Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Thursday, November 17, 2022

Oncologic Outcomes After Clinically Node-Negative Salvage Laryngectomy

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This cohort study investigates the association of elective nec k dissection vs observation with oncologic outcomes among patients who received clinically node-negative salvage total laryngectomy.
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Multimodale Therapie bei lokal fortgeschrittenem kutanem Plattenepithelkarzinom

alexandrossfakianakis shared this article with you from Inoreader

Laryngorhinootologie
DOI: 10.1055/a-1949-2936

Die Therapieoptionen für lokal fortgeschrittene oder metastasierte Plattenepithelkarzinome waren bisher stark begrenzt und nicht standardisiert. Durch die Zulassung des monoklonalen Antikörpers Cemiplimab, der gegen den programmed death-1-Rezeptor (PD-1) gerichtet ist, hat sich die Prognose der betroffenen Patienten deutlich gebessert, wobei z.T. anhaltende Komplettremissionen erzielt werden können.In der vorgestellten Kasuistik wurde ein multimorbider, 81-jähriger Patient aufgrund eines ausgedehnten Plattenepithelkarzinoms frontoparietal mit Schädelkalotteninfiltration und Einbruch nach intrakraniell zunächst mit Cemiplimab behandelt. Immunvermittelte Nebenwirkungen sind nicht aufgetreten. Bei klinischer und radiologischer Remission wurde der Restbefund interdisziplinär operativ versorgt, wobei die defekte Schädelkalotte rekonstruiert wurde. Histologisch wurde eine pathologische Komplettremissio n des Plattenepithelkarzinoms nachgewiesen. 6 Monate postoperativ ergab sich kein Anhalt für ein Lokalrezidiv oder Metastasen.Dieser Fall zeigt exemplarisch einen Patienten, der trotz seines hohen Alters und Ko-Morbidität von der Therapie mit Cemiplimab profitiert hat. Darüber hinaus demonstriert dieser Fall die Relevanz eines interdisziplinären/multimodalen Therapieregimes im Management dieser in der Inzidenz deutlich ansteigenden Tumorentität.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Staphylococcus aureus Carrier Types are not Evidence of Population Heterogeneity

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Abstract
Asymptomatic colonization by Staphylococcus aureus is a precursor for infection, so identifying the mode and source of transmission which leads to colonization could help target interventions. Longitudinal studies have shown that some people are persistently colonized for years, while others seem to carry S. aureus for weeks or less, and conventional wisdom attributes this disparity to an underlying risk factor in the persistently colonized. We analyze published data with mathematical models of acquisition and carriage to compare this hypothesis with alternatives. The null model assumes a homogeneous population and still produces highly variable colonization durations (mean of 1.94 years, 5th percentile 0.1 years, 95th percentile 5.8 years). Simulations show that this inherent variability, combined with censoring in longitudinal cohort studies, i s sufficient to produce the appearance of "persistent carriers," "intermittent carriers," and "noncarriers" in data. Our estimates for colonization duration exhibit sensitivity to the assumption that false positives can occur despite being rare, but our model-based approach simultaneously estimates specificity and sensitivity along with epidemiological parameters. Our results show it is plausible that S. aureus colonizes people indiscriminately, and improved understanding of the types of exposures which result in colonization is essential.
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Wednesday, November 16, 2022

Cardiovascular outcomes after tixagevimab and cilgavimab use for pre-exposure prophylaxis against COVID-19: a population-based propensity-matched cohort study

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Abstract
Tixagevimab and cilgavimab treatment was associated with higher rates of cardiovascular events in a post-hoc analysis of a phase 3 trial. In this large population-based propensity-matched study, we found no increased risk of cardiovascular events up to 90 days after tixagevimab and cilgavimab administration, including in patients with pre-existing cardiovascular disease.
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DNA virus oncoprotein HPV18 E7 selectively antagonizes cGAS‐STING‐triggered innate immune activation

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Cellular infections by DNA viruses trigger innate immune responses mediated by DNA sensors. The cyclic GMP–AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway has been identified as a DNA-sensing pathway that activates interferons in response to viral infection and, thus, mediates host defense against viruses. Previous studies have identified oncogenes E7 and E1A of the DNA tumor viruses, human papillomavirus 18 (HPV18) and adenovirus, respectively, as inhibitors of the cGAS-STING pathway. However, the function of STING in infected cells and the mechanism by which HPV18 E7 antagonizes STING-induced IFNβ production remain unknown. We report that HPV18 E7 selectively antagonizes STING-triggered NF-κB activation but not IRF3 activation. HPV18 E7 binds to STING in a region critical for NF-κB activation and blocks the nuclear accumulation of p65. Moreover, E7 inhibition of STING-triggered NF-κB activation is related to HPV pathogenic ity but not E7–Rb binding. HPV18 E7, SARS-CoV-2 ORF3a, HIV-2 Vpx, and KSHV vIRF1 selectively inhibited STING-triggered NF-κB or IRF3 activation, suggesting a convergent evolution among these viruses toward antagonizing host innate immunity. Collectively, selective suppression of the cGAS-STING pathway by viral proteins is likely to be a key pathogenic determinant, making it a promising target for treating oncogenic virus-induced tumor diseases.

This article is protected by copyright. All rights reserved.

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DNA virus oncoprotein HPV18 E7 selectively antagonizes cGAS‐STING‐triggered innate immune activation

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Cellular infections by DNA viruses trigger innate immune responses mediated by DNA sensors. The cyclic GMP–AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway has been identified as a DNA-sensing pathway that activates interferons in response to viral infection and, thus, mediates host defense against viruses. Previous studies have identified oncogenes E7 and E1A of the DNA tumor viruses, human papillomavirus 18 (HPV18) and adenovirus, respectively, as inhibitors of the cGAS-STING pathway. However, the function of STING in infected cells and the mechanism by which HPV18 E7 antagonizes STING-induced IFNβ production remain unknown. We report that HPV18 E7 selectively antagonizes STING-triggered NF-κB activation but not IRF3 activation. HPV18 E7 binds to STING in a region critical for NF-κB activation and blocks the nuclear accumulation of p65. Moreover, E7 inhibition of STING-triggered NF-κB activation is related to HPV pathogenic ity but not E7–Rb binding. HPV18 E7, SARS-CoV-2 ORF3a, HIV-2 Vpx, and KSHV vIRF1 selectively inhibited STING-triggered NF-κB or IRF3 activation, suggesting a convergent evolution among these viruses toward antagonizing host innate immunity. Collectively, selective suppression of the cGAS-STING pathway by viral proteins is likely to be a key pathogenic determinant, making it a promising target for treating oncogenic virus-induced tumor diseases.

This article is protected by copyright. All rights reserved.

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Reply to Letter to the Editor on disease severity and efficacy of homologous vaccination among patients infected with SARS‐CoV‐2 Delta or Omicron VOCs, compared to unvaccinated using main biomarkers

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Abstract

We appreciate the commenters' interest in our article detailing the "Disease severity and efficacy of homologous vaccination among patients infected with SARS-CoV-2 Delta or Omicron VOCs, compared to unvaccinated using main biomarkers

This article is protected by copyright. All rights reserved.

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