Mesalazine dose modification based on faecal calprotectin levels in patients with ulcerative colitis in clinical remission. / Modificación de la dosis de mesalazina en función de los niveles de calprotectina fecal en pacientes con colitis ulcerosa en remisión clínica.

BACKGROUND: Faecal calprotectin (FC) shows an excellent correlation with endoscopic and histological activity of ulcerative colitis (UC) and it is the best predictor of clinical relapse. Our aim was to evaluate the usefulness of modifying the dose of mesalazine based on FC levels, in clinical practice. METHODS: Retrospective, single-centre study in UC patients in clinical remission while treated with mesalazine which dosage was decreased (DOWN) or increased (UP) according to FC levels. The main endpoint was the long-term maintenance of clinical remission. RESULTS: A total of 56 patients were included (39 DOWN, 17 UP). In the DOWN group, the median baseline dose of mesalazine was 3.6g/day and the median baseline FC was 36µg/g. After a median follow-up of 22 months, 28% required rescue therapy. The cumulative relapse-free survival after tapering was 91% and 82% at 12 and 24 months, respectively. In the UP group, the median baseline dose of mesalazine was 2.4g/day, with a median baseline FC of 524µg/g. After a median follow-up of 12 months, 29% required rescue therapy. The cumulative relapse-free survival after dose increase was 86% and 72% at 12 and 24 months, respectively. CONCLUSIONS: Mesalazine dose modification based on FC monitoring seems to be a safe strategy in patients with UC in clinical remission, with a probability of clinical relapse around 20% at two years.

Combined evaluation of fecal calprotectin and C-reactive protein as a therapeutic target in the management of patients with Crohn's disease.

OBJECTIVES: Proper management of the inflammatory process in Crohn's disease (CD) results in lower rates of complications. The objective of this study was to investigate the performance of isolated and combined use of fecal calprotectin (FC) and serum levels of C-reactive protein (CRP) as markers of inflammatory activity in CD and the possibility of their use as a therapeutic target. PATIENTS AND METHODS: Patients with CD and indication for colonoscopy were prospectively enrolled in the study and allocated according to the presence or absence of endoscopic inflammatory activity. The correlation between FC and CRP levels and the Simplified Endoscopic Score of Crohn's Disease (SES-CD) was performed, and the accuracy of these markers was evaluated for the diagnosis of inflammatory activity, when used alone or in series. RESULTS: Eighty colonoscopies were performed in patients with CD. The FC cut-off value of 155µg/g showed high sensitivity (96%) and accuracy (78%) for the diagnosis of endoscopic activity. For CRP, the value of 6.7mg/L demonstrated sensitivity of 75% and specificity of 67%. The sequential usage of these markers (FC+CRP) showed greater specificity (82%) when compared to the use of these markers alone. Depending on the probability of inflammatory activity, different scenarios were used to evaluate the performance of these markers and an algorithm is proposed. DISCUSSION: Combined analysis of FC and CRP, when performed consecutively, allows decisions to be made with a high degree of certainty and even eliminates the need for colonoscopy in many situations.

Limitations of the determination of faecal calprotectin in patients with ulcerative colitis and inflammatory polyps. / Limitaciones de la determinación de calprotectina fecal en pacientes con colitis ulcerosa y pólipos inflamatorios.

INTRODUCTION: Faecal calprotectin is a useful technique for detecting activity in patients with ulcerative colitis. However, there may be high levels due to factors other than the activity of ulcerative colitis. Our aim was to analyse possible false positive results of calprotectin for the activity of ulcerative colitis owing to the presence of inflammatory polyps. PATIENTS AND METHODS: Retrospective, observational, descriptive study. Data was collected from patients monitored for 2 years in whom a colonoscopy had been requested within 3 months after detecting high calprotectin values (>150µg/g) and before modifying the treatment. RESULTS: We reviewed 39 patients and in 5 of them, with previous diagnosis of extensive ulcerative colitis, inflammatory polyps were detected. Three patients were on treatment with mesalazine, one with azathioprine and other with infliximab. All of them were asymptomatic and the endoscopy did not show macroscopic activity (endoscopic Mayo score=0) or histological activity. The median values of calprotectin were 422µg/g (IQR: 298-2,408) and they remained elevated in a second measurement. In 4 of the patients the inflammatory polyps were multiple and small in size. The other patient had a polyp measuring 4cm. DISCUSSION: In clinical practice we can find high faecal calprotectin levels not due to the presence of ulcerative colitis activity, but due to other lesions such as inflammatory polyps. This fact must be taken into account before carrying out relevant changes such as step-up therapy to immunosuppressive drugs or biological drugs in patients with confirmed high calprotectin levels.

Role of faecal calprotectin as a predictor of endoscopic activity in paediatric patients with ulcerative colitis.

