Involution Of Hemangioma Research Articles

Propranolol-induced Involution of Infantile Hemangioma

A 4-week-old girl with infantile (capillary) hemangioma involving the periocular area (A) underwent a 12-month course of oral propranolol, leading to significant involution (B). The residual lesion, unresponsive to propranolol, was excised to treat anisometropic amblyopia. Histopathologic evaluation revealed lobules of capillary-sized vascular channels lined by flattened endothelium that expressed glucose transporter-1 (GLUT1), compatible with infantile hemangioma (arrow), adjacent to non-lesional GLUT1-negative vessels (arrowheads) (C, original magnification ×100). Endothelial cell apoptotic debris (arrows; D, original magnification ×400) and focally hyalinized vascular channels with concentric Periodic acid-Schiff-positive material (arrowheads) are classic histologic findings seen in β-blocker-induced involution of infantile hemangioma (Magnified version of Figure A-D is available online at www.aaojournal.org).

Infantile hemangioma cured with homoeopathy - A case report

Introduction: Infantile hemangioma (IH) is the most common benign vascular neoplasm in infants. It is characterized by endothelial cell proliferation which usually develops shortly after birth and grows most rapidly over the first 6 months. It is self-limiting in nature. However, in a small percentage of patients, hemangioma does not disappear completely. It may result in serious ocular or systemic complications. These patients may require drug therapy, surgical intervention, and/or laser therapy often during childhood at the cost of certain adverse events. Case Summary: The case reported here is of IH affecting the right eye in a 5-month-old female child who was cured completely with the help of homoeopathic medicine within 4 months. Arnica montana was prescribed as a specific remedy based on its physiological action. Follow-up was done every 2 weeks for 4 months. Vancouver scar scale (VSS) score and photographs were considered every month to assess the involution of hemangioma. For confirming complete recovery and no recurrence, follow-up for another 3 months was done after involution. VSS score reduced from 9 to 0 in 4 months duration. Complete cure in this case of hemangioma with homoeopathy can be considered as a reference to explore the utility of alternative modes of treatment like Homoeopathy to give a better therapeutic option for such conditions and avoid any kind of surgical intervention.

Propranolol in the Treatment of Infantile Hemangiomas.

Propranolol, as the first generation of β-blocker family, was initially introduced in the clinical application for tachycardia and hypertension in the 1960s. However, the occasional discovery of propranolol in the involution of infantile hemangiomas (IHs) brought us a new perspective. IHs are the most common infantile tumor, affecting 4–10% newborns. So far, oral propranolol is the first-line medication for IHs treatment. At the same time, local injection and topical propranolol are developing. Despite the worldwide application, the precise mechanism of propranolol of IHs has not been completely studied. In this article, we reviewed and summarized the current information on pharmacology, mechanism, efficacy, and adverse effects of propranolol. Novel design of biomaterials and bioactive molecules are needed for new treatment and ideal pathway to attain the minimal effective treatment concentration and eliminate the adverse effects.

