A one year follow-up on quality of adherent scars after autologous fat grafting processed by a filtration technique.

Autologous fat grafting (AFG), mostly in combination with adhesiolysis, has become the workhorse for reconstructing a dysfunctional or absent subcutaneous layer. In a previous study we showed that fat grafts isolated by centrifuging led to more than 20 % improvement in scar pliability. Nevertheless, there is still debate on which technique should be used to process and purify fat grafts. Therefore, a cohort with matured scars was obtained using the same study protocol but with filtration as processing technique. Scar quality was evaluated by the Patient and Observer Scar Assessment Scale (POSAS version 2.0), the Cutometer (pliability) and the DSM II ColorMeter (erythema and melanin). Scar evaluation was performed pre-operatively (baseline) and at 3 and 12 months after AFG. Between 2014 and 2018, 46 patients were included. Mean scar age was 20 ± 17 years and the majority of scars was caused by burns. Compared with baseline, patients showed improvement in scar quality measured by POSAS items at 12 months follow-up. The item score of 'pliability' improved the most from 7.4 to 5.8 (p = 0.001). Item scores of 'pain', 'itch' and 'color' also improved significantly. Clinicians also scored 'pliability' as most improved, but this was not statistically significant (p = 0.111). Objectively measured pliability and erythema and melanin showed no statistically significant differences at 12 months follow-up. Patient-reported outcomes revealed a significant improvement in scar quality, especially scar pliability, after AFG processed by filtration in patients with adherent scars. However, no scar quality improvement was found when assessed with objective tools.

Subcutaneous fat sclerosis in a domestic short-hair cat.

The authors describe a case of presumptive feline subcutaneous fat sclerosis, a condition reported only once previously (in 1987) and diagnosed with postmortem examination. We describe radiographic, computed tomography scan and histopathological findings, and partial response to oral methylprednisolone and Vitamin E.

Ultrasound Detected Subcutaneous Changes in a Pediatric Cohort After Initiation of a New Insulin Pump or Glucose Sensor.

Objective: This study examined subcutaneous tissue changes at sites used by continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM), and tested whether these changes, if any, were associated with glycated hemoglobin (HbA1c). Research Design and Methods: This prospective study investigated recently used CSII or CGM sites in 161 children and adolescents during the first year after initiation of a new diabetes device. Subcutaneous changes such as echogenicity, vascularization, and the distance from the skin surface to the muscle at CSII and CGM sites were assessed by ultrasound. Results: The distance from skin surface to muscle fascia at both the upper arm and abdomen was influenced by age, body mass index z-score, and sex. Especially in boys and the youngest, the depth of many devices outreached the mean distance. The mean distance for boys at the abdomen and upper arm ranged from 4.5-6.5 mm and 5-6.9 mm for all ages, respectively. Hyperechogenicity at CGM sites was 4.3% after 12 months. The frequency of subcutaneous hyperechogenicity and vascularization at CSII sites increased significantly over time (41.2% to 69.3% and 2% to 16% respectively, P < 0.001 and P = 0.009). Hyperechogenicity in the subcutis was not a predictor of elevated HbA1c (P = 0.11). Conclusion: There is large variation in the distance from the skin surface to the muscle fascia and many diabetes devices reach even deeper. Hyperechogenicity and vascularization increased significantly over time at CSII sites, but not CGM sites. The importance of hyperechogenicity for insulin absorption is unclear and further investigations are needed. Clinical Trial Registration number: NCT04258904.

Nanovaccines Mediated Subcutis-to-Intestine Cascade for Improved Protection against Intestinal Infections.

Parenteral vaccines typically can prime systemic humoral immune response, but with limited effects on cellular and mucosal immunity. Here, a subcutis-to-intestine cascade for navigating nanovaccines to address this limitation is proposed. This five-step cascade includes lymph nodes targeting, uptaken by dendritic cells (DCs), cross-presentation of antigens, increasing CCR9 expression on DCs, and driving CD103+ DCs to mesenteric lymph nodes, in short, the LUCID cascade. Specifically, mesoporous silica nanoparticles are encapsulated with antigen and adjuvant toll-like receptor 9 agonist cytosine-phosphate-guanine oligodeoxynucleotides, and further coated by a lipid bilayer containing all-trans retinoic acid. The fabricated nanovaccines efficiently process the LUCID cascade to dramatically augment cellular and mucosal immune responses. Importantly, after being vaccinated with Salmonella enterica serovar Typhimurium antigen-loaded nanovaccine, the mice generate protective immunity against challenge of S. Typhimurium. These findings reveal the efficacy of nanovaccines mediated subcutis-to-intestine cascade in simultaneously activating cellular and mucosal immune responses against mucosal infections.

