[Pan American Crohn's and Colitis Organization (PANCCO) and the Interamerican Society of Endoscopy (SIED) consensus on endoscopy in inflammatory bowel disease]. / Consenso de endoscopia en enfermedad inflamatoria intestinal de la Organización Panamericana de Crohn y Colitis (PANCCO) y la Sociedad Interamericana de endoscopia (SIED).

INTRODUCTION: Endoscopy plays a fundamental role in inflammatory bowel disease (IBD), and becomes essential in diagnosis, treatment monitoring, and detection and management of complications. MATERIALS AND METHODS: The Pan American Crohn's and Colitis Organization (PANCCO) and the Inter-American Society of Endoscopy (SIED) appointed 22 Latin American experts in IBD to develop a consensus study using the modified Delphi method, based on the best available evidence. A working group of 22 members from 9 countries identified 15 topics and formulated 98 statements, who participated in 2 rounds of voting. It was defined as agreement of ≥80% of experts for each statement. RESULTS: After the voting of all the statements, 8 statements were obtained that did not reach 80% consensus among the participants, so the questions were reconsidered in the Coordinating Committee of the consensus with the participation of the expert reviewers of these questions and 7 final statements were voted again by all the experts in a second round and 1 was eliminated with consensus. After two rounds of voting, the experts reached consensus with literature review with the best available evidence, the most important issues were developed with scientific evidence supporting each of the statements around the topic of endoscopy in IBD. CONCLUSIONS: Consensus statements were developed and based on the best available evidence about endoscopy in inflammatory bowel disease.

Serum calgranulin C as a non-invasive predictor of activity among inflammatory bowel disease.

Inflammatory bowel disease is a chronic immune-mediated disorder with a relapsing and remitting course. It leads to disabling gastrointestinal symptoms, low quality of life, and a significant burden for healthcare utilization and associated costs. Therefore, non-invasive biomarkers are needed for early diagnosis and follow up to avoid the complications of invasive diagnostic procedures. Calgranulin C is a calcium binding protein with proinflammatory properties. The aim of this study was to evaluate the role of serum calgranulin C as a non-invasive biomarker for diagnosis and prediction of activity in comparison to different biomarkers and endoscopic activity scores in inflammatory bowel disease. The study included 80 inflammatory bowel disease patients (50 Ulcerative colitis and 30 Chron's patients) and 20 normal controls. Complete blood picture, C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin and serum calgranulin C were measured. Colonoscopies with histopathological examination were done and different activity scoring systems assessed. Among ulcerative colitis group, serum calgranulin C was statistically significantly higher in comparison to control group [723.640±529.055 ng/ml versus 80.850±24.416 ng/ml]. Depending on the American college of gastroenterology ulcerative colitis activity index, fecal calprotectin and serum calgranulin C were statistically significantly higher among moderate to severe ulcerative colitis than those with mild activity and those in remission (p < 0.001, for both). Regarding Crohn's disease group, serum calgranulin C was statistically significantly higher in comparison to control group [759.233±797.963 ng/ml versus 80.850±24.416 ng/mL]. Depending on Crohn's disease activity index, both serum calgranulin C and fecal calprotectin were statistically significantly higher among active disease than those in remission (p < 0.001, for both). In conclusion, serum calgranulin C could be used as a non-invasive marker to predict activity and severity and to ensure remission among inflammatory bowel disease patients.

Non-destructive diagnosis of Inflammatory Bowel Disease by near-infrared spectroscopy and aquaphotomics.