СТРАТЕГИЯ И ОПЫТ ЛЕЧЕНИЯ ИНФАНТИЛЬНЫХ ГЕМАНГИОМ

Objective. To analyze the treatment results of patients with infantile hemangiomas using various methods. Methods. The study is grounded on the treatment results of children (n=189) with infantile hemangiomas during the period of 2000-2018 years. All patients were divided into the groups: 1) dynamic observation - 23 (12.2%) children; 2) local destruction - 78 (41.3%); 3) surgical treatment - 22 (11.6%); 4) drug therapy - 66 (34.9%) patients. The interstitial coagulation (n=28) and electrocoagulation of hemangioma (n=50) were applied for the local destruction. 18 patients underwent the complete removal of hemangioma and 4 - segmental resection of tumor with the subsequent propranolol treatment. Propranolol was used for the drug treatment and it was combined with the topical application of timolol (n=13). Results. Hemangioma regression was registered in 18 (78.3%) patients of the first group. Among the patients of the second group, involution of hemangioma was observed in 26 (92.6%) patients when the interstitial coagulation was applied and 2 (7.4%) children had hemangioma recurrence. A strongpositiveeffect can be reached by electrocoagulation of superficial hemangiomas (all patients). With primary radical intervention, complete cure was noted in all children, and with segmental resection only one (4.5%) child had a relapse. Keloid scars were formed in 3 (13.6%) children after surgery. Propranolol seemed to be effective in treating hemangiomasinchildrenof all ages, and in 41 (62.1%) patients hemangiomas completely disappeared. Conclusion. Before initiatingtherapy, thechildrenneed to be assessed for the contraindications and the treatment strategy.In case of infantile hemangioma should be individual based on the results of clinical investigation. Systemic propranolol treatment has gained rapid popularity as the treatment of choice for infantile hemangiomas and may be applied not only as the basic treatment, but also in combination with other methods. Surgical removal of hemangioma remains one of the common treatments components for children with infantile hemangiomas. What this paper adds Different variants of infantile hemangioma treatment have been analyzed: ranging from dynamic observation to surgical and systemic treatment. It has been shown, that in case of infantile hemangiomas, Beta-blockers have become the treatment of choice in case of the absence of contraindications; and surgical treatment is indicated in children with the risk of complications development.

INFLUENCE OF AGE AND MORPHOLOGICAL FEATURES ON THE CLINICAL MANIFESTATIONS AND TREATMENT EFFICACY OF HEMANGIOMAS IN CHILDREN

Background. Infantile hemangioma (IH) is a neoplasm that is most common in childhood. Morphologically, hemangiomas are divided into superficial, deep and mixed, focal, segmental, indeterminate and multifocal. The course of IH includes phases of rapid growth followed by slow involution. The degree of involution of hemangioma is variable. Hemangiomas can lead to the appearance of permanent deformities of soft tissues or functional disorders, especially when localized on the face and vital structures. Clinical heterogeneity of hemangiomas creates significant difficulties for physicians in resolving issues of treatment tactics. Specific characteristics of the clinical behavior of hemangiomas of various morphological types can be crucial in the choice of management tactics for such patients. Objectives. The aim of the work is to study the effect of different morphological types of hemangioma in children on the effectiveness of treatment of age-related clinical features. Subjects and Methods. The study group consisted of 100 children in age from birth to 6 years who have hemangiomas of different morphological types and localizations and did not receive previous treatment. All research participants for hemangioma severity scale (HSS), hemangioma activity scale (HAS), visual analogue scale (VAS) before, during and after treatment were scored. Serum levels sFas/sFasLs before and during treatment evaluated. Results. With increasing the child’s age, the indicator as for HAS reliably decreases for all types of hemangiomas. In all types of hemangiomas predominantly an active growth took place. An abortive growth in 10% of patients was noted. For focal hemangiomas, the indicator of sFas decreases with age, and for multifocal hemangiomas it increases. In both cases, there is an increase in the sFasL indicator with increasing age of the child. In our study, in age group before 1 year in the factor structures, “age” factor was considered to be the main one and manifested by a decrease in the activity of hemangioma with an increase in the age of the child. Among children over 1 year age, during the course of treatment, the greatest contribution the “hemangioma severity factor”, the influence of which leads to a decrease in the cosmetic effect of hemangioma treatment against the background of its high severity and an increase in the indicator of apoptosis inhibition of sFas. The influence of the “treatment efficacy” factor leads to a decrease in its cosmetic effect and an increase in the severity of the manifestations of hemangioma against the background of blocking the manifestations of apoptosis. Conclusions. When starting treatment of hemangioma in the early stages, the cosmetic effect increases significantly. A decrease in sFasL in the younger age group may indicate a decrease or absence of apoptosis processes, which is clinically expressed by active proliferation. An increase in sFas in the older age group (over a year old) may indicate a blockage of apoptosis processes and, as a consequence, a slow regression of hemangioma.