Update on Superficial Spindle Cell Mesenchymal Tumors in Children.

The diagnosis of cutaneous and subcutaneous spindle cell neoplasms in children is often challenging and has potential therapeutic and prognostic implications. Although correctly diagnosing dermatofibrosarcoma protuberans and infantile fibrosarcoma is paramount, pathologists should not ignore a number of diagnostic pitfalls linked to mostly rare tumors with completely different clinical outcomes. In the last decade, a spectrum of novel entities has been described; information from molecular biology has helped to shape this new landscape for spindle cell tumors. Here, we review the most noteworthy neoplasms in this spectrum, with a focus on their histological similarities: fibroblastic connective tissue nevus, medallion-like dermal dendrocyte hamartoma, or plaque-like CD34-positive dermal fibroma, which share features with fibrous hamartoma of infancy; lipofibromatosis and lipofibromatosis-like neural tumor; and plexiform myofibroblastoma, a recently described neoplasm that should be distinguished from plexiform fibrohistiocytic tumor. These tumors also have genetic similarities, particularly gene rearrangements involving NTRK3 or NTRK1. These genetic features are not only essential for the differential diagnosis of infantile fibrosarcoma but are also of diagnostic value for lipofibromatosis-like neural tumors. The more recently described RET, RAF1, and BRAF gene fusions are also discussed.

Massive emphysema subcutis, pneumothorax, pneumomediastinum and pneumoperitoneum as uncommon complication of covid-19 pneumonia, a rare case.

We should be aware of the uncommon presentation during the pandemic scenario of the Coronavrus disease 2019 (COVID-19). Pneumothorax, pneumomediastinum, pneumoperitoneum, and massive emphysema subcutis are uncommon complications of COVID-19 Pneumonia. The presence of pneumomediastinum and massive emphysema subcutis were rarely reported in the literature. We present a 69-year-old man with COVID-19 Pneumonia with these complications who were managed conservatively and experienced spontaneous resolution of the complications two weeks later. He was admitted to the intensive care unit and was given a ventilator. Pneumonia, massive emphysema subcutis, pneumomediastinum, and pneumothorax are identified from chest X-ray. An Unenhanced thoraco-abdominal computed tomography Scan revealed the presence of a small pneumoperitoneum. However, a computed tomography scan of the abdomen and pelvis did not show any evidence of bowel perforation. It is necessary to detect these complications earlier, so the management can reduce the associated morbidity and mortality.

Rare case of Dioctophyme renale (Nematoda: Enoplida) and Dirofilaria sp. (Nematoda: Spirurida) in the subcutaneous tissue of a cat in Espírito Santo, Brazil.

Dioctophyme renale is the largest parasitic nematode of animals. It is most often found in the right kidney, but can also occur in the urinary system, ears, free abdominal cavity, mammary gland, thoracic cavity, and more rarely in subcutaneous tissue. The genus Dirofilaria has specific parasitic characteristics according to its location, and may parasitize the respiratory tract or even the skin, varying according to species. This report describes a case of Dioctophyme renale and Dirofilaria sp. in the subcutaneous tissue of a cat in the state of Espírito Santo, Brazil. An adult male mongrel cat showed physical enlargement in the left inguinal region, diagnosed as a subcutaneous nodule. Surgical excision and histopathological evaluation of the nodule were performed, and Dioctophyme renale and Dirofilaria sp. were found inside. Dioctophymosis and heartworm disease are present in Brazil and most other countries, but this is the unprecedented case of the association of Dioctophyme renale and Dirofilaria sp. in the subcutaneous tissue of a cat.

Transbuccal platform for delivery of lipogenic actives to facial skin: Because fat matters.

The ability to control facial skin physiology and appearance through the oral mucosa (transbuccally) is largely unexplored. Here, a hypothesis was tested that transbuccal delivery of fat tissue-supportive actives may trigger beneficial cosmetic responses at the level of the skin. First, the importance of the fat tissue for skin structure and function was established by comparative analysis of human biopsies cultured defatted or in the presence of hypodermis, using macroscopic observation, quantitative polymerase chain reaction, and histochemistry. Then, the ability to improve epidermal function and structure through the application of a lipoactive patch to oral mucosa was demonstrated in a clinical case study by the quantification of several epidermal microRNAs (miRNAs). It was found that removal of the hypodermal fat layer accelerated skin biopsy aging as demonstrated by the deterioration of the physical appearance at the macroscopic and microscopic (hematoxylin and eosin stain) levels and the decrease of expression of genes implicated in the structure and function of the skin, such as AQP3 and LOR. Furthermore, when adipogenic actives were applied to the oral mucosa under a form of bioadhesive film in a clinical case study, an improvement in the expression of miRNA biomarkers of senescence and inflammation was observed in the epidermis. Taken together, these results indicate that the transbuccal delivery of lipogenic compounds to face is a novel method for the improvement of facial skin structure and function.

