Orthotopic liver transplant for multifocal lymphangioendotheliomatosis with thrombocytopenia.

An eight-yr-old female with a history of multifocal lymphangioendotheliomatosis and thrombocytopenia presented for MVT. The patient had multiple vascular lesions in the skin and stomach in infancy. Although her cutaneous lesions resolved with vincristine and methylprednisolone, her gastric lesions persisted. Eight yr later, she was diagnosed with portal hypertension and decompensating liver function despite therapy with bevacizumab, propranolol, furosemide, and spironolactone. Upon presentation, she was found to have a Kasabach-Merritt-like coagulopathy in association with multiple lesions in her GI tract and persistent gastric lesions. Although treatment with methylprednisolone and sirolimus normalized her coagulation factors and d-dimer levels, she never developed sustained improvement in her thrombocytopenia. Her liver function continued to deteriorate and she developed hepatorenal syndrome. Given better outcomes after OLT in comparison with MVT, she underwent OLT, with the plan to manage her GI lesions with APC post-transplant. Post-transplant, her liver function and coagulopathy normalized, and GI tract lesions disappeared upon screening with capsule endoscopy. The patient is doing well, without recurrence of either GI lesions or thrombocytopenia, at 18 months after transplantation.

Exome sequencing finds a novel PCSK1 mutation in a child with generalized malabsorptive diarrhea and diabetes insipidus.

OBJECTIVES: Congenital diarrhea disorders are a group of genetically diverse and typically autosomal recessive disorders that have yet to be well characterized phenotypically or molecularly. Diagnostic assessments are generally limited to nutritional challenges and histologic evaluation, and many subjects eventually require a prolonged course of intravenous nutrition. Here we describe next-generation sequencing techniques to investigate a child with perplexing congenital malabsorptive diarrhea and other presumably unrelated clinical problems; this method provides an alternative approach to molecular diagnosis. METHODS: We screened the diploid genome of an affected individual, using exome sequencing, for uncommon variants that have observed protein-coding consequences. We assessed the functional activity of the mutant protein, as well as its lack of expression using immunohistochemistry. RESULTS: Among several rare variants detected was a homozygous nonsense mutation in the catalytic domain of the proprotein convertase subtilisin/kexin type 1 gene. The mutation abolishes prohormone convertase 1/3 endoprotease activity as well as expression in the intestine. These primary genetic findings prompted a careful endocrine reevaluation of the child at 4.5 years of age, and multiple significant problems were subsequently identified consistent with the known phenotypic consequences of proprotein convertase subtilisin/kexin type 1 (PCSK1) gene mutations. Based on the molecular diagnosis, alternate medical and dietary management was implemented for diabetes insipidus, polyphagia, and micropenis. CONCLUSIONS: Whole-exome sequencing provides a powerful diagnostic tool to clinicians managing rare genetic disorders with multiple perplexing clinical manifestations.

Implementing a Novel Quality Improvement-Based Approach to Data Quality Monitoring and Enhancement in a Multipurpose Clinical Registry.

OBJECTIVE: To implement a quality improvement based system to measure and improve data quality in an observational clinical registry to support a Learning Healthcare System. DATA SOURCE: ImproveCareNow Network registry, which as of September 2019 contained data from 314,250 visits of 43,305 pediatric Inflammatory Bowel Disease (IBD) patients at 109 participating care centers. STUDY DESIGN: The impact of data quality improvement support to care centers was evaluated using statistical process control methodology. Data quality measures were defined, performance feedback of those measures using statistical process control charts was implemented, and reports that identified data items not following data quality checks were developed to enable centers to monitor and improve the quality of their data. PRINCIPAL FINDINGS: There was a pattern of improvement across measures of data quality. The proportion of visits with complete critical data increased from 72 percent to 82 percent. The percent of registered patients improved from 59 percent to 83 percent. Of three additional measures of data consistency and timeliness, one improved performance from 42 percent to 63 percent. Performance declined on one measure due to changes in network documentation practices and maturation. There was variation among care centers in data quality. CONCLUSIONS: A quality improvement based approach to data quality monitoring and improvement is feasible and effective.

