Development of a photosynthetic hydrogel as potential wound dressing for the local delivery of oxygen and bioactive molecules.

The development of biomaterials to improve wound healing is a critical clinical challenge and an active field of research. As it is well described that oxygen plays a critical role in almost each step of the wound healing process, in this work, an oxygen producing photosynthetic biomaterial was generated, characterized, and further modified to additionally release other bioactive molecules. Here, alginate hydrogels were loaded with the photosynthetic microalgae Chlamydomonas reinhardtii, showing high integration as well as immediate oxygen release upon illumination. Moreover, the photosynthetic hydrogel showed high biocompatibility in vitro and in vivo, and the capacity to sustain the metabolic oxygen requirements of zebrafish larvae and skin explants. In addition, the photosynthetic dressings were evaluated in 20 healthy human volunteers following the ISO-10993-10-2010 showing no skin irritation, mechanical stability of the dressings, and survival of the photosynthetic microalgae. Finally, hydrogels were also loaded with genetically engineered microalgae to release human VEGF, or pre-loaded with antibiotics, showing sustained release of both bioactive molecules. Overall, this work shows that photosynthetic hydrogels represent a feasible approach for the local delivery of oxygen and other bioactive molecules to promote wound healing. STATEMENT OF SIGNIFICANCE: As oxygen plays a key role in almost every step of the tissue regeneration process, the development of oxygen delivering therapies represents an active field of research, where photosynthetic biomaterials have risen as a promising approach for wound healing. Therefore, in this work a photosynthetic alginate hydrogel-based wound dressing containing C. reinhardtii microalgae was developed and validated in healthy skin of human volunteers. Moreover, hydrogels were modified to additionally release other bioactive molecules such as recombinant VEGF or antibiotics. The present study provides key scientific data to support the use of photosynthetic hydrogels as customizable dressings to promote wound healing.

Five-point liquid rhinoplasty: Results from a retrospective analysis of a novel standardized technique and considerations on safety.

BACKGROUND: Nonsurgical aesthetic improvement of the nose with hyaluronic acid (HA) fillers is becoming increasingly popular but comes with important safety considerations. AIMS: To assess the safety and effectiveness of the standardized "five-point liquid rhinoplasty" approach. METHODS: This was a retrospective, single-center analysis of consecutive adult patients undergoing nonsurgical aesthetic treatment of the nose. All had one of the three main indications (insufficient nasal projection, nasal hump, or deep glabella) and were injected using HA fillers with high elastic modulus. Treatments were given using some or all of the injection points of the "five-point liquid rhinoplasty" technique: P1 (nasal tip, 0.2-0.3 ml supracartilaginous); P2 (nasal root, 0.1-0.2 ml supraperiostal); P3 (cartilaginous dorsum, 0.1-0.2 ml supracartilaginous/supraperiostal); P4 (subnasal, 0.1-0.2 ml supraperiostal); and P5 (nasal alar, 0.1-0.2 ml per side supraperiostal). The risk of complications was minimized by injecting deep and staying in the midline as far as possible. RESULTS: Twenty patients were enrolled (n = 15 female [75%]; mean age: 37.8 ± 11.7 years). The mean volume of filler used was 0.66 ± 0.35 ml per patient. Nineteen subjects (95%) said they were "very satisfied" with results, and the physician was also "very satisfied" with outcomes in 19 patients (95%). Two individuals experienced hematoma, which was managed conservatively; there were no other significant complications. CONCLUSIONS: The "five-point liquid rhinoplasty" is a simple and effective method designed to maximize safety. It offers a good alternative to surgery in selected patients.

Evaluation of the Usability of a Low-Cost 3D Printer in a Tissue Engineering Approach for External Ear Reconstruction.