INTRODUCTION: Colonoscopy is currently considered to be the gold standard for evaluation of colonic mucosa inflammation in patients with ulcerative colitis (UC), but the procedure is invasive and cannot be repeated frequently, especially in the paediatric population. The aim of this study was to assess the role of faecal calprotectin (FC) as a predictor of endoscopic disease activity in paediatric patients with UC in clinical remission. MATERIAL AND METHODS: Single-centre prospective study. Clinical remission was defined as Paediatric Ulcerative Colitis Activity Index <10. Endoscopic findings were assessed according to the Mayo Endoscopic Subscore (MES). MES≤1 was defined as endoscopic remission. All participants provided fresh faecal samples for measurement of FC. RESULTS: A total of 34 visits of 24 children with UC were included in the study. There was a strong positive correlation between FC levels and endoscopic disease activity (n=34, r=0.83, p<0.001). The median FC levels in the subgroup with endoscopic activity (MES 2-3) were significantly higher than the median FC levels in the subgroup without endoscopic activity (MES≤1) (1000µg/g, IQR 575-1800µg/g vs. 100µg/g, IQR 80-223µg/g, p<0.001). At a cut-off of 298.5µg/g, FC had 92.3% sensitivity, 95.2% specificity and an AUROC 0.974 (SE 0.023, 95% CI 0.93-1, p<0.001) to predict endoscopic activity. DISCUSSION: FC is an accurate surrogate marker of endoscopic activity in children with clinically quiescent UC.

Relevance of dynamic studies with magnetic resonance enterography in Crohn's disease.

INTRODUCTION: A proper quantification of the inflammatory activity in Crohn's disease (CD) lesions is needed to establish the appropriate management for each patient. The aim of this study is to evaluate the inflammatory activity of affected segments in small bowel lesions using dynamic studies of magnetic resonance enterography (MRE) in patients undergoing surgery, and their correlation with the level of inflammation and histological fibrosis of the surgical piece. METHODS: A prospective, consecutive, observational, clinical study was conducted that included all the patients with small bowel CD that underwent surgery in this center between March 2011 and September 2013. Diagnosis was established according to Lennard-Jones criteria and the Montreal classification. All the patients underwent MRE within three months before surgery, using a routine protocol involving Liver Acquisition with Volume Acceleration-Extended Volume (LAVA-XV) sequence for the dynamic studies before intravenous administering of gadolinium and 30, 70, 120, and 420s after administering this. The results allowed the designing of graphics with different uptake patterns. The Chiorean classification was used in the histological analysis, as well as a modified version published previously by this study group. RESULTS: A total of 28 patients with 47 lesions were analyzed. There was a significant correlation between both curve patterns, including the modified Chiorean classification (P<0.0001) as well as the level of inflammation (P<0.0001) and fibrosis (P<0.002). Inflammatory patterns of dynamic studies are related to histological findings with 80.9% accuracy (sensitivity=75.7%; specificity=100%). CONCLUSION: There is a high correlation between dynamic enhancement studies and the level of inflammatory activity. MRE is a suitable tool to differentiate between inflammatory and fibrotic lesions, making it useful to decide the appropriate management of each patient.

Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the utility of the determination of faecal calprotectin in inflammatory bowel disease. / Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre la utilidad de la determinación de calprotectina fecal en la enfermedad inflamatoria intestinal.

The management of inflammatory bowel disease (IBD) is currently based on the objective evaluation of intestinal lesions. It would therefore be interesting to have access to simple and non-invasive tools to monitor IBD activity and to identify the presence of lesions. Faecal calprotectin (FC) is the main cytosolic protein of neutrophils, it is resistant to bacterial degradation and it is stable at room temperature for several days, characteristics that make it suitable for use in clinical practice. It can be used to differentiate between inflammatory and functional processes, it correlates with endoscopic activity, it is associated with clinical and endoscopic response to treatment and it has short-term prognostic value. This paper offers an up-to-date perspective on the information that FC can provide clinicians to aid diagnosis, monitoring and management of IBD.

Faecal calprotectin, an useful marker in discriminating between inflammatory bowel disease and functional gastrointestinal disorders. / Calprotectina fecal, marcador eficaz en la diferenciación de enfermedades inflamatorias intestinales y trastornos funcionales gastrointestinales.