Endoscopic subfascial perforator vein surgery for patients with severe, chronic venous insufficiency.

Before 1985, surgery on incompetent perforator veins in patients with severe, chronic, venous insufficiency and venous ulcerations was generally performed utilizing long skin incisions through diseased skin and subcutaneous tissues. Known as "the Linton operation," wound infections and poor healing complicated this procedure. In 1985 G. Hauer demonstrated a new surgical technique for identifying and ligating incompetent perforator veins using an endoscopic approach in the limbs' subfascial space. This seminal contribution marked the advent of subfascial endoscopic perforator surgery (SEPS). From 1996 to 2003 our group prospectively collected data on 86 patients with chronic venous insufficiency (CVI) who underwent a SEPS procedure. Preoperative assessment consisted of color-flow duplex ultrasound scanning and ascending and descending phlebography. The patient's ages ranged from 42 to 82 years (mean 60). A total of 98 limbs underwent the SEPS procedure from the cohort group of 86 patients. The CHEAP classification of the limb disease was used: 45 limbs were classified as group C5, 53 limbs group C6. Ninety-eight SEPS procedures were performed without significant morbidity on 86 patients. Of the 53 limbs in class C6, 41 had ulcer healing within 12 weeks. The remaining 12 limbs in class C6 had ulcer healing within 6 months. In this latter group, 9 had ulcers greater than 4 cm in widest diameter. These patients underwent a split-thickness skin graft at the time the SEPS procedure was performed. The grafts have remained intact after 2 years in this cohort group. The results of this study demonstrate that the SEPS procedure incorporated into the overall treatment plan for patients with CVI produces excellent healing with minimal postoperative complications. The study also underscores the important role incompetent perforator veins have in the formation of venous ulcers.

Effectiveness of anti-TNFα for Crohn disease: research in a pediatric learning health system.

OBJECTIVES: ImproveCareNow (ICN) is the largest pediatric learning health system in the nation and started as a quality improvement collaborative. To test the feasibility and validity of using ICN data for clinical research, we evaluated the effectiveness of anti-tumor necrosis factor-α (anti-TNFα) agents in the management of pediatric Crohn disease (CD). METHODS: Data were collected in 35 pediatric gastroenterology practices (April 2007 to March 2012) and analyzed as a sequence of nonrandomized trials. Patients who had moderate to severe CD were classified as initiators or non-initiators of anti-TNFα therapy. Among 4130 patients who had pediatric CD, 603 were new users and 1211 were receiving anti-TNFα therapy on entry into ICN. RESULTS: During a 26-week follow-up period, rate ratios obtained from Cox proportional hazards models, adjusting for patient and disease characteristics and concurrent medications, were 1.53 (95% confidence interval [CI], 1.20-1.96) for clinical remission and 1.74 (95% CI, 1.33-2.29) for corticosteroid-free remission. The rate ratio for corticosteroid-free remission was comparable to the estimate produced by the adult SONIC study, which was a randomized controlled trial on the efficacy of anti-TNFα therapy. The number needed to treat was 5.2 (95% CI, 3.4-11.1) for clinical remission and 5.0 (95% CI, 3.4-10.0) for corticosteroid-free remission. CONCLUSIONS: In routine pediatric gastroenterology practice settings, anti-TNFα therapy was effective at achieving clinical and corticosteroid-free remission for patients who had Crohn disease. Using data from the ICN learning health system for the purpose of observational research is feasible and produces valuable new knowledge.

Prevalence and epidemiology of overweight and obesity in children with inflammatory bowel disease.

