The discriminative role of PROX-1 immunohistochemistry between venous malformation and lymphatic malformation of the deep type with no visible diagnostic surface skin lesion.

BACKGROUND: Venous malformations (VMs) are distinguished from lymphatic malformations (LMs) when specific diagnostic skin lesions are present. In the deep type, this is difficult by clinico-radiologic evaluation alone. We aimed to investigate the usefulness of lymphatic vessel endothelial cell (LEC) markers for the differential diagnosis of the deep VMs and LMs. METHODS: A retrospective study was conducted based on the medical records of patients with VMs and LMs who underwent biopsy with both D2-40 and PROX-1 immunohistochemistry. We compared the initial clinico-radiological diagnosis with the final pathological diagnosis and identified which ones showed a difference. RESULTS: From 261 patients who had VMs and LMs, 111 remained after the exclusion of those who showed definite surface diagnostic features. After pathological diagnosis with the expressions of D2-40 and PROX-1, 38 of 111 (34.2%) patients' final diagnoses were changed. Among these 38 cases, diagnosis was not changed by D2-40 positivity alone, but changed by PROX-1 positivity alone (52.6%) or by both (47.4%). The diagnostic changes were more frequent in the deep category (43.7%) than in the superficial category. CONCLUSIONS: Identifying the expression of D2-40, and especially PROX-1, in the differential diagnosis of VMs and LMs may provide important treatment guidelines and understanding their natural course.

Mesenchymal stromal cell therapy for patients with rheumatoid arthritis.

Management of relapses and refractory rheumatoid arthritis (RA) patients is complex and difficult. Even after the administration of new biological disease-modifying anti-rheumatic drugs (DMARDs), only a few patients achieve the complete remission phase. DMARDs help only in modifying the disease activity, which sooner or later fails. They do not manage the disease at the patho-etiological level. There are some serious side effects as well as drug interaction with DMARDs. There are few subsets of RA patients who do not respond to DMARDs, reasons unknown. Mesenchymal stem cells (MSCs) provide a promising alternative, especially in such cases. This review elaborates on the studies pertaining to the application of MSCs in rheumatoid arthritis over the last two decades. A total of 14 studies (one review article) including 447 patients were included in the study. Most of the studies administered MSCs in refractory RA patients through the intravenous route with varied dosages and frequency of administration. MSCs help in RA treatment via various mechanisms including paracrine effects. All the studies depicted a better clinical outcome with minimal adverse events. The functional scores including the VAS scores improved significantly in all studies irrespective of dosage and source of MSCs. The majority of the studies depicted no complications. Although the use of MSCs in RA is still in the early stages requiring further refinement in the source of MSCs, dosage, and frequency. The role of MSCs in the management of RA has a promising prospect. MSCs target the RA at the molecular level and has the potential to manage refractory RA cases not responding to conventional treatment. Multicentric, large sample populations, and long-term studies are required to ascertain efficacy and safety.

A Study on the Effectiveness of Helmet Therapy for Cranial Deformations According to Cranial Shape.

BACKGROUND: To investigate the effects of helmet therapy on plagiocephaly, according to head circumference, cephalic index (CI), and skull height. Plagiocephaly is a condition in which the skull is congenitally asymmetrical or affected by acquired factors such as compression in the womb or the habit of sleeping on one side. Although there are numerous studies on the effectiveness of helmet therapy for plagiocephaly, research on its effectiveness on skull shape is lacking. METHODS: We conducted a prospective study on 400 patients who underwent helmet therapy. The infants were enrolled and the therapy was explained to the caregiver when the child had positional plagiocephaly and had a cranial vault asymmetry (CVA) exceeding 10 mm or a CVA index (CVAI) exceeding 3.5%. The CVA and CVAI changes were compared to investigate the effectiveness of helmet therapy according to head circumference, CI, and skull height. RESULTS: A significant treatment effect was observed for CI values between 90 and 103. The treatment effect was found to increase with greater skull height. However, no significant difference was observed in the effectiveness of helmet therapy according to head circumference. CONCLUSIONS: According to the findings, the effectiveness of helmet therapy in children with positional plagiocephaly is greater for children with higher skulls and for those with CI values between 90 and 103; it is unrelated to head circumference. Based on these results, we can provide predictions of the effectiveness of helmet therapy to caregivers of children with positional plagiocephaly.

