Αρχειοθήκη ιστολογίου

Τρίτη 25 Μαΐου 2021

lncRNA PVT1 promotes cetuximab resistance of head and neck squamous cell carcinoma cells by inhibiting miR‐124‐3p

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Abstract

Background

Cetuximab has been widely used in the clinical treatment of head and neck squamous cell carcinoma (HNSCC). However, whether long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) is correlated with cetuximab resistance remains unclear.

Methods

Western blot and qRT-PCR were performed to quantify the levels of genes and proteins, respectively. Cell functions were measured using Cell Counting Kit-8 (CCK-8), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and flow cytometry assays. The methylation level was tested using methylation-specific PCR (MSP).

Results

PVT1 was upregulated and positively correlated with the poor prognosis of HNSCC. PVT1 overexpression markedly promoted the survival and weakened the cetuximab sensitivity of HNSCC cells, while miR-124-3p overexpression showed opposite effects. Mechanistically, the silence of PVT1 indirectly promoted miR-124-3p expression by reducing its promoter methylation. Importantly, miR-124-3p overexpression impeded the regulatory roles of PVT1 overexpression.

Conclusion

PVT1 decreased the sensitivity of HNSCC cells to cetuximab by enhancing methylation-mediated inhibition of miR-124-3p, which might provide a new insight for the cetuximab chemoresistance of HNSCC.

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Yin and Yang: a disrupted skin microbiome and an aberrant host immune response in Hidradenitis Suppurativa

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Abstract

The skin microbiome plays an important role in maintaining skin homeostasis by controlling inflammation, providing immune education, and maintaining host defense. However, in many inflammatory skin disorders the skin microbiome is disrupted. This dysbiotic community may contribute to disease initiation or exacerbation through the induction of aberrant immune responses in the absence of infection. Hidradenitis Suppurativa (HS) is a complex, multifaceted disease involving the skin, innate and adaptive immunity, microbiota, and environmental stimuli. Herein, we discuss the current state of HS skin microbiome research and how microbiome components may activate pattern recognition receptor (PRR) pathways, metabolite sensing pathways, and antigenic receptors to drive anti-microbial peptide, cytokine, miRNA, and adaptive immune cell responses in HS. We highlight the major open questions that remain to be addressed and how antibiotic therapies for HS likely influence both microbial burden and inflammation. Ultimately, we hypothesize that the two-way communication between the skin microbiome and host immune response in HS skin generates a chronic positive feed-forward loop that perpetuates chronic inflammation, tissue destruction, and disease exacerbation.

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Defining dipeptidyl peptidase‐4 inhibitors‐related bullous pemphigoid: A single‐centre retrospective study

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Abstract

Background

Many studies have corroborated the association of dipeptidyl peptidase-4 inhibitors (DPP4i) use with bullous pemphigoid (BP). It has been speculated that this drug-induced variant presents with a different clinical spectrum than conventional BP.

Objective

To determine the prevalence of DPP4i-induced cases of BP and to evaluate whether gliptin-related BP has specific clinicopathological and immunological features.

Methods

We conducted a retrospective, observational study of BP cases attended at our centre between January 2000 and June 2020. Epidemiological, clinical, histopathological and laboratory data were collected.

Results

A total of 257 cases of BP were collected; 51 (24.3%) were on treatment with DPP4i. When analysing DPP4i-induced BP cases, generalized BP was the predominant pattern and scalp/mucosal involvement was found in 13 patients. Gliptin-related BP cases were associated to a decrease in the eosinophilic infiltrate (p = 0.000) and both the detection rate and concentration of anti-BP180 IgG were lower (p = 0.004, p = 0.001, respectively) than non-DPP4i cases.

Limitations

Retrospective, single-centre study.

Conclusion

Our large DPP4i-induced BP case series has highlighted that DPP4i-induced BP is characterized by generalized lesions and scalp involvement. Lower titres of anti-BP180 antibodies and a decrease in eosinophils infiltrating into the skin may be distinct features of DPP4i-related BP.

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“The Pruritogenic Role of the Type 2 Immune Response in Diseases Associated with Chronic Itch”

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Abstract

While there is a vast array of etiologies that may lead to chronic pruritus, recent data suggests that many of these conditions share similar interactions between keratinocytes, nerves, and the immune system. Specifically, the type 2 immune response, including Th2 T-Cells and their related cytokines, has been noted to play a major role in the development of pruritus in a variety of itchy conditions. To date, atopic dermatitis is the most striking example of this pathogenesis. However, the body of literature supporting its role in many other itchy conditions, including other inflammatory, bullous, as well as systemic diseases, continues to grow. In addition, new treatments targeting this type 2 immune system continue to be developed and investigated. In the current review, we present the current body of literature supporting the role of the type 2 immune response in itchy conditions beyond atopic dermatitis as well as potential therapeutic options that target this pathway for chron ic itch.

