Background Large unilateral facial hemangiomas, particularly those involving the parotid gland, are significant due to their potential to cause severe facial asymmetry. No universally accepted classification exists for assessing the severity or determining appropriate surgical interventions. This study proposes an algorithm for managing involuting or involuted hemangiomas with facial asymmetry, based on magnetic resonance imaging (MRI) findings. Methods Sixteen patients presenting with facial asymmetry who underwent surgical procedures for involuting or involuted hemangiomas were included in this study. Patients were categorized into four types based on the association between MRI findings of hemangiomas and surgical procedures. Those without facial asymmetry who did not require surgery were classified as Type I and were therefore excluded from analysis. Results Ten patients who received liposuction were classified as Type II, three patients who underwent lipectomy with a minimal access cranial suspension lift were classified as Type III, and three patients who underwent lipectomy with formal facial nerve dissection were classified as Type IV. All 16 patients showed improvement in facial asymmetry and deformity. The mean postoperative follow-up period was 7.8 months. No major complications were observed in any of the types. Conclusion Surgical interventions of hemangiomas associated with facial asymmetry are typically performed during the involuting or involuted phase, offering a less invasive approach with lower morbidity. Preoperative MRI findings can effectively delineate the extent and depth of fibrofatty tissue, assisting surgeons in selecting the optimal therapeutic strategy. Our classification system may serve as a practical guide for surgical planning.

Diabetes-associated skin defects represent a significant global health challenge. While flap grafts have been a preferred treatment for soft-tissue injuries in diabetic patients, their survival is often compromised by impaired vascularization, infection, and the adverse diabetic pathological microenvironment. To address these limitations, a hybrid photo-crosslinkable hydrogel (HPC) integrated hemangioma stem cell-derived nanovesicle (HemV)-loaded dual-metal-polyphenol network (dMPN) (HemV@dMPN/HPC) is developed. HemVs, derived from highly vascularized infantile hemangioma tissues, play a key role in promoting cell proliferation and angiogenesis. The dMPN facilitates the gradual release of copper (Cu2+) and magnesium ions (Mg2+), stimulating angiogenesis and mitigating inflammation. The HPC further sustains ion release while preserving the therapeutic efficacy of HemVs. Moreover, both HPC and Cu2+ act to confer antibacterial properties, further accelerating wound healing. This multifunctional HemV@dMPN/HPC platform offers a promising therapeutic strategy for treating large diabetic skin defects and can potentially improve flap graft survival.

PHACE syndrome is a neurocutaneous syndrome characterized by large facial segmental hemangiomas as the most typical manifestation. Its prevalence in East Asian is not well studied. The retrospective study included 98 infants with facial segmental hemangiomas who underwent brain MRI/MRA, cardiac ultrasound, and ophthalmology examinations. The prevalence along with documentation of its clinical characteristics of PHACE syndrome was analyzed. Among 98 patients, 5 (5.1%) were diagnosed with “definite” PHACE, while none (0.0%) exhibited “possible” PHACE. Most patients with PHACE syndrome had 2 or more segments, of which the frontotemporal segment was most frequently involved. Structural brain anomalies were identified in two patients, four exhibited cerebrovascular anomalies, four displayed cardiovascular anomalies, and two presented ocular anomalies. Following standardized oral propranolol therapy, all patients showed significant regression. One patient received laser treatment for a residual hemangioma. The prevalence of PHACE syndrome in facial segmental hemangiomas was 5.1%, predominantly characterized by anomalies in the cerebrovascular and cardiovascular systems. Collaborative multidisciplinary diagnosis and treatment are critical for PHACE patients.

Facial infiltrating lipomatosis(FIL)is a congenital disorder caused by the hyperproliferation of adipose and skeletal tissue within the facial region.Infiltration of mature adi-pose tissue into adjacent structures is a hallmark pathologic finding.In addition to the aesthetic implications,patients may suffer from impaired facial function,including diffi-culty in swallowing and breathing,sleep disturbances,and visual field displacement.FIL is associated with phospha-tidylinositol 3-kinase catalytic subunit alpha(PIK3CA)vari-ants.