MicroRNA-135b-5p Is a Pathologic Biomarker in the Endothelial Cells of Arteriovenous Malformations.

Arteriovenous malformations (AVMs) are congenital vascular anomalies with a poor prognosis. AVMs are considered intractable diseases, as there is no established approach for early diagnosis and treatment. Therefore, this study aimed to provide new evidence by analyzing microRNAs (miRNAs) associated with AVM. We present fundamental evidence for the early diagnosis and treatment of AVM by analyzing miRNAs in the endothelial cells of AVMs. This study performed sequencing and validation of miRNAs in endothelial cells from normal and AVM tissues. Five upregulated and two downregulated miRNAs were subsequently analyzed under hypoxia and vascular endothelial growth factor (VEGF) treatment by one-way analysis of variance (ANOVA). Under hypoxic conditions, miR-135b-5p was significantly upregulated in the AVM compared to that under normal conditions, corresponding to increased endothelial activity (p-value = 0.0238). VEGF treatment showed no significant increase in miR-135b-5p under normal conditions, however, a surge in AVM was observed. Under both hypoxia and VEGF treatment, comparison indicated a downregulation of miR-135b-5p in AVM. Therefore, miR-135b-5p was assumed to affect the pathophysiological process of AVM and might play a vital role as a potential biomarker of AVMs for application related to diagnosis and treatment.

Three-dimensional culture conditioned bone marrow MSC secretome accelerates wound healing in a burn injury mouse model.

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising regenerative therapeutic approach for wound healing. To determine the effects of cultured MSCs as a 2D monolayer (2D-MSCs) and 3D spheroids (3D-MSCs) on their secretomes, and to examine the effect of 3D-MSC secretomes on endothelial cells (ECs) and MSCs in a burn injury mouse model. MSCs were cultured as 2D monolayers (2D-MSCs) and 3D spheroids (3D-MSCs) and their cellular characteristics were evaluated by western blotting. 2D-MSC and 3D-MSC secretomes (condition medium: CM) were analyzed using an angiogenic array. The activation of ECs by 2D-MSC and 3D-MSC CMs was examined in cellular proliferation, migration, and tube formation assays. The wound healing effects of 2D-MSCs and 3D-MSCs were determined in vivo using a burn injury mouse model. 3D culture conditions altered the markers of components that regulate cell survival, cytoskeletal, adhesion, and proliferation. Interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA), IL-8, and chemokine (CXC motif) ligand 1 (CXCL1) were present at high levels in the CM of 3D-MSCs compared with 2D-MCs. 3D-MSC-CMs promoted the proliferation, migration, and tube formation of ECs. Furthermore, 3D-MSC treatment enhanced wound healing in a burn injury mouse model. 3D culture improves proangiogenic factors in the MSC secretome and 3D-MSCs represent a new cell-based treatment strategy for wound healing.

Treatment of Sagittal Fracture of the Zygomatic Arch Root.

A sagittal fracture at the temporal root of the zygomatic arch (ZAR) often occurs as a component of zygomaticomaxillary complex (ZMC) fractures. However, this area is difficult to access, and anchorage is limited due to the unstable structure around it. Therefore, a preauricular approach using single-screw fixation is proposed, and this study reports its results and usefulness. Forty-four patients with sagittal fractures of ZAR occurring with ZMC fractures were evaluated from 2012 to 2021. Open reduction and internal fixation were performed on all patients with ZMC fractures. Closed reduction using Dingman incision and external finger pressure in group A (indirect approach; 30 patients) and single-screw fixation using a preauricular approach in group B (direct approach; 14 patients) were performed to address sagittal fractures in ZAR. For single-screw fixation, the additional mean operation time was 11.34±3.25 minutes. On postoperative 3-dimensional computed tomography and plain radiographs, group B showed more accurate reduction and less deformity and trismus ( P <0.05). Moreover, a normal diet was initiated more quickly in group B than in group A ( P <0.05). Some cases in group A showed nonunion or malunion. This study revealed that a direct approach (group B) toward sagittal fractures of ZAR is recommended due to more accurate results and fewer complications than those observed with the indirect approach (group A). Moreover, the total operation time and complications may be lesser than those with the bicoronal approach.

Influence of Transforming Growth Factors beta 1 and beta 3 in the Scar Formation Process.