Inflammatory Bowel Disease includes Crohn's Disease and Ulcerative Colitis. Currently, diagnosing involves a series of current diagnostic methods that are invasive, time-consuming, and expensive. Near-infrared spectroscopy and aquaphotomics can detect changes in biofluids and thus have the potential to diagnose disease. This study aimed to investigate the diagnostic ability of near infrared spectroscopy and aquaphotomics for Inflammatory Bowel Disease and its types. This method used blood plasma and saliva samples absorbance spectrum and multivariate analysis with the Principal Component Analysis and, Linear Discriminant Analysis, Quadratic Discriminant Analysis, and Support Vector Machine in the range 1300-1600 nm and 12 water absorbance bands in this range, separately. In the near-infrared range, total accuracy of 100% led to the separation of the healthy group and Inflammatory Bowel Disease and then the separation of the healthy group and patients with Ulcerative Colitis and Crohn's Disease. The aquaphotomics approach was used to investigate the changes in the 12 water absorbance bands and their impact on the accuracy of the diagnostic method. Aquaphotomics also detected 100% of the mentioned samples. We achieved a fast, accurate, non-invasive method based on near-infrared spectroscopy and aquaphotomics to diagnose Inflammatory Bowel Disease and its types using blood plasma or saliva samples. The current study found that monitoring blood plasma or saliva using near-infrared spectra offers an opportunity to thoroughly investigate biofluids and changes in their water spectral patterns caused by complex physiological changes due to Inflammatory Bowel Disease and its types, and to visualize these changes using aquagram.

The role of fecal biomarkers in individuals with inflammatory bowel disease.

INTRODUCTION: Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and Ulcerative Colitis (UC), is a relapsing and remitting condition. Noninvasive biomarkers have an increasingly important role in the diagnosis of IBD and in the prediction of future disease course in individuals with IBD. Strategies for the management of IBD increasingly rely upon close monitoring of gastrointestinal inflammation. AREAS COVERED: This review provides an update on the current understanding of established and novel stool-based biomarkers in the diagnosis and management of IBD. It also highlights key gaps, identifies limitations, and advantages of current markers, and examines aspects that require further study and analysis. EXPERT OPINION: Current noninvasive inflammatory markers play an important role in the diagnosis and management of IBD; however, limitations exist. Future work is required to further characterize and validate current and novel markers of inflammation. In addition, it is essential to better understand the roles and characteristics of noninvasive markers to enable the appropriate selection to accurately determine the condition of the intestinal mucosa.

Inflammatory Bowel Disease: A Comprehensive Analysis of Molecular Bases, Predictive Biomarkers, Diagnostic Methods, and Therapeutic Options.

In inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), the immune system relentlessly attacks intestinal cells, causing recurrent tissue damage over the lifetime of patients. The etiology of IBD is complex and multifactorial, involving environmental, microbiota, genetic, and immunological factors that alter the molecular basis of the organism. Among these, the microbiota and immune cells play pivotal roles; the microbiota generates antigens recognized by immune cells and antibodies, while autoantibodies target and attack the intestinal membrane, exacerbating inflammation and tissue damage. Given the altered molecular framework, the analysis of multiple molecular biomarkers in patients proves exceedingly valuable for diagnosing and prognosing IBD, including markers like C reactive protein and fecal calprotectin. Upon detection and classification of patients, specific treatments are administered, ranging from conventional drugs to new biological therapies, such as antibodies to neutralize inflammatory molecules like tumor necrosis factor (TNF) and integrin. This review delves into the molecular basis and targets, biomarkers, treatment options, monitoring techniques, and, ultimately, current challenges in IBD management.

Platelet indices and inflammatory bowel disease: a Mendelian randomization study.

Background: Platelets play a significant role in the innate and adaptive processes of immunity and inflammation. Inflammatory bowel disease (IBD) is an autoimmune disease that is widely understood to be caused by a combination of genetic predisposition, aberrant immune responses, etc. Methods: To examine the relationships between genetically determined platelet indices and IBD, we conducted a Mendelian randomization (MR) study. Data associated with platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT) were used from the UK Biobank. The outcome data, including IBD, Crohn's disease (CD), ulcerative colitis (UC), were from the FinnGen database. The inverse variance-weighted (IVW), MR-Egger, weighted median methods were used for MR analyses. Results: The MR estimations from the IVW approach show a significant connection between PLT and IBD. Similarly, PCT and IBD have a relationship following the IVW and MR-Egger approaches. While PLT and PCT have strong relationships with CD, according to the findings of all three approaches respectively. Nevertheless, PDW was the only relevant indicator of UC. The only significant result was IVW's. Conclusion: Our findings suggest that the fluctuation of platelet indicators is of great significance in the development of IBD. PLT and PCT have a close association with IBD and CD, respectively; PDW only has a connection with UC. Platelets play an important role in the progression of IBD (UC, CD).

