Monday, November 30, 2020

LRP1/CD91 is Highly Expressed in Monocytes from Patients with Vitiligo, Even After Repigmentation.

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Abstract

Vitiligo pathophysiology is mediated by antigen‐specific cytotoxic T cells. Environmental stressors cause susceptible melanocytes to secrete damage‐associated molecular patterns (DAMPs). DAMPs are recognized by receptors such as the endocytic low‐density‐lipoprotein receptor‐related‐protein (LRP1/CD91), expressed in antigen presenting cells, which activate self‐reactive CD8+ T cells, leading to melanocyte destruction. Within this response, interferon‐gamma triggers production of cytokine CXCL10, recruiting more activated T cells causing further melanocytic damage. We hypothesized that expression of LRP1/CD91 was higher in vitiligo patients compared to non‐vitiligo individuals. And further that levels/expression of CXCL10 in plasma were linked to disease severity. We enrolled forty individuals in this study: 18 patients with vitiligo and 22 healthy volunteers. We assessed LRP1/CD91 expression and plasma CXCL10 in patients with vitiligo and healthy volunteers. Addi tionally, vitiligo patients received combined treatment for 16‐weeks following which the said parameters were reassessed. Vitiligo Area Scoring Index were calculated before and after treatment for these patients. Analysis of LRP1/CD91 MFI values in monocytes from vitiligo patients showed high surface levels of LRP1/CD91 than from healthy volunteers (10.50±0.77 vs 6.55±0.77 MFI units, p<0.001). This expression did not change after treatment. Plasma levels of CXCL10 were higher in vitiligo patients than healthy volunteers (93.78±7.73 vs 40.17±6.25 pg/mL). The patients with a good clinical response to treatment had a parallel reduction in plasma CXCL10 levels (105.8±18.44 vs 66.13±4.87 pg/mL) before and after treatment. LRP1/CD91 expression may reflect susceptibility to vitiligo. Plasma levels of CXCL10 can represent a biomarker for monitoring treatment response. LRP1 and CXCL10 may represent therapeutic targets.

IRB approval status: Reviewed and approved by Hospital de la Santa Creu I Sant Pau clinical research ethics committee identified as IIBSP‐VIT‐2015‐69

ClinicalTrials.gov identifier: NCT03249064

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Long non‐coding RNA LINC00665 promotes melanoma cell growth and migration via regulating the miR‐224‐5p/VMA21 axis

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Abstract

Background

Melanoma is an aggressive malignant skin tumor endangering the health of patients. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been increasingly reported to be implicated in the carcinogenesis of melanoma. Long intergenic non‐coding RNA 00665 (LINC00665) has been found to exert important regulatory roles in some cancers, yet its function in melanoma remains to be investigated.

Methods

QRT‐PCR analysis was conducted to evaluate the relative expression of RNAs. Functional experiments in vitro including colony formation, EdU, wound‐healing and transwell assays, as well as in vivo xenograft assays, were utilized to study the role of LINC00665 in melanoma. Mechanical experiments were implemented to probe into the molecular linkage of LINC00665, miR‐224‐5p and VMA21.

Results

LINC00665 was abnormally highly expressed in melanoma cells. Silencing LINC00665 could inhibit the proliferation and migration of melanoma cells. LINC00665 sponged miR‐224‐5p to up‐regulate VMA21. VMA21 knockdown exerted similarly interfering effects on above biological processes in melanoma cells. However, VMA21 overexpression abolished the in vitro and in vivo outcomes of LINC00665 silencing.

Conclusion

LINC00665 promotes proliferative and migrating abilities of melanoma cells via targeting miR‐224‐5p/VMA21 axis.