Improvement of a Three-Layered in vitro Skin Model for Topical Application of Irritating Substances.

In the field of skin tissue engineering, the development of physiologically relevant in vitro skin models comprising all skin layers, namely epidermis, dermis, and subcutis, is a great challenge. Increasing regulatory requirements and the ban on animal experiments for substance testing demand the development of reliable and in vivo-like test systems, which enable high-throughput screening of substances. However, the reproducibility and applicability of in vitro testing has so far been insufficient due to fibroblast-mediated contraction. To overcome this pitfall, an advanced 3-layered skin model was developed. While the epidermis of standard skin models showed an 80% contraction, the initial epidermal area of our advanced skin models was maintained. The improved barrier function of the advanced models was quantified by an indirect barrier function test and a permeability assay. Histochemical and immunofluorescence staining of the advanced model showed well-defined epidermal layers, a dermal part with distributed human dermal fibroblasts and a subcutis with round-shaped adipocytes. The successful response of these advanced 3-layered models for skin irritation testing demonstrated the suitability as an in vitro model for these clinical tests: only the advanced model classified irritative and non-irritative substances correctly. These results indicate that the advanced set up of the 3-layered in vitro skin model maintains skin barrier function and therefore makes them more suitable for irritation testing.

Cutaneous Pyogranulomas Associated with Nocardia jiangxiensis in a Cat from the Eastern Caribbean.

Nocardia spp. are worldwide, ubiquitous zoonotic bacteria that have the ability to infect humans as well as domestic animals. Herein, we present a case of a five-year-old female spayed domestic shorthair cat (from the island of Nevis) with a history of a traumatic skin wound on the ventral abdomen approximately two years prior to presenting to the Ross University Veterinary Clinic. The cat presented with severe dermatitis and cellulitis on the ventral caudal abdomen, with multiple draining tracts and sinuses exuding purulent material. Initial bacterial culture yielded Corynebacterum spp. The patient was treated symptomatically with antibiotics for 8 weeks. The cat re-presented 8 weeks after the initial visit with worsening of the abdominal lesions. Surgical intervention occurred at that time, and histopathology and tissue cultures confirmed the presence of Nocardia spp.-induced pyogranulomatous panniculitis, dermatitis, and cellulitis. Pre-operatively, the patient was found to be feline immunodeficiency virus (FIV)-positive. The patient was administered trimethoprim/sulfamethoxazole (TMS) after antimicrobial sensitivity testing. PCR amplification and 16S rRNA gene sequencing confirmed Nocardia jiangxiensis as the causative agent. To our knowledge, N. jiangxiensis has not been previously associated with disease. This case report aims to highlight the importance of a much-needed One Health approach using advancements in technology to better understand the zoonotic potential of Nocardia spp. worldwide.

Malignant solitary fibrous tumor in the subcutis: Report of a rare superficial malignant type and review of published work.

An 82-year-old Japanese man presented with a 90 mm × 80 mm subcutaneous nodule on the left chest, not connected to the pleura, described as hypointense on T1 -weighted magnetic resonance imaging. Histologically, a well-demarcated nodule demonstrated a patternless pattern composed of hemangiopericytoma-like and short storiform patterns from the subcutis into deeper tissue. Antler-like branching blood vessels and keloidal-type collagen bundles were seen. Myxoid change was seen in hypocellular areas. Bizarre cells and multinucleated giant cells could be easily identified. Approximately 5 mitoses per 10 high-power fields could be detected. The majority of proliferating spindle cells were positive for CD34, CD99 and BCL2 expression. Signal transducer and activator of transcription (STAT)6 was strongly expressed in the nuclei. The Ki-67 proliferation index was 60%. We performed wide local excision with a 30-mm margin, along with resection of intercostal muscles, fasciae and periostea. Neither local recurrence nor distant metastases have occurred in 16 months of follow up. The present case is consistent with malignant solitary fibrous tumor in the subcutis histologically mimicking myxofibrosarcoma or undifferentiated pleomorphic sarcoma, definitively diagnosed by immunoexpression of STAT6. We performed a review of the published work and identified six previously reported patients with malignant superficial solitary fibrous tumor to validate the characteristics of this rare type. Four men and two women were included. The sarcomas involved the head area, trunk and thigh. Only one tumor-associated death occurred despite excision and radiotherapy. Complete excision is a possible treatment choice for this tumor type.

