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Browsing by Author "Griffiths, Anne"
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Item A multi-disciplinary, comprehensive approach to management of children with heterotaxy(BMC, 2022-09-09) Saba, Thomas G.; Geddes, Gabrielle C.; Ware, Stephanie M.; Schidlow, David N.; del Nido, Pedro J.; Rubalcava, Nathan S.; Gadepalli, Samir K.; Stillwell, Terri; Griffiths, Anne; Bennett Murphy, Laura M.; Barber, Andrew T.; Leigh, Margaret W.; Sabin, Necia; Shapiro, Adam J.; Medical and Molecular Genetics, School of MedicineHeterotaxy (HTX) is a rare condition of abnormal thoraco-abdominal organ arrangement across the left-right axis of the body. The pathogenesis of HTX includes a derangement of the complex signaling at the left-right organizer early in embryogenesis involving motile and non-motile cilia. It can be inherited as a single-gene disorder, a phenotypic feature of a known genetic syndrome or without any clear genetic etiology. Most patients with HTX have complex cardiovascular malformations requiring surgical intervention. Surgical risks are relatively high due to several serious comorbidities often seen in patients with HTX. Asplenia or functional hyposplenism significantly increase the risk for sepsis and therefore require antimicrobial prophylaxis and immediate medical attention with fever. Intestinal rotation abnormalities are common among patients with HTX, although volvulus is rare and surgical correction carries substantial risk. While routine screening for intestinal malrotation is not recommended, providers and families should promptly address symptoms concerning for volvulus and biliary atresia, another serious morbidity more common among patients with HTX. Many patients with HTX have chronic lung disease and should be screened for primary ciliary dyskinesia, a condition of respiratory cilia impairment leading to bronchiectasis. Mental health and neurodevelopmental conditions need to be carefully considered among this population of patients living with a substantial medical burden. Optimal care of children with HTX requires a cohesive team of primary care providers and experienced subspecialists collaborating to provide compassionate, standardized and evidence-based care. In this statement, subspecialty experts experienced in HTX care and research collaborated to provide expert- and evidence-based suggestions addressing the numerous medical issues affecting children living with HTX.Item Analysis of Using the Total White Blood Cell Count to Define Severe New-onset Ulcerative Colitis in Children(Wolters Kluwer, 2020-09) Mack, David R.; Saul, Bradley; Boyle, Brendan; Griffiths, Anne; Sauer, Cary; Markowitz, James; LeLeiko, Neal; Keljo, David; Rosh, Joel R.; Baker, Susan S.; Steiner, Steve; Heyman, Melvin B.; Patel, Ashish S.; Baldassano, Robert; Noe, Joshua; Rufo, Paul; Kugathasan, Subra; Walters, Thomas; Marquis, Alison; Thomas, Sonia M.; Denson, Lee; Hyams, Jeffrey; Pediatrics, School of MedicineObjectives: The aim of this study was to assess common laboratory tests in identifying severe ulcerative colitis in children at diagnosis. Methods: A cohort of 427 children 4 to 17 years of age newly diagnosed with ulcerative colitis (UC) was prospectively enrolled. Boosted classification trees were used to characterize predictive ability of disease attributes based on clinical disease severity using Pediatric Ulcerative Colitis Activity Index (PUCAI), severe (65+) versus not severe (<65) and total Mayo score, severe (10-12) versus not severe (<10); mucosal disease by Mayo endoscopic subscore, severe (3) versus not severe (<3); and extensive disease versus not extensive (left-sided and proctosigmoiditis). Results: Mean age was 12.7 years; 49.6% (n = 212) were girls, and 83% (n = 351) were Caucasian. Severe total Mayo score was present in 28% (n = 120), mean PUCAI score was 49.8 ± 20.1, and 33% (n = 142) had severe mucosal disease with extensive involvement in 82% (n = 353). Classification and regression trees identified white blood cell count, erythrocyte sedimentation rate, and platelet count (PLT) as the set of 3 best blood laboratory tests to predict disease extent and severity. For mucosal severity, albumin (Alb) replaced PLT. Classification models for PUCAI and total Mayo provided sensitivity of at least 0.65 using standard clinical cut-points with misclassification rates of approximately 30%. Conclusions: A combination of the white blood cell count, erythrocyte sedimentation rate, and either PLT or albumin is the best predictive subset of standard laboratory tests to identify severe from nonsevere clinical or mucosal disease at diagnosis in relation to objective clinical scores.Item Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course(Elsevier, 2018-10-10) Schirmer, Melanie; Denson, Lee; Vlamakis, Hera; Franzosa, Eric A.; Thomas, Sonia; Gotman, Nathan M.; Rufo, Paul; Baker, Susan S.; Sauer, Cary; Markowitz, James; Pfefferkorn, Marian; Oliva-Hemker, Maria; Rosh, Joel; Otley, Anthony; Boyle, Brendan; Mack, David; Baldassano, Robert; Keljo, David; LeLeiko, Neal; Heyman, Melvin; Griffiths, Anne; Patel, Ashish S.; Noe, Joshua; Kugathasan, Subra; Walters, Thomas; Huttenhower, Curtis; Hyams, Jeffrey; Xavier, Ramnik J.; Medicine, School of MedicineEvaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for 1 year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies. Depletion of core gut microbes and expansion of bacteria typical of the oral cavity were associated with baseline disease severity. Remission and refractory disease were linked to species-specific temporal changes that may be implicative of therapy efficacy, and a pronounced increase in microbiome variability was observed prior to colectomy. Finally, microbial associations with disease-associated serological markers suggest host-microbial interactions in UC. These insights will help improve existing treatments and develop therapeutic approaches guiding optimal medical care