Hemangioma segmentario de la barba / Segmental Beard Hemangioma

Los hemangiomas infantiles son el resultado de la proliferación de células del endotelio vascular y representan los tumores benignos más frecuentes en la infancia, con una incidencia estimada del 4-10% en bebés caucásicos. Se clasifican según el número, la profundidad y la distribución. Dentro de esta última clasificación se encuentran aquellos denominados segmentarios, que se caracterizan por su distribución extensa en áreas de prolongaciones mesodérmicas embrionarias. Se comunica el caso de una paciente evaluada al mes y medio de vida, con un hemangioma extenso del área mandibular y cuello anterior (hemangioma segmentario de la barba). Se describe la importancia de los estudios complementarios para evaluar el compromiso de órganos subyacentes, para detectar síndromes asociados y definir el tratamiento sobre la base de estos resultados. (AU)

Infantile hemangiomas arise from the proliferation of vascular endothelial cells and represent the most common benign tumors in infancy, with an estimated incidence of 4-10% in Caucasian infants. They vary according to their number, depth, and distribution. Within the latter classification are the so-called segmental ones, which feature an extensive distribution in areas of embryonic mesodermal extensions. We report the case of a patient evaluated at one and a half months of life with an extensive hemangioma of the mandibular area and anterior neck (segmental hemangioma of the beard). We describe the importance of complementary studies for evaluating the involvement of underlying organs, detecting associated syndromes, and defining the treatment based on these findings. (AU)

A MULTIFACTORIAL APPROACH FOR IMPROVING THE SURGICAL PERFORMANCE OF NOVICE VITREORETINAL SURGEONS.

PURPOSE: To quantitatively analyze and compare the novice vitreoretinal surgeons' performance after various types of external exposures. METHODS: This prospective, self-controlled, cross-sectional study included 15 vitreoretinal fellows with less than 2 years of experience. Surgical performance was assessed using the Eyesi simulator after each exposure: Day 1, placebo, 2.5, and 5 mg/kg caffeine; Day 2, placebo, 0.2, and 0.6 mg/kg propranolol; Day 3, baseline simulation, breathalyzer reading of 0.06% to 0.10% and 0.11% to 0.15% blood alcohol concentration; Day 4, baseline simulation, push-up sets with 50% and 85% repetition maximum; Day 5, 3-hour sleep deprivation. Eyesi-generated total scores were the main outcome measured (0-700, worst to best). RESULTS: Performances worsened after increasing alcohol exposure based on the total score (χ2 = 7; degrees of freedom = 2; P = 0.03). Blood alcohol concentration 0.06% to 0.10% and 0.11% to 0.15% was associated with diminished performance compared with improvements after propranolol 0.6 and 0.2 mg/kg, respectively (∆1 = -22 vs. ∆2 = +13; P = 0.02; ∆1 = -43 vs. ∆2 = +23; P = 0.01). Propranolol 0.6 mg/kg was positively associated with the total score, compared with deterioration after 2.5 mg/kg caffeine (∆1 = +7 vs. ∆2 = -13; P = 0.03). CONCLUSION: Surgical performance diminished dose dependently after alcohol. Caffeine 2.5 mg/kg was negatively associated with dexterity, and performance improved after 0.2 mg/kg propranolol. No changes occurred after short-term exercise or acute 3-hour sleep deprivation.

Evaluation of Depressive and Anxious Behavior with the Use of Propranolol in Melanoma-Bearing Mice

HIGHLIGHTS: Tumor progression and anxiety and depression behaviors under evaluation during propranolol use in murine melanoma. Evaluation of anxiety and depression through forced swimming behavior tests, elevated plus maze, open field and marble-burying test.

Abstract Melanoma, a severe form of skin cancer, has rapid growth and has been prone to behavioral disorders that worsen the patient's prognosis and survival. Among these psychic disorders can occur anxiety and depression, in addition to cognitive deficit. In order to try to elucidate the neuropsychological disorders that occur in melanoma, the objective of this study was to evaluate propranolol in tumor progression and in anxious and depressive behaviors in an animal model with melanoma. B16F10 cells were injected into C57BL6/J mice subsequently treated with propranolol at doses of 1.43 mg/kg and 5.71 mg/kg and evaluated for tumor growth and in open field, forced swimming, elevated plus maze and marble-burying test at initial time and consolidated tumor. As a result, the group treated with propranolol at a dose of 5.71 mg/kg showed less tumor growth. In the initial behavioral tests, melanoma altered the animals' motility, but anxious behavior was not detected. Depressive behavior was detected in the forced swimming test in the two doses of the treatment used. When taking time with consolidated tumor, there was a reduction in the locomotor activity of the animals in the open field test, impairing the analysis of anxious and depressive behavior. The data suggest that there was a reduction in the progression of melanoma, there was no anxious behavior in the animals, only the depressive behavior and the use of propranolol did not improve the evaluated behavior.

