Large Skin Research Articles

Peanut anaphylaxis in 2022: Decoupling epinephrine usage from emergency department evaluation

Peanut anaphylaxis in 2022: Decoupling epinephrine usage from emergency department evaluation

Abstract 3332: LNG-451 is a potent, CNS-penetrant, wild-type EGFR sparing inhibitor of EGFR exon 20 insertion mutations

Abstract Exon 20 insertion mutations (Ex20ins) are the third most common type of EGFR oncogenic mutation in lung cancer patients. While several small molecules have been approved (mobocertinib) or are in clinical development (e.g. CLN-081, BDTX-189) none have demonstrated meaningful CNS activity and they can be associated with treatment-limiting adverse events, including wild-type (WT) EGFR-mediated toxicities. LNG-451 is a CNS-penetrant, wild-type EGFR-sparing, covalent inhibitor of EGFR Ex20ins. In cell viability assays dependent on five EGFR Ex20ins mutations, LNG-451 was a potent inhibitor (IC50 7 - 78 nM) including the three most prevalent insertions (V769_D770insASV IC50 = 78 nM, D770_N771insSVD IC50 = 53 nM, H773_V774insNPH IC50 = 75 nM). LNG-451 had low potency in WT EGFR dependent cell assays (WT EGFR Ba/F3 IC50=1,960 nM, cell panel IC50 = 1630 nM). LNG-451 was 21-fold selective for its least potent Ex20ins (V769_D770insASV) relative to WT EGFR. LNG-451 potently inhibited cells dependent on EGFR L861Q (IC50 = 6 nM), EGFR G719S (IC50 = 8 nM), and EGFR G719S/T263P (IC50 = 11 nM). LNG-451 is a highly selective kinase inhibitor (1 μM LNG-451, >90% inhibition for 7 of 409 WT kinases) with screening hits having a similarly positioned cysteine as EGFR. In a Ba/F3 cell-derived xenograft model harboring an EGFR V769_D770insASV exon 20 insertion mutation (EGFR V769_D770insASV CDX), 10 and 50 mg/kg LNG-451 QD PO dosing for 15 days was well-tolerated and resulted in tumor growth inhibition (TGI) of 75.7% and 105.4%, respectively. LNG-451 was efficacious and well-tolerated in the EGFR Ex20ins HuPrime® LU0387 H773-V774insNPH patient-derived xenograft tumor model: 10 mg/kg LNG-451 QD, 67% TGI; 50 mg/kg LNG-451 QD, 91% tumor regression. LNG-451 was highly active in the intracranial PC9-luc xenograft mouse model. In a single dose PK/PD study using the EGFR V769_D770insASV CDX, similar LNG-451 concentrations were observed in tumor, large intestine, and skin tissues (e.g. 50 mg/kg LNG-451 3h post dose: tumor, 8387 ng/mL; large intestine tissue, 14483 ng/mL; skin, 4623 ng/mL). LNG-451 potently suppressed EGFR phosphorylation in tumor tissue (e.g. 99%, 3 h post 50 mg/kg dose) but had minimal-to modest suppression of phospho-EGFR in large intestine tissue (e.g. 4.2%, 3h post 50 mg/kg dose) and skin tissue (e.g 1.9%, 3h post 50 mg/kg dose). Taken together, LNG-451 is a wild-type EGFR-sparing, CNS-penetrant EGFR Ex20ins inhibitor that is expected to provide strong anti-tumor efficacy for patients with advanced/metastatic solid cancers harboring oncogenic EGFR exon 20 insertions with reduced WT EGFR-driven toxicities. Citation Format: Brion W. Murray, Anjali Pandey, Bruce Roth, Tracy Saxton, Daniel J. Estes, Himanshu Agrawal, Santosh Vishwakarma, Gurulingappa Hallur, Ishtiyaque Ahmad, Ravi Trivedi, Helen Jenkins, Paul G. Pearson. LNG-451 is a potent, CNS-penetrant, wild-type EGFR sparing inhibitor of EGFR exon 20 insertion mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3332.

