Level of interleukin 17 in inflammatory bowel disease and its relation with disease activity.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the gastrointestinal tract (GIT).It results in progressive intestinal epithelium structural and functional damage that necessitates lifetime medication.Thereis imbalance in the production of T helper 1 (Th1), Th2 and Th17 cytokines. This plays a crucial role in the chronic inflammatory process and the defective immune response to pathogenic agents; thus promoting the recurrence of the disease.Our aim of this study was to detect serum IL-17 levels in IBD patients and its relation with disease activity. METHODS: This was a single center case control study, conducted at hepatology and gastroenterology unit, Mansoura specialized Medical Hospital, Egypt.Patients who were included were aged 18-65 years, diagnosed either Ulcerative Colitis (UC)or Crohn's Disease (CD) based on previous colonoscopy.IBD activity was measured for UC using the MAYO score and CD using the CD activity index (CDAI). Fifty five patients were UC, 24 patients were CD, 21 patients were control.Patients who were excluded were under 15 years old, with history of GIT malignancy, or any serious comorbidities. Study protocol was approved by Institution Research Board (IRB) of Mansoura Medical College.All patients were subjected to full history taking, routine physical examination, colonoscopy and laboratory investigations including serum IL-17 levels by ELISA besides CBC, CRP, ESR and fecal calprotectin. RESULTS: Serum IL-17 level was increased significantly among UC; median (min-max) = 72(21-502)pg/ml, in CD 54.5(25-260) versus control 19 (14-35), P < 0.001.However, it was not correlated to the disease activity either Mayo score of UC or CDAI of CD.There was significant correlation to the extent of inflammation in UC affecting the colon (either proctosigmoiditis, left sided colitis or pan colitis), also to the type of CD (either inflammatory, stricturing or fistulizing) by P < 0.05.It was not correlated significantly with any of the IBD activity markers (CRP, ESR, or fecal calprotectin).Yet there was negative significant correlation with Hb level (r =-0.28, p = 0.005).There was not significant association between median serum level of IL-17 & duration of disease (P = 0.6).However, median IL-17 was higher among hospitalized cases than non-hospitalized (73 & 55, pg/ml respectively; p < 0.002). AUC was significantly differentiating between IBD and control group = 0.993 with the best-detected cut off point from curve 32 pg/ml yielding sensitivity of 97.5% and specificity of 95.2%. CONCLUSION: Serum IL-17 increases in colonic inflammation significantly more than in control group, however its increase is not correlated to IBD activity.

Serum Amyloid A as a non-invasive predictive biomarker of mucosal healing in ulcerative colitis patients.

Ulcerative colitis is a chronic immune-mediated inflammatory condition of large intestine that is frequently associated with inflammation of the rectum but often extends proximally to involve other areas of the colon. The ultimate target of therapy is complete healing in the form of clinical remission, complete endoscopic and histological healing, and transmural healing for which endoscopy is mandatory. Colonoscopy may not always be applicable due to possible complications in active ulcerative colitis. Therefore, non-invasive biomarkers are needed to avoid the disadvantageous complications of invasive diagnostic procedures. The aim of this study was to evaluate the role of serum Amyloid-A (SAA) as a non-invasive predictive biomarker of mucosal healing in comparison to different laboratory biomarkers, and endoscopic activity scores. The study included 100 ulcerative colitis patients classified into two groups: 50 patients in clinical, and biochemical remission and 50 patients in activity. Complete blood picture, C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin, and SAA were measured and recorded, colonoscopies with histopathological examination were done for all patients. SAA levels were significantly higher in patients with active ulcerative colitis than in clinical remission patients (p < 0.001). In clinical, remission patients without full mucosal healing, SAA was positively correlated with endoscopic disease activity represented with Mayo score, Mayo endoscopic sub-score and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) (p < 0.001). However, there was no significant correlation between SAA and endoscopic scores among the activity patients' group. The cut off value of SAA for determining disease activity was > 5.199 µg/ml with 100 % sensitivity, specificity of 92 %, and accuracy of 99.6%. In conclusion, SAA can be used for prediction of mucosal healing in ulcerative colitis remission patients despite not being superior to fecal calprotectin. However, it was unable to differentiate between the different disease activities or extents.

Role of Calprotectin, IL-6, and CRP in Distinguishing Between Inflammatory Bowel Disease and Diarrhea Predominant Irritable Bowel Syndrome.