The use of alloplastic materials instead of autologous cartilage grafts offers a new perspective in craniofacial reconstructive surgery. Particularly for regenerative approaches, customized implants enable the surgeon to restore the cartilaginous framework of the ear without donor site morbidity. However, high development and production costs of commercially available implants impede clinical translation. For this reason, the usability of a low-cost 3D printer (Ultimaker 2+) as an inhouse-production tool for cheap surgical implants was investigated. The open software architecture of the 3D printer was modified in order to enable printing of biocompatible and biologically degradable polycaprolactone (PCL). Firstly, the printing accuracy and limitations of a PCL implant were compared to reference materials acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA). Then the self-made PCL-scaffold was seeded with adipose-tissue derived stem cells (ASCs), and biocompatibility was compared to a commercially available PCL-scaffold using a cell viability staining (FDA/PI) and a dsDNA quantification assay (PicoGreen). Secondly, porous and solid patient-customized ear constructs were manufactured from mirrored CT-imagining data using a computer-assisted design (CAD) and computer-assisted manufacturing (CAM) approach to evaluate printing accuracy and reproducibility. The results show that printing of a porous PCL scaffolds was possible, with an accuracy equivalent to the reference materials at an edge length of 10 mm and a pore size of 0.67 mm. Cell viability, adhesion, and proliferation of the ASCs were equivalent on self-made and the commercially available PCL-scaffolds. Patient-customized ear constructs could be produced well in solid form and with limited accuracy in porous form from all three thermoplastic materials. Printing dimensions and quality of the modified low-cost 3D printer are sufficient for selected tissue engineering applications, and the manufacturing of personalized ear models for surgical simulation at manufacturing costs of EUR 0.04 per cell culture scaffold and EUR 0.90 (0.56) per solid (porous) ear construct made from PCL. Therefore, in-house production of PCL-based tissue engineering scaffolds and surgical implants should be further investigated to facilitate the use of new materials and 3D printing in daily clinical routine.

Anatomy behind the Paramedian Platysmal Band: A Combined Cadaveric and Computed Tomographic Study.

BACKGROUND: The muscular hypothesis explanation of the pathophysiology behind paramedian platysmal bands does not seem to provide a sufficient explanation for the clinical presentation of these platysmal bands in aged individuals with cervical soft-tissue laxity. The purpose of this study was to investigate the fascial relationships of the anterior neck to enhance appropriate surgical treatment. METHODS: Retrospective analysis of computed tomographic scans of 50 Caucasian individuals (mean age, 55.84 ± 17.5 years) and anatomical dissections of 20 Caucasian and 10 Asian body donors (mean age, 75.88 ± 10.6 years) were conducted. Fascial adhesions were classified according to platysma fusion types, and platysma mobility was tested during dissection procedures. RESULTS: Fusion between the left and right platysma muscles occurred in 64 percent in the suprahyoid region and in 20 percent at the thyroid cartilage, and in 16 percent, the platysma attached to the mandible without fusion. In the absence of muscular fibers, a fascial adhesion zone with limited mobility was observed where the superficial cervical fascia fused with the investing layer of the deep cervical fascia. CONCLUSIONS: Muscular contraction of the platysma results in elevation of the most medial platysma muscle fibers, which are not attached in the fascial adhesion zone. The presence of a fatty layer deep to the platysma enables platysmal movement and anterior and inferior gliding of the skin and platysma when cervical soft-tissue laxity exists. Surgical treatments should include transection of the fascial adhesion; this could potentially prevent the recurrence of paramedian platysmal bands.

Digital Leg Volume Quantification: Precision Assessment of a Novel Workflow Based on Single Capture Three-dimensional Whole-Body Surface Imaging.

