Comparative Effectiveness of Anti-TNF in Combination With Low-Dose Methotrexate vs Anti-TNF Monotherapy in Pediatric Crohn's Disease: A Pragmatic Randomized Trial.

BACKGROUND & AIMS: Tumor necrosis factor inhibitors, including infliximab and adalimumab, are a mainstay of pediatric Crohn's disease therapy; however, nonresponse and loss of response are common. As combination therapy with methotrexate may improve response, we performed a multicenter, randomized, double-blind, placebo-controlled pragmatic trial to compare tumor necrosis factor inhibitors with oral methotrexate to tumor necrosis factor inhibitor monotherapy. METHODS: Patients with pediatric Crohn's disease initiating infliximab or adalimumab were randomized in 1:1 allocation to methotrexate or placebo and followed for 12-36 months. The primary outcome was a composite indicator of treatment failure. Secondary outcomes included anti-drug antibodies and patient-reported outcomes of pain interference and fatigue. Adverse events (AEs) and serious AEs (SAEs) were collected. RESULTS: Of 297 participants (mean age, 13.9 years, 35% were female), 156 were assigned to methotrexate (110 infliximab initiators and 46 adalimumab initiators) and 141 to placebo (102 infliximab initiators and 39 adalimumab initiators). In the overall population, time to treatment failure did not differ by study arm (hazard ratio, 0.69; 95% CI, 0.45-1.05). Among infliximab initiators, there were no differences between combination and monotherapy (hazard ratio, 0.93; 95% CI, 0.55-1.56). Among adalimumab initiators, combination therapy was associated with longer time to treatment failure (hazard ratio, 0.40; 95% CI, 0.19-0.81). A trend toward lower anti-drug antibody development in the combination therapy arm was not significant (infliximab: odds ratio, 0.72; 95% CI, 0.49-1.07; adalimumab: odds ratio, 0.71; 95% CI, 0.24-2.07). No differences in patient-reported outcomes were observed. Combination therapy resulted in more AEs but fewer SAEs. CONCLUSIONS: Among adalimumab but not infliximab initiators, patients with pediatric Crohn's disease treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile. CLINICALTRIALS: gov, Number: NCT02772965.

Can species naming drive scientific attention? A perspective from plant-feeding arthropods.

How do researchers choose their study species? Some choices are based on ecological or economic importance, some on ease of study, some on tradition-but could the name of a species influence researcher decisions? We asked whether phytophagous arthropod species named after their host plants were more likely to be assayed for host-associated genetic differentiation (or 'HAD'; the evolution of cryptic, genetically isolated host specialists within an apparently more generalist lineage). We chose 30 arthropod species (from a Google Scholar search) for which a HAD hypothesis has been tested. We traced the etymologies of species names in the 30 corresponding genera, and asked whether HAD tests were more frequent among species whose etymologies were based on host-plant names (e.g. Eurosta solidaginis, which attacks Solidago) versus those with other etymologies (e.g. Eurosta fenestrata, from Latin fenestra, 'window'). Species with host-derived etymologies were more likely to feature in studies of HAD than those with other etymologies. We speculate that the etymology of a scientific name can draw a researcher's attention to aspects of life-history and thus influence the direction of our scientific gaze.

Use, Durability, and Risks for Discontinuation of Initial and Subsequent Biologics in a Large Pediatric-Onset IBD Cohort.