BACKGROUND:Lip infantile hemangiomas tend to show less volumetric regression and are more susceptible to visible sequelae in the involuted stage. Some of them still require surgical management after propranolol therapy. This study aimed to evaluate the efficacy and safety of the Stepwise, Multi-Incisional, and Single-Stage (SMISS) approach applied to lip reduction for those with involuted lip hemangiomas.METHODS:A retrospective review was performed to evaluate patients with lip hemangioma who received previous propranolol treatment and underwent the aforementioned procedure. Demographic characteristics, lesion morphology, and medical history were reviewed. The Visual Analog Scale was applied to assess the postoperative appearance. Complications within 12 months postoperatively were recorded.RESULTS:A total of 18 patients with lip hemangioma were eligible. All patients received oral propranolol therapy before surgery, with treatment duration ranging from 6.0 to 23.0 months. Their age at surgery ranged from 2.5 to 9.0 years. The median Visual Analog Scale scores were 8.0, ranging from 4.0 to 10.0. No severe complications were reported.CONCLUSIONS:This modified technique based on the SMISS approach has proven reliable and effective in improving the aesthetic outcome for involuted lip infantile hemangiomas. Practical surgical techniques still play an important part in the propranolol era.

Large involuted infantile hemangioma remains a challenge in facial reconstruction. The characteristic fibrofatty residuum and multiple subunits/tissues involvement contribute significantly to the difficulty of surgical management. Tissue expander plays an important role in facial reconstruction, allowing plastic surgeons to repair skin damaged by both congenital and acquired defects. Between 2009 and 2021, 30 patients who underwent tissue expansion surgery were reviewed in a single hospital. The demographic data, lesion characteristics, surgical approaches, complication rate, and aesthetic outcomes were analyzed. Thirty patients (5 men and 25 women) with a mean age of 14.03 ± 7.25 years (range, 4–33 years) were included. The mean follow-up is 35.92 months, ranging from 9 to 75 months. Tissue expansion-related complications include closed infection, 2/30 (6.67 www.springer.com/00266 .

Background The distribution and response to propranolol of problematic facial infantile haemangiomas (IHs) has rarely been described in the literature. Aim To map problematic facial IHs and observe their response to propranolol. Methods Eligible patients were categorized according to focal location and cohorts corresponding to these (buccal, medial, zygomatic, lateral and multiregional) were created. The primary efficacy variable was regression score ranging from 1 to 4, calculated using results of colour Doppler ultrasonography. Results In total, 104 patients met the inclusion criteria. There were 32 (30·8%) IHs located in the buccal area, 12 (11·5%) in the medial area, 49 (47·1%) in the lateral area and 1 (1·0%) in the zygomatic area, with 10 (9·6%) IH cases having multiregional lesions. We found that the distribution pattern of most IHs matched the surface projection of the trunk of the external carotid and the facial arteries. Further analysis showed that the median regression score in the buccal and medial groups were significantly lower than those in the lateral and multiregional groups. Conclusion Treatment of buccal and medial haemangiomas tends to be more challenging and their distribution pattern mainly reflects the direction of the facial vessels.

Infantile hemangiomas (IHs) of the lips are associated with an increased risk of incomplete involution and ulceration, causing disfigurement. Treatment with oral propranolol (OPT) has credible efficacy but takes months to complete. Thus, this study aimed to investigate the efficacy of intralesional betamethasone injection (IBI) as an alternative treatment for protruding localized IHs of the lips. To investigate the efficacies of OPT and IBI, we designed a prospective, noninferiority, parallel-group study. The primary outcome assessed was treatment response rate. Secondary outcome assessments included lesion size changes and surgical rate. Additionally, complication rates and treatment durations of OPT and IBI were compared. The treatment response rate of IBI was not inferior to that of OPT (95.7% vs. 76.0%, respectively; a difference of 19.7%, 95% confidence interval [CI], -4.4% to 41.6%). The average surgical rate in the IBI group was significantly lower than that in the OPT group (8.7% vs. 40%, respectively; p = 0.012), and the average duration of treatment for IBI was shorter than that of OPT (2.1 months vs. 6.3 months, respectively; p < 0.001). There were no severe adverse drug events in either group. If not managed properly, small, localized lip IHs may cause disfigurement in a child. Our study demonstrated that IBI is as effective as OPT in treating protruding localized lip IHs. Moreover, IBI treatment has a shorter duration and lower surgical rate than OPT. With proper care, IBI is an effective treatment modality for small and localized lip IHs.(c) 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