Use of the Tongue Tip Flap for Lower Lip Reconstruction in Involuted Hemangioma

Two young female patients underwent lower lip reconstruction after the loss of tissue secondary to the involution of infantile hemangiomas. A proximally based dorsal tongue flap was raised from the tip of the tongue, including a layer of intrinsic muscle. The second stage of the flap division was performed after 3 weeks. Lip contour was improved in both patients, and oral competence was obtained. The papillary appearance of the tongue mucosa smoothened in approximately 2 weeks. Tongue mobility was not compromised. When the defect involves only the vermilion, reconstruction options must be considered on an individual basis. The dorsal portion of the tongue is thicker than the ventral surface and provides better fullness for the lower lip, with a good color match. The 2-staged tongue tip flap (TTF) surgery is an effective alternative to reconstruct vermilion defects after sequelae from infantile hemangioma.

The Impact of Combined Steroid-propranolol Therapy on the Involution of Infantile Hemangioma

Infantile hemangioma (IH) is the most common benign vascular neoplasm of infancy, occurring in 1.0–2.5% of white infants, especially girls. Steroids and propranolol are the most widely used drugs as a primary treatment for IH. Although their mechanism of action is not well understood, their beneficial effect is documented. Our purpose was to compare the clinical efficacy of propranolol alone and propranolol combined with steroids on the outcome of IH. A total of 450 children (median age: 9 months; range: 7 days to 3 years) were included in this randomized controlled study, being treated with combined steroid and propranolol (Group A: 230 children) compared to those treated with propranolol plus placebo (Group B: 220 children). The steroid was given as a loading dose of 2–3 mg/kg/day and then gradually tapered over 6 months, whereas propranolol was given as an incremental dose starting at 0.16 mg/kg/day and reaching a maximum of 2 mg/kg/day maintained for 18 months (duration of therapy). Frequent monitoring of the blood sugar level was mandatory in the first 2 months: electro- and echocardiograms were recorded initially but not repeated. A more rapid involution rate, recognized by color fading and flattening of the lesions, was noted in Group A compared to Group B, with the peak response reached after 10 months of therapy followed by a slower but steady rate of further improvement. No major adverse effects were observed in Group A with regard to hypoglycemia or hypotension. On the other hand, ten cases of vomiting and diarrhea, one case of fungal infection and twelve cases of somnolence and fatigue were observed in Group B. Steroid induction seems to cover the gap at initiation of therapy where propranolol cannot be given as a full dose, especially in neonates. Steroid combination minimizes the adverse effects of propranolol, namely, hypoglycemia, hypotension and bradycardia. Children treated with a combined regimen showed more effective clearing of lesions, were less likely to require surgery for residual lesions and had minimal adverse effects compared to the single-drug group. In both groups there was a faster clearing rate for the head and neck lesions than elsewhere in the body, which can be explained by the higher blood flow to this region, magnifying the level of medication to these lesions and achieving a better response.

M1 Macrophage–Induced Endothelial-to-Mesenchymal Transition Promotes Infantile Hemangioma Regression

