Propranolol For Infantile Hemangiomas Research Articles

To study the role of propranolol in infantile hemangioma: A prospective randomized study

To study the role of propranolol in infantile hemangioma: A prospective randomized study

Association of Attention Deficit Hyperactivity Disorder with the Use of Oral Propranolol in Infantile Haemangiomas: An Ambispective Comparative Study.

Previous studies have raised concerns about the effects of oral propranolol on the central nervous system in infants, the exact measure and mechanism and the long-term follow-up of which is less well studied. This was an ambispective comparative study of children with infantile haemangioma (IH) followed by a repeat visit 4-10 years after completion of propranolol therapy. Parents were asked about psychologic functioning along with an initial screening examination. All patients were evaluated by a paediatric psychiatrist. After evaluation by the Strength and Difficulties Questionnaire, and subsequently by the paediatric psychiatrist, 2 of 12 patients (16.67%) showed features of attention deficit hyperactivity disorder in comparison to 0 of 40 subjects in the control group (0.0498; α = 0.05). These results indicate an increased risk of neuropsychiatric illnesses such as attention deficit hyperactivity disorder (ADHD) in patients given propranolol for IH, as supporting evidence to previous claims.

Predictors of poor response to oral propranolol in infantile hemangiomas

BackgroundPropranolol is the first-line treatment for infantile hemangiomas (IH). Cases of propranolol-resistant infantile hemangiomas are rarely reported. The purpose of our study was to investigate the predictive factors for poor response to propranolol. MethodsA prospective analytical study was conducted between January 2014 and January 2022 including all patients with IH who received oral propranolol therapy at a dose of 2–3 mg/kg/day maintained for at least 6 months. ResultsA total of 135 patients with IH were treated with oral propranolol. Poor response was reported in 18 (13.4%) of the patients: 72% were girls and 28% were boys. Overall, 84% of the IH were mixed, and hemangiomas were multiple in three cases (16%), nasal tip hemangiomas accounted for four cases (22%), and 15 patients (83%) had segmental hemangiomas. There was no significant association between the age or sex of the children and type of response to treatment (p > 0.05). No significant association was found between the type of hemangioma and the therapeutic outcome as well as the recurrence after treatment discontinuation (p > 0.05). Multivariate logistic regression analysis revealed that nasal tip hemangiomas, multiple hemangiomas, and segmental hemangiomas were at greater risk of poor response to beta-blockers (p < 0.05). ConclusionPoor response to propranolol therapy has rarely been reported in the literature. In our series, it was approximately 13.4%. To our knowledge, no previous publications have focused on the predictive factors of poor response to beta-blockers. However, the reported risk factors for recurrence are discontinuation of treatment before 12 months of age, mixed or deep type IH, and female gender. In our study, the predictive factors for poor response were multiple type IH, segmental type IH, and location on the nasal tip.

Our experience with propranolol for infantile hemangioma.

The most frequent benign vascular tumor in children is infantile hemangioma (IH). For severe IHs, propranolol has become the first-line Treatment. Despite the fact that several studies have comprehensive therapy regimens, including the best time to start Treatment, dosage, visit frequency, and treatment duration, there is still controversy about the best time to start and stop propranolol medication. Between January 2016 and February 2019, dermatologists experienced hemangioma treatment and recommended propranolol treatment for 232 IHs. A total of 90 patients completed the treatment process after undergoing a color Doppler ultrasound test. Propranolol uniquely affects each IH. Ninety patients were divided into two groups in this study: entire regression (n=40) and partial regression (n=50). The entire regression group's initial treatment period (4.3±2.97 months) was substantially shorter than the partial regression group's (5.2±4.57 months) (p<0.05). Between the entire regression group (23.4±12.8 months) and the partial regression group (24.5±16.6 months), there was no significant difference in time to reduce propranolol. The partial regression group (32.9±25.3month) had a lengthier treatment course than the entire regression group (23.4±13.7 months) (p<0.05). The partial regression group (22%), like the entire regression group, had a higher recurrence rate (5%). The overall proportion of hemangiomas on the face (particularly periocular hemangioma) in the regression group was greater than in the control group. The entire regression group's initial treatment time was significantly shorter than the partial regression group's. As a result, as soon as a hemangioma is discovered, it should be treated. To determine the appropriate time to reduce propranolol, we must evaluate the patient's age and the percentage of tumor regression. Periocular hemangioma may have a better prognosis than other types. Given the small number of patients in our study, we will need to do more research in the future to confirm our findings.