Faecal volatile organic compounds differ according to inflammatory bowel disease sub-type, severity, and response to treatment in paediatric patients.

BACKGROUND: Faecal volatile organic compounds (VOCs) differ with disease sub-type and activity in adults with established inflammatory bowel disease (IBD) taking therapy. OBJECTIVE: To describe patterns of faecal VOCs in children newly presented with IBD according to disease sub-type, severity, and response to treatment. METHODS: Children presenting with suspected IBD were recruited from three UK hospitals. Children in whom IBD was diagnosed were matched with a non-IBD child for age, sex, and recruitment site. Faecal VOCs were characterised by gas chromatography-mass spectrometry at presentation and 3 months later in children with IBD. RESULTS: In 132 case/control pairs, median (inter-quartile range) age in IBD was 13.3 years (10.2-14.7) and 38.6% were female. Compared with controls, the mean abundance of 27/62 (43.6%) faecal VOCs was statistically significantly decreased in Crohn's disease (CD), ulcerative colitis (UC) or both especially amongst ketones/diketones, fatty acids, and alcohols (p < 0.05). Short-chain, medium chain, and branched chain fatty acids were markedly reduced in severe colitis (p < 0.05). Despite clinical improvement in many children with IBD, the number and abundance of almost all VOCs did not increase following treatment, suggesting persistent dysbiosis. Oct-1-en-3-ol was increased in CD (p = 0.001) and UC (p = 0.012) compared with controls and decreased following treatment in UC (p = 0.01). In CD, propan-1-ol was significantly greater than controls (p < 0.001) and extensive colitis (p = 0.001) and fell with treatment (p = 0.05). Phenol was significantly greater in CD (p < 0.001) and fell with treatment in both CD (p = 0.02) and UC (p = 0.01). CONCLUSION: Characterisation of faecal VOCs in an inception cohort of children with IBD reveals patterns associated with diagnosis, disease activity, and extent. Further work should investigate the relationship between VOCs and the microbiome in IBD and their role in diagnosis and disease monitoring.

Very Early Onset Inflammatory Bowel Disease: Diagnostic and Therapeutic Challenges for Pediatric Gastroenterologists.

Very early onset inflammatory bowel disease (VEO-IBD) is called when age of onset of IBD occurs below 6 years. Though it is rare, it has been increasing over last decade with decreasing age of onset. VEO-IBD is different compared with pediatric and adult-onset IBD in many aspects, including the disease type, location of the lesion, disease behavior and genetic susceptibility. These children with VEO-IBD are usually present with more severe disease than older children and adults. VEO-IBD is associated with monogenic defect. The thought of a monogenic cause of VEO-IBD was first confirmed by the detection of mutations of interleukin 10 (IL-10) receptor genes that cause impaired IL-10 signaling. Monogenic IBD possesses significant concern because it usually presents with refractory to conventional IBD treatment or fistulous Crohn's disease, so early treatment with biologics or an alternative approach such as hematopoietic stem cell transplantation (HSCT) might be looked-for. Before establishing IBD, we must think of more common diseases of this age group. Infection and Cow's milk protein allergy (CMPA) are two common conditions and it can cause severe colitis. Confirmation of chronic intestinal inflammation by endoscopies is of greatest significance for the diagnosis of IBD. There should be no age limit for performing endoscopies. Severe disease should be treated with biologic agents and surgery. Identification of genes associated with IBD leads to better understanding of its pathogenesis, which could help to provide more targeted interventions. We discuss the topic here to create awareness among Pediatricians so that the patients can be benefited.

