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however&#44; treatment response is variable and the side effects are insidious&#44; difficult to monitor&#44; and potentially severe&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Other drugs used to treat high-risk lesions could prove more harmful and have potentially more severe side effects&#44; with even more uncertain results&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;5&#44;10</span></a> These include vincristine&#44; interferon alfa&#44; and cyclophosphamide&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;13</span></a> Propranolol is a &#946;-blocker that has been used for several years to treat heart conditions&#46; The incidental finding of a rapid regression of hemangioma in a patient with obstructive hypertrophic cardiomyopathy who had received oral propranolol &#40;3 mg&#47;kg&#47;d&#41; pointed to a possible therapeutic effect of this agent on hemangioma of infancy&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> A recently published series of pediatric patients with hemangioma of infancy revealed a marked improvement after treatment with oral propranolol&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> This and other studies have led pediatric dermatologists to consider oral propanolol as an option for the treatment of high-risk hemangioma of infancy&#46; At present&#44; however&#44; there are no studies comparing propranolol with alternative drugs&#44; and the largest published series comprises only 32 patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#8211;19</span></a> Furthermore&#44; no case series on the use of propanolol to treat this disease have been published in Spain&#46; Although propranolol is a well-known and widely used drug&#44; many doubts still surround its use for the treatment of hemangioma of infancy&#44; for example&#44; with regard to optimal dose&#44; duration of treatment&#44; and relapse after discontinuation&#46; Consequently&#44; until a controlled clinical trial can be performed&#44; it is of paramount importance that local case series be reported in order to broaden our experience with the use of propranol to treat this tumor&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The objectives of the present study were to determine the effectiveness and safety profile of oral propranolol solution for the treatment of hemangioma of infancy&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Materials and Methods</span><p id="par0015" class="elsevierStylePara elsevierViewall">We performed a descriptive&#44; observational study in which we reviewed all patients with hemangioma of infancy referred to the Department of Pediatric Dermatology at Hospital Universitario Virgen del Roc&#237;o in Seville&#44; Spain over an 18-month period &#40;July 2008 to December 2009&#41;&#46; Follow-up continued until September 30&#44; 2010&#46; The criteria for initiating propranolol for the treatment of hemangioma of infancy in the proliferative phase were risk of functional impairment&#44; local complications&#44; or deformity and age more than 1 month&#46; In the case of involuting hemangioma&#44; the more residually deformed lesions were treated in order to accelerate the natural course before surgery&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Patients with suspected PHACE syndrome were hospitalized for additional investigations &#40;cranial magnetic resonance imaging&#44; cerebral magnetic resonance angiography&#44; abdominal ultrasound&#44; echocardiography&#44; baseline electrocardiogram &#91;ECG&#93;&#44; blood biochemistry&#44; complete blood count&#44; and evaluation by a cardiologist and an ophthalmologist&#41;&#46; Once these had been performed&#44; treatment with propranolol was started during hospitalization&#46; Blood pressure &#40;BP&#41; and heart rate were monitored every 8 hours&#44; blood glucose every 12 hours&#44; and ECG daily for 2 days&#46; The remaining patients underwent a study before initiation of treatment &#40;ECG and evaluation by a pediatric cardiologist&#44; BP and heart rate&#44; blood biochemistry&#44; and complete blood count&#41;&#46; Outpatient treatment was then started&#44; with monitoring of BP and heart rate every 3 days during dose escalation &#40;12 days&#41; and subsequently every week&#46; Monitoring was performed at the patient&#39;s health center under the supervision of the area pediatrician&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Once parental informed consent was obtained&#44; treatment with oral propranolol suspension was started at 5 mg&#47;mL&#46; The initial dose was 0&#46;5 mg&#47;kg&#47;d &#40;0&#46;25 mg&#47;kg&#47;d taken in 2 doses&#41;&#44; with an increase of 0&#46;5 mg&#47;kg&#47;d every 3 days&#44; until a final dose of 2 mg&#47;kg&#47;d was reached&#46; Patients included in the initial stages of the study were reassessed at 1&#44; 3&#44; 6&#44; 9&#44; 12&#44; and 18 months&#46; Patients included in the final stages of the study were reassessed at 1&#44; 3&#44; 6&#44; and 9 months&#46; A digital photograph was taken of all the patients before the study and at each follow-up visit in order to evaluate the response to treatment&#46; Baseline epidemiologic characteristics were analyzed&#44; as was response at each visit&#44; according to the decrease in color intensity and in volume&#46; Treatment response was classified as growth&#44; stabilization&#44; partial response&#44; or complete response &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Adverse effects were also recorded&#46; All the data were collected and processed using SPSS version 17&#46;0&#46; Qualitative variables were expressed as absolute and relative frequency &#40;percentage&#41;&#44; and quantitative variables were expressed as mean &#40;SD&#41;&#46; The Pearson &#967;<span class="elsevierStyleSup">2</span> test was applied to detect a possible relationship between the response to treatment and age at initiation of treatment &#40;less than or more than 6 months and less than or more than 12 months&#41;&#44; as well as the association between location of the lesion and response to treatment&#46; The differences between the duration of treatment in patients aged less than and more than 6 months and between patients aged less than and more than 12 months were analyzed using the <span class="elsevierStyleItalic">t</span> test with a Levene correction&#46; The Shapiro-Wilk test was applied to determine whether the quantitative variables were normally distributed &#40;n &#60; 50&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0030" class="elsevierStylePara elsevierViewall">We analyzed 28 patients with 36 hemangiomas&#46; Demographic data are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; Mean age at onset was 1&#46;29 weeks and the mean number of tumors per child was 1&#46;28&#46; The characteristics of the tumors are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46; Ulceration developed in 38&#46;89&#37; of tumors before initiation of treatment&#46; Twenty-one patients &#40;27 tumors&#41; started treatment before age 12 months&#46; The mean age at the initiation of treatment with propranolol was 3&#46;86 months &#40;95&#37; confidence interval &#91;CI&#93;&#44; 2&#46;80-4&#46;92&#59; range&#44; 1&#46;43-10&#46;23&#41; for patients aged less than 12 months and 20&#46;10 months &#40;95&#37; CI&#44; 13&#46;75-26&#46;44&#59; range&#44; 14&#46;00-32&#46;67&#41; for patients aged more than 12 months&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the location and subtype of the hemangiomas&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Five patients received oral corticosteroids before initiating propranolol&#46; In 4 cases&#44; these drugs were withdrawn after a few weeks&#44; with no signs of regrowth&#46; Four patients had large segmental hemangiomas on the face and 1 had a focal lesion on the upper eyelid&#46; In 3 of these patients &#40;aged 1&#46;5&#44; 2&#44; and 6 months&#41;&#44; the lesion continued to grow despite treatment with oral prednisolone &#40;3 or 5 mg&#47;kg&#47;d&#41;&#44; and oral propranolol was started while the dose of prednisolone was tapered