The Role of PARP‐1 and NF‐κB in Bile‐Induced DNA Damage and Oncogenic Profile in Hypopharyngeal Cells

alexandrossfakianakis shared this article with you from Inoreader The Role of PARP‐1 and NF‐κB in Bile‐Induced DNA Damage and Oncogenic Profile in Hypopharyngeal Cells via The Laryngoscope Objectives/Hypothesis We recently documented that acidic bile, a gastroesophageal reflux content, can cause invasive hypopharyngeal squamous cell carcinoma, by inducing widespread DNA damage and promoting nuclear factor kappa B (NF-κB)-related oncogenic molecular events. Poly or adenosine diphosphate (ADP)-ribose polymerase-1 (PARP-1), a sensitive sensor of DNA damage, may interact with NF-κB. We hypothesized that PARP-1 is activated in hypopharyngeal cells (HCs) with marked DNA damage caused by acidic bile, hence there is an association between PARP-1 and NF-κB activation or its related oncogenic profile, in this process. Study Design In vitro study. Methods We targeted PARP-1 and NF-κB(p65), using pharmacologic inhibitors, 1.0 μM Rucaparib (AG014699) and 10 μM BAY 11–7082 {3-[4=methylphenyl)sulfonyl]-(2E)-propenenitrile}, respectively, or silencing their gene expression (siRNAs) and used immunofluorescence, luciferase, cell viability, direct enzyme-linked immunosorbent assays, and qPCR analysis to detect the effect of targeting PARP-1 or NF-κB in acidic bile-induced DNA damage, PARP-1, p-NF-κB, and B-cell lymphoma 2 (Bcl-2) expression, as well as NF-κB transcriptional activity, cell survival, and mRNA oncogenic phenotype in HCs. Results We showed that (i) PARP-1 is overexpressed by acidic bile, (ii) targeting NF-κB adequately prevents the acidic bile-induced DNA double-strand breaks (DSBs) by gamma H2A histone family member X (γH2AX), oxidative DNA/RNA damage, PARP-1 overexpression, anti-apoptotic mRNA phenotype, and cell survival, whereas (iii) targeting PARP-1 preserves elevated DNA damage, NF-κB activation, and anti-apoptotic phenotype. Conclusion We document for the first time that the activation of PARP-1 is an early event during bile reflux-related head and neck carcinogenesis and that NF-κB can mediate DNA damage and PARP-1 activation. Our data encourage further investigation into how acidic bile-induced activated NF-κB mediates DNA damage in hypopharyngeal carcinogenesis. Level of Evidence NA Laryngoscope, 2022 View on Web

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Early Neurocognitive Function With Propofol or Desflurane Anesthesia After Laser Laryngeal Surgery With Low Inspired Oxygen

alexandrossfakianakis shared this article with you from Inoreader Early Neurocognitive Function With Propofol or Desflurane Anesthesia After Laser Laryngeal Surgery With Low Inspired Oxygen via The Laryngoscope •End-tidal oxygen fraction decreases to 21% in approximately 6 min after inspired oxygen concentration is set to 30%. •Mini-mental state examination test (MMSE) score increases slightly as being measured repeatedly after surgery. •Postoperative (MMSE) scores are comparable between patients under either propofol- or desflurane-based anesthesia in the first 24 h after surgery. •Only a few patients develop cognitive impairment after short laser surgery even in elderly individuals with low inspired oxygen concentration. Purpose The effects of general anesthetics on cognitive impairment are unclear and complicated. Laser laryngeal surgery (LLS) requires the administration of low levels of oxygen, which may increase the risk of desaturation and brain function impairment. This prospective randomized trial aimed to compare the effects of desflurane and propofol-based general anesthesia on the occurrence of early postoperative cognitive decline in elderly patients undergoing LLS. Methods Seventy-three patients classified as American Society of Anesthesiologists grade I or II and at least 65 years of age were randomly allocated to receive either desflurane-based (Group D) or propofol-based (Group P) anesthesia during LLS. The standard anesthesia protocol was performed, with a bispectral index between 40 and 60 and a mean arterial pressure within 20% of baseline values. Intraoperative regional oxygen saturation values were recorded. Each patient was assessed using the mini-mental state examination (MMSE) test during the preoperative period (baseline), 30 min after extubation in the postanesthesia care unit, and 1, 3, and 24 h after surgery. Results MMSE scores improved slightly in both groups compared to baseline during the early postoperative period, but these increases were not statistically significant. No significant differences were identified in MMSE scores between groups. Only three patients (9.6%) in group D and one patient (3.1%) in group P developed cognitive impairment (p = 0.583). Conclusion Low intraoperative inspired oxygen concentration during short-duration LLS did not reduce early postoperative cognitive function in elderly patients. Desflurane or propofol-based anesthesia had similar effects on early neurocognition after LLS. Level of Evidence 2 Laryngoscope, 2022 View on Web

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Impact of Expanding Eligibility Criteria for Cochlear Implantation – Dynamic Modeling Study

alexandrossfakianakis shared this article with you from Inoreader Impact of Expanding Eligibility Criteria for Cochlear Implantation – Dynamic Modeling Study via The Laryngoscope The aim of this study was to explore the impact of further expanding unilateral CI criteria in those with severe hearing loss (HL) (61–80 dBHL) in terms of number of CI recipients, costs, quality of life, and cost-effectiveness. Based on its outcomes, the described expansion appears to constitute a cost-effective use of healthcare resources. However, it would require a significant increase in diagnostic, operative and rehabilitative capacity. These quantitative estimates can serve as a basis for wider societal deliberation on the question wheter such an increase can and should be pursued. Objectives Eligibility criteria for cochlear implantation (CI) are shifting due to technological and surgical improvements. The aim of this study was to explore the impact of further expanding unilateral CI criteria in those with severe hearing loss (HL) (61–80 dBHL) in terms of number of CI recipients, costs, quality of life, and cost-effectiveness. Methods A dynamic population-based Markov model was constructed mimicking the Dutch population in three age categories over a period of 20 years. Health states included severe HL (61–80 dBHL), profound HL (>81 dBHL), CI recipients, and no-CI recipients. Model parameters were based on published literature, (national) databases, expert opinion, and model calibration. Results If persons with severe HL would qualify and opt for CI similar to those with profound HL now, this would lead to a 6–7 times increase of new CI recipients and an associated increase in costs (€550 million) and QALYs (54.000) over a 20-year period (incremental cost utility ratio: 10.771 euros/QALY [2.5–97.5 percentiles: 1.252–23.171]). One-way-sensitivity analysis indicated that model outcomes were most sensitive to regaining employment, utility associated with having a CI, and costs of surgery and testing. Conclusion Our findings suggest that expanding eligibility for CI to persons with severe HL could be a cost-effective use of resources. Clearly, however, it would require a significant increase in diagnostic, operative, and rehabilitative capacity. Our quantitative estimates can serve as a basis for a wider societal deliberation on the question whether such an increase can and should be pursued. Level of Evidence N/A Laryngoscope, 2022 View on Web

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Stereotactic body radiotherapy extends the clinical benefit of PD-1 inhibitors in refractory recurrent/metastatic nasopharyngeal carcinoma

alexandrossfakianakis shared this article with you from Inoreader Stereotactic body radiotherapy extends the clinical benefit of PD-1 inhibitors in refractory recurrent/metastatic nasopharyngeal carcinoma via Radiation Oncology - Latest Articles Emerging evidence shows that immune checkpoint inhibitors lead to durable responses in a variety of cancers, including nasopharyngeal carcinoma (NPC), however, combination approaches (i.e., stereotactic body r... View on Web

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