Diagnosis and management of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic and relapsing immune-mediated disease of the gastrointestinal tract with a gradually increasing global incidence and prevalence. A prolonged course of IBD leads to a decline in patient quality of life and the creation of a substantial economic burden on society. Owing to the lack of specific diagnostic markers, the diagnosis of IBD still needs a gold standard based on a combination of clinical manifestations, imaging, laboratory, and endoscopic results. Accordingly, the current goals of IBD treatment are to alleviate clinical symptoms and reduce recurrence rates. Therefore, it is imperative to develop a standard set of procedures to diagnose and treat IBD. In this review, we summarize prominent and emerging studies, outline classical and contemporary approaches to diagnosing and managing IBD, and integrate multiple guidelines. Furthermore, we propose the possibility of establishing an early and comprehensive diagnostic workflow and personalized management strategy in the future. We aim to enhance the quality and standardization of diagnostic and treatment procedures for IBD.

Strategies to Improve Colonoscopy Preparation in Inflammatory Bowel Disease. A Systematic Review and Network Meta-analysis of Randomized Trials.

BACKGROUND AND AIMS: Colonoscopy has a vital role in the diagnosis of inflammatory bowel disease (IBD), as well as in the estimation of disease severity, monitoring response to therapy, and surveillance for neoplasia. We performed a systematic review of randomised trials of various bowel preparations for colonoscopy in IBD. METHODS: We searched various electronic databases (PubMed, Embase, and CENTRAL) for studies reporting about the use of various strategies to improve colonoscopy preparation in IBD. We included only randomized clinical trials (RCTs). A network meta-analysis was done using a frequentist approach to compare the effectiveness of various bowel preparations. The risk of bias was assessed using Cochrane risk of bias tool 2.0. Other outcome parameters like compliance, tolerance, acceptance, and adverse effects were assessed qualitatively. RESULTS: Seven RCTs reporting about 960 patients were included. On comparison with 4 liter (L) of poliethylen glycol (PEG), oral sulfate solution (OR=1.1, 95%CI: 0.65-1.86); PEG2L/Ascorbate (OR=0.98, 95%CI: 0.65-1.48); PEG1L (OR=1, 95%CI: 0.55-1.81); PEG2L plus bisacodyl (OR=1.08, 95%CI: 0.71-1.65); PEG4L plus simethicone (OR=1, 95%CI: 0.67-1.50); PEG/ sodium picosulfate and magnesium citrate (SPMC) 1.5L (OR=0.99, 95%CI: 0.55-1.78); SPMC 2L (OR=1.09, 95%CI: 0.61-1.97) had similar effectiveness. Three RCTs reported compliance, five RCTs reported tolerance, two studies reported patient acceptance and five RCTs reported data on the willingness of patients to repeat the procedure in the future. Low-volume preparations had better compliance, tolerance, acceptance, and willingness to repeat. No difference in additional outcomes like change in disease activity after colonoscopy, procedure-related outcomes after colonoscopy like cecal intubation rate, and change in electrolyte levels were found. CONCLUSION: Various bowel preparations had similar effectiveness in respect to colonoscopy preparation in IBD patients. Low-volume preparations have better compliance, tolerance, and acceptance. The systematic review was limited by a small number of included RCTs.

Bile acid profiles and classification model accuracy for inflammatory bowel disease diagnosis.