ObjectiveInfantile hemangioma (IH), the most common infantile vascular neoplasm, is uniquely characterized by rapid proliferation followed by slow spontaneous involution lasting for years. In IH lesions, perivascular cells are the most dynamic cell subset during the transition from the proliferation phase to the involution phase, and we aimed to systematically study this kind of cell.Methods and resultsCD146-selective microbeads were used to isolate IH-derived mural-like cells (HemMCs). Mesenchymal markers of HemMCs were detected by flow cytometry, and the multilineage differentiation potential of HemMCs was detected by specific staining after conditioned culture. CD146-selected nonendothelial cells from IH samples showed characteristics of mesenchymal stem cells with distinct angiogenesis-promoting effects detected by transcriptome sequencing. HemMCs spontaneously differentiated into adipocytes 2 weeks after implantation into immunodeficient mice, and almost all HemMCs had differentiated into adipocytes within 4 weeks. HemMCs could not be induced to differentiate into endothelial cells in vitro. However, 2 weeks after implantation in vivo, HemMCs in combination with human umbilical vein endothelial cells (HUVECs) formed GLUT1+ IH-like blood vessels, which spontaneously involuted into adipose tissue 4 weeks after implantation.ConclusionsIn conclusion, we identified a specific cell subset that not only showed behavior consistent with the evolution of IH but also recapitulated the unique course of IH. Thus, we speculate that proangiogenic HemMCs may be a potential target for the construction of hemangioma animal models and the study of IH pathogenesis.

Infantile hemangioma (IH), the most common benign tumor in infancy, is generally sensitive to propranolol treatment. However, the challenge remains because resistance or recurrence could occur in some patients, and the mechanism or target of propranolol remains unknown. Therefore, advancement in the drug development is needed. In this study, we explored whether apelin receptor (APJ) can become a candidate target. We found that APJ is expressed only in endothelial cells of IH (HemECs) but not in other vascular anomalies, and its antagonist, ML221, can negatively regulate cellular viability and functions of HemECs. This inhibitory effect could be replicated in a murine hemangioma model. Importantly, in vitro experiments also indicated that ML221 failed to affect the proliferation or angiogenesis of normal endothelial cells or APJ-knockout HemECs. Through analysis of the phosphoantibody microarray data, ML221 was revealed to have an inhibitory effect on HemECs by suppressing the activation of mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. These results verified the distinctive expression of APJ in IH and specific inhibition of HemEC activity caused by ML221. In addition, APJ was also detected in propranolol-resistant IH. Collectively, we propose that APJ can act as a specific marker and a promising therapeutic target for IH, which will facilitate further drug development.

传统的"血管瘤"(Vascular Anomalies)包含了各种血管性肿瘤和血管/淋巴管畸形,在中国有逾2千万病例.疾病谱中既涵盖常见病,如婴幼儿血管瘤,在新生儿中发病率高达1％～ 10％;也涵盖罕见疑难病,如颅外动静脉畸形,发病率约为1/20万,却是国际公认的疑难疾病.这些疾病可发生于全身各部位,累及多器官,造成多种多样的临床表现,治疗所涉跨越各学科解剖界限、知识和技术,远非传统单一学科所能胜任.

Infantile hemangiomas (IH) leave sequelae after involution. Topical application of timolol maleate (TM) is the mainstream treatment for superficial lesions but is limited by its low penetrable properties. We aimed to develop a superior skin permeation drug while maintaining the therapeutic properties of timolol. We predict that this drug will promote the involution of thick and deep IH lesions and avoid sequelae. We chemically modified drug structure to prepare butyryl timolol maleate (BT) prodrug and conducted in vitro and in vivo toxicity evaluations of BT with rat dorsal skin and normal skin cells. Skin permeation and absorption comparisons of TM and BT were conducted using rat and porcine skin models. Conversion efficiency of BT to timolol was also tested on human skin ex vivo. BT did not cause skin irritation on rat dorsal skin and exhibited low cytotoxicity overall. BT exhibited superior skin permeation ability compared with that of TM, whilst maintaining a low systemic absorbance. Further, BT was converted to timolol in human skin in a time-dependent manner. Noticeably, timolol accumulation in the skin from BT was higher than that from TM. Finally, BT demonstrated similar biocompatibility with TM in the IH tumor. BT enhances local delivery of timolol and its skin permeation. Using BT, we could eliminate thicker IH lesions that are prone to leave sequelae, and potentially help young children avoid dermal sequelae, disfigurement, and concomitant therapy.