Beta-adrenergic blocker inhibits oral carcinogenesis and reduces tumor invasion.

PURPOSE: Beta-adrenergic signaling can influence cancer progression and the use of beta blockers as adjuvant drugs in oncologic patients has been suggested. However, the involvement of beta-adrenergic blockers in tumorigenesis is poorly understood. This study investigated the action of beta-adrenergic blocker propranolol on tumor onset using a preclinical model of chemically induced oral cancer. METHODS: Thirty-two male Wistar rats were subjected to daily subcutaneous injection of beta-blocker propranolol (10 mg/kg; SubQ), while another 32 rats received only a PBS injection (sham group). One week after starting propranolol treatment, all rats were submitted to chemical induction of oral carcinogenesis with 4-nitroquinoline-1-oxide (4NQO). After 16 weeks, they were assessed for occurrence of oral squamous cell carcinoma (OSCC), in addition to measurement of tumor volume and thickness, and tissue levels of cytokines IL-6, TNF-alpha and IL-10 in the tumor microenvironment. RESULTS: Propranolol treatment reduced the occurrence of OSCC by 31%, 95% CI ( - 127, 216). Beta-adrenergic blocker significantly decreased thickness of OSCC when compared with PBS. Rats treated with propranolol exhibited a lower tumor volume when compared with control rats, but this result did not reach statistical significance. Tumors from propranolol-treated rats exhibited reduced concentrations of pro-inflammatory cytokines IL-6 and TNF-α. There was no difference in the IL-10 levels between tumors from propranolol- and sham-treated rats. CONCLUSION: Beta-adrenergic signaling may be one of the mechanisms associated with chemically induced oral carcinogenesis.

Experiencia en el uso de propranolol para el tratamiento de la taquicardia supraventricular en pacientes menores de un año / Experience using propranolol for the management of supraventricular tachycardia in patients younger than 1 year

Objetivo. Evaluar los resultados y efectos adversos de la terapia con propranolol en menores de un año con taquicardia supraventricular. Población y métodos. Menores de 1 año con taquicardia supraventricular documentada, que recibieron tratamiento y prevención con propranolol por vía oral. Se analizaron sexo y edad, cardiopatía congénita asociada, pre excitación ventricular en el electrocardiograma basal, recurrencia intratratamiento y efectos adversos. Resultados. Se identificaron 107 pacientes. El primer episodio de taquicardia supraventricular ocurrió a una edad mediana de 190 días. En 10 pacientes, se observó cardiopatía congénita asociada. El 23,3 % presentó pre excitación ventricular en el electrocardiograma basal. El rango de la dosis de propranolol fue de 2 a 5 mg/kg/día. En el 30,8 %, se observó recurrencia intratratamiento. En 2 pacientes, se suspendió la medicación por efectos adversos graves. Conclusión. El propranolol evitó la recurrencia en el 70 % de los casos. En 2 pacientes, fue necesario suspenderlo por efectos adversos graves

Objective. To assess the results and adverse events of propranolol therapy in infants younger than 1 year with supraventricular tachycardia. Population and methods. Infants younger than 1 year with documented supraventricular tachycardia who received oral treatment and prophylaxis with propranolol. Sex and age, associated congenital heart disease, ventricular preexcitation in the base line electrocardiogram, on-treatment recurrence, and adverse events were analyzed. Results. A total of 107 patients were identified. The first supraventricular tachycardia event occurred at a median age of 190 days. Associated congenital heart disease was observed in 10 patients. Ventricular preexcitation in the baseline electrocardiogram was detected in 23.3 %. Propranolol dose ranged from 2 to 5 mg/kg/day. On-treatment recurrence was observed in 30.8 %. Medication was discontinued in 2 patients due to severe adverse events. Conclusion. Propranolol prevented recurrence in 70 % of cases. It was discontinued in 2 patients due to severe adverse events.

Experience using propranolol for the management of supraventricular tachycardia in patients younger than 1 year. / Experiencia en el uso de propranolol para el tratamiento de la taquicardia supraventricular en pacientes menores de un año.

