Systemic Propranolol Research Articles

Rare complication – skin atrophy – after systemic conservative therapy of infantile hemangioma

BackgroundHemangiomas, also called infantile hemangiomas (IH) or hemangiomas of infancy are the most frequently seen benign vascular tumors of infancy. Different types of hemangiomas are described in the literature. The current approach is to assess the risk and, if needed, first line treatment is to initiate systemic propranolol.Case presentationA 3-month-old Caucasian female patient was brought as an outpatient. The main complaint was an infantile hemangioma in the facial area, which as per the parents’ story appeared within a week of birth like a small reddish line and it rapidly grew. Systemic propranolol was proposed as a first-line treatment and the adverse effects were explained. The parents, afraid of the side effects, wanted to explore other possibilities such as topical timolol, however, since it had no effect, propranolol was initiated in the end. Hemangioma was completely reduced in size; however, a skin defect was detected. As per the dermatologist’s counsel, topical cream was initiated. The skin defect was reduced but not fully healed. The child is still being monitored periodically.ConclusionAfter successful treatment of hemangioma, we identified a skin defect, which was very similar to steroid-induced skin atrophy. However, we cannot attribute this to a single factor. The only thing that can be concluded is that the subject needs a thorough studying, since rate of infantile hemangioma is high, and pediatricians need a clear management strategy of how to approach skin atrophy after successfully treating the hemangioma itself.

Treatment of infantile hemangioma: case report

Background: Although benign in origin, infantile hemangiomas can occasionally cause lifelong deformity, functional disability, and even life-threatening consequences. As a result, therapy is favored above an active observation plan. When treating infantile hemangiomas at high risk, the first line of therapy should be systemic propranolol. While oral propranolol is generally regarded as a safe and effective medication, it is important to consider potential adverse effects. Further research and evidence-based practices are needed to improve clinical results. Case report: Here, we describe a 3-month-old child who had an infantile hemangioma and how oral propranolol significantly improved the lesion. The patient's mother takes her to the hospital when she notices a reddish mass that extends from her nasal bridge to her right cheek. After three days, the patient's red mass had lessened. The kid was monitored in the clinic for three hours following the initial increase in propranolol dosage, which was raised to 2 mg/kg/day. Every week, the patient was monitored at the clinic. The child's weight had climbed to 7 kg after 4 weeks, and she had no side effects from an increased propranolol dosage. Conclusion: A critical factor is the early diagnosis of at-risk infantile haemangiomas, which calls for pediatricians, general practitioners, and health visitors to be more alert in order to spot potentially troublesome infantile haemangiomas in the first two to three weeks of life.

Treatment of infantile hemangioma with topical β-blockers in pediatric practice: a review of the literature

The purpose of this review is to acquaint the audience with the benefits of infantile hemangioma (IH) treatment with local β-blockers, which are safe for the child, allow for the complete cure of hemangiomas without surgery, complications, scars, and cosmetic defects, and have practically no systemic side effects. We aimed to analyze the effectiveness and limitations of the use of local β-blockers, to show the possibility and expediency of IH management in pediatric practice, and to demonstrate that the goal of therapy is not the treatment of complications, but the prevention of their occurrence and complete resolution of the hemangioma without surgical intervention. The use of topical β-blockers, such as timolol gel or solution, provides a non-surgical, non-invasive treatment option for IH, minimizing the systemic exposure and possible side effects associated with oral β-blockers. Local treatment is best started before the age of 2 months - at an early stage, when IHs are small in size, potentially preventing the need for more invasive treatment methods. Topical use is associated with a lower risk of systemic side effects, such as hypotension or bradycardia, that can occur with oral β-blockers. Topical treatment can be applied at home, which can be more convenient for parents and caregivers, and also increases the opportunity for treatment and follow-up by pediatricians. In case of natural disasters or military operations, treatment can be done remotely using teledermatology. The effectiveness of local β-blockers mostly depends on the age at which treatment was started: the earlier it was started, the higher the effectiveness. Treatment of complicated IH with deep soft tissue, mucosal, or airway involvement usually requires a combination of systemic propranolol and topical β-blockers or other interventions such as laser therapy. The choice of treatment should be selected individually according to the degree of risk of IH, its size, localization, child's age, weight, and other parameters in each clinical case. β-adrenoblockers are the most modern, effective, non-surgical, and safe method of treating IH, they can be used both for systemic and local application. IH can be successfully treated by pediatricians and dermatologists. No conflict of interests was declared by the authors.

