Παρασκευή 10 Φεβρουαρίου 2023

Endoscopic Multiport Approach for Exenteration of the Infratemporal Fossa

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Endoscopic Multiport Approach for Exenteration of the Infratemporal Fossa

New minimally endoscopic multiport approach to infratemporal fossa. Step-by-step cadaveric dissection.


Objective

To demonstrate anatomic relationships pertinent to the endoscopic multiport approach to the infratemporal fossa (ITF). Discuss advantages and limitations of each individual approach.

Study Design

Cadaveric study.

Methods

Endoscopic and endoscopic-assisted endonasal transpterygoid, sublabial transmaxillary, endoscopic transorbital, and endoscopic transoral approaches to accessing the ITF were completed in five silicone-injected fresh cadaveric specimens (10 sides) with the assistance of 0, 30, and 450 rods-lens endoscopes. Image guidance was used to confirm and document the anatomical relationships encountered in each approach.

Results

The endonasal endoscopic transpterygoid approach provides better visualization and more direct exposure to median structures. Endoscopic-assisted sublabial transmaxillary approach enhances the field of exposure, angle of attack, and ease of instrumentation to the lateral part of the ITF. Endoscopic-assisted transorbital approach via the inferior orbital fissure provided cephalic and anterior access. Endoscopic-assisted transoral approach complements the access to lesions extending inferior to the hard palate or far lateral to the mandibular condyle.

Conclusions

A combination of minimal access infratemporal approaches can provide adequate exposure of the entire ITF while avoiding some of the morbidity associated with open approaches.

Level of Evidence

NA Laryngoscope, 2023
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Office‐based Blue Laser Therapy of Vocal Fold Polyps: A Cohort of 18 Patients

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Objective

To investigate the effect of office-based blue laser therapy of vocal fold polyps on voice.

Methods

The medical records and video recordings of patients who underwent office-based laser therapy in a tertiary referral center between February 2020 and May 2020, and May 2021 and October 2022 was conducted. Only patients with vocal fold polyps who had undergone office-based blue laser therapy were included. The voice was evaluated before and after surgery using the Voice Handicap Index-10 (VHI-10), GRB perceptual evaluation, acoustic analysis, and maximum phonation time.

Results

A total of 18 patients were included. The mean age of the study group was 52.5 ± 11.94 years. The male-to-female ratio was 2:1. Ten patients of the total group (53.6%) had hemorrhagic polyps and the most common site was the mid-third of the vocal fold. All patients who presented for follow-up (n = 15) had partial or complete regression of the lesion (4 and 11, respectively). There was a significant decrease in the mean score of VHI-10 (17.6 ± 9.97 vs. 4.27 ± 5.76, p < 0.001) and in the means of grade of dysphonia (2.0 ± 0.73 to 0.5 ± 0.63, p < 0.001), roughness (1.88 ± 0.81 to 0.44 ± 0.51, p < 0.001) and breathiness (0.81 ± 0.75 to 0.13 ± 0.34 p < 0.001). There was also a marked decrease in the perturbation parameters (jitter and shimmer) and a significant increase in the MPT from 10.66 ± 4.22 s to 14.26 ± 6.26 s (p = 0.028).

Conclusion

Office-based blue laser therapy is an effective treatment modality in patients with vocal fold polyps.

Level of Evidence

4 Laryngoscope, 2023
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Dose‐Dependent Glucocorticoid Regulation of Transcription Factors in Vocal Fold Fibroblasts and Macrophages

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Dose-Dependent Glucocorticoid Regulation of Transcription Factors in Vocal Fold Fibroblasts and Macrophages

Steroid-based therapies are associated with variable outcomes for laryngeal disease. This study provides incremental data related to potential mechanisms of this variability including divergent effects on the glucocorticoid receptor phosphorylation.


Objective

Variable outcomes of glucocorticoid (GC) therapy for laryngeal disease are putatively due to diverse interactions of the GC receptor (GR) with cell signaling pathways, limited consideration regarding concentration-dependent effects, and inconsistent selection of GCs. In the current study, we evaluated the concentration-dependent effects of three frequently administered GCs on transcription factors with an emphasis on the phosphorylation of GR at Ser203 and Ser211 regulating the nuclear translocation of GR. This study provides foundational data regarding the diverse functions of GCs to optimize therapeutic approaches.