Background: The early establishment of prophylaxis and immediate administration of anticoagulant therapy upon the diagnosis of venous thromboembolism should be the treatment objectives in these patients. Objective: The study aimed to determine the optimal cut-off point of Calprotectin, IL-6 (interleukin-6), CRP (C reactive protein) to differentiate UC, IBS-D. Methods: A cross-sectional descriptive study of 335 individuals ≥15 years old was performed, including 31 healthy controls, 215 with IBS-D, 71 diagnosed with UC, and 18 diagnosed with CD. Receiver Operating Characteristics (ROC), sensitivity, specificity, and area under curve (AUC) were computed. Results: The results showed that the median value of calprotectin (IQR) in healthy participants was 20.0 (6.0 - 34.0) µg/g; 17,7 (8,7-38,9) µg/g in IBS-D group; 1710.0 (588 - 4260,0) µg/g in UC group; and 560.5 (177.8 - 1210.0) µg/g in CD group. Calprotectin concentration in IBD group including UC and CD was higher than IBS-D with p<0.05. The median value of CRP (range IQR) was 1,3 (0,9 - 2,3) mg/L in IBS-D group; 7.0 (2.4 -16.6) mg/L in UC group; and 10.1 (2.2 - 42.5) mg/L in CD group. CRP concentration in IBD group including UC and CD was higher than IBS-D with p<0.05. The median value of IL-6 (range IQR) was 2.3 (1.6 - 5.7) pg/mL in IBS-D group; 16.8 (9.4 - 47.0) pg/mL in UC group; and 9.4 (7.9 - 11.0) pg/mL in CD group. Calprotectin concentration in IBD group including UC and CD was higher than IBS-D with p<0.05. The optimal cut-off point of calprotectin that differentiated IBS-D from IBD was 110.5 µg/g, with sensitivity and specificity of 93.3% and 91.4%, respectively; of IL-6 was 7.2 pg/mL with sensitivity and specificity of 92.0% and 78.0%, respectively; of CRP of 2.4 mg/L had specific sensitivities of 83.3% and 86.0%, respectively. Conclusion: The Calprotectin immunoassay has the best value in discriminating between IBD and IBS-D.

Formation of Calprotectin Inhibits Amyloid Aggregation of S100A8 and S100A9 Proteins.

Calcium-binding S100A8 and S100A9 proteins play a significant role in various disorders due to their pro-inflammatory functions. Substantially, they are also relevant in neurodegenerative disorders via the delivery of signals for the immune response. However, at the same time, they can aggregate and accelerate the progression of diseases. Natively, S100A8 and S100A9 exist as homo- and heterodimers, but upon aggregation, they form amyloid-like oligomers, fibrils, or amorphous aggregates. In this study, we aimed to elucidate the aggregation propensities of S100A8, S100A9, and their heterodimer calprotectin by investigating aggregation kinetics, secondary structures, and morphologies of the aggregates. For the first time, we followed the in vitro aggregation of S100A8, which formed spherical aggregates, unlike the fibrillar structures of S100A9 under the same conditions. The aggregates were sensitive to amyloid-specific ThT and ThS dyes and had a secondary structure composed of ß-sheets. Similarly to S100A9, S100A8 protein was stabilized by calcium ions, resulting in aggregation inhibition. Finally, the formation of S100A8 and S100A9 heterodimers stabilized the proteins in the absence of calcium ions and prevented their aggregation.

Intraoperative calprotectin lateral flow immunoassay can assist decision-making between one- and two-stage revision total hip arthroplasty for patients with suspected periprosthetic joint infection.