over 3 weeks&#46; In the 2 remaining cases&#44; including the patient with the eyelid lesion&#44; the hemangioma decreased in size with prednisolone at 3 mg&#47;kg&#47;d&#59; however&#44; prednisolone was tapered over 3 weeks as oral propranolol began&#46; The patients were aged 3 and 4 months when propranolol was initiated&#46; One had a mixed segmental hemangioma on the parotid region and ear and needed simultaneous treatment for 4 months with oral corticosteroids &#40;3 mg&#47;kg&#47;d&#41; and oral propranolol &#40;4 mg&#47;kg&#47;d&#41; due to regrowth when corticosteroids were stopped or the dose of propranolol reduced&#46; Only 1 of these patients had PHACE syndrome with persistent trigeminal artery and long segment hypoplasia &#40;&#62;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>cm&#41; in both vertebral arteries and the basilar artery&#46; The segmental cervicofacial hemangioma occluded the midline of the right eye&#46; The patient did not respond to oral prednisolone&#59; therefore&#44; treatment with propranolol was started and administered up to 2 mg&#47;kg&#47;d&#44; with a complete response at 16 months and no adverse effects&#46; Only 1 patient was treated using previous local infiltration of corticosteroids&#59; no patients received vincristine or interferon&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">A response to propranolol was observed in all patients at 48 hours&#46; In all patients &#40;both less than and more than 12 months&#41;&#44; the color of the tumor changed from bright red to dull red&#44; and the lesion softened&#46; The eye opened spontaneously in all affected patients within 7 days of treatment &#40;range&#44; 2-7 days&#41;&#46; In 9 cases of ulcerated hemangioma &#40;25&#37;&#41;&#44; cure was complete after a mean of 61 days &#40;range&#44; 15-120 days&#41;&#46; In one patient with 3 ulcerated tumors&#44; treatment was combined with pulsed dye laser&#44; as the ulceration was persistent&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">After 1 month of treatment&#44; a complete response was observed in 6&#46;1&#37; of the hemangiomas and a partial response in 93&#46;9&#37;&#46; At 3 months&#44; a complete response was observed in 27&#46;7&#37; of patients and a partial response in 66&#46;6&#37;&#46; At this point&#44; the dose was increased in 2 patients with hemangioma to 2-4 mg&#47;kg&#47;d&#44; owing to stabilization or growth of the lesion accompanied by severe deformity&#46; At 6 months&#44; the response was complete in 66&#46;6&#37; of patients and partial in 30&#46;5&#37;&#59; the response was stable in 2&#46;7&#37; of the treated tumors &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1&#8211;4</a>&#41;&#46; Response by patient age &#40;less than or more than 12 months&#41; is shown in <a class="elsevierStyleCrossRef" href="#fig0025">Figure 5</a>&#46; The differences in response found between patients aged less than or more than 6 months or less than or more than 12 months were not statistically significant &#40;Pearson &#967;<span class="elsevierStyleSup">2</span>&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;261 and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;432&#44; respectively&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Analysis of the response to treatment by location showed that response was complete at 6 months in the 6 tumors affecting the eyelids &#40;4 focal and 2 segmental&#41; and the 4 tumors on the scalp&#46; Of the 5 tumors on the tip of the nose&#44; 4 had a complete response and 1 had a partial response at 6 months&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Mean duration of treatment was 8&#46;7 months &#40;range&#44; 2-16 months&#41;&#46; No statistically significant differences were observed in duration of treatment between patients aged less than or more than 6 months or between patients aged less than and more than 12 months &#40;<span class="elsevierStyleItalic">t</span> test with a Levene correction&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;341 and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;643&#44; respectively&#41;&#46; In all the treated patients&#44; the criterion for discontinuing propranolol was absence of a visible improvement for at least 1 month and absence of regrowth when the dose of propranolol was reduced to 1 mg&#47;kg&#47;d and after complete suspension&#46; When the dose of propranolol was reduced from 2 to 1 mg&#47;kg&#47;d&#44; it was necessary to increase the dose to 2 mg&#47;kg&#47;d due to regrowth in some cases &#40;4 segmental hemangiomas in children aged less than 12 months&#44; 2 deep focal tumors&#44; and 1 mixed focal tumor in children aged over 12 months&#41;&#46; After complete suspension in children aged less than 12 months&#44; 2 tumors grew again and a further 2 had a slight increase in coloring of the residual telangiectasia that did not require treatment to be restarted&#46; Regrowth was only observed in 1 patient from the group of children aged more than 12 months&#44; and there was no requirement for treatment to be restarted&#46; We did not find a statistically significant association between the location of the lesions and response to treatment &#40;Pearson &#967;<span class="elsevierStyleSup">2</span>&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;412&#41;&#46; Adverse effects were only observed in 2 patients&#44; both of whom had an episode of hypotension during the first month of treatment &#40;at 2 mg&#47;kg&#47;d&#41;&#46; The first case &#40;BP&#44; 62&#47;45 mm Hg&#41; was asymptomatic and resolved spontaneously in 15 minutes&#46; Treatment for regrowth was reintroduced at 1 mg&#47;kg&#47;d&#59; hypotension &#40;BP&#44; 50&#47;35 mm Hg&#41; was again recorded&#44; although it was asymptomatic and self-limiting&#44; and treatment was discontinued&#46; In the second case&#44; hypotension &#40;BP&#44; 60&#47;35 mm Hg&#41; was accompanied by lethargy and the patient was seen in the emergency department of Hospital Infantil Virgen del Roc&#237;o&#46; The condition resolved spontaneously after 30 mintues and treatment was discontinued&#46; During treatment&#44; 3 patients had acute bronchitis&#44; which resolved without complications after temporary suspension of oral propranolol and treatment with inhaled salbutamol and oral corticosteroids&#46; No regrowth of the hemangioma was observed&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Of the 6 patients with hemangiomas affecting the eyes &#40;4 focal hemangiomas and 2 segmental tumors&#41;&#44; the midline was affected in only 2 cases&#46; The eyelid was completely occluded after the first month of life in 1 of these patients&#44; although only for a short period &#40;7 days&#41;&#46; Anisometropia was ruled out in all cases based on refraction assessed using retinoscopy with dilated pupils&#46; Visual acuity was assessed in children aged less than 2 years using the fix and follow reflex&#44; which made it possible to rule out moderate and severe ambliopia&#46; According to the judgement of the pediatric ophthalmologist&#44; no children required treatment&#46; Nevertheless&#44; these patients are still being monitored by the pediatric ophthalmology unit&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">We found treatment with propranolol to be effective in all cases&#44; with a complete response at 6 months in 66&#46;6&#37;&#46; The results were apparent during the first hours of treatment in the form of changes in the color and consistency of the lesions&#46; This finding is consistent with those of other published series&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#8211;19</span></a> The action of the drug was particularly striking in tumors on the eyelid&#44; scalp&#44; and tip of the nose&#46; However&#44; we did not find a statistically significant association between the location of the lesions and response to treatment&#44; probably as a result of the small sample size&#46; Of note&#44; oral propranolol did not only lead to stabilization of growth&#8212;as occurs with corticosteroids&#8212;but the improvement also continued in many cases until regression was complete at very young