Background Oral propranolol can effectively activate and accelerate infantile hemangioma (IH) involution; however, could the final outcome of oral propranolol treatment for IHs commensurate that of spontaneous involution? Objective This study aimed to investigate the long-term therapeutic effect of oral propranolol for IHs. Methods We present an individual matching comparative study with (1) oral propranolol therapy for mixed and deep IHs on the lips, nose, and parotid and (2) lesion type– and lesion location–matched untreated IHs as controls. Patients' follow-up photographs were assessed by 3 surgeons blinded of their treatment. Outcome measures were the quantification of the degree of sequelae ranging from 1 to 4 and the age at which IH achieved involution arrest. Results Ten groups of oral propranolol and untreated patients with matched lesions were assessed. Average age at which lesions stabilized and reached no change in appearance was 1.7 years old and 6.3 years old for propranolol group and untreated group ( t = 5.663, P < 0.001). There was no significant difference in the quantified degree of sequelae for oral propranolol group and untreated group upon follow-up (1.60 vs 1.40, respectively; t = 1.259, P = 0.240). Conclusions Oral propranolol therapy accelerates IH involution but does not have a superior effect than spontaneous involution on the overall outcome of problematic IHs.

BACKGROUND:Postsurgical scar management significantly affects patient satisfaction. However, reliable skin support options are limited.OBJECTIVES:The present study aimed to determine the efficacy and safety of using tissue adhesive zippers in postsurgical scar prevention among patients undergoing surgical excision of the face. The primary outcome was a reduction in scar width, which was evaluated 1, 3, 6, and 12 months postoperatively. Scar width at Month 12 was considered the final outcome.METHODS:This was a prospective, randomized, controlled, rater-blinded trial. Sixty-four patients were randomly assigned to 2 groups (the zip group, defined as those using a tissue adhesive zipper for 3 months after surgery, and the control group). Outcomes were evaluated 1, 3, 6, and 12 months postoperatively based on scar width and Patient Observer Scar Assessment Scale score. Skin irritation was monitored during the first 3 months after surgery. The incidence of hypertrophic scar formation was recorded at a 12-month follow-up.RESULTS:Scar width differed significantly between the zip (mean [standard deviation], 1.68 [0.45] mm) and control groups (2.15 [0.64] mm). The scars spread rapidly in the first month after surgery but slowed down and stabilized after 6 months. The Patient Observer Scar Assessment Scale scores of the zip group were significantly lower than those of the control group. Neither group experienced significant complications.CONCLUSIONS:Prolonged use of tissue adhesive zippers immediately after surgery reduced scar width and improved scar appearance without obvious side effects.LEVEL OF EVIDENCE: 2:

INTRODUCTION:Different from Western culture, prominent zygoma and rectangular facial contour are deemed as unaesthetic and masculine in Asians. To achieve an ideal oval facial shape, reduction malarplasty is often performed.METHODS:Twenty-two eligible patients who underwent reduction malarplasty between November 2008 and December 2018 were reviewed. The reduction malarplasty involved repositioning of the osteotomized zygomatic arch and subperiosteal lift via a limited temporal incision. Photographs were collected both preoperatively and postoperatively. Complications and postoperative outcomes were evaluated.RESULTS:Twenty-two patients underwent reduction malarplasty with subperiosteal lift between November 2008 and December 2018. Their mean age was 35 ± 2.30 years. Prominent zygoma and facial contour were significantly improved after surgery. Patients demonstrated satisfaction with outcome (73.77 ± 6.83) and with facial appearance (75.00 ± 5.60). No cheek drooping and major complications were observed during the long-term follow-up.CONCLUSIONS:Prominent zygoma treated with reduction malarplasty with subperiosteal lift via limited temporal incision has a stable and long-lasting effect. This approach can be regarded as a true alternative for facial contour reshaping.