Study design

In vitro.

Methods

Human vocal fold fibroblasts and THP1-derived macrophages were treated with different concentrations of dexamethasone, methylprednisolone, and triamcinolone in combination with IFN-γ, TNF-α, or IL4. Phosphorylated STAT1, NF-κB family molecules, and phosphorylated STAT6 were analyzed by Western blotting. Ser211-phosphorylated GR (S211-pGR) levels relative to GAPDH and Ser203-phosphorylated GR (S203-pGR) were also analyzed.

Results

GCs differentially altered phosphorylated STAT1 and NF-κB family molecules in different cell types under IFN-γ and TNF-α stimuli. GCs did not alter phosphorylated STAT6 in IL4-treated macrophages. The three GCs were nearly equivalent. A lower concentration of dexamethasone increased S211-pGR/GAPDH ratios relative to increased S211-pGR/S203-pGR ratios regardless of cell type and treatment.

Conclusion

The three GCs employed in two cell lines had nearly equivalent effects on transcription factor regulation. Relatively high levels of Ser203-phosphorylation at low GC concentrations may be related to concentration-dependent differential effects of GCs in the two cell lines.

Level of Evidence

NA Laryngoscope, 2023
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Immunogenicity of novel DNA vaccines encoding receptor‐binding domain (RBD) dimer‐Fc fusing antigens derived from different SARS‐CoV‐2 variants of concern

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Abstract

The continuously emerging of SARS-CoV-2 variants of concern (VOCs) led to a decline in effectiveness of the first-generation vaccines. Therefore, optimized vaccines and vaccination strategies, which show advantages in protecting against VOCs, are urgently needed. Here we constructed an optimized DNA vaccine plasmid containing built-in CpG adjuvant, and designed vaccine candidates encoding five forms of antigens derived from Wuhan-Hu-1. The results showed that plasmid with RBD dimer-Fc fusing antigen (2RBD-Fc) induced the highest level of RBD-specific IgG and neutralizing antibodies in mice. Then 2dRBD-Fc and 2omRBD-Fc vaccines, respectively derived from delta and omicron VOCs, were constructed. The 2dRBD-Fc induced potent humoral and cellular immune responses, while the immunogenicity of 2omRBD-Fc was low. We also observed that sequential immunization with 2RBD-Fc, 2dRBD-Fc and 2omRBD-Fc effectively elicited neutralizing antibodies against each immunized strain, and RBD-specific T cell responses. To be noted, the Wuhan-Hu-1, delta and omicron neutralizing antibody titers induced by sequential immunization were comparable to that induced by repetitive immunization with 2RBD-Fc, 2dRBD-Fc or 2omRBD-Fc respectively. The results suggest that sequential immunization with DNA vaccines encoding potent antigens derived from different VOCs, may be a promising strategy to elicit immune responses against multiple variants.

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Comparable humoral and cellular immunity against Omicron variant BA.4/5 of once‐boosted BA.1/2 convalescents and twice‐boosted COVID‐19‐naïve individuals

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Abstract

The fourth vaccination dose confers additional protective immunity against SARS-CoV-2 infection in individuals with no prior coronavirus disease-19 (COVID-19). However, its immunological benefit against currently circulating BA.4/5 is unclear in individuals who have received a booster shot and been infected with Omicron variant BA.1/2. We analyzed immune responses in whom had been boosted once and did not have COVID-19 (n = 16), boosted once and had COVID-19 when BA.1/2 was dominant in the Korea (Hybrid-6M group, n = 27), and boosted twice and did not have COVID-19 (Vx4 group, n = 15). Antibody binding activities against RBDo BA.1 and RBDo.BA.4/5, antigen-specific memory CD4+ and CD8+ T-cell responses against BA.4/5, and B-cell responses against SARS-CoV-2 wild-type did not differ statistically between the Hybrid-6M and Vx4 groups. The humoral and cellular immune responses of the Hybrid-6M group against BA.4/5 were c omparable to those of the Vx4 group. Individuals who had been boosted and had an Omicron infection in early 2022 may not have high priority for an additional vaccination.

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SARS‐CoV‐2 NSP7 inhibits type I and III IFN production by targeting the RIG‐