Additive value of single intralesional bleomycin injection to propranolol in the management of proliferative infantile hemangioma

/Objective: We aimed to evaluate whether additional intralesional bleomycin injections benefit children with proliferative infantile hemangiomas (IHs). In this retrospective case-control study, we examined the medical records of 216 infants who were followed up for proliferative IH. Patients in group 1 were treated with propranolol orally at 2mg/kg/day. Group 2 was treated with oral propranolol combined with intralesional bleomycin injections. We retrospectively reviewed 95 and 121 patients in groups 1 and 2, respectively. No significant differences were observed between both groups regarding visiting age, sex, lesion thickness, or risk site. The overall cure rates in groups 1 and 2 were 77.89% (74/95) and 84.30% (102/121), respectively. The overall distribution of the length of cure significantly differed between both groups (P=0.035). From the survival analysis (P=0.026), the median survival time was 198 days (95% confidence interval (CI) 174.46-221.54) for group 1 and 139 days (95% CI 114.58-163.42) for group 2. The effect of treatment modality (hazard ratio (HR)=1.41, P=0.031) and risk site on survival time (HR=.54, P<0.001) was significant. No significant differences were observed in the resolution of proliferative IH; however, intralesional bleomycin injection with systemic propranolol for proliferative IH treatment may provide a more rapid resolution.

Clinical features of cutaneous infantile hemangioma combined with asymptomatic infantile hepatic hemangioma and efficacy of propranolol treatment.

Infantile hepatic hemangioma (IHH) is a common liver tumor in infants and shares the same characteristics as cutaneous infantile hemangioma (IH). Propranolol is effective for symptomatic IHH. The clinical features between cutaneous IH and IHH, and treatment efficacy of IHH (smaller than 4 cm) is unclear. To evaluate the correlation of clinical features between cutaneous IH and IHH, as well as efficacy of systemic propranolol in the treatment of cutaneous IH combined with IHH. The clinical data of infants with complicated cutaneous IH combined with IHH treated with systemic propranolol (1.5 ~ 2 mg/(kg d)) from January 2011 to October 2020 were retrospectively analyzed. Forty-five cases with IHH combined with complicated cutaneous IH were reviewed. Single cutaneous IH is more likely to be combined with focal IHH, cutaneous IH greater than 5, more likely to be combined with multiple IHH (Pearson = 0.546, p < 0.01). The mean age of focal and multiple IHH regression was 11.93 ± 14.42 months and 10.20 ± 9.15 months, respectively. The number of cutaneous IH were correlated with the number of IHH. There was no difference in the age of complete remission for focal and multiple IHH.

Nd:YAG 1064-nm laser for residual infantile hemangioma after propranolol treatment

Infantile hemangiomas (IH) are common benign tumors of infancy. Most IH involute, either spontaneously, or secondary to pharmacological treatment with systemic propranolol. Propranolol treatment mostly leads to regression of hemangiomas with satisfactory aesthetic results, but unfortunately not in all cases. To assess the safety and efficacy of long pulsed Nd:YAG 1064 nm laser in treating patients with residual infantile hemangioma after systemic propranolol treatment. This is an open-label prospective cohort study. 30 patients with focal residual IH that had sub-optimal responses to systemic propranolol treatment were enrolled in the study. The patients were treated with 1 to 3 sessions with long pulsed Nd:YAG 1064 nm laser. The maximal response of the IH was assessed using a 4-point scale evaluation scale system. Of the 30 patients enrolled, 18 patients exhibited a great response (> 76% improvement), 10 patients had a good response (> 51–75% improvement), while only 2 patients showed a moderate response (< 50% improvement) to the treatment. No patients had an unsatisfactory response. No serious side effects were observed, and only minor side effects were reported. The treatment with long pulsed Nd:YAG 1064 nm laser for residual IH, which were resistant to systemic propranolol treatment, is safe and effective. Thus, we suggest its use as a second-line treatment for patients with sub-optimal aesthetic results following systemic propranolol.

