Recent advances in the early treatment of cystic fibrosis: Bridging the gap to highly effective modulator therapy.

Highly effective modulator therapy (HEMT) for cystic fibrosis (CF) has been touted as one of the greatest advances to date in CF care. As these therapies are now available for many older children and adults with CF, marked improvement of their nutritional status, pulmonary and gastrointestinal symptoms has been observed. However, most infants and younger children are not current candidates for HEMT due to age and/or cystic fibrosis transmembrane conductance regulator (CFTR) mutation. For these young children, it is essential to provide rigorous monitoring and care to avoid potential disease sequelae while awaiting HEMT availability. The following article highlights recent advances in the care of infants and young children with CF with regard to surveillance and treatment of nutritional, pulmonary, and gastrointestinal disorders. Recent clinical trials in this population are also reviewed.

Delayed Presentation of Meconium Ileus in an Infant With Cystic Fibrosis.

Although infants with meconium ileus usually present with apparent symptoms shortly after birth, the diagnosis of meconium ileus and cystic fibrosis (CF) may be delayed, awaiting newborn screening (NBS) results. We present the case of an 11-day-old term girl with delayed passage of meconium at 48 hours who had 2 subsequent small meconium stools over the following week. There was a normal feeding history and no signs of abdominal distension or distress. She then presented with an acute abdomen, decompensated shock, bowel perforation, and peritonitis, requiring multiple intestinal surgeries. Her NBS for CF was positive, and CF was ultimately confirmed with mutation analysis. Her course was complicated by prolonged parenteral feedings and mechanical ventilation via tracheostomy. The infant was managed with soy oil, medium chain triglycerides, olive oil, fish oil lipids and experienced only transaminitis without cholestasis and no chronic liver sequelae, with subsequent normalization of her transaminases without treatment. Because her only symptom was decreased stool output and NBS results were unavailable, the CF diagnosis was delayed until she presented in extremis. Delayed meconium passage and decreased stool output during the first week of life should lead to suspicion and additional evaluation for CF while awaiting NBS results. Careful monitoring is indicated to prevent serious, life-threatening complications. The use of soy oil, medium chain triglycerides, olive oil, fish oil lipids for infants requiring prolonged parenteral nutrition may also be considered proactively to prevent cholestasis, particularly for high risk groups.

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.

Nutrition: Prevention and management of nutritional failure in Cystic Fibrosis.

Close monitoring of nutritional status is critical to the overall health of a patient with CF. As part of routine CF care, measurement of weight and height (and calculation of weight/length or BMI as appropriate) should be performed and analyzed at each visit. Early recognition of nutritional risk is imperative and evaluation with a multidisciplinary team should be performed to assess for caloric intake, caloric malabsorption, and other causes of poor weight gain and growth. Many tools are available to use for intervention, including oral supplementation, behavioral interventions, medications, nutritional therapies, and enteral tube feeding.

Obstructive sleep apnea and hypoxemia are associated with advanced liver histology in pediatric nonalcoholic fatty liver disease.

OBJECTIVE: To determine whether obstructive sleep apnea (OSA) and/or nocturnal hypoxemia are associated with the severity of liver injury in patients with pediatric nonalcoholic fatty liver disease (NAFLD). STUDY DESIGN: Obese children aged 10-18 years with liver biopsy-proven NAFLD were enrolled. Demographic, clinical, and laboratory data were collected, polysomnography was performed, and liver histology was scored. Subjects were divided into those with OSA/hypoxemia and those without OSA/hypoxemia for analysis. RESULTS: Of 25 subjects with NAFLD, OSA/hypoxemia was present in 15 (60%) (mean age, 12.8 ± 1.9 years; 68% male; 88% Hispanic; mean body mass index z-score, 2.3 ± 0.3). Subjects with and without OSA/hypoxemia had similar levels of serum aminotransferases, serum lipids, and inflammatory and insulin resistance markers. Although there were no differences between groups in the histological severity of steatosis, inflammation, ballooning degeneration, NAFLD activity score, or histological grade, subjects with OSA/hypoxemia had significantly more severe hepatic fibrosis. Moreover, oxygen saturation nadir during polysomnography was related to hepatic fibrosis stage (r = -0.49; P = .01) and aspartate aminotransferase level (r = 0.42; P < .05). Increasing percentage of time with oxygen saturation ≤90% was related to NAFLD inflammation grade (r = 0.44; P = .03), degree of hepatic steatosis (r = -0.50; P = .01), NAFLD activity score (r = 0.42; P = .04), aspartate aminotransferase level (r = 0.56; P = .004), and alanine aminotransferase level (r = 0.44; P = .03). CONCLUSION: Moderate OSA/hypoxemia is common in pediatric patients with biopsy-proven NAFLD. OSA and the severity/duration of hypoxemia are associated with biochemical and histological measures of NAFLD severity.

Parenteral nutrition supplementation in biliary atresia patients listed for liver transplantation.

The objective of this study was to determine the impact of parenteral nutrition (PN) on the outcomes of biliary atresia (BA) patients listed for liver transplantation (LT). We retrospectively reviewed the charts of all BA patients at our institution who underwent hepatoportoenterostomy and were listed for LT before the age of 36 months between 1990 and 2010. The initiation of PN was based on clinical indications. Twenty-five PN subjects and 22 non-PN subjects (74% female) were studied. The median PN initiation age was 7.7 months, the mean duration was 86 days, and the mean amount of energy supplied by PN was 77 kcal/kg/day. Before PN, the triceps skinfold thickness (TSF) and the mid-arm circumference (MAC) z scores were decreasing. After PN, TSF (P < 0.001) and MAC (P < 0.001) improved significantly. The PN group had lower MAC and TSF scores than the non-PN group at the time of LT listing. Between listing and LT, MAC and TSF improved in the PN group and worsened in the non-PN groups; as a result, the 2 groups had the same z scores at LT. The PN group had a higher incidence of gastrointestinal bleeding and ascites before LT, but there were no differences in the rates of pre-LT bacteremia, days in the intensive care unit after LT, or patient or graft survival. In conclusion, PN improves the nutritional status of malnourished BA patients awaiting LT, and this is associated with post-LT outcomes comparable to those of patients not requiring PN.