BACKGROUND: Biologic medications are recommended for treatment of moderately-to-severely active Crohn disease (CD) or ulcerative colitis (UC) in children. However, many patients require sequential biologic treatment because of nonresponse or loss of response to the initial biologic. METHODS: We analyzed pediatric inflammatory bowel disease (IBD) data from the ImproveCareNow Network registry between May 2006 and September 2016, including time to biologic initiation, choice of first subsequent biologics, biologic durability, and reasons for discontinuation. RESULTS: Of 17,649 patients with IBD [CD: 12,410 (70%); UC: 5239 (30%)], 7585 (43%) were treated with a biologic agent before age 18 (CD: 50%; UC: 25%). Biologic treatment was more likely for CD than UC (odds ratio, 3.0; 95% CI: 2.8-3.2; P < 0.0001). First biologic agents for all patients were anti-tumor necrosis factor agents (88% infliximab, 12% adalimumab). Probability of remaining on the first biologic was significantly higher in CD than UC ( P < 0.0001). First biologics were discontinued because of loss of response (39%), intolerance (23%), and nonresponse (19%). In univariate analysis, factors associated with discontinuation of first and/or second biologics in CD include colonic-only disease, corticosteroid use, upper gastrointestinal tract involvement, and clinical and biochemical markers of severe disease. Biologic durability improved with later induction date. CONCLUSIONS: Treatment with biologic medications is common in pediatric IBD. Patients with CD are more likely to receive biologics, receive biologics earlier in disease course, and remain on the first biologic longer than patients with UC. Multiple factors may predict biologic durability in children with IBD.

Fecal Microbiota Transplantation for Clostridioides difficile Infection in Immunocompromised Pediatric Patients.

OBJECTIVES: We sought to evaluate the safety and effectiveness of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) in pediatric immunocompromised (IC) patients. METHODS: This is a multicenter retrospective cohort study of pediatric participants who underwent FMT between March 2013 and April 2020 with 12-week follow-up. Pediatric patients were included if they met the definition of IC and were treated with FMT for an indication of recurrent CDI. We excluded patients over 18 years of age, those with incomplete records, insufficient follow-up, or not meeting study definition of IC. We also excluded those treated for Clostridioides difficile recurrence without meeting the study definition and those with inflammatory bowel disease without another immunocompromising condition. RESULTS: Of 59 pediatric patients identified at 9 centers, there were 42 who met inclusion and no exclusion criteria. Included patients had a median age of 6.7 years. Etiology of IC included: solid organ transplantation (18, 43%), malignancy (12, 28%), primary immunodeficiency (10, 24%), or other chronic conditions (2, 5%). Success rate was 79% after first FMT and 86% after 1 or more FMT. There were no statistically significant differences in patient characteristics or procedural components when patients with a failed FMT were compared to those with a successful FMT. There were 15 total serious adverse events (SAEs) in 13 out of 42 (31%) patients that occurred during the follow-up period; 4 (9.5%) of which were likely treatment-related. There were no deaths or infections with multidrug resistant organisms during follow-up and all patients with a SAE fully recovered. CONCLUSIONS: The success rate of FMT for recurrent CDI in this pediatric IC cohort is high and mirrors data for IC adults and immunocompetent children. FMT-related SAEs do occur (9.5%) and highlight the need for careful consideration of risk and benefit.

Spinosad-associated modulation of select cytochrome P450s and glutathione S-transferases in the Colorado potato beetle, Leptinotarsa decemlineata.

The Colorado potato beetle (Leptinotarsa decemlineata (Say)) is an insect pest that threatens potato crops. Multiple options exist to limit the impact of this pest even though insecticides remain a primary option for its control. Insecticide resistance has been reported in Colorado potato beetles and a better understanding of the molecular players underlying such process is of utmost importance to optimize the tools used to mitigate the impact of this insect. Resistance against the insecticide spinosad has been reported in this insect and this work thus aims at exploring the expression of targets previously associated with insecticide response in Colorado potato beetles exposed to this compound. Amplification and quantification of transcripts coding for cytochrome P450s and glutathione S-transferases were conducted via qRT-PCR in insects treated with varying doses of spinosad and for different time duration. This approach notably revealed differential expression of CYP6a23 and CYP12a5 in insects exposed to low doses of spinosad for 4 h as well as modulation of CYP6a13, CYP6d4, GST, GST1, and GST1-Like in insects treated with high doses of spinosad for the same duration. RNAi-based targeting of CYP4g15 and CYP6a23 was associated with marked reduction of transcript expression 7 days following dsRNA injection and reduction of the former had a marked impact on insect viability. In general, results presented here provide novel information regarding the expression of transcripts relevant to spinosad response in Colorado potato beetles and reveal a novel target to consider in the development of RNAi-based strategies aimed at this potato pest.

Personalized Research on Diet in Ulcerative Colitis and Crohn's Disease: A Series of N-of-1 Diet Trials.

