Influence of IL1B (rs16944) and IL1R2 (rs4141134) polymorphisms on aggressiveness and prognosis of cutaneous melanoma

xlomafota13 shared this article with you from Inoreader Influence of IL1B (rs16944) and IL1R2 (rs4141134) polymorphisms on aggressiveness and prognosis of cutaneous melanoma Via Melanoma Research - Published Ahead-of-Print Cutaneous melanoma is the most aggressive skin cancer with high mortality. Proinflammatory cytokines can modulate the proliferation and survival of cutaneous melanoma cells. Higher levels of interleukin-1β (IL1B) were associated with tumor cell proliferation, invasion, and migration, and the IL-1 type II receptor ( IL1R2) serves as an endogenous inhibitor of IL1B signaling. Single-nucleotide variations (SNVs) in these genes (IL1B rs16944 and IL1R2 rs4141134) can modulate cytokine production and binding; however, their role in cutaneous melanoma is still unknown. Thus, we investigated the influence of the above SNVs in clinicopathological aspects and cutaneous melanoma patients' survival. In the present study, we analyzed 193 patients with cutaneous melanoma for IL1B c.-598T>C (rs16944) and IL1R2 c.-2009G>A (rs4141134) genotypes with TaqMan assays. Differences between groups were calculated using χ2 or Fisher's exact test and multiple logistic regression. Progression-free survival (PFS) and melanoma-specific survival were calculated by Kaplan–Meier and Cox methods. The prognostic value of IL1R2 was also analyzed by the online consensus survival webserver for skin cutaneous melanoma (OSskcm). We found that IL1R2 rs4141134 GG genotype was more common in patients with nodular subtype (49.1% vs. 29.8%, P = 0.01) and the frequency of IL1R2 rs4141134 GG or GA was higher in patients with Clark levels III–V (87.4% vs. 75.8%, P = 0.04). Patients with IL1R2 rs4141134 GG or GA genotypes presented lower PFS (hazard ratio: 3.12, 95% confidence interval, 1.10–8.79, P = 0.03) when compared with AA genotype, supported by OSskcm results. Thus, our study presented for the first time preliminary evidence that IL1R2 rs4141134 SNV may modulate cutaneous melanoma clinicopathological aspects and survival possible by allowing IL1B signaling. * Caroline Torricelli and Juliana Carron contributed equally to the writing of this article. Received 4 May 2021 Accepted 12 June 2021 Supplemental Digital Content is available fowr this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.melanomaresearch.com. Correspondence of Gustavo Jacob Lourenço, PhD, Laboratory of Cancer Genetics, School of Medical Sciences, University of Campinas, 50 Vital Brasil Street, Barão Geraldo, Campinas, São Paulo 13083-888, Brazil, Tel: +55 19 35219120; e-mail: guslour@unicamp.br Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Updates on the diagnosis, current and future therapeutic options in Merkel-cell carcinoma

xlomafota13 shared this article with you from Inoreader Updates on the diagnosis, current and future therapeutic options in Merkel-cell carcinoma Via Melanoma Research - Published Ahead-of-Print Merkel-cell carcinoma (MCC) is a rare and extremely aggressive nonmelanocytic cutaneous neuroendocrine carcinoma. Historically, it has been associated with limited therapy options and poor prognosis. While its incidence has been rising over the last two decades, recent discoveries and a better understanding of its pathog enesis, viral association and immunologic features have allowed for the emergence of new therapies. Surgical excision with or without radiotherapy remains the first-line therapy for primary lesions without evidence of metastatic disease. The majority of MCC cases are regrettably diagnosed at advanced stages and oftentimes require systemic therapy. There have been several significant advances in the treatment of MCC in the last decade. Among these have been the development of immune checkpoint inhibitors targeting the programmed death protein-1 (PD-1)/programmed death ligand-1 (PDL-1). Despite recent success of immunotherapy, nearly 50% of patients diagnosed with MCC still succumb to the disease. Fortunately, there has been a number of new targeted therapies that hold great promise. Among them are phosphatidylinositide-3kinase (Pl3K) inhibitors, adoptive T-cell immunotherapy, activated NK-92 cells infusions and therapeutic vaccines. Additional emerging therapeutic targets include cel lular ubiquitin-specific processing protease 7 (Usp7) that restricts viral replication and IFN genes (STING), activation of which promotes an antitumor inflammatory response. Received 23 April 2021 Accepted 28 June 2021 Correspondence to Alla Turshudzhyan, DO, Department of Internal Medicine, University of Connecticut, 263 Farmington Avenue, Farmington, CT 06030-1235, USA, Tel: +1 860 679 2562; e-mail: turshudzhyan@uchc.edu Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Technical aspects of pediatric robotic pancreatic enucleation based on a case of an insulinoma