BACKGROUND: Transforming growth factor-beta (TGF-ß) plays an instrumental role in forming scars and keloids. TGF-ß isoforms exhibit differential expression, indicating distinct wound healing and scar formation functions. However, the role of TGF-ß1 and TGF-ß3 in wound healing and scar formation remains unclear. This study aimed to compare the specific roles of TGF-ß1 and TGF-ß3 in wound healing and scar formation by biomolecular analysis. MATERIALS AND METHODS: The study was conducted by cell isolation and culture cells from a total of 20 human samples. Normal human fibroblasts (NHF) were isolated from normal human samples and myofibroblasts from the different scar types, namely hypertrophic (HT) and keloid (K) scars. NHF and cells from the HT, and K scar, each of which were divided into 3 sample groups: the untreated control, TGF-ß1 (10 µg/mL)-treated group, and TGF-ß3 (10 µg/mL)-treated group. The results of confocal microscopy and fluorescence-activated cell sorting experiments were compared. RESULTS: Both the HT and K groups had higher α-smooth muscle actin (α-SMA) expression than the NHF group in the untreated control group. In comparison with the untreated group, NHFs showed a significant increase in α-SMA expression in the TGF-ß1-treated group. HT showed a high α-SMA level, which was statistically significant compared with the normal fibroblasts. In the TGF-ß3-treated group, α-SMA expression was slightly increased in NHF as compared with the untreated group. TGF-ß3 treated HT exhibited a greater reduction in α-SMA expression than in the TGF-ß1 treated HT. K, on the other hand, had only a minimal effect on the treatment of TGF-ß1 and TGF-ß3. CONCLUSIONS: The findings suggest that TGF-ß3 may play a regulatory role in the wound repair process, which could be useful in the development of scar-reducing therapies for patients with scar-related cosmetic concerns.

Anatomical View of Thoracodorsal Artery Variants Using Computed Tomography Angiography.

BACKGROUND: The latissimus dorsi (LD) muscle has a dominant pedicle with one thoracodorsal artery and receives sufficient blood by segmental circulation through several perforators. Thus, it is widely used in various reconstructive surgeries. We are reporting on the patterns of the thoracodorsal artery analyzed by chest computed tomography (CT) angiography. METHODS: We analyzed the preoperative chest CT angiography results of 350 patients scheduled to undergo LD flap breast reconstruction following complete mastectomy for breast cancer between October 2011 and October 2020. RESULTS: A total of 700 blood vessels were classified according to the Kyungpook National University Plastic Surgery-Thoracodorsal Artery (KNUPS-TDA) classification: 388 (185 right and 203 left), 126 (64 right and 62 left), 91 (49 right and 42 left), 57 (27 right and 30 left), and 38 (25 right and 13 left) vessels were classified as type I, type II, type III, type IV, and type V, respectively. Among 350 patients, 205 patients showed matching types for left and right vessels, whereas 145 patients showed mismatching types. For 205 patients with matching types, the distribution by type was 134, 30, 30, 7, and 4 patients with type I, type II, type III, type IV, and type V, respectively. For 145 patients with mismatching types, the distribution by different combinations was 48, 25, 28, 19, 2, 9, 7, 3, 1, and 3 patients with type I + type II, type I + type III, type I + type IV, type I + type V, type II + type III, type II + type IV, type II + type V, type III + type IV, type III + type V, and type IV + type V, respectively. CONCLUSION: While there is some diversity in the vascular anatomical structures of the LD flap, the dominant vessel can be found in a similar location in almost all cases and no flap had absence of a dominant vessel. Therefore, in surgical procedures using the thoracodorsal artery as the pedicle, preoperative radiological confirmation is not absolutely necessary; however, due to variants, performing the surgery with an understanding of this aspect should lead to good outcomes.

Extracellular vesicles derived from fibroblasts promote wound healing by optimizing fibroblast and endothelial cellular functions.