INTRODUCTION: Evidence about specific carbohydrate diet (SCD) for inflammatory bowel disease (IBD) is limited. We conducted 54 single-subject, double-crossover N-of-1 trials comparing SCD with a modified SCD (MSCD) and comparing each with the participant's baseline, usual diet (UD). METHODS: Across 19 sites, we recruited patients aged 7-18 years with IBD and active inflammation. Following a 2-week baseline (UD), patients were randomized to 1 of 2 sequences of 4 alternating 8-week SCD and MSCD periods. Outcomes included fecal calprotectin and patient-reported symptoms. We report posterior probabilities from Bayesian models comparing diets. RESULTS: Twenty-one (39%) participants completed the trial, 9 (17%) completed a single crossover, and 24 (44%) withdrew. Withdrawal or early completion occurred commonly (lack of response [n = 11], adverse events [n = 11], and not desiring to continue [n = 6]). SCD and MSCD performed similarly for most individuals. On average, there was <1% probability of a clinically meaningful difference in IBD symptoms between SCD and MSCD. The average treatment difference was -0.3 (95% credible interval -1.2, 0.75). There was no significant difference in the ratio of fecal calprotectin geometric means comparing SCD and MSCD (0.77, 95% credible interval 0.51, 1.10). Some individuals had improvement in symptoms and fecal calprotectin compared with their UD, whereas others did not. DISCUSSION: SCD and MSCD did not consistently improve symptoms or inflammation, although some individuals may have benefited. However, there are inherent difficulties in examining dietary changes that complicate study design and ultimately conclusions regarding effectiveness.

Microgranulomas at Diagnosis Are Associated With Need for Antitumor Necrosis Factor Escalation in Pediatric Crohn Disease.

INTRODUCTION: Granulomas are a pathologic hallmark of Crohn disease (CD) although they are found in only a subset of patients. Well-formed granulomas are associated with an aggressive phenotype although it is unknown if microgranulomas confer a similar phenotype. This study sought to define the incidence of microgranulomas in pediatric CD and compare the clinical course with cases with granulomas and those without granulomatous inflammation. METHODS: We performed a single-center, retrospective study of pediatric CD patients who had at least 3 years of follow-up. initial diagnostic biopsies were systematically re-examined by a gastrointestinal pathologist. A priori definitions of granuloma (10+ histiocytes) and microgranuloma (4-9 histiocytes) were used. Disease outcomes of hospitalization, development of complicated disease behavior, perianal disease, and the use of anti-tumor necrosis factor (anti-TNF) therapy were assessed by Kaplan-Meier survival plots. RESULTS: This study included 138 subjects with an average follow-up of 4.6 years. Granulomas were seen in 38 of 138 subjects (27.5%) and an additional 38 subjects (27.5%) had at least 1 microgranuloma (in the absence of granulomas). Escalation to anti-TNF therapy was higher in CD with granulomas (P  = 0.001) and microgranulomas (P  = 0.0001) compared with those without granulomatous inflammation. CONCLUSIONS: A significant subset of pediatric CD patients have microgranulomas (in the absence of well-defined granulomas). Children with CD who have microgranulomas are escalated to anti-TNF therapy more frequently than those without granulomatous inflammation (and at a similar rate to those with granulomas). Pathologists should have a low threshold to report microgranulomas as they may help to predict disease behavior.

From the voices of supervisees: A theoretical model of reflective supervision (Part II).

Empirical study of reflective supervision/consultation (RS/C) has been gaining ground over the past decade. However, much of this literature is focused on the supervisor perspective of what RS/C is, what makes it effective, and how it impacts the work of the supervisee. This paper, Part II of a two-part series, presents a theoretical model of RS/C that was developed from the perspectives and experiences of supervisees who work with infants, young children, and families and participate in either group or individual RS/C. This qualitative study built upon themes that emerged from data obtained from 50 IECMH professionals in the United States who participated in focus groups or individual interviews aimed at investigating their experiences of RS/C. Data were analyzed using a Grounded Theory approach. A developmental and ecological theoretical model of RS/C emerged from the data that includes three domains of influence - individual, relational, and contextual - on the supervisee's capacity to understand and use their experience of RS/C in their work. These novel data contribute to our understanding of RS/C from the supervisee perspective. The theoretical model provides a framework from which to investigate outcomes, train supervisors and supervisees, and advocate for RS/C within agencies and programs.