Results of Infantile Hemangioma Laser Therapy in Children with Persistent Residual Signs after Systemic Propranolol Therapy: Clinical Cases

Background. Infantile hemangiomas are revealed in 1-3% of newborns and 10-12% of infants. There are only anecdotal reports on the laser therapy efficacy in this pathology management. However, there is no common approach to the use of this method in the complex treatment of infantile hemangioma in infants. Clinical Cases Description. Two clinical cases of infantile hemangioma are presented. Patients underwent complex treatment: systemic propranolol and laser therapy via pulsed dye laser. Laser exposure modes ware selected individually: laser spot sizes were 10 and 12 mm, energy levels were 5-10 J/cm2, burst duration was short (0.45 ms) or long (10-20 ms), procedure duration was from 15 to 40 minutes, number of procedures varied from 1 to 8. Laser therapy has shown its efficacy in treatment of superficial infantile hemangioma. Conclusion. The indication for using laser therapy in management of infants with hemangiomas is especially persistent residual signs such as telangiectasias and erythema after spontaneous or drug involution phase. Laser therapy allows us to avoid aggressive methods and improves the quality of life of our patients according to this article.

Effects of Systemic Propranolol Application on the New Bone Formation in Periimplant Guided Bone Regeneration.

ABSTRACTObjectivesThe aim of this experimental animal study was to evaluate the effects of systemic propranolol on new bone formation in peri-implant bone defects.Material and MethodsImplant slots were created 4mm long and 2.5 mm wide. After the titanium implants were placed in the sockets, 2 mm defects were created in the neck of the implants. Bone grafts were placed in these defects. Then the rats were randomly divided into three equal groups: control (n = 8), propranolol dose-1 (PRP-1) (n = 8), and propranolol dose-2 (PRP-2) (n = 8) groups. In the control group, the rats received no further treatment during the eight-week experimental period after the surgery. The rats in the PRP-1 and PRP-2 groups were given 5 mg/kg and 10 mg/kg propranolol, respectively, every three days for the eight-week experimental period after the surgery. At the end of the experimental period, the rats were euthanized. Blood serum was collected for biochemical analysis, and the implants and surrounding bone tissues were used for the histological analysis.ResultsThere were no significant differences in the histological analysis results and the biochemical parameters (alkaline phosphatase, calcium, creatinine and phosphorus) of the groups (P > 0.05). Also, in the test groups, there was numerically but not statistically more new bone formation detected compared with the controls.ConclusionsWithin the limitations of this study, propranolol did not affect the new bone formation in peri-implant defects.

СТРАТЕГИЯ И ОПЫТ ЛЕЧЕНИЯ ИНФАНТИЛЬНЫХ ГЕМАНГИОМ

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

Infantile Hemangioma Treated with Systemic Propranolol

Infantile Hemangioma Treated with Systemic Propranolol

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

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

Topical timolol versus oral propranolol for the treatment of hemangioma in children

Objective To evaluate the clinical efficacy and adverse effects of oral propranolol in comparison with topical timolol for the treatment of hemangioma. BackgroundPrevious research declares that hemangioma is the most common tumor of infancy and childhood, occurring in 4–10% of white infants.Patients and methodsTo reach the goal of this research, a prospective randomized study was performed by selecting 20 patients with hemangioma attending the Pediatric Surgery Clinic at Menoufia Main University Hospital and Damanhur National Medical Institute. All patients were subjected to detailed history taking, clinical examination, echocardiogram, complete blood picture, liver and kidney functions, and blood glucose level. Determination of the location and dimensions of hemangioma was based on direct measurement and photographic analysis. Doppler ultrasound was used for baseline data regarding site, size, depth, vascularity, and flow.ResultsThere was a statistically significant difference regarding dimensions of the lesion (mm) when comparing propranolol patients before treatment and after treatment (P = 0.010) and also when comparing timolol patients before treatment and after treatment (P = 0.008). There was a statistically significant difference regarding to dimensions of the lesion (mm) by ultrasound when comparing propranolol patients before treatment and after treatment (P = 0.003) and also, when comparing timolol patients before treatment and after treatment (P = 0.008).ConclusionOur study reveals that both systemic and topical beta-blockers can be used effectively for treatment of hemangioma; however, much better improvements were obtained on using systemic propranolol than topical timolol. Topical timolol can be used as a first-line treatment for superficial infantile hemangiomas.

