Propranolol therapy for infantile hemangioma is less toxic but longer in duration than corticosteroid therapy

BACKGROUND: Infantile hemangioma is the most common benign, self-limiting tumour of childhood. Treatment is reserved for hemangiomas that obstruct vital structures or cause significant disfigurement. Traditionally, corticosteroids have been the medical treatment of choice. Since 2008, however, propranolol has been rapidly adopted as an effective pharmacological treatment for infantile hemangioma. Published data regarding the long-term side effects of propranolol are currently lacking. OBJECTIVE: To describe the long-term effects of propranolol and corticosteroids on anthropometric measurements (height, body mass index [BMI]) and blood pressure in children. METHODS: A prospective database analysis of all infantile hemangioma patient visits to the pediatric vascular abnormality clinic at the authors\u27 institution between October 2007 and February 2012 was performed. Anthropometric measures (height and BMI) and blood pressure were analyzed. RESULTS: A total of 290 visits (119 patients) to the pediatric vascular abnormality clinic were reviewed. Of these, 18 patients received medical treatment and their anthropometry was analyzed. BMI percentile increased significantly in patients treated with corticosteroids (P=0.0039). Corticosteroid treatment also resulted in a significant decrease in height percentile (P=0.0078). Anthropometric measures did not cross percentiles in children treated with propranolol. A significant decrease in systolic blood pressure was noted in the propranolol group (P=0.03), but no hypotensive values were recorded. Median treatment duration was significantly longer when patients received propranolol (372 versus 133 days; P=0.0033). CONCLUSION: Propranolol for the treatment of infantile vascular abnormalities does not share the unfavourable effects on patient anthropometry that corticosteroids exhibit; however, a longer duration of therapy is required

Early experimental results of using a novel delivery carrier, hyaluronan-phosphatidylethanolamine (HA-PE), which may allow simple bladder instillation of botulinum toxin A as effectively as direct detrusor muscle injection

Introduction: Botulinum toxin A (BTX-A) is a neurotoxin that inhibits acetylcholine release by cleaving cytosolic synaptosome-associated protein 25 (SNAP-25) and results in bladder relaxation. A BTX-A intravesical injection has been established as an effective option for treating detrusor overactivity. Study design: Sixty female Sprague Dawley rats were equally divided into control and experimental groups. Control Groups 1 to 3 received: BTX-A 10 units + saline instillation; hyaluronan-phosphatidylethanolamine (HA-PE) 0.5 g + saline instillation; and BTX-A 5 Uintra-detrusor injections, respectively. Treatment Groups 4 to 6 received: Alexa ® 594-labeled BTX-A 10 U + HA-PE 0.5 g + saline instillation; BTX-A 5 U + HA-PE 0.2–0.5 g instilled for 60 min; and BTX-A 10 U + HA-PE 0.2–0.5 g instilled for 30 min, respectively. All procedures were performed under isoflurane general anesthesia. The primary outcome of this study was the degree of SNAP-25 staining in control and experimental groups compared to Group 3 (detrusor muscle injection). Urodynamic studies were performed at baseline and at day 14 after 1% acetic acid (AA) instillation, to evaluate the maximum pressure during filling (MP) and inter-contraction intervals (ICI). Group 4 rats were examined for Alexa ® 594 fluorescence to demonstrate physical translocation of BTX-A-HA-PE complex. Standard histology was performed to assess the effect of HA-PE on bladder mucosa and detrusor muscle. Results: Group 3 showed the least SNAP-25 staining (7.3 ± 5.0%) compared with all groups except Group 5A (12.4 ± 12.27%, P = 1.0). Group 6A, which had high HA-PE dose but a shorter instillation time, showed fairly extensive SNAP-25 staining (22.9 ± 10%). Confocal microscopy of Group 4 confirmed the presence of Alexa ® 594 fluorescence across the urothelium. Urodynamic parameters were not significantly different at baseline (P = 1.0). After acetic acid instillation, Group 5A showed minimal change in ICI, which was comparable to ICI in Group 3 rats. Discussion: SNAP-25 staining in Group 5A was comparable to Group 3, suggesting that adequate HA-PE and instillation time allows the efficacy of this carrier mechanism to be comparable to standard intra-detrusor injections. All other groups showed significantly higher SNAP-25 staining compared to Group 3. A dose response effect was demonstrated; higher dose of HA-PE (Group 5A vs Group 5B) and longer instillation time (Group 5 vs Group 6) led to lower SNAP-25 staining. Conclusion: This novel method of BTX-A delivery to the bladder using a carrier (HA-PE) is promising and requires further investigation. Using a larger animal model, identifying an optimal dose of HA-PE and instillation time, and reproducing the current results are further required to validate this carrier

