Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Δευτέρα 2 Ιανουαρίου 2023

Small Molecule-mediated Disruption of Ribosome Biogenesis Synergizes With FGFR Inhibitors to Suppress Glioma Cell Growth

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Abstract
Background
High-grade gliomas are malignant brain tumors characterized by aggressiveness and resistance to chemotherapy. Prognosis remains dismal, highlighting the need to identify novel molecular dependencies and targets. Ribosome biogenesis (RiBi), taking place in the nucleolus, represents a promising target as several cancer types rely on high RiBi rates to sustain proliferation. Publicly available transcriptomics data of glioma patients revealed a positive correlation between RiBi rates and histological grades. We, therefore, hypothesized that glioma cells could be susceptible to RiBi inhibition.
Methods
Transcriptomics data from glioma patients were analyzed for RiBi-related processes. BMH-21, a small molecule inhibitor of RNA polI transcription, was tested in adult and pediatric high-grade glioma cell lines and a zebrafish transplant model. Cellular phenotypes were evaluated by transcriptomics, cell cycle analysis, and vi ability assays. A chemical synergy screen was performed to identify drugs potentiating BMH-21-mediated effects.
Results
BMH-21 reduced glioma cell viability, induced apoptosis, and impaired the growth of transplanted glioma cells in zebrafish. Combining BMH-21 with TMZ potentiated cytotoxic effects. Moreover, BMH-21 synergized with FGFR inhibitor Erdafitinib, a top hit in the chemical synergy screen. RiBi inhibition using BMH-21, POLR1A siRNA, or Actinomycin D revealed engagement of the FGFR-FGF2 pathway. BMH-21 downregulated FGFR1 and SOX2 levels, whereas FGF2 was induced and released from the nucleolus.
Conclusions
This study conceptualizes the implementation of RiBi inhibition as a viable future therapeutic strategy for glioma and reveals an FGFR connection to the cellular response upon RiBi inhibition with potential translational value.
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Πέμπτη 29 Δεκεμβρίου 2022

Diagnosis and Management of Vocal Complications after Chondrolaryngoplasty

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Diagnosis and Management of Vocal Complications after Chondrolaryngoplasty

Anterior commissure dislocation should be suspected with signs of vocal impairment after chondrolaryngoplasty. Following proper diagnosis, resuspension of the anterior commissure via feminization laryngoplasty approach can be an effective reparative technique.


Objective

Transfeminine patients (transwomen/feminine nonbinary folks assigned male at birth) can undergo chondrolaryngoplasty ("tracheal shave") to feminize their neck appearance. While isolated cases of vocal complications have been reported following the procedure, aggregated outcomes have not been quantitatively studied. We present acoustic and stroboscopic data to describe a patient cohort with vocal complications after chondrolaryngoplasty and discuss reparative surgical technique.

Methods

Subjective and objective data, including videostroboscopy, were collected from patients with voice complaints after chondrolaryngoplasty. Dislocated anterior commissures were reconstructed with feminization laryngoplasty. Postoperative voice data were recorded and statistically compared to preoperative data using paired t-tests.

Results

On consecutive chart review, of the 94 transfeminine women with prior outside history of chondrolaryngoplasty, 27 (29%) reported chronic postoperative hoarseness, deepened pitch, or loss of upper register. On endoscopy, short, lax vocal folds with persistent anterior glottic gap and phase asymmetry were commonly noted; anterior commissure dislocation was confirmed in-office by using needle localization through absent thyroid cartilage. After open resuspension of the anterior commissure with feminization laryngoplasty, post-repair modal-speaking, minimum, and maximum fundamental frequencies (F0) increased on average by 7, 8, and 5 semitones, respectively (p < 0.01), when compared to pre-repair values. On average, perioperative maximum phonation time did not change significantly (p = 0.15). Average self-assessment of vocal femininity increased by 48% (p < 0.01).

Conclusion

Anterior commissure dislocation should be suspected with signs of vocal impairment after chondrolaryngoplasty. Following proper diagnosis, resuspension of the anterior commissure via feminization laryngoplasty approach can be an effective reparative technique.

Level of Evidence

This work represents a 2011 OCEBM Level 4 evidence as a case series Laryngoscope, 2022

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Reassessing Endotracheal Tube Size in Critically Ill Patients

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To the Editor We read with great interest the article by Esianor and colleagues on endotracheal tube (ETT) size in critically ill patients. Laryngotracheal injuries after invasive mechanical ventilation range from reversible pressure injuries to permanent damage, scarring, fistulas, and transmural lesions. Endotracheal tubes larger than 7.0 mm pose greater risk of laryngeal injury, and ETTs larger than 7.5 mm are often selected for critically ill patients in efforts to improve airflow resistance, avoid blockage, and facilitate procedural int erventions. Little is known as to whether larger ETTs improve recovery. Esianor and colleagues found no difference in 30-day all-cause in-hospital survival between patients with small, appropriate, or large-for-height endotracheal tubes. If larger tubes do not improve survival, is survivorship a better focus? Even with optimally sized tubes, translaryngeal intubation carries risks for impaired speech, swallowing, and airway protection. The investigation presented new questions around selection of ETT size, and has several implications for current practice and future investigation.
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Τετάρτη 28 Δεκεμβρίου 2022

three-dimensional airway changes after fibula flap reconstruction for benign and malignant tumours in the anterior mandible

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Surgical treatment of tumours in the anterior mandible and surrounding tissues may result in defects which can be restored by a fibula free flap. The upper airway may change during this process. The purpose of this retrospective study was to evaluate upper airway changes after fibula free flap reconstruction. A total of 37 patients who underwent anterior mandibulectomy and fibula free flap reconstruction between 2012 and 2020 were recruited. Patients with benign and malignant tumours involving the anterior mandible were included. (Source: International Journal of Oral and Maxillofacial Surgery)
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Esthetic and clinical outcomes after immediate placement and restoration: Comparison of two implant systems in the anterior maxilla—A cross‐sectional study

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Abstract

Aim

To assess the esthetic and clinical performance of a novel self-tapping implant system for single-tooth restorations in the esthetic zone after immediate placement and provisionalization.