ages&#44; thus considerably reducing the duration of these lesions&#46; Furthermore&#44; this rapid and significant response was also observed in all tumors in patients aged over 12 months&#46; With corticosteroids&#44; on the other hand&#44; treatment is only effective during the proliferative phase&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;19</span></a> We observed a more marked response at 6 months of treatment in patients treated before they were 12 months old &#40;74&#37; vs 44&#46;6&#37;&#41;&#46; It is noteworthy that&#44; in patients aged more than 12 months&#44; both complete response and partial response were the same at 3 and 6 months of treatment&#44; probably because&#44; at this age&#44; it is more difficult to obtain a complete response with no residual deformity using medical treatment alone&#46; In cases treated early&#44; complete remission occurred at a mean age of 8&#46;7 months&#44; suggesting that treatment with propranolol should be started during the proliferative phase and before most lesions reach their maximum size&#44; at around 5 months of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16&#44;18&#44;19</span></a> We believe that empirical treatment should be maintained in involuting lesions &#40;late treatment&#41; until the optimal result is obtained&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Oral propranolol should not be used as a first-line treatment option in patients with hemangioma of infancy and intracranial vascular abnormalities&#46; However&#44; we elected to initiate treatment with oral propranolol in the patient with PHACE syndrome included in this study&#44; since a large segmental hemangioma completely occluded the midline of the right eye despite treatment with oral corticosteroids&#44; and the cerebral vascular abnormalities did not affect the internal carotid artery&#44; which has been implicated in all cases of cerebrovascular accidents associated with PHACE&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Furthermore&#44; that patient needed the longest course of treatment &#40;until 18 months of age&#41; of all those who started propranolol early &#40;16 months of treatment&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In our experience&#44; propranolol should be withdrawn gradually&#58; when the dose is reduced&#44; recoloring or regrowth can be observed in some cases&#44; thus making it necessary to prolong treatment&#46; By adopting this approach&#44; we did not have to reintroduce the drug after complete withdrawal&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In the case of ulceration&#44; the results obtained with oral propranolol to date have been variable&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;21&#44;22</span></a> The mean healing time for ulcerated hemangiomas in our series was 61 days&#44; and in 1 patient pharmacotherapy was combined with pulsed dye laser&#46; We think that the presence of ulceration does not in itself indicate administration of propranolol&#44; as in our series we observed no differences in improvement of symptoms or healing time compared with other treatments&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#8211;30</span></a> Randomized comparative studies are necessary to clarify this point&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">We found most adverse effects to be mild and predictable at the dose administered&#44; although one of the patients who experienced hypotension required emergency care&#46; Blood glucose was not monitored during treatment&#46; Given that one of the possible adverse effects of oral propranolol is low blood glucose&#44; parents were advised to administer treatment every 12 hours with meals and to withdraw treatment temporarily in case of vomiting&#59; however&#44; it was not necessary to stop treatment for this reason at any time during follow-up&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Our study is limited by its small sample size&#44; which could mean that the differences detected did not reach statistical significance&#46; Nevertheless&#44; our sample size is similar to that of other studies&#44; and our findings increase worldwide clinical experience with propranolol in the treatment of hemangioma of infancy&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">In conclusion&#44; according to the present study&#44; treatment with oral propranolol solution at 2 mg&#47;kg&#47;d is an effective&#44; safe&#44; and well-tolerated option for the treatment of hemangioma of infancy&#46; The effect is apparent during the first few hours after starting treatment&#44; which should be maintained for several weeks&#44; generally up to 6 months&#44; in order to obtain a considerable improvement and halt the natural course of the lesion&#46; This treatment seems to be more effective in lesions in the proliferative phase&#59; however&#44; in our experience&#44; it does not significantly reduce symptom severity or time to scarring when ulceration is present&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of Interest</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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            0 => "Resumen"
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            4 => "Conclusiones"
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          "titulo" => "Materials and Methods"
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    "fechaRecibido" => "2010-04-04"
    "fechaAceptado" => "2011-02-28"
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            0 => "Propranolol"
            1 => "Hemangioma"
            2 => "Prednisolone"
            3 => "Management"
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            0 => "Propranolol"
            1 => "Hemangioma"
            2 => "Prednisolona"
            3 => "Manejo"
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Background and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Recent reports have described the successful use of propranolol to treat severe hemangiomas of infancy&#46; The few case series that have been reported&#44; however&#44; have included only a small number of patients&#46; The aim of this study was to describe the results of oral propranolol treatment for severe hemangiomas of infancy in terms of treatment outcome and the occurrence of adverse events&#46;</p> <span class="elsevierStyleSectionTitle">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A descriptive&#44; observational study was undertaken in a series of children with severe hemangiomas of infancy seen in the pediatric dermatology unit at Hospital Universitario Virgen del Roc&#237;o in Seville&#44; Spain between July 2008 and December 2009&#46; Patients were included if they had hemangiomas in the proliferative phase or involuting lesions with substantial residual deformity&#46; All children were treated with oral propranolol &#40;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d&#41; and followed until September 2010&#46; Epidemiologic characteristics were analyzed along with treatment response at 3&#44; 6&#44; 9&#44; 12&#44; and 18 months&#59; adverse events were also recorded at those times&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Thirty-six hemangiomas were treated in 28 patients&#46; Propranolol treatment was effective in all cases&#44; with a good or complete response in 88&#46;2&#37; at 6 months&#46; Effects were apparent within a few hours of treatment&#44; which was effective in both growing and involuting hemangiomas&#46; In ulcerated hemangiomas&#44; the mean healing time was 61<span class="elsevierStyleHsp" style=""></span>days&#46; Adverse events were mild and self-limiting&#46; Only 2 patients discontinued treatment due to hypotension&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In the majority of cases&#44; oral propranolol produced rapid and sustained improvements in hemangiomas of infancy and shortened the natural course of the disease with few side effects&#46; However&#44; no significant reductions in symptoms or healing time were observed in ulcerated hemangiomas&#46;</p>"
      ]