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Transcriptional and signaling regulation of skin epithelial stem cells in homeostasis, wounds, and cancer

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Abstract

The epidermis and skin appendages are maintained by their resident epithelial stem cells, which undergo long‐term self‐renewal and multi‐lineage differentiation. Upon injury, stem cells are activated to mediate re‐epithelialization and restore tissue function. During this process, they often mount lineage plasticity and expand their fates in response to damage signals. Stem cell function is tightly controlled by transcription machineries and signaling transductions, many of which derail in degenerative, inflammatory, and malignant dermatologic diseases. Here, by describing both well‐characterized and newly emerged pathways, we discuss the transcriptional and signaling mechanisms governing skin epithelial homeostasis, wound repair, and squamous cancer. Throughout, we highlight common themes underscoring epithelial stem cell plasticity and tissue‐level crosstalk in the context of skin physiology and pathology.

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Molecular targets of tyrosine kinase inhibitors in thyroid cancer.

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Molecular targets of tyrosine kinase inhibitors in thyroid cancer.

Semin Cancer Biol. 2020 Nov 26;:

Authors: Fallahi P, Ferrari SM, Galdiero MR, Varricchi G, Elia G, Ragusa F, Paparo SR, Benvenga S, Antonelli A

Abstract
Thyroid cancer (TC) is the eighth most frequently diagnosed cancer worldwide with a rising incidence in the past 20 years. Surgery is the primary strategy of therapy for patients with medullary TC (MTC) and differentiated TC (DTC). In DTC patients, radioactive iodine (RAI) is administered after thyroidectomy. Neck ultrasound, basal and thyroid-stimulating hormone-stimulated thyroglobulin are generally performed every three to six months for the first year, with subsequent intervals depending on initial risk assessment, for the detection of possible persistent/recurrent disease during the follow up. Distant metastases are present at the diagnosis in ∼5% of DTC patients; up to 15% of patients have recurrences during the follow up, with a survival reduction (70% to 50%) at 10-year. During tumor progression, the iodide uptake capability of DTC cancer cells can be lost, making them refractory to RAI, with a negative impact on the prognosis. Significant advances have been done re cently in our understanding of the molecular pathways implicated in the progression of TCs. Several drugs have been developed, which inhibit signaling kinases or oncogenic kinases (BRAFV600E, RET/PTC), such as those associated with Platelet-Derived Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor. Tyrosine kinase receptors are involved in cancer cell proliferation, angiogenesis, and lymphangiogenesis. Several tyrosine kinase inhibitors (TKIs) are emerging as new treatments for DTC, MTC and anaplastic TC (ATC), and can induce a clinical response and stabilize the disease. Lenvatinib and sorafenib reached the approval for RAI-refractory DTC, whereas cabozantinib and vandetanib for MTC. These TKIs extend median progression-free survival, but do not increase the overall survival. Severe side effects and drug resistance can develop in TC patients treated with TKIs. Additional studies are needed to identify a potential effective targeted therapy for aggressive TCs, a ccording to their molecular characterization.

PMID: 33249201 [PubMed - as supplied by publisher]

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The systolic pulmonary artery pressure and the E/e' ratio decrease after septoplasty in patients with grade 2 and 3 pure nasal septal deviation.

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The systolic pulmonary artery pressure and the E/e' ratio decrease after septoplasty in patients with grade 2 and 3 pure nasal septal deviation.

Braz J Otorhinolaryngol. 2020 Nov 09;:

