PMNs and monocytes were investigated at baseline and after in vitro Escherichia coli stimulation. Seventeen healthy blood donors served as controls. Baseline clinical and laboratory data as well as follow-up data on the development of cirrhosis complications, including acute-on-chronic liver failure (ACLF), and bacterial infections were collected. Sixty patients were included (70 % male, median age 63 years, 52 % with alcoholic cirrhosis). Compared to controls, cirrhotics showed increased resting and stimulated burst as well as reduced phagocytosis of PMNs, and increased stimulated monocyte burst (p < 0.05 for all). Alcoholic etiology was not related to PMN or monocyte dysfunction (p > 0.05 for all). In Cox regression analysis, increased stimulated monocyte and PMN burst were independent predictors of sepsis, severe sepsis and ACLF occurrence. Also, increased stimulated monocyte burst was associated with worse transplant-free survival (p < 0.05 for all). Stimulated PMN and monocyte oxidative burst are increased in ambulatory cirrhotics without acute decompensation. In turn, these changes are associated to sepsis and ACLF occurrence.
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  • Tjellstrom, B, et al. (författare)
  • A Role for Bacteria in Celiac Disease?
  • 2016
  • Ingår i: Digestive diseases and sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; 61:7, s. 2140-2140
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Trindade, Inês A., 1990-, et al. (författare)
  • Ulcerative Colitis Symptomatology and Depression : The Exacerbator Role of Maladaptive Psychological Processes
  • 2015
  • Ingår i: Digestive Diseases and Sciences. - : Springer. - 0163-2116 .- 1573-2568. ; 60:12, s. 3756-3763
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies have indicated that depressive symptomatology plays a pertinent role in the clinical recurrences of ulcerative colitis (UC). Due to the self-perpetuating cycle between UC symptomatology and depressive mood, it is considered that more investment should be given to the study of factors that influence depressive symptomatology in UC patients.This study aimed therefore at analyzing the exacerbator effect of maladaptive psychological strategies, such as cognitive fusion and brooding, on the relationship between UC symptomatology and depressive symptoms.The sample of the current study included 84 Portuguese patients with UC that completed an Internet-based survey (comprising demographic and medical questions, and self-report measures of depression, cognitive fusion, and brooding).Results showed that UC symptomatology explained 21 % of depression severity's variance. In addition, a significant interaction between UC symptomatology and cognitive fusion was found and explained 50 % of depressive symptoms' severity. A similar interaction was revealed between UC symptomatology and brooding, which accounted for 42 % of depression's variance. These findings demonstrated that, for the same level of UC symptomatology, those participants who revealed more cognitive fusion or more brooding presented significant higher levels of depression.The present study revealed cognitive fusion and brooding as moderators that exacerbate the impact of UC symptomatology on reported levels of depression. Psychological interventions that focus on the promotion of adaptive emotion regulation strategies to deal with adverse and stressful events should therefore be developed and implemented in UC patients' health care.
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  • Youssef, Omar, et al. (författare)
  • Stool Microbiota Composition Differs in Patients with Stomach, Colon, and Rectal Neoplasms
  • 2018
  • Ingår i: Digestive Diseases and Sciences. - : SPRINGER. - 0163-2116 .- 1573-2568. ; 63:11, s. 2950-2958
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundMicrobial ecosystems that inhabit the human gut form central component of our physiology and metabolism, regulating and modulating both health and disease. Changes or disturbances in the composition and activity of this gut microbiota can result in altered immunity, inflammation, and even cancer.AimTo compare the composition and diversity of gut microbiota in stool samples from patient groups based on the site of neoplasm in the gastrointestinal tract (GIT) and to assess the possible contribution of the bacterial composition to tumorigenesis.MethodsWe studied gut microbiota by16S RNA gene sequencing from stool DNA of 83 patients, who were diagnosed with different GIT neoplasms, and 13 healthy individuals.ResultsAs compared to healthy individuals, stools of patients with stomach neoplasms had elevated levels of Enterobacteriaceae, and those with rectal neoplasms had lower levels of Bifidobacteriaceae. Lower abundance of Lactobacillaceae was seen in patients with colon neoplasms. Abundance of Lactobacillaceae was higher in stools of GIT patients sampled after cancer treatment compared to samples collected before start of any treatment. In addition to site-specific differences, higher abundances of Ruminococcus, Subdoligranulum and lower abundances of Lachnoclostridium and Oscillibacter were observed in overall GIT neoplasms as compared to healthy controlsConclusionOur study demonstrates that the alterations in gut microbiota vary according to the site of GIT neoplasm. The observed lower abundance of two common families, Lactobacillaceae and Bifidobacteriaceae, and the increased abundance of Enterobacteriaceae could provide indicators of compromised gut health and potentially facilitate GIT disease monitoring.
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