To investigate the utility of serum bile acid profiling for the diagnosis of inflammatory bowel disease (IBD). We analyzed 15 specific bile acids in the serum of 269 IBD patients, 200 healthy controls (HC), and 174 patients with other intestinal diseases (OID) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Serum bile acid levels were compared between IBD group, HC group, and OID group. Binary logistic regression-based models were developed to model the bile acids and diagnose IBD. Furthermore, receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic accuracy of each bile acid and the model. Compared to HC group, IBD group exhibited significantly lower levels of chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), glycodeoxycholic acid (GDCA), taurodeoxycholic acid (TDCA), lithocholic acid (LCA), glycolithocholic acid (GLCA), taurolithocholic acid (TLCA), and an elevated primary-to-secondary bile acid ratio. DCA had an area under the curve (AUC) of 0.860 for diagnosing IBD, with a sensitivity of 80.67% and a specificity of 82.50%. A model Y0 combining DCA and CDCA to distinguish between IBD group and HC group further improved accuracy (AUC = 0.866, sensitivity = 76.28%, specificity = 89.37%). Compared to non-IBD group (which combined healthy controls and those with other intestinal diseases), IBD group had significantly lower levels of DCA, GDCA, TDCA, LCA, GLCA, and TLCA, and elevated levels of glycocholic acid (GCA) and glycochenodeoxycholic acid (GCDCA). A model Y1 incorporating GCDCA, DCA and TLCA to distinguish between IBD group and non-IBD group yielded an AUC of 0.792, with a sensitivity of 77.67% and specificity of 71.91%. IBD patients exhibit decreased serum secondary bile acid levels and an elevated primary-to-secondary bile acid ratio. Serum bile acid alterations are associated with the onset of IBD. A model consisting of CDCA and DCA has potential for distinguishing between IBD group and HC group, while a model incorporating GCDCA, DCA and TLCA may be suitable for distinguishing between IBD group and non-IBD group.

Identification and validation of a blood- based diagnostic lipidomic signature of pediatric inflammatory bowel disease.

Improved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a discovery cohort of incident treatment-naïve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making.

Development of Luminescent Biosensors for Calprotectin.

Calprotectin, a metal ion-binding protein complex, plays a crucial role in the innate immune system and has gained prominence as a biomarker for various intestinal and systemic inflammatory and infectious diseases, including inflammatory bowel disease (IBD) and tuberculosis (TB). Current clinical testing methods rely on enzyme-linked immunosorbent assays (ELISAs), limiting accessibility and convenience. In this study, we introduce the Fab-Enabled Split-luciferase Calprotectin Assay (FESCA), a novel quantitative method for calprotectin measurement. FESCA utilizes two new fragment antigen binding proteins (Fabs), CP16 and CP17, that bind to different epitopes of the calprotectin complex. These Fabs are fused with split NanoLuc luciferase fragments, enabling the reconstitution of active luciferase upon binding to calprotectin either in solution or in varied immobilized assay formats. FESCA's output luminescence can be measured with standard laboratory equipment as well as consumer-grade cell phone cameras. FESCA can detect physiologically relevant calprotectin levels across various sample types, including serum, plasma, and whole blood. Notably, FESCA can detect abnormally elevated native calprotectin from TB patients. In summary, FESCA presents a convenient, low-cost, and quantitative method for assessing calprotectin levels in various biological samples, with the potential to improve the diagnosis and monitoring of inflammatory diseases, especially in at-home or point-of-care settings.

Long non-coding RNAs as pathophysiological regulators, therapeutic targets and novel extracellular vesicle biomarkers for the diagnosis of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic relapsing disease of the gastrointestinal (GI) system that includes two groups, Crohn's disease (CD) and ulcerative colitis (UC). To cope with these two classes of IBD, the investigation of pathogenic mechanisms and the discovery of new diagnostic and therapeutic approaches are crucial. Long non-coding RNAs (lncRNAs) which are non-coding RNAs with a length of longer than 200 nucleotides have indicated significant association with the pathology of IBD and strong potential to be used as accurate biomarkers in diagnosing and predicting responses to the IBD treatment. In the current review, we aim to investigate the role of lncRNAs in the pathology and development of IBD. We first describe recent advances in research on dysregulated lncRNAs in the pathogenesis of IBD from the perspective of epithelial barrier function, intestinal immunity, mitochondrial function, and intestinal autophagy. Then, we highlight the possible translational role of lncRNAs as therapeutic targets, diagnostic biomarkers, and predictors of therapeutic response in colon tissues and plasma samples. Finally, we discuss the potential of extracellular vesicles and their lncRNA cargo in the pathophysiology, diagnosis, and treatment of IBD.