Authors: Avcı D, Hartoka Sevinç A, Güler S

Abstract
INTRODUCTION: Nasal septal deviation may contribute to a wide range of symptoms including nasal obstruction, headache, increased secretion, crusting, mucosal damage, and loss of taste and smell. Excessive increase in the respiratory resistance, as seen in nasal septal deviation, results in reduced lung ventilation, thereby potentially leading to hypoxia, hypercapnia, pulmonary vasoconstriction. The deformities in the nasal cavity can be associated with major respiratory and circulatory system diseases.
OBJECTIVE: To investigate cardiovascular effects of septoplasty by comparing pre- and postoperative transthoracic echocardiography findings in nasal septal deviation patients undergoing septoplasty.
METHODS: The prospective study included 35 patients with moderate and severe nasal septal deviation (mean age, 23.91±7.01) who underwent septoplasty. The Turkish version of the nasal obstruction symptom evaluation, NOSE questionnaire, was administered to each participant both pre- and postoperatively in order to assess their views on the severity of nasal septal deviation, the effect of nasal obstruction, and the effectiveness of surgical outcomes. A comprehensive transthoracic echocardiography examination was performed both preoperatively and at three months postoperatively for each patient and the findings were compared among patients.
RESULTS: Mean preoperative NOSE score was 17.34±1.62 and the mean postoperative score was 2.62±1.68 (p=0.00). Mean preoperative systolic pulmonary artery pressure value was 22.34±4.31mmHg and postoperative value was 18.90±3.77mmHg (p=0.00). Mean E/e' ratio was 5.33±1.00 preoperatively and was 5.01±0.90 postoperatively (p=0.01). The NOSE scores, systolic pulmonary artery pressure values, and the E/e' ratios decreased significantly after septoplasty (p<0.05 for all), whereas no significant difference was found in other transthoracic echocardiography parameters (p>0.05).
CONCLUSION: The decrease in NOSE scores following septoplasty indicated that the satisfaction levels of the patients were increased. Upper airway obstruction secondary to nasal septal deviation may be a cardiovascular risk factor and may affect transthoracic echocardiography measurements. Moreover, the significant decrease in the systolic pulmonary artery pressure value and E/e's ratio following septoplasty indicated that negative echocardiographic findings may be prevented by this surgery.

PMID: 33248927 [PubMed - as supplied by publisher]

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The 'Double hit': Free tissue transfer is optimal in comorbid population with irradiated wounds for successful limb salvage.

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The "Double hit": Free tissue transfer is optimal in comorbid population with irradiated wounds for successful limb salvage.

J Plast Reconstr Aesthet Surg. 2020 Nov 04;:

Authors: Deldar R, Black CK, Zolper EG, Wirth P, Luvisa K, Fan KL, Evans KK

Abstract
BACKGROUND: Radiation therapy causes histopathologic changes in tissues, including fibrosis, loss of tissue planes, and vascular damage, which can lead to chronic wound formation. Patients with nonhealing, irradiated wounds and comorbidities that affect microvasculature suffer a "double hit", which leads to delayed wound healing. Local wound care and grafts are commonly insufficient. In this study, we evaluated limb salvage outcomes and long-term complications after free tissue transfer (FTT) in patients with chronic, irradiated leg wounds.
METHODS: We retrospectively reviewed patients with irradiated lower extremity wounds who underwent FTT from 2012 to 2017. Primary outcomes included limb salvage, ambulation, and overall flap success. Reconstruction involved complete excision of irradiated tissue and coverage with well-vascularized tissue.
RESULTS: Seven free flaps in six patients were identified. Average age was 68.4 years and average BMI was 27.8 kg/m2. Comorbid conditions included hypertension (57.1%), peripheral vascular disease (57.1%), underlying hypercoagulability (42.9%), diabetes (14.3%), and tobacco use (14.3%). Wounds were present for an average of 25.5 months prior to FTT. Donor sites included anterolateral thigh (71.4%), vastus lateralis (14.3%), and latissimus dorsi (14.3%). Overall flap success rate was 100% with one patient requiring reoperation for dehiscence. Limb salvage rate was 85.7% with one patient undergoing elective amputation due to pain. All patients could ambulate (one used a prosthesis) at a mean follow-up time of 1.4 years.
CONCLUSIONS: Radiation therapy in a comorbid population often leads to the formation of chronic nonhealing wounds. We advocate for earlier consideration of FTT to provide healthy vascularized tissues, thereby avoiding prolonged wound care and patient burden. Successful limb salvage outcomes can be achieved.

PMID: 33248934 [PubMed - as supplied by publisher]

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,Single-Unit technique for the use of acellular dermal matrix in immediate expander-based breast reconstruction.

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Single-Unit technique for the use of acellular dermal matrix in immediate expander-based breast reconstruction.