INTRODUCTION: Diagnostic discrimination between inflammatory bowel disease (IBD) and functional gastrointestinal disorders is complex, as they cause similar signs and symptoms. Faecal calprotectin (FC) is a useful marker in this context, and can be used to select patients who will most benefit from colonoscopy. The aim of this study was to evaluate the utility of FC in discriminating between organic disease and functional disorders. MATERIAL AND METHODS: The study included 264 patients presenting with gastrointestinal complaints consistent with an organic pathology. FC levels were determined and diagnostic accuracy was assessed using the area under the curve obtained from the final diagnosis. RESULTS: Calprotectin levels in organic bowel disease patients were significantly higher (median 254µg/g; 95% confidence interval [CI], interquartile range 105-588.5) than in functional disease patients (95µg/g; 95% CI, 47.25-243.92) (P<.0001). Similarly, in patients with IBD, the values obtained were higher (270.85µg/g; 95% CI, 96.85-674.00) than in those with irritable bowel syndrome (79.70µg/g; 95% CI, 36.50-117.25) (P<.0001). For a cut-off of 150µg/g, FC had an area under the ROC curve to discriminate between organic and functional disease of 0.718, and 0.872 to discriminate between irritable bowel syndrome and IBD. CONCLUSION: Our study supports the importance of FC as a marker in the evaluation of patients with IBD. The best diagnostic accuracy is obtained at a cut-off value of 150µg/g.

Mortality prediction model from combined serial lactate, procalcitonin and calprotectin levels in critically ill patients with sepsis: A retrospective study according to Sepsis-3 definition.

OBJECTIVE: 1) To evaluate the ability of baseline and on 24 h serum calprotectin, in comparison to canonical biomarkers (lactate and procalcitonin), for prognosis of 28-day mortality in critically ill septic patients; and 2) To develop a predictive model combining the three biomarkers. DESIGN: A single-center, retrospective study. SETTING: Intensive Care Unit of a university hospital. PATIENTS OR PARTICIPANTS: One hundred and seventy three septic pacientes were included. INTERVENTIONS: Measurement of baseline lactate, procalcitonin and calprotectin level and procalcitonin and calprotectin levels on 24 h. MAIN VARIABLES OF INTEREST: Demographics and comorbidities, SOFA score on ICU admission, baseline lactate, procalcitonin and calprotectin on admission and on 24 h and 28-day mortality. RESULTS: 1) On ICU admission, lactate was the only biomarker achieving a significant accuracy (AUC: 0.698); 2) On 24 h, no differences were found on procalcitonin and calprotectin levels. Procalcitonin and calprotectin clearances were significantly lower in non-survivors and both achieved a moderate performance (AUCs: 0.668 and 0.664, respectively); 3) A biomarker based-model achieved a significant accuracy (AUC: 0.766), trending to increase (AUC: 0.829) to SOFA score alone; y 4) Baseline lactate levels and procalcitonin and calprotectin clearance were independent predictors for the outcome. CONCLUSIONS: 1) Baseline and on 24 h calprotectina and procalcitonin levels lacked ability in predicting 28-day mortality; 2) Accuracy of clearance of both biomarkers was moderate; and 3) Combination of SOFA score and the predictive biomarker based-model showed a high prognostic accuracy.

The clinical utility of faecal calprotectin in patients with differentiated and undifferentiated spondyloarthritis: Relevance and clinical implications.

OBJECTIVES: There is cumulative evidence in the literature supporting a potential role of faecal calprotectin (FCP) as a biomarker for gut inflammation in spondyloarthritis (SpA). However its relevance in undifferentiated SpA (USpA) is still uncertain. The aim of the current study is to assess the diagnostic significance of FCP levels in patients with differentiated and undifferentiated SpA. MATERIAL AND METHODS: A total of 52 differentiated SpA, 33 USpA and 50 controls could be included. For all patients, clinical evaluation, routine laboratory investigations, FCP levels, and occult blood in stool were performed. When indicated imaging and/or endoscopies were performed. RESULTS: The differentiated SpA patients were 12 (23.1%) with ankylosing spondylitis, 21 (40.4%) with psoriatic arthritis, 13 (25%) with ulcerative colitis, 5 (9.6%) with Crohn's disease (CD) and one (1.9%) with reactive arthritis. The mean FCP level in 85 patients correlated with CRP and ESR. Within the SpA group ulcerative colitis and Crohn's disease patients had increased FCP levels compared to other SpA subgroups and USpA patients (p<0.001). The mean FCP levelwas significantly higher in the SpA patients compared to USpA and controls (p<0.001). CONCLUSIONS: Elevated FCP levels may identify patients who are most likely to have SpA already in the unclassified phase of the disease. Further studies in different series of patients are needed to evaluate the potential diagnostic and prognostic roles of FCP in both differentiated and undifferentiated phases of the disease.

The Clinical Utility of Faecal Calprotectin in Patients with Differentiated and Undifferentiated Spondyloarthritis: Relevance and Clinical Implications.