Whole-body three-dimensional surface imaging (3DSI) offers the ability to monitor morphologic changes in multiple areas without the need to individually scan every anatomical region of interest. One area of application is the digital quantification of leg volume. Certain types of morphology do not permit complete circumferential scan of the leg surface. A workflow capable of precisely estimating the missing data is therefore required. We thus aimed to describe and apply a novel workflow to collect bilateral leg volume measurements from whole-body 3D surface scans regardless of leg morphology and to assess workflow precision. For each study participant, whole-body 3DSI was conducted twice successively in a single session with subject repositioning between scans. Paired samples of bilateral leg volume were calculated from the 3D surface data, with workflow variations for complete and limited leg surface visibility. Workflow precision was assessed by calculating the relative percent differences between repeated leg volumes. A total of 82 subjects were included in this study. The mean relative differences between paired left and right leg volumes were 0.73 ± 0.62% and 0.82 ± 0.65%. The workflow variations for completely and partially visible leg surfaces yielded similarly low values. The workflow examined in this study provides a precise method to digitally monitor leg volume regardless of leg morphology. It could aid in objectively comparing medical treatment options of the leg in a clinical setting. Whole-body scans acquired using the described 3DSI routine may allow simultaneous assessment of other changes in body morphology after further validation.

Zone-Dependent Architecture and Biochemical Composition of Decellularized Porcine Nasal Cartilage Modulate the Activity of Adipose Tissue-Derived Stem Cells in Cartilage Regeneration.

Previous anatomical studies have shown different functional zones in human nasal septal cartilage (NC). These zones differ in respect to histological architecture and biochemical composition. The aim of this study was to investigate the influence of these zones on the fate of stem cells from a regenerative perspective. Therefore, decellularized porcine septal cartilage was prepared and subjected to histological assessment to demonstrate its equivalence to human cartilage. Decellularized porcine NC (DPNC) exposed distinct surfaces depending on two different histological zones: the outer surface (OS), which is equivalent to the superficial zone, and the inner surface (IS), which is equivalent to the central zone. Human adipose tissue-derived stem cells (ASCs) were isolated from the abdominal fat tissue of five female patients and were seeded on the IS and OS of DPNC, respectively. Cell seeding efficiency (CSE), vitality, proliferation, migration, the production of sulfated glycosaminoglycans (sGAG) and chondrogenic differentiation capacity were evaluated by histological staining (DAPI, Phalloidin, Live-Dead), biochemical assays (alamarBlue®, PicoGreen®, DMMB) and the quantification of gene expression (qPCR). Results show that cell vitality and CSE were not influenced by DPNC zones. ASCs, however, showed a significantly higher proliferation and elevated expression of early chondrogenic differentiation, as well as fibrocartilage markers, on the OS. On the contrary, there was a significantly higher upregulation of hypertrophy marker MMP13 (p < 0.0001) and GAG production (p = 0.0105) on the IS, whereas cell invasion into the three-dimensional DPNC was higher in comparison to the OS. We conclude that the zonal-dependent distinct architecture and composition of NC modulates activities of ASCs seeded on DPNC. These findings might be used for engineering of cartilage substitutes needed in facial reconstructive surgery that yield an equivalent histological and functional structure, such as native NC.

Artificial decellularized extracellular matrix improves the regenerative capacity of adipose tissue derived stem cells on 3D printed polycaprolactone scaffolds.

Ideal tissue engineering frameworks should be both an optimal biological microenvironment and a shape and stability providing framework. In this study we tried to combine the advantages of cell-derived artificial extracellular matrix (ECM) with those of 3D printed polycaprolactone (PCL) scaffolds. In Part A, both chondrogenic and osteogenic ECMs were produced by human adipose derived stem cells (hASCs) on 3D-printed PCL scaffolds and then decellularized to create cell free functionalized PCL scaffolds, named acPCL and aoPCL respectively. The decellularization resulted in a significant reduction of the DNA content as well as the removal of nuclei while the ECM was largely preserved. In Part B the bioactivation and the effect of the ac/aoPCL scaffolds on the proliferation, differentiation, and gene expression of hASCs was investigated. The ac/aoPCL scaffolds were found to be non-toxic and allow good adhesion, but do not affect proliferation. In the in vitro investigation of cartilage regeneration, biochemical analysis showed that acPCL scaffolds have an additional effect on chondrogenic differentiation as gene expression analysis showed markers of cartilage hypertrophy. The aoPCL showed a large influence on the differentiation of hASCs. In control medium they were able to stimulate hASCs to produce calcium alone and all genes relevant investigated for osteogenesis were significantly higher expressed on aoPCL than on unmodified PCL. Therefore, we believe that ac/aoPCL scaffolds have a high potential to improve regenerative capacity of unmodified PCL scaffolds and should be further investigated.

