D-2-hydroxyglutarate dehydrogenase in breast carcinoma as a potent prognostic marker associated with proliferation

xlomafota13 shared this article with you from Inoreader D-2-hydroxyglutarate dehydrogenase in breast carcinoma as a potent prognostic marker associated with proliferation Via Cellular and Molecular Biology Histol Histopathol. 2021 Jul 23:18362. doi: 10.14670/HH-18-362. Online ahead of print. ABSTRACT BACKGROUND: D-2-hydroxyglutarate dehydrogenase (D2HGDH) catalyzes D-2-hydroxyglutarate to α-ketoglutarate and is involved in the regulation of cellular energy and biosynthetic intermediates. Previously, D2HGDH was reported to decrease 2-hydroxyglutarate level in breast carcinoma cells, but no other report has examined D2HGDH in breast carcinoma, and its significance remains unknown. METHODS: We first immunolocalized D2HGDH in 224 invasive breast carcinomas and evaluated its clinicopathological significance. We next examined associations between gene expression of D2HGDH and α-ketoglutarate-dependent dioxygenases in 23 breast carcinoma tissues using the gene expression profile data. Finally, we examined the effects of D2HGDH on the proliferation in three breast carcinoma cells. RESULTS: D2HGDH immunoreactivity was detected in 49 % of invasive breast carcinomas, and the immunohistochemical D2HGDH status was positively associated with histological grade, HER2 and Ki-67, while it was inversely associated with estrogen receptor. Moreover, it was significantly associated with worse prognosis of the breast cancer patients, and it turned out to be an independent prognostic factor for both the disease-free and breast cancer-specific survival in these patients. Gene expression profile data revealed that D2HGDH expression was positively associated with the expression of 6 α-ketoglutarate-dependent dioxygenases (KDM3A, PLOD1, EGLN2, ALKBH1, ASPH and ALKBH7). Consequent in vitro experiments demonstrated that D2HGDH overexpression significantly increased the cell proliferation activity of MCF-7, T47D and MDA-MB-231 cells. CONCLUSION: These results suggest that D2HGDH plays an important role in the growth of breast carcinoma, possibly through regulating functions of α-ketoglutarate-dependent dioxygenases, and tha t D2HGDH status is a potent worse prognostic factor in breast cancer patients. PMID:34296423 | DOI:10.14670/HH-18-362 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Biologics for severe uncontrolled chronic rhinosinusitis with nasal polyps: a change management approach. Consensus of the Joint Committee of Italian Society of Otorhinolaryngology on biologics in rhinology

xlomafota13 shared this article with you from Inoreader Biologics for severe uncontrolled chronic rhinosinusitis with nasal polyps: a change management approach. Consensus of the Joint Committee of Italian Society of Otorhinolaryngology on biologics in rhinology Via Acta Otorhinolaryngol Ital Acta Otorhinolaryngol Ital. 2021 Jul 23. doi: 10.14639/0392-100X-N1614. Online ahead of print. NO ABSTRACT PMID:34297014 | DOI:10.14639/0392-100X-N1614 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Sclerotherapy with polidocanol microfoam in head and neck venous and lymphatic malformations

xlomafota13 shared this article with you from Inoreader Sclerotherapy with polidocanol microfoam in head and neck venous and lymphatic malformations Via Acta Otorhinolaryngol Ital Acta Otorhinolaryngol Ital. 2021 Jul 23. doi: 10.14639/0392-100X-N1310. Online ahead of print. ABSTRACT OBJECTIVE: Polidocanol sclerotherapy of head and neck venous malformations (VMs) and lymphatic malformations (LMs) has been reported only in limited series. In this manuscript we evaluated the efficacy and safety of polidocanol sclerotherapy in a series of head and neck venous and lymphatic malformations. METHODS: This retrospective observational study analysed data on 20 head and neck VMs and LMs that underwent to percutaneous or endoscopic intra-lesional 3% polidocanol microfoam sclerotherapy at our institution. Clinical response was ranked as excellent, moderate and poor based on volume reduction by MRI and resolution of symptoms. RESULTS: The median volume decreased from 19.3 mL to 5.8 mL after sclerotherapy (mean volume reduction: 72.98 ± 16.1%). An excellent-moderate response was observed in 94.4% of cases. We observed a mean volume reduction of 79.5 ± 16.1 in macrocystic LMs, of 76.1 ± 13.0% in VMs, of 60.5 ± 10.9% in mixed lymphatic ones and 42.5% in microcystic lymphatic ones. CONCLUSIONS: Polidocanol sclerotherapy appears to be an effective and safe treatment for venous and lymphatic head and neck malformations. We observed the best responses in macrocystic LMs and VMs, whereas mixed lymphatic ones showed a moderate response and microcystic lymphatic ones a poor response. PMID:34297013 | DOI:10.14639/0392-100X-N1310 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