OBJECTIVE: To assess the results and adverse events of propranolol therapy in infants younger than 1 year with supraventricular tachycardia. POPULATION AND METHODS: Infants younger than 1 year with documented supraventricular tachycardia who received oral treatment and prophylaxis with propranolol. Sex and age, associated congenital heart disease, ventricular preexcitation in the base line electrocardiogram, on-treatment recurrence, and adverse events were analyzed. RESULTS: A total of 107 patients were identified. The first supraventricular tachycardia event occurred at a median age of 190 days. Associated congenital heart disease was observed in 10 patients. Ventricular preexcitation in the baseline electrocardiogram was detected in 23.3 %. Propranolol dose ranged from 2 to 5 mg/kg/day. On-treatment recurrence was observed in 30.8 %. Medication was discontinued in 2 patients due to severe adverse events. CONCLUSION: Propranolol prevented recurrence in 70 % of cases. It was discontinued in 2 patients due to severe adverse events.

Objetivo. Evaluar los resultados y efectos adversos de la terapia con propranolol en menores de un año con taquicardia supraventricular. Población y métodos. Menores de 1 año con taquicardia supraventricular documentada, que recibieron tratamiento y prevención con propranolol por vía oral. Se analizaron sexo y edad, cardiopatia congènita asociada, pre excitación ventricular en el electrocardiograma basal, recurrencia intratratamiento y efectos adversos. Resultados. Se identificaron 107 pacientes. El primer episodio de taquicardia supraventricular ocurrió a una edad mediana de 190 días. En 10 pacientes, se observó cardiopatia congènita asociada. El 23,3 % presentó pre excitación ventricular en el electrocardiograma basal. El rango de la dosis de propranolol fue de 2 a 5 mg/kg/día. En el 30,8 %, se observó recurrencia intratratamiento. En 2 pacientes, se suspendió la medicación por efectos adversos graves. Conclusión. El propranolol evitó la recurrencia en el 70 % de los casos. En 2 pacientes, fue necesario suspenderlo por efectos adversos graves.

Propranolol for infantile hepatic hemangioendothelioma: Clinical evaluation of drug efficacy and safety using a single-center patient cohort.

INTRODUCTION AND OBJECTIVES: Infantile hepatic hemangioendothelioma (IHHE) is a benign liver tumor, associated with hypothyroidism and vascular malformations along the skin, brain, digestive tract and other organs. Here, we determined a single-center patient cohort by evaluating the effectiveness and safety of propranolol and sirolimus for the treatment of IHHE. PATIENTS AND METHODS: We performed a monocentric and observational study, based on clinical data obtained from 20 cases of IHHE treated with oral propranolol and sirolimus at the Shanghai Children's Medical Center (SCMC), between December 2017 and April 2019. All cases were confirmed by abdominal enhanced CT examination (18/20, 90%) and sustained decrease of alpha fetoprotein (AFP) (2/20, 10%). Propranolol treatment was standardized as once a day at 1.0mg/kg for patients younger than 2 months, and twice a day at 1.0mg/kg (per dose) for patients older than 2 months. Sirolimus was used to treat refractory IHHE patients after 6 months of propranolol treatment, and initial dosing was at 0.8mg/m2 body surface per dose, administered every 12h. Upon treatment, abdominal ultrasound scanning was regularly performed to evaluate any therapeutic effects. All children were followed up for 6-22 months (mean value of 12.75 months). The clinical manifestations and therapeutic effects, including complications during drug management, were reviewed after periodic follow-up. RESULTS: The effective rate of propranolol for the treatment of children with IHHE was 85% (17/20). In most cases, the AFP levels gradually decreased into the normal range. A complete response (CR) was achieved in 3 cases, partial response (PR) for 14 cases, progressive disease (PD) for 2 cases and stable disease (SD) was only detected once. Lesions decreased in two PD patients after administration of oral sirolimus. No serious adverse reactions were observed. CONCLUSION: This study indicates that both propranolol and sirolimus were effective drugs for the treatment of children with IHHE at SCMC.

Association of Weight-Adjusted Caffeine and ß-Blocker Use With Ophthalmology Fellow Performance During Simulated Vitreoretinal Microsurgery.