Infantile hemangiomas are benign tumors of vascular endothelial cells (ECs), characterized by three distinct stages: proliferating phase, involuting phase, and involuted phase. The mechanisms that trigger involution of hemangioma into fibro-fatty tissue remain unknown. We report a novel mechanism by which M1-polarized macrophages induce endothelial-to-mesenchymal transition (EndMT) and promote hemangioma regression. M1- but not M2-polarized macrophages induced EndMT in ECs. Tumor necrosis factor-α and, to a lesser extent, IL-1β and interferon-γ were the most potent cytokines produced by the M1 macrophages that induce invitro EndMT. Western blot analysis and gene expression profiling showed that ECs treated with M1 macrophages, tumor necrosis factor-α, or IL-1β decreased the expression of endothelial markers, whereas mesenchymal markers increased concomitantly. Immunohistochemical staining of patient samples revealed that a significant perivascular infiltration of M1, but not M2, macrophages coincides with endothelial expression of the critical EndMT transcription factors Snail/Slug in involuting hemangiomas. Most strikingly, M1 macrophage-treated ECs isolated from patient hemangiomas (HemECs) but not untreated HemECs readily differentiated into adipocytes on adipogenic induction. Thus, invitro EndMT and adipogenesis of HemECs have, in part, recapitulated the natural history of hemangioma regression. In conclusion, our findings indicate that EndMT induced by M1 macrophages promotes infantile hemangioma regression and may lead to novel therapeutic treatments for this vascular tumor.

Expression of β-Adrenergic Receptor Subtypes in Proliferative, Involuted, and Propranolol-Responsive Infantile Hemangiomas.

Propranolol hydrochloride has become the primary medical treatment for problematic infantile hemangioma; however, the expression of propranolol's target receptors during growth, involution, and treatment of hemangioma remains unclear. To measure and compare the expression of β1-, β2-, and β3-adrenergic receptors (ADBR1, ADBR2, and ADBR3, respectively) in proliferative (n = 10), involuted (n = 11), and propranolol-responsive (n = 12) hemangioma tissue. Infantile hemangioma specimens were harvested for molecular investigation. Messenger RNA (mRNA) expression of the ADBR1, ADBR2, and ADBR3 genes was detected by real-time polymerase chain reaction. Protein level expression was measured by Western blot and standardized with densitometry. A total of 33 specimens were collected from patients in a tertiary pediatric hospital who underwent excision of problematic hemangiomas. This study was conducted from January 18, 2011, to September 24, 2013, and data analysis was performed from February 25, 2015, to June 25, 2016. Of the 33 patients included, 21 were female (64%). The mean (SD) patient age at the time of excision was 7 (2.5) months for the proliferative group lesions, 23.5 (10) months for the involuted group, and 16 (10) months for the propranolol group. The mean level of ADBR1 mRNA expression was significantly higher in proliferative hemangioma than in propranolol-responsive hemangioma (1.05 [0.56] vs 0.52 [0.36]; P = .01; 95% CI, 0.12-0.94). There was no difference in ADBR2 expression among the groups. Protein expression of ADBR3 was significantly higher in involuted (0.64 [0.12] vs 0.26 [0.04]; P < .01; 95% CI, 0.26-0.49) and propranolol-responsive hemangioma (0.66 [0.31] vs 0.26 [0.04]; P = .01; 95% CI, 0.16-0.68) compared with proliferative hemangioma. These data demonstrate the variable expression of ADBR subtypes among infantile hemangiomas during growth, involution, and response to treatment. These findings may have clinical implications regarding the use of selective vs nonselective β-blockade. 2.

Propranolol for infantile hemangioma: An evaluation of its efficacy and safety in Iranian infants

Background: Propranolol has been recently indicated to inhibit the rapid growth and involution of infantile hemangioma. In the present study, we investigated the efficacy and safety of propranolol in Iranian infants. Methods: A total of 30 infants with indications for medical intervention, such as large hemangiomas, wounds with or without secondary infection, or active trauma-induced bleeding, were selected. First, a total concentration of 1 mg/kg/day was orally administered to the infants; the dosage further increased (2-3 mg/kg/day) in case the infants experienced no adverse effects. Following weekly (one month after treatment) and monthly (up to six months) follow-ups, hemangioma activity score (HAS) was calculated to evaluate swelling, color of the lesion, and ulcer size. Results: In the present study, infants with the mean age of 5.33±3.50 years received therapy. Improvement was observed in the lesions of all patients, characterized by a significant decline in size, change in color, and reduction in ulcer size (P<0.001). No serious adverse effects were recorded, except agitation which was overcome by reducing the drug concentration. Conclusion: It seems that propranolol can be considered as an efficacious and safe alternative to other pharmaceutical and surgical interventions for infantile hemangiomas in Iranian infants.

