Trametinib for Refractory Chylous Effusions and Systemic Complications in Children with Noonan Syndrome.

OBJECTIVE: To evaluate the effect of the RAS-MAPK pathway inhibitor trametinib on medically refractory chylous effusions in 3 hospitalized patients with Noonan syndrome. STUDY DESIGN: Pharmacologic MEK1/2 inhibition has been used to treat conditions associated with Noonan syndrome, given that activation of RAS-MAPK pathway variants leads to downstream MEK activation. We describe our experience with 3 patients with Noonan syndrome (owing to variants in 3 distinct genes) and refractory chylous effusions treated successfully with MEK inhibition. A monitoring protocol was established to standardize medication dosing and monitoring of outcome measures. RESULTS: Subjects demonstrated improvement in lymphatic leak with additional findings of improved growth and normalization of cardiac and hematologic measurements. Trametinib was administered safely, with only moderate skin irritation in 1 subject. CONCLUSIONS: Improvements in a variety of quantifiable measurements highlight the potential utility of MEK1/2 inhibition in patients with Noonan syndrome and life-threatening lymphatic disease. Larger, prospective studies are needed to confirm efficacy and assess long-term safety.

How we approach pediatric congenital chylous effusions and ascites.

Congenital lymphatic leak may develop in patients with maldeveloped lymphatics and result in life-threatening fluid and electrolyte imbalance, protein deficiency, and immunodeficiency. Rapid diagnosis and therapy are necessary to prevent these complications; however, the field lacks clinical trials to support standardized diagnostic treatment guidelines. We present our current multidisciplinary approach to the diagnosis and management of congenital lymphatic leak including chylous pleural effusions and ascites. Depending on the rate of lymphatic leak, therapy can range from observation with nutritional modifications to surgical and interventional procedures aimed to reduce lymphatic drainage. Modalities to image central and peripheral lymphatics have advanced considerably. Genetic variants and subsequent targets that drive lymphatic maldevelopment have expanded the repertoire of possible pharmacotherapeutic options.

The benefits of limiting scheduled blood draws in children with a blunt liver or spleen injury.

BACKGROUND: Nonoperative management protocols of blunt liver and spleen injury in children usually call for serial monitoring of the child's hemoglobin and hematocrit (H/H) at scheduled intervals. We previously demonstrated that the need for emergent intervention is triggered by changes in vital signs, not the findings of scheduled blood draws and changed our protocol accordingly. The current aim is to evaluate the safety of this change. METHODS: We performed a retrospective review of all children admitted following blunt liver or spleen injury during two periods; the historic cohort 1/09-12/13 and the protocol cohort 8/15-7/17. Data evaluated included the need for intervention, number of H/H checks, and outcomes. RESULTS: 330 children were included (216 historic; 114 protocol). Groups did not differ in percentage of male patients, injury severity score, or GCS. Median age in the historic cohort was younger than the protocol cohort (9 vs 12 years; p = 0.02). More children in the protocol group had a grade 5 injury (1% vs 9%; p < 0.0001). Groups did not differ in the number who required intervention or discharge disposition (including mortality). The protocol group had fewer H/H checks (median 5 vs 4, p < 0.0001); the two groups did not differ in their nadir H/H. The historic group had a longer median hospital length of stay (3 days vs 2, p = 0.0007). CONCLUSIONS: Decreasing the number of scheduled blood draws following a blunt liver or spleen injury in children is safe. Additional benefits include a decrease in the number of blood draws and a decrease in length of hospital stay. STUDY TYPE: Cost-effectiveness. LEVEL OF EVIDENCE: Level III.

Pediatric appendicitis: Is referral to a regional pediatric center necessary?

BACKGROUND: Acute appendicitis is the most common emergent surgical procedure performed among children in the United States, with an incidence exceeding 80,000 cases per year. Appendectomies are often performed by both pediatric surgeons and adult general/trauma and acute care (TACS) surgeons. We hypothesized that children undergoing appendectomy for acute appendicitis have equivalent outcomes whether a pediatric surgeon or a TACS surgeon performs the operation. METHODS: A retrospective chart review was performed for patients 6 to 18 years of age, who underwent appendectomy at either a regional children's hospital (Children's Hospital of Colorado [CHCO], n = 241) or an urban safety-net hospital (n = 347) between July 2010 and June 2015. The population of patients operated on at the urban safety-net hospital was further subdivided into those operated on by pediatric surgeons (Denver Health Medical Center [DHMC] pediatric surgeons, n = 68) and those operated on by adult TACS surgeons (DHMC TACS, n = 279). Baseline characteristics and operative outcomes were compared between these patient populations utilizing one-way analysis of variance and χ test for independence. RESULTS: When comparing the CHCO and DHMC TACS groups, there were no differences in the proportion of patients with perforated appendicitis, operative time, rate of operative complications, rate of postoperative infectious complications, or rate of 30-day readmission. Length of stay was significantly shorter for the DHMC TACS group than that for the CHCO group. CONCLUSIONS: Our data demonstrate that among children older than 5 years undergoing appendectomy, length of stay, risk of infectious complications, and risk of readmission do not differ regardless of whether they are operated on by pediatric surgeons or adult TACS surgeons, suggesting resources currently consumed by transferring children to hospitals with access to pediatric surgeons could be allocated elsewhere. LEVEL OF EVIDENCE: Therapeutic/Care management, level III.

Rapid Response Team Activations in Pediatric Surgical Patients.

Introduction The rapid response team (RRT) is a multidisciplinary team who evaluates hospitalized patients for concerns of nonemergent clinical deterioration. RRT evaluations are mandatory for children whose Pediatric Early Warning System (PEWS) score (assessment of child's behavior, cardiovascular and respiratory status) is ≥4. We aimed to determine if there were differences in characteristics of RRT calls between children who were admitted primarily to either medical or surgical services. We hypothesized that RRT activations would be called for less severely ill children with lower PEWS score on surgical services compared with children admitted to a medical service. Materials and Methods We performed a retrospective review of all children with RRT activations between January 2008 and April 2015 at a tertiary care pediatric hospital. We evaluated the characteristics of RRT calls and made comparisons between RRT calls made for children admitted primarily to medical or surgical services. Results A total of 2,991 RRT activations were called, and 324 (11%) involved surgical patients. Surgical patients were older than medical patients (median: 7 vs. 4 years; p < 0.001). RRT evaluations were called for lower PEWS score in surgical patients compared with medical (median: 3 vs. 4, p < 0.001). Surgical patients were more likely to remain on the inpatient ward following the RRT (51 vs. 39%, p < 0.001) and were less likely to require an advanced airway than medical patients (0.9 vs. 2.1%; p = 0.412). RRT evaluations did not differ between day and night shifts (52% day vs. 48% night; p = 0.17). All surgical patients and all but one medical patient survived the event; surgical patients were more likely to survive to hospital discharge (97 vs. 91%, p < 0.001) Conclusions RRT activations are rare events among pediatric surgical patients. When compared with medical patients, RRT evaluation is requested for surgical patients with a lower PEWS score and these children are less likely to require transfer to a higher level of care, suggesting that pediatric surgery team, families, and nursing staff may not be as comfortable with clinical deterioration.