Aims: Accurate diagnosis of chronic periprosthetic joint infection (PJI) presents a significant challenge for hip surgeons. Preoperative diagnosis is not always easy to establish, making the intraoperative decision-making process crucial in deciding between one- and two-stage revision total hip arthroplasty (THA). Calprotectin is a promising point-of-care novel biomarker that has displayed high accuracy in detecting PJI. We aimed to evaluate the utility of intraoperative calprotectin lateral flow immunoassay (LFI) in THA patients with suspected chronic PJI. Methods: The study included 48 THAs in 48 patients with a clinical suspicion of PJI, but who did not meet European Bone and Joint Infection Society (EBJIS) PJI criteria preoperatively, out of 105 patients undergoing revision THA at our institution for possible PJI between November 2020 and December 2022. Intraoperatively, synovial fluid calprotectin was measured with LFI. Cases with calprotectin levels ≥ 50 mg/l were considered infected and treated with two-stage revision THA; in negative cases, one-stage revision was performed. At least five tissue cultures were obtained; the implants removed were sent for sonication. Results: Calprotectin was positive (≥ 50 mg/l) in 27 cases; out of these, 25 had positive tissue cultures and/or sonication. Calprotectin was negative in 21 cases. There was one false negative case, which had positive tissue cultures. Calprotectin showed an area under the curve of 0.917, sensitivity of 96.2%, specificity of 90.9%, positive predictive value of 92.6%, negative predictive value of 95.2%, positive likelihood ratio of 10.6, and negative likelihood ratio of 0.04. Overall, 45/48 patients were correctly diagnosed and treated by our algorithm, which included intraoperative calprotectin measurement. This yielded a 93.8% concordance with postoperatively assessed EBJIS criteria. Conclusion: Calprotectin can be a valuable tool in facilitating the intraoperative decision-making process for cases in which chronic PJI is suspected and diagnosis cannot be established preoperatively.

Reverse-engineered exclusive enteral nutrition in pediatric Crohn's disease: A pilot trial.

BACKGROUND: In pediatric Crohn's disease (CD), commercial formulas used as exclusive enteral nutrition (EEN) are effective at inducing remission. This study aims to assess the impact of a whole-food blended smoothie as EEN on CD activity and the intestinal microbiome. METHODS: A 4-week prospective trial assessed the impact of EEN with a whole-food smoothie on newly diagnosed mild-to-moderate active pediatric CD. The smoothie with a multivitamin were developed to meet age-appropriate nutritional requirements. Assessment over 4 weeks included Pediatric Crohn's Disease Activity Index (PCDAI), serum laboratories, fecal calprotectin (FCP), and stool collection for metagenomic shotgun sequencing and microbiota composition analysis. Clinical remission was defined as PCDAI ≤ 10 at week 4. RESULTS: Ten participants were enrolled with median age 14.5 years, and 8 completed the trial. Baseline mean PCDAI was 26.3 ± 9.1 and mean FCP 1149 ± 718 µg/g. At week 4, 80% of participants achieved clinical remission. FCP decreased by over half in 60% of participants, with FCP below 250 µg/g in 60% and below 100 µg/g in 40%. Microbiome analysis showed a significant increase in species richness over 4 weeks (p = 0.01). Compared to baseline, the relative abundance at week 2 and at week 4 was significantly increased for Bifidobacterium and Streptococcus and decreased for Blautia (p < 0.05 for all). CONCLUSION: A whole-food blended smoothie was effective for inducing clinical remission and decreasing FCP in pediatric CD similar to commercial EEN formulas. Further research may give insight into data-driven whole-food dietary approaches for CD management. CLINICALTRIALS: gov NCT03508193.

Calprotectin as a new inflammatory marker of abdominal aortic aneurysm: A pilot study.

INTRODUCTION: Abdominal aortic aneurysm (AAA) is a relevant clinical problem due to the risk of rupture of progressively dilated infrarenal aorta. It is characterized by degradation of elastic fibers, extracellular matrix, and inflammation of the arterial wall. Though neutrophil infiltration is a known feature of AAA, markers of neutrophil activation are scarcely analyzed; hence, the main objective of this study. METHODS: Plasma levels of main neutrophil activation markers were quantified in patients with AAA and a double control group (CTL) formed by healthy volunteers (HV) and patients with severe atherosclerosis submitted for carotid endarterectomy (CE). Calprotectin, a cytoplasmic neutrophil protein, was quantified, by Western blot, in arterial tissue samples from patients with AAA and organ donors. Colocalization of calprotectin and neutrophil elastase was assessed by immunofluorescence. RESULTS: Plasma calprotectin and IL-6 were both elevated in patients with AAA compared with CTL (p ⩽ 0.0001) and a strong correlation was found between both molecules (p < 0.001). This difference was maintained when comparing with HV and CE for calprotectin but only with HV for IL-6. Calprotectin was also elevated in arterial tissue samples from patients with AAA compared with organ donors (p < 0.0001), and colocalized with neutrophils in the arterial wall. CONCLUSIONS: Circulating calprotectin could be a specific AAA marker and a potential therapeutical target. Calprotectin is related to inflammation and neutrophil activation in arterial wall and independent of other atherosclerotic events.

