Fecal calprotectin as an inflammatory biomarker in small bowel Crohn disease.

Background: Small bowel capsule endoscopy (SBCE) is an essential tool for evaluation of small bowel (SB) Crohn disease (CD). Fecal calprotectin (FC) represents an important biomarker of intestinal inflammation, widely used in ulcerative colitis and CD. Our aim was to evaluate the role of FC for diagnosing inflammatory activity in patients with isolated SB CD and how it correlates with SBCE findings. Methods: This is a retrospective study conducted in a tertiary inflammatory bowel disease referral center that included patients with SB CD who underwent SBCE between January 2017 and February 2023. FC value was obtained from the closest stool examination to SBCE. Results: One hundred ninety-six patients were included: 123 were women (63%) with a mean age of 44.2 years. In the SBCE, 127 (65%) patients had a Lewis Score ≥135 and, among the 94 patients with FC >200 µg/g, 23 had LS <135, 36 had LS between 135 and 790, and 35 had LS ≥790. FC levels were predictive of endoscopic lesions in SBCE, with significant correlation between FC level and total LS (Pearson correlation coefficient 0.43, P<.001). The sensitivity and specificity were calculated for each cut-off value being respectively 78% and 45% for FC = 100 µg/g, 69% and 59% for FC = 150 µg/g and 67% and 67% for FC = 200 µg/g. Conclusion: FC showed moderate correlation with endoscopic findings in SBCE in SB CD. It is, therefore, a reasonable marker for predicting significant inflammatory lesions in SBCE; however, none of the cut-off had a high sensitivity or specificity.

Fecal calprotectin diagnostic level gradient along the small bowel in patients with Crohn's disease.

BACKGROUND AND AIMS: Fecal calprotectin (FC) is known to be a sensitive biomarker of colonic inflammation but to a lesser degree of small bowel (SB) inflammation. Moreover, data on FC's diagnostic levels in different SB segments are scarce. We aimed to examine FC's diagnostic levels along the SB-axis in CD. METHODS: This was a post-hoc aggregated analysis of five prospective studies of adult CD patients, who underwent FC testing and SB video capsule endoscopy (VCE). Lewis score (LS) inflammation in different SB segments was tested for correlation with FC level after exclusion of colonic disease. The diagnostic levels of FC for SB inflammatory topographical-gradient were assessed using a receiver operating characteristic. RESULTS: 214 patients were included (age:30 [24-43] year-old, males-57%). For a similar SB inflammatory-activity (LS≥135), FC levels incrementally increased from proximal to distal SB segments (63 [30-121] versus 190 [78-549], p=0.005) and from distal SB segment to the colon (190 [78-549] versus 542 [185-1000], p=0.010). The best FC cutoffs to identify isolated mild proximal/distal SB-inflammation (LS≥135) were 77µgg and 123µgg, respectively. A cutoff of 234µgg was best to detect more significant proximal inflammation (LS≥350) when only mild distal SB-inflammation was present. In sensitivity analyses, this proximal-to-distal FC gradient was maintained when LS≥350 and LS≥790 were used as the inflammatory reference-values. Unlike FC, the magnitude of CRP elevation was unrelated to the topography of inflammation along the SB-axis. CONCLUSIONS: FC may serve as a topographical biomarker of CD-activity, with its sensitivity to identify mucosal inflammation increases from proximal to distal SB segments.

Changes in endoscopic activity and classification of lesions with panenteric capsule endoscopy in patients treated for Crohn's disease - a prospective blinded comparison with ileocolonoscopy, faecal calprotectin and C-reactive protein.

BACKGROUND AND AIMS: Panenteric capsule endoscopy (PCE) is a minimally invasive modality that may replace ileocolonoscopy (IC) in selected patients with Crohn's disease (CD). This study aimed to evaluate the dynamics of repeated assessment with PCE in patients receiving medical treatment for ileocolonic CD. METHODS: This prospective, blinded, multicentre study included patients with endoscopically active CD. Patients were scheduled for IC, PCE, faecal calprotectin and C-reactive protein before and 12 weeks after treatment with corticosteroids or biological therapy. The endoscopic disease activity was assessed with the Simple Endoscopic Score for Crohn's Disease (SES-CD). RESULTS: 31 patients entered the study, and PCE visualized 148 (95.5%) and 128 (82.6%) ileocolonic bowel segments before and after medical treatment, respectively. The median SES-CD decreased from 14 (IQR 8-17) to 5 (IQR 0-14) (P < 0.001) and 14 (IQR 10-17) to 6 (IQR 3-12) (P < 0.001) with IC and PCE, respectively. The repeated measurement correlation between PCE and IC was very strong (r = 0.77, P < 0.001), strong compared to faecal calprotectin (r = 0.42, P = 0.003) and moderate compared to C-reactive protein (r = 0.36, P = 0.005). The mean score for ulcer size, ulcerated surface and affected surface was equal to that of IC before and after treatment. PCE had a sensitivity and specificity of 80.6% (CI 62.5-92.5) and 93.8% (CI 79.2-99.2) for ulcer healing compared to IC. CONCLUSION: PCE is responsive in patients treated for CD and may serve as a minimally invasive alternative to IC in selected patients.