Risk Factors for Degree and Type of Sequelae After Involution of Untreated Hemangiomas of Infancy

Infantile hemangiomas involute to some extent, but they often leave sequelae that may cause disfigurement. Factors determining the risk of permanent sequelae after regression are of crucial importance in treatment decision making. To describe the sequelae left by infantile hemangiomas after natural involution and to identify clinical characteristics that could predict the most severe or a particular type of sequelae. Multicentric retrospective cohort study of images from 187 infantile hemangiomas that had not received systemic treatment and had follow-up pictures until regression that were selected from photographic files taken between 2003 and 2013 at 4 university hospitals with large vascular clinics in 3 different countries. Outcome measures were the type of sequelae classified as residual telangiectasia, anetodermal skin, redundant skin, persistent superficial component, and the degree of sequelae ranging from 1 to 4. A total of 184 hemangiomas were included. The overall incidence of significant sequelae was 101 of 184 (54.9%). The most common sequelae after involution were telangiectasias (145, 84.3%), fibrofatty tissue (81, 47.1%), and anetodermic skin (56, 32.6%). The average age at which hemangioma completed involution was 3.5 years. Superficial and deep hemangiomas left significantly fewer sequelae than combined hemangiomas (Mann-Whitney; superficial vs deep, OR, 1.6; 95% CI, 0.6-3.8; P = .81; superficial vs combined, OR, 3.3; 95% CI, 1.7-6.3; P < .001; deep vs combined, OR, 2.1; 95% CI, 0.9-5.1; P < .001). Hemangiomas with a step or abrupt border of the superficial component left more severe sequelae than those with a smooth border (χ2,OR, 3.4; 95% CI, 1.8-6.6; P < .001). Superficial hemangiomas with a cobblestone appearance or rough surface left more severe sequelae than those with a smooth surface (Kruskal-Wallis; α, 0.05; P < .001). Using multivariate analysis, combined hemangiomas with a superficial component and a step border were associated with more sequelae. In this retrospective study of sequelae in a large cohort of untreated infants, we quantified the prevalence of permanent scarring and identified clinical features predictive of permanent sequelae. Our observations provide useful information at a time when the treatment paradigm for hemangiomas has changed. Such knowledge may help primary care physicians predict the risk of sequelae and identify high-risk lesions to implement early treatment.

Cost-utility analysis of propranolol versus corticosteroids in the treatment of proliferating infantile hemangioma in Italy

Objectives Infantile hemangioma (IH) is the most common childhood benign tumour. A recent phase II/III study has demonstrated the success of propranolol for involution of infantile hemangioma as well as a better efficacy and safety when indirectly compared with corticosteroids. The purpose of this study was to estimate the cost-utility of propranolol (Hemangiol), a new medicinal product and the first to be authorized for this specific paediatric indication, versus corticosteroids in the treatment of proliferating infantile hemangioma requiring systemic therapy.

Role of pigment epithelium-derived factor in the involution of hemangioma: Autocrine growth inhibition of hemangioma-derived endothelial cells

Hemangioma is a benign tumor derived from abnormal blood vessel growth. Unlike other vascular tumor counterparts, a hemangioma is known to proliferate during its early stage but it is followed by a stage of involution where regression of the tumor occurs. The critical onset leading to the involution of hemangioma is currently not well understood. This study focused on the molecular identities of the involution of hemangioma. We demonstrated that a soluble factor released from the involuting phase of hemangioma-derived endothelial cells (HemECs) and identified pigment epithelium-derived factor (PEDF) as an anti-angiogenic factor that was associated with the growth inhibition of the involuting HemECs. The growth inhibition of the involuting HemECs was reversed by suppression of PEDF in the involuting HemECs. Furthermore, we found that PEDF was more up-regulated in the involuting phase of hemangioma tissues than in the proliferating or the involuted. Taken together, we propose that PEDF accelerates the involution of hemangioma by growth inhibition of HemECs in an autocrine manner. The regulatory mechanism of PEDF expression could be a potential therapeutic target to treat hemangiomas.