xlomafota13 shared this article with you from Inoreader Technical aspects of pediatric robotic pancreatic enucleation based on a case of an insulinoma Via The International Journal of Medical Robotics and Computer Assisted Surgery Abstract Background Insulinomas are rare insulin-producing pancreatic neuroendocrine tumors leading to severe episodes of hypoglycemia. Surgery is the predominant curative therapy. Methods We report here the first pediatric case of an insulinoma of the pancreatic body resected completely robotically under ultrasound guidance in a 10-year-old male with multiple endocrine neoplasia type 1. The port set-up was adapted for the narrowed dimensions of the pediatric peritoneal space. We comment on technical key steps for the organ preserving procedure that was performed in close proximity to critical anatomic structures, with supporting video. Preoperative diagnostics, including endoscopic ultrasound, to determine surgical management are highlighted. Results Following an uneventful post-operative course, the boy was discharged on day 11 with normalized glucose-metabolism. A pseudocyst developing after 4 weeks was treated with endoscopic stenting. Conclusions The applicability of a robotic surgical system in limited space conditions such as found in the pediatric abdominal cavity, is demonstrated here for pancreatic surgery. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A Novel Encountered‐type Master Device with Precise Manipulation for Robot‐Assisted Microsurgery

xlomafota13 shared this article with you from Inoreader A Novel Encountered‐type Master Device with Precise Manipulation for Robot‐Assisted Microsurgery Via The International Journal of Medical Robotics and Computer Assisted Surgery ABSTRACT Background The unconstrained master devices have emerged as attractive alternatives to the existing linkage-based counterparts. However, the conventional unconstrained master device's manipulation methods have several disadvantages in efficiency and precision. Methods We propose an encountered-type master device based on an electromagnetic tracking solution with a prismatic joint at the tip, capable of continuous spatial manipulation with the tip supported on the surface. We performed path-following task and pointing tasks to analyze the performance of the master device. Results The most convenient, efficient, accurate positioning and precise pointing were possible with a closed loop support condition. Moreover, the tasks under this condition were also completed with higher accuracy, and precision when applying lower motion scale factors. Conclusions The proposed master device allowed precise and accurate manipulation for microsurg ical tasks. Compared with the conventional unconstrained master devices, the proposed master device provides the ability to perform precise work with a clutching-free motion. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Initial Experience With a Recently Developed Lateral Wall Electrode

xlomafota13 shared this article with you from Inoreader Initial Experience With a Recently Developed Lateral Wall Electrode Via The Laryngoscope Objective To review our hearing preservation rates and speech recognition outcomes in patients undergoing cochlear implantation with a recently developed lateral wall electrode. Study design Retrospective cohort study. Methods Retrospective case series of all patients, both pediatric and adult, undergoing cochlear implantation with the Advanced Bionics Hifocus™ SlimJ electrode between December 2017 and January 2020. Main outcomes included hearing preservation rates using several definitions, speech recognition testing primarily through Arizona Biosciences (AzBio) and Consonant-Nucleus-Consonant (CNC) testing, intra- and postoperative complications. Results Sixty-one ears underwent implantation with the new electrode. Hearing preservation rates were 13.0% to 36.0% depending on the definition used. Speech recognition testing showed significant increases from pre- to postoperative condition (Implant-only AzBio: 24.1 to 48.3, P = .004, binaural AzBio: 46.1 to 65.9, P = .002, Implant-only CNC: 9.7 to 35.1, P < .001, binaural CNC: 29.8 to 59.40, P < .001) with last speech recognition testing occurring an average of 8.8 months postoperatively. The elderly population had the worst hearing preservation rates across all definitions. Five explantations were required due to two infections and three device failures. Conclusion Hearing preservation rates varied significantly depending on the definition used, but users experienced a significant improvement in speech recognition testing after implantation. More work is needed in the community to standardize the definition of residual hearing and hearing preservation. Level of Evidence 4 Laryngoscope, 2021 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Surgeon Positioning During Awake Laryngeal Surgery: An Ergonomic Analysis