El estudio empírico de la supervisión/consulta con reflexión (RS/C) ha estado ganando terreno en la pasada década. Sin embargo, la mayoría de estas publicaciones se enfocan en la perspectiva del supervisor acerca de lo que RS/C es, lo que la hace eficaz y qué impacto tiene en el trabajo del supervisado. Este ensayo, Parte II de una serie de dos partes, presenta un modelo teórico de RS/C que se desarrolló a partir de las perspectivas y experiencias de los supervisados que trabajan con infantes, niños pequeños y familias y participan en RS/C de grupo o individual. Este estudio cualitativo tuvo como base los temas que surgieron de datos obtenidos de cincuenta profesionales de IECMH en los Estados Unidos, quienes participaron en grupos de enfoque o entrevistas individuales dirigidas a investigar sus experiencias de RS/C. La información se analizó usando un acercamiento de Teoría Fundamentada. De la información surgió un modelo teorético de desarrollo y ecológico de RS/C que incluye tres dominios de influencia - individual, relacional y contextual - sobre la capacidad de los supervisados de comprender y usar sus experiencias de RS/C en el trabajo. Esta novedosa información contribuye a nuestro conocimiento de RS/C desde la perspectiva del supervisado. El modelo teórico provee un marco de trabajo desde el cual se investigan los resultados, se entrenan los supervisores y supervisados, y se aboga por la inclusión de RS/C dentro de agencias y programas.

Les études empiriques de la supervision / consultation réflexive (RS/C pour reprendre l'anglais) a gagné du terrain ces dix dernières années. Cependant beaucoup de ces recherches sont focalisées sur la perspective du superviseur de ce qu'est la RS/C, ce qui rend la rend efficace, et comment elle influence le travail de la personne supervisée. Cet article, la deuxième partie d'une série en deux parties, présente un modèle théorique de la RS/C qui a été développé à partir des perspectives et des expériences de personnes supervisées travaillant avec des nourrissons, de jeunes enfants et des familles et participant à soit une RS/C de groupe ou individuelle. Cette étude qualitative s'est bâtie sur des thèmes ayant émergé de données obtenues de cinquante professionnels de la santé mentale du nourrisson et de la petite enfance se trouvant aux Etats-Unis qui ont participé à des groupes de discussion ou à des entretiens individuels destinés à enquêter sur leurs expériences de la RS/C. Les données ont été analysées en utilisant une approche de Théorie Ancrée. Un modèle théorique développemental et écologique de RS/C a émergé des données, incluant trois domaines d'influence - individuel, relationnel, et contextuel - sur la capacité de la personne supervisée à comprendre et à utiliser ses expériences de la RS/C dans le travail. Ces nouvelles données contribuent à notre compréhension de la RS/C du point de vue de la personne supervisée. Le modèle théorique offre une structure à partir de laquelle on peut faire des recherches sur les résultats, former les superviseurs et les personnes supervisées, et se faire les avocats de la RS/C au sein des agences et des programmes.

From the voices of supervisees: What is reflective supervision and how does it support their work? (Part I).

Reflective supervision/consultation (RS/C) is a relationship for learning that embraces reflection and reflective practice strategies. It is considered best practice within the infant and early childhood mental health (IECMH) field. Based on research with supervisors, essential components of RS/C have been operationalized and used to develop evaluative tools. Little is known, however, about the essential components that supervisees find most useful. This paper, part I of a two-part series, describes the essential components that supervisees identify as fundamental and ways they believe their work is supported by participation in RS/C. Fifty IECMH professionals located in the United States who received RS/C participated in focus groups or individual interviews. Data were analyzed using a Grounded Theory approach. Essential components of RS/C from the supervisee perspective included supervisee feelings of safety, the development of trust, holding a non-judgmental stance, being available and present, and consistency and predictability. Additionally, supervisees identified outcomes of RS/C that included components of professional wellness, personal growth, and infant and family engagement. This study adds the supervisee's voice to the identification and operationalization of essential RS/C components and elucidates outcomes of RS/C that supervisees view as connected to their professional role.