Extracellular vesicles (EVs) have been exhibited as promising candidates for delivering endogenous therapeutic cargos for regenerative therapies. Fibroblasts could be candidate source cells for EVs, to investigate their therapeutic effects in wound healing. Here we demonstrated the isolation and characterization of fibroblast-derived (L929 cell line) EVs (L929-EVs). Furthermore, L929-EVs treatment showed pro-wound healing effects in vitro by enhancing proliferation, migration, and scarless wound healing related genes in fibroblast cells. L929-EVs treatment also enhanced the migration and tube formation of endothelial cells. The combination of L929-EVs with fibrin glue accelerated wound healing in the mouse skin wound model by enhancing collagen formation, collagen maturation, and blood vessels in the wounded skin. The role of fibroblast-derived EVs in wound healing could be an important phenomenon, and fibroblast-derived EVs could be harnessed for wound healing therapies.

Reconstruction after ablative treatment of arteriovenous malformations of the head and neck.

Arteriovenous malformations are high-flow congenital vascular malformations that are characterized by abnormal connections between arteries and veins across an abnormal capillary bed. The head and neck region is the most common location for extracranial arteriovenous malformations. Due to their highly invasive, aggressive, and locally destructive nature, arteriovenous malformations are difficult to treat, and management through a multimodal, multidisciplinary approach is recommended. The mainstay of treatment is embolization and surgical excision. With the advent of genetic research, adjuvant targeted medical therapy is starting to play a larger role. Successful surgical treatment with or without embolization requires removal of the nidus. Large, focal, or diffuse lesions involving multiple anatomic areas usually necessitates surgical reconstruction. Free tissue transfer has many advantages over more conservative methods with restoration of function and contour. Herein, the authors describe the surgical treatment and reconstruction in head and neck arteriovenous malformations.

Useful Reduction Mammoplasty Technique in Oncoplastic Breast Surgery and Reconstruction.

Background: A combination of the reduction mammoplasty technique and breast reconstruction allows surgeons to lift ptotic breasts through local flaps and skin reduction during surgery for breast cancer. This study presents a reliable course for the combination of partial and skin or nipple-sparing mastectomy with reduction-reconstruction surgery. Methods: Fifty-seven patients underwent a partial mastectomy before reduction mammoplasty of both breasts during the same time period between 2014 and 2021 at our institution and thirteen patients underwent skin or nipple-sparing mastectomy, breast reconstruction with an extended latissimus dorsi flap or silicone implant, and aesthetic reduction mammoplasty of the contralateral breast during the same time period. Additional photos were obtained preoperatively, immediately after the operation, and at one, three, six, and twelve months postoperatively. Patient satisfaction was evaluated preoperatively and postoperatively and postoperative complications were noted. Results: Among the patients who underwent a partial mastectomy, the mean age was 45.18 ± 11.05 years, the mean body mass index (BMI) was 26.74 ± 3.53 kg/m2, and the mean preoperative right and left breast volumes were 663.85 (±28.12) cc and 664.34 (±37.13) cc, respectively, and the mean excised mass weight was 177.74 (±213.93) g. Among the patients who underwent a skin-sparing mastectomy, the mean age was 51.62 ± 8.96 years, the mean BMI was 26.91 ± 4.34 kg/m2, and the mean preoperative right and left breast volumes were 624.17 (±98.52) cc and 562.31 (±80.81) cc, respectively, and the mean excised mass weight was 618.05 (±338.17) g. Four patients (5.3%) in the partial mastectomy group had fat necrosis. The mean patient satisfaction score was higher postoperatively in both groups. Conclusion: Patients with breast cancer and large and/or ptotic breasts can successfully undergo reduction mammoplasty for both breasts immediately following partial mastectomy and nipple or skin-sparing mastectomy.

Useful vertical latissimus dorsi flap for partial breast reconstruction in every tumor location.

BACKGROUND: We conducted a prospective cohort study to evaluate effective techniques for breast reconstruction after partial mastectomy due to breast cancer. Determining the method of reconstruction is often difficult as it depends on the location of the cancer and the amount of tissue excised.. Here, we present a new technique, using the vertical latissimus dorsi (LD) flap, that can be used in all partial mastectomies and can almost conceal scarring. We also compared these results to those of the mini LD flap. METHODS: We analyzed the data of a total of 50 and 47 patients, who underwent breast reconstruction with the mini LD flap and the vertical LD flap, respectively. Immediately after tumor excision, breast reconstruction was initiated. The skin flap for vertical LD was designed in a planarian shape, such that it may be hidden as much as possible and minimize bulging during closure, and the LD muscle flap was designed with a sufficient distance in the inferior direction. RESULTS: Our finding showed that the vertical LD flap group required significantly less total operation time than the mini LD flap group. While the mini-LD flap resulted in a scar that was difficult to conceal, the donor site scar of the vertical LD flap could not be seen easily, and no scar was visible on the back. CONCLUSIONS: The vertical LD flap is useful for partial breast reconstruction, in all breast regions requires a rather small volume of the flap. Moreover, recovery was relatively fast with high patient satisfaction.