PO-0035 Propranolol Administration For Treatment Of Immature Infantile Haemangiomas(iih) In Infants; Any Cardiac Effects?

<h3>Introduction</h3> Propranolol is now being used as an alternative to steroid treatment for IIH. Aim of the study To evaluate the cardiac effects of propranolol in infancy. <h3>Methods</h3> All patients with IIH between January 2011–December 2013, treated with propranolol, underwent cardiac examination: heart rate (HR), blood pressure (BP), satO2, electrocardiogram and echocardiography (shortening fraction and ejection fraction). Cardiac evaluation was repeated after 1 week, 4 weeks, and then every 6 months. <h3>Results</h3> We have analysed 42 patients divided into 2 groups: 33 patients (1–6 months, mean weight 6.5 ± 1.3 kg) and 9 patients (6–15 months, mean weight 10.6 ± 2.4 kg). No adverse effects in any patients and none required discontinuation of treatment. In the first group the median HR centile was 50th at baseline, 41thafter 1month and 44th at the end of treatment. In the second group the median HR centile was 43th at baseline, 34th after 1 month and 37th at the end of treatment. In the first group the mean SF was 39% at baseline, 40% and 40% at the end of treatment: the mean EF was respectively 74.5%, 72% and 73%. For the second group the mean SF was 38%, 39% and 39%: the mean EF respectively was 73.1% at baseline, 74% after 1 month and 74.2% at the end of treatment. <h3>Conclusion</h3> In our study we have observed signs of rapid involution of hemangioma within the 2–3 first weeks of treatment in all patients. All patients have responded well to treatment, with no side effects and especially no cardiac effect.

Infrared thermography to assess proliferation and involution of infantile hemangiomas: a prospective cohort study.

Infantile hemangiomas (IHs) are common benign tumors of infancy that have the potential to interfere with vital organ function and cause permanent disfigurement. Currently, few objective and validated measures exist to assess IHs. To determine the utility of infrared thermography in assessing and monitoring the growth of IHs. In a prospective cohort study conducted at an outpatient dermatology clinic of a tertiary care hospital between February 2011 and December 2012, a convenience sample of 42 infants aged 0 to 6 months with an IH were enrolled. The mean age of the study group was 3.7 months, with the majority of IHs being mixed type (57%) affecting the head and neck (81%). Of the infants, 36 (86%) were receiving active treatment during the study period, and patients were followed for a minimum of 3 clinical visits, at least 1 month apart. Ability of infrared thermography to assess the proliferation and involution of IHs compared with a visual analog scale. Secondary outcomes were reliability, ease of use, and parental acceptance of the instrument. The mean temperature difference at baseline was 1.9°F (95% CI, 1.2°F to 2.7°F), which peaked at 3 months to 2.5°F (95% CI, 0.8°F to 4.2°F), and decreased progressively to 0.2°F (95% CI, -1.1°F to 1.4°F) at 18.5 months (P < .001). This change in temperature was inversely correlated with mean visual analog scale (r = -0.25). Mean temperature differences recorded at baseline and 30 minutes later were not significant (least squares mean baseline temperature, 87.9°F [95% CI, 87.4°F to 88.3°F], vs least squares mean temperature after 30 minutes, 88.1°F [95% CI, 87.7°F to 88.6°F] [P = .14]). Multivariate analysis demonstrated facial location (F(1,365) = 47.63, P < .001), IH type (F(2,365) = 3.26, P = .04), age (F(2,365) = 7.03, P = .001), and surface area at baseline (F(2,365) = 8.18, P < .001) as factors significantly affecting temperature difference over time. Only IH type (Wald χ(22) = 6.79, P = .03) and treatment (Wald χ(21) = 4.29, P = .04) significantly affected time to reach a zero-temperature difference. All caregivers (100%) reported IRT to be easy to implement, quick to perform, and comfortable for their child. Infrared thermography is a reliable and valid measure of IH growth that is noninvasive, convenient, and well tolerated by infants, making it well suited to daily clinical practice. It has the potential to provide real-time objective results that can be used for routine monitoring and evaluating treatment efficacy.

