Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm with high morbidity and mortality. The initiating mechanism during the pathogenesis of KHE has yet to be discovered. The main pathological features of KHE are abnormal angiogenesis and lymphangiogenesis. KHEs are clinically heterogeneous and may develop into a life-threatening thrombocytopenia and consumptive coagulopathy, known as the Kasabach-Merritt phenomenon (KMP). The heterogeneity and the highly frequent occurrence of disease-related comorbidities make the management of KHE challenging. Currently, there are no medications approved by the FDA for the treatment of KHE. Multiple treatment regimens have been used with varying success, and new clinical trials are in progress. In severe patients, multiple agents with variable adjuvant therapies are given in sequence or in combination. Recent studies have demonstrated a satisfactory efficacy of sirolimus, an inhibitor of mammalian target of rapamycin, in the treatment of KHE. Novel targeted treatments based on a better understanding of the pathogenesis of KHE are needed to maximize patient outcomes and quality of life. This review summarizes the epidemiology, etiology, pathophysiology, clinical features, diagnosis and treatments of KHE. Recent new concepts and future perspectives for KHE will also be discussed.

Data that indicate vitamin A status in critically ill children with sepsis are sparse. The association between serum vitamin A levels and the clinical outcomes of sepsis has not been well assessed. The aim of this study was to assess the prevalence of vitamin A deficiency in critically ill children with sepsis and its association with clinical outcomes. Critically ill children with sepsis admitted to the pediatric intensive care unit were engaged in this prospective study. Sex- and age-matched approximate-health children from the Department of Pediatric Surgery were enrolled as the control group. Blood samples were collected from all patients in the first 24 h of admission for the measurement of serum vitamin A status. We compared vitamin A status between the sepsis group and the control group. In addition, we compared the clinical characteristics of the two subgroups of septic patients with vitamin A deficiency and those without vitamin A deficiency. Univariate and multivariable methods were used to evaluate the association between vitamin A deficiency and septic shock. One hundred sixty septic children and 49 approximate-health children were enrolled in this study. Vitamin A deficiency was found in 94 (58.8%) subjects in the study group and 6 (12.2%) subjects in the control group (P < 0.001). In septic patients, 28-day mortality and hospital mortality in patients with vitamin A deficiency were not significantly higher than that in patients without vitamin A deficiency (P > 0.05). However, vitamin A levels were inversely associated with higher PRISM scores in septic children with VAD (r = − 0.260, P = 0.012). Vitamin A deficiency was associated with septic shock with an unadjusted odds ratio (OR) of 3.297 (95% confidence interval (CI), 1.169 to 9.300; P = 0.024). In a logistic model, vitamin A deficiency (OR, 4.630; 95% CI, 1.027–20.866; P = 0.046), procalcitonin (OR, 1.029; 95% CI, 1.009–1.048; P = 0.003), and the Pediatric Risk of Mortality scores (OR, 1.132; 95% CI, 1.009–1.228; P = 0.003) were independently associated with septic shock. The prevalence of vitamin A deficiency was high in children with sepsis. Vitamin A deficiency may be a marker of mortality in critically ill children with sepsis. Clinicaltrials.gov , NCT03598127

Laparoscopic Kasai portoenterostomy (LKPE) is performed for biliary atresia (BA). As LKPE is a technically demanding operation, a learning curve should be defined to guide training. The aim of this study was to identify the learning curve of LKPE for BA. Metrics of perioperative safety and efficiency for 100 cases of LKPE were evaluated. Outcomes were followed to 67.2 ± 12.1 months. Cumulative sum (CUSUM) analysis was used to identify inflexion point corresponding to the learning curve. Outcome measures included operative time (ORT), rate of clearance of jaundice (CJ) and survival with native liver (SNL). Between May 2009 and May 2013, 100 consecutive patients with BA underwent LKPE. The rate of conversion from LKPE to open Kasai portoenterostomy (OKPE), intraoperative transfusion and any perioperative complications was 11, 26 and 16%, respectively. There was no perioperative mortality. The CUSUM analysis revealed a learning curve of 50 for LKPE. Precipitous ORT reductions from an initial mean operative time of 316.3 min that was observed in the first 50 to 232.2 min of the late 50 cases (P < 0.01). Subsequently, cases 1 to 50 were considered ‘early experience’, whereas cases 51 and higher were considered as ‘late experience’ for statistical analysis. The rate of CJ and SNL was significantly higher after the early 50 cases (P < 0.05). In contrast, the rate of intraoperative transfusion, the median time of oral feeding initiated after operation, and the length of hospital stay was not different between the both groups (P > 0.05). In this experience, improved perioperative and postoperative parameters for LKPE were observed in the last 50 patients when compared with the first 50 patients. The dedicated training is likely to contribute to significantly shorter learning curves in future adopters.