Bowel movement alterations predict the severity of diverticular disease and the risk of acute diverticulitis: a prospective, international st.

Background/Aims: Patients with diverticular disease (DD) frequently have abnormal bowel movements. However, it is unknown whether the entity of these alterations is associated with the severity of DD. We aimed to assess bowel habits and their relationship with the severity of DD according to Diverticular Inflammation and Complication Assessment (DICA) classification, Combined Overview on Diverticular Assessment (CODA) score, and fecal calprotectin (FC). Methods: An international, multicenter, prospective cohort study was conducted in 43 centers. A 10-point visual analog scale (VAS) was used to assess the severity of constipation and diarrhea. The association of constipation and diarrhea with DICA classification, CODA score, and basal FC was tested using non-parametric tests. Survival methods for censored observations were applied to test the association of constipation and diarrhea with the incidence of acute diverticulitis over a 3-year follow-up. Results: Of 871 patients with DD were included in the study. Of these, 208 (23.9%) and 199 (22.9%) reported a VAS score for constipation and diarrhea at least 3 at baseline, respectively. Higher constipation and diarrhea scores were associated with increasing DICA classification, CODA score and basal FC (P< 0.001). Constipation and diarrhea scores were independently associated with an increased hazard of developing acute diverticulitis (hazard ratio [HR]constipation = 1.15 per 1-VAS point increase, 95% confidence interval [CI], 1.04-1.27; P=0.004; and HRdiarrhea =1.14; 95% CI, 1.03-1.26; P=0.014, respectively). Conclusions: In newly diagnosed patients with DD, higher endoscopic and combined scores of DD severity were associated with higher scores of constipation and diarrhea at baseline. Both constipation and diarrhea were independent prognostic factors of acute diverticulitis.

Markers of Intestinal Permeability and Inflammation in Enterally Fed Children with Cerebral Palsy.

Cerebral palsy (CP) results in non-progressive damage to the central nervous system, leading to functional disorders of the gastrointestinal tract and requiring enteral nutrition via gastrostomy in some patients. The aim of the study was to assess the impact of enteral nutrition on intestinal inflammation expressed by stool calprotectin and intestinal permeability determined by fecal zonulin and IFABP, and to determine whether CP affects these parameters. The study group consisted of 30 children with CP, fed enterally (Cerebral Palsy Enteral Nutrition-CPEN), and two reference groups: 24 children with CP, fed orally with a standard diet (CPC-Cerebral Palsy Controls) and 24 healthy children (HC-healthy controls). The differences between these groups and between the combined CP groups (CPG and CPEN + CPC) and HC were analyzed. Fecal zonulin, calprotectin, and intestinal fatty acid-binding protein 2 (IFABP2) levels were determined by ELISA. The concentrations of fecal calprotectin and zonulin were significantly higher in the CPEN group than in the CPC group (p = 0.012, p = 0.025). When comparing the CPG (n = 53) with the HC group (n = 24), statistically significant differences were observed for calprotectin (p = 0.000018, higher in the CPG) and IFABP (p = 0.021, higher in HC). Enteral nutrition was associated in our cohort with increased fecal calprotectin and zonulin. Children with cerebral palsy presented with increased fecal calprotectin but not increased intestinal permeability expressed by stool zonulin.

Fecal calprotectin in pediatric gastrointestinal diseases: Pros and cons.