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Κυριακή 23 Μαΐου 2021

Cadaveric study of arterial renal anatomy and its surgical implications in partial nephrectomy

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Surg Radiol Anat. 2021 May 22. doi: 10.1007/s00276-021-02769-8. Online ahead of print.

ABSTRACT

PURPOSE: Partial nephrectomy is gaining, nowadays, more interest in oncologic kidney surgery. This type of surgery requires the good knowledge of vascular renal anatomy to make it safe and to guarantee good functional and oncological outcomes. This paper exposes the clinical implication of the arterial renal anatomy in nephron-sparing surgery.

METHODS: This is a cadaveric st udy of 71 human kidneys performed at Charles Nicolle mortuary. The right and left kidneys with surrounding tissues were removed en bloc with the adjacent part of the aorta and inferior vena cava, cleared and studied. Colored resin was injected in each artery, vein, and urinary ducts, with a specific color code for each structure. Corrosion technique was used to eliminate the surrounding tissue, leaving only the colored resin matrix. The Ternon anatomic classification of the inferior polar artery, based on its emergence point was used.

RESULTS: Multiple renal arteries were noted in 9.85% of casts. Anterior and posterior division of main renal artery was found in 95.7% of cases. Posterior segmental artery crossed posteriorly the upper caliceal infundibulum and the renal pelvis in 93% of cases. The upper renal pole was vascularized by an apical segmental artery in 16.9% of cases and a superior polar artery in one case (1.4%). The mid pole of the kidney was supplied by a unique an terior branch and a single posterior branch in 40% of cases. Inferior polar artery was found in 52 casts (73.23%). Type I of Ternon was found in 6 casts (11.53%), Type II in 25 cases (48.07%), Type III in 19 cases (36.53%), Type IV in 2 cases (3.84%), and type V in 13 casts (25%).

CONCLUSION: Renal vascular anatomy presents large variations. Good knowledge of the segmental arterial anatomy of the kidney is a primordial to a safe partial nephrectomy. Good preoperative vascular mapping can be of great help for the surgeon.

PMID:34021803 | DOI:10.1007/s00276-021-02769-8

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Association between duration of peripheral facial palsy, severity, and age of the patient, and psychological distress

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J Plast Reconstr Aesthet Surg. 2021 Apr 18:S1748-6815(21)00196-0. doi: 10.1016/j.bjps.2021.03.092. Online ahead of print.

ABSTRACT

BACKGROUND: Peripheral facial palsy (PFP) (paralysis) can be a devastating condition that has been shown to have associations with increased depression and worse quality of life. The aim of the present study is to better understand the complex association of psychological distress with the duration, severity, and age of patients with PFP. We hypothesize that a shorter duration of PFP is associated with higher levels of psychological distress.

METHODS: Fifty-nine patients with PFP that existed longer than 3 months were included in this study. The Hospital Anxiety and Depression Scale (HADS) was used to assess the presence and severity of anxiety and depressions. Spearman's correlation analysis was used to determine correlation between psychological distress, duration, severity of the PFP, and age.

< p>RESULTS: Fifty-nine patients were included in this study, of whom 22 were male and 37 were female. The mean age was 55.6 ± 14.6 years and mean duration of PFP from onset ranged from 3 months to 35 years (with a mean duration of 5.39 ± 6.06 years). Twenty-eight patients had left-sided PFP, 30 patients had right-sided PFP, and one patient had bilateral PFP. The majority were caused by Bell's palsy (50.8%). In the group with a duration less than 5 years, there were five (12.8%) patients having a score between 11 and 15 (on HADS) compared to two (10%) patients in the group with a duration of 5 years or more(p = 0.04).

CONCLUSION: There seems to be an association between moderate depression and duration of the PFP. Further studies need to substantiate our findings.

PMID:34020901 | DOI:10.1016/j.bjps.2021.03.092

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The sternohyoid muscle flap for new dynamic facial reanimation technique: Anatomical study and clinical results

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J Plast Reconstr Aesthet Surg. 2021 Apr 20:S1748-6815(21)00188-1. doi: 10.1016/j.bjps.2021.03.085. Online ahead of print.