Influence of Rheological Properties and Needle Size on Extrusion Forces of Hyaluronic Acid Based Soft Tissue Fillers.

BACKGROUND: To date no precise data are available for extrusion forces related to the G-prime and G-double-prime of fillers in combination with different 27G and 30G needles. Therefore, the objective of this study was to analyze extrusion forces of various product-needle-combinations containing two different 27G and two different 30G needles in combination with fillers of a wide range of elastic moduli starting from 2.0 – 166.0 Pa. MATERIAL AND METHODS: Four different fillers with the following elastic moduli 1.87, 11.65, 61.80, 165.50 Pa were combined with four different needles: 27G ½”, internal diameter: 0.300 μm; 27G ½”, internal diameter: 0.241 μm; 30G ½”, internal diameter: 0.241 μm and 30G ½“, internal diameter: 0.240 μm. Product-needle-combination were subjected to uni-axial mechanical testing and the respective extrusion force was measured. RESULTS: The results of this study revealed that the G-prime and the G-double-prime of a product are statistically significantly related to their extrusion force, with higher G-prime/G-double-prime products requiring higher extrusion forces. The results additionally revealed that whether the size of the needle was described as 27G or 30G by the respective manufacturer statistically significant differences between the measured extrusion forces were detected. CONCLUSION: Injectors need to be aware that not every 27G/30G needle has the same extrusion force even though the external diameter is similar (27G or 30G); this might additionally influence the ability to withdraw blood during a pre-injection aspiration manoeuvre. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5237.

Quantitative Analysis of the Lifting Effect of Facial Soft-Tissue Filler Injections.

BACKGROUND: Although injectable soft-tissue fillers are frequently used for facial rejuvenation, there is a dearth of objective data evaluating the tissue-lifting effects. Current practices for efficacy evaluation include some subjectivity. This study seeks to evaluate the lifting effects of facial soft-tissue fillers in a quantifiable, objective setting. METHODS: Twenty fresh hemifaces obtained from 10 Caucasian body donors (seven women and three men) with a mean age of 83.5 ± 6.8 years and a mean body mass index of 25.3 ± 4.3 kg/m2 were injected with soft-tissue fillers following a predefined treatment algorithm. Three-dimensional surface scanning procedures were performed to assess postinjection effects. RESULTS: Injections in the medial face [i.e., forehead, medial midface, and perioral (chin and labiomandibular sulcus)] increased the local surface volume by 0.67, 0.56, and 0.87 cc and created local (but not regional) lifting effects of 1.11, 0.11, and 0.74 mm. Injections in the lateral face (temple, lateral midface, and jawline) changed the local surface volume by 0.45, 0.02, and -0.38 cc, and created local lifting effects of 0.57, 0.81, and 0.29 mm, respectively. Lateral face injections, however, created additional regional lifting effects by co-influencing neighboring lateral facial regions, which was not observed for medial face injections. CONCLUSIONS: This cadaveric study provides evidence that soft-tissue fillers, although typically classified as volumizers, can induce lifting effects of the face. Whereas temporal deep supraperiosteal injections have limited lifting effects, the combined effects of subdermal injections of the temple, lateral midface, and mandibular angle can induce lifting effects of the total lateral face. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Use of photosynthetic transgenic cyanobacteria to promote lymphangiogenesis in scaffolds for dermal regeneration.