BACKGROUND: Fecal calprotectin is a valuable biomarker for assessing intestinal inflammation in pediatric gastrointestinal diseases. However, its role, pros, and cons in various conditions must be comprehensively elucidated. AIM: To explore the role of fecal calprotectin in pediatric gastrointestinal diseases, including its advantages and limitations. METHODS: A comprehensive search was conducted on PubMed, PubMed Central, Google Scholar, and other scientific research engines until February 24, 2024. The review included 88 research articles, 56 review articles, six meta-analyses, two systematic reviews, two consensus papers, and two letters to the editors. RESULTS: Fecal calprotectin is a non-invasive marker for detecting intestinal inflammation and monitoring disease activity in pediatric conditions such as functional gastrointestinal disorders, inflammatory bowel disease, coeliac disease, coronavirus disease 2019-induced gastrointestinal disorders, gastroenteritis, and cystic fibrosis-associated intestinal pathology. However, its lack of specificity and susceptibility to various confounding factors pose challenges in interpretation. Despite these limitations, fecal calprotectin offers significant advantages in diagnosing, monitoring, and managing pediatric gastrointestinal diseases. CONCLUSION: Fecal calprotectin holds promise as a valuable tool in pediatric gastroenterology, offering insights into disease activity, treatment response, and prognosis. Standardized protocols and guidelines are needed to optimize its clinical utility and mitigate interpretation challenges. Further research is warranted to address the identified limitations and enhance our understanding of fecal calprotectin in pediatric gastrointestinal diseases.

Assessing the correlation between fecal calprotectin, blood markers and disease activity in pediatric inflammatory bowel disease.

Background: Crohn's disease (CD) and ulcerative colitis (UC) are the 2 main types of inflammatory bowel disease (IBD), a chronic inflammatory condition of the gastrointestinal tract. Management of IBD necessitates frequent clinical monitoring, including blood tests and occasionally endoscopy. Fecal calprotectin (FC) is a non-invasive measurement of luminal inflammatory activity, and can therefore be used as a useful monitoring tool. This study aimed to assess the relationship between FC, IBD activity indices and the commonly used blood markers in pediatric IBD. Methods: Electronic patient records were accessed to retrospectively collect patient data from a tertiary pediatric hospital from 2015-2021. CD and UC disease activity was quantified using the Pediatric CD Activity Index (PCDAI) and Pediatric UC Activity Index (PUCAI), respectively. The Paris classification was used for phenotype identification. Results: A total of 208 patients were included in the study, 115 with CD (18% <10 years and 82% 10-17 years) and 93 with UC (32% <10 years and 68% 10-17 years). There was a positive correlation between FC and PCDAI (rs=0.546, P<0.001) and between FC and PUCAI (rs=0.485, P<0.001). FC and activity indices were correlated positively with inflammatory markers/platelets and negatively with albumin and hemoglobin. FC correlated positively with PCDAI in all CD phenotypes, including isolated ileal disease. Conclusion: In pediatric IBD, FC shows a positive correlation with the clinical picture and blood markers in all disease phenotypes, and can provide an accurate non-invasive measure of disease activity.

Circulating Levels of Calprotectin as a Biomarker in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Calprotectin, also known as MRP8/14, is generated by immune cells and is altered in several inflammatory diseases. Studies have assessed their levels in patients with coronary artery disease (CAD) and its subtypes (stable CAD and acute coronary syndrome [ACS]). Herein, we aimed to systematically investigate these associations through a systematic review and meta-analysis. METHODS: A systematic search was conducted in four online databases, including PubMed, Scopus, Embase, and the Web of Science. Relevant studies were retrieved, screened, and extracted. Random-effect meta-analysis was performed for the calculation of standardized mean difference (SMD) and 95% confidence interval (CI). Blood calprotectin levels were compared between CAD patients and controls, as well as CAD subtypes. RESULTS: A total of 20 studies were included in the systematic review and meta-analysis, comprising 3300 CAD patients and 1230 controls. Patients with CAD had significantly higher calprotectin levels (SMD 0.81, 95% CI 0.32-1.30, p < 0.01). Similarly, patients with ACS were reported to have higher levels compared to those with stable CAD. However, there was no significant difference in terms of blood calprotectin levels between stable CAD cases and healthy controls. Finally, studies have shown that calprotectin could be used as a diagnostic biomarker of CAD while also predicting major adverse events and mortality in these patients. CONCLUSION: Based on our findings, calprotectin, as an inflammatory marker, could be used as a possible biomarker for patients with CAD and ACS. These suggest the possibility of pathophysiological pathways for this involvement and warrant further research on these associations as well as their clinical utility.

Synovial calprotectin in prosthetic joint infection. A systematic review and meta-analysis of the literature.