A parasite outbreak in notothenioid fish in an Antarctic fjord

SummaryClimate changes can promote disease outbreaks, but their nature and potential impacts in remote areas have received little attention. In a hot spot of biodiversity on the West Antarctic Peninsula, which faces among the fastest changing climates on Earth, we captured specimens of two notothenioid fish species affected by large skin tumors at an incidence never before observed in the Southern Ocean. Molecular and histopathological analyses revealed that X-cell parasitic alveolates, members of a genus we call Notoxcellia, are the etiological agent of these tumors. Parasite-specific molecular probes showed that xenomas remained within the skin but largely outgrew host cells in the dermis. We further observed that tumors induced neovascularization in underlying tissue and detrimentally affected host growth and condition. Although many knowledge gaps persist about X-cell disease, including its mode of transmission and life cycle, these findings reveal potentially active biotic threats to vulnerable Antarctic ecosystems.

Derma-like antibacterial polysaccharide gel dressings for wound care

Large skin wound infections have high morbidity, which threaten the health of human beings severely. It is essential to develop new wound dressings that can block microbial invasion, eliminate bacteria effectively, adhere to wounds firmly, and have good biocompatibility. In this work, we designed a kind of polysaccharide gel (DLG) dressings with derma-like structure that had good wound care performances. With a facile penetration cross-linking method by the Schiff base reaction between oxidized hyaluronic acid solution and carboxymethyl chitosan solution with higher viscosity, a gradient porous structure was formed inside DLG to mimic the structure of derma, which was due to the simultaneous penetration and reaction processes between two viscous solutions. This derma-like structure endowed the gel dressings with the abilities of self-adhesion to wounds and barriers against bacteria. Through the introduction of cuttlefish juice and gentamycin, the modified gel dressings (DLG-GS) showed mild photothermal effects under the near infrared irradiation at the wavelength of 808 nm, which could reach and maintain the temperature of 45 °C. The mild heat could act together with gentamycin to produce a rapid bactericidal performance within 5 min. Meanwhile, the polysaccharide gel dressings had good biocompatibility. The in vivo anti-infection properties of DLG-GS was demonstrated by an animal model of infected full-thickness skin defect. This strategy provided a feasible solution for the prevention and treatment of infected large wounds. Statement of significanceDerma-like antibacterial gel dressings (DLG-GS) with high bacterial barrier ability, strong tissue adhesive property and good biocompatibility were constructed by a penetration cross-linking method. DLG-GS could eliminate bacterial infection within 5 min due to the rational combination of a mild photothermal effect and antibiotics. DLG-GS showed high anti-infection and wound healing properties in an animal model of infected full-thickness skin defect. This study provides a flexible and universal strategy for the development of antibacterial wound dressings.

The Therapeutic Role of ADSC-EVs in Skin Regeneration.

Large skin defects caused by burns, unhealing chronic wounds, and trauma, are still an intractable problem for clinicians and researchers. Ideal skin regeneration includes several intricate and dynamic stages of wound repair and regeneration of skin physiological function. Adipose-derived stem cells (ADSCs), a type of mesenchymal stem cells (MSCs) with abundant resources and micro-invasive extraction protocols, have been reported to participate in each stage of promoting skin regeneration via paracrine effects. As essential products secreted by ADSCs, extracellular vesicles (EVs) derived from ADSCs (ADSC-EVs) inherit such therapeutic potential. However, ADSC-EVs showed much more clinical superiorities than parental cells. ADSC-EVs carry various mRNAs, non-coding RNAs, proteins, and lipids to regulate the activities of recipient cells and eventually accelerate skin regeneration. The beneficial role of ADSCs in wound repair has been widely accepted, while a deep comprehension of the mechanisms of ADSC-EVs in skin regeneration remains unclear. In this review, we provided a basic profile of ADSC-EVs. Moreover, we summarized the latest mechanisms of ADSC-EVs on skin regeneration from the aspects of inflammation, angiogenesis, cell proliferation, extracellular matrix (ECM) remodeling, autophagy, and oxidative stress. Hair follicle regeneration and skin barrier repair stimulated by ADSC-EVs were also reviewed. The challenges and prospects of ADSC-EVs-based therapies were discussed at the end of this review.

Thickness-adjustable Injectable Poly-D,L-Lactic Acid: A Versatile Filler.