Impaired wound healing represents an unsolved medical need with a high impact on patients´ quality of life and global health care. Even though its causes are diverse, ischemic-hypoxic conditions and exacerbated inflammation are shared pathological features responsible for obstructing tissue restoration. In line with this, it has been suggested that promoting a normoxic pro-regenerative environment and accelerating inflammation resolution, by reinstating the lymphatic fluid transport, could allow the wound healing process to be resumed. Our group was first to demonstrate the functional use of scaffolds seeded with photosynthetic microorganisms to supply tissues with oxygen. Moreover, we previously proposed a photosynthetic gene therapy strategy to create scaffolds that deliver other therapeutic molecules, such as recombinant human growth factors into the wound area. In the present work, we introduce the use of transgenic Synechococcus sp. PCC 7002 cyanobacteria (SynHA), which can produce oxygen and lymphangiogenic hyaluronic acid, in photosynthetic biomaterials. We show that the co-culture of lymphatic endothelial cells with SynHA promotes their survival and proliferation under hypoxic conditions. Also, hyaluronic acid secreted by the cyanobacteria enhanced their lymphangiogenic potential as shown by changes to their gene expression profile, the presence of lymphangiogenic protein markers and their capacity to build lymph vessel tubes. Finally, by seeding SynHA into collagen-based dermal regeneration materials, we developed a viable photosynthetic scaffold that promotes lymphangiogenesis in vitro under hypoxic conditions. The results obtained in this study lay the groundwork for future tissue engineering applications using transgenic cyanobacteria that could become a therapeutic alternative for chronic wound treatment. STATEMENT OF SIGNIFICANCE: In this study, we introduce the use of transgenic Synechococcus sp. PCC 7002 (SynHA) cyanobacteria, which were genetically engineered to produce hyaluronic acid, to create lymphangiogenic photosynthetic scaffolds for dermal regeneration. Our results confirmed that SynHA cyanobacteria maintain their photosynthetic capacity under standard human cell culture conditions and efficiently proliferate when seeded inside fibrin-collagen scaffolds. Moreover, we show that SynHA supported the viability of co-cultured lymphatic endothelial cells (LECs) under hypoxic conditions by providing them with photosynthetic-derived oxygen, while cyanobacteria-derived hyaluronic acid stimulated the lymphangiogenic capacity of LECs. Since tissue hypoxia and impaired lymphatic drainage are two key factors that directly affect wound healing, our results suggest that lymphangiogenic photosynthetic biomaterials could become a treatment option for chronic wound management.

Performing Distance Measurements in Curved Facial Regions: A Comparison between Three-Dimensional Surface Scanning and Ultrasound Imaging.

Facial flap surgery depends strongly on thorough preoperative planning and precise surgical performance. To increase the dimensional accuracy of transferred facial flaps, the methods of ultrasound and three-dimensional (3D) surface scanning offer great possibilities. This study aimed to compare different methods of measuring distances in the facial region and where they can be used reliably. The study population consisted of 20 volunteers (10 males and 10 females) with a mean age of 26.7 ± 7.2 years and a mean body mass index of 22.6 ± 2.2 kg/m2. Adhesives with a standardized length of 20 mm were measured in various facial regions through ultrasound and 3D surface scans, and the results were compared. Regardless of the facial region, the mean length measured through ultrasound was 18.83 mm, whereas it was 19.89 mm for 3D surface scans, with both p < 0.0001. Thus, the mean difference was 1.17 mm for ultrasound measurements and 0.11 mm for 3D surface scans. Curved facial regions show a great complexity when it comes to measuring distances due to the concavity and convexity of the face. Distance measurements through 3D surface scanning showed more accurate distances than the ultrasound measurement. Especially in "complex" facial regions (e.g., glabella region and labiomental sulcus), the 3D surface scanning showed clear advantages.

Intraarterial Degradation of Calcium Hydroxylapatite Using Sodium Thiosulfate - An In Vitro and Cadaveric Study.