Hyaluronan-Phosphatidylethanolamine Polymers Form Pericellular Coats on Keratinocytes and Promote Basal Keratinocyte Proliferation

Aged keratinocytes have diminished proliferative capacity and hyaluronan (HA) cell coats, which are losses that contribute to atrophic skin characterized by reduced barrier and repair functions. We formulated HA-phospholipid (phosphatidylethanolamine, HA-PE) polymers that form pericellular coats around cultured dermal fibroblasts independently of CD44 or RHAMM display. We investigated the ability of these HA-PE polymers to penetrate into aged mouse skin and restore epidermal function in vivo. Topically applied Alexa647-HA-PE penetrated into the epidermis and dermis, where it associated with both keratinocytes and fibroblasts. In contrast, Alexa647-HA was largely retained in the outer cornified layer of the epidermis and quantification of fluorescence confirmed that significantly more Alexa647-HA-PE penetrated into and was retained within the epidermis than Alexa647-HA. Multiple topical applications of HA-PE to shaved mouse skin significantly stimulated basal keratinocyte proliferation and epidermal thickness compared to HA or vehicle cream alone. HA-PE had no detectable effect on keratinocyte differentiation and did not promote local or systemic inflammation. These effects of HA-PE polymers are similar to those reported for endogenous epidermal HA in youthful skin and show that topical application of HA-PE polymers can restore some of the impaired functions of aged epidermis

Hyaluronan-Phosphatidylethanolamine Polymers Form Pericellular Coats on Keratinocytes and Promote Basal Keratinocyte Proliferation

Aged keratinocytes have diminished proliferative capacity and hyaluronan (HA) cell coats, which are losses that contribute to atrophic skin characterized by reduced barrier and repair functions. We formulated HA-phospholipid (phosphatidylethanolamine, HA-PE) polymers that form pericellular coats around cultured dermal fibroblasts independently of CD44 or RHAMM display. We investigated the ability of these HA-PE polymers to penetrate into aged mouse skin and restore epidermal function in vivo. Topically applied Alexa647-HA-PE penetrated into the epidermis and dermis, where it associated with both keratinocytes and fibroblasts. In contrast, Alexa647-HA was largely retained in the outer cornified layer of the epidermis and quantification of fluorescence confirmed that significantly more Alexa647-HA-PE penetrated into and was retained within the epidermis than Alexa647-HA. Multiple topical applications of HA-PE to shaved mouse skin significantly stimulated basal keratinocyte proliferation and epidermal thickness compared to HA or vehicle cream alone. HA-PE had no detectable effect on keratinocyte differentiation and did not promote local or systemic inflammation. These effects of HA-PE polymers are similar to those reported for endogenous epidermal HA in youthful skin and show that topical application of HA-PE polymers can restore some of the impaired functions of aged epidermis

Mallet Finger in a Toddler: A Rare But Easily Missed Injury

A mallet finger is a flexion deformity of a finger at the distal interphalangeal joint due to an injury of the extensor mechanism at the base of the distal phalanx. Most common in middle-aged men, injuries in the pediatric population are less common and rare in toddlers. We describe a case of missed mallet finger and its subsequent treatment in a female toddler

Application of a Novel Semi-Automatic Technique for Determining the Bilateral Symmetry Plane of the Facial Skeleton of Normal Adult Males

Copyright © 2015 by Mutaz B. Habal, MD. The accurate assessment of symmetry in the craniofacial skeleton is important for cosmetic and reconstructive craniofacial surgery. Although there have been several published attempts to develop an accurate system for determining the correct plane of symmetry, all are inaccurate and time consuming. Here, the authors applied a novel semi-automatic method for the calculation of craniofacial symmetry, based on principal component analysis and iterative corrective point computation, to a large sample of normal adult male facial computerized tomography scans obtained clinically (n=32). The authors hypothesized that this method would generate planes of symmetry that would result in less error when one side of the face was compared to the other than a symmetry plane generated using a plane defined by cephalometric landmarks. When a threedimensional model of one side of the face was reflected across the semi-automatic plane of symmetry there was less error than when reflected across the cephalometric plane. The semi-automatic plane was also more accurate when the locations of bilateral cephalometric landmarks (eg, frontozygomatic sutures) were compared across the face. The authors conclude that this method allows for accurate and fast measurements of craniofacial symmetry. This has important implications for studying the development of the facial skeleton, and clinical application for reconstruction

