RESUMEN
BACKGROUND AND AIMS: STRIDE-II recommends early biomarker targets for treatment optimization to achieve treat-to-target [T2T] endoscopic remission [ER] in Crohn's disease [CD]. The predictive capabilities of intestinal ultrasound [IUS] for T2T ER remain unknown. We aimed to evaluate IUS response to predict ER in children with CD. METHODS: This was a prospective longitudinal cohort study of children with ileal [TI] CD initiating biologic therapy undergoing IUS, clinical disease activity, and C-reactive protein [CRP] assessments at baseline, week 8, 6 months, and T2T within 1 year. The primary outcome was the accuracy of optimal cut-points to predict TI ER [SES-CD ≤ 2] for change in bowel wall thickness [BWT] on IUS from baseline to week 8, and BWT at week 8. Area under the receiver operating curve [AUROC] analysis was performed and univariate analysis tested associations. RESULTS: In total, 44 children (median age 13 [IQR 12-17] years, 29 [66%] biologic naïve) were included, and 29 [66%] achieved ER. A ≥18% decrease in TI BWT at week 8 predicted ER with an AUROC of 0.99 [95% CI 0.98-1.00], 100% sensitivity, 93% specificity, 97% positive predictive value, and 100% negative predictive value, superior to a ≥46% decrease in PCDAI (AUROC 0.67 [95% CI 0.49-0.84]) and ≥84% decrease in CRP (AUROC 0.49 [95% CI 0.31-0.67]) at week 8. CONCLUSIONS: Early change in TI BWT on IUS is highly predictive of ER in children with CD and superior to symptoms and CRP. Our findings suggest that IUS could be used for treatment optimization and tight control to guide T2T strategies.
Asunto(s)
Enfermedad de Crohn , Inducción de Remisión , Ultrasonografía , Humanos , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/terapia , Masculino , Femenino , Adolescente , Estudios Prospectivos , Niño , Ultrasonografía/métodos , Inducción de Remisión/métodos , Estudios Longitudinales , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Valor Predictivo de las Pruebas , Íleon/diagnóstico por imagen , Íleon/patología , Terapia Biológica/métodosRESUMEN
INTRODUCTION: High rates of screen failure for the minimum Simple Endoscopic Score for Crohn's Disease (SES-CD) plague Crohn's disease (CD) clinical trials. We aimed to determine the accuracy of segmental intestinal ultrasound (IUS) parameters and scores to detect segmental SES-CD activity. METHODS: A single-center, blinded, cross-sectional cohort study of children and young adult patients with CD undergoing IUS and ileocolonoscopy, comparing segmental IUS bowel wall thickness (BWT), hyperemia (modified Limberg score [MLS]), and scores to detect segmental SES-CD activity: (i) SES-CD ≤2, (ii) SES-CD ≥6, and (iii) SES-CD ≥4 in the terminal ileum (TI) only. Primary outcome was accuracy of BWT, MLS, and IUS scores to detect SES-CD ≤2 and SES-CD ≥6. Secondary outcomes were accuracy of TI BWT, MLS, and IUS scores to detect SES-CD ≥4 and correlation with the SES-CD. RESULTS: Eighty-two patients (median [interquartile range] age 16.5 [12.9-20.0] years) underwent IUS and ileocolonoscopy of 323 bowel segments. Segmental BWT ≤3.1 mm had a similar high accuracy to detect SES-CD ≤2 as IUS scores (area under the receiver operating curve [AUROC] 0.833 [95% confidence interval 0.76-0.91], 94% sensitivity, and 73% specificity). Segmental BWT ≥3.6 mm and ≥4.3 mm had similar high accuracy to detect SES-CD ≥6 (AUROC 0.950 [95% confidence interval 0.92-0.98], 89% sensitivity, 93% specificity) in the colon and an SES-CD ≥4 in the TI (AUROC 0.874 [0.79-0.96], 80% sensitivity, and 91% specificity) as IUS scores. Segmental IUS scores strongly correlated with the SES-CD. DISCUSSION: Segmental IUS BWT is highly accurate to detect moderate-to-severe endoscopic inflammation. IUS may be the ideal prescreening tool to reduce unnecessary trial screen failures.
Asunto(s)
Colonoscopía , Enfermedad de Crohn , Ultrasonografía , Humanos , Enfermedad de Crohn/diagnóstico por imagen , Femenino , Masculino , Estudios Transversales , Adolescente , Ultrasonografía/métodos , Adulto Joven , Niño , Índice de Severidad de la Enfermedad , Íleon/diagnóstico por imagen , Íleon/patología , Sensibilidad y Especificidad , Ensayos Clínicos como Asunto , Curva ROCRESUMEN
The COVID-19 pandemic has caused millions of deaths and massive societal distress worldwide. Therapeutic solutions are urgently needed, but de novo drug development remains a lengthy process. One promising alternative is computational drug repurposing, which enables the prioritization of existing compounds through fast in silico analyses. Recent efforts based on molecular docking, machine learning, and network analysis have produced actionable predictions. Some predicted drugs, targeting viral proteins and pathological host pathways are undergoing clinical trials. Here, we review this work, highlight drugs with high predicted efficacy and classify their mechanisms of action. We discuss the strengths and limitations of the published methodologies and outline possible future directions. Finally, we curate a list of COVID-19 data portals and other repositories that could be used to accelerate future research.