La supervisión/consulta con reflexión (RS/C) es una relación para el aprendizaje (Fenichel, 1992) que abarca la reflexión y las estrategias de reflexión en la práctica. La misma es considerada como una de las buenas prácticas dentro del campo de la salud mental del infante y la temprana niñez (IECMH). Con base en la investigación con supervisores, los componentes esenciales de RS/C han sido puestos en operación y usados para desarrollar herramientas de evaluación. Sin embargo, poco se sabe acerca de los componentes esenciales que los supervisados ven como los más útiles. Este ensayo, primera parte de una serie de dos partes, describe los componentes esenciales que los supervisados identifican como fundamentales y las maneras como ellos creen que su trabajo es apoyado por la participación en RS/C. Cincuenta profesionales de IECMH que recibieron RS/C participaron en grupos de enfoque o entrevistas individuales. Se analizaron los datos usando un acercamiento de la Teoría Fundamentada. Entre los componentes esenciales de RS/C desde la perspectiva del supervisado se incluyen los sentimientos de seguridad del supervisado, el desarrollo de la confianza, el mantener una actitud imparcial, estar disponible y presente, y consistencia y previsibilidad. Adicionalmente, los supervisados identificaron resultados de RS/C que incluyen componentes de bienestar profesional, crecimiento personal, así como la participación del infante y la familia. Este estudio agrega la voz del supervisado a la identificación y funcionamiento de los componentes esenciales de RS/C y dilucida resultados de RS/C que los supervisados ven como conectados con su papel profesional.

La supervision / consultation réflexive (RS/C pour reprendre l'anglais) est une relation d'apprentissage (Fenichel, 1992) qui embrasse la réflexion et des stratégies de pratique réflective. Elle est considérée comme étant la meilleure pratique au sein du domaine de la santé mentale du nourrisson et de la petite enfance. A partir des recherches avec des superviseurs les composants essentiels de la RS/C ont été opérationnalisés et utilisés pour développer des outils évaluatifs. On sait peu de choses, cependant, sur les composants essentiels que les personnes supervisées estiment être les plus utiles. Cet article, la première partie d'une série de deux parties, décrit les composants essentiels que les personnes supervisées identifient comme étant fondamentaux et les manières dont ils estiment que leur travail est soutenu par la participation à la RS/C. Cinquante professionnels de la santé mentale du nourrisson et de la petite enfance se trouvant aux Etats-Unis et ayant reçu la RS/C ont participé à des groupes de discussion ou à des entretiens individuels. Les données ont été analysées en utilisant une approche de Théorie Ancrée. Les composants essentiels à la RS/C du point de vue des personnes supervisées ont inclus le sentiment de sûreté de la personne supervisée, le développement de la confiance, le fait de ne pas juger, le fait d'être disponible et présent, ainsi que la cohérence et la prévisibilité. De plus les personnes supervisées ont identifié des résultats de la RS/C qui ont inclus des composants de bien-être professionnel, d'épanouissement personnel et d'engagement avec le nourrisson et la famille. Cette étude ajoute la voix de la personne supervisée à l'identification et à l'opérationnalisation des composants essentiels de la RS/C et élucide les résultats de la RS/C que les personnes supervisées considèrent comme étant lié à leur rôle professionnel.

A Switchable Palladium(II) Trefoil Entangled Tetrahedron with Temperature Dependence and Concentration Independence.

Self-assembly makes metallo-interlocked architectures attractive targets, but being in equilibrium with smaller species means that they can suffer from dilution effects. We show that a junctioned system gives rise to a [Pd4 (L)2 ]8+ trefoil entangled tetrahedron irrespective of concentration. Heating the sample reversibly shifts the equilibrium from the knot to an isomeric non-interlocked dual metallo-cycle, demonstrating that thermodynamic equilibria can still be exploited for switching even in the absence of concentration effects.

Tree phyllospheres are a habitat for diverse populations of CO-oxidizing bacteria.