Evaluation of the Effects of ß-Adrenergic Receptor-Propranolol on Osseointegration of the Titanium Implants.

This study aimed to investigate the effects of systemic propranol on the osseointegration of titanium implants. After the surgical insertion of titanium implants into the metaphyseal part of the tibial bone, the rats were randomly divided into 2 equal groups: the control (CNT) (n = 10) and propranol group (P) (n = 10); CNT: Rats received no further treatment during the 4 week experimental period after surgery. Rats received 10 mg/kg propranol in every day during the 4 week experimental period in PRP group after the surgical insertion of the implants. After the experimental period, the rats were euthanized, blood serum were collected to biochemical analysis and the implants and surrounding bone tissues were used for the histopathologic analysis. To analysis of the data between tests and controls student T test was used. There were no significant differences in the biochemical parameters (alcaline phosphatase, calcium, phosphor) of the groups (P > 0.05). Bone implant connection (BIC) ratios was detected higher in test animals compared with the controls (P < 0.05). Systemic propranolol may increases titanium implant osseointegration.

Combination therapy of oral propranolol and combined Nd:YAG/pulsed dye laser therapy in infantile hemangiomas: a retrospective analysis of 48 treated hemangiomas in 30 children.

Infantile hemangiomas can be successfully treated by both systemic propranolol and neodymium:YAG (Nd:YAG)-dye laser combination therapy. In this retrospective study, the efficacy and safety of sequential and parallel therapy of complicated hemangiomas treated with both methods were evaluated. 30 children with 48 complicated hemangiomas were treated with propranolol and Nd:YAG-dye laser combination therapy. Using photo comparison, the percentage remission rate was evaluated by three investigators on a four-step scale (I: 0-25%, II: 26-50%, III: 51-75% and IV: 76-100%). Eleven children received propranolol and laser therapy in parallel (A), twelve children received laser therapy after propranolol (B) and seven children received propranolol after laser therapy (C). Due to emigration abroad, one child was lost to follow-up. A strong improvement (IV) was observed in 23/29 (79.3%) of all treated children (A: 90.9%, B 75%, C 66.7%). The mean duration of propranolol therapy in all children was 8.6months (A: 8.9months, B: 8.2months, C: 8.9months). On average, 2.33 laser treatments were performed per hemangioma (A: 1.95, B: 3.2, C: 1.91). Serious side effects caused by propranolol and laser therapy were not observed. Propranolol and Nd:YAG-dye laser combination therapy can be used sequentially or in parallel safely and effectively. They complement each other in a meaningful manner.

Biomechanical and Biochemical Analyses of the Effects of Propranolol on the Osseointegration of Implants.

This study aimed to investigate the effects of systemic propranolol on the osseointegration of titanium implants. After the surgical insertion of titanium implants into the metaphyseal part of the tibiae of rats, the rats were randomly divided into three equal groups: the control (n = 8), propranolol dosage-1 (PRP-1) (n = 8), and propranolol dosage-2 (PRP-2) (n = 8) groups. In the control group, the rats received no further treatment during the 4-week experimental period after the surgery. After the surgical insertion of the implants, the rats in the PRP-1 and PRP-2 groups were given 5 mg/kg and 10 mg/kg propranolol, respectively, every 3 days for the 4-week experimental period. After the experimental period, the rats were euthanized. Blood sera were collected for biochemical analysis, and the implants and surrounding bone tissues were used for the biomechanical reverse torque analysis. One-way ANOVA and Tukey's honest significant difference test were used for statistical analysis. The student t-test was used to analyze the data obtained from the tests and the controls. There were no significant differences in the reverse torque analysis results and the biochemical parameters (alkaline phosphatase, calcium, and phosphorus) of the groups (P > 0.05). Alkaline phosphatase was, however, found to be higher in test animals compared to the controls (P < 0.05). Also, propranolol did not biomechanically affect the osseointegration of titanium implants, while alkaline phosphatase activity was higher in the test animals.

Oral propranolol administration is effective for infantile hemangioma in late infancy: A retrospective cohort study.