Editorial (Thematic Issue: Cardiovascular Drug Therapy in Paediatric Age: From Metabolomics to Clinical Practice)

In adult patients, cardiovascular drugs are widely administered in the treatment of numerous diseases. The indications and doses are strictly codified by international Guidelines, which are periodically updated by the American and European Societies of Cardiology. In paediatric patients, however, the situation is substantially different. The lack of large interventional studies on the use of these compounds has led to a greater uncertainty, with a less extensive administration and more limited indications. Furthermore, some important differences in therapeutic approach for the same diseases are present between the U.S. and Europe. The purpose of this Special Issue is to review the pharmacological treatment of certain heart diseases, such as heart failure, and arterial blood pressure, which can result in both adult and pediatric patients [1, 2]. Differences and similarities have been highlighted. Regarding the differences in medical treatment for the same disease in the U.S. and Europe, it has been emphasized that the regulation of drugs is largely determined not only by scientific considerations, but also by other concerns - legal, cultural - which vary in different parts of the world. Such discrepancies are found even in the informational documents provided by pharmaceutical companies (different in USA and Europe for the same drug) and drug agencies (different between FDA and equivalent agencies in Europe). In this issue of Current Medicinal Chemistry, a specific paper is dedicated to the pharmacological treatment of the patency of ductus arteriosus in neonates, which is still a controversial issue. In fact, notwithstanding ibuprofen appears to be lesser dangerous for newborns than indomethacin, with a similar efficacy in closing the ductus; in a number of countries the latter is still administered to all preterm subjects as a prophylactic tool [3]. An unusual case report is the interesting starting point to perform an extensive literature review about the new indications of beta blockers [4]. In this respect, beta blockers, most specifically propranolol, have serendipitously been shown to induce involution of infantile hemangiomas. Mechanisms of action, target doses, formulation, contraindications and cardiovascular monitoring for beta blockers have been analyzed as well. It has recently been demonstrated that preterm birth is negatively associated with an early onset of cardiovascular diseases. Cardiovascular mortality is higher among former preterm adults than those born at term. This condition is referred to as cardiovascular perinatal programming. Metabolomics, a new and promising technique which allows the systematic study of the complete set of metabolites in a biological sample, has been recently applied to the identification of a possible future cardiovascular system involvement in subjects born preterm. Based on these premises, the purpose of the last review was to analyse the relationship between impaired growth during intrauterine life and adult cardiovascular disease risk and death [5].

Treatment of Infantile Hemangiomas with Propranolol

Infantile hemangioma is a vascular tumor and requires treatment in lesions manifested by potentially dangerous symptoms. Several publications have reported that involution of infantile hemangioma could be accelerated by propranolol but have used only invalidated subjective measures of assessment. The authors aimed to objectively validate the aesthetic results after propranolol treatment for infantile hemangioma, and to produce a therapy protocol, including optimal timing for introduction, pretreatment preparation, dosage, frequency of visits, duration, and patient safety. For the nonrandomized comparative cohort study, the authors enrolled 60 patients treated with propranolol. Medical two-dimensional photographs, taken before and after treatment, were subjectively analyzed by three plastic surgery consultants and objectively analyzed with a computer program. Aesthetic results were analyzed using the following parameters: subjective overall outcome, subjective color fading, and objective color fading. Reliability of subjective and objective methods was quantified and compared, as described with accuracy and repeatability. Volumetric parameters were obtained from three-dimensional scans taken before and after treatment and objectively analyzed with a computer program. Numerous patients' data were recorded from the medical notes. This study proved high efficiency of propranolol in treatment of infantile hemangioma, as assessed with the objective measures for the first time. The authors outlined an optimal treatment protocol, including introduction, dosage, duration, and cessation of therapy. Propranolol is an effective, well-tolerated, and safe first-line treatment for proliferative hemangioma. Therapy should begin early, continue with the target dosage of 2 mg/kg/day in three divided doses through the proliferative phase of infantile hemangioma, and be stopped gradually. Therapeutic, IV.