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        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Introducci&#243;n y objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Recientemente se ha comunicado el &#233;xito del tratamiento con propranolol para hemangiomas infantiles &#40;HI&#41; graves&#46; Existen escasas series publicadas con reducido n&#250;mero de pacientes&#46; El objetivo del presente estudio fue conocer la efectividad y seguridad de propranolol oral para HI graves&#46;</p> <span class="elsevierStyleSectionTitle">Material y m&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional y descriptivo de una serie de ni&#241;os con HI graves en fase proliferativa&#44; o en fase involutiva si presentaban importante deformidad residual&#44; que acudieron a la Unidad de Dermatolog&#237;a Pedi&#225;trica de nuestro hospital desde junio de 2008 hasta diciembre de 2009 y fueron tratados con propranolol oral &#40;dosis de 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d&#237;a&#41;&#46; Fueron seguidos hasta septiembre de 2010&#46; Se analizaron las caracter&#237;sticas epidemiol&#243;gicas&#44; la respuesta al mes&#44; 3&#44; 6&#44; 9&#44; 12 y 18 meses y se registraron los efectos adversos&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se trataron 36 HI en 28 pacientes&#46; El tratamiento con propranolol fue efectivo en todos los casos&#44; con respuesta completa o buena en el 88&#44;2&#37; de los casos a los 6 meses de tratamiento&#46; El efecto fue evidente en las primeras horas tras instaurar el tratamiento&#44; siendo &#250;til tanto en fase proliferativa como involutiva&#46; En HI ulcerados el tiempo medio de cicatrizaci&#243;n fue de 61 d&#237;as&#46; Los efectos adversos fueron leves y autolimitados&#46; S&#243;lo dos pacientes discontinuaron el tratamiento por hipotensi&#243;n&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El propanol oral induce una mejor&#237;a r&#225;pida y mantenida en la gran mayor&#237;a de los HI&#44; acortando considerablemente su evoluci&#243;n natural y con escasos efectos secundarios&#46; En HI ulcerados no observamos una reducci&#243;n significativa de la sintomatolog&#237;a o tiempo de cicatrizaci&#243;n&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; Bernabeu-Wittel J&#44; et al&#46; Tratamiento con propanolol oral para hemangiomas infantiles graves&#58; serie de 28 pacientes&#46; Actas Dermosifiliogr&#46; 2011&#59;102&#58;510&#8211;16&#46;</p>"
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            "imagen" => "gr1.jpeg"
            "Alto" => 597
            "Ancho" => 900
            "Tamanyo" => 68894
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Segmental hemangioma of infancy in S1&#44; S2&#44; and S4 on a 2-month-old girl&#46; Note the marked deformity on the nasal columella and philtrum&#46; Additional tests ruled out PHACE syndrome&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 598
            "Ancho" => 900
            "Tamanyo" => 46778
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Patient from Figure 1 after 5&#46;5 months of treatment &#40;age 7&#46;5 months&#41;&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 600
            "Ancho" => 900
            "Tamanyo" => 61253
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Hemangioma of infancy on the tip of the nose in a child aged 9 months&#44; when a local corticosteroid infiltration was administered&#46; At the age of 18 months&#44; the child began treatment with oral propranolol because of persistence of the lesion&#46; Treatment was maintained for 7 months&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Figure 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 600
            "Ancho" => 900
            "Tamanyo" => 57921
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Patient from Figure 3 at 2 years and 10 months of age &#40;9 months after finishing treatment with propanolol&#41;&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Figure 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 2146
            "Ancho" => 2708
            "Tamanyo" => 252648
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Response to treatment as a percentage by comparing hemangioma of infancy treated in the proliferative phase and those treated in the involutive phase at 1&#44; 3&#44; and 6 months of follow-up&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">In cases of different responses for volume and color&#44; the finding was classified in the next lowest category&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Color&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Volume&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Growth&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased intensity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased volume&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stabilization&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maintenance or clearance &#60;25&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maintenance or reduction &#60;25&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Partial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Partial clearance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Partial volume reduction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total clearance or residual telangiectasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete flattening&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab181781.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Classification of Treatment Response&#46;</p>"
        ]
      ]
      6 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Abbreviation&#58; CI&#44; confidence interval&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sex</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;57&#46;16&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;42&#46;84&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Mean &#40;SD&#41; follow-up</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;09 &#40;4&#46;9&#41; mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Age at first consultation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;12 mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;86 mo &#40;95&#37; CI&#44; 2&#46;80-4&#46;92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#62;12 mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#46;10 mo &#40;95&#37; CI&#44; 13&#46;75-6&#46;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Birth weight</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2951&#46;78 g &#40;1000-4310&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab181780.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Demographic Data&#46;</p>"
        ]
      ]
      7 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Age at onset</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;29 wk &#40;range&#44; 0-4 wk&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Mean &#40;SD&#41; number of hemangiomas</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;28 &#40;1-3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Mean age at first consultation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;53 mo &#40;range&#44; 0&#46;5-30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Type</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Focal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77&#46;78&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Segmental&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#46;22&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Mixed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">88&#46;89&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Superficial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;33&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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Original Article
Propranolol for the Treatment of Severe Hemangiomas of Infancy: Results From a Series of 28 Patients
Tratamiento con propranolol oral para hemangiomas infantiles graves: serie de 28 pacientes
J. Bernabeu-Wittela,
Autor para correspondencia
jbernabeuw@gmail.com

Corresponding author.
