Combined evaluation of fecal calprotectin and C-reactive protein as a therapeutic target in the management of patients with Crohn's disease / Evaluación combinada de Calprotectina Fecal y Proteína C-reactiva como objetivo terapéutico en el tratamiento de pacientes con Enfermedad de Crohn

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.(AU)

Introducción: Un adecuado control del proceso inflamatorio en la enfermedad de Crohn (EC) supone menores tasas de complicaciones. El objetivo de este estudio es evaluar la utilidad de la calprotectina fecal (CF) y los niveles séricos de la proteína C-reactiva (PCR), aisladamente o en combinación, como marcadores de actividad inflamatoria en la EC, así como la posibilidad de ser utilizados como objetivo terapéutico. Pacientes y métodos: Se incluyeron prospectivamente en el estudio pacientes con EC e indicación para colonoscopia siendo distribuidos de acuerdo a la presencia o no de actividad inflamatoria endoscópica. Se determinó la correlación entre CF y niveles de PCR con el índice SES-CD, y se evaluó la precisión de estos marcadores en el diagnóstico de la actividad inflamatoria, utilizados individualmente o en combinación. Resultados: Se realizaron un total de 80 colonoscopias en pacientes con EC. Para la CF, el punto de corte de 155μg/g mostró una elevada sensibilidad del 96% y una especificidad del 78% en el diagnóstico de actividad endoscópica. En cuanto a la PCR, el valor de 6,7mg/l proporcionó una sensibilidad del 75% y una especificidad del 67%. El uso combinado de estos marcadores (CF+PCR) obtuvo mayor especificidad (82%) cuando se comparó con su utilización individual. De acuerdo al riesgo de actividad inflamatoria, se manejaron diferentes escenarios para evaluar la eficacia de estos marcadores y se propuso un algoritmo de uso. Discusión: La monitorización conjunta de CF y PCR, cuando se realiza de forma consecutiva, permite tomar decisiones con un mayor grado de certeza, eliminando, incluso, la necesidad de colonoscopia en muchas situaciones.(AU)

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.

Clinical Response to Donepezil in Mild and Moderate Dementia: Relationship to Drug Plasma Concentration and CYP2D6 and APOE Genetic Polymorphisms.

The clinical response to donepezil in patients with mild and moderate dementia was investigated in relation to the drug plasma concentration and APOE and CYP2D6 polymorphisms. In a prospective naturalistic observational study, 42 patients with Alzheimer's disease (AD) and AD with cerebrovascular disease who took donepezil (10 mg) for 12 months were evaluated. Their DNA was genotyped, and the donepezil plasma concentrations were measured after 3, 6, and 12 months. Good responders scored ≥-1 on the Mini-Mental State Examination at 12 months in comparison to the baseline score. The study results indicated the good response pattern was influenced by the concentration of donepezil, but not by APOE and CYP2D6 polymorphisms.

Predictive factors of clinical response to cholinesterase inhibitors in mild and moderate Alzheimer's disease and mixed dementia: a one-year naturalistic study.

BACKGROUND: Naturalistic studies evaluate individuals in their usual way of living, presenting more "real-life" data regarding patients and their diseases. OBJECTIVE: To investigate demographic, clinical, and genetic factors that could be predictive of good response to cholinesterase inhibitors (ChEI) treatment in Alzheimer's disease (AD) and AD + cerebrovascular disease (CVD). PATIENTS AND METHODS: A total of 129 patients were diagnosed with AD or AD + CVD and with mild-to-moderate dementia. After a 12-month treatment, 97 patients completed the study. They were evaluated at baseline and after three, six, and 12 months of ChEI (donepezil or rivastigmine or galantamine) use. APOE genotype and CYP2D6 polymorphisms were determined for all of the participants. In each visit, we used cognitive, functional, mood, and behavior scales. We classified patients according to their scores in the Mini-Mental State Examination (MMSE). Good responders were defined as those scoring ≥2 in the MMSE at 12 months. RESULTS: The rate of good clinical response was 27.8%. In a longitudinal analysis, the patients with mild AD and also good responders at three months were considered to be good responders at 12 months. There was no correlation between ChEI dose, APOE and CYP2D6 polymorphisms, and the pattern of clinical response. CONCLUSION: A higher rate of good response was observed in this study compared to that in previous investigations. The pharmacogenetic aspects do not seem to have an influence in the response.