Importance: Vitreoretinal surgery can be technically challenging and is limited by physiologic characteristics of the surgeon. Factors that improve accuracy and precision of the vitreoretinal surgeon are invaluable to surgical performance. Objectives: To establish weight-adjusted cutoffs for caffeine and ß-blocker (propranolol) intake and to determine their interactions in association with the performance of novice vitreoretinal microsurgeons. Design, Settings, and Participants: This single-blind cross-sectional study of 15 vitreoretinal surgeons who had less than 2 years of surgical experience was conducted from September 19, 2018, to September 25, 2019, at a dry-laboratory setting. Five simulations were performed daily for 2 days. On day 1, performance was assessed after sequential exposure to placebo, low-dose caffeine (2.5 mg/kg), high-dose caffeine (5.0 mg/kg), and high-dose propranolol (0.6 mg/kg). On day 2, performance was assessed after sequential exposure to placebo, low-dose propranolol (0.2 mg/kg), high-dose propranolol (0.6 mg/kg), and high-dose caffeine (5.0 mg/kg). Interventions: Surgical simulation tasks were repeated 30 minutes after masked ingestion of placebo, caffeine, or propranolol pills during the 2 days. Main Outcomes and Measures: An Eyesi surgical simulator was used to assess surgical performance, which included surgical score (range, 0 [worst] to 700 [best]), task completion time, intraocular trajectory, and tremor rate (range, 0 [worst] to 100 [best]). The nonparametric Friedman test followed by Dunn-Bonferroni post hoc test was applied for multiple comparisons. Results: Of 15 vitreoretinal surgeons, 9 (60%) were male, with a mean (SD) age of 29.6 (1.4) years and mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 23.15 (2.9). Compared with low-dose propranolol, low-dose caffeine was associated with a worse total surgical score (557.0 vs 617.0; difference, -53.0; 95% CI, -99.3 to -6.7; P = .009), a lower antitremor maneuver score (55.0 vs 75.0; difference, -12.0; 95% CI, -21.2 to -2.8; P = .009), longer intraocular trajectory (2298.6 vs 2080.7 mm; difference, 179.3 mm; 95% CI, 1.2-357.3 mm; P = .048), and increased task completion time (14.9 minutes vs 12.7 minutes; difference, 2.3 minutes; 95% CI, 0.8-3.8 minutes; P = .048). Postcaffeine treatment with propranolol was associated with performance improvement; however, surgical performance remained inferior compared with low-dose propranolol alone for total surgical score (570.0 vs 617.0; difference, -51.0; 95% CI, -77.6 to -24.4; P = .01), tremor-specific score (50.0 vs 75.0; difference, -16.0; 95% CI, -31.8 to -0.2; P = .03), and intraocular trajectory (2265.9 mm vs 2080.7 mm; difference, 166.8 mm; 95% CI, 64.1-269.6 mm; P = .03). Conclusions and Relevance: The findings suggest that performance of novice vitreoretinal surgeons was worse after receiving low-dose caffeine alone but improved after receiving low-dose propranolol alone. Their performance after receiving propranolol alone was better than after the combination of propranolol and caffeine. These results may be helpful for novice vitreoretinal surgeons to improve microsurgical performance.

Success in the use of oral propranolol in the treatment of infantile hemangioma in nasal tip - Report of two cases

Abstract Infantile hemangioma is the most common pediatric vascular tumor, with the following risk factors: low birth weight, prematurity, white skin, female gender, multiparity and advanced maternal age. The use of oral and topical beta-blockers, although recent, has emerged as the first line of treatment, with superior safety and efficacy to previously used therapies, such as corticosteroids and surgeries. This report describes two cases of nasal tip infantile hemangioma, treated with oral propranolol. Both presented excellent therapeutic responses.

Success in the use of oral propranolol in the treatment of infantile hemangioma in nasal tip - Report of two cases.

Infantile hemangioma is the most common pediatric vascular tumor, with the following risk factors: low birth weight, prematurity, white skin, female gender, multiparity and advanced maternal age. The use of oral and topical beta-blockers, although recent, has emerged as the first line of treatment, with superior safety and efficacy to previously used therapies, such as corticosteroids and surgeries. This report describes two cases of nasal tip infantile hemangioma, treated with oral propranolol. Both presented excellent therapeutic responses.

Propranolol inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats.

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for ß-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.

Interventions for infantile haemangiomas of the skin: abridged Cochrane systematic review and GRADE assessments.