Materials and Methods

This cross-sectional study included 52 patients contributing a total of 52 immediately placed and restored implants with ≥12 months after functional loading, comparing two different implant systems: Straumann® BLX (Institut Straumann AG, Basel, Switzerland; 25 patients) and Ankylos® (Dentsply Sirona, Hanau, Germany; 27 patients). As the primary outcome measure, peri-implant tissue esthetics were assessed by means of pink esthetics score (PES) rated by three independent clinicians. Moreover, as secondary outcome measures, the peri-implant tissue health was assessed by means of bleeding on probing, probing depth, and suppuration. Apart from that, the modified plaque index, keratinized mucosa width, and the presence of mucosal recessions were also assessed. When clinical signs suggested the possibility of peri-implantitis, radiographs were indicated to assess progressive bone loss.

Results

The mean PES ratings were 12.10 ± 1.10 for Ankylos versus 11.2 ± 1.86 for BLX, both achieving good esthetic results without significant differences (p = 0.143). There were no differences among most clinical parameters (plaque, bleeding on probing, probing depth, peri-implant mucosal recession), although peri-implant mucositis was present in one-third of the cases. The inter-rater agreement on esthetics was not significant (p < 0.250).

Conclusion

Within the limitations of the present study, it was concluded that the use of either BLX or Ankylos implant systems was associated to comparable peri-implant health and good pink esthetic outcomes during immediate implantation and restoration protocols, for at least 12 months.

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Τρίτη 27 Δεκεμβρίου 2022

Risk of waning humoral responses after inactivated or subunit recombinant SARS‐CoV‐2 vaccination in patients with chronic diseases: Findings from a prospective observational study in China

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Abstract

Heterogeneity of antibody responses has been reported in SARS-CoV-2 vaccination recipients with underlying diseases. We investigated the impact of the presence of comorbidities on the humoral response to SARS-CoV-2 vaccination in patients with chronic disease (PWCD) and assessed the effect of the number of comorbidities on the humoral response to vaccination. In this study, neutralizing antibodies (NAbs) and IgG antibodies against the receptor-binding domain (RBD-IgG) were monitored following a full-course vaccination. In total, 1400 PWCD (82.7%, inactivated vaccines; 17.3%, subunit recombinant vaccine) and 245 healthy controls (65.7% inactivated vaccines, 34.3% subunit recombinant vaccine) vaccinated with inactivated or subunit recombinant SARS-CoV-2 vaccines, were included. The seroconversion and antibody levels of the NAbs and RBD-IgG were different in the PWCD group compared with those in the control group. Chronic hepatitis B (odds ratio [OR]: 0.65; 95% confidence interval [C I]: 0.46–0.93), cancer (OR: 0.65; 95% CI: 0.42–0.99), and diabetes (OR: 0.50; 95% CI: 0.28–0.89) were associated with lower seroconversion of NAbs. Chronic kidney disease (OR: 0.29; 95% CI: 0.11–0.76), cancer (OR: 0.38; 95% CI: 0.23–0.62), and diabetes (OR: 0.37; 95% CI: 0.20–0.69) were associated with lower seroconversion of RBD-IgG. Only the presence of autoimmune disease showed significantly lower NAbs and RBD-IgG titers. Patients with most types of chronic diseases showed similar responses to the controls, but humoral responses were still significantly associated with the presence of ≥2 coexisting diseases. Our study suggested that humoral responses following SARS-CoV-2 vaccination are impaired in patients with certain chronic diseases.

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Coronavirus disease 2019 rebounds following nirmatrelvir/ritonavir treatment

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Abstract

Nirmatrelvir/ritonavir (NMV-r) is an effective anti-SARS-CoV-2 agent and has been recommended in the treatment of non-hospitalized patients with COVID-19. In rare occasions, some patients experience virologic and symptomatic rebound after initial resolution, which we call COVID-19 rebound after NMV-r. Although COVID rebound can also occur after molnupiravir treatment or even no antiviral treatment, we have more serious concern about the rebound after NMV-r, which remains the most effective antiviral. Due to a lack of information about its frequency, mechanism, outcomes, and management, we conducted this review to provide comprehensive and updated information to address these questions. Based on the limited evidence, the incidence of COVID-19 rebound after NMV-r was less than 2%, and most cases developed 5–15 days after initiating NMV-r treatment. Almost all reported cases had mild symptoms, and the clinical condition gradually subsided without additional treatment. Overall, the clinical outcome was favourable, and only a small number of patients required emergency department visits or hospitalization. Regarding virologic rebound, culturable SARS-CoV-2 with possible transmission was observed, so re-isolation may be needed.

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