OBJECTIVES: There is cumulative evidence in the literature supporting a potential role of faecal calprotectin (FCP) as a biomarker for gut inflammation in spondyloarthritis (SpA). However its relevance in undifferentiated SpA (USpA) is still uncertain. The aim of the current study is to assess the diagnostic significance of FCP levels in patients with differentiated and undifferentiated SpA. MATERIAL AND METHODS: A total of 52 differentiated SpA, 33 USpA and 50 controls could be included. For all patients, clinical evaluation, routine laboratory investigations, FCP levels, and occult blood in stool were performed. When indicated imaging and/or endoscopies were performed. RESULTS: The differentiated SpA patients were 12 (23.1%) with ankylosing spondylitis, 21 (40.4%) with psoriatic arthritis, 13 (25%) with ulcerative colitis, 5 (9.6%) with Crohn's disease (CD) and one (1.9%) with reactive arthritis. The mean FCP level in 85 patients correlated with CRP and ESR. Within the SpA group ulcerative colitis and Crohn's disease patients had increased FCP levels compared to other SpA subgroups and USpA patients (p<0.001). The mean FCP levelwas significantly higher in the SpA patients compared to USpA and controls (p<0.001). CONCLUSIONS: Elevated FCP levels may identify patients who are most likely to have SpA already in the unclassified phase of the disease. Further studies in different series of patients are needed to evaluate the potential diagnostic and prognostic roles of FCP in both differentiated and undifferentiated phases of the disease.

Relationship between fecal calprotectin, anti-Saccharomyces cerevisiae antibodies and other markers of disease activity in patients with spondyloarthritis. / Relación de calprotectina fecal y anti saccharomyces antisacaromices con otros marcadores de actividad en pacientes con espondiloartritis.

OBJECTIVE: To assess the relationship between the increase of fecal calprotectin, anti-Saccharomyces cerevisiae antibodies (ASCA) and disease markers in a group of patients with spondyloarthritis. METHODS: We evaluated patients who were at least 18-years-old and met the Assessment in Spondyloarthritis International Society (ASAS) criteria for spondyloarthritis or the New York modified criteria. We analyzed activity criteria, physical function, analytical criteria (human leukocyte antigen [HLA] B27, fecal calprotectin, presence of ASCA, among others) and demographic data. RESULTS: We included 33 patients. All but one patient had normal ASCA values. We found statistical significance in the correlation of calprotectin with C-reactive protein (CRP) but not with other parameters. We also found a relationship between calprotectin levels and nonsteroidal anti-inflammatory drug (NSAID) intake (P=.001). We found no relationship between CRP levels and NSAID use. After discontinuation of NSAIDs for one month, we found no significant differences in calprotectin levels (P=.9). CONCLUSION: Fecal calprotectin is elevated in patients with spondyloarthritis and correlates positively with CRP. Level of fecal calprotectin is not altered by NSAID use. The amount of ASCA present does not change and does not correlate with any clinical parameters in the study population.

Avaliação da lactoferrina e da calprotectina como marcadores de inflamação intestinal na pancreatite crônica / Evaluating lactoferrin and calprotectin as markers of intestinal inflammation inchronic pancreatitis

ABSTRACT Background: The treatment of chronic pancreatitis does not consistently solve intestinal abnormalities, and despite the implementation of various therapeutic measures, patients often continue to experience persistent diarrhea. Therefore, it is imperative to recognize that diarrhea may stem from factors beyond pancreatic insufficiency, and intestinal inflammation emerges as a potential contributing factor. Objective: The aim of this study was to assess fecal lactoferrin and calprotectin levels as indicators of intestinal inflammation in patients with chronic pancreatitis experiencing persistent diarrhea. Methods: In this study, 23 male patients with chronic pancreatitis primarily attributed to alcohol consumption and presenting with diarrhea (classified as Bristol stool scale type 6 or 7), underwent a comprehensive evaluation of their clinical and nutritional status. Fecal lactoferrin and calprotectin levels were mea­sured utilizing immunoassay techniques. Results: The average age of the participants was 54.8 years, 43.5% had diabetes, and 73.9% were smokers. Despite receiving enzyme replacement therapy and refraining from alcohol for over 4 years, all participants exhibited persistent diarrhea, accompanied by elevated calprotectin and lactoferrin levels indicative of ongoing intestinal inflammation. Conclusion: The findings of this study underscore that intestinal inflammation, as evidenced by elevated fecal biomarkers calprotectin and lactoferrin, may contribute to explaining the persistence of diarrhea in patients with chronic pancreatitis.