Carbon monoxide (CO) is both a ubiquitous atmospheric trace gas and an air pollutant. While aerobic CO-degrading microorganisms in soils and oceans are estimated to remove ~370 Tg of CO per year, the presence of CO-degrading microorganisms in above-ground habitats, such as the phyllosphere, and their potential role in CO cycling remains unknown. CO-degradation by leaf washes of two common British trees, Ilex aquifolium and Crataegus monogyna, demonstrated CO uptake in all samples investigated. Based on the analyses of taxonomic and functional genes, diverse communities of candidate CO-oxidizing taxa were identified, including members of Rhizobiales and Burkholderiales which were abundant in the phyllosphere at the time of sampling. Based on predicted genomes of phyllosphere community members, an estimated 21% of phyllosphere bacteria contained CoxL, the large subunit of CO-dehydrogenase. In support of this, data mining of publicly available phyllosphere metagenomes for genes encoding CO-dehydrogenase subunits demonstrated that, on average, 25% of phyllosphere bacteria contained CO-dehydrogenase gene homologues. A CO-oxidizing Phyllobacteriaceae strain was also isolated from phyllosphere samples which contains genes encoding both CO-dehydrogenase as well as a ribulose-1,5-bisphosphate carboxylase-oxygenase. These results suggest that the phyllosphere supports diverse and potentially abundant CO-oxidizing bacteria, which are a potential sink for atmospheric CO.

The Impact of Vitamin D on Response to Anti-tumor Necrosis Factor-α Therapy in Children With Inflammatory Bowel Disease.

OBJECTIVES: Experimental studies have shown that vitamin D has an immunomodulatory effect on the innate and adaptive immune systems. Associations between vitamin D deficiency and development or progression of inflammatory bowel diseases (IBDs) are reported, but a cause-and-effect relationship between pretreatment 25 hydroxyvitamin D [25(OH)D] levels and response to anti-tumor necrosis factor-α (anti-TNF) therapy is not established. METHODS: This retrospective study evaluated pediatric IBD patients who had 25(OH)D levels drawn within 3 months of initiating infliximab and/or adalimumab treatment. Demographic features, Paris classification, baseline 25(OH)D levels, disease activity, and laboratory results before and after 3 months of anti-TNF therapy were collected. The interaction between vitamin D insufficiency at induction and lack of response to anti-TNF therapy at 3 months was determined. RESULTS: Of the 383 patients, 76 met inclusion criteria. Sixty-five patients (85.5%) had Crohn disease (CD) and 11 (14.5%) had ulcerative colitis. Seven patients had 25(OH)D levels obtained during both infliximab and adalimumab induction; hence 83 subjects were evaluated (infliximab: 70 patients, adalimumab: 13 patients). 25(OH)D <30 ng/mL was found in 55 of 83 (66.3%) subjects. There were no differences in gender, IBD type, disease activity scores between vitamin D-sufficient and vitamin D-insufficient groups. In CD, proximal gastrointestinal tract inflammation was associated with vitamin D insufficiency (P = 0.019), but other Paris classification parameters and laboratory results were similar in 2 groups. Early termination of anti-TNF therapy was significantly higher in patients who had vitamin D insufficiency (14.5% vs 0%, P = 0.034). CONCLUSIONS: Vitamin D insufficiency before anti-TNF treatment may result in poor response to induction therapy.

Additional Intestinal Mucosal Biopsy Sampling for Research Is Safe During Pediatric Endoscopic Procedures.

Advancing the understanding of inflammatory bowel disease (IBD) pathogenesis has been facilitated by mechanistic studies that require human intestinal tissue. Enrolling pediatric subjects into these studies improves our knowledge of IBD in this underserved population. Given the additional research protections granted to children, institutional review boards (IRBs) must weigh the benefit of obtaining research biopsies against perceived risks. Although obtaining clinical biopsies from children is generally considered safe, there are only limited data on the safety of obtaining research biopsies in children.1-6.

Efficacy of Fecal Microbiota Transplantation for Clostridium difficile Infection in Children.

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI. METHODS: We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMT at 18 pediatric centers, from February 1, 2004, to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT. RESULTS: Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39-5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26-4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05-4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04-1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations. CONCLUSIONS: Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients-factors associated with success differ from those of adult patients.