J Plast Reconstr Aesthet Surg. 2020 Nov 02;:

Authors: Luan A, Patel AA, Martin SA, Nazerali RS

Abstract
BACKGROUND: The use of acellular dermal matrices (ADMs) in immediate two-stage prosthetic breast reconstruction following mastectomy is now a common practice. The procedure confers several compelling benefits, including coverage of the inferior pole, enhanced definition of the inframammary fold, and reduction of capsular contracture. However, operative techniques used to create the ADM inferolateral sling can be unwieldy in practice, typically involving the placement of the ADM followed by positioning and anchoring of the prosthetic expander. At best, this may be a relatively minor nuisance, but may potentially influence outcomes, including discrepancies in symmetry.
METHODS: We present a novel modification that aims to streamline this procedure. Perforations are made through the allograft, through which the tissue expander tabs are brought through and sutured together ex vivo to allow the ADM and expander to be placed into the inframammary fold position as a single unit. A retrospective chart review was then performed of patients who underwent breast reconstruction utilizing this technique between July 2015 and December 2018. Outcomes including postsurgical complications such as infection, malposition, and reoperation were analyzed.
RESULTS: Sixty-two patients met the inclusion criteria, corresponding to 108 breasts. The average follow-up was 18 months. The overall complication rate was 29.6% of breasts. The most commonly observed complications were mastectomy skin necrosis (9.3%) and major infection (8.3%). There was a 7.4% rate of malposition.
CONCLUSIONS: This simple but effective modification in ADM technique is associated with a comparable complication rate and allows for greater ease and consistency in tissue expander placement.

PMID: 33248935 [PubMed - as supplied by publisher]

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The role of plastic surgery in major trauma

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The role of plastic surgery in major trauma in the United Kingdom and workforce recommendations.

J Plast Reconstr Aesthet Surg. 2020 Nov 06;:

Authors: Hendrickson SA, Young K, Gardiner MD, Phillips G, Wallace DL, Hettiaratchy S, Giblin AV

Abstract
INTRODUCTION: The 22 major trauma centres (MTCs) in England were appointed in 2012 to provide care to severely injured patients despite variation in existing infrastructure, resources, culture and skillset. Six MTCs remain unsupported by a co-located plastic surgery department. We describe the plastic surgical major trauma workload in England, the plastic surgical workforce and skillset available in each centre, and suggest what plastic surgical skills are required in an MTC.
METHODS: A multi-centre, prospective cohort study was performed to collect operative workload data. Eleven MTCs in England submitted complete datasets. Workforce data were provided by the British Association of Plastic Reconstructive and Aesthetic Surgeons (BAPRAS).
RESULTS: Fifty-three percent (n = 1582) of Trauma and Audit Research Network (TARN)-eligible patients admitted during the study period underwent at least one operation during their index admission. Of these, 14% (n = 227) required plastic surgery. The majority of plastic surgical operative work involved the extremities: 62% of index procedures involved the lower limb and 38% involved the upper limb. The number of full-time plastic surgical consultants per MTC ranged from 1 to 22. Only 10 MTCs had at least one plastic surgeon with a primary interest in lower limb trauma.
CONCLUSION: Plastic surgery contributes substantially to major trauma care and the majority of this workload relates to extremity trauma. However, there is significant variability in the size, accessibility and skillset of the workforce available. On the basis of these data, we suggest a plastic surgical skillset which should be represented in plastic surgical departments supporting an MTC.

PMID: 33248936 [PubMed - as supplied by publisher]

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Salvaging exposed microtia cartilage framework with negative pressure wound therapy.

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Salvaging exposed microtia cartilage framework with negative pressure wound therapy.

J Plast Reconstr Aesthet Surg. 2020 Nov 23;:

Authors: Sasaki K, Sasaki M, Oshima J, Nishijima A, Aihara Y, Sekido M

Abstract
One of the most severe complications of auricular reconstruction for microtia is exposure of the cartilage framework. Recently, negative pressure wound therapy (NPWT) has become popular for a variety of complex wounds but reports on methods for microtia reconstruction are scarce. Thus, we aimed to detail the use of NPWT for cartilage exposure in microtia reconstruction. We retrospectively analyzed 7 cartilage exposure wounds in 6 patients treated by NPWT after auricular reconstruction for microtia. All wounds appeared from postoperative days 3 to 30 with 3 on the antihelix, 2 on the helix, 1 on the triangular fossa and 1 on the scaphoid fossa. Skin defect sizes ranged from 1 to 24 mm2 and 2 cartilage frames were infected at onset. Our NPWT system was the KCI Negative Pressure Wound Therapy with V.A.C.Ⓡ GranuFoam Black™ or Silver™ and continuous suction was applied in a range of 25-125 mmHg. All wounds healed within 8 to 39 days with NPWT antecedent cases taking longer than surgery ones. All cartilage frames survived but partial cartilage atrophies remained in 4 cases. Although a secondary infection occurred in an NPWT antecedent case it was still useful as a continuous external drainage system to remove dead space exudate and stimulate granulated tissue formation. In addition to vigilance against secondary infection, surgeons should consider an additional surgical intervention if the wound fails to improve within 7 days.

PMID: 33248937 [PubMed - as supplied by publisher]

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Anatomic landmarks for masseteric nerve identification: Anatomic study for a new reference point.

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Anatomic landmarks for masseteric nerve identification: Anatomic study for a new reference point.

J Plast Reconstr Aesthet Surg. 2020 Nov 08;:

Authors: Copelli C, Manfuso A, Aragona T, Cama T, Topazio D, Hirt B

Abstract
The masseteric nerve is often used as a donor nerve in the treatment of facial paralysis. Even if several anatomical studies described landmarks for its identification, their main disadvantages are the anatomical variability and the changes due to surgery. Sixteen dissections were performed on cadaveric specimens. The masseteric muscle (MM), the zygomatic arch (ZA), the masseteric nerve (MN) and the zygomatic branch of the facial nerve (ZB) were identified and their relationships were measured. The relationships between MN and ZB resulted to be constant, with MN intersecting ZB at a depth of 0,78 cm in the muscle, 1,6 cm below ZA and 0,8 cm from the posterior border of MM. The measures obtained demonstrated as the main zygomatic branch of the facial nerve can be a suitable landmark for the identification of the masseteric nerve, with no variations due to the surgical procedure or patient characteristics.

PMID: 33248938 [PubMed - as supplied by publisher]

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Decreasing donor site morbidity after groin vascularized lymph node transfer with lessons learned from a 12-year experience and review of the literature.

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Decreasing donor site morbidity after groin vascularized lymph node transfer with lessons learned from a 12-year experience and review of the literature.

J Plast Reconstr Aesthet Surg. 2020 Oct 24;:

Authors: Hamdi M, Ramaut L, De Baerdemaeker R, Zeltzer A

Abstract
INTRODUCTION: Donor site morbidity related to vascularized lymph node transfer (VLNT) remains a cause of worry among surgeons. As such, our study explores donor site morbidity after VLNT with or without concomitant deep inferior epigastric artery perforator (DIEP) flap breast reconstruction. Furthermore, we evaluate our surgical approach to ascertain whether it reduces the morbidity rate.
MATERIALS AND METHODS: A retrospective chart review of donor site complications and surgical techniques was performed from 2006 to 2018. The patients' medical histories and demographic data were analyzed for risk factors. Patients were contacted by telephone for a long-term follow-up questionnaire. A literature review was implemented to evaluate the reported donor site complications and surgical strategies in literature. Complications were evaluated with and without concomitant autologous breast reconstruction (DIEP flap).
RESULTS: Eighty-nine patients were included in our case series. Sixty-five cases (73%) were combined with DIEP flap breast reconstruction. Seroma rate diminished from 60% in the first 39 cases to 18% in the last five years (50 cases) (p < 0,001). Lymphedema of the afferent lower limb is described in the literature but did not occur in our series.
CONCLUSIONS: Seroma formation is the most common donor site morbidity after groin VLNT flap harvest, particularly when combined with DIEP flap breast reconstruction. This paper contains the largest reported series of combined VLNT + DIEP flaps and describes surgical strategies on how to decrease seroma formation and avoid iatrogenic lymphedema of the lower limb.

PMID: 33248939 [PubMed - as supplied by publisher]

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