Early initiation of treatment with oral propranolol for infantile hemangioma improves success rate.

Early referral and treatment of infantile hemangioma (IH) is a major challenge for treatment success. However, there is a lack of data supporting a specific threshold for initiating treatment with oral propranolol. The aim of this analysis was to find factors, such as age at treatment initiation, leading to a higher success rate with oral propranolol treatment. Based on data from the pivotal phase 2-3 clinical trial of oral propranolol in IH, we used Generalized Additive Model (GAM) charts with Generalized Linear Models (GLM), then a rule discovery algorithm, to identify sub-groups presenting a high probability of occurrence of the predefined outcome (i.e., success [complete or nearly complete resolution of the target hemangioma] at 6months of treatment). Our analyses identified that patients who started oral propranolol 3mg/kg/day before the age of 10 weeks had a success rate of 86%, higher than the 60% success rate for all patients that received the same regimen commencing after 10 weeks of age. Treatment initiation before 10 weeks of age was associated with a significantly higher rate of treatment success with oral propranolol 3mg/kg/day. Infants with IH requiring treatment should be referred to an expert center and treated as soon as possible.

PA33: A tertiary centre experience of the use of propranolol in infantile haemangiomas

PA33: A tertiary centre experience of the use of propranolol in infantile haemangiomas

Noninferiority and Safety of Nadolol vs Propranolol in Infants With Infantile Hemangioma

Propranolol for infantile hemangiomas (IH) has been shown to be effective and relatively safe. However, other less lipophilic β-blockers, such as nadolol, may be preferable in individuals who experience propranolol unresponsiveness or adverse events. To document the noninferiority and safety of oral nadolol compared with oral propranolol in infants with IH. This double-blind noninferiority prospective study with a noninferiority margin of 10% compared propranolol with nadolol in infants aged 1 to 6 months with problematic IH. The study was conducted in 2 academic pediatric dermatology centers in Canada between 2016 and 2020. Infants aged 1 to 6 months with a hemangioma greater than 1.5 cm on the face or 3 cm or greater on another body part causing or with potential to cause functional impairment or cosmetic disfigurement. Oral propranolol and nadolol in escalating doses up to 2 mg/kg/d. Between-group differences comparing changes in the bulk (size and extent) and color of the IH at week 24 with baseline using a 100-mm visual analog scale. The study included 71 patients. Of these, 36 were treated with propranolol. The mean (SD) age in this group was 3.1 (1.4) months, and 31 individuals (86%) were female. Thirty-five infants were treated with nadolol. The mean (SD) age in this group was 3.2 (1.6) months, and 26 individuals (74%) were female. The difference in IH between groups by t test was 8.8 (95% CI, 2.7-14.9) for size and 17.1 (95% CI, 7.2-30.0) for color in favor of the nadolol group, demonstrating that nadolol was noninferior to propranolol. Similar differences were noted at 52 weeks: 6.0 (95% CI, 1.9-10.1) and 10.1 (95% CI, 2.9-17.4) for size and color improvement, respectively. For each doubling of time unit (week), the coefficient of involution was 2.4 (95% CI, 0.5-4.4) higher with nadolol compared with propranolol. Safety data were similar between the 2 interventions. Oral nadolol was noninferior to oral propranolol, indicating it may be an efficacious and safe alternative in cases of propranolol unresponsiveness or adverse events, or when faster involution is required. ClinicalTrials.gov Identifier: NCT02505971.

Propranolol inhibits the angiogenic capacity of hemangioma endothelia via blocking β-adrenoceptor in mast cell.