RESUMO Contexto: O tratamento da pancreatite crônica não resolve de forma consistente as anomalias intestinais e, apesar da implementação de várias medidas terapêuticas, os pacientes muitas vezes continuam a apresentar diarreia persistente. Portanto, é imperativo reconhecer que a diarreia pode resultar de fatores além da insuficiência pancreática, e a inflamação intestinal surge como um potencial fator contribuinte. Objetivo: O objetivo deste estudo foi avaliar os níveis fecais de lactoferrina e calprotectina como indicadores de inflamação intestinal em pacientes com pancreatite crônica com diarreia persistente. Métodos: Neste estudo, 23 pacientes do sexo masculino com pancreatite crônica atribuída principalmente ao consumo de álcool e apresentando diarreia (classificada na escala de fezes de Bristol tipo 6 ou 7), foram submetidos a uma avaliação abrangente de seu estado clínico e nutricional. Os níveis fecais de lactoferrina e calprotectina foram medidos utilizando técnicas de imunoensaio. Resultados: A idade média dos participantes foi de 54,8 anos, 43,5% tinham diabetes e 73,9% eram fumantes. Apesar de receber terapia de reposição enzimática e abster-se de álcool por mais de 4 anos, todos os participantes apresentaram diarreia persistente, acompanhada por níveis elevados de calprotectina e lactoferrina, indicativos de inflamação intestinal contínua. Conclusão: Os achados deste estudo ressaltam que a inflamação intestinal, evidenciada pelos biomarcadores fecais elevados calprotectina e lactoferrina, pode contribuir para explicar a persistência da diarreia em pacientes com pancreatite crônica.

The importance of calprotectin for differentiating organic inflammatory disease and avoiding unnecessary procedures in paediatrics.

BACKGROUND AND OBJECTIVE: The objective of the study was to determine the ability of faecal calprotectin to differentiate functional and organic intestinal diseases in paediatric patients, and to evaluate the correlation between inflammatory parameters and levels of faecal calprotectin. PATIENTS AND METHODS: This retrospective study involved clinical data from 129 paediatric patients with symptoms of intestinal pathology. Faecal calprotectin was determined by quantitative immunoassay. Patients were classified into three groups: functional (32.8% of patients); organic non-inflammatory bowel disease (IBD, 53.9%); and organic IBD (13.3%). RESULTS: Calprotectin levels were significantly different among the three groups; between patients with IBD and the others, and also between patients with non-organic IBD and functional. Positive associations were found between high levels of calprotectin and higher erythrocyte sedimentation rate (rho=0.497), C-reactive protein (rho=0.460), and platelet count (rho=0.232). Nevertheless, an inverse correlation was found between high levels of calprotectin and transferrin saturation (rho=-0.310), albumin (rho=-0.412), and haemoglobin levels (rho=-0.309). DISCUSSION: Determination of faecal calprotectin is a complementary tool in clinical practice for discriminating between functional and organic IBD, avoiding, according to the levels of calprotectin, unnecessary invasive procedures in paediatric patients.

Fecal calprotectin levels in acute anterior uveitis in patients with spondyloarthritis / Níveis de calprotectina fecal na uveite anterior aguda em pacientes com espondiloartrites

ABSTRACT Purpose: This study measured fecal calprotectin levels in a series of patients with anterior uveitis in order to determine whether anterior uveitis patients with associated spondyloarthritis have higher levels of fecal calprotectin than patients with anterior uveitis of other etiologies. A third group of patients with spondyloarthritis without uveitis was also evaluated to understand the role of acute anterior uveitis in increasing fecal calprotectin. Methods: In this cross-sectional study, 28 patients were divided into three groups: (a) Group 1, spondyloarthritis and uveitis (n=9); (b) Group 2, spondyloarthritis without uveitis (n=10); and (c) Group 3, uveitis without spondyloarthritis (n=9). The levels of fecal calprotectin were determined. Results: Groups 1 and 2 showed higher median fecal calprotectin levels (101.0 and 93.0 µg/g, respectively) compared with Group 3 (9.0 µg/g) (p=0.02). However, no relationship between fecal calprotectin levels and the presence of uveitis with spondyloarthritis could be demonstrated. Conclusion: Patients with spondyloarthritis with or without acute anterior uveitis have significantly elevated levels of fecal calprotectin. This test may be useful for differentiating spondyloarthrit-associated uveitis from uveitis of other etiologies.

RESUMO Objetivo: Este estudo avaliou os níveis de calprotectina fecal em uma série de pacientes com uveíte anterior na tentativa de determinar se pacientes com uveíte associada com espondiloartrites apresentam níveis mais elevados desta proteína do que pacientes com uveíte anterior de outras etiologias. Um terceiro grupo com espondiloartrites sem uveíte também foi incluído na avaliação para entendimento do papel da uveíte anterior no aumento da calprotectina fecal. Métodos: Estudo transversal de 28 pacientes divididos em três grupos: (a) com espondiloartrites e uveíte (n=9); (b) com espondiloartrites sem uveíte (n=10) e (c) com uveíte sem espondiloartrites (n=9). A dosagem de calprotectina fecal foi avaliada. Resultados: Pacientes com uveíte anterior associada a espondiloartrites apresentaram valores medianos maiores de calprotectina fecal (101 µg/g) que os valores dos pacientes com uveíte sem espondiloartrites (9 µg/g), pacientes com espondiloartrites sem uveíte que também demonstraram valores maiores (93.0 µg/g) que os dos pacientes com uveíte sem espondiloartrites (p=0,02). Conclusão: Pacientes com espondiloartrites com e sem uveíte anterior aguda demonstraram níveis significativamente elevados de calprotectina fecal. Este teste pode ser útil na diferenciação entre uveítes associadas com espondiloartrites de uveítes de outras etiologias. Entretanto, não foi possível demonstrar associação entre o aumento dos níveis de calprotectina fecal e a presença da uveíte em espondiloartrites.