THE 2021 EUROPEAN GROUP ON GRAVES' ORBITOPATHY (EUGOGO) CLINICAL PRACTICE GUIDELINES FOR THE MEDICAL MANAGEMENT OF GRAVES' ORBITOPATHY

xlomafota13 shared this article with you from Inoreader THE 2021 EUROPEAN GROUP ON GRAVES' ORBITOPATHY (EUGOGO) CLINICAL PRACTICE GUIDELINES FOR THE MEDICAL MANAGEMENT OF GRAVES' ORBITOPATHY Via radioactive iodine Eur J Endocrinol. 2021 Jul 1:EJE-21-0479.R1. doi: 10.1530/EJE-21-0479. Online ahead of print. ABSTRACT Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease (GD). Choice of treatment should be based on assessment of clinical activity and severity of GO. Early referral to specialized centers is fundamental for most patients with GO. Risk factors include smoking, thyroid dysfunction, high serum level of thyrotropin receptor antibodies, radioactive iodin e (RAI) treatment, and hypercholesterolemia. In mild and active GO, control of risk factors, local treatments and selenium (selenium-deficient areas) are usually sufficient; if RAI treatment is selected to manage GD, low-dose oral prednisone prophylaxis is needed, especially if risk factors coexist. For both active moderate-to-severe and sight threatening GO, antithyroid drugs are preferred when managing Graves' hyperthyroidism. In moderate-to-severe and active GO, intravenous (iv) glucocorticoids are more effective and better tolerated than oral glucocorticoids. Based on current evidence and efficacy/safety profile, costs and reimbursement, drug availability, long-term effectiveness and patient choice after extensive counselling, a combination of iv methylprednisolone and mycophenolate sodium is recommended as first-line treatment. A cumulative dose of 4.5 grams (g) of iv methylprednisolone in 12 weekly infusions is the optimal regimen. Alternatively, higher cumulative doses not ex ceeding 8 g can be used as monotherapy in most severe cases and constant/inconstant diplopia. Second-line treatments for moderate-to-severe and active GO include: a) a second course of iv methylprednisolone (7.5 g) subsequent to careful ophthalmic and biochemical evaluation, b) oral prednisone/prednisolone combined with either cyclosporine or azathioprine; c) orbital radiotherapy combined with oral or iv glucocorticoids, d) teprotumumab; e) rituximab and f) tocilizumab. Sight threatening GO is treated with several high single doses of iv methylprednisolone per week and, if unresponsive, with urgent orbital decompression. Rehabilitative surgery (orbital decompression, squint and eyelid surgery) is indicated for inactive residual GO manifestations. PMID:34297684 | DOI:10.1530/EJE-21-0479 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Status quo after one year of COVID-19 pandemic in otolaryngological hospital-based departments and private practices in Germany

xlomafota13 shared this article with you from Inoreader Status quo after one year of COVID-19 pandemic in otolaryngological hospital-based departments and private practices in Germany Via http://link.springer.com/journal/405,European archives of oto-rhino-laryngology,The European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino Eur Arch Otorhinolaryngol. 2021 Jul 23. doi: 10.1007/s00405-021-06992-2. Online ahead of print. ABSTRACT PURPOSE: The COVID-19 pandemic has affected healthcare systems worldwide. Data on the impact on otolaryngological clinics and private practices is sparse. This study aimed to present data on healthcare worker (HCW) screening, status of HCW, pre-interventional testing, the use of personal protective equipment (PPE) and the economic impact of the pandemic. METHODS: Otolaryngological private practices and hospital-based departments were surveyed nationwide using an online questionnaire. Participating facilities were recruited via the German Society for Oto-Rhino-Laryngology and the German Association for Otolaryngologists in Bavaria. RESULTS: 365 private practices (2776 employees) and 65 hospitals (2333 employees) were included. Significantly more hospitals (68.7%) than practices (40.5%) performed pre-interventional testing in their outpatients (p < 0.00). Most inpatients were tested in practices and hospitals (100.0% and 95.0%; p = 0.08). HCW screening was performed in 73.7% of practices and in 77.3% of hospitals (p = 0.54). Significantly more HCW infections were reported in private practices (4.7%) than in hospital (3.6%; p = 0.03). The private or home environment was the most frequent source of infection among HCW in hospitals (44%) and practices (63%). The use of PPE increased over the course of the pandemic. The number of procedures and the revenue decreased in 2020. CONCLUSION: The rate of pre-interventional testing among outpatients in otolaryngological practices is low and HCW infections were found to be more frequent in practices than in hospitals. In addition, a high rate of infections in otolaryngological HCW seems to stem from the private or home environment. PMID:34297182 | DOI:10.1007/s00405-021-06992-2 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