The highest efficacy of oral propranolol is for infantile hemangioma (IH) in the proliferative phase. Evaluation of the effectiveness of oral propranolol is less established when it is administered in late infancy following the proliferative phase. We aimed to assess the clinical outcomes of pediatric patients managed by oral propranolol beyond the proliferative phase of IH. A retrospective cohort study in a tertiary health care referral center was conducted to track all patients with IH receiving systemic propranolol following the proliferative phase. Twenty-eight eligible patients were managed by 2 to 3 mg/kg per day of oral propranolol for IH beyond the proliferative phase, defined at 9 months of age. The mean age at the initiation of propranolol was estimated at 11.25 (SD 2.24) months. All eligible patients experienced some degree of clinical resolution, with the average improvement rate being estimated at 77.1% (SD 16.1). Comparable results were achieved among patients who were placed on propranolol at an age older than 12 months and those managed between the age of 9 and 12 months. No serious adverse events were observed during the follow-up duration. In conclusion, oral propranolol is a safe and effective treatment for patients with IH initiating this agent beyond the proliferative phase.

Locus Coeruleus Norepinephrine Drives Stress-Induced Increases in Basolateral Amygdala Firing and Impairs Extinction Learning.

Stress impairs extinction learning, and these deficits depend, in part, on stress-induced norepinephrine (NE) release in the basolateral amygdala (BLA). For example, systemic or intra-BLA administration of propranolol reduces the immediate extinction deficit (IED), an impairment in extinction learning that occurs when extinction trials are administered soon after fear conditioning. Here, we explored whether locus coeruleus (LC)-NE regulates stress-induced changes in spike firing in the BLA and consequent extinction learning impairments. Rats were implanted with recording arrays in the BLA and, after recovery from surgery, underwent a standard auditory fear conditioning procedure. Fear conditioning produced an immediate and dramatic increase in the spontaneous firing of BLA neurons that persisted (and in some units, increased further) up to an hour after conditioning. This stress-induced increase in BLA firing was prevented by systemic administration of propranolol. Conditioning with a weaker footshock caused smaller increases in BLA firing rate, but this could be augmented by chemogenetic activation of the LC. Conditioned freezing in response to a tone paired with a weak footshock was immune to the IED, but chemogenetic activation of the LC before the weak conditioning protocol increased conditioned freezing behavior and induced an IED; this effect was blocked with intra-BLA infusions of propranolol. These data suggest that stress-induced activation of the LC increases BLA spike firing and causes impairments in extinction learning. Stress-induced increases in BLA activity mediated by LC-NE may be a viable therapeutic target for individuals with stress- and trauma-related disorders.SIGNIFICANCE STATEMENT Patients with post-traumatic stress disorder (PTSD) show heightened amygdala activity; elevated levels of stress hormones, including norepinephrine; and are resistant to the extinction of fear memories. Here, we show that stress increases basolateral amygdala (BLA) spike firing. This could be attenuated by systemic propranolol and mimicked by chemogenetic activation of the locus coeruleus (LC), the source of forebrain norepinephrine (NE). Finally, we show that LC-NE activation is sufficient to produce extinction deficits, and this is blocked by intra-BLA propranolol. Stress-induced increases in BLA activity mediated by LC-NE may be a viable therapeutic target for individuals with PTSD and related disorders.

Lip Infantile Hemangiomas Involving the Vermillion Border Have Worse Outcomes and Prognosis to Oral Propranolol Than Lesions Confined to One Side of the Vermillion

Oral propranolol has been widely used for problematic infantile hemangiomas (IHs). Lip IHs present a high risk of disfigurement and associated psychosocial dysfunction and require early treatment. Lips are compound parts that consist of the upper and lower lips and include the mucosal and cutaneous lips histologically. The present retrospective study aimed to determine the response and prognosis of different subtypes of lip IHs to the use of systemic propranolol. The data from 81 patients with lip IHs treated with systemic propranolol (2mg/kg/day) were reviewed. Localized and segmental lip IHs were evaluated separately. The outcomes and prognosis of localized hemangiomas were further evaluated stratified by different features: 1) upper and lower lip; and 2) crossing the vermilion border. The lesions involving the upper lips and those involving the lower lips had the same outcomes and prognosis. Lesions involving the vermillion border required longer treatment and had poorer outcomes and prognosis compared with lesions confined to 1 side of the vermilion. After oral propranolol treatment, IHs localized to upper lip had the same outcomes and prognosis as IHs localized to the lower lip. Lip IHs involving the vermillion border had worse outcomes and prognosis than lesions confined to 1 side of the vermillion.

