Delivery of hepatocyte growth factor mRNA from nanofibrillar scaffolds in a pig model of peripheral arterial disease.

Background: Chemical modification of mRNA (mmRNA) substantially improves their stability and translational efficiency within cells. Nanofibrillar collagen scaffolds were previously shown to enable the spatially localized delivery and temporally controlled release of mmRNA encoding HGF both in vitro and in vivo. Materials & methods: Herein we developed an improved slow-releasing HGF mmRNA scaffold and tested its therapeutic efficacy in a porcine model of peripheral arterial disease. Results & conclusion: The HGF mmRNA was released from scaffolds in a temporally controlled fashion in vitro with preserved transfection activity. The mmRNA scaffolds improved vascular regeneration when sutured to the ligated porcine femoral artery. These studies validate the therapeutic potential of HGF mmRNA delivery from nanofibrillar scaffolds for treatment of peripheral arterial disease.

Regulatory T cell transfer ameliorates lymphedema and promotes lymphatic vessel function.

Secondary lymphedema is a common postcancer treatment complication, but the underlying pathological processes are poorly understood and no curative treatment exists. To investigate lymphedema pathomechanisms, a top-down approach was applied, using genomic data and validating the role of a single target. RNA sequencing of lymphedematous mouse skin indicated upregulation of many T cell-related networks, and indeed depletion of CD4+ cells attenuated lymphedema. The significant upregulation of Foxp3, a transcription factor specifically expressed by regulatory T cells (Tregs), along with other Treg-related genes, implied a potential role of Tregs in lymphedema. Indeed, increased infiltration of Tregs was identified in mouse lymphedematous skin and in human lymphedema specimens. To investigate the role of Tregs during disease progression, loss-of-function and gain-of-function studies were performed. Depletion of Tregs in transgenic mice with Tregs expressing the primate diphtheria toxin receptor and green fluorescent protein (Foxp3-DTR-GFP) mice led to exacerbated edema, concomitant with increased infiltration of immune cells and a mixed TH1/TH2 cytokine profile. Conversely, expansion of Tregs using IL-2/anti-IL-2 mAb complexes significantly reduced lymphedema development. Therapeutic application of adoptively transferred Tregs upon lymphedema establishment reversed all of the major hallmarks of lymphedema, including edema, inflammation, and fibrosis, and also promoted lymphatic drainage function. Collectively, our results reveal that Treg application constitutes a potential new curative treatment modality for lymphedema.

A 35-year-old woman presenting with an unusual post-traumatic leiomyoma of the nipple: a case report.

INTRODUCTION: Leiomyoma of the mammary papilla is one of the most uncommon nipple tumors with only 50 cases reported in the literature until now. To the best of our knowledge we present the first report of a nipple leiomyoma that originated from a traumatic abrasion caused by breastfeeding. CASE PRESENTATION: A 35-year-old healthy Caucasian female with a cauliflower-like tender and pink nodular mass that was approximately 10mm in diameter presented to our out-patients department. The patient suggested that the mass originated from a traumatic abrasion caused by breastfeeding three years ago and it has been slowly growing ever since.An excision biopsy was performed. The histological and immunohistochemical examination confirmed the diagnosis of leiomyoma. There were no postoperative complications or any sign of local recurrence four years postoperatively. CONCLUSIONS: Leiomyoma of the mammary papilla is a rare benign neoplasm that usually appears as a solid tender nodule. Differential diagnosis comprises breast carcinoma, leiomyosarcoma and myoid hamartoma. The recommended treatment is complete excision of the tumor with histologically confirmed tumor-free margins otherwise recurrence is possible. A detailed history of the patient's disease can reveal the original etiology. This is an original case report that will have particular interest to plastic surgeons, dermatologists, and pathologists. The pathogenetic mechanism was trauma of the nipple. According to our review of the literature this particular information has never been reported and we think that it may advance our knowledge of this very infrequent tumor.

Paramuscular and paraneural perforators in DIEAP flaps: radiographic findings and clinical application.

The computed tomography microangiography revolutionized the planning of abdominal flaps, and enabled us to identify perforators from the deep inferior epigastric system with a medial extramuscular or minimal medial intramuscular trajectory. We define these perforators as paramuscular and paraneural, since their main course is retromuscular and they emerge medial to the medial border of rectus muscle or medial to its motor nerve supply, respectively. Studying the different perforator distributions in the abdomen of 58 patients who underwent breast reconstruction with deep inferior epigastric artery perforator flap, we have recorded that 46.4% of the abdominal walls have a dominant paramuscular/paraneural perforator (25.8% paramuscular and 20.6% paraneural) with an average diameter 1.56 +/- 0.2 mm. Although, the comparison of the rectus muscle morbidity following deep inferior epigastric artery perforator flap dissection based on paramuscular/paraneural and based on other perforator patterns, did not reveal significant differences, paraneural/paramuscular type perforators are not related anatomically to the motor nerves, and the donor site morbidity should be negligible in any operator's hands.