BACKGROUND: Infantile haemangiomas (IH) are soft swellings of the skin that occur in 3-10% of infants. When haemangiomas occur in high-risk areas or when complications develop, active intervention is necessary. OBJECTIVE: To update a Cochrane Review assessing the interventions for the management of IH in children. METHODS: We searched for randomized controlled trials in CENTRAL, MEDLINE, Embase, LILACS, AMED, PsycINFO, CINAHL and six trials registers up to February 2017. We included 28 trials (1728 participants) assessing 12 interventions. RESULTS: We downgraded evidence from high to moderate/low for issues related to risk of bias and imprecision. Oral propranolol (3 mg kg-1 daily) probably improves clinician-assessed clearance vs placebo [risk ratio (RR) 16·61, 95% confidence interval (CI) 4·22-65·34; moderate quality of evidence (QoE)]; we found no evidence of a difference in terms of serious adverse events (RR 1·05, 95% CI 0·33-3·39; low QoE). We found the chance of reduction of redness may be improved with topical timolol maleate (0·5% gel applied twice daily) when compared with placebo (RR 8·11, 95% CI 1·09-60·09; low QoE). We found no instances of bradycardia or hypotension for this comparison. CONCLUSIONS: Our key results indicate that oral propranolol and topical timolol maleate are more beneficial than placebo in terms of clearance or other measures of resolution, or both, without an increase in harm.

Propranolol inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for β-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.

Cloridrato de propranolol (solução oral 3, 75 mg/mL) para pacientes com hemangioma infantil / Propranolol hydrochloride (oral solution 3. 75 mg/mL) for patients with childhood hemangioma

INTRODUÇÃO: Os hemangiomas infantis (HI) são os tumores vasculares benignos mais comuns na infância, presentes em cerca de 4%-5% da população. A grande maioria dos HI não apresenta complicações nem necessita de intervenção terapêutica, mas alguns deles podem estar associados a alterações estéticas relevantes e morbidade manifesta. São caracterizados por uma fase de rápida proliferação de vasos sanguíneos no primeiro ano de vida, seguida por uma fase de involução, na qual ocorre uma regressão gradual do tecido vascular, que é substituído por tecido fibroso, e uma fase na qual não há mais modificação na lesão, chamada involuída. Para pacientes com HI complicados, que necessitam tratamento, a conduta medicamentosa é a escolha para a maioria dos pacientes. As principais opções terapêuticas são o propranolol, os glicocorticoides e a alfainterferona. Contudo, antes da escolha terapêutica, é fundamental a avaliação do risco/benefício de cada uma das opções. TECNOLOGIA: Cloridrato de Propranolol (Promangiol®). PERGUNTA: O uso do Cloridrato de Propranolol (Promangiol®) 3,75 mg/mL de solução oral é mais eficaz, seguro ou custo-efetivo em pacientes com hemangioma infantil proliferativo quando comparado as alternativas já disponíveis atualmente no SUS? EVIDÊNCIAS CIENTÍFICAS: Os estudos demostram eficácia e segurança do Cloridrato de Propranolol em comparação ao placebo, mas nenhum estudo que avaliasse comparativamente as duas formas farmacêuticas de Cloridrato de Propranolol (comprimido e solução oral), ou outros comparadores foi encontrado. Portanto não podemos inferir sobre a superioridade, inferioridade ou igualdade entre Promangiol® e as alternativas já disponíveis no SUS. Também não encontramos nenhum estudo que avaliou adesão ao tratamento ou qualidade de vida entre os comparadores. AVALIAÇÃO ECONÔMICA: O demandante apresentou uma análise de custo-utilidade, os dados de eficácia e efetividade resultaram em um total de anos de vida ajustados à qualidade de 15,45 anos para o Cloridrato de Propranolol (Promangiol®) e de 10,80 para o placebo (resultado considerando desconto). O resultado incremental foi de 4,65 anos de vida ganhos ajustados à qualidade para o Promangiol® (propranolol) quando comparado com a opção de tratamento placebo. A relação entre esses dois resultados é a taxa de custo-utilidade incremental. Esse foi de R$ 776,34/QALY ganho para o Promangiol® (propranolol) comparado com placebo. O modelo possui grandes limitações nos dados de utilidades e no levantamento dos custos, limitando a interpretação dos resultados. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: O impacto orçamentário estimado da incorporação do Cloridrato de Propranolol (Promangiol®) solução oral 3,75 mg/ml no SUS, dados os parâmetros considerados, é de R$166.086.958,58 em cinco anos. O valor anual do impacto variou entre R$ 12.987.986,92 (2019) e R$50.674.403,28 (2023). O modelo possui grandes limitações na análise, o que inviabiliza a interpretação dos resultados. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Foi encontrada uma tecnologia nova no horizonte para tratamento do hemangioma infantil: o nadolol suspensão oral. O estudo clínico NCT02505971, de fase 3, que está em andamento, compara nadalol com propranolol suspensão oral. A previsão de término do estudo é dezembro de 2018. CONSIDERAÇÕES: Embora o Cloridrato de Propranolol tem sido usado off-label durante vários anos para o tratamento de hemangioma infantil, ainda devemos ser cautelosos quanto à sua segurança. O perfil de segurança do tratamento em longo prazo em pacientes pediátricos ainda não foi estabelecido. Além disso, apesar das evidências clínicas demonstradas nos estudos apresentados, uma redução de preço seria necessária para justificar o financiamento da tecnologia. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros presentes em sua 71º reunião ordinária, no dia 04 de outubro de 2018, deliberaram que o tema fosse submetido à consulta pública com recomendação preliminar desfavorável à incorporação do Cloridrato de Propranolol (Promangiol®) 3,75 mg/mL de solução oral para tratamento de pacientes com hemangioma infantil proliferativo. CONSULTA PÚBLICA: Foram recebidas 5 contribuições técnico-científicas e 35 contribuições de experiência e opinião durante o período de consulta pública, entre 16 de outubro a 05 de novembro de 2018. Dentre as contribuições, a maioria foram contrárias à recomendação da CONITEC. Nenhuma evidência científica adicional foi encontrada nas contribuições. Os principais argumentos abordados foram a segurança de dosagem, formulação especifica para pacientes pediátricos e eficácia comprovada da tecnologia. O plenário da CONITEC entendeu que não houve argumentação suficiente para alterar a recomendação inicial. RECOMENDAÇÃO FINAL DA CONITEC: Os membros da CONITEC presentes na 73ª reunião ordinária, nos dias 05 e 06 de dezembro de 2018, deliberaram, por unanimidade, a não recomendação de incorporação ao SUS do medicamento Cloridrato de Propranolol (Promangiol®) solução oral. Foi assinado em 06 de dezembro o registro de deliberação nº 412/2018 pela não incorporação do Cloridrato de Propranolol (Promangiol®) solução oral ao SUS. DECISÃO: Não incorporar o cloridrato de propranolol (solução oral 3,75 mg/ml) para pacientes com hemangioma infantil, no âmbito do Sistema Único de Saúde - SUS. Dada pela Portaria nº 89, publicada no Diário Oficial da União (DOU) nº 249, seção 1, página 434, em 28 de dezembro de 2018.