In recent years, there has been increasing popularity and interest in injectable fillers for facial rejuvenation. Hyaluronic acid (HA) fillers are the most widely used injectable fillers. Although there are many kinds of HA fillers on the market, each HA filler has its own rheological properties. Various facial regions may need fillers with different rheological properties. Therefore, there is no one HA filler suitable for all indications.1 Injectable poly-D,L-lactic acid (PDLLA; AestheFill, REGEN Biotech, Seoul, South Korea) is a collagen-stimulating filler.2,3 Recently, we published two articles in the Plastic and Reconstructive Surgery—Global Open journal.4,5 A vial of injectable PDLLA can be reconstituted by 1.5–24 mL of sterile water.4,5 The suspensions are further divided into four groups of density for different indications of injection: thickest (D1.5–D3), thick (D3–D6), thin (D6–D12), and super-thin (D12–D24).4 Various suspensions have different rheological properties. However, they have never been discussed in previous articles. The purpose of this article is to discuss the properties and volume effect variations of four groups on their different indications. According to our experience and the animal studies,2 by using D1.5 suspension, volume decrease after injectable PDLLA administration is found to be minimal. Thereafter, the volume effect could last for 2 years. By using suspensions other than D1.5, volume decrease occurs several days after injection due to absorption of additional water. Then, the residual volume remains the same and lasts for 2 years. Therefore, additional water approximately equals the water that exceeds 1.5 mL per vial. (See table, Supplemental Digital Content 1, which illustrates the properties and indications of four groups of PDLLA, https://links.lww.com/PRSGO/C50.) For nasal and chin injection, “thickest” suspension is used because of its high elastic modulus (G’) and cohesivity. With high G’, the projection can be maintained because it can resist the compression force of overlying skin, fat, and muscle over bony prominences. With high cohesivity, lateral spreading of the filler is minimal.1 For wrinkle correction or volume augmentation, it is better to use a filler that can spread easily so as to prevent the occurrence of obvious edges and bumps from happening. A filler with medium-to-low cohesivity would be the best choice.1 Accordingly, “thick” suspension for deep wrinkle correction and “thin” suspension for shallow wrinkle correction are used. Additional water in these suspensions will be absorbed several days after injection. Therefore, overcorrection by using “thick” and “thin” suspensions seldom happens. For texture improvement over a large area skin, only the property of easy spreading is needed, instead of the volumizing effect of the filler. As a result, “super-thin” suspension would be the choice (Fig. 1).Fig. 1.: A 24-year-old woman who received “thickest” suspension of injectable poly-D,L-lactic acid injection for her chin and hump nose, “thick” suspension for her naso-labial folds, “thin” suspension for her tear-trough deformities, and “super-thin” suspension for her mid-facial skin texture. A, Preoperative view. B, Eight-month postoperative view. (Photographs courtesy of Chuan-Yuan Lin, MD.)There are some limitations in using this filler. The injection planes are the supra-periosteum and subcutaneous layers. Care must be taken not to inject the filler into other layers. For example, intramuscular injection easily causes nodule formation. Additionally, there is no dissolving enzyme for injectable PDLLA. Practitioners who intend to administer injectable PDLLA must be aware of potential risks and the management of adverse effects should they arise. Nevertheless, injectable PDLLA is a versatile filler for a wide range of indications. PATIENT CONSENT The patient provided written consent for the use of her image. DISCLOSURE Drs. Lin and Lin are medical consultants of Jiangsu Wuzhong Aesthetic Biotech., and medical directors of REGEN Biotech. ACKNOWLEDGMENT The authors want to give special thanks to Normand Mailhot-ME-TESL for his kind assistance with manuscript editing.