, J.J. Pereyra-Rodrígueza, M.E. Mantrana-Bermejob, I. Fernández-Pinedac, J.C. de Agustínc, J. Conejo-Mira
a Unidad de Dermatología Pediátrica, Hospitales Universitarios Virgen del Rocío, Sevilla, Spain
b Servicio de Oftalmología, Hospital San Juan de Dios del Aljarafe, Bormujos, Sevilla, Spain
c Servicio de Cirugía Pediátrica, Hospitales Universitarios Virgen del Rocío, Sevilla, Spain
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        "titulo" => "Tratamiento con propranolol oral para hemangiomas infantiles graves&#58; serie de 28 pacientes"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Patient from Figure 1 after 5&#46;5 months of treatment &#40;age 7&#46;5 months&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Hemangioma of infancy is a benign self-limiting vascular tumor&#46; Although it is estimated to affect 3&#37; to 10&#37; of children during the first year of life&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;5</span></a> a significant percentage of these lesions are associated with marked morbidity&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4&#44;6</span></a> No well-studied or approved systemic treatment is available&#46; Oral prednisolone &#40;2-5 mg&#47;kg&#47;d&#41; is considered a first-line treatment&#44;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#8211;9</span></a> yet only 1 small randomized controlled clinical trial has compared this regimen with intravenous methylprednisolone&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Systemic corticosteroids can prove effective in cases of high-risk lesions&#59; however&#44; treatment response is variable and the side effects are insidious&#44; difficult to monitor&#44; and potentially severe&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Other drugs used to treat high-risk lesions could prove more harmful and have potentially more severe side effects&#44; with even more uncertain results&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;5&#44;10</span></a> These include vincristine&#44; interferon alfa&#44; and cyclophosphamide&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;13</span></a> Propranolol is a &#946;-blocker that has been used for several years to treat heart conditions&#46; The incidental finding of a rapid regression of hemangioma in a patient with obstructive hypertrophic cardiomyopathy who had received oral propranolol &#40;3 mg&#47;kg&#47;d&#41; pointed to a possible therapeutic effect of this agent on hemangioma of infancy&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> A recently published series of pediatric patients with hemangioma of infancy revealed a marked improvement after treatment with oral propranolol&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> This and other studies have led pediatric dermatologists to consider oral propanolol as an option for the treatment of high-risk hemangioma of infancy&#46; At present&#44; however&#44; there are no studies comparing propranolol with alternative drugs&#44; and the largest published series comprises only 32 patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#8211;19</span></a> Furthermore&#44; no case series on the use of propanolol to treat this disease have been published in Spain&#46; Although propranolol is a well-known and widely used drug&#44; many doubts still surround its use for the treatment of hemangioma of infancy&#44; for example&#44; with regard to optimal dose&#44; duration of treatment&#44; and relapse after discontinuation&#46; Consequently&#44; until a controlled clinical trial can be performed&#44; it is of paramount importance that local case series be reported in order to broaden our experience with the use of propranol to treat this tumor&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The objectives of the present study were to determine the effectiveness and safety profile of oral propranolol solution for the treatment of hemangioma of infancy&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Materials and Methods</span><p id="par0015" class="elsevierStylePara elsevierViewall">We performed a descriptive&#44; observational study in which we reviewed all patients with hemangioma of infancy referred to the Department of Pediatric Dermatology at Hospital Universitario Virgen del Roc&#237;o in Seville&#44; Spain over an 18-month period &#40;July 2008 to December 2009&#41;&#46; Follow-up continued until September 30&#44; 2010&#46; The criteria for initiating propranolol for the treatment of hemangioma of infancy in the proliferative phase were risk of functional impairment&#44; local complications&#44; or deformity and age more than 1 month&#46; In the case of involuting hemangioma&#44; the more residually deformed lesions were treated in order to accelerate the natural course before surgery&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Patients with suspected PHACE syndrome were hospitalized for additional investigations &#40;cranial magnetic resonance imaging&#44; cerebral magnetic resonance angiography&#44; abdominal ultrasound&#44; echocardiography&#44; baseline electrocardiogram &#91;ECG&#93;&#44; blood biochemistry&#44; complete blood count&#44; and evaluation by a cardiologist and an ophthalmologist&#41;&#46; Once these had been performed&#44; treatment with propranolol was started during hospitalization&#46; Blood pressure &#40;BP&#41; and heart rate were monitored every 8 hours&#44; blood glucose every 12 hours&#44; and ECG daily for 2 days&#46; The remaining patients underwent a study before initiation of treatment &#40;ECG and evaluation by a pediatric cardiologist&#44; BP and heart rate&#44; blood biochemistry&#44; and complete blood count&#41;&#46; Outpatient treatment was then started&#44; with monitoring of BP and heart rate every 3 days during dose escalation &#40;12 days&#41; and subsequently every week&#46; Monitoring was performed at the patient&#39;s health center under the supervision of the area pediatrician&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Once parental informed consent was obtained&#44; treatment with oral propranolol suspension was started at 5 mg&#47;mL&#46; The initial dose was 0&#46;5 mg&#47;kg&#47;d &#40;0&#46;25 mg&#47;kg&#47;d taken in 2 doses&#41;&#44; with an increase of 0&#46;5 mg&#47;kg&#47;d every 3 days&#44; until a final dose of 2 mg&#47;kg&#47;d was reached&#46; Patients included in the initial stages of the study were reassessed at 1&#44; 3&#44; 6&#44; 9&#44; 12&#44; and 18 months&#46; Patients included in the final stages of the study were reassessed at 1&#44; 3&#44; 6&#44; and 9 months&#46; A digital photograph was taken of all the patients before the study and at each follow-up visit in order to evaluate the response to treatment&#46; Baseline epidemiologic characteristics were analyzed&#44; as was response at each visit&#44; according to the decrease in color intensity and in volume&#46; Treatment response was classified as growth&#44; stabilization&#44; partial response&#44; or complete response &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Adverse effects were also recorded&#46; All the data were collected and processed using SPSS version 17&#46;0&#46; Qualitative variables were expressed as absolute and relative frequency &#40;percentage&#41;&#44; and quantitative variables were expressed as mean &#40;SD&#41;&#46; The Pearson &#967;<span class="elsevierStyleSup">2</span> test was applied to detect a possible relationship between the response to treatment and age at initiation of treatment &#40;less than or more than 6 months and less than or more than 12 months&#41;&#44; as well as the association between location of the lesion and response to treatment&#46; The differences between the duration of treatment in patients aged less than and more than 6 months and between patients aged less than and more than 12 months were analyzed using the <span class="elsevierStyleItalic">t</span> test with a Levene correction&#46; The Shapiro-Wilk test was applied to determine whether the quantitative variables were normally distributed &#40;n &#60; 50&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0030" class="elsevierStylePara elsevierViewall">We analyzed 28 patients with 36 hemangiomas&#46; Demographic data are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; Mean age at onset was 1&#46;29 weeks and the mean number of tumors per child was 1&#46;28&#46; The characteristics of the tumors are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46; Ulceration