BACKGROUND: The most severe complications following soft tissue filler injections result from the intraarterial administration of the filler product. Although hyaluronic acid-based filler can be trans-arterially dissolved with hyaluronidase, no information is available on calcium hydroxylapatite (CaHA)-based fillers. OBJECTIVE: The authors sought to test whether CaHA-based fillers can be trans-arterially dissolved by sodium thiosulfate (STS) when evaluated in cadaveric and in vitro models. METHODS: Human cadaveric facial arterial segments were each filled with 0.2 cc of commercially available CaHA product and submerged for 24 hours in 4 different STS-containing solutions: 10 cc STS (300 mg/cc) (pure, 1:1 dilution, 1:2 dilution), 0.9% saline and 10 cc STS (300 mg/cc), and 300 IU (bovine) hyaluronidase in a 1:1 ratio. RESULTS: Intraarterial CaHA was detected in human facial artery segments after 24 hours independent of the STS concentration employed. Submerging the arterial segments in STS (300 mg/cc) and 300 IU (bovine) hyaluronidase (1:1 ratio) also did not dissolve the intraarterial CaHA product. Gray scale analyses did show, however, that increasing concentrations of STS resulted in increased disintegration of CaHA in an in vitro experimental setting. CONCLUSIONS: The results of this study indicate that STS is limited in its potential to dissolve intraarterial CaHA of cadaveric human facial arteries, despite the fact that it appears effective when in direct contact with the CaHA. Adverse events caused by intraarterial administration of CaHA-based fillers still lack a suitable antidote.

Revisit, Reform, and Redesign: A Novel Dissection Approach for Demonstrating Anatomy of the Orbit for Continuing Professional Development Education.

Advanced postgraduate medical education for health-care professionals is constantly evolving. Understanding facial anatomy and especially its vascular system is crucial when performing soft tissue filler injections to avoid adverse events including tissue loss or irreversible blindness. Standard anatomical resources often fall short of elucidating clinically relevant concepts in more highly specialized areas of interest. A novel dissection approach for demonstrating the anatomy of the lateral orbit was presented at scientific meetings to participants from dermatology, plastic surgery, and general practice. Results from the post-course online survey (n = 52) were analyzed. The results of the survey reveal a high educational impact and a high clinical relevance of the novel dissection approach. In addition, the majority of respondents (97.7%; n = 51) felt that the exposed anatomical structure of the orbit and face improved their ability to safely perform cosmetic procedures on the face. More experienced respondents who had previously attended at least five cadaveric dissections were more likely to strongly agree that reviewing anatomy through this novel dissection approach increased their confidence in avoiding periorbital vascular danger zones. As minimally invasive outpatient procedures continue to evolve, practicing physicians and mid-level providers often face the challenge of having to reconcile preexisting anatomical knowledge with new clinical practice. Skills required to navigate high impact anatomy include visualization of structures that form the navigational landscape and avoidance of key danger zones. The novel dissection approach to the lateral orbit reflects the increasing focus on revisiting, reforming, and redesigning anatomy for continuing professional development activities.

Simulating Surgical Skills in Animals: Systematic Review, Costs & Acceptance Analyses.

Background: Modern surgery demands high-quality and reproducibility. Due to new working directives, resident duty hours have been restricted and evidence exists that pure on-the-job training provides insufficient exposure. We hypothesize that supplemental simulations in animal models provide a realistic training to augment clinical experiences. This study reviews surgical training models, their costs and survey results illustrating academic acceptance. Methods: Animal models were identified by literature research. Costs were analyzed from multiple German and Austrian training programs. A survey on their acceptance was conducted among faculty and medical students. Results: 915 articles were analyzed, thereof 91 studies described in-vivo animal training models, predominantly for laparoscopy (30%) and microsurgery (24%). Cost-analysis revealed single-training costs between 307€ and 5,861€ depending on model and discipline. Survey results illustrated that 69% of the participants had no experience, but 66% would attend training under experienced supervision. Perceived public acceptance was rated intermediate by medical staff and students (4.26; 1-low, 10 high). Conclusion: Training in animals is well-established and was rated worth attending in a majority of a representative cohort to acquire key surgical skills, in light of reduced clinical exposure. Animal models may therefore supplement the training of tomorrow's surgeons to overcome limited hands-on experience until virtual simulations can provide such educational tools.