Diagnostic Efficacy of Fecal Calprotectin in Inflammatory Bowel Disease: Systematic Literature Review

Introduction: Inflammatory bowel disease is a group of pathologies that include ulcerative colitis and Crohn's disease, which have similar manifestations. Currently, the diagnosis and monitoring of this disease rely mainly on endoscopic studies. Still, this method can hardly be applied to periodic disease monitoring as it is expensive, invasive, and not readily available. Fecal calprotectin is widely known, easy to use, and affordable, and it is currently the best-characterized biomarker for this pathology. Materials and methods: The research design is a systematic diagnostic test validation literature review. A search was conducted in different databases using the QUADAS-2 checklist to evaluate the methodological quality. Results: The initial search yielded 352,843 articles published chiefly in PubMed, followed by Scopus and Science Direct. After multiple filters, 221 papers were selected and wholly reviewed. They were evaluated with inclusion and exclusion criteria, with 18 articles being chosen. Conclusions: Fecal calprotectin is a reliable surrogate marker of endoscopic activity in IBD. However, there is a lack of consensus on delimiting a cut-off point and improving applicability and diagnostic accuracy. Colonoscopy remains the gold standard in all studies.

Introducción: La enfermedad inflamatoria intestinal es un conjunto de patologías entre las que están incluidas la colitis ulcerativa y la enfermedad de Crohn, las cuales tienen presentación similar. En la actualidad, el diagnóstico y seguimiento de dicha enfermedad se basa principalmente en estudios endoscópicos, pero este método difícilmente puede aplicarse a la monitorización periódica de la enfermedad al ser costoso, invasivo y con disponibilidad limitada. La calprotectina fecal cumple con ser ampliamente disponible, fácil de usar y de precio asequible, y actualmente es el biomarcador mejor caracterizado para el uso en esta patología. Metodología: Diseño de investigación tipo revisión sistemática de la literatura de validación de prueba diagnóstica. Se realizó una búsqueda en diferentes bases de datos y para la evaluación de la calidad metodológica se empleó la lista verificación QUADAS-2. Resultados: La búsqueda inicial para la selección de los artículos arrojó un total de 352.843 artículos publicados principalmente en PubMed seguido de Scopus y Science Direct. Después de múltiples filtros se logró elegir 221 artículos, los cuales se llevaron a revisión completa. Se valoraron con criterios de inclusión y exclusión, lo que determinó la elección final de 18 artículos. Conclusiones: La calprotectina fecal es un marcador sustituto fiable de la actividad endoscópica en la EII. Se evidencia la falta de consenso para delimitar un punto de corte y mejorar la aplicabilidad y la precisión diagnóstica. La colonoscopia sigue siendo en todos los estudios el estándar de oro.

Treatment with Quinoline-3-carboxamide does not successfully prevent immune-mediated glomerulonephritis in mice.

INTRODUCTION: Quinoline-3-carboximide compounds, such as paquinimod, which targets the protein S100A9, have demonstrated efficacy in treating autoimmune diseases. S100A9, in association with S100A8, forms the heterodimer S100A8/S100A9, known as calprotectin; that has been shown to be upregulated in numerous inflammatory disorders. We had previously demonstrated protection from glomerular disease in S100A9-deficient mice. The aim of this study was to assess the efficacy of paquinimod in the prevention and treatment of experimental glomerulonephritis. METHODS: Nephrotoxic nephritis (NTN) was induced in C57BL/6 mice according to our standard protocol. Mice were treated with different doses of paquinimod either at disease induction (prevention group) or two days following induction (therapeutic group) and sacrificed 8 days following induction. Disease was assessed histologically (number of glomerular crescents, degree of glomerular thrombosis, number of infiltrating leucocytes and calprotectin expression) and biochemically (serum creatinine and urea levels, and urinary levels of protein). RESULTS: Neither treatment with low (0.5mg/kg) or high (25mg/kg) doses of paquinimod, given preventatively or therapeutically, led to disease attenuation, as assessed by biochemical or histological parameters. Additionally, we found trends for an increase in renal glomerular calprotectin expression in the high dose groups, suggesting a possible feedback regulation of calprotectin expression. CONCLUSIONS: Our results show that paquinimod does not successfully prevent or treat mice with NTN. Other models of immune-mediated glomerulonephritis need to be tested to investigate the therapeutic potential of this compound in renal disease.

Fecal calprotectin levels in preterm infants with and without feeding intolerance.