Correction of Severe Secondary Cleft Lip Nasal Deformity.

BACKGROUND: The lower lateral cartilages (LLCs) are key elements for alar and tip support. Repositioning of both LLCs is an effective procedure for correcting a laterally spreading dome of LLCs and drooping nasal tip in cleft lip nasal deformity (CLND). The alar contour graft has become an essential component of rhinoplasty for correcting the concave or collapsed and retracted alar. Herein, onlay cartilage graft was combined with nasal tip plasty to correct hypoplastic cleft lateral crus or alar rim retraction, and with columella strut to obtain better aesthetic outcomes in patients with severe CLND. METHODS: Seven patients with severe secondary unilateral CLND, including hypoplastic cleft lateral crus or alar rim retraction, underwent rhinoplasty from October 2013 to April 2020. Both LLCs were isolated and repositioned approximated medially using tip suture technique combined with columella strut. A septal cartilage onlay graft was applied on the hypoplastic cleft lateral crus. Cartilage graft on the nasal tip was performed to further project and enhance the nasal tip. Photogrammetric evaluation of the operated patients and statistical analysis of the obtained data were performed. RESULTS: The average age at operation was 23.5 (range: 17-36) years. The follow-up period was 6-36 (mean, 14.3) months. All patients were enrolled by photogrammetric evaluation. Height of the medial nostril and short axis of the nostril on the cleft side were increased with a statistical significance of P < 0.05, indicating that depressed ala on the cleft side, which is a feature of CLND, was corrected similar to that of the noncleft side. CONCLUSIONS: The alar contour cartilage graft, as an effective adjunctive technique, improves the alar margin, prevents the alar rim from collapsing, and provides supports to the cleft-side alar rim. It can be a prophylactic measure to prevent postoperative retraction in patients with weakened LLCs. Lower lateral cartilage repositioning, columellar strut, and nasal tip plasty are useful for correcting severe secondary unilateral CLND.

Prognosis of Continuous Positive Airway Pressure Treatment to Velopharyngeal Insufficiency: Preliminary Study.

BACKGROUND: Cleft palate is a congenital malformation that causes hypernasality and decreases the intelligibility of pronunciation and leads to velopharyngeal insufficiency. It causes difficulty in language development. Many studies and treatments have been conducted to reduce this problem, but there are limitations. In this study, the effect obtained through continuous positive airway pressure (CPAP) treatment was analyzed by statistical methods. METHODS: From May 2012 to December 2018, using patient demographics, computed tomography (CT) scan, and nasalance test was performed on 25 patient groups treated with CPAP devices for 8 weeks to confirm the effect after 6 months. RESULTS: After CPAP treatment in a total of 25 patients, 13 patients had a therapeutic effect. The average age of the patient group with treatment effect (effective group [EG]) was 51.2months, and the patient group with no treatment effect (ineffective group [iG]) was 73.6 months. ( P < 0.05). In CT data analysis, the highest palatal arch point was 6.31 mm in EG and 7.36 mm in IG, which was lower in EG ( P < 0.01), and the distance from incisive foramen to posterior pharyngeal wall was 41.39 mm in EG and 49.07 mm in IG ( P < 0.05). CONCLUSIONS: Through the statistical analysis, the group of patients who were effective in treatment had a low age at the beginning of treatment, the height of highest palatal arch point was low on CT data, and the length of distance from incisive foramen to posterior pharyngeal wall was short. It will be helpful to set the CPAP treatment patient group with respect to the results and age and CT data when treating VPI patients.

The Effect of Orthognathic Surgery on Changes in Masticatory Muscle Volume in Patients With Facial Asymmetry.