Helicobacter pylori infection found during upper endoscopy performed for the diagnosis of celiac, inflammatory bowel diseases, and eosinophilic esophagitis: A multicenter pediatric European study.

BACKGROUND: Helicobacter pylori may be found during upper gastrointestinal endoscopy (UGE) performed to diagnose celiac disease (CeD), inflammatory bowel disease (IBD), and eosinophilic esophagitis (EoE). We aimed to describe the frequency of H. pylori in children undergoing UGE for CeD, IBD, and EoE and the number of children receiving eradication treatment. MATERIALS AND METHODS: A retrospective multicenter study from 14 countries included pediatric patients diagnosed with CeD, IBD, and EoE between January 2019 and December 2021. DATA COLLECTED: age, gender, hematologic parameters, endoscopic, histologic, and H. pylori culture results, and information on eradication treatment. RESULTS: H. pylori was identified in 349/3890 (9%) children [167 (48%) male, median 12 years (interquartile range 8.1-14.6)]. H. pylori was present in 10% (173/1733) CeD, 8.5% (110/1292) IBD and 7.6% (66/865) EoE patients (p = NS). The prevalence differed significantly between Europe (Eastern 5.2% (28/536), Southern 3.8% (78/2032), Western 5.6% (28/513)) and the Middle East 26.6% (215/809) [odds ratio (OR) 7.96 95% confidence interval (CI) (6.31-10.1) p < 0.0001]. Eradication treatment was prescribed in 131/349 (37.5%) patients, 34.6% CeD, 35.8% IBD, and 56.1% EoE. Predictors for recommending treatment included erosions/ulcers [OR 6.45 95% CI 3.62-11.47, p < 0.0001] and nodular gastritis [OR 2.25 95% CI 1.33-3.81, p 0.003]. Treatment rates were higher in centers with a low H. pylori prevalence (<20%) [OR 3.36 95% CI 1.47-7.66 p 0.004]. CONCLUSIONS: Identifying H. pylori incidentally during UGE performed for the most common gastrointestinal diseases varies significantly among regions but not among diseases. The indications for recommending treatment are not well defined, and less than 40% of children received treatment.

Erythema nodosum in northern Finland between 1996 and 2019: A register-based study.

Erythema nodosum (EN) is seen at any age with varying and often unidentified etiology. We studied the etiology and characteristics of EN in Northern Finland. Medical records of all patients with a diagnosis code for EN between 1996 and 2019 from Oulu University Hospital were retrieved and analyzed. There were in total 142 EN cases with a female predominance (n = 112, 72.9%). The mean age of the patients was 35.9 years. There were five cases diagnosed with EN in those younger than 2 years of age. Almost one third had EN nodules in multiple anatomical locations. In addition to skin findings, systemic symptoms were common (81.0%), and seen more often in men (p < 0.05). In children and adolescents, the most common etiological factors were gastroenteritis caused by 'Yersinia, Salmonella or Campylobacter', followed by inflammatory bowel diseases and hormonal contraception. Bacterial infections were the most common etiological factor among adults. In 28.2% of the cases there was no identified causative factor. In this study, EN was seen surprisingly often in small children. Etiological factors varied markedly among different age groups and symptoms differed between the sexes in adults. These aspects should be taken into account when diagnosing EN patients.

Approach to Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) in the horse encompasses a group of infiltrative gastrointestinal disorders resulting in malabsorption, maldigestion, weight loss, colic, and sometimes diarrhea. The type of IBD can be classified as granulomatous, lymphocytic-plasmacytic, or eosinophilic enterocolitis. The diagnosis of IBD in equids is based on consistent clinical signs and clinicopathologic findings in conjunction with confirmatory histopathology from a gastrointestinal biopsy. Treatment usually consists of a combination of immunosuppressive medications, anthelmintics, and dietary modifications. The prognosis of IBD in horses is variable and dependent on the horse's response to treatment; however, horses can show improvement or resolution of clinical signs.