A tactics for treating large skin wounds on the head

An open wound on the head is an injury (skin tear) of all scalp external layers including dermis, subcutaneous fatty tissue, aponeurosis, muscles, vessels and nerves with intact skull bones and intact neurological reactions [1].Extensive wounds of the external head layers, in addition to a standard threat to the human health, bear an additional risk due to their close localization to the brain. Because of the abundant blood supply to scalp soft tissues, high rate of volumetric blood flow (50–60 milliliters per 100 g of brain tissue), numerous extra-, intracranial arterial and venous anastomoses, there is a real danger of spreading the infection inside the skull and developing meningitis or encephalitis.Problems of care of patients with extensive head wounds, risk of complications that can cause severe consequences determine the relevance of the issue presented in this work.Objective. To analyze treatment results of patients admitted to the emergency department of Mariinskaya State City Hospital in St. Petersburg within three months in 2021 and to develop an optimal tactics for treating patients with extensive wounds of the scalp.Material and research methods. 2245 patients with various types of head injury were admitted to the hospital; 610 (27.2 %) of them had damage of the external scalp layers. Each patient had standard clinical and laboratory examination and multislice computed tomography (MSCT) examination of the head at 64-slice Definition AS (Siemens, Germany) CT scanner. In the emergency department, all patients who were injured by high-energy traumatic objects had the primary surgical debridement; all patients who were injured by low-energy traumatic objects had wound toilet and wound suturing. Three most representative cases with extensive wounds of the external scalp (over 10 cm) with illustrations are presented in the article as clinical examples.Results. All patients had good outcomes. There were no any signs of wound infection either.Conclusion. A thorough primary surgical debridement of scalp wounds with their drainage followed by observation and treatment in the hospital is a necessary condition for successful healing of large scalp wounds.

Role of Preoperative Skin Stretching in Single-Stage Wound Closure.

Background Mechanical skin stretching (SS) is now becoming one of the commonly sought after procedures for wound healing. This study was aimed to assess the efficacy of preoperative SS for the closure of large wounds and to evaluate various postoperative outcome parameters. Methodology An observational study was conducted from December 2017 to May 2019 where a sample size of 30 patients was included with inclusion criteria being wounds of ≥5 cm width that require surgical management, presence of sufficient healthy skin edge of the wound/scar (at least one) for the stretching procedure, and age between 18 and 70 years. SS devices used were the top closure tension relief system. Postoperatively, various parameters were recorded to evaluate outcomes and complications. Results Majority of wounds that is 16 (53.3%) were <50 cm 2 , 9 (30%) were between 50 and 75 cm 2 , and 5 (16.7%) were >75 cm 2 . The mean duration of stretch was 2.3 ± 0.82 weeks. For 30 wounds treated with staged cycles of wound closure, there was a significant difference between every two visit points, i.e., 10%. The mean patient-reported patient and observer scar assessment scale score was 3.5 ± 0.93. Twenty-five cases (83.3%) had uneventful postoperative recovery. Twenty-seven patients (90%) reported an improved aesthetic outcome. Fourteen patients (46.7%) reported some improvement in function. Conclusion The study concluded that the SS devices are the simple and effective method for the primary closure of large and challenging wounds and skin defects.

HOW WE DO IT: the Keystone flap for large skin defects: our experience with 30 consecutive cases

Background The keystone perforator-based fasciocutaneous island flap is a method of locoregional skin defect reconstruction, consisting of two conjoined V to Y advancement flaps. In this article, we report a series of 30 consecutive cases in various body parts with the aim to demonstrate the versatility of the keystone flap in the reconstruction of various skin defects after removal of a suspected malignant skin lesion and evaluate our clinical experience while maintaining oncological safety and good aesthetic results. Methods Patients who underwent keystone flap reconstruction between January 2016 and January 2021 were retrospectively reviewed. Their demographics, operative details, oncological data and postoperative details were obtained from the institution’s internal electronic patient records system. Results The majority of the skin defects were the result of an oncologic resection (97%, n = 29) and were located in the pretibial region (47%, n = 14). In five cases (17%) there was a need for a double keystone flap to cover the skin defect. One or more risk factors (hypertension, smoking, anticoagulation, …) were identified in 22 patients (73%). Minor complications (partial wound dehiscence, effusion or surgical site infection) occurred in ten cases (33%) which were resolved with conservative wound management or systemic antibiotics. There were no major postoperative flap-related complications such as flap failure or need for re-surgery. Conclusion In our experience, the keystone island flap is an effective and reliable technique to attain a single stage tension-free closure of large skin defects. Due to its low technical complexity and high success rate, we consider it a feasible alternative to other reconstructive flaps and grafts for direct closure of secondary defects.