Voluntary exercise or systemic propranolol ameliorates stress-related maladaptive behaviors in female rats

Many people will experience at least one traumatic event in their lifetime, with up to 20% developing Post-Traumatic Stress Disorder (PTSD) or PTSD-like symptoms. In addition, the likelihood that females will develop PTSD after trauma is more than twice that of males. Despite its prevalence, current treatment strategies for trauma victims are limited and substantial portions of affected individuals remain resistant to treatment, suggesting that additional interventions are necessary. Using an animal model of traumatic stress, the present studies tested the hypothesis that either voluntary exercise and/or administration of the adrenergic beta-receptor antagonist propranolol, would ameliorate stress-related maladaptive behaviors. In Study 1 four groups of female rats were exposed to a sequence of stressors that included anesthesia, restraint, forced swim, exposure to predator scent and fear conditioning. Rats then underwent re-exposure sessions in which stress-related conditioned stimuli were presented. In addition to re-exposure, stressed rats were treated with propranolol (10 mg/kg) and/or given the opportunity to engage in voluntary wheel running intermittently for 4 weeks. Stress-associated maladaptive behavior was assessed using the elevated plus and open field mazes and fear memory tests. Cognitive ability was assessed using a novel odor recognition task. A main effect of exercise on behaviors related to anxiety and resilience was observed, but neither a main effect of propranolol nor a synergistic effect of propranolol and exercise were observed. Neither stress induction nor treatment influenced recognition memory. In contrast, in Study 2 in which the timing and dosage of propranolol (0.25–2.0 mg/kg), and the number and timing of re-exposure sessions were adjusted, propranolol produced both a reduction in anxiety-like behaviors as well as resilience to a subsequent stressor. These results are consistent with the notion that combining re-exposure therapy with additional interventions is beneficial for female trauma victims. Furthermore, the findings support the view that in pre-clinical models, voluntary exercise, which bolsters hippocampal function and propranolol, which affects amygdala-dependent memory reconsolidation and peripheral noradrenergic signaling, can ameliorate stress-related symptoms.

Hearing loss in PHACE syndrome: clinical and radiologic findings.

To characterize the types of hearing loss, auditory-related imaging findings, and hemangioma characteristics in patients with Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects, and abnormalities of the Eye (PHACE) syndrome. Retrospective medical records, audiologic data, and imaging review of all patients presenting to a tertiary care children's hospital with a proven diagnosis of PHACE syndrome from 2005 to 2016. Twelve patients were identified with hearing and imaging data. 5/12 had hearing loss, 1 had unilateral severe sensorineural loss with minor conductive component, 1 had unilateral moderate sensorineural loss with minor conductive component, 1 had mild bilateral conductive loss, 1 had bilateral hearing loss (left severe mixed and right severe sensorineural), and 1 had moderate bilateral conductive loss. All patients passed their newborn hearing screening. Of the 5 patients with hearing loss, 3 had IAC hemangiomas (1 bilateral), 3 had enlarged IACs with prominent posterior petrous bones (1 bilateral), 2 had dysgenesis of the cerebellar vermis and hemispheres, there was 1 patient each with a deformed pinna and middle ear and mastoid effusions, and 1 patient had no abnormal auditory-related imaging findings. Patients with hearing loss were more likely to have more areas of cutaneous hemangioma involvement (mean 6.4 vs 3.1, p = .05). Laterality of hearing impairment correlated with the side of cutaneous hemangioma in all patients with hearing loss. Treatment with systemic propranolol did not improve hearing. Patients with PHACE are at risk for hearing loss and may demonstrate radiologic abnormalities within the ear structures, although the type of hearing loss, imaging findings, and their respective correlation vary. While our results are limited by our small sample size, comprehensive audiology evaluations (as opposed to newborn screening testing only) should be considered for PHACE patients who have extensive cutaneous hemangioma or auditory-related imaging abnormalities, such as internal auditory canal hemangiomas.