xlomafota13 shared this article with you from Inoreader Surgeon Positioning During Awake Laryngeal Surgery: An Ergonomic Analysis Via The Laryngoscope Objectives While it is acknowledged that otolaryngologists performing microlaryngeal surgery can develop musculoskeletal symptoms due to suboptimal body positioning relative to the patient, flexible laryngoscopy and awake laryngeal surgeries (ALSs) can also pose ergonomic risk. This prospective study measured the effects of posture during ergonomically good and bad positions during laryngoscopy using ergonomic analysis, skin-surface electromyography (EMG), and self-reported pain ratings. Study Design Prospective cohort study. Methods Eight participants trained in laryngoscopy assumed four ergonomically distinct standing positions (side/near, side/far, front/near, front/far) at three different heights (neutral—top of patient's head in line with examiner's shoulder, high—6 inches above neutral, and low—6 inches below neutral) in relation to a simulated patient. Participants' postures were analyzed using the validated Rapid Upper Limb Assessment (RULA, 1 [best] to 7 [worst]) tool for the 12 positions. Participants then simulated ALS for 10 minutes in a bad position (low-side-far) and a good position (neutral-front-near) with 12 EMG sensors positioned on the limbs and torso. Results The position with the worst RULA score was the side/near/high (7.0), and the best was the front/near/neutral (4.5). EMG measurements revealed significant differences between simulated surgery in the bad and good positions, with bad position eliciting an average of 206% greater EMG root-mean-squared magnitude across all sampled muscles compared to the good posture (paired t-test, df = 7, P < .01), consistent with self-reported fatigue/pain when positioned poorly. Conclusion Quantitative and qualitative measurements demonstrate the impact of surgeon posture during simulated laryngoscopy and suggest ergonomically beneficial posture that should facilitate ALSs. Level of Evidence 3 Laryngoscope, 2021 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Salvage Following Transoral Laser Microsurgery for Early Glottic Cancer in National Veteran Database

xlomafota13 shared this article with you from Inoreader Salvage Following Transoral Laser Microsurgery for Early Glottic Cancer in National Veteran Database Via The Laryngoscope Objectives Transoral laser microsurgery (TLM) is commonly utilized for early glottic cancer and offers favorable oncologic and functional outcomes. However, the survival implications of salvage therapy for recurrent or persistent disease have not been definitively characterized. Study Design Retrospective, national database cohort study. Methods Data were extracted from Veterans Health Affairs (VHA) Informatics and Computing Infrastructure (VINCI) concerning the TLM-based management of T1–T2 glottic squamous cell carcinoma patients between 2000 and 2017. Patients were characterized as either requiring TLM-only, or in cases of persistent or recurrent local disease, TLM plus change in treatment modality (radiotherapy, chemoradiotherapy, or open surgery). Predictors of overall survival (OS), cancer-specific survival (CSS), and salvage-free survival were evaluated via Cox and Fine-Gray models. Results About 553 patients (70.9% T1a, 13.4% T1b, 15.7% T2) were included, with a median follow-up time of 74.5 months. The need for non-TLM salvage increased along with more advanced disease (11.7% T1a, 29.7% T1b, 32.2% T2). Compared to patients with T1a disease, those with T1b and T2 tumors initially treated with TLM had a significantly higher probability of receiving non-TLM salvage (T1b: HR 2.70, 95% CI: 1.61–4.54; T2: HR 3.02, 95% CI: 1.88–4.84). In a multivariable model, receipt of non-TLM salvage was not a significant predictor of either OS (HR = 0.91, 95% CI: 0.62–1.33, P = .624) or CSS (HR 1.21 95% CI 0.51–2.86, P = .667). Conclusion The majority of patients with early glottic cancer that are managed with TLM do not require additional salvage therapy. When non-TLM salvage was required, there was no decrement in OS or CSS. Level of Evidence 4 Laryngoscope, 2021 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hyperpigmentation in a Chinese family with autosomal dominant Cole disease