Performance of Surveillance MR Enterography (MRE) in Asymptomatic Children and Adolescents With Crohn's Disease.

BACKGROUND: MR enterography (MRE) is the primary modality for evaluating small bowel disease in pediatric Crohn's patients. Standard clinical practice includes imaging patients at diagnosis and during symptomatic recurrence. The role for MRE in surveillance of asymptomatic Crohn's patients has not yet been established. PURPOSE: To determine whether MRE imaging features are associated with clinical recurrence. STUDY TYPE: Retrospective. POPULATIONS: Pediatric Crohn's patients who underwent MRE while asymptomatic, defined by pediatric gastroenterologists using a physician global assessment; 35 MREs were identified. FIELD STRENGTH/SEQUENCE: 1.5T including T2 -weighted single-shot fast spin echo, balanced steady-state free precession, diffusion-weighted, and contrast-enhanced multiphase T1 -weighted gradient recalled echo sequences. ASSESSMENT: MREs were reviewed by three radiologists independently for mural thickening, T2 -weighted hyperintensity, diffusion restriction, hyperenhancement, vasa recta engorgement, and overall assessment of disease activity. Two pediatric gastroenterologists reviewed patient medical records for 6 months following MRE to evaluate for recurrence, defined as Crohn's-related treatment escalation, surgery, or hospitalization. STATISTICAL TESTS: Fisher's exact test, Wald chi-square test, and model selection by Akaike information criterion minimization were used to assess statistical significance of MRE imaging features. RESULTS: Of 35 MREs identified, seven cases demonstrated clinical recurrence at 6 months (20%); 28 cases remained in remission (80%). Imaging features of active disease were present in 86% of patients with recurrence compared to 29% of patients in remission (P = 0.01). Wall thickening, T2 -weighted hyperintensity, hyperenhancement, and diffusion restriction were significantly associated with recurrence. Multivariate regression analysis determined diffusion restriction to be the best predictor of recurrence within 6 months (P = 0.001, area under the curve 0.786). DATA CONCLUSION: MRE performed on young asymptomatic Crohn's patients can identify patients who have a high probability of developing clinical recurrence in a 6-month period, indicating a potential role for surveillance imaging to assess for subclinical active disease. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage 5 J. Magn. Reson. Imaging 2019;50:1955-1963.

Serum Monitoring and Phenotype Identification of Stage I Non-Small Cell Lung Cancer Patients.

A stage I non-small cell lung cancer (NSCLC) serum profiling platform is presented which is highly efficient and accurate. Test sensitivity (0.95) for stage I NSCLC is the highest reported so far. Test metrics are reported for discriminating stage I adenocarcinoma vs squamous cell carcinoma subtypes. Blinded analysis identified 23 out of 24 stage I NSCLC and control serum samples. Group-discriminating mass peaks were targeted for tandem mass spectrometry peptide/protein identification, and yielded a lung cancer phenotype. Bioinformatic analysis revealed a novel lymphocyte adhesion pathway involved with early-stage lung cancer.

NASPGHAN Clinical Report on Postoperative Recurrence in Pediatric Crohn Disease.

Pediatric Crohn disease is characterized by clinical and endoscopic relapses. The inflammatory process is considered to be progressive and may lead to strictures, fistulas, and penetrating disease that may require surgery. In addition, medically refractory disease may be treated by surgical resection of inflamed bowel in an effort to reverse growth failure. The need for surgery in childhood suggests severe disease and these patients have an increased risk for recurrent disease and potentially more surgery. Data show that up to 55% of patients had clinical recurrence in the first 2 years after initial surgery. The current clinical report on postoperative recurrence in pediatric Crohn disease reviews the risk factors for early surgery and postoperative recurrence, operative risk factors for recurrence, and prevention and monitoring strategies for postoperative recurrence. We also propose an algorithm for postoperative management in pediatric Crohn disease.

Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection.