Elevated level of circulating calprotectin correlates with severity and high mortality in patients with COVID-19.

BACKGROUND: Patients with coronavirus disease-2019 (COVID-19) are characterized by hyperinflammation. Calprotectin (S100A8/S100A9) is a calcium- and zinc-binding protein mainly secreted by neutrophilic granulocytes or macrophages and has been suggested to be correlated with the severity and prognosis of COVID-19. AIM: To thoroughly evaluate the diagnostic and prognostic utility of calprotectin in patients with COVID-19 by analyzing relevant studies. METHODS: PubMed, Web of Science, and Cochrane Library were comprehensively searched from inception to August 1, 2023 to retrieve studies about the application of calprotectin in COVID-19. Useful data such as the level of calprotectin in different groups and the diagnostic efficacy of this biomarker for severe COVID-19 were extracted and aggregated by using Stata 16.0 software. RESULTS: Fifteen studies were brought into this meta-analysis. First, the pooled standardized mean differences (SMDs) were used to estimate the differences in the levels of circulating calprotectin between patients with severe and non-severe COVID-19. The results showed an overall estimate of 1.84 (95% confidence interval [CI]: 1.09-2.60). Diagnostic information was extracted from 11 studies, and the pooled sensitivity and specificity of calprotectin for diagnosing severe COVID-19 were 0.75 (95% CI: 0.64-0.84) and 0.88 (95% CI: 0.79-0.94), respectively. The AUC was 0.89 and the pooled DOR was 18.44 (95% CI: 9.07-37.51). Furthermore, there was a strong correlation between elevated levels of circulating calprotectin and a higher risk of mortality outcomes in COVID-19 patients (odds ratio: 8.60, 95% CI: 2.17-34.12; p < 0.1). CONCLUSION: This meta-analysis showed that calprotectin was elevated in patients with severe COVID-19, and this atypical inflammatory cytokine might serve as a useful biomarker to distinguish the severity of COVID-19 and predict the prognosis.

Hormonal Contraceptives Reduce Active Symptomatic Disease but May Increase Intestinal Inflammation in IBD.

BACKGROUND: Among women of reproductive age with inflammatory bowel disease (IBD), we aimed to assess the relationship of hormonal contraceptives (HCs) with IBD-related symptoms, and intestinal inflammation. METHODS: A nested cohort of women in the longitudinal Manitoba Living with IBD Study, ages 18 to 49, were followed for 1 year, with bi-weekly online surveys. This included a validated measure of disease activity; IBD Symptom Inventory (IBDSI), and stool samples obtained at 3 time-points for assessment of fecal calprotectin (FCAL). Use of HC included oral and vaginal intrauterine devices. Logistic regression analysis was used to assess the association between HC and IBD-related symptoms (IBDSI>14 for Crohn disease, >13 for ulcerative colitis), or inflammation (FCAL>250 ug/g) at any measurement point in the study. RESULTS: Of 71 women, 17 (24%) reported taking HC in the 1 year period. Adjusting for age, disease type, disease duration, and smoking status, the odds of having increased IBD-related symptoms (IBDSI) during the year were lower for women using HC compared with women not using HC [adjusted odds ratio 0.16, 95% CI, 0.02-0.90]. Conversely, women using HC were more likely to have inflammation during the year [adjusted odds ratio 5.7, 95% CI, 1.23-43.6]. CONCLUSIONS: HC use among women with IBD was associated with a lower likelihood of IBD-related symptoms but a higher likelihood of experiencing intestinal inflammation (FCAL>250 ug/g) over 1 year. Further work is needed to examine this dichotomous result, potentially examining aspects such as duration of HC use, and the types of HC.

Matrix gla protein, a potential marker of tissue remodelling and physiological ageing of the gut in crohn's disease.