The use of propranolol for complicated infantile hemangiomas

To assess propranolol efficacy and safety in complicated infantile hemangiomas in two different age groups. We report on 68 infants with infantile hemangiomas treated with oral propranolol at the lowest effective dose at different ages for a period of sixmonths. Inclusion criteria were life-threatening hemangiomas, function-threatening hemangiomas, facial hemangiomas with risk for disfigurement, and extensive and ulcerated hemangiomas. A previously designed safety protocol was applied to all patients. The evolution of all hemangiomas since baseline (pre-therapy) until the end of follow-up was assessed on the basis of clinical features (color, palpable softening, size, and volume) and taken at follow-up visits. Our results showed that propranolol was effective in arresting the proliferative phase and in accelerating the involution of infantile hemangiomas in 92.6% of cases. Propranolol efficacy was clear even when it was started after 12months of life at low dose; after discontinuation of therapy there was a moderate-to-severe regrowth in 9.3% of cases and a mild regrowth in 22.5%. No adverse events were observed. Propranolol should be used as first-line medical treatment in all cases of complicated infantile hemangiomas.

Propranolol is more effective than pulsed dye laser and cryosurgery for infantile hemangiomas

Propranolol hydrochloride is a nonselective β-blocker that is used for the treatment of hypertension, arrhythmia, and angina pectoris. In Japan, it was recently approved for the treatment of childhood arrhythmia. It has been observed to produce drastic involution of infantile hemangiomas. The aim of this prospective study was to examine propranolol's superiority to classical therapy with pulsed dye laser and/or cryosurgery in treating proliferating infantile hemangiomas. Fifteen patients between the ages of 1 and 4 months with proliferating infantile hemangiomas received grinded propranolol tablets 2 mg/kg per day divided in three doses. Twelve patients with proliferating infantile hemangiomas receiving pulsed dye laser and/or cryosurgery were enrolled as controls. Baseline electrocardiogram, echocardiogram, and chest x-ray were performed. Monitoring of heart rate, blood pressure, and blood glucose was performed every 2 weeks. Efficacy was assessed by performing blinded volume measurements and taking photographs at every visit. Propranolol induced significantly earlier involution and redness reduction of infantile hemangiomas, compared to pulsed dye laser and cryosurgery. Adverse effects such as hypoglycemia, hypotension, or bradycardia did not occur. The dramatic response of infantile hemangiomas to propranolol and few side effects suggest that early treatment of infantile hemangiomas could result in decreased disfigurement. Propranolol should be considered as a first-line treatment of infantile hemangiomas.

Treatment of Infantile Hemangiomas

1.Recognize infantile hemangiomas that are associated with a higher risk for complications and associated anomalies.2.Appreciate the typical timing of growth and involution of infantile hemangiomas.3.Become familiar with recently reported treatments for infantile hemangiomas.Infantile hemangiomas are common proliferations of endothelial tissue that affect approximately 4% to 5% of infants.1 Lesions represent a broad clinical spectrum and their management has to be individualized. Fortunately, most infantile hemangiomas do not require active therapy and may be managed with "active nonintervention";2 however, it is important to recognize those that do require therapeutic intervention and to be familiar with the therapeutic options.