developed in 38&#46;89&#37; of tumors before initiation of treatment&#46; Twenty-one patients &#40;27 tumors&#41; started treatment before age 12 months&#46; The mean age at the initiation of treatment with propranolol was 3&#46;86 months &#40;95&#37; confidence interval &#91;CI&#93;&#44; 2&#46;80-4&#46;92&#59; range&#44; 1&#46;43-10&#46;23&#41; for patients aged less than 12 months and 20&#46;10 months &#40;95&#37; CI&#44; 13&#46;75-26&#46;44&#59; range&#44; 14&#46;00-32&#46;67&#41; for patients aged more than 12 months&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the location and subtype of the hemangiomas&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Five patients received oral corticosteroids before initiating propranolol&#46; In 4 cases&#44; these drugs were withdrawn after a few weeks&#44; with no signs of regrowth&#46; Four patients had large segmental hemangiomas on the face and 1 had a focal lesion on the upper eyelid&#46; In 3 of these patients &#40;aged 1&#46;5&#44; 2&#44; and 6 months&#41;&#44; the lesion continued to grow despite treatment with oral prednisolone &#40;3 or 5 mg&#47;kg&#47;d&#41;&#44; and oral propranolol was started while the dose of prednisolone was tapered over 3 weeks&#46; In the 2 remaining cases&#44; including the patient with the eyelid lesion&#44; the hemangioma decreased in size with prednisolone at 3 mg&#47;kg&#47;d&#59; however&#44; prednisolone was tapered over 3 weeks as oral propranolol began&#46; The patients were aged 3 and 4 months when propranolol was initiated&#46; One had a mixed segmental hemangioma on the parotid region and ear and needed simultaneous treatment for 4 months with oral corticosteroids &#40;3 mg&#47;kg&#47;d&#41; and oral propranolol &#40;4 mg&#47;kg&#47;d&#41; due to regrowth when corticosteroids were stopped or the dose of propranolol reduced&#46; Only 1 of these patients had PHACE syndrome with persistent trigeminal artery and long segment hypoplasia &#40;&#62;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>cm&#41; in both vertebral arteries and the basilar artery&#46; The segmental cervicofacial hemangioma occluded the midline of the right eye&#46; The patient did not respond to oral prednisolone&#59; therefore&#44; treatment with propranolol was started and administered up to 2 mg&#47;kg&#47;d&#44; with a complete response at 16 months and no adverse effects&#46; Only 1 patient was treated using previous local infiltration of corticosteroids&#59; no patients received vincristine or interferon&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">A response to propranolol was observed in all patients at 48 hours&#46; In all patients &#40;both less than and more than 12 months&#41;&#44; the color of the tumor changed from bright red to dull red&#44; and the lesion softened&#46; The eye opened spontaneously in all affected patients within 7 days of treatment &#40;range&#44; 2-7 days&#41;&#46; In 9 cases of ulcerated hemangioma &#40;25&#37;&#41;&#44; cure was complete after a mean of 61 days &#40;range&#44; 15-120 days&#41;&#46; In one patient with 3 ulcerated tumors&#44; treatment was combined with pulsed dye laser&#44; as the ulceration was persistent&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">After 1 month of treatment&#44; a complete response was observed in 6&#46;1&#37; of the hemangiomas and a partial response in 93&#46;9&#37;&#46; At 3 months&#44; a complete response was observed in 27&#46;7&#37; of patients and a partial response in 66&#46;6&#37;&#46; At this point&#44; the dose was increased in 2 patients with hemangioma to 2-4 mg&#47;kg&#47;d&#44; owing to stabilization or growth of the lesion accompanied by severe deformity&#46; At 6 months&#44; the response was complete in 66&#46;6&#37; of patients and partial in 30&#46;5&#37;&#59; the response was stable in 2&#46;7&#37; of the treated tumors &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1&#8211;4</a>&#41;&#46; Response by patient age &#40;less than or more than 12 months&#41; is shown in <a class="elsevierStyleCrossRef" href="#fig0025">Figure 5</a>&#46; The differences in response found between patients aged less than or more than 6 months or less than or more than 12 months were not statistically significant &#40;Pearson &#967;<span class="elsevierStyleSup">2</span>&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;261 and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;432&#44; respectively&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Analysis of the response to treatment by location showed that response was complete at 6 months in the 6 tumors affecting the eyelids &#40;4 focal and 2 segmental&#41; and the 4 tumors on the scalp&#46; Of the 5 tumors on the tip of the nose&#44; 4 had a complete response and 1 had a partial response at 6 months&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Mean duration of treatment was 8&#46;7 months &#40;range&#44; 2-16 months&#41;&#46; No statistically significant differences were observed in duration of treatment between patients aged less than or more than 6 months or between patients aged less than and more than 12 months &#40;<span class="elsevierStyleItalic">t</span> test with a Levene correction&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;341 and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;643&#44; respectively&#41;&#46; In all the treated patients&#44; the criterion for discontinuing propranolol was absence of a visible improvement for at least 1 month and absence of regrowth when the dose of propranolol was reduced to 1 mg&#47;kg&#47;d and after complete suspension&#46; When the dose of propranolol was reduced from 2 to 1 mg&#47;kg&#47;d&#44; it was necessary to increase the dose to 2 mg&#47;kg&#47;d due to regrowth in some cases &#40;4 segmental hemangiomas in children aged less than 12 months&#44; 2 deep focal tumors&#44; and 1 mixed focal tumor in children aged over 12 months&#41;&#46; After complete suspension in children aged less than 12 months&#44; 2 tumors grew again and a further 2 had a slight increase in coloring of the residual telangiectasia that did not require treatment to be restarted&#46; Regrowth was only observed in 1 patient from the group of children aged more than 12 months&#44; and there was no requirement for treatment to be restarted&#46; We did not find a statistically significant association between the location of the lesions and response to treatment &#40;Pearson &#967;<span class="elsevierStyleSup">2</span>&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;412&#41;&#46; Adverse effects were only observed in 2 patients&#44; both of whom had an episode of hypotension during the first month of treatment &#40;at 2 mg&#47;kg&#47;d&#41;&#46; The first case &#40;BP&#44; 62&#47;45 mm Hg&#41; was asymptomatic and resolved spontaneously in 15 minutes&#46; Treatment for regrowth was reintroduced at 1 mg&#47;kg&#47;d&#59; hypotension &#40;BP&#44; 50&#47;35 mm Hg&#41; was again recorded&#44; although it was asymptomatic and self-limiting&#44; and treatment was discontinued&#46; In the second case&#44; hypotension &#40;BP&#44; 60&#47;35 mm Hg&#41; was accompanied by lethargy and the patient was seen in the emergency department of Hospital Infantil Virgen del Roc&#237;o&#46; The condition resolved spontaneously after 30 mintues and treatment was discontinued&#46; During treatment&#44; 3 patients had acute bronchitis&#44; which resolved without complications after temporary suspension of oral propranolol and treatment with inhaled salbutamol and oral corticosteroids&#46; No regrowth of the hemangioma was observed&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Of the 6 patients with hemangiomas affecting the eyes &#40;4 focal hemangiomas and 2 segmental tumors&#41;&#44; the midline was affected in only 2 cases&#46; The eyelid was completely occluded after the first month of life in 1 of these patients&#44; although only for a short period &#40;7 days&#41;&#46; Anisometropia was ruled out in all cases based on refraction assessed using retinoscopy with dilated pupils&#46; Visual acuity was assessed in children aged less than 2 years using the fix and follow reflex&#44; which made it possible to rule out moderate and severe ambliopia&#46; According to the judgement of the pediatric ophthalmologist&#44; no children required treatment&#46; Nevertheless&#44; these patients are still being monitored by the pediatric ophthalmology