Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies-Insights From a Retrospective Case Series.

Background: Despite recent developments, the role of sirolimus in the heterogeneous spectrum of vascular anomalies is yet to be defined, in terms of indication, dosage, and therapy duration, recognizing both its potential and limitations. Methods: We retrospectively analyzed 16 children with vascular anomalies treated with sirolimus in two pediatric centers between 2014 and 2020 [male: n = 7, the median age at diagnosis: 4.6 months (range, 0-281.4)]. In addition, repetitive volumetric analyses of the vascular anomalies were performed when possible (11 cases). Results: Ten patients were diagnosed with vascular malformations and 6 with vascular tumors. The mean therapy duration was 27.2 months (range, 3.5-65). The mean sirolimus level was 8.52 ng/ml (range, 5.38-12.88). All patients except one with central conducting lymphatic anomaly responded to sirolimus, with the most noticeable volume reduction in the first 4-6 months. Additional administration of vincristine was needed in five patients with kaposiform hemangioendothelioma and yielded a response, even in cases, refractory to sirolimus monotherapy. As a single agent, sirolimus led to impressive improvement in a patient with another vascular tumor-advanced epithelioid hemangioendothelioma. Complicated vascular malformations required long-term sirolimus therapy. Side effects of sirolimus included mucositis and laboratory abnormalities. No major infectious episodes were recorded. An infant with COVID-19, diagnosed while on sirolimus therapy, presented with a mild course. Conclusion: In the current series, we reported limitations of sirolimus as monotherapy, addressing the need to redefine its indications, and explore combination regimens and multimodal treatment strategies. Tools for objective evaluation of response trends over time could serve as a basis for the establishment of future therapeutic algorithms.

Does bronchodilator responsiveness in infants with bronchiolitis depend on age?

OBJECTIVE: To assess the relation between age and bronchodilator responsiveness in infants with bronchiolitis. STUDY DESIGN: In 41 infants (age, 2 to 18 months) with bronchiolitis, lung function was measured with the raised volume rapid thoracoabdominal compression technique before and after salbutamol inhalation. Lung function was quantified in terms of timed volumes (FEV(0.5), FEV(0.75), and FEV(1.0)). A significant change was defined as a postbronchodilator value that differed from baseline by more than twice the within-subject coefficient of variation. RESULTS: For the group, postbronchodilator values did not differ significantly from baseline (DeltaFEV(0.5), 3.8% +/- 9.3%; DeltaFEV(0.75), 3.5% +/- 9.5%; and DeltaFEV(1.0), 4.0 +/- 9.8%). Eleven subjects showed significantly increased timed volumes; 3 presented with a decreased lung function; the remaining patients failed to show a significant change. The mean age of subjects with improved lung function did not differ significantly from the mean age of those with no or paradoxical responses (9.7 +/- 4.7 vs 8.1 +/- 4.1 months); there was no correlation of age with the size of the bronchodilator response. CONCLUSIONS: The results of the current study indicate that bronchodilator responsiveness in infants with bronchiolitis is not age-dependent.