Propranolol, a non-selective blocker of the β-adrenoceptor (AR), is a first-line treatment for infantile hemangioma (IH). Mast cells have been implicated in the pathophysiology of propranolol-treated hemangioma. However, the function of mast cells remains unclear. HMC-1s (Human mast cell line) having been treated with propranolol for 24 h were centrifuged, washed with PBS twice, and maintained in cell culture medium for another 24 h. The supernatants with propranolol which were named as propranolol-treated HMC-1s supernatants were obtained. The expression of cytokines and mediators was examined among HMC-1s dealt with propranolol. HemECs (hemangioma endothelial cells) were co-cultured with propranolol-treated HMC-1s supernatants, and their proliferation and apoptosis were investigated. The autophagic-related protein was examined in HemECs using immunoblot. In propranolol-treated HMC-1s, the expressions of ADRB1 (β1-AR) and ADRB2 (β2-AR) were reduced by 70% and 60%, respectively, and that of cytokines and mediators were reduced. The proliferation was decreased, but apoptosis and autophagy were induced in HemECs treated with propranolol-treated HMC-1s supernatants. However, propranolol can work well in shRNA-ADRB1 or shRNA-ADRB2 transfected HMC-1s. Propranolol inhibit the proliferation of HemECs and promote their apoptosis and autophagy through acting on both β1 and β2 adrenoceptor in mast cell. Treated with propranolol, β1, and β2 adrenoceptor on human mast cell expression was reduced significantly. After hemangioma endothelial cell treated with the supernatants from propranolol-treated human mast cell, its proliferation was decreased, but apoptosis and autophagy were significantly induced. Propranolol can work well in shRNA-ADRB1 or shRNA-ADRB2 transfected HMC-1s. Mast cells may have a role in the action of propranolol in infantile hemangioma through both β1 and β2 adrenoceptors to inhibit the angiogenic capacity of hemangioma endothelial cells.

271 Critical role of Aquaporin-1 and telocytes in infantile hemangioma response to propranolol beta blockade

Propranolol is currently the first-line treatment for severe infantile hemangioma (IH), the most frequent tumor in childhood. Neither the molecular mechanism of action nor the cellular target of the drug has been identified with a strong proof of concept. We showed that propranolol antitumor activity was associated with alteration of Aquaporin 1 (AQP1), a water and ion channel involved in tumor cell migration and angiogenesis. In pathological context, elevated AQP1 is involved in the development and progression of tumors and associated with poor prognosis. We developed an IH in vitro model using lesional patient-derived endothelial cells (EC), pericytes (PER) and CD34+/ PDGFR-α+ stromal cells named telocytes (TC) that we first described in IH. Thus, we investigated the role of these perivascular cells in the antiangiogenic effect of propranolol in IH and tested AQP1 as a marker and target of the beta-blockade response in IH. Immunuhistofluorescence staining revealed a unique AQP1 expression in IH-TC compared to normal dermis. IH-TC maintain high in vitro AQP1 protein levels compared to foreskin control-TC. We performed a Matrigel based tube formation assay including IH-EC, IH-PER and IH-TC, which highlights migration and cell-cell interaction alterations. This 3D model has a unique response to low doses of propranolol. Indeed 3 μM of propranolol highly decreased IH angiogenesis in our in vitro model and this effect is abolished when control foreskin-TC are used instead of IH-TC. Interestingly, the knockdown of AQP1 in IH-TC shows the same anti-angiogenic effect as propranolol and the combination is not additive. Moreover, we show that this beta-blockade downregulates AQP1 in patient derived telocytes. All together, these data suggest that IH sensitivity to propranolol rely at least in part to a cross talk between lesional vascular cells and stromal telocytes and reveal a critical role of AQP1 in this antitumor response.

Adverse Drug Reactions Following Propranolol in Infantile Hemangioma

To assess the adverse effects of propranolol therapy in infantile hemangioma. An ambispective study was conducted from August 2011 to December 2019. In retrospective arm all children managed for infantile hemangioma with propranolol were included and case records were assessed for adverse reactions. In prospective arm the adverse reactions were identified on the basis of predefined criteria. A total of 514 patients (358 retrospective records) were included. A majority, 378 (73.5%) patients had an excellent response, 75 (14.5%) had partial response and 61 (11.8 %) had no response. A total of 82 (15.9%) patients experienced at least one adverse effect. Diarrhea with weight loss (27, 32.9%) and irritability with decreased sleep (21, 25.6%) were the most common adverse effects. The adverse effects in 22 (4.2%) cases lead to the discontinuation of propranolol. Younger age, low body weight and early onset were risk factors for development of severe adverse reactions. Young children with low body weight were at higher risk for adverse effects of propranolol.