BACKGROUND: Fecal microbiota transplantation (FMT) has been shown to be safe and effective in treating refractory or relapsing C. difficile infection (CDI), but its use has been limited by practical barriers. We recently reported a small preliminary feasibility study using orally administered frozen fecal capsules. Following these early results, we now report our clinical experience in a large cohort with structured follow-up. METHODS: We prospectively followed a cohort of patients with recurrent or refractory CDI who were treated with frozen, encapsulated FMT at our institution. The primary endpoint was defined as clinical resolution whilst off antibiotics for CDI at 8 weeks after last capsule ingestion. Safety was defined as any FMT-related adverse event grade 2 or above. RESULTS: Overall, 180 patients aged 7-95 years with a minimal follow-up of 8 weeks were included in the analysis. CDI resolved in 82 % of patients after a single treatment, rising to a 91 % cure rate with two treatments. Three adverse events Grade 2 or above, deemed related or possibly related to FMT, were observed. CONCLUSIONS: We confirm the effectiveness and safety of oral administration of frozen encapsulated fecal material, prepared from unrelated donors, in treating recurrent CDI. Randomized studies and FMT registries are still needed to ascertain long-term safety.

MR Enterographic Findings as Biomarkers of Mucosal Healing in Young Patients With Crohn Disease.

OBJECTIVE: The purpose of this study was to investigate the MR enterographic findings that best correlate with mucosal healing assessed with ileocolonoscopy. MATERIALS AND METHODS: Patients with Crohn disease who underwent two ileocolonoscopic examinations and also underwent MR enterography close in time to the second endoscopic examination were included in a retrospective study. Two pediatric gastroenterologists blinded to the imaging findings reviewed the endoscopic examinations to assess for mucosal healing, defined as resolution of inflammation within a bowel segment at subsequent ileocolonoscopy. Two radiologists blinded to endoscopic and clinical data interpreted the MR enterographic images. Sensitivity, specificity, and accuracy for mucosal healing were calculated for several imaging features. RESULTS: A total of 30 patients (15 female patients, 15 male patients; age range, 8-24 years; mean, 17.2 ± 3.2 years) with pediatric-onset Crohn disease were examined. The average time between MR enterography and the second ileocolonoscopic examination was 12.7 ± 7.9 days. A total of 202 bowel segments from the terminal ileum to rectum were evaluated in the 60 ileocolonoscopic examinations. Forty-four bowel segments exhibited mucosal healing, and 37 segments exhibited persistent inflammation. At imaging, the MR index of activity score in mucosal healing segments was 6.6 ± 3.4, compared with 13.7 ± 9.7 in segments without mucosal healing (p = 0.0001). The average bowel wall thickness in healing segments was 2.7 ± 0.9 mm compared with 4.7 ± 3.1 mm in persistently inflamed segments (p = 0.0004). An MR index of activity score less than 8 had the highest accuracy for mucosal healing (accuracy, 74%; sensitivity, 84%; specificity, 62%; p < 0.0001). Mucosal hyperenhancement (72%, 98%, 41%), mesenteric hypervascularity (72%, 98%, 41%), bowel wall edema (72%, 93%, 46%), and bowel wall thickness less than 4 mm (72%, 84%, 57%) were also strongly associated with mucosal healing (p < 0.0003). CONCLUSION: In this study MR enterography was accurate for assessing mucosal healing, an important therapeutic endpoint in pediatric patients with Crohn disease.

CT and MRI of Rare Extraintestinal Manifestations of Inflammatory Bowel Disease in Children and Adolescents.

Inflammatory bowel disease (IBD) is associated with a spectrum of extraintestinal manifestations (EIMs) affecting many organ systems. EIMs can occur in more than 40% of patients with IBD and are associated with significant morbidity. They occur at any time point in the course of disease, often during an active phase of bowel inflammation, but sometimes preceding bowel disease. Prompt recognition of EIMs enables timely and more effective therapy. Physicians who image patients with IBD should be aware of the myriad extraintestinal conditions that may be detected on imaging studies, both within and outside of the abdomen, as they may predate the diagnosis of IBD. Cross-sectional imaging of unusual conditions associated with IBD will be presented, including pathology in the hepatobiliary, pancreatic, genitourinary, musculoskeletal, mucocutaneous, vascular, neurologic, and pulmonary systems.