As concepts that should not be thrown out of focus, aesthetic and social appearance anxiety in neurosurgery

The concept of aesthetics originates from the Greek word “aisthetikos” which means emotional perception. It is a philosophy aiming to find the beauty. According to German philosopher Baumgarten, aesthetics is “the art of thinking about beauty, understanding what it is, and inquire into it”. For people, the concept of beauty and aesthetics form the basis of self-confidence. The aim of this study is to investigate the effect of aesthetic and social appearance anxiety in neurosurgical surgery especially on the post-operative period. Therefore, 20 patients who were operated for olfactory groove meningioma in our clinic were divided into two groups and investigated their postoperative period. The first group consists of 10 patients were operated with the pterional route performed with a large skin incision and the second group consists of 10 patients operated with the subfrontal route performed with a small incision hidden under the eyebrow. Social appearance anxiety that may develop in the postoperative period was compared with each other in these two patient groups. As expected, minimally invasive approaches are found to cause less anxiety in postoperative period.

Effects of captivity and rewilding on amphibian skin microbiomes

Captive breeding to safeguard against extirpation in the wild is a practice for many animal groups. Animals in captivity experience reduced contact with natural substrates and other animals, and consume atypical diets that may alter naturally occurring microbial associations. Amphibian skin microbiomes are vital for amphibian health, protecting them from pathogens and aiding in development, immune system training, and fecundity. Thus, understanding how changes associated with captivity influence microbial communities and the health of captive-reared amphibians is an important consideration in captive breeding and reintroduction programs. Overarching patterns of amphibian microbial diversity in captivity have not been previously explored. Therefore, we conducted a meta-analysis of skin microbes from captive-managed and wild individuals of 18 salamander and frog species from temperate and tropical biomes. We found that microbial composition of captive and wild amphibians differed for all species. However, while the overall captivity effect on amphibian skin richness was significant, the direction of the captivity effect on diversity metrics and antifungal function differed depending on the host species. One species exhibiting a large skin microbiome shift in captivity is the variable harlequin frog, Atelopus varius. A soft-release of A. varius to outdoor mesocosms “restored” the microbiome through time, and frogs also increased antifungal function of their skin microbiome with time in mesocosms. Rewilding the microbiome may influence resistance to diseases such as chytridiomycosis. Indeed, evaluating the outcome of individual species is necessary until we have a cohesive approach to mediate shifts of amphibian skin microbes that result from captivity.

Reynolds stresses transport in a turbulent channel flow subjected to streamwise traveling waves

Turbulent flows generate large skin friction over surfaces, dissipating significant energy and causing a significant waste of fuel. Various skin-friction control techniques have been proposed in the past, among which transverse wall oscillation (TWO) has been proven one of the most effective approaches. We examine the key modifications induced by the TWO technique in the turbulent flow field with the aim of elucidating the physical mechanism responsible for mitigating skin friction. We find that traveling-wave TWO significantly damps turbulence production and coherent structures, resulting in a decrease in turbulence intensity and hence skin friction.

Sensitization to trometamol in patients with delayed local reactions after administration of the Moderna mRNA-1273 vaccine against SARS-CoV-2

Sensitization to trometamol in patients with delayed local reactions after administration of the Moderna mRNA-1273 vaccine against SARS-CoV-2

Hybrid confocal fluorescence and photoacoustic microscopy for the label-free investigation of melanin accumulation in fish scales

Lower vertebrates, including fish, can rapidly alter skin lightness through changes in melanin concentration and melanosomes’ mobility according to various factors, which include background color, light intensity, ambient temperature, social context, husbandry practices and acute or chronic stressful stimuli. Within this framework, the determination of skin chromaticity parameters in fish species is estimated either in specific areas using colorimeters or at the whole animal level using image processing and analysis software. Nevertheless, the accurate quantification of melanin content or melanophore coverage in fish skin is quite challenging as a result of the laborious chemical analysis and the typical application of simple optical imaging methods, requiring also to euthanize the fish in order to obtain large skin samples for relevant investigations. Here we present the application of a novel hybrid confocal fluorescence and photoacoustic microscopy prototype for the label-free imaging and quantification of melanin in fish scales samples with high spatial resolution, sensitivity and detection specificity. The hybrid images are automatically processed through optimized algorithms, aiming at the accurate and rapid extraction of various melanin accumulation indices in large datasets (i.e., total melanin content, melanophores’ area, density and coverage) corresponding to different fish species and groups. Furthermore, convolutional neural network-based algorithms have been trained using the recorded data towards the classification of different scales’ samples with high accuracy. In this context, we demonstrate that the proposed methodology may increase substantially the precision, as well as, simplify and expedite the relevant procedures for the quantification of melanin content in marine organisms.