Infantile haemangiomas are the most common benign tumours affecting infants. Over time, the tumours may involute to some extent. However, sequelae, such as telangiectasia or fibrofatty tissue, often occur following this condition, which may cause disfigurement and influence patients’ psychosocial development. This prospective, randomized, self-controlled study aimed to assess the effects of topical timolol (0.5%) on involuting infantile haemangiomas. Each involuting superficial infantile haemangioma (n = 29) was randomly divided into two regions; one region was treated with topical timolol (0.5%) cream, three times daily, and the other region was untreated. The comparative treatments continued for three months. Five independent assessors, blinded to the treatment regimen, judged the treated and untreated regions by comparing photographs before and after treatment. The topical timolol-treated tumour sections showed no difference compared with the untreated sites (p = 0.355) after three months of treatment, and by the end of the treatment, the untreated lesions showed significant differences relative to pre-treatment (p<0.001). Topical timolol was not observed to have any effect on the regression of infantile haemangiomas in the involuting phase.

Background Ethanol embolotherapy is considered an optimal choice for the treatment of arteriovenous malformations（AVMs）; however, there are some complications associated with this treatment. This study aimed to prospectively investigate systemic hemodynamic changes in high-flow AVMs using ethanol embolotherapy.Methods From September 2012 to September 2014, 34 male patients and 26 female patients with AVMs who underwent embolotherapy（100 sessions in total） with absolute ethanol were included in this study. Invasive systolic blood pressure（SBP） and heart rate（HR） were recorded before and after each injection and throughout the procedure. Differences between the initial and highest SBP（?maxSP） and HR values（?maxHR）, as well as the initial and final SBP（?SP） and HR（?HR） values, were analyzed. We aimed to explore the potential association between these values and the amount of ethanol that was used.Results The total ethanol used was variable（0.01–0.40 mL/kg; mean, 0.20 mL/kg）. SBP and HR increased after ethanol injection in most sessions（91 in 100 sessions）. SBP decreased in 9 sessions（9 in 100 sessions）, while HR, oxygen saturation, and end-tidal CO 2 decreased in one of the 9 sessions. ?maxSP and ?maxHR averaged 38.4 mmHg and 27.8 bpm, respectively（both P＜0.05）, while ?SP and ?HR averaged 3.4 mmHg and 4.0 bpm, respectively（both P＜0.05）. ?maxSP and ?maxHR were positively correlated with the total dose of ethanol injected.Conclusions Elevations in SBP and HR during ethanol embolotherapy are common, temporary, and most likely pain-mediated; these increases tend to be positively correlated with ethanol dose. Hypotension may be regarded as an acute complication of ethanol embolotherapy. Hypotension combined with bradycardia, oxygen desaturation, and decreased end-tidal CO 2 may be a potential predictor of cardiovascular collapse.

Background: Additional skin support is promising in scar management, especially for wounds under high tension. Options for effective skin support are limited. This study aimed to determine whether prolonged use of an adhesive wound closure (AWC) device prevents scar spread and improves final appearance. Patients and Methods: This is a split-wound randomized evaluator-blinded study of 14 patients with facial wounds under high tension. After surgical closure, one half of each wound was randomly allocated to receive either standard care or additional 3-month treatment with an AWC device. Scar width, scar scale, and side effects were evaluated 12 months after surgery. Results: A significant difference was observed in scar width between the treated and nontreated sites at 12-month, with a mean difference of 1.024 (95% confidence interval, 0.347-1.700) mm in favor of the treated group. Scar widths in both groups increased rapidly in the first month after surgery and gradually increased until the sixth month. Scale for vascularization and relief were significantly lower in the treated sites. No significant differences were found in complications between two groups. Conclusions and Relevance: Prolonged usage of the AWC device prevented scar spread at 12 months and improved final scar scores in vascularization and relief. Clinical Trial Registration number: ChiCTR1900027155.

Abstract The authors have requested that this preprint be removed from Research Square.