BACKGROUND: The inactive dephosphorylated and uncarboxylated form of the matrix Gla protein (dp-ucMGP) has been shown to be increased in plasma of inflammatory bowel disease (IBD) patients. Our aim was to assess if the plasmatic level of dp-ucMGP could reflect disease endoscopic activity, presence of strictures and cumulative structural bowel damage in Crohn's disease (CD) patients. METHODS: The plasmatic level of dp-ucMGP was measured in a monocentric cohort of prospectively recruited patients. The analysis was done by chemiluminescent immunoassay on blood samples collected the day of a planned ileocolonoscopy. In addition to classical clinical data (gender, age, body mass index (BMI), disease duration, current treatment), endoscopic data (disease location, Crohn's Disease Endoscopic Index of Severity (CDEIS), mucosal healing (MH), presence of 9 CD lesion types) and biological markers (faecal calprotectin and C-reactive protein (CRP)) were collected. The association between dp-ucMGP level and Lémann index was also investigated. Univariate linear regression was used to investigate the relationship between dp-ucMGP level and different parameters collected. RESULTS: A total of 82 ileocolonoscopies and dp-ucMGP assays were performed in 75 CD patients (45 females; 37 ileocolonic, 19 ileal and 19 colonic diseases) between October 2012 and November 2019. A total of 24 patients (29.3%) showed MH. The dp-ucMGP levels were not associated with MH, CDEIS, faecal calprotectin or CRP levels. Plasmatic dp-ucMGP levels increased significantly with age (p = 0.0032), disease duration (p = 0.0033), corticosteroids use (p = 0.019) and tended to increase in patients with intestinal strictures (p = 0.086) but not with the Lémann index. CONCLUSION: The significant increase of plasmatic dp-ucMGP levels with age, disease duration and the trend observed in patients with non-ulcerated strictures may suggest that this extracellular matrix protein could be a marker of tissue remodelling and physiological ageing of the gut.

Modulation of faecal miRNAs highlights the preventive effects of a Mediterranean low-inflammatory dietary intervention.

BACKGROUND: Dietary interventions have been proposed as therapeutic approaches for several diseases, including cancer. A low-inflammatory Mediterranean dietary intervention, conducted as a pilot study in subjects with Familial Adenomatous Polyposis (FAP), reduced markers of local and systemic inflammation. We aim to determine whether this diet may modulate faecal microRNA (miRNA) and gene expression in the gut. METHODS: Changes in the faecal miRNome were evaluated by small RNA sequencing at baseline (T0), after the three-month intervention (T1), and after an additional three months (T2). Changes in the transcriptome of healthy rectal mucosa and adenomas were evaluated by RNA sequencing at T0 and T2. The identification of validated miRNA-gene interactions and functional analysis of miRNA targets were performed using in silico approaches. RESULTS: Twenty-seven subjects were included in this study. It was observed that the diet modulated 29 faecal miRNAs (p < 0.01; |log2 Fold Change|>1), and this modulation persisted for three months after the intervention. Levels of miR-3612-3p and miR-941 correlated with the adherence to the diet, miR-3670 and miR-4252-5p with faecal calprotectin, and miR-3670 and miR-6867 with serum calprotectin. Seventy genes were differentially expressed between adenoma and normal tissue, and most were different before the dietary intervention but reached similar levels after the diet. Functional enrichment analysis identified the proinflammatory ERK1/2, cell cycle regulation, and nutrient response pathways as commonly regulated by the modulated miRNAs and genes. CONCLUSIONS: Faecal miRNAs modulated by the dietary intervention target genes that participate in inflammation. Changes in levels of miRNAs and genes with oncogenic and tumour suppressor functions further support the potential cancer-preventive effect of the low-inflammatory Mediterranean diet. CLINICAL TRIAL NUMBER REGISTRATION: NCT04552405, Registered in ClinicalTrials.gov.

Home-based fecal calprotectin utilization in a general pediatric gastroenterology clinic.

OBJECTIVE: Remote investigation and monitoring have gained importance in ambulatory practice. A home-based fecal calprotectin (FC) test has been developed where the sample is processed and analyzed at home through a smartphone application. We aimed to assess the use of standard ELISA (sFC) versus home-based (hFC) FC testing in a general pediatric gastroenterology clinic. METHODS: Ambulatory pediatric patients with hFC or sFC performed between August 2019 and November 2020 were included. Data regarding demographics, clinical characteristics, medication use, investigations, and final diagnosis, categorized as inflammatory bowel disease (IBD), functional gastrointestinal (GI) disorders, organic non-IBD (ONI) GI disorders, non-GI disorders, and undetermined after 6 months of investigation, were recorded. RESULTS: A total of 453 FC tests from 453 unique patients were included. Of those, 249 (55%) were hFC. FC levels (median) were higher in children with IBD compared to non-IBD diagnosis (sFC 795 vs. 57 µg/g, hFC 595 vs. 47 µg/g, p < 0.001), and in ONI compared to functional GI disorders (sFC 85 vs. 54 µg/g, p = 0.003, hFC 57 vs. 40 µg/g, p < 0.001). No significant difference was observed between different ONI GI disorders or subtypes of functional disorders. Age did not significantly influence levels. CONCLUSIONS: Overall, hFC and sFC provide similar results in the general pediatric GI ambulatory setting. FC is a sensitive but not disease-specific marker to identify patients with IBD. Values appear to be higher in ONI GI disorders over functional disorders, although cut-off values have yet to be determined.