Tiempo de respuesta terapéutica al propranolol sistémico en el manejo de hemangiomas subglóticos pediátricos: serie de casos y revisión de la literatura / Therapeutic time of response of systemic propranolol in the management of pediatric subglottic hemangiomas: case series and review of the literature

Resumen: Introducción: Los hemangiomas de la vía aérea son neoplasias congénitas de baja incidencia. Su presentación clínica consiste en una obstrucción de la vía aérea superior con disnea progresiva y estridor, ocasionando una obstrucción grave, aguda y grave de la vía aérea. Los hemangiomas infantiles tienen una incidencia al nacimiento del 2%, incrementándose al 9% a los 12 meses de vida. Casi el 60% de los hemangiomas infantiles afectan la región de la cabeza y el cuello. Sin embargo, la localización en la vía aérea superior no es tan frecuente y solo se informa en el 1.8% de los pacientes con hemangiomas cutáneos. El tratamiento tradicional de los hemangiomas laríngeos ha sido la administración de corticoides sistémicos por periodos largos, la cirugía endolaríngea con láser de CO2, la cirugía abierta, la traqueostomía y, recientemente, el propranolol oral. Casos clínicos: Se presentan cinco casos de hemangiomas subglóticos tratados con propranolol sistémico y la evaluación del tiempo de respuesta terapéutica, definido como el control satisfactorio de los síntomas obstructivos y aseguramiento de la vía aérea. En estos casos, el propranolol mostró ser una opción efectiva y segura para el tratamiento de hemangiomas laríngeos, con un tiempo de respuesta terapéutica de 48 a 72 horas. Conclusiones: El tratamiento con propranolol oral se ha convertido en los últimos años en la primera opción terapéutica debido a su alta eficacia y su buen perfil de seguridad.