INTRODUCTION: Calprotectin is a protein endowed with antimicrobial properties, rendering it a distinctive marker for infection. Two methods are currently available for the assay of calprotectin: the enzyme-linked immunosorbent assay (ELISA) and the lateral flow test (LFT). We aimed to assess the diagnostic accuracy of synovial fluid calprotectin and to compare the accuracy of the laboratory-based test and the qualitative assessment for the diagnosis of hip and knee prosthetic infection. MATERIALS AND METHODS: We searched (from inception to November 2023) MEDLINE, Scopus, EMBASE, Web of Science, and Cochrane for studies on calprotectin in the diagnosis of periprosthetic joint infection (PJI). Sensitivity, specificity, positive and negative likelihood ratio (LR), and diagnostic odds ratio were analyzed. The receiver-operating curve for each method was calculated. RESULTS: We included 14 articles in our meta-analysis, including 902 patients who underwent total hip and knee arthroplasties revision; 331 (37%) had a joint infection according to MSIS, MSIS-modified criteria, ICM 2018 and EBJIS 2021. Considering the false-positive result rate of 6% and false-negative result rate of 7%, pooled sensitivity and specificity were 0.92 (95% CI 0.89-0.94) and 0.93 (0.91-0.95), respectively. The area under the curve (AUC) was 0.93 (95% CI 0.91-0.94). No statistical differences in terms of sensitivity and specificity were found between ELISA and LFT. The pooled sensitivity and specificity of the two calprotectin assessment methods were: LFT 0.90 (95% CI 0.869-0.935) and 0.92 (95% CI 0.894-0.941), respectively; ELISA 0.96 (95% CI 0.914-0.986) and 0.97 (95% CI 0.934-0.988), respectively. The diagnostic odds ratio of the ELISA was superior to that of the LFT (906.6667, 95% CI 271.2686-3030.3712 versus 113.8886, 95% CI 70.4001-184.2414; p < 0.001). The AUC for ELISA and LFT was 0.968 (95% CI 0.944-0.984) and 0.915 (95% CI 0.895-0.933), respectively. CONCLUSIONS: Detection of synovial calprotectin is an accurate test for diagnosis of hip and knee prosthetic infections. The diagnostic accuracy of the two calprotectin assessment methods is almost comparable. The LFT is a valid, rapid, and more available diagnostic tool, particularly to rule out PJI.

Diagnostic accuracy of serum calprotectin measured by CLIA and EIA in juvenile idiopathic arthritis: a proof-of-concept study.

Objective: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are used to assess disease activity in juvenile idiopathic arthritis (JIA). However, because these biomarkers do not always differentiate between active and inactive disease, there is a need for alternative markers such as serum calprotectin (sCal). The main aim of this proof-of-concept study was to assess the diagnostic accuracy of sCal in patients with JIA. Secondary aims were to identify the optimal sCal cut-off levels to define active disease and evaluate the association between these biomarkers and disease activity status. Methods: Serum samples were obtained from 25 pediatric patients with JIA. Serum calprotectin levels were determined by two different assays, the QUANTA FLASH chemiluminescence immunoassay (CLIA) from Inova Diagnostics and the solid-phase enzyme immunoassay (EIA) from Bühlmann Laboratories. Diagnostic accuracy was assessed for sCal CLIA, sCal EIA, CRP, and ESR. The results obtained by the CLIA and EIA methodologies were compared. We also evaluated the association between the individual each biomarkers (sCal CLIA, sCal EIA, CRP, and ESR) and disease activity (according to JADAS-27 criteria and the ACR criteria modified by Anink and colleagues). Results: For both sCal assays (CLIA and EIA), the optimal cut-off level (ROC analysis) was the same (2.3 µg/ml). Serum calprotectin levels measured by CLIA and EIA were strongly correlated with each other (Kendall's tau-b, 0.71; p < 0.001). Compared to ESR and CRP, sCal CLIA and EIA were both more accurate (i.e., greater sensitivity) in identifying patients with active disease. By contrast, ESR and CRP were more effective in identifying patients in remission (i.e., better specificity). Conclusion: This proof-of-concept study shows that determination of serum calprotectin levels with CLIA or EIA can accurately identify the presence of active disease in patients with JIA.

Fecal calprotectin and endoscopic scores: The cornerstones in clinical practice for evaluating mucosal healing in inflammatory bowel disease.