A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial.

BACKGROUND: Management strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn's disease. We evaluated the use of a putative prognostic biomarker to guide therapy by assessing outcomes in patients randomised to either top-down (ie, early combined immunosuppression with infliximab and immunomodulator) or accelerated step-up (conventional) treatment strategies. METHODS: PROFILE (PRedicting Outcomes For Crohn's disease using a moLecular biomarker) was a multicentre, open-label, biomarker-stratified, randomised controlled trial that enrolled adults with newly diagnosed active Crohn's disease (Harvey-Bradshaw Index ≥7, either elevated C-reactive protein or faecal calprotectin or both, and endoscopic evidence of active inflammation). Potential participants had blood drawn to be tested for a prognostic biomarker derived from T-cell transcriptional signatures (PredictSURE-IBD assay). Following testing, patients were randomly assigned, via a secure online platform, to top-down or accelerated step-up treatment stratified by biomarker subgroup (IBDhi or IBDlo), endoscopic inflammation (mild, moderate, or severe), and extent (colonic or other). Blinding to biomarker status was maintained throughout the trial. The primary endpoint was sustained steroid-free and surgery-free remission to week 48. Remission was defined by a composite of symptoms and inflammatory markers at all visits. Flare required active symptoms (HBI ≥5) plus raised inflammatory markers (CRP >upper limit of normal or faecal calprotectin ≥200 µg/g, or both), while remission was the converse-ie, quiescent symptoms (HBI <5) or resolved inflammatory markers (both CRP ≤ the upper limit of normal and calprotectin <200 µg/g) or both. Analyses were done in the full analysis (intention-to-treat) population. The trial has completed and is registered (ISRCTN11808228). FINDINGS: Between Dec 29, 2017, and Jan 5, 2022, 386 patients (mean age 33·6 years [SD 13·2]; 179 [46%] female, 207 [54%] male) were randomised: 193 to the top-down group and 193 to the accelerated step-up group. Median time from diagnosis to trial enrolment was 12 days (range 0-191). Primary outcome data were available for 379 participants (189 in the top-down group; 190 in the accelerated step-up group). There was no biomarker-treatment interaction effect (absolute difference 1 percentage points, 95% CI -15 to 15; p=0·944). Sustained steroid-free and surgery-free remission was significantly more frequent in the top-down group than in the accelerated step-up group (149 [79%] of 189 patients vs 29 [15%] of 190 patients, absolute difference 64 percentage points, 95% CI 57 to 72; p<0·0001). There were fewer adverse events (including disease flares) and serious adverse events in the top-down group than in the accelerated step-up group (adverse events: 168 vs 315; serious adverse events: 15 vs 42), with fewer complications requiring abdominal surgery (one vs ten) and no difference in serious infections (three vs eight). INTERPRETATION: Top-down treatment with combination infliximab plus immunomodulator achieved substantially better outcomes at 1 year than accelerated step-up treatment. The biomarker did not show clinical utility. Top-down treatment should be considered standard of care for patients with newly diagnosed active Crohn's disease. FUNDING: Wellcome and PredictImmune Ltd.

Diagnostic accuracy of multimodal noninvasive follow-up for pediatric ulcerative colitis: A single-center prospective study.