OBJECTIVES: To assess the level of fecal calprotectin in preterm neonates with feeding intolerance, as well as to evaluate it as a marker of feeding intolerance and to determine a cut-off level of fecal calprotectin in feeding intolerance. METHODS: Analytical, multicenter, case-control study, which was carried out in neonatal intensive care units in Egypt, in a period from August 1, 2014 to March 1, 2015 on 52 preterm neonates. Neonates were classified into two groups; a study group including 26 neonates who met inclusion criteria and a control group including 26 neonates for comparison. RESULTS: Fecal calprotectin levels ranged from 3.9µg/g to 971.8µg/g, and there was a significant increase in fecal calprotectin in the study group when compared to the control group (334.3±236.6µg/g vs. 42.0±38.2µg/g, respectively) with moderate inverse significant correlation between fecal calprotectin and birth weight. Furthermore, there was moderate, significant correlation between fecal calprotectin and duration of breastfeeding range. On the other hand, there was no correlation between fecal calprotectin and post-natal age, gestational age, or volume of feeding. A cut-off at the 67.0µg/g level, with 100.0% sensitivity and 76.9% specificity, was considered. CONCLUSION: Fecal calprotectin level increased significantly in neonates with feeding intolerance; it can be used to detect early cases with necrotizing enterocolitis in neonates, but this subject still needs more investigations on more patients.

[Faecal calprotectin as an aid to the diagnosis of non-IgE mediated cow's milk protein allergy]. / Calprotectina fecal como apoyo al diagnóstico en la alergia a las proteínas de leche de vaca no IgE mediada.

INTRODUCTION: The aim of the study was to assess the use of faecal calprotectin (FCP) in infants with signs and symptoms of non-IgE-mediated cow's milk protein allergy (CMA) for both diagnosis and prediction of clinical response at the time of withdrawal of milk proteins. PATIENTS AND METHODS: A one year prospective study was conducted on 82 infants between 1 and 12 months of age in the Eastern area of Málaga-Axarquía, of whom 40 of them had been diagnosed with non-IgE-mediated CMA (with suggestive symptoms and positive response to milk withdrawal), 12 not diagnosed with CMA, and 30 of them were the control group. FCP was measured at three different times: time of diagnosis, and one and three months later. ANOVA for repeated measures, nominal logistic regression and ROC curves were prepared using the SPSS.20 package and Medcalc. RESULTS: Differences between diagnostic and control groups were assessed: there was a statistically significant relationship (p<.0001) between high FCP levels and infants suffering CMA, as well as the levels at time of diagnosis, 1 and 3 months (p <.001). A ROC curve was constructed between FCP levels and diagnosis of CMA, with 138 ug/g, with the best cut-off being with an area under the curve of 0.89. However, it is only 0.68 to predict a clinical response. CONCLUSIONS: FCP levels lower than 138ug/g could be useful to rule out non-IgE-mediated CMA diagnosis. Calprotectin is not a good test to predict clinical response to milk withdrawal.

Niveles de calprotectina fecal en pacientes con anticuerpos anti-transglutaminasa positivos y pacientes con dieta libre de gluten / Fecal calprotectin levels in patients with positive anti-transglutaminase antibodies and patients on a gluten free diet / Niveis de calprotectina fecal em pacientes com anticorpos anti-transglutaminase positivos e pacientes com dieta livre de gluten

La calprotectina fecal se ha afianzado en los últimos años como un marcador útil de las patologías gastrointestinales. El objetivo de este estudio fue determinar los niveles de calprotectina fecal (CPF), interleuquina-6 (IL-6) y proteína C reactiva (PCR) en tres grupos de pacientes: con diagnóstico de novo de enfermedad celíaca, con diagnóstico previo y dieta libre de gluten (DLG) y un grupo control. Se colectaron muestras de 79 pacientes entre 18 y 65 años. A todos se les determinó CPF, IL-6 y PCR como marcadores de inflamación y anticuerpos anti-transglutaminasa IgA y anti-gliadinas desaminadas IgA e IgG como marcadores serológicos. Se encontraron valores significativamente incrementados de PCR en el grupo de novo (124,06 μg/g) comparados con el grupo con DLG (23,61 μg/g) y el grupo control (16,91 μg/g) respectivamente. No se encontraron diferencias entre el grupo con DLG y el negativo (control). Idéntico comportamiento se observó para IL-6 con valores en el grupo de novo de 2,39 μg/dL, 1,74 μg/dL en el grupo con DLG y 1,41 μg/dL en el control negativo. No se encontraron diferencias significativas en el análisis de resultados de PCR. Se encontró una excelente sensibilidad (98,0%) y especificidad (96,6%) en la capacidad de la CPF para diferenciar valores de anti-transglutaminasa IgA superiores o inferiores al punto de corte cuando se estimó el índice de Youden. Se podría considerar a la CPF como un posible marcador sensible para indicar inflamación intestinal de manera no invasiva en la enfermedad celíaca.