unit&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">We found treatment with propranolol to be effective in all cases&#44; with a complete response at 6 months in 66&#46;6&#37;&#46; The results were apparent during the first hours of treatment in the form of changes in the color and consistency of the lesions&#46; This finding is consistent with those of other published series&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#8211;19</span></a> The action of the drug was particularly striking in tumors on the eyelid&#44; scalp&#44; and tip of the nose&#46; However&#44; we did not find a statistically significant association between the location of the lesions and response to treatment&#44; probably as a result of the small sample size&#46; Of note&#44; oral propranolol did not only lead to stabilization of growth&#8212;as occurs with corticosteroids&#8212;but the improvement also continued in many cases until regression was complete at very young ages&#44; thus considerably reducing the duration of these lesions&#46; Furthermore&#44; this rapid and significant response was also observed in all tumors in patients aged over 12 months&#46; With corticosteroids&#44; on the other hand&#44; treatment is only effective during the proliferative phase&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;19</span></a> We observed a more marked response at 6 months of treatment in patients treated before they were 12 months old &#40;74&#37; vs 44&#46;6&#37;&#41;&#46; It is noteworthy that&#44; in patients aged more than 12 months&#44; both complete response and partial response were the same at 3 and 6 months of treatment&#44; probably because&#44; at this age&#44; it is more difficult to obtain a complete response with no residual deformity using medical treatment alone&#46; In cases treated early&#44; complete remission occurred at a mean age of 8&#46;7 months&#44; suggesting that treatment with propranolol should be started during the proliferative phase and before most lesions reach their maximum size&#44; at around 5 months of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16&#44;18&#44;19</span></a> We believe that empirical treatment should be maintained in involuting lesions &#40;late treatment&#41; until the optimal result is obtained&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Oral propranolol should not be used as a first-line treatment option in patients with hemangioma of infancy and intracranial vascular abnormalities&#46; However&#44; we elected to initiate treatment with oral propranolol in the patient with PHACE syndrome included in this study&#44; since a large segmental hemangioma completely occluded the midline of the right eye despite treatment with oral corticosteroids&#44; and the cerebral vascular abnormalities did not affect the internal carotid artery&#44; which has been implicated in all cases of cerebrovascular accidents associated with PHACE&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Furthermore&#44; that patient needed the longest course of treatment &#40;until 18 months of age&#41; of all those who started propranolol early &#40;16 months of treatment&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In our experience&#44; propranolol should be withdrawn gradually&#58; when the dose is reduced&#44; recoloring or regrowth can be observed in some cases&#44; thus making it necessary to prolong treatment&#46; By adopting this approach&#44; we did not have to reintroduce the drug after complete withdrawal&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In the case of ulceration&#44; the results obtained with oral propranolol to date have been variable&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;21&#44;22</span></a> The mean healing time for ulcerated hemangiomas in our series was 61 days&#44; and in 1 patient pharmacotherapy was combined with pulsed dye laser&#46; We think that the presence of ulceration does not in itself indicate administration of propranolol&#44; as in our series we observed no differences in improvement of symptoms or healing time compared with other treatments&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#8211;30</span></a> Randomized comparative studies are necessary to clarify this point&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">We found most adverse effects to be mild and predictable at the dose administered&#44; although one of the patients who experienced hypotension required emergency care&#46; Blood glucose was not monitored during treatment&#46; Given that one of the possible adverse effects of oral propranolol is low blood glucose&#44; parents were advised to administer treatment every 12 hours with meals and to withdraw treatment temporarily in case of vomiting&#59; however&#44; it was not necessary to stop treatment for this reason at any time during follow-up&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Our study is limited by its small sample size&#44; which could mean that the differences detected did not reach statistical significance&#46; Nevertheless&#44; our sample size is similar to that of other studies&#44; and our findings increase worldwide clinical experience with propranolol in the treatment of hemangioma of infancy&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">In conclusion&#44; according to the present study&#44; treatment with oral propranolol solution at 2 mg&#47;kg&#47;d is an effective&#44; safe&#44; and well-tolerated option for the treatment of hemangioma of infancy&#46; The effect is apparent during the first few hours after starting treatment&#44; which should be maintained for several weeks&#44; generally up to 6 months&#44; in order to obtain a considerable improvement and halt the natural course of the lesion&#46; This treatment seems to be more effective in lesions in the proliferative phase&#59; however&#44; in our experience&#44; it does not significantly reduce symptom severity or time to scarring when ulceration is present&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of Interest</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Background and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Recent reports have described the successful use of propranolol to treat severe hemangiomas of infancy&#46; The few case series that have been reported&#44; however&#44; have included only a small number of patients&#46; The aim of this study was to describe the results of oral propranolol treatment for severe hemangiomas of infancy in terms of treatment outcome and the occurrence of adverse events&#46;</p> <span class="elsevierStyleSectionTitle">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A descriptive&#44; observational study was undertaken in a series of children with severe hemangiomas of infancy seen in the pediatric dermatology unit at Hospital Universitario Virgen del Roc&#237;o in Seville&#44; Spain between July 2008 and December 2009&#46; Patients were included if they had hemangiomas in the proliferative phase or involuting lesions with substantial residual deformity&#46; All children were treated with oral propranolol &#40;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d&#41; and followed until September 2010&#46; Epidemiologic characteristics were analyzed along with treatment response at 3&#44; 6&#44; 9&#44; 12&#44; and 18 months&#59; adverse events were also recorded at those times&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Thirty-six hemangiomas were treated in 28 patients&#46; Propranolol treatment was effective in all cases&#44; with a good or complete response in 88&#46;2&#37; at 6 months&#46; Effects were apparent within a few hours of treatment&#44; which was effective in both growing and involuting hemangiomas&#46; In ulcerated hemangiomas&#44; the mean healing time was 61<span class="elsevierStyleHsp" style=""></span>days&#46; Adverse events were mild and self-limiting&#46; Only 2 patients discontinued treatment due to hypotension&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In the majority of cases&#44; oral propranolol produced rapid and sustained improvements in hemangiomas of infancy and shortened the natural course of the disease with few side effects&#46; However&#44; no significant reductions in symptoms or healing time were observed in ulcerated hemangiomas&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Introducci&#243;n y objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Recientemente se ha comunicado el &#233;xito