Managing inflammatory bowel disease (IBD) is becoming increasingly complex and personalized, considering the advent of new advanced therapies with distinct mechanisms of action. Achieving mucosal healing (MH) is a pivotal therapeutic goal in IBD management and can prevent IBD progression and reduce flares, hospitalization, surgery, intestinal damage, and colorectal cancer. Employing proactive disease and therapy assessment is essential to achieve better control of intestinal inflammation, even if subclinical, to alter the natural course of IBD. Periodic monitoring of fecal calprotectin (FC) levels and interval endoscopic evaluations are cornerstones for evaluating response/remission to advanced therapies targeting IBD, assessing MH, and detecting subclinical recurrence. Here, we comment on the article by Ishida et al Moreover, this editorial aimed to review the role of FC and endoscopic scores in predicting MH in patients with IBD. Furthermore, we intend to present some evidence on the role of these markers in future targets, such as histological and transmural healing. Additional prospective multicenter studies with a stricter MH criterion, standardized endoscopic and histopathological analyses, and virtual chromoscopy, potentially including artificial intelligence and other biomarkers, are desired.

Performance evaluation of a smartphone-based home test for fecal calprotection.

OBJECTIVES: Fecal calprotectin (FC) serves as a non-invasive marker for the assessment of gut inflammation in patients with inflammatory bowel disease (IBD). Laboratory measurements are usually performed with immunologic methods like enzyme-linked immunosorbent assay. Recently, quantitative home tests based on the lateral flow technology with smartphones as read-out devices have been developed. We compared the quantitative and qualitative performance of the quantitative lateral flow home test Preventis SmarTest® Calprotectin Home and the immunological test used in our laboratory (Eurospital Calprest® Turbo). METHODS: Fourty-five routine samples were analyzed in parallel with both tests according to the manufacturer's instructions. The read-out of the home test was performed with two smartphones (Apple iPhone 14 Pro and Samsung Galaxy XCover 5). The qualitative interpretation (positive, negative, borderline) was conducted using the cut-offs provided by the manufacturers. RESULTS: Statistically significant correlations with the laboratory standard method were observed for both smartphones (Spearman's rho 0.703 and 0.715, all p<0.005). The home test showed systematically higher concentrations compared to the routine assay. We found minimal qualitative agreement between the two tests (Cohen's kappas (κ)=0.323 and 0.300; p=0.003 and 0.005) showing a lower rate of positives with the home test. Both used smartphones showed good quantitative and qualitative agreement. CONCLUSIONS: The tests are quantitatively not interchangeable. However, the home test may be applicable for the serial follow-up management of patients with IBD. The higher rate of samples classified as negative with the home test may lead to an underestimation of affected patients.

Increasing plasma calprotectin (S100A8/A9) is associated with 12-month mortality and unfavourable functional outcome in critically ill COVID-19 patients.

BACKGROUND: Calprotectin (S100A8/A9) is a pro-inflammatory mediator primarily released from neutrophils. Previous studies have revealed associations between plasma calprotectin, disease severity and in-hospital mortality in unselected COVID-19 patients. OBJECTIVE: We aimed to assess whether plasma calprotectin dynamics during the first week of intensive care are associated with mortality and functional outcome in critically ill COVID-19 patients. METHODS: This prospective study included 498 COVID-19 patients admitted to six intensive care units (ICUs) in Sweden between May 2020 and May 2021. Blood samples were collected on ICU admission and on day 7. The primary outcome was 12-month mortality. Secondary outcomes were functional outcome of survivors at 3 and 12 months, and the need for invasive mechanical ventilation (IMV) or continuous renal replacement therapy (CRRT) during the ICU stay. Functional outcome was assessed by the Glasgow Outcome Scale Extended (GOSE, range 1-8, with < 5 representing an unfavourable outcome). Associations between plasma calprotectin and outcomes were examined in binary logistic regression analyses adjusted for age, sex, BMI, hypertension, smoking, and creatinine. RESULTS: High plasma calprotectin on admission and day 7 was independently associated with increased 12-month mortality. Increasing calprotectin from admission to day 7 was independently associated with higher mortality at 12 months [OR 2.10 (95% CI 1.18-3.74), p = 0.012], unfavourable functional outcome at 3 months [OR 2.53 (95% CI 1.07-6.10), p = 0.036], and the use of IMV [OR 2.23 (95% CI 1.10-4.53), p = 0.027)] and CRRT [OR 2.07 (95% CI 1.07-4.00), p = 0.031)]. A receiver operator characteristic (ROC) model including day 7 calprotectin and age was a good predictor of 12-month mortality [AUC 0.79 (95% CI 0.74-0.84), p < 0.001]. Day 7 calprotectin alone predicted an unfavourable functional outcome at 3 months [AUC 0.67 (95% CI 0.58-0.76), p < 0.001]. CONCLUSION: In critically ill COVID-19 patients, increasing calprotectin levels after admission to the ICU are associated with 12-month mortality and unfavourable functional outcome in survivors. Monitoring plasma calprotectin dynamics in the ICU may be considered to evaluate prognosis in critical COVID-19. STUDY REGISTRATION: ClinicalTrials.gov Identifier: NCT04974775, registered April 28, 2020.