Sleep behavior of infants with infantile hemangioma treated with propranolol\u2014a cohort study

Sleep problems are frequently reported in infants treated with propranolol for infantile hemangiomas, possibly serving as a marker for a negative impact on central nervous system function. In this cohort study, we objectively investigate the sleep behavior of infants with infantile hemangiomas on propranolol compared to a healthy, untreated control group. Sleep of propranolol-treated infants and controls was investigated using ankle actigraphy and a 24-h diary for 7–10 days at ages 3 and 6 months. The main outcome measures were the Number of Nighttime Awakenings and Sleep Efficiency. The main secondary outcome measures included 24-hour Total Sleep, daytime sleep behavior, and parent-rated infant sleep quality and behavioral development based on the Brief Infant Sleep Questionnaire (BISQ) and the age-appropriate Ages-and-Stages Questionnaire (ASQ), respectively. Fifty-four term-born infants were included in each cohort. No group difference in any investigated parameter was seen at age 3 months. At age 6 months, the propranolol group exhibited a decrease in Sleep Efficiency and a trend towards an increased Number of Nighttime Awakenings compared to the control group. Treated infants at 6 months also had shorter daytime waking periods. 24-hour Total Sleep was unaffected by propranolol. No negative impact of propranolol on subjective sleep quality and behavioral development was noted.Conclusion: Propranolol exerts a measurable yet mild impact on objectively assessed infants’ sleep measures. Behavioral developmental scores were unaffected. Our results support propranolol as first-line therapy for complicated infantile hemangiomas.What is Known:• Sleep disorders are frequently reported in infants with infantile hemangiomas treated with propranolol and often lead to treatment discontinuation.• Investigations of the sleep pattern in this patient group using objective measures are lacking.What is New:• The sleep pattern of propranolol-treated infants is assessed using actigraphy and a 24-h sleep diary and compared to healthy, untreated controls.• Propranolol leads to a decreased sleep efficiency at night and an increased demand of daytime sleep, yet effects are mild overall.

Propranolol for infantile hemangioma: Evaluating efficacy and predictors of response and rebound growth

Propranolol emerged as the first-line therapy for infantile hemangioma (IH). Determinants of interindividual variation in drug response and predictors of rebound growth after drug discontinuation are yet to be firmly established. We aimed to evaluate the outcomes of a relatively large cohort of patients with IH treated by propranolol and to determine predictors of (a) an excellent response to treatment (≥90 improvement) and (b) of rebound growth after drug cessation. A retrospective cohort study was conducted to follow all patients with IH receiving systemic propranolol in a referral center-based specialized clinic. Multivariate logistic regression analysis was performed to identify predictors of excellent response and rebound growth. The study included 206 patients who completed oral propranolol treatment. The mean (SD) age in which the drug was initiated was 4.8 (3.1) months. The average improvement rate was estimated at 85.5 (13.8)%. Initiation of propranolol at the age of 0 to 3 (adjusted odds ratio [OR], 3.43; 95% confidence interval [CI], 1.25-9.40; P = .016) and 3 to 6 (adjusted OR, 3.71; 95% CI, 1.50-9.19; P = .005) months was associated with an increased likelihood of excellent response. Twenty-four (11.7%) patients developed rebound growth following cessation of propranolol. No significant predictors of rebound were identified in the multivariate analysis. Eleven (5.3%) patients experienced mild adverse events, which necessitated drug discontinuation in only two (1.0%) patients. Propranolol is highly effective and safe based on the real-life experience of a referral center for IH. The current study supports early initiation of propranolol.

Atenolol vs. propranolol for the treatment of infantile haemangiomas: A systematic review and meta-analysis.