OBJECTIVES: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) often requiring endoscopic evaluations, which can be uncomfortable and costly, especially for children. This study aimed to evaluate the diagnostic accuracy of a noninvasive approach combining fecal calprotectin (FCP), colonic ultrasonography (US), and colon capsule endoscopy (CCE) compared with standard ileocolonoscopy in pediatric UC. METHODS: UC children were enrolled and underwent FCP and US on Day 0, followed by CCE on Day 1 and ileocolonoscopy on Day 2. All procedures were performed by operators who were blinded to the patient's clinical history and all test results. The accuracy for disease activity and extension of each technique and their combination was assessed and compared. Tolerability and safety were also evaluated. RESULTS: Thirty-two patients were enrolled (15 males, mean age 13.2 ± 3.2 years). CCE showed a sensitivity of 95% and specificity of 100% in detecting colonic inflammation, with positive predictive value (PPV) and negative predictive value (NPV) of 100% and 92%, respectively. US demonstrated a sensitivity of 85% and specificity of 92%, with PPV and NPV of 94% and 79%. The combination of FCP, US, and CCE achieved 95% sensitivity and 100% specificity, with PPV of 100% and NPV of 92%. The noninvasive approach was better tolerated than colonoscopy (p < 0.05), and no serious adverse events were reported. CONCLUSION: The noninvasive approach combining fecal calprotectin (FCP), ultrasonography, and colon capsule endoscopy demonstrated high diagnostic accuracy and better tolerability compared with standard ileocolonoscopy in pediatric ulcerative colitis follow-up. Further multicenter studies are needed to confirm these findings and evaluate the reproducibility of this noninvasive approach.

The presence of enteropathy in HIV infected children on antiretroviral therapy in Malawi.

BACKGROUND: Undernutrition and malnutrition in children in low- and middle-income countries contribute to high mortality rates. Stunting, a prevalent form of malnutrition, is associated with educational and productivity losses. Environmental enteric dysfunction (EED) and human immunodeficiency virus (HIV) infection worsen these conditions. This study seeks to investigate the presence of enteropathy using EED fecal biomarkers in HIV-infected children who are stable on antiretroviral therapy (ART) across various nutritional statuses. By understanding the interplay between EED, HIV, and nutritional status, this study aims to provide insights that can inform targeted interventions to optimize nutritional outcomes in HIV infected children. METHODS/PRINCIPAL FINDINGS: This study evaluated the levels of alpha-1-antitrypsin, calprotectin and myeloperoxidase in frozen fecal samples from 61 HIV infected (mean age 9.16 ±3.08 years) and 31 HIV uninfected (6.65 ±3.41 years) children in Malawi. Anthropometric measurements and clinical data were collected. The height-for-age z-score (-1.66 vs -1.27, p = 0.040) and BMI-for-age z-score (-0.36 vs 0.01, p = 0.037) were lower in HIV infected children. Enzyme-linked immunosorbent assays were used to measure biomarker concentrations. Statistical tests were applied to compare biomarker levels based on HIV status and anthropometric parameters. Myeloperoxidase, alpha-1-antitrypsin, and calprotectin concentrations did not differ between HIV infected and HIV uninfected children of different age groups. In HIV infected children from 5-15 years, there is no difference in biomarker concentration between the stunted and non-stunted groups. CONCLUSION/SIGNIFICANCE: Our study found a higher prevalence of stunting in HIV infected children compared to uninfected children, but no significant differences in biomarker concentrations. This suggests no causal relationship between enteropathy and stunting in HIV infected children. These results contribute to the understanding of growth impairment in HIV infected children and emphasize the need for further research, particularly a longitudinal, biopsy-controlled study.

The gut-brain axis: Correlation of choroid plexus volume and permeability with inflammatory biomarkers in Crohn's disease.

BACKGROUND: The dysregulation of the gut-brain axis in chronic inflammatory bowel diseases can cause neuro-psychological disturbances, but the underlying mechanisms are still not fully understood. The choroid plexus (CP) maintains brain homeostasis and nourishment through the secretion and clearance of cerebrospinal fluid. Recent research has demonstrated the existence of a CP vascular barrier in mice which is modulated during intestinal inflammation. This study investigates possible correlations between CP modifications and inflammatory activity in patients with Crohn's disease (CD). METHODS: In this prospective study, 17 patients with CD underwent concomitant abdominal and brain 3 T MRI. The volume and permeability of CP were compared with levels of C-reactive protein (CRP), fecal calprotectin (FC), sMARIA and SES-CD scores. RESULTS: The CP volume was negatively correlated with CRP levels (R = -0.643, p-value = 0.024) and FC (R = -0.571, p-value = 0.050). DCE metrics normalized by CP volume were positively correlated with CRP (K-trans: R = 0.587, p-value = 0.045; Vp: R = 0.706, p-value = 0.010; T1: R = 0.699, p-value = 0.011), and FC (Vp: R = 0.606, p-value = 0.037). CONCLUSIONS: Inflammatory activity in patients with CD is associated with changes in CP volume and permeability, thus supporting the hypothesis that intestinal inflammation could affect the brain through the modulation of CP vascular barrier also in humans.