Intestinal Ultrasonography as an Alternative to Fecal Calprotectin to Monitor Patients with Crohn's Disease: Experience from a Novice Sonographer.

BACKGROUND: While fecal calprotectin (Fcal) is now recommended, the positioning of intestinal ultrasonography (IUS) is still unknown to monitor patients with CD. AIMS: To assess the agreement between IUS performed by a novice sonographer and Fcal to detect active CD and to compare these two monitoring tools to determine the need for therapeutic escalation. METHODS: In this cross-sectional prospective study, we consecutively included CD patients ≥ 18 years-old with concomitant IUS and Fcal testing within 7 days. IUS was performed by a novice sonographer. The endpoints were the agreement between IUS and Fcal (> 150 µg/g) to detect active CD and the need for therapeutic escalation. RESULTS: Among 66 patients undergoing IUS, 56 patients had also Fcal testing. The agreement between IUS and Fcal to detect an active CD was 80.4% (κ-coefficient = 0.536 ± 0.127). Fcal, IUS or both had respectively the following positive (76.9%[54.0-99.8], 70.0%[49.9-90.1], and 81.8%[59.0-100.0]) and negative (81.4%[69.8-93.0], 88.9%[78.6-99.2], and 80.0%[68.3-91.7]) predictive values to detect active CD requiring therapeutic escalation. Using a 10 points-acceptability numerical scale, IUS presented with a better acceptability than Fcal (9.5 ± 1.2 vs 8.0 ± 2.3, p < 0.0001). Contrary to the agreement with Fcal and the performances of IUS to identify the need for therapeutic escalation, the duration of IUS procedure decreased over time (correlation coefficient = - 0.54, p = 0.001) and plateaued between 15 and 20 min-long from the 24th procedure. CONCLUSION: IUS and fecal calprotectin do not give the same information and could be complementary to monitor patients with CD.

Releasing Dynamic of Serum ST2 and Calprotectin in Patients with Acute Ischemic Stroke.

This study investigated the releasing dynamics of serum ST2 and calprotectin in patients with acute IS. The study included acute IS patients (N = 20) with an NIH Stroke Scale score ≥8. Sampling was performed at seven time points: after admission (T0) and at the following 24 h consecutive intervals (T1-T6). Primary outcome at 90 days was evaluated using the modified Rankin scale: 0-2 for good and 3-6 for poor functional outcome. The secondary outcome was all-cause mortality after 90 days. Fifteen patients had a poor outcome, and eight died. Results showed a statistically significant difference in ST2 concentrations between good and poor outcomes at T0 (p = 0.04), T1 (p = 0.006), T2 (p = 0.01), T3 (p = 0.021), T4 (p = 0.007), T5 (p = 0.032), and for calprotectin T6 (p = 0.034). Prognostic accuracy was highest for ST2 at T1 for a cut-off > 18.9 µg/L (sensitivity 80% and specificity 100.0%) and for calprotectin at T5 for a cut-off > 4.5 mg/L (sensitivity 64.3% and specificity 100.0%). Serum ST2 and calprotectin-releasing dynamics showed a valuable prognostic accuracy for IS outcomes.

Assessment of intestinal inflammation via fecal calprotectin for early prediction of adverse outcomes in advanced chronic liver disease.