Infantile haemangioma (IH) is a benign vascular tumour type that occurs in 3-10% of infants. In the present meta-analysis, previous studies comparing clinical outcomes, including the recovery rate and haemangioma activity score (HAS), adverse effects and relapse rates, were compared between patients treated with atenolol and those treated with propranolol for IH. A systematic search in various databases, including Medline, Cochrane Controlled Register of Trials, ScienceDirect and Google Scholar from inception until July 2019 was performed. The Cochrane risk of bias tool was used to assess the quality of published trials. A meta-analysis with a random-effects model and reported pooled mean differences (MD) or odds ratios (OR) with 95% CIs was performed. In total, 8 studies including 608 participants were analyzed. Only 2 studies were randomized controlled trials, while the majority of studies had low or unclear bias risks. Except for the response to medication (pooled OR=1.49; 95% CI, 0.85-2.18), all other outcomes (HAS, adverse reactions and relapse rate) were better for the atenolol group than the propranolol group. Atenolol resulted in better HAS (pooled MD=0.16; 95% CI, -0.42 to 0.73). Propranolol had more adverse reactions (pooled OR=2.17; 95% CI, 0.93-5.06) and a higher relapse rate (pooled OR, 1.67; 95% CI, 0.44-6.41) when compared to atenolol. However, these findings were not statistically significant. The results of this analysis suggest that atenolol may be non-inferior to propranolol and may offer advantages, including lower adverse reactions and relapse rates.

PIH39 EVALUATION OF PROPRANOLOL OFF-LABEL USE IN INFANTILE HEMANGIOMA AND EFFECTIVENESS OF RISK MINIMISATION MEASURES TO MITIGATE ADVERSE REACTIONS: A FRENCH AND GERMAN DRUG UTILIZATION STUDY

The approval of propranolol in infantile hemangioma (IH) by the EMA was conditional upon the submission of a Risk Management Plan (RMP) designed to monitor and minimise safety concerns. This Drug Utilization Study aimed to evaluate the off-label use of propranolol and the effectiveness of the risk minimisation measures (RMM) to mitigate the important risks characterized in the RMP. A retrospective multicentre hospital cohort study of patients treated with propranolol was conducted in France and Germany. Off-label criteria were assessed by an independent adjudication committee. Data from the French Système National d’Information Inter-Régimes de l’Assurance Maladie (SNIIRAM) and IQVIA® longitudinal Pharmacy prescription database (LRx) in Germany were also used. A total of 273 patients from 37 French centres and 247 patients from 18 German centres were included. Patients with IH requiring systemic treatment were ≥85% in both countries, in line with the Summary of Product Characteristics (SmPC). The reason for treatment was adjudicated as off-label in 6% of cases in both countries. Age at treatment initiation (corrected for prematurity) was in line with the SmPC (<5 weeks or >5 months) for ≥70% of patients. The mean treatment duration (including temporary discontinuation) was more than the recommended 6 months in both France (8.7 months) and Germany (8.4 months). Overall, there was a low incidence of adverse events (<4%). Overall conditions of usage of propranolol in IH comply to the SmPC and identified off-label conditions of use that could jeopardize the safety of infants were considered as very limited. Propranolol usage in infants with IH, when used along with adequate RMM, has demonstrated no new safety concern and no new signal that could impact the benefit/risk of the product.

Deep coma in a child treated with propranolol for infantile hemangioma

BackgroundPropranolol hydrochloride is the first-line agent recommended for the treatment of infantile hemangiomas (IH). Serious adverse effects of propranolol therapy for hemangiomas are infrequent.Case presentationWe report a case presented in deep hypoglycemic coma during his treatment with propranolol for IH. Through our case report and the review of the literature, we aimed to underline the importance of recognizing adverse effects during propranolol therapy. Although propranolol has a long history of safe and effective use in infants and children, pediatricians should be aware that life-threatening adverse effects can happen during propranolol therapy for IH.ConclusionEarly identification of these adverse effects can be of great importance for patient management and prognosis. It must certainly be noted that not just early identification among doctors, but education for parents is crucial.