ABSTRACT

BACKGROUND: Long-term facial nerve palsy has a highly negative impact on patients' quality of life. In 2016, Alam reported one case of facial reanimation with the sternohyoid muscle after publishing a preclinical study in 2013. Despite the potentially ideal characteristics of this muscle for reanimation of facial palsy, this technique is still not widely used. The objective of our description of cases was to present the clinical results obtained with the surgical procedure and the study on cadavers to confirm the anatomical findings.

METHODS: This work describes the anatomical study of the vascular and nervous pedicle of the sternohyoid muscle compared with clinical results from a series of patients with long-term facial paralysis who underwent facial reanimation between June 2016 and September 2019, through the insertion of the sternohyoid muscle into the masseteric nerve.

RESULTS: The anatomical study was conducted in eight human hemi-necks. In five cases (62%), the vascular pedicle was provided by the superior thyroid artery, and the entrance of the ansa cervicalis to the muscle was constant 1.8 cm from the distal insertion. This series included ten patients who underwent the surgery technique of facial reanimation using the sternohyoid muscle, with a 90% (n = 9) of reinnervation; 100% (n = 10) of flaps were viable, and none of the patients showed complications in the donor area.

CONCLUSIONS: The sternohyoid muscle showed itself as a reliable muscle as a free flap in facial reanimation, and alternative to the gracilis flap. The surgical technique was safe, without any complications, with excellent excursion, recovery, and aesthetic results.

PMID:34020902 | DOI:10.1016/j.bjps.2021.03.085

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Modified anterior intercostal artery perforator flap (AICAP) for autologous breast volume restoration after explantation

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J Plast Reconstr Aesthet Surg. 2021 Apr 23:S1748-6815(21)00227-8. doi: 10.1016/j.bjps.2021.03.123. Online ahead of print.

ABSTRACT

Explantation of breast implants has become increasingly common. This study aimed to analyze breast auto-augmentation following implant explantation (using a laterally designed anterior intercostal artery perforator [AICAP] flap) in patients who did not need new implants and required volume preservation. Twenty-four patients (48 breasts) aged 31-67 years (mean, 52.4 years) with body mass index (BMI) between 24.43 and 29.34 (mean, 27.32) kg/m2 underwent this procedure. All patients had implant-related problems, such as recurrent capsular contracture (n=11), seroma (n=2), animation deformity (n=3), rupture-induced bleeding (n=5), and breast implant disease (n=3). Sizes of implants removed ranged from 215 to 355 ml. The mean flap size was 23.9 cm × 7.5 cm, and the average flap thickness was 2.3 cm (range, 2.0- 3.2 cm). Flap survival was clinically examined postoperatively by ultrasonography. Pre- and postoperative final breast volumes were compared by direct patient observation and independent photograph observation by three plastic surgeons according to a 4-point scale (bad=1, regular=2, good=3, and excellent=4) and the brassiere size. All flaps were completely viable after harvesting. No postoperative signs of fat necrosis were observed, and independent plastic surgeon evaluation revealed good and excellent results in all cases. Patient satisfaction evaluated by BREAST-Q data was >90%. This new design, AICAP flap (with a lateral thoracic extension), can be safely used for breast volume restitution after breast implant explantation with high patient satisfaction. This flap exhibited reasonable potential of providing additional volume in patients who undergo implant explantation and require the preservation of similar volume.

PMID:34020904 | DOI:10.1016/j.bjps.2021.03.123

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Where does subcutaneous lymph from the chest wall flow into after mastectomy?

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J Plast Reconstr Aesthet Surg. 2021 Apr 18:S1748-6815(21)00216-3. doi: 10.1016/j.bjps.2021.03.112. Online ahead of print.

ABSTRACT

BACKGROUND: Changes of the lymph flow from the chest wall after mastectomy and sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (Ax) has yet to be understood. This study aimed to investigate the effect of axillary surgery on lymphatic flow from the chest wall in patients who have undergone mastectomy, including those have undergone breast reconstruction and vascularized lymph node transfer (VLNT).

METHODS: Following mastectomy in 100 breasts, the directions of lymph flow from the chest wall was compared between the SLNB omission, SLNB, Ax, and Ax followed by VLNT groups using indocyanine green (ICG) lymphography in cross-sectional study. Lymph flow on the deep epigastric artery perforator (DIEP) flap was also investigated.