BACKGROUND: Obesity is a significant public health threat to children in the United States. The aims were to: 1) Determine the prevalence of obesity in a multicenter cohort of children with inflammatory bowel disease (IBD); 2) Evaluate whether overweight and obese status is associated with patient demographics or disease characteristics. METHODS: We used data from the ImproveCareNow Collaborative for pediatric IBD, a multicenter registry of children with IBD, collected between April 2007 and December 2009. Children ages 2-18 years were classified into body mass index (BMI) percentiles. Bivariate analyses and multivariate logistic regression were used to compare demographic and disease characteristics by overweight (BMI >85%) and obese (BMI >95%) status. RESULTS: The population consisted of 1598 children with IBD. The prevalence of overweight/obese status in pediatric IBD is 23.6%, (20.0% for Crohn's disease [CD] and 30.1% for ulcerative colitis [UC] and indeterminate colitis [IC]). African American race (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.10-2.48) and Medicaid insurance (OR 1.67, 95% CI 1.19-2.34) were positively associated with overweight/obese status. Prior IBD-related surgery (OR 1.73, 95% CI 1.07-2.82) was also associated with overweight and obese status in children with CD. Other disease characteristics were not associated with overweight and obesity in children with IBD. CONCLUSIONS: Approximately one in five children with CD and one in three with UC are overweight or obese. Rates of obesity in UC are comparable to the general population. Obese IBD patients may have a more severe disease course, as indicated by increased need for surgery. Sociodemographic risk factors for obesity in the IBD population are similar to those in the general population.

ImproveCareNow: The development of a pediatric inflammatory bowel disease improvement network.

UNLABELLED: There is significant variation in diagnostic testing and treatment for inflammatory bowel disease. Quality improvement science methods can help address unwarranted variations in care and outcomes. METHODS: The ImproveCareNow Network was established under the sponsorship of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the American Board of Pediatrics as a prototype for a model of improving subspecialty care that included three components: 1) creating enduring multicenter collaborative networks of pediatric subspecialists, 2) sharing of performance data collected in patient registries, and 3) training in quality improvement. The network began with a focus on improving initial diagnostic testing and evaluation, the classification of the severity and extent of disease, the detection and treatment of inadequate nutrition and growth, and the appropriate dosing of immunomodulator medications. Changes are based on an evidence-based model of chronic illness care involving the use of patient registries for population management, previsit planning, decision support, promoting self-management, and auditing of care processes. RESULTS: Currently, patients are being enrolled at 23 sites. Through 2009, data have been analyzed on over 2500 patients from over 7500 visits. Initial results suggest improvements in both care processes (e.g., appropriate medication dosing and completion of a classification bundle that includes the patient's diagnosis, disease activity, distribution and phenotype, growth status, and nutrition status) and outcomes (e.g., the percentage of patients in remission). CONCLUSIONS: These improvements suggest that practice sites are learning how to apply quality improvement methods to improve the care of patients.

Correction of celiac disease after allogeneic hematopoietic stem cell transplantation for acute myelogenous leukemia.

Allogeneic hematopoietic stem cell transplantation has been shown to correct or improve a variety of autoimmune disorders. This has not been reported for celiac disease, but transmission to a hematopoietic stem cell transplantation recipient from a donor with celiac disease has been reported. We report a 12-year-old girl with celiac disease who was diagnosed with acute leukemia and received an allogeneic hematopoietic stem cell transplant. Her celiac disease resolved after the hematopoietic stem cell transplant.

Multifocal lymphangioendotheliomatosis with thrombocytopenia: a rare cause of gastrointestinal bleeding in the newborn period.

Severe gastrointestinal bleeding in the newborn period is a serious but uncommon phenomenon that has a broad differential diagnosis. In the following case report we describe a rare phenomenon in which a newborn presents with severe hematemesis, hematochezia, and thrombocytopenia that are resistant to repeated platelet and packed red blood cell transfusions. Previous cases have been reported, but none of the patients described presented within the first 8 days of life. The early age of presentation and refractory nature of this disease entity to multiple therapies make it a diagnostic and therapeutic dilemma for all physicians involved in the care of newborns.