Background: Sirolimus, a mammalian target of rapamycin inhibitor, has been widely used in pediatric patients, but the safety of sirolimus in pediatric patients has not been well determined. Objective: The objective of this study was to systematically evaluate prospective studies reporting the safety of sirolimus in the treatment of childhood diseases. Methods: The following data were extracted in a standardized manner: study design, demographic characteristics, intervention, and safety outcomes. Results: In total, 9 studies were included, encompassing 575 patients who received oral sirolimus for at least 6 months. Various adverse events occurred. The most common adverse event was oral mucositis (8.2%, 95% CI: 0.054 to 0.110). Through comparative analysis of the subgroups based on the targeted concentration range, we discovered that many adverse events were significantly higher in the high concentration group (≥10 ng/mL) than in the low concentration group (<10 ng/mL) (p < 0.01). More interestingly, we found that oral mucositis was more frequently reported in children with vascular anomalies than tuberous sclerosis complex. Conclusions: This study shows that oral sirolimus in the treatment of childhood diseases is safe and reliable. However, sirolimus treatment in the pediatric population should be strictly monitored to reduce the occurrence of serious or fatal adverse events.

Background: Propranolol, a nonselective β-blocker, is the first-line treatment for infantile hemangioma (IH). Topical timolol has recently been proposed as a novel IH treatment with fewer adverse effects. This study was conducted to compare the efficacy and safety of oral propranolol and topical timolol for treating IH.Methods: Studies were included after searching PubMed, Embase, Web of Science, and the Cochrane Library via the keywords of “propranolol”, “timolol”, “infantile hemangioma” and their synonyms. A meta-analysis with pooled odds ratios was performed using the fixed-effect model.Results: Seven articles with 2071 patients were included in this meta-analysis. Compared with topical timolol, oral propranolol had a greater response rate (OR = 2.12, P < 0.001), but it was also associated with a greater risk of adverse events (OR = 2.31, P < 0.001). For superficial IH, timolol demonstrated similar efficacy to propranolol (OR = 1.28, P = 0.34) but with fewer adverse events (OR = 2.30, P = 0.001). Additionally, compared with topical timolol, propranolol at a dosage of 2 mg/kg/d had a better response rate (OR = 2.62, P < 0.001), whereas the 1.0∼1.5 mg/kg/d propranolol group showed no significant difference (OR = 1.34, P = 0.38).Conclusion: Oral propranolol presents superior therapeutic efficacy in the treatment of IH compared to topical timolol. However, topical timolol can serve as an alternative to oral propranolol for treating superficial IH, providing similar efficacy with fewer adverse effects. Additionally, propranolol at a dosage of 2 mg/kg/d offers greater efficacy with a comparable safety profile, whereas the 1.0∼1.5 mg/kg/d propranolol dosage shows no significant difference in efficacy compared to timolol but is associated with more adverse events.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024603724, identifier CRD42024603724.

Infantile hemangioma (IH) is the most common vascular tumor in children. It is controversial whether IHs has effects on the quality of life (QOL) in patients of whom IH poses no threat or potential for complication. Thus, we conducted this study to evaluate the q QOL in patients with IH and find the predictors of poor QOL. The PedsQL 4.0 Genetic Core Scales and the PedsQL family information form were administered to parents of children with IH and healthy children both younger than 2-year-old. The quality-of-life instrument for IH (IH-QOL) and the PedsQL 4.0 family impact module were administered to parents of children with IH. We compared the PedsQL 4.0 Genetic Core Scales (GCIS) scores of the two groups. Multiple step-wise regression analysis was used to determine factors that influenced QOL in children with IH and their parents. Except for physical symptom, we found no significant difference in GCIS between patient group and healthy group (P = 0.409). The internal reliability of IH-QOL was excellent with the Cronbach’s alpha coefficient for summary scores being 0.76. Multiple step-wise regression analysis showed that the predictors of poor IH-QOL total scores were hemangioma size, location, and mother’s education level. The predictors of poor FIM total scores were hemangioma location and father’s education level. The predictors of poor GCIS total scores were children’s age, hemangioma location and father’s education level. The findings support the feasibility and reliability of the Chinese version of IH-QOL to evaluate the QOL in children with IH and their parents. Hemangioma size, location and education level of mother are important impact factors for QOL in children with IH and their parents.