xlomafota13 shared this article with you from Inoreader Hyperpigmentation in a Chinese family with autosomal dominant Cole disease Via Experimental Dermatology Abstract Cole disease (OMIM 615522), caused by mutations in ENPP1, is a rare autosomal dominant or recessive genodermatosis characterized by guttate hypopigmentation and punctate palmoplantar keratoderma. To date, a few cases with autosomal recessive inheritance had been reported with hyperpigmentation. The aim of this case report is to investigate the molecular basis of individuals with hyperpigmentation, hypopigmentation, and punctate keratoderma in a Chinese family. A Chinese pedigree of suspected Cole disease with hyperpigmentation was subjected to mutation detection in the ENPP1 gene. All exons of the ENPP1 gene and adjacent exon-intron border sequences were amplified using polymerase chain reaction and directly sequenced. Three-dimensional (3D) models of the wild-type and mutated ENPP1 proteins were predicted by PyMOL viewer. Both of the proband and his affected father carried a heterozygous missense mutation p.C176R in ENPP1. In silico modeling of the ENPP1 wild-type and ENPP1 with the p.C176R mutation showed the residue Arg-176 disturbed the fold of the loop conformation. Based on clinical and genetic findings, a diagnosis of Cole disease was made. We identified a heterozygous mutation, p.C176R, in the ENPP1 gene in a Chinese family with Cole disease. This study clearly showed that hyperpigmentation could also occur in Cole disease in cases with autosomal dominant inheritance. Our data expand the phenotypic spectrum of ENPP1 mutations underlying Cole disease. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Morphological analysis of interstitial cells in murine epididymis using light microscopy and transmission electron microscopy

xlomafota13 shared this article with you from Inoreader Morphological analysis of interstitial cells in murine epididymis using light microscopy and transmission electron microscopy Via histochem Acta Histochem. 2021 Jul 20;123(6):151761. doi: 10.1016/j.acthis.2021.151761. Online ahead of print. ABSTRACT Smooth muscle contraction of the epididymis plays an important role in sperm transport. Although PDGFRα-positive interstitial cells (PDGFRα (+) ICs) are thought to be involved in controlling smooth muscle movement via intercellular signaling, they have not yet been reported to date in the epididymis. Therefore, we aimed to investigate the morphological characterist ics of PDGFRα (+) ICs in the interstitial space of the murine epididymis. Immunohistochemistry showed that PDGFRα (+) ICs co-labeled with CD34 (PDGFRα (+) CD34 (+) ICs were distributed in the interstitial space of the murine epididymis from the initial segment (IS) to the cauda of the epididymis. PDGFRα (+) ICs that were not co-labeled with CD34 (PDGFRα (+) CD34 (-) ICs) were observed just beneath the epithelium from the corpus to the cauda but not in the IS. Both types of PDGFRα (+) ICs were in close proximity to each other as well as the surrounding nerves and macrophages. In addition, PDGFRα (+) CD34 (-) ICs beneath the epithelium were also in close proximity to the basal cells. Using transmission electron microscopy, we identified ICs that possessed elongated and woven cellular processes and were in close proximity to each other, surrounding the cells in the interstitial space. In the murine epididymis, it is suggested that there are two subtypes of ICs that show differen t distribution patterns depending on the segment, which may reflect segmental differences in mechanisms of sperm transport, forming a cellular network by physical interactions in the murine epididymis. PMID:34298316 | DOI:10.1016/j.acthis.2021.151761 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