ABSTRACT: The masseter muscle changes remarkably with orthognathic surgery and has a marked influence on the contours of the lower face. If the postoperative volume change of masticatory muscles, including the masseter muscles, can be predicted, it will facilitate preoperative planning and outcome prediction. This study investigated the association of masticatory muscle volume according to the presence or absence of facial asymmetry, and evaluated whether the volume of masticatory muscles, including that of the masseter muscle, changes after orthognathic surgery in facial asymmetry patients.Twenty patients who underwent LeFort I osteotomy and bilateral sagittal segmentation ramus osteotomy (BSSRO) with facial asymmetry between 2011 and 2017 were assigned to the asymmetric group. Additionally, 207 patients with a simple nasal fracture between 2016 and 2019 were included as the common group. Threedimensional computed tomography images were retrospectively analyzed and compared between the asymmetric group and common group.The volume of both temporal and masseter muscles differed according to facial asymmetry, with the asymmetry in the muscle volume increasing in proportion to the degree of facial asymmetry. The difference in masseter volume on the shortened and lengthened sides was significantly reduced after orthognathic surgery, but a difference of about 1 cm 3 remained. Additionally, the masticatory muscle volume on the lengthened side tended to be decreased more than that on the shortened side.Consideration of the postoperative change in the volume of the masticatory muscles may be helpful in planning orthognathic surgery in facial asymmetry patients.

Usefulness of Incisional Negative Pressure Wound Therapy for Decreasing Wound Complication Rates and Seroma Formation Following Prepectoral Breast Reconstruction.

BACKGROUND: Seroma is a common complication in prepectoral breast reconstruction. PICOTM dressing, a type of incisional negative pressure wound therapy (iNPWT), was used to reduce complications postoperatively. METHODS: This study was a retrospective cohort study that included patients who underwent prepectoral breast reconstruction between February 2017 and July 2019. There were two groups: one that received PICOTM dressing and a control group. The frequencies of overall complications, major seromas, and reoperations were analyzed. The durations and total amounts of seromas were also analyzed. RESULT: Sixty patients were included in this study (PICOTM : 37 and non-PICOTM patients: 23). The overall incidence of complications, major seromas, and frequency of reoperations were lower in the PICO group compared to the non-PICOTM group (18.9% vs. 52.2%, p = 0.007; 16.2% vs. 43.5%, p = 0.020; 2.7% vs. 26.1%, p = 0.006, respectively). Univariate analysis was used to analyze the risk factors for complications due to the application of PICOTM dressing and showed statistically significant results for any complication. When univariate analysis was performed on risk factors for seroma, the duration of seroma showed statistical significance in association with PICOTM dressing status and mastectomy volume. The total number of patients who developed seroma was statistically correlated with age, PICOTM dressing status, and mastectomy volume. CONCLUSIONS: PICOTM dressing after prepectoral breast reconstruction could be a useful tool for reducing the frequency of complications and major seroma, as well as the duration and total incidences of seroma. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effect of Topical Tranexamic Acid on Seroma Formation in a Rat Mastectomy Model.

BACKGROUND: Seroma is the most common complication after mastectomy and reconstruction surgery. Therefore, this study aimed to determine whether the topical application of tranexamic acid would be useful to reduce seromas in a rat mastectomy model. METHODS: Forty-eight Sprague-Dawley rats were divided into four groups. After mastectomy and axillary lymph node dissection, 0.4 mL of normal saline was administered to group A in the dead space. In group B, 0.4 mL of a triamcinolone mixed solution was administered. In group C, 0.4 mL of a tranexamic acid (10 mg/kg) mixed solution was administered. In group D, 0.4 mL of a tranexamic acid (50 mg/kg) mixed solution was administered. Gross examination, assessment with micro-computed tomography (CT), quantitative analysis via aspiration, and histopathologic assessment were implemented 7 and 14 days postoperatively. RESULTS: No other complications such as wound infection and skin necrosis were observed. At postoperative week 1, groups B and C showed significantly lower seroma volume values on micro-CT (P < 0.001 and P < 0.05, respectively) and seroma volume values at aspiration (P < 0.01 and P < 0.001, respectively) than group A. According to histopathologic analysis, inflammation was observed more frequently in groups A and D than in the other groups, and angiogenesis was more active in groups B and C than in the other groups. CONCLUSIONS: Topical application of tranexamic acid was as effective as topical application of triamcinolone to prevent seroma formation. The stability of tranexamic acid was confirmed when the high dose of tranexamic acid was used. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

MicroRNA-365a/b-3p as a Potential Biomarker for Hypertrophic Scars.