Fibula free flap perforasomes: vascular anatomical study and clinical applications

This study assesses the anatomical features of the cutaneous fibular perforators and perforasomes of fibular free flap to determine the clinical implications therein. This anatomical study was performed with 16 fresh cadavers after selective arterial injections of inked serum. The numbers of perforators, diameter, location of the perforasome center, perforator course, the distance between perforator origin and tibiofibular division, and the perforasome area were all documented. Thirty-one lower legs were dissected. Eighty-eight cutaneous perforators were found, averaging 2.8 per leg (1-4). The mean diameter was 1.7mm and decreased from proximal to distal (p < 0.001). The centers of the perforasomes were aligned on an oblique projection from proximal to distal and anterior to posterior. Seventeen perforators (19%) were musculocutaneous, all in the proximal half of the leg, whereas 71 perforators were septocutaneous (81%), including 18 in the proximal half of the leg. Six of the uppermost perforators originated from the fibular artery less than 10mm from the tibiofibular division. The mean area perforasome was 37.2cm2 (7.9-106cm2) and decreased from proximal to distal (p < 0.01). Distal and proximal fibular flap perforasomes sported different features. Large skin paddles supplied by large and often intramuscular perforators were found in the proximal half of the leg. Distal skin paddles were smaller, more posterior, and featured septocutaneous perforators. These factors should be considered in the skin paddle choice during the fibular free flap harvest.

Advances in Topical Management of Adolescent Facial and Truncal Acne: A Phase 3 Pooled Analysis of Safety and Efficacy of Trifarotene 0.005% Cream.

Acne vulgaris is very common among adolescents and young adults. It is important for clinicians who provide care to these patients to have a plan of action for assessing and managing acne in daily practice. Post-hoc analysis of two large-scale phase 3 pivotal trials of trifarotene 0.005% cream, focusing on efficacy, safety, and tolerability in the subgroup of subjects aged 12 to 17, inclusive. Trifarotene was effective and well tolerated on both the face and trunk in patients ages 12-17 with moderate acne. There was a low and acceptable rate of adverse events and tolerability was favorable. Trifarotene monotherapy was associated with good clinical efficacy, safety, and tolerability. Once-daily application offers convenience for patients, and the low concentration of trifarotene makes it well-suited to use on large skin areas such as the trunk. J Drugs Dermatol. 2022;21(6):582-586. doi:10.36849/JDD.6778.

Keratinocyte Culture: Siriraj’s Experience

Objective: Cell-based therapy is gaining increasing prominence in medicine, where it has the potential to replace or repair damaged tissue using new engineered cells. Skin cell engineering, also known as keratinocyte culture or cultured epithelial autograft (CEA), is a promising field in cell-based therapy. CEA is now used in many parts of the world as an alternative treatment for some diseases that require large defects to be covered, such as severe and major burn patients and congenital melanocytic nevus. The use of CEA in conjunction with acellular skin substitution is rapidly expanding.Materials and Methods: This study is an initiative aimed at supporting the production and use of keratinocyte cultures at Siriraj Hospital. This is the first stage of developing sheet keratinocyte culture in vitro.Results: Our study yielded very promising results. As feeder cells, we used irradiated 3T3 murine fibroblasts, as per the standard protocol for keratinocyte culture. The growth duration was four weeks: 2 weeks for the 3T3 murine fibroblasts and 2 weeks for the keratinocytes. The keratinocytes grew rapidly and formed sheets with irradiated 3T3 murine fibroblasts. The retrieval of the cell sheets was straightforward thanks to the temperature-response cell culture dish and halo-ring cell recovery sheet. Flow cytometry revealed that the cells had a very high viability and purity. H&amp;E staining revealed the sheets comprised two to four layers of stratified epithelial tissue.Conclusion: From this study, our method of manufacturing the CEA can offer a promising result. This can be use in the treatment which require large skin coverage. However, we aim to initiate animal and human trial phase next.