RESULTS: Lymph flow directing to the ipsilateral axill a was observed more frequently after SLNB than Ax (48% vs. 12.5%; p = 0.005); however, no significant difference was observed in the frequency of contralateral axillary route adoption between them (8% vs. 15%; p = 0.65). In the VLNT group, lymph flow to the ipsilateral axilla was not observed at a significantly higher frequency than in the Ax group (12.5% vs. 12.5%, p = 1.00). On the transferred DIEP flap, the lymph flowed anterograde or retrograde parallel to the anatomic course of the lymphatic vessels.

CONCLUSION: To visualize the direction of lymph flow of the chest following mastectomy, ICG lymphography may be useful to discern the direction in which malignant neoplasms, including lymphoma, are transported and to plan for lymph flow restoration.

PMID:34020906 | DOI:10.1016/j.bjps.2021.03.112

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Long-term Follow-up and Trends in Breast Augmentation in 527 Transgender Women and Nonbinary Individuals: A 30-year experience in Amsterdam

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J Plast Reconstr Aesthet Surg. 2021 Apr 20:S1748-6815(21)00212-6. doi: 10.1016/j.bjps.2021.03.107. Online ahead of print.

ABSTRACT

BACKGROUND: Transgender women and transfeminine spectrum nonbinary individuals may opt for breast augmentation. The aim of the study is to analyze the complications, surgical trends, and long-term follow-up of breast augmentations in this population over the past 30 years.

METHODS: All transgender women and nonbinary individuals who underwent breast augmentation at our center between 01-1990 and 01-2020 were retrospectively identified. A retrospective chart study was conducted, recording individual demographics, implant characteristics, surgical timing, postoperative complications or other reasons requiring reoperation, and implant survival. A literature search was performed in MEDLINE on clinical outcomes and revision surgery of this procedure.

RESULTS: A total of 527 individuals were identifie d. Median clinical follow-up time was 11.2 years (interquartile range 3.3-17.5). Median implant size increased significantly over the last years (1990-1990 median 275cc, 2000-2009 252cc, 2010-2019 375cc, p<0.01). Most individuals underwent breast augmentation and genital gender-affirming surgery in one-stage. Reoperations due to short-term complications were infrequent (hematoma (0.4%) or infection (0.4%)). Reoperations due to long-term complications comprised: implant rupture (5.7%), capsular contracture (4.9%), aesthetic problems (3.8%), low-grade infection (0.4%), or seroma (0.6%). In total, 2.5% of individuals requested larger implants. After performing the literature search and manuscript screening, 9 out of 115 identified studies were included for review. Follow-up time ranged from 30 days to 5.5 years. Reported complications requiring reoperation were capsular contraction (range 0.0-5.6%), asymmetry (3.6%), hematoma (range 0.0-2.9%), infection (range 0.0-0.9%) and implant rupture (0.7%), CONCLUSION: Implant-based breast augmentation is a safe procedure in transgender individuals.

PMID:34020905 | DOI:10.1016/j.bjps.2021.03.107

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Computer-assisted versus traditional freehand technique for mandibular reconstruction with free vascularized fibular flap: A matched-pair study

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J Plast Reconstr Aesthet Surg. 2021 Apr 22:S1748-6815(21)00226-6. doi: 10.1016/j.bjps.2021.03.121. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to perform a surgery-related and patient-related outcome analysis of a case-matched series of patients treated with computer-assisted surgery (CAS) and traditional freehand surgery.

METHODS: A total of 153 patients who underwent mandibular reconstruction by VFF were included from Jan 1999 to Dec 2019. The mandibular resection and reconstruction were performed by four experienced oral and maxillofacial surgeons. Reasons for reconstruction were oncologic, osteoradionecrosis, trauma, and osteoporosis. All the patients were followed up postoperatively for at least 1 year. Eighteen pairs were formed with the matched cohort consisting of a total of 36 patients who underwent primary mandibular reconstruction without additional combined flaps. The surgery-related and patient-relat ed continuous and categorical parameters were assessed in both groups.

RESULTS: The average operation time and bleeding volume in the CAS group were less than those in the non-CAS group. Additionally, both hospitalization and ICU days were lower in the CAS group without any significant difference. The only significant finding related to surgical parameters was observed for the ischemia time, which was lower in the CAS group.

CONCLUSIONS: Computer-assisted surgery indicated improved efficiency considering reduced ischemia time, operation time, and length of hospital stay with lower early complications than that of conventional surgical procedures. It can thus be considered as an optimized alternative to the freehand approach.

PMID:34020903 | DOI:10.1016/j.bjps.2021.03.121

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