Factors associated with corticosteroid use in Crohn's disease and ulcerative colitis patients in Israel: A multicenter cross-sectional study.

BACKGROUND: We examined corticosteroid use among Israeli patients with Inflammatory Bowel Disease (IBD), focusing on demographic, disease-related, and psychosocial factors. The objective was to contribute to the development of strategies minimizing corticosteroid dependence and improving patient outcomes, given the adverse effects associated with prolonged corticosteroid use. METHODS: A comprehensive analysis was conducted on data collected from adult IBD patients attending six gastroenterological outpatient clinics in Israel. The data collected encompassed disease characteristics, demographic information, service level characteristics, social data, and steroid use. Statistical analyses were performed to associate these variables with steroid use. RESULTS: Out of 402 patients, 26 % had been treated with corticosteroids in the previous year, with a majority of these having only one treatment course. Of patients treated with steroids, 57% (n-44) met steroid dependent/excess criteria. Steroid use was more common in patients diagnosed with ulcerative colitis (UC) compared to those with Crohn's disease. Factors such as a diagnosis of UC, male gender, elevated C-reactive protein and fecal calprotectin, and decreased albumin and hemoglobin were associated with steroid use. CONCLUSION: Corticosteroid use among Israeli IBD patients was associated with disease-related factors and some demographic characteristics. The results highlight the need for continued research to inform strategies aimed at reducing corticosteroid dependence in managing IBD, thereby improving patient outcomes.

Methanogenic Archaea in the Pediatric Inflammatory Bowel Disease in Relation to Disease Type and Activity.

The inflammatory bowel disease (IBD) is associated with gut microbiota dysbiosis; however, studies on methanogens-especially those focused on children-are extremely limited. The aim of this study was to determine the abundance of total methanogenic archaea and their three subgroups: Methanobrevibacter (Mb.) smithii, Methanosphaera (Ms.) stadtmanae, and Methanomassiliicoccales, in the feces of children with both active and inactive Crohn's disease (CD) and ulcerative colitis (UC). The results of a quantitative real-time PCR were cross-referenced with the disease type (CD vs. UC) and activity assessed with the use of Pediatric Crohn's Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index (PUCAI) indices, and fecal calprotectin (FCP) concentration, and compared with controls. There was a significant decrease in the number of total methanogens in CD and UC compared to controls. The prevalence of total methanogens was also lower in UC compared to controls. Furthermore, patients from the inactive UC group were colonized by a lower number of Mb. smithii, and demonstrated the most pronounced positive correlation between the number of Ms. stadtmanae and the FCP concentration. Our results demonstrate that gut methanogens are related to the type and activity of pediatric IBD.

Validation of rapid fecal calprotectin assay using particle enhanced turbidimetric immunoassay for inflammatory bowel disease.

Fecal calprotectin (FC) is a promising biomarker for diagnosis and treatment of inflammatory bowel disease, ulcerative colitis (UC), and Crohn's disease. An enzyme immunoassay (EIA) is widely used for FC detection, though the considerable lag time, up to several days, causes clinical management delay. This study was performed to examine the new rapid kit fCAL-turbo, which is based on a particle-enhanced turbidimetric immunoassay (15 min), by comparing FC values with other EIAs (EliA, PhiCal, Bühlmann) and endoscopic scores. Using 94 samples, fCAL-turbo showed strong significant positive correlations with the other kits (Spearman's r = 0.9178-0.9886). Of 74 UC patients, 69 underwent an endoscopy and fCAL-turbo reflected endoscopic activity with a moderate correlation with Mayo endoscopic subscore (MES) (r = 0.6945, others r = 0.6682-0.7013). Receiver operating characteristic analyses based on MES 0 versus 1-3 showed a similar efficacy as compared to the other kits (cut-off and area under the curve: 89.70 µg/g and 0.8592, respectively, others 62.35-138.4 µg/g and 0.8280-0.8611, respectively). Furthermore, multiple regression analysis confirmed that fCAL-turbo results significantly contributed to prediction of MES 0 with a higher t-value as compared to the other biomarkers. fCAL-turbo showed strong correlations with the other kits and also demonstrated excellent performance for predicting endoscopic remission of UC.