The determination of fecal calprotectin has been strengthened in recent years as a useful marker of gastrointestinal pathologies. The objective of this study was to determine the levels of fecal calprotectin (FCP), interleukin-6 (IL-6) and C-reactive protein (CRP) in three groups of patients: with de novo diagnosis of celiac disease, with previous diagnosis and gluten-free diet (GFD) and a control group. Samples were collected from 79 patients between 18 and 65 years old. In all cases, FCP, IL-6 and RCP were determined as markers of inflammation and anti-transglutaminase IgA and deaminated anti-gliadin IgA and IgG antibodies as serological markers. Significantly more increased FCP values were found in the de novo group (124.06 μg/g) than in the group with DLG (23.61 μg/g) and the control group (16.91 μg/g). No differences were found between the group with GFD and the negative. The same trend was observed for IL-6 with values in the de novo group of 2.39 μg/dL, 1.74 μg/dL in the group with gluten free diet and 1.41 μg/dL in the negative control. No significant differences were found in the analysis of RCP results. Excellent sensitivity (98.0%) and specificity (96.6%) were found in the capability of the FCP to differentiate anti-transglutaminase IgA values higher or lower than the cut-off point when the Youden index was estimated. The FCP could be considered as a possible sensitive marker to indicate intestinal inflammation in a non-invasive manner in celiac disease.

A calprotectina fecal se consolidou nos ultimos anos como um marcador util das patologias gastrointestinais. O objetivo deste estudo foi determinar os niveis de calprotectina fecal (CPF), interleucina-6 (IL-6) e proteina C-reativa (PCR) em tres grupos de pacientes; com diagnostico de novo de doenca celiaca, com diagnostico previo e dieta livre de gluten (DLG) e um grupo controle. Foram coletadas amostras de 79 pacientes entre 18 e 65 anos. Em todos os casos CPF, IL-6 e PCR foram determinadas como marcadores de inflamacao e anticorpos anti-transglutaminase IgA e anti-gliadinas desaminadas IgA e IgG como marcadores sorologicos. Valores significantemente mais altos de PCR foram detectados no grupo de novo (124,06 μg/g) comparados com o grupo com DLG (23,61 μg/g) e o grupo controle (16,91 μg/g) respectivamente. Nao foram encontradas diferencas entre o grupo com DLG e o negativo (controle). O mesmo comportamento foi observado para IL-6 com valores no grupo de novo de 2,39 μg/dL, 1,74 μg/dL no grupo com DLG e 1,41 μg/dL no controle negativo. Na analise de resultados da PCR nao foram encontradas diferencas significativas. Foram detectadas uma sensibilidade excelente (98,0%) e especificidade (96,6%) na habilidade da CPF para diferenciar valores de anti-transglutaminase IgA superiores ou inferiores ao ponto de corte quando o indice de Youden foi estimado. Poderia ser considerada a CPF como um possivel marcador sensivel para identificar inflamacao intestinal de forma nao invasiva na doenca celiaca.

[Exclusive enteral nutrition continues to be first line therapy for pediatric Crohn's disease in the era of biologics]. / La nutrición enteral exclusiva continua siendo el tratamiento de primera línea en la enfermedad de Crohn pediátrica en la era de los biológicos.

INTRODUCTION: Exclusive enteral nutrition (EEN) has been to be more effective than corticosteroids in achieving mucosal healing without their side effects. OBJECTIVES: To determine the efficacy of EEN in terms of inducing clinical remission in newly diagnosed CD children and to study the efficacy of this therapeutic approach in improving the degree of intestinal mucosa inflammation. MATERIALS AND METHODS: The medical records of patients with newly diagnosed Crohn's disease treated with EEN were reviewed retrospectively. The degree of mucosal inflammation was assessed by fecal calprotectin (FC). Remission was defined as a PCDAI<10. RESULTS: Forty patients (24 males) were included, the age at diagnosis was 11.6 ± 3.6 years. Of the 34 patients who completed the EEN period, 32 (94% per-protocol analysis) achieved clinical remission. This percentage fell to 80% in the intention-to-treat analysis. The compliance rate was 95%. Duration of EEN was 6.42 weeks (IQR 6.0-8.14). FC was significantly higher in patients with moderate and severe disease. Median baseline FC levels (680 µg/g) decreased significantly to 218 µg/g (P<0.0001) after EEN. We found a statistically significant correlation between FC and PCDAI (rho=0.727; P<0.0001). Early use of thiopurines (< 8 weeks) versus subsequent use was not associated with improved outcomes during the follow-up. CONCLUSIONS: EEN administered for 6-8 weeks is effective for inducing clinical remission and decreasing the degree of mucosal inflammation. We did not find differences in terms of maintenance of remission in patients treated early with thiopurines.