Abstract: Background: Airway hemangiomas are congenital neoplasms of low incidence. Its clinical presentation consists of obstruction of the upper airway with progressive dyspnea and stridor and the life of the patient at risk. Infantile hemangiomas have an incidence at birth of 2%, increasing to 9% at 12 months of life. Almost 60% of childhood hemangiomas affect the head and neck region. However, localization in the upper airway is not as frequent and it is only reported in 1.8% of patients with cutaneous hemangiomas. The traditional treatment of laryngeal hemangiomas has been the administration of systemic corticosteroids for long periods, endolaryngeal surgery with CO2 laser, open surgery, tracheostomy or, recently, oral propranolol. Case report: Five cases of subglottic hemangioma treated with systemic propranolol are presented. The therapeutic time of response with the satisfactory control of obstructive symptoms and assurance of the airway was evaluated. In these cases, propranolol was shown to be an effective and safe option for the treatment of laryngeal hemangiomas with a therapeutic response time of 48 to 72 hours. Conclusions: In recent years, the treatment with oral propranolol has become the first therapeutic option due to its high efficacy and safety profile.

[Tiempo de respuesta terapéutica al propranolol sistémico en el manejo de hemangiomas subglóticos pediátricos: serie de casos y revisión de la literatura]. / Therapeutic time of response of systemic propranolol in the management of pediatric subglottic hemangiomas: case series and review of the literature.

Background: Airway hemangiomas are congenital neoplasms of low incidence. Its clinical presentation consists of obstruction of the upper airway with progressive dyspnea and stridor and the life of the patient at risk. Infantile hemangiomas have an incidence at birth of 2%, increasing to 9% at 12 months of life. Almost 60% of childhood hemangiomas affect the head and neck region. However, localization in the upper airway is not as frequent and it is only reported in 1.8% of patients with cutaneous hemangiomas. The traditional treatment of laryngeal hemangiomas has been the administration of systemic corticosteroids for long periods, endolaryngeal surgery with CO2 laser, open surgery, tracheostomy or, recently, oral propranolol. Case report: Five cases of subglottic hemangioma treated with systemic propranolol are presented. The therapeutic time of response with the satisfactory control of obstructive symptoms and assurance of the airway was evaluated. In these cases, propranolol was shown to be an effective and safe option for the treatment of laryngeal hemangiomas with a therapeutic response time of 48 to 72 hours. Conclusions: In recent years, the treatment with oral propranolol has become the first therapeutic option due to its high efficacy and safety profile.

Introducción: Los hemangiomas de la vía aérea son neoplasias congénitas de baja incidencia. Su presentación clínica consiste en una obstrucción de la vía aérea superior con disnea progresiva y estridor, ocasionando una obstrucción grave, aguda y grave de la vía aérea. Los hemangiomas infantiles tienen una incidencia al nacimiento del 2%, incrementándose al 9% a los 12 meses de vida. Casi el 60% de los hemangiomas infantiles afectan la región de la cabeza y el cuello. Sin embargo, la localización en la vía aérea superior no es tan frecuente y solo se informa en el 1.8% de los pacientes con hemangiomas cutáneos. El tratamiento tradicional de los hemangiomas laríngeos ha sido la administración de corticoides sistémicos por periodos largos, la cirugía endolaríngea con láser de CO2, la cirugía abierta, la traqueostomía y, recientemente, el propranolol oral. Casos clínicos: Se presentan cinco casos de hemangiomas subglóticos tratados con propranolol sistémico y la evaluación del tiempo de respuesta terapéutica, definido como el control satisfactorio de los síntomas obstructivos y aseguramiento de la vía aérea. En estos casos, el propranolol mostró ser una opción efectiva y segura para el tratamiento de hemangiomas laríngeos, con un tiempo de respuesta terapéutica de 48 a 72 horas. Conclusiones: El tratamiento con propranolol oral se ha convertido en los últimos años en la primera opción terapéutica debido a su alta eficacia y su buen perfil de seguridad.

Compatibility of Baclofen, Carvedilol, Hydrochlorothiazide, Mercaptopurine, Methadone Hydrochloride, Oseltamivir Phosphate, Phenobarbital, Propranolol Hydrochloride, Pyrazinamide, Sotalol Hydrochloride, Spironolactone, Tacrolimus Monohydrate, Ursodeoxycholic Acid, and Vancomycin Hydrochloride Oral Suspensions Compounded with SyrSpend SF pH4.