The clinical aspects of hypertrophic scarring vary according to personal constitution and body part. However, the mechanism of hypertrophic scar (HS) formation remains unclear. MicroRNAs (miRNAs) are known to contribute to HS formation, however, their detailed role remains unknown. In this study, candidate miRNAs were identified and analyzed as biomarkers of hypertrophic scarring for future clinical applications. HSfibroblasts and normal skin fibroblasts from patients were used for profiling and validation of miRNAs. An HS mouse model with xenografted human skin on nude mice was established. The miRNA expression between normal human, normal mouse, and mouse HS skin tissues was compared. Circulating miRNA expression levels in the serum of normal mice and mice with HSs were also analyzed. Ten upregulated and twenty-one downregulated miRNAs were detected. Among these, miR-365a/b-3p and miR-16-5p were identified as candidate miRNAs with statistically significant differences; miR-365a/b-3p was significantly upregulated (p = 0.0244). In mouse studies, miR-365a/b-3p expression levels in skin tissue and serum were higher in mice with HSs than in the control group. These results indicate that miRNAs contribute to hypertrophic scarring and that miR-365a/b-3p may be considered a potential biomarker for HS formation.

Hypoxia Promotes Angiogenic Effect in Extracranial Arteriovenous Malformation Endothelial Cells.

Arteriovenous malformation (AVM) is characterized by high-flow blood vessels connecting arteries and veins without capillaries. This disease shows increased angiogenesis and a pathophysiological hypoxic environment in proximal tissues. Here, we analyzed the effects of hypoxia on angiogenesis in the endothelial cells (ECs) of AVM and normal tissues. ECs from human normal and AVM tissues were evaluated using immunocytochemistry with CD31. In vitro tube formation under hypoxia was tested in both ECs using Matrigel. The relative expression of angiogenesis-related genes was measured using real-time PCR. Under normoxia, CD31 was significantly higher in AVM ECs (79.23 ± 0.65%) than in normal ECs (74.15 ± 0.70%). Similar results were observed under hypoxia in AVM ECs (63.85 ± 1.84%) and normal ECs (60.52 ± 0.51%). In the tube formation test under normoxic and hypoxic conditions, the junction count and total vessel length were significantly greater in AVM ECs than normal ECs. Under both normoxia and hypoxia, the angiogenesis-related gene FSTL1 showed a significantly higher expression in AVM ECs than in normal ECs. Under hypoxia, CSPG4 expression was significantly lower in AVM ECs than in normal ECs. Accordingly, the angiogenic effect was increased in AVM ECs compared with that in normal ECs. These results provide a basic knowledge for an AVM treatment strategy.

Oscillatory shear stress promotes angiogenic effects in arteriovenous malformations endothelial cells.

BACKGROUND: Vascular endothelial cells (ECs) are subject to continuous shear stress due to blood circulation. Mechanical stress due to high shear flow can also cause arteriovenous malformation (AVM) when ECs respond hyper-sensitively to shear flow. This study was conducted to test the hypothesis that angiogenesis could be promoted in response to mechanical stress via regulation of pro-angiogenic factors in AVM cells. METHODS: ECs were extracted from the tissue samples from six AVM patients and six normal patients. Shear stress at 7 dynes/cm2 were applied for 24 h. Before and after application of shear stress to each group, RT-PCR was performed to access the expression levels of angiopoietin2(AGP2), aquaporin1(AQP1) and TGFßR1. Immunofluorescences was also performed to evaluate the level of protein expressions. RESULTS: In both normal and AVM tissues, AGP2 and TGFßR1 under the shear stress showed increased expression in the ECs compared to the non-sheared samples. When AVMs and normal arterial vasculature were compared, the expression levels of both AGP2 and TGFßR1 in AVMs were higher when compared to normal arterial vasculature with or without shear stress. Immunofluorescence-based protein analysis also confirmed shear-induced AGP2 and TGFßR1 in both samples of normal and AVM patients. CONCLUSIONS: AVMs exhibited higher sensitivity to shear stress by producing higher expressions of some marked genes and proteins that regulate the endothelial functions upon exposure to shear stress. While the physiological mechanism for AVMs remain elusive, our study shows the plausibility of physical stress imposed by the shearing flow can cause the occurrence of AVMs.