Use of Propranolol in Infantile Hemangioma Resulting in Scarless Healing

Infantile hemangiomas (IHs) are the most common childhood tumors. Some can ulcerate causing pain, bleeding, and scarring, leading to cosmetical disfigurement. The use of propranolol has beaten the traditional high-dose systemic corticosteroids therapy, which falls short on its infamous adverse effects. In these case series, regimen of propranolol was highlighted when surgery is not an option. Two cases were presented. Case 1 involveda three-month-old baby girl was presented with a 0.6x0.6 cm disfiguring purple tumor on her nasal tip and columella and Case 2 involveda three-month-old baby girl with a 2x0.5 cm sharply bordered and bulging red tumor on her left labium major.Both lesions became visible at the age of 3 months and grew rapidly since then. Propranolol was initiated at 2 mg/kgBW per day with careful administration. Adverse effects and drug tolerance were closely monitored under pediatrician and plastic surgery care with none reported. Dramatic results was seen after 2 weeks of treatment and no scar was found at the end of the therapy. This confirmed that propranolol is an effective and well tolerated treatment when commenced early and continued with the minimum protocol of 2 mg/kgBW/day through the proliferative phase of infantile hemangioma. It is concluded that propranolol is beneficial for managing infantile hemagioma cases with a scarless outcome that cannot be achieved through surgery. The use of propanolol is extremely beneficial when the case involves a tumor in a site that makes it impossible for reconstruction. Penggunaan Propranolol pada Hemangioma Infantil yang Menghasilkan Penyembuhan Tanpa Bekas Luka Hemangioma infantil adalah tumor yang paling sering pada anak. Tumor ini dapat mengalami ulserasi, nyeri, perdarahan, parut buruk, sampai menyebabkan penampilan cacat. Terapi propranolol telah mengalahkan kortikosteroid, yang dikenal mempunyai banyak efek samping yang buruk. Pada serial kasus ini, kami akan menyoroti regimen penggunaan propranolol, ketika pembedahan tidak mungkin dilakukan. Kasus 1: Bayi perempuan, 3 bulan, datang dengan tumor keunguan yang menyebabkan disfigurasi pada nasal tip dan kolumela. Kasus 2: Bayi perempuan, 3 bulan, datang dengan tumor kemerahan, berbatas tegas dan benjol, pada labium mayor sinistra. Kedua lesi timbul pada usia 3 bulan dan membesar dalam hitungan hari. Propranolol dimulai dengan dosis 2 mg/kg/BB per hari, dengan pengawasan ketat oleh spesialis anak dan bedah plastik. Kedua kasus tidak terdapat efek samping dan toleransi obat baik. Hasil drastis terlihat dalam dua minggu dan pada akhir terapi didapatkan parut yang kasat mata. Kasus kami mengonfirmasi bahwa terapi propranolol adalah efektif dan dapat ditoleransi dengan baik, diberikan dini dan stabil pada dosis 2 mg/kg/BB per hari pada fase proliferasi, dengan hasil tanpa bekas yang tidak dapat dicapai dengan pembedahan. Kami ingin meningkatkan kesadaran pada dokter dalam penggunaan propranolol yang telah dibuktikan bermanfaat, terutama pada tumor yang berada di tempat yang tidak dapat dioperasi dan sulit direkonstruksi.

Oral Propranolol in Infantile Hemangiomas: Analysis of Factors that Affect the Outcome.

Aim:The primary treatment for the subset of infantile hemangiomas (IHs) which develops complication is pharmacological intervention, and propranolol has become a popular choice. Here, we evaluated the efficacy and safety of propranolol in a clinical cohort of IHs and analyzed clinical characteristics associated with a good outcome.Materials and Methods:We retrospectively reviewed a total of 52 IHs patients, between ages 1 and 48 months (median age: 7.5 months), who were treated with oral propranolol, with dose ranging from 2 to 3 mg/kg/day. Efficacy was evaluated using mean percentage reduction, visual analog scale (VAS), and parental satisfaction levels at week 2 and months 1, 2, 6, and 12. The adverse effects were noted and responses after 6 months were graded. Statistical analyses of the outcome were also performed for the responses with regard to age at propranolol initiation, site of lesion, and mean duration of treatment.Results:A therapeutic response with at least 50% mean percentage reduction in size was noted in 84.6% at the end of 6 months. VAS score and parental satisfaction levels correlated well with mean percentage reduction (63.7 ± 15.6) at 6 months. Patients aged <6 months and those with cephalic lesions exhibited a greater therapeutic response rate with shorter overall mean duration of the treatment.Conclusions:Oral propranolol at 2–3 mg/kg/day dosing has shown to be effective and safe for IHs in pediatric age group. Intervention in the early proliferative phase, with especially, the cephalic lesions result in better resolution rates with shorter duration of overall treatment.