Epithelial sheath neuroma with extension to the subcutis.

Epithelial sheath neuroma (ESN) is a rare entity, histologically showing enlarged nerves in the superficial dermis surrounded by cytologically bland keratinocytes, classically presenting clinically as an erythematous papule or nodule on the back of middle-aged to elderly individuals. Clear-cut recommendations for treatment are not available, with many reports citing biopsy alone or simple excision as curative. We report a case of biopsy-proven ESN presenting as a significantly painful nodule in an elderly woman. Surgical excision was performed for symptom control and the residual ESN was found to extend deep into the subcutis.

Subcutaneous lipomas: A minimally invasive method for resection of subcutaneous lipomas preserving retaining ligaments.

BACKGROUND: Lipomas are common benign tumors usually located in the subcutaneous tissues. Resection of lipomas frequently requires incisions equal to the diameter of the tumor. The "squeeze technique" with a small incision is well-described, but is frequently not successful, particularly for lipomas in the shoulder region. We report a method for resection of subcutaneous lipomas that preserves retaining ligaments. METHODS: Lipomas are characterized by high signal intensity on T1- and T2-weighted images on magnetic resonance imaging. Retaining ligaments demonstrate low signal intensity on T1-weighted images and high signal intensity on T2-weighted images with fat-suppression. Through a 1 in. incision, lipomas were detached from the retaining ligaments bluntly with a finger. Tumors were then extracted either in a piecemeal fashion or with the "squeeze technique." Complete lipoma resection was visually confirmed through the incisions. For the current report, we analyzed 18 large lipomas resected by this method, with "large" defined as equal to or greater than 5 cm in diameter. RESULTS: The 18 patients included four males and 14 females with a mean age of 53.4 (26-72). The mean lipoma size was 6.6 cm (5-12). Locations included the shoulder in nine cases (50%), the upper arm in five cases (28%), the back in two cases (11%), and the thigh in two cases (11%). Retaining ligaments were identified by MRI in all cases. Lipomas were located between retaining ligaments at the periphery of the tumor. All three lipomas larger than 10 cm were located in the shoulder. There was no difference in the technical difficulty of resection of these compared with lipomas less than 10 cm in diameter. There were no cases of chronic pain or residual hypoesthesia at the incision sites. CONCLUSIONS: The method is an easy and minimally invasive way to achieve complete resection, even for large lipomas, regardless of anatomical location. The method may contribute to reduction of side effects including residual hypoesthesia and chronic pain at the incision site, due to the small incision and preservation of retaining ligaments, which may contain cutaneous nerves.Level of Evidence: Level IV, therapeutic study.

Nodular presentation of Dirofilaria repens infection in a cat mimicking a fibrosarcoma.

A cat with multiple subcutaneous nodules suggesting a soft tissue sarcoma by physical and computed tomographic examination was diagnosed as being affected by subcutaneous filariosis based on cytologic and ultrasonographic assessments. Nodules were surgically removed and extracted nematodes were identified by PCR as Dirofilaria repens. Furthermore, DNA of Dipetalonema dracunculoides (syn. Acantocheilonema dracunculoides) was detected by PCR, with no evidence of circulating microfilariae. To the best of the authors' knowledge, this represents the first report describing adults of D repens in multiple subcutaneous nodules in a cat. Cytopathologic examination allowed characterization of the parasitic nature of the nodules. Veterinary practitioners should be aware of the possible nodular presentation of D repens in cats and should include D repens in the differential diagnosis of subcutaneous neoformations in the cat.

Angiogenic effect of platelet-rich plasma combined with gelatin hydrogel granules injected into murine subcutis.

Platelet-rich plasma (PRP), which contains highly concentrated platelets, is produced by centrifuging whole blood. It is a safe and readily available source of a wide range of growth factors necessary for angiogenesis. Gelatin hydrogel granules have been designed and prepared for the controlled release of many growth factors. The angiogenic effect of human PRP was examined in vitro, and the effect of its subcutaneous injection with gelatin hydrogel granules into murine subcutis was evaluated. Human PRP was prepared using a double-spin method. The concentration of growth factors and the platelet count were examined in PRP and in vitro, and the angiogenic activity of human umbilical vein endothelial cells (HUVECs) in co-culture with human dermal fibroblast cells (NHDFs) in the presence and absence of PRP was evaluated. Then, in vivo, PRP, either free or with gelatin hydrogel granules, was injected subcutaneously into tiebacks on mice. Using a microscope and Kurabo angiogenesis image analyser software, the area containing newly formed capillaries was evaluated histologically and the microvascular network score was calculated. PRP was shown to contain high concentrations of PDGF, VEGF and TGFß and had an angiogenic effect on the co-culture system. PRP with gelatin hydrogel granules significantly enlarged the area containing newly formed capillaries and promoted the microvascular network in murine subcutaneous tissue. PRP encapsulated in gelatin hydrogel microspheres shows promise for enhancing angiogenic effects in murine subcutis and could represent a potential therapeutic combination for the treatment of ischaemic disorders. Copyright © 2015 John Wiley & Sons, Ltd.