BACKGROUND AND AIMS: Intestinal inflammation assessed by fecal calprotectin (F-CAL) in advanced chronic liver disease (ACLD) may represent an early sign of intestinal barrier dysfunction. We aimed to explore the usefulness of F-CAL testing in ACLD in the prediction of adverse outcomes (AO, death, or LT) and refinement of prognostic stratification. PATIENTS AND METHODS: We explored the RH7 cirrhosis registry comprising consecutive hospitalized patients and a control group with data on disease phenotype, demographics, anthropometrics, prognostic indices, and medication. The F-CAL was evaluated on admission and reported in multiples of the upper limit of normal or terciles. Predictive power was tested in the Cox model for AO over 180 days. Additional risk refinement by F-CAL was tested for both groups. RESULTS: We enrolled 263 cases in the study group with a median age of 57.2 years, M/F ratio 167/96, with alcohol, metabolic dysfunction-associated steatotic liver disease, MetALD, and viral etiologies in 72.2%, 9.1, 8.0, 3.4%. The median F-CAL was 3.92 × ULN. The control group comprised 108 cases. The adjusted Cox model confirmed F-CAL (hazard ratio [HR] = 1.05, p < 0.001) and F-CAL terciles (HR = 1.413, p = 0.009) as independent predictors of AO. F-CAL terciles had higher predictive accuracy in CLIF-C-AD<50 (HR = 2.49, p = 0.013) and Child stages A and B (HR = 1.706, p = 0.025), in whom high F-CAL (cut-off >11 × ULN) could identify patients having 2-3 times higher risk of AO. This approach has been validated in the control group. CONCLUSION: Among hospitalized patients with ACLD, F-CAL values were independently proportional to the risk of AO, particularly in early disease stages when high F-CAL values could refine prognostic stratification.

What Happens to Patients with Inflammatory Bowel Disease Who Are Intolerant to Thiopurines?

Introduction: The clinical consequences for patients with inflammatory bowel disease (IBD) who stop treatment owing to side effects have not been fully investigated. Methods: This retrospective observational study aimed to compare patients who discontinued thiopurine treatment due to side effects with those who tolerated thiopurine treatment in the use of other IBD drugs, surgery, and fecal calprotectin values in the first 5 years after the start of thiopurine treatment. Results: The proportion of patients with IBD who initiated thiopurine treatment at our clinic was 44% (32% ulcerative colitis and 64% Crohn's disease) and 31% (n = 94) of those patients had to stop thiopurine treatment within 5 years due to side effects. Patients who discontinued thiopurine treatment due to intolerance were significantly older (median age 33 vs. 27 years, p = 0.003), significantly more often used prednisolone (89 vs. 76%, p = 0.009), and used to a lesser extent TNF inhibitors at the start of thiopurine treatment (3% vs. 9%, p = 0.062). Budesonide treatment and non-TNF inhibitor second-line therapy were significantly more commonly used in patients who discontinued thiopurine treatment owing to side effects, but there were no statistically significant differences in the use of other treatments. The proportion of patients with a median FC >200 µg/g was significantly higher during follow-up in patients with UC who discontinued thiopurine treatment owing to side effects. Conclusions: Patients who discontinued thiopurines owing to side effects were prescribed more budesonide and non-TNF inhibitor second-line therapy, but there were no differences in the use of TNF inhibitors, prednisolone, or surgery.

Quantum Medicine and Irritable Bowel Syndrome-Associated Chronic Low-Back Pain: A Pilot Observational Study on the Clinical and Bio-Psycho-Social Effects of Bioresonance Therapy.

Background and Objectives: Irritable bowel syndrome (IBS) is an invasive and potentially disabling syndrome characterized by a multitude of symptoms capable of reducing the quality of life of patients. Among the most disabling symptoms of IBS is certainly physical pain, which manifests itself mainly at the abdominal level but can also appear in other areas of the body, particularly in the form of chronic low-back pain (CLBP). Among the non-invasive methods of treating organ-specific pathologies and organ-related musculoskeletal problems, the use of Bioresonance Therapy (BT)-based on the administration of self-modulating Extremely Low-Frequency Electromagnetic Fields, capable of determining a rebalance of bio-electrical and metabolic activity in the presence of various functional alterations-is currently gaining acceptance. Therefore, we decided to monitor results obtained from patients suffering from IBS and CLBP subjected to a cycle of treatments with BT. Materials and Methods: We monitored 20 patients (12 women and 8 men, average age of 51 years) suffering from CLBP and other visceral symptoms related to IBS. Patients were monitored through the use of the Bristol Stool Form Scale (BSFS), the Fecal Calprotectin test and the Short-Form Health Survey 36 (SF-36), collected before (T0) and after (T1) the execution of the cycle of treatments. They undertook a treatment protocol consisting of eight sessions of BT carried out over about a month. Results: At the end of the treatments with BT, it was possible to observe a general and significant improvement in all the parameters observed, as well as a close inversely proportional correlation between the Calprotectin values detected and the quality of life experienced by the patients in relation to their perceived IBS symptoms. Conclusions: Overall, our pilot study would seem to suggest a potential beneficial effect of BT in modulating organic and musculoskeletal symptoms derived from IBS.