PERSISTENT DYSPHONIA IN HOSPITALISED COVID-19 PATIENTS

xlomafota13 shared this article with you from Inoreader PERSISTENT DYSPHONIA IN HOSPITALISED COVID-19 PATIENTS Via Journal of Voice INTRODUCTION: the main objective of this study is to estimate the prevalence of persistent dysphonia in hospitalised COVID-19 patients.METHODS: data were collected from those COVID-19 patients who, during the months of March to July 2020, were hospitalised in ward or intensive care unit at the University Hospital of Fuenlabrada. Patients with dysphonia prior to SARS-CoV-2 were excluded. Informed consent was obtained orally by a telephone call, as well as clinical and epidemiological data. Patients who reported persistent dysphonia were assessed using the Voice Handicap Index 10, the maximum phonation time, the s/z ratio and a fibrolaryngoscope examination. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Vocal self-perception of singers during COVID-19 pandemic

xlomafota13 shared this article with you from Inoreader Vocal self-perception of singers during COVID-19 pandemic Via Journal of Voice Objective: to compare the self-perception of vocal fatigue and use of singing voice during the COVID-19 pandemic between professional and amateur singers and to relate this self-perception with vocal use characteristics during this period. Methodology: Participants were 121 singers divided into professional singers group (PSG) (12 men and 20 women) comprising singers who depended exclusively on singing as a profession and an amateur singers group (ASG) (37 men and 52 women) of singers who did not depend exclusively on singing for their livelihood. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Low-dose ipilimumab combined with anti-PD-1 immunotherapy in patients with metastatic melanoma following anti-PD-1 treatment failure

xlomafota13 shared this article with you from Inoreader Low-dose ipilimumab combined with anti-PD-1 immunotherapy in patients with metastatic melanoma following anti-PD-1 treatment failure Via Melanoma Research - Published Ahead-of-Print Combined immunotherapy is associated with a significant risk of severe and potentially fatal immune-related adverse events (irAEs). Therefore, we retrospectively analyzed the side profile and efficacy of low-dose ipilimumab (1 mg/kg, IPI1) combined with anti-PD-1 immunotherapy in patients who progressed after anti-PD-1 mo notherapy. Nine patients with unresectable stage III or IV melanoma treated with combined low-dose ipilimumab (1 mg/kg, IPI1) and anti-PD-1 immunotherapy, following progression after anti-PD-1 treatment, were identified. Treatment response and irAEs were recorded. Grade 3 irAEs occurred in one-third of patients. Interestingly, there were no grade 4 or 5 irAEs. In fact, four out of the nine patients experienced no irAEs at all. One patient discontinued combined immunotherapy due to immune-related colitis. The mean time to the onset of grade 3 irAEs was 14.3 weeks. The objective response rate was 33.3% and a disease control rate of 66.7% was achieved. Median progression-free survival (PFS) was 5.7 months and median overall survival (OS) was 21.6 months. The median PFS when IPI1 and anti-PD-1 treatment was administered in the second-line setting was not reached, but only 2.8 months when used in subsequent treatment settings. Combined IPI1 and anti-PD-1 immunotherapy was well to lerated. Its use in the third-line or above setting was associated with a significantly poorer prognosis than in the second-line setting. Larger, prospective studies are required to evaluate the safety and efficacy of this dosing regimen following anti-PD-1 treatment failure. * Dr. Ewan A. Langan and Dr. Patrick Terheyden contributed equally to the writing of this article. Received 10 May 2021 Accepted 21 May 2021 Correspondence to Patrick Terheyden, MB, ChB, PhD, Department of Dermatology, University Clinic, Schleswig Holstein, Ratzeburger Allee, Luebeck, 23560, Germany Tel: +49 451 500 41510; e-mail: patrick.terheyden@uksh.de 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.

Proteomic profiles of melanoma cell-derived exosomes in plasma: discovery of potential biomarkers of melanoma progression

xlomafota13 shared this article with you from Inoreader Proteomic profiles of melanoma cell-derived exosomes in plasma: discovery of potential biomarkers of melanoma progression Via Melanoma Research - Published Ahead-of-Print Cancer liquid biopsy encompassing circulating tumor cells (CTC), circulating tumor DNA (ctDNA) and/or tumor-derived exosomes (TEX) emerges as a novel approach to early detection, noninvasive monitoring of responses to therapy and predicting patient survival. TEX are a key component of liquid biopsy because they mimic tumo r cells in their proteomic and genetic content. Two recent proteomic analyses of TEX released into plasma by melanoma cells confirms the potential of TEX as diagnostic and prognostic markers in melanoma. Received 22 April 2021 Accepted 10 June 2021 Correspondence to Theresa L. Whiteside, PhD, UPMC Hillman Cancer Center, UPCI Research Pavilion, Suite 1.27, 5117 Centre Avenue, Pittsburgh, PA 15213, USA, Tel: +1 412 624 0096; fax: +1 412 624 0264; e-mail: whitesidetl@upmc.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.

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.