Case of pleomorphic rhabdomyosarcoma arising on subcutaneous tissue in an adult patient: Review of the published works of 13 cases arising on cutaneous or subcutaneous tissue.

Rhabdomyosarcoma (RMS) is a malignant mesenchymal tumor usually occurring in children, young adults, and predominantly arising in the head and neck or deep soft tissue of the extremities. Pleomorphic RMS (PRMS) arising on subcutaneous tissue in an adult patient's trunk is extremely rare. We present a case of primary PRMS occurring on the back of a 50-year-old man. The tumor was diagnosed by histological and immunohistochemical findings of the resected specimen. One month after the surgery, axillary lymph node metastases were found. Subsequently, the patient received three cycles of combined chemotherapy. The rest of those axillary lymph nodes were reduced in size and there was no local recurrence 6 months postoperatively. PRMS is a very rare but aggressive tumor. Thus, it is important to confirm the diagnosis and provide adequate treatments.

Preliminary data on dermis and subcutis thickness in adults with type 1 and 2 diabetes mellitus.

We compared the thickness of both dermis and subcutis (measured using ultrasound) in overweight and obese adults with type 1 (n = 10) or type 2 (n = 8) diabetes mellitus. When adjusted for confounding factors, patients with type 1 diabetes had thicker subcutis than those with type 2 diabetes, with this difference being particularly marked in the abdomen. There were no observed differences in dermal thickness between the groups.

Unilateral Pleomorphic Lipoma of the Eyebrow.

AIM: Epithelial and soft tissue tumours of the eyebrow skin and subcutis are rare occurrences. We describe an unusual eyebrow subcutis mass in a 65-year-old female. METHODS: A 65-year-old female presented with an 8- to 9-month history of a painless swelling over the right eyebrow that was sausage-shaped. The clinical differential diagnosis included neurofibroma/schwannoma, cyst, prolapsed fat or metastasis. The lesion was excised. RESULTS: The histology revealed a lesion composed of rope-like collagen, some spindle cells, mature adipocytes and hyperchromatic multi-nucleate floret cells. The spindle and multi-nucleate floret cells showed immunohistochemical positivity for CD34. The features were of a primary pleomorphic lipoma. CONCLUSIONS: This is the first reported case of a pleomorphic lipoma of the eyebrow subcutis. We discuss the clinical and histological differential diagnosis, especially related to histological conditions with which pleomorphic lipoma can be confused, such as well-differentiated liposarcoma.

Expression pattern of zinc-finger transcription factor Odd-skipped related 2 in murine development and neonatal stage.

The Odd-skipped gene, first identified as a Drosophila pair-rule zinc-finger transcription factor, plays an important role in Drosophila development. The mammalian homolog, Odd-skipped related 2 (Osr2), regulates limb, tooth, and kidney development in mouse embryos. However, the detailed expression pattern of Osr2 during neonatal development remains unclear. In this study, we investigated Osr2 expression patterns in mouse neonatal and embryo tissues using qPCR and in situ hybridization methods. First, we examined the tissue distribution of Osr2 by qPCR, and found it to be highly expressed in the uterus and moderately in the testes, small intestine, and prostate. That expression was also found in eye, kidney, placenta, lung, thymus, lymph node, stomach, and skeletal muscle tissues, and in all embryonic stages. On the other hand, Osr2 was not expressed in brain, heart, liver, or spleen samples. Next, we examined the tissue localization of Osr2 using in situ hybridization. Osr2 was found in the craniofacial region on E13.5, with notable expression in dental germ mesenchyme as well as the renal corpuscle on E17.5. As for neonatal tissues, Osr2 was expressed in the dental papilla, dental follicle, Harderian gland, nasal bone, eyelid dermis, synovial joint, and tibial subcutis. Our findings suggest that Osr2 functions in reproductive system organs, such as the uterus, testes, prostate, placenta, and ovaries. Furthermore, based on its expression in kidney, Harderian gland, eyelid dermis, and tibial subcutis tissues, this transcription factor may be involved in hormone synthesis and function. Together, our results demonstrate the role of Osr2 in postnatal development and embryogenesis.