del tratamiento con propranolol para hemangiomas infantiles &#40;HI&#41; graves&#46; Existen escasas series publicadas con reducido n&#250;mero de pacientes&#46; El objetivo del presente estudio fue conocer la efectividad y seguridad de propranolol oral para HI graves&#46;</p> <span class="elsevierStyleSectionTitle">Material y m&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional y descriptivo de una serie de ni&#241;os con HI graves en fase proliferativa&#44; o en fase involutiva si presentaban importante deformidad residual&#44; que acudieron a la Unidad de Dermatolog&#237;a Pedi&#225;trica de nuestro hospital desde junio de 2008 hasta diciembre de 2009 y fueron tratados con propranolol oral &#40;dosis de 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d&#237;a&#41;&#46; Fueron seguidos hasta septiembre de 2010&#46; Se analizaron las caracter&#237;sticas epidemiol&#243;gicas&#44; la respuesta al mes&#44; 3&#44; 6&#44; 9&#44; 12 y 18 meses y se registraron los efectos adversos&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se trataron 36 HI en 28 pacientes&#46; El tratamiento con propranolol fue efectivo en todos los casos&#44; con respuesta completa o buena en el 88&#44;2&#37; de los casos a los 6 meses de tratamiento&#46; El efecto fue evidente en las primeras horas tras instaurar el tratamiento&#44; siendo &#250;til tanto en fase proliferativa como involutiva&#46; En HI ulcerados el tiempo medio de cicatrizaci&#243;n fue de 61 d&#237;as&#46; Los efectos adversos fueron leves y autolimitados&#46; S&#243;lo dos pacientes discontinuaron el tratamiento por hipotensi&#243;n&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El propanol oral induce una mejor&#237;a r&#225;pida y mantenida en la gran mayor&#237;a de los HI&#44; acortando considerablemente su evoluci&#243;n natural y con escasos efectos secundarios&#46; En HI ulcerados no observamos una reducci&#243;n significativa de la sintomatolog&#237;a o tiempo de cicatrizaci&#243;n&#46;</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; Bernabeu-Wittel J&#44; et al&#46; Tratamiento con propanolol oral para hemangiomas infantiles graves&#58; serie de 28 pacientes&#46; Actas Dermosifiliogr&#46; 2011&#59;102&#58;510&#8211;16&#46;</p>"
      ]
    ]
    "multimedia" => array:8 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 597
            "Ancho" => 900
            "Tamanyo" => 68894
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Segmental hemangioma of infancy in S1&#44; S2&#44; and S4 on a 2-month-old girl&#46; Note the marked deformity on the nasal columella and philtrum&#46; Additional tests ruled out PHACE syndrome&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 598
            "Ancho" => 900
            "Tamanyo" => 46778
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Patient from Figure 1 after 5&#46;5 months of treatment &#40;age 7&#46;5 months&#41;&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 600
            "Ancho" => 900
            "Tamanyo" => 61253
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Hemangioma of infancy on the tip of the nose in a child aged 9 months&#44; when a local corticosteroid infiltration was administered&#46; At the age of 18 months&#44; the child began treatment with oral propranolol because of persistence of the lesion&#46; Treatment was maintained for 7 months&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Figure 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 600
            "Ancho" => 900
            "Tamanyo" => 57921
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Patient from Figure 3 at 2 years and 10 months of age &#40;9 months after finishing treatment with propanolol&#41;&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Figure 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 2146
            "Ancho" => 2708
            "Tamanyo" => 252648
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Response to treatment as a percentage by comparing hemangioma of infancy treated in the proliferative phase and those treated in the involutive phase at 1&#44; 3&#44; and 6 months of follow-up&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">In cases of different responses for volume and color&#44; the finding was classified in the next lowest category&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Color&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Volume&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Growth&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased intensity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased volume&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stabilization&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maintenance or clearance &#60;25&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maintenance or reduction &#60;25&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Partial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Partial clearance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Partial volume reduction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total clearance or residual telangiectasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete flattening&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab181781.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Classification of Treatment Response&#46;</p>"
        ]
      ]
      6 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Abbreviation&#58; CI&#44; confidence interval&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sex</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;57&#46;16&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;42&#46;84&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Mean &#40;SD&#41; follow-up</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;09 &#40;4&#46;9&#41; mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Age at first consultation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;12 mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;86 mo &#40;95&#37; CI&#44; 2&#46;80-4&#46;92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#62;12 mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#46;10 mo &#40;95&#37; CI&#44; 13&#46;75-6&#46;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Birth weight</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2951&#46;78 g &#40;1000-4310&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab181780.png"
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            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Demographic Data&#46;</p>"
        ]
      ]
      7 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Age at onset</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;29 wk &#40;range&#44; 0-4 wk&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Mean &#40;SD&#41; number of hemangiomas</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;28 &#40;1-3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Mean age at first consultation</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5&#46;53 mo &#40;range&#44; 0&#46;5-30&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Type</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">77&#46;78&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">22&#46;22&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">8&#46;33&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;78&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5 &#40;13&#46;89&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Lip&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4 &#40;11&#46;11&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;11&#46;11&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;11&#46;11&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3 &#40;8&#46;33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;16&#46;67&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Extremities&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2 &#40;5&#46;56&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Segmental</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Face&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;5&#46;56&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Face and neck&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3 &#40;8&#46;33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Characteristics of Hemangioma of Infancy&#46;</p>"
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