Photosymbiosis for Biomedical Applications.

Without the sustained provision of adequate levels of oxygen by the cardiovascular system, the tissues of higher animals are incapable of maintaining normal metabolic activity, and hence cannot survive. The consequence of this evolutionarily suboptimal design is that humans are dependent on cardiovascular perfusion, and therefore highly susceptible to alterations in its normal function. However, hope may be at hand. "Photosynthetic strategies," based on the recognition that photosynthesis is the source of all oxygen, offer a revolutionary and promising solution to pathologies related to tissue hypoxia. These approaches, which have been under development over the past 20 years, seek to harness photosynthetic microorganisms as a local and controllable source of oxygen to circumvent the need for blood perfusion to sustain tissue survival. To date, their applications extend from the in vitro creation of artificial human tissues to the photosynthetic maintenance of oxygen-deprived organs both in vivo and ex vivo, while their potential use in other medical approaches has just begun to be explored. This review provides an overview of the state of the art of photosynthetic technologies and its innovative applications, as well as an expert assessment of the major challenges and how they can be addressed.

Occult Pathologic Findings in Reduction Mammaplasty in 5781 Patients-An International Multicenter Study.

Breast cancer is among the most commonly diagnosed cancers in the world, affecting one in eight women in their lifetimes. The disease places a substantial burden on healthcare systems in developed countries and often requires surgical correction. In spite of this, much of the breast cancer pathophysiology remains unknown, allowing for the cancer to develop to later stages prior to detection. Many women undergo reduction mammaplasties (RM) to adjust breast size, with over 500,000 operations being performed annually. Tissue samples from such procedures have drawn interest recently, with studies attempting to garner a better understanding of breast cancer's development. A number of samples have revealed nascent cancer developments that were previously undetected and unexpected. Investigating these so-called "occult" findings of cancer in otherwise healthy patients may provide further insight regarding risk factors and countermeasures. Here, we detail occult findings of cancer in reduction mammaplasty samples provided from a cohort of over 5000 patients from 16 different institutions in Europe. Although the majority of our resected breast tissue specimens were benign, our findings indicate that there is a continued need for histopathological examination. As a result, our study suggests that preoperative imaging should be routinely performed in patients scheduled for RM, especially those with risk factors of breast cancer, to identify and enable a primary oncologic approach.

Anatomy of the Dorsum of the Foot and Its Relevance for Nonsurgical Cosmetic Procedures.

BACKGROUND: Operative procedures to enhance the aesthetic appearance of the feet are associated with risks. Minimally invasive procedures to volumize the dorsum of the foot are to this point not described. The present study investigates the safety and efficacy of such procedures in a retrospective clinical, anatomical, and ultrasound-based study. METHODS: A total of 106 feet from 53 female patients (mean age, 64.1 ± 8.3 years) were investigated retrospectively after the injection of a commercially available calcium hydroxylapatite product using a single-entry proximal-to-distal fanning injection technique. Anatomical dissections in 20 fresh, nonembalmed feet from 10 human body donors (mean age, 83.1 ± 8.8 years) were dissected, and 20 feet from 10 healthy volunteers (mean age, 26.5 ± 6.2 years) were examined by ultrasound imaging to help guide conclusions. RESULTS: Aesthetic outcome after 3 months was graded by the patients as 4, connoting good improvement (range, 3 to 5). No allergic reactions or other types of adverse events were documented. The layered anatomy of the dorsum of the foot was confirmed by anatomical dissections and ultrasound imaging as follows: skin, dorsal superficial fatty layer, dorsal superficial fascia, dorsal intermediate fatty layer, superficial lamina of the dorsal deep fascia, dorsal deep fatty layer, and deep lamina of the dorsal deep fascia. CONCLUSIONS: Minimally invasive injections of soft-tissue filler in the dorsum of the foot can provide an alternate solution to enhance the aesthetic appearance of feet. The present study provides support for the safety and efficacy of volumizing procedures using a 22-gauge, 50-mm, blunt-tip cannula. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Anatomy of the Superior and Inferior Labial Arteries Revised: An Ultrasound Investigation and Implication for Lip Volumization.