Saffron as a Promising Therapy for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory illness of the gastrointestinal tract (GI), characterized by recurrent episodes of inflammation and tissue destruction. It affects an increasing number of individuals worldwide who suffer from Crohn's disease (CD) or ulcerative colitis (UC). Despite substantial advances in understanding the underlying causes of IBD, the available treatments remain restricted and are sometimes accompanied by severe consequences. Consequently, there is an urgent need to study alternate therapeutic options. This review assesses the present drugs, identifies their limitations, and proposes the use of saffron, a natural plant with great therapeutic potential based on preclinical and clinical investigations. Saffron has gained attention for its potential therapeutic benefits in treating various ailments due to its established bioactive compounds possessing antioxidant and anti-inflammatory properties. This review covers how saffron impacts the levels of calprotectin, an inflammatory marker, for various inflammatory responses in multiple diseases including IBD. Data from clinical trials were assessed to determine the efficacy and safety of using saffron to counter inflammation in multiple diseases. Studies have shown that saffron may protect against inflammatory bowel disease (IBD) through several mechanisms by inhibiting pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6), reducing oxidative stress through antioxidant effects, enhancing mucosal barrier function by upregulating tight junction proteins, and modulating the gut microbiota composition to promote beneficial bacteria while suppressing pathogenic ones; these combined actions contribute to its therapeutic potential in managing and alleviating the symptoms of IBD. This will enable future research endeavors and expedite the translation of saffron-based interventions into clinical practice as a valuable adjunctive therapy or a potential alternative to conventional treatments, thereby enhancing the quality of life for individuals suffering from inflammatory diseases including IBD.

The utility of capsule endoscopy in the phenotype of Crohn's disease. Data from England 2016-2021.

BACKGROUND AND STUDY AIMS: Isolated small bowel Crohn's disease (SBCD) is reported to have a worse prognosis compared to other CD phenotypes. The aim of this study was to understand the correlation between Isolated SBCD and ileocolonic disease with blood and faecal biomarkers and also to identify differences in outcome and management between the two phenotypes. PATIENTS AND METHODS: Patients with ileocolonic or isolated small bowel Crohn's Disease (SBCD) were identified from an existing capsule endoscopy (CE) database. Harvey Bradshaw Index (HBI), biomarkers: c-reactive protein (CRP) and faecal calprotectin (FC), Lewis score and findings on CE and subsequent follow up data were collected. SPSS was used to analyse the data. RESULTS: In total 248 patients were included in the study. Patients were split into two groups- Isolated SBCD with 178 patient (median age 44 years (IQR 31-56); 41.5 % male) and Ileocolonic Crohn's with 70 patients (median age 31 years (IQR 22.7-49); 31.5 % male). A new diagnosis of SBCD was made in 38.7 % (n = 96), whilst 60.0 % (n = 144) had established CD. Patients with ileocolonic disease had a higher HBI in comparison to isolated SBCD [HBI = 7 (IQR 5-10) vs HBI = 6(IQR 4-9); P = 0.04 ]. There was no significant difference in the FC levels between isolated SBCD and ileocolonic disease [136ug/g (IQR 53.8-363.3) vs 171ug/g (IQR 68.5-485.5); p = 0.98]. In isolated SBCD group, 30.3 % (n = 54) CE showed proximal disease, 96 % (n = 171) showed distal disease and 26.4 % (n = 47) showed extensive disease. SBCE was superior to MRI at diagnosing proximal SBCD (P < 0.01). On multivariate logistic regression, we did not identify any predictors of disease severity defined as Lewis score > 790. Following SBCE, 68.5 % (n = 170) of the total patients had a management change. This included commencement or dose escalation of corticosteroids in 123 (49.5 %) patients, azathioprine in 80 (33.3 %) patients, methotrexate in 22 (9.1 %) patients and biological therapy in 110 (44.3 %) patients. HBI predicted a change in management (p < 0.01). CONCLUSION: CE is an important modality for the diagnosis of active SBCD. It also helps guide treatment in patients identified with active disease.