Compounded liquid medication is frequently required in children to allow easy dose adjustment and overcome swallowing difficulties. The objective of this study was to evaluate the stability of oral suspensions compounded with SyrSpend SF PH4 and the commonly used active pharmaceutical ingredients baclofen 2.0 mg/mL, carvedilol 5.0 mg/mL, hydrochlorothiazide 2.0 mg/mL, mercaptopurine 10.0 mg/mL, methadone hydrochloride 10.0 mg/mL, oseltamivir phosphate 6.0 mg/mL, phenobarbital 9.0 mg/mL and 15.0 mg/mL, propranolol hydrochloride 0.5 mg/mL and 5.0 mg/mL, pyrazinamide 100.0 mg/mL, spironolactone 2.0 mg/mL and 2.5 mg/mL, sotalol hydrochloride 5.0 mg/mL, tacrolimus monohydrate 0.5 mg/mL, ursodeoxycholic acid 20.0 mg/mL, and vancomycin hydrochloride 25.0 mg/mL. Suspensions were compounded with raw powders, except for mercaptopurine, pyrazinamide, and sotalol hydrochloride, which were made from commercial tablets. Stability was assessed by measuring the percentage recovery at 0 (baseline), 60 days, and 90 days after compounding for suspensions made with raw powders, which were stored at 2ÅãC to 8ÅãC. The stability of tablets, which were stored at 2ÅãC to 8ÅãC and 20ÅãC to 25ÅãC, was assessed by measuring the percentage recovery at 0 (baseline), 7 days, 14 days, 30 days, 60 days, and 90 days. Active pharmaceutical ingredients quantification was performed by ultraviolet high-performance liquid chromatography via a stability-indicating method. Given the percentage of recovery of the active pharmaceutical ingredients within the suspensions, the beyond-use date of the final products (active pharmaceutical ingredients + vehicle) was at least 90 days for all suspensions in the conditions tested. This suggests that SyrSpend SF PH4 is suitable for compounding active pharmaceutical ingredients from different pharmacological classes.

Behavior and histopathology as biomarkers for evaluation of the effects of paracetamol and propranolol in the neotropical fish species Phalloceros harpagos.

Pharmaceutical drugs in the aquatic environment can induce adverse effects on nontarget organisms. This study aimed to assess the short-term effects of sublethal concentrations of both paracetamol and propranolol on the fish Phalloceros harpagos, specifically light/dark preference, swimming patterns, skin pigmentation, histopathology, and liver glycogen levels. Fish were acutely exposed to sublethal concentrations of both paracetamol (0.008, 0.08, 0.8, 8, 80 mg L-1) and propranolol (0.0001, 0.001, 0.01, 0.1, 1 mg L-1) under controlled conditions. For scototaxis, a significant preference for the dark compartment was observed for the group exposed to the highest concentration of paracetamol (80 mg L-1). Propranolol exposure significantly altered the swimming pattern, especially in fish exposed to the 0.001 mg L-1 concentration. Pigmentation was reduced in propranolol-exposed fish (0.1, 1 mg L-1). The lowest concentration of propranolol (0.0001 mg L-1) induced a decrease of histochemical reaction for hepatic glycogen. These data demonstrate that pharmaceuticals can induce sublethal effects in nontarget organisms, even at low concentrations, compromising specific functions of the individual with ecological relevance, such as energy balance and behavior.

Comparison of botulinum toxin and propranolol for essential and dystonic vocal tremors.

OBJECTIVES: Vocal tremors, which cause social difficulties for patients, may be classified as resting or action tremors. Of the vocal action tremors, essential and dystonic tremors are the most common. Botulinum toxin and oral medications have been used to treat vocal tremors, but no comparative clinical trials have been performed. The aim of this study was to compare the effects of botulinum toxin injection and the oral administration of propranolol in the treatment of essential and dystonic vocal tremors. METHODS: This clinical trial recruited 15 patients, divided into essential and dystonic vocal tremor groups. Patients in both groups received successive treatment with botulinum toxin and propranolol. The treatments were administered at different times; the order of treatment was randomly selected. Patients were assessed with flexible nasofibrolaryngoscopy and with perceptual and acoustic voice evaluations. A statistical significance level of 0.05 (5%) was used. RESULTS: Botulinum toxin produced statistically significant improvements in perceptual measures of vocal instability in patients with dystonic vocal tremors compared with baseline values and treatment with propranolol. The acoustic measure of variability in the fundamental frequency was significantly lower in patients with dystonic vocal tremors after treatment with botulinum toxin. CONCLUSION: Essential and dystonic vocal tremors responded differently to treatment. Dystonic vocal tremors responded significantly to treatment with botulinum toxin but not oral propranolol. Essential vocal tremors did not respond significantly to either treatment, perhaps due to the small number of patients, which is a limitation of this research.