BACKGROUND: Lips are considered a key element of facial attractiveness due to their central position in the face and their elemental role in verbal and nonverbal communication. OBJECTIVES: The authors sought to provide clinically relevant information on the 3-dimensional pathway of the superior and inferior labial arteries within the lips to increase safety during labial soft tissue filler injections. METHODS: The study enrolled 41 healthy volunteers with a mean age of 26.17 ±â€…9.6 years and a mean body mass index of 23.09 ±â€…2.3 kg/m2. Ultrasound imaging was performed at 6 different locations. The position of the labial arteries within the lips, depth of the arteries, cranio-caudal location of each artery in relation to the vermilion border, and diameter of the superior/inferior labial arteries were recorded. RESULTS: The most frequent location of both the superior and inferior labial arteries was the submucosal plane (58.5%) followed by intramuscular (36.2%) and subcutaneous (5.3%) planes. The depth of the superior labial artery in the upper lip was 5.6 ±â€…0.13 mm, whereas the depth of the inferior labial artery in the lower lip was 5.2 ±â€…0.14 mm. Both arteries were more frequently located within the red lip: upper lip (83% vs 18.7%) and lower lip (86.2% vs 13.8%). In the midline, the artery coursed within the red lip in all investigated volunteers. CONCLUSIONS: Clinically, results of this study favor a superficial injection plane for lip volumization procedures. A perpendicular approach to the lip (coming from the cutaneous lip) might increase safety because the artery is located most frequently within the red lip.

Relationship Between Vertical Glabellar Lines and the Supratrochlear and Supraorbital Arteries.

BACKGROUND: Glabellar soft tissue filler injections have been shown to be associated with a high risk of causing injection-related visual compromise. OBJECTIVES: The aim of this study was to identify the course of the superficial branch of the supratrochlear and of the deep branch of the supraorbital artery in relation to the ipsilateral vertical glabellar line and to test whether an artery is located deep to this line. METHODS: Forty-one healthy volunteers with a mean age of 26.17 [9.6] years and a mean BMI of 23.09 [2.3] kg/m2 were analyzed. Ultrasound imaging was applied to measure the diameters, distance from skin surface, distance between the midline, distance between vertical glabella lines, and the cutaneous projection of the supratrochlear/supraorbital arteries at rest and upon frowning. RESULTS: The mean distance between the superficial branch of the supratrochlear artery and the ipsilateral vertical glabellar line was 10.59 [4.0] mm in males and 8.21 [4.0] mm in females, whereas it was 22.38 [5.5] mm for the supraorbital artery in males and 20.73 [5.6] mm in females. Upon frowning, a medial shift in supratrochlear arterial position of 1.63 mm in males and 1.84 mm in females and of 3.9 mm in supraorbital arterial position for both genders was observed. The mean depth of the supratrochlear artery was 3.34 [0.6] mm at rest, whereas the depth of the supraorbital artery was 3.54 [0.8] mm. CONCLUSIONS: The hypothesis that injecting soft tissue fillers next to the vertical glabellar line is safe because the supratrochlear artery courses deep to the crease should be rejected. Additionally, the glabella and the supraorbital region should be considered as an area of mobile, rather than static, soft tissues.