Noonan syndrome is a genetic disorder caused by mutations in the RAS/MAPK pathway. Multiple giant cell lesions are a rare sequelae of disruptions in this pathway, termed Noonan-like multiple giant cell lesions (NL/MGCLs). Medical management of these tumors rather than surgical intervention is preferential as the lesions are benign but locally destructive and recurring. This case series describes four male pediatric patients with Noonan syndrome and multiple giant cell lesions of the jaw treated with denosumab, a monoclonal antibody to receptor activator of nuclear factor kappa B ligand (RANKL), which has been approved for the treatment of malignant giant cell tumors in adults but not evaluated for safety or efficacy in children. All four pediatric patients responded clinically and radiographically to the treatment. Adverse events occurred in a predictable pattern and included hypocalcemia and joint pain during the initiation of treatment and symptomatic hypercalcemia after the cessation of treatment. Growth was not significantly impaired in these skeletally immature patients. This case series demonstrates how a weight-adjusted denosumab dose can effectively treat NL/MGCLs and provides laboratory data for consideration of the timing of monitoring for known side effects.

BACKGROUND:The ability to rapidly and precisely evaluate patients in respiratory distress is essential. Due to limited opportunities for formal instruction during training, textbooks are the main educational source to teach junior physicians how to interpret the signs of respiratory distress. The quality of the textbook content relevant to respiratory distress is unknown. OBJECTIVE: To examine the content on the evaluation of a patient in respiratory distress in a representative sample of textbooks and Internet resources. METHODS: Two physicians individually reviewed the most recent edition of 21 standard textbooks from a variety of specialties. Smartphone applications, UptoDate, and MD Consult were examined. Each physician reviewed the source for 14 different signs. For each sign, the reviewers determined 3 parameters: a mention of the sign, its pathophysiology, and its detection. The reviews were compared for discrepancies, and a third reviewer resolved them. RESULTS: The normal respiratory rate was mentioned in 10 (48%) of textbooks, and ranged between 10 and 22 breaths/min. Each sign was mentioned by a mean of 45 ؎ 26% of the textbooks. The pathophysiology of the signs was described by a mean of 33 ؎ 30% of the textbooks. The most and least commonly mentioned inspection signs were cyanosis and retraction of suprasternal notch, respectively. They were mentioned in 20 (95%) and 4 (19%) textbooks, respectively. The most and least commonly mentioned palpation signs were thoracoabdominal asynchrony or paradox and tracheal tug, respectively. They were mentioned in 17 (81%) and 4 (19%) textbooks, and their pathophysiology was described in 15 (71%) and 4 (19%) textbooks, respectively. The reviewers also found inconsistency in the descriptions of the meaning of scalene muscle contraction and thoracoabdominal asynchrony and paradox. CONCLUSIONS: The content of the reviewed textbooks on the evaluation of respiratory distress is inconsistent and deficient.

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