TNF-alpha May Exert Different Antitumor Effects in Response to Radioactive Iodine Therapy in Papillary Thyroid Cancer with/without Autoimmune Thyroiditis

xlomafota13 shared this article with you from Inoreader TNF-alpha May Exert Different Antitumor Effects in Response to Radioactive Iodine Therapy in Papillary Thyroid Cancer with/without Autoimmune Thyroiditis Via radioactive iodine Cancers (Basel). 2021 Jul 19;13(14):3609. doi: 10.3390/cancers13143609. ABSTRACT Autoimmune thyroiditis (AIT) may impair radioiodine (131I) uptake in papillary thyroid cancer (PTC). Finding the mechanisms that govern immune cells during 131I therapy of PTC with concomitant AIT (PTC + AIT) could provide a rationale. Our study aimed to evaluate the effects of 131I on anti-thyroglobulin antibodies (TgAb), matrix metalloproteinase-9 (MMP-9) and its tiss ue inhibitor TIMP-1 and tumor necrosis factor-α (TNF-α) and its receptors TNFR1 and TNFR2, in PTC and PTC + AIT patients. Peripheral blood was collected from 56 female patients with PTC and 32 with PTC + AIT before and 4 days after 131I (3.7 GBq). The serum levels of TgAb, MMP-9, TIMP-1, TNF-α, TNFR1 and TNFR2 were measured by ELISA. The mean radioactivity of blood samples collected after 131I intake was higher in the PTC + AIT group than in PTC (p < 0.001). In the PTC + AIT group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios decreased by 0.38-fold and 0.32-fold after 131I and were positively correlated with the MMP-9/TIMP-1 ratio (r = 0.48, p = 0.005, and r = 0.46, p = 0.007). In the PTC group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios increased by 3.17-fold and 3.33-fold and were negatively correlated with the MMP-9/TIMP-1 ratio (r = -0.62, p < 0.001 and r = -0.58, p < 0.001). Our results demonstrate that TNF-α ma y exert different antitumor effects in response to 131I therapy depending on the patient's immune profile. PMID:34298820 | DOI:10.3390/cancers13143609 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Pre-Therapeutic Measurements of Iodine Avidity in Papillary and Poorly Differentiated Thyroid Cancer Reveal Associations with Thyroglobulin Expression, Histological Variants and Ki-67 Index

xlomafota13 shared this article with you from Inoreader Pre-Therapeutic Measurements of Iodine Avidity in Papillary and Poorly Differentiated Thyroid Cancer Reveal Associations with Thyroglobulin Expression, Histological Variants and Ki-67 Index Via radioactive iodine Cancers (Basel). 2021 Jul 20;13(14):3627. doi: 10.3390/cancers13143627. ABSTRACT Papillary thyroid cancer (PTC) and poorly differentiated thyroid cancer (PDTC) are treated with radioiodine to reduce recurrence and to treat the spread of disease. Adequate iodine accumulation in cancer tissue, iodine avidity, is important for treatment effect. This study investigated which clinical and histological tumour characteristics correlate with avidity. To quantify avidity in cancer tissue, t racer amounts of iodine-131 were given to 45 patients with cytologically confirmed thyroid cancer. At pathology grossing, representative samples of tumour and lymph nodes were taken and subjected to radioactivity quantification ex vivo to determine avidity. Afterwards, samples underwent extended pathology work-up and analysis. We found that tumoural Tg expression and Ki-67 index were correlated with avidity, whereas tumour size and pT stage were not. The histological variant of thyroid cancer was also correlated with iodine avidity. Variants associated with worse clinical prognoses displayed lower avidity than variants with better prognoses. This work provides new information on which tumours have low iodine avidity. Lower avidity in aggressive histological PTC variants may explain their overall poorer prognoses. Our findings also suggest that radioiodine dosage could be adapted to Tg expression, Ki-67 index or histological variant instead of pT stage, potentially improving the effi cacy of radioiodine therapy. PMID:34298840 | DOI:10.3390/cancers13143627 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.