MSC-derived sEV-loaded hyaluronan hydrogel promotes scarless skin healing by immunomodulation in a large skin wound model

Designing hydrogel-based constructs capable of adjusting immune cell functions holds promise for skin tissue regeneration. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) have attracted increasing attention owing to their anti-inflammatory and proangiogenic effects. Herein, we constructed a biofunctional hydrogel in which MSC-derived sEVs were incorporated into the injectable hyaluronic acid hydrogel, thus endowing the hydrogel with immunomodulatory effects. When implanted onto the wound site in a mouse large skin injury model, this functional hydrogel facilitates wound healing and inhibits scar tissue formation by driving macrophages towards an anti-inflammatory and anti-fibrotic (M2c) phenotype. Further investigation showed that the M2c-like phenotype induced by MSC-derived sEVs markedly inhibited the activation of fibroblasts, which could result in scarless skin wound healing. Taken together, these results suggest that modulation of the immune response is a promising and efficient approach to prevent fibrotic scar formation.

Reconstruction of complex oro-mandibular defects by four different modifications of free fibula osteomyocutaneous flap: A prudent alternative to multiple flaps

Resection of advanced oral squamous cell carcinoma results in complex oro-mandibular defects involving external skin, oral mucosa, and bone. Reconstruction of such defects by a single free fibula flap (FFF) is limited by the lack of soft tissue bulk and adequate skin paddle for both intra- and extra-oral coverage. In this study, the reconstruction of large defects was achieved by four modifications of free fibula osteomyocutaneous flap as an alternative to multiple flaps. In this prospective study, 29 patients with complex oro-mandibular defects were reconstructed by FFF from December 2018 to October 2020. Reconstruction was done with any one of the four FFF modifications involving large proximal skin paddle from lateral leg: Strip de-epithelialization (De-Ep), chimeric bipaddle (Ch-Bp), muscle orally and skin extra-orally (Mo-Se), and double microvascular (Db-Mi). Outcome variables assessed were functional and esthetic results, early/late complications, donor site morbidity, and operative time. An algorithm based on Cordeiro's classification is proposed to assist in the selection of appropriate FFF modification. Among 29 patients, De-Ep was used in 13, Ch-Bp in 8, Mo-Se in 7, and Db-Mi in 1 case. None of the flaps underwent total loss. Two cases required re-exploration. The median operative time was 775min. Wound dehiscence and oro-cutaneous fistula were common early and late complications, respectively. Partial split skin graft loss (SSG) was the most common donor site morbidity. Functional and facial aesthetics were acceptable at the end of follow-up. Specific FFF modifications can be recommended in selected scenarios. It is reliable for single-stage reconstruction with satisfactory esthetic and functional outcomes. When used for reconstruction in first primary tumors, the second donor site is preserved, which can prove valuable in the event of a recurrence or second primary.

Outcome Analysis of Advanced Oral Cancers Requiring Large Composite Fibular Osteocutaneous Flap Reconstruction: Experience From a Tertiary Care Cancer Hospital.

Advanced oral cancer entailing extensive resection of large parts of the mucosa, bone, and skin require reconstructions with composite free flaps. Our aim was to analyze the outcomes of those oral squamous cell carcinomas requiring fibular osteocutaneous free flaps with large skin defects. Perioperative course and histopathological and survival outcomes of 246 consecutive patients warranting composite fibular flaps from January 2010 to June 2015 at Tata Memorial Hospital, Mumbai, India, were retrospectively analyzed. Despite majority of T4 disease (88.2%) and stage IV disease (92%) patients, the 5-year overall survival was 52.1% and the 5-year recurrence-free survival was 48.6% with a median follow-up of 42 months with minimal complications. Reconstruction with composite fibular osteocutaneous flaps has comparable outcomes of survival with acceptable complications in mega oral squamous cell carcinomas requiring extensive resection.