A Three-dimensional Analysis of Zygomatic Symmetry in Normal, Uninjured Faces

Current approaches to facial reconstruction are based on the assumption of facial symmetry, though this has yet to be established in the literature. Through quantitative and qualitative analysis, symmetry of normal, male faces is examined here using the zygomatic complex as a bellwether for the rest of the facial skeleton. Three-dimensional models reconstructed from the computed tomography scans of 30 adult male patients displaying normal facial skeletal anatomy were analyzed. Seven zygomatic landmarks were identified on all craniofacial models, and asymmetry scores were calculated based on the average deviation distance upon reflection of 1 hemiface across the midfacial plane. Deviation maps were then generated for each zygomatic pair to enable visualization of the asymmetry. All landmarks displayed a slight (\u3c3 mm) deviation from perfect symmetry, and analysis of zygomatic form asymmetry revealed an average of 0.4mm of surface deviation between hemifaces. The presence of such slight asymmetries in the zygoma warrants further investigation as to the clinical relevance of such skeletal asymmetries from both an esthetic and biomechanical consideration to provide insight as to the proper approach to zygomatic restoration in cases of zygomatic fracture

Congenital Calvarial Hemangioma

Objectives The authors describe a case of congenital calvarial hemangioma successfully managed using propranolol therapy. Presenting symptoms, radiological and pathological features, differential diagnosis, and management of this rare congenital mass are described. Case Presentation A 2-year-old boy presented with a 1-year history of a growing right parietal skull mass. No obvious etiology was apparent. No focal neurological deficits or associated craniofacial anomalies were identified. Plain film imaging demonstrated focal thickening of the right parietal bone with internal trabeculations in a sunburst appearance. Computed tomography (CT) scan showed bone thickening with coarsening of the bony trabeculae, minor irregularity of the outer table, unaffected inner table, and no evidence of aggressive features. A diagnostic biopsy of the lesion was performed in the operating room. Microscopic examination was consistent with hemangioma. Based on histological and radiological features of the lesion, it was identified as a cavernous hemangioma. Medical treatment utilizing propranolol was initiated for over 3 years with interval reduction in the lesion size. MRI head following treatment with propranolol demonstrated reduction of the mass compared to preoperative imaging. Conclusions Although a rare entity, it is important to consider congenital calvarial hemangioma in the differential diagnosis of slow growing skull lesions due to the possibility of complications as a result of the hemangioma\u27s intracranial extension, and the potential for treatment. En bloc resection has classically been described as a treatment for such lesions, although our case demonstrates that medical treatment with propranolol therapy may be appropriate in certain situations

Fat grafting versus implants: who's happier? A systematic review and meta-analysis

Background: Breast implants were first introduced in the 1960s and have long been used for augmentation and reconstructive breast surgery. More recently, fat grafting for breast augmentation has gained popularity due to the ‘natural’ outcome and lack of implant-related complications. The aim of this study was to conduct a systematic review and meta-analysis comparing patient-related outcome measures between fat grafting and implant-based primary augmentation using the validated BREAST-Q questionnaire.  Methods: A systematic review of the literature according to the PRISMA guidelines was conducted in PubMed®, Cochrane Library®, EMBASE®, MEDLINE®, and Scopus® databases. Papers were screened by two independent blinded reviewers. Quality was assessed using MINORS criteria.  Results: Fourteen studies were included in the meta-analysis representing a total of 81 fat grafting augmentations and 1535 implant augmentations. The average overall patient satisfaction mean post-operative scores were 13.0 points higher in the implant group based on meta-regression (95% CI: 2.4-23.5; P = .016). There was no statistical difference in reported post-operative sexual well-being, psychosocial well-being, or physical well-being BREAST-Q scores.  Conclusion: Although implant-based augmentation resulted in higher post-operative overall satisfaction scores, fat grafting remains a highly desirable alternative for augmentation in the right patient. This meta-analysis strongly highlights that careful patient selection and evaluation of patient goals must be assessed when selecting an augmentation method. </p