Vectra 3D Imaging for Quantitative Volumetric Analysis of the Efficacy of Propranolol in Infantile Hemangioma

Infantile hemangioma (IH) is a common tumor in infants. After the proliferative phase, hemangiomas regress, but sometimes leave scars. Propranolol is now the recommended first-line oral therapy for IH. To evaluate the effectiveness of oral propranolol administration, we measured quantitative changes in an IH by digital camera and Computed Tomography (CT) or Magnetic Resonance Imaging (MRI). Although digital cameras are very simple, changes in color tones occur with time, lesions are evaluated in two dimensions, and changes in the thickness of the hemangioma are difficult to evaluate. Therefore, we investigated the feasibility of 3D photography to quantify volumes in IH during oral propranolol treatment.

Propranolol suppresses HUVEC viability, migration, VEGF expression, and promotes apoptosis by downregulation of miR-4295.

Infantile hemangioma (IH) is a common benign tumor. Human umbilical vein endothelial cells (HUVECs) have the potential of stem cells, which has been widely used in vascular endothelial cell experiments. Oral propranolol was first reported to treat hemangioma in 2008. However, the role of propranolol in IH remains unclear. Therefore, in this study, we investigated the effects of propranolol on HUVECs in vitro, to explore the underlying mechanism of propranolol in IH. HUVECs were treated with 0.15, 1.5, and 15 μM of propranolol, and transfected with microRNA-4295 (miR-4295) mimic. Cell viability, migration, and apoptosis were examined using Cell Counting Kit-8, transwell assay, and flow cytometry analysis, respectively. In addition, the expressions and concentrations of miR-4295, vascular endothelial growth factor (VEGF), VEGF-A, FLT1, FLT2, and FOXF1 were assessed using real-time polymerase chain reaction, Western blot assay, and enzyme-linked immunosorbent assay. We found that 15 μM of propranolol decreased HUVEC viability the most. Then, cell migration and the concentrations of VEGF and VEGF-A were reduced, and apoptosis was increased when treated with propranolol. Meanwhile, the expressions of VEGF, VEGF-A, FLT1, FLT2, and FOXF1 were downregulated by propranolol exposure. Further study showed that miR-4295 expression was upregulated in IH tissues, and propranolol treatment downregulated miR-4295 expression in HUVECs. MiR-4295 overexpression alleviated the reductions of viability, migration, and factors expression, as well as the increase of apoptosis. Propranolol suppressed HUVEC viability, migration, the expression of VEGF, VEGF-A, FLT1/2,FOXF1, and promoted apoptosis via downregulation of miR-4295. This study lays a foundation for further study of the effect of propranolol on IH.

Efficacy of Propranolol Between 6 and 12 Months of Age in High-Risk Infantile Hemangioma

There is no consensus on optimal treatment duration for propranolol in infantile hemangioma (IH). We evaluated the efficacy and safety of oral propranolol solution administered for a minimum of 6 months up to a maximum of 12 months of age in high-risk IH. This single-arm, open-label, phase 3 study was conducted in patients aged 35 to 150 days with high-risk IH in 10 hospitals between 2015 and 2017. The study comprised a 6-month initial treatment period (ITP) plus continuation up to 12 months of age if complete success was not achieved, a follow-up, and a retreatment period. Patients received oral propranolol twice daily (3 mg/kg per day). The primary end point was the success rate at the end of the ITP. Furthermore, the persistence of IH response and efficacy of retreatment was evaluated. The success rate after 6 months of treatment was 47%, increasing to 76% at the end of the ITP. Of the patients who achieved success, 68% sustained success for 3 months without treatment, and 24% required retreatment. Of the 8 patients who were retreated, 7 achieved success. Adverse events, reported by 80% of patients, were mild, which were expected in this population or known propranolol side effects. Oral propranolol administered beyond 6 months and up to 12 months of age meaningfully increases the success rate in high-risk IH. Success was sustained in most patients up to 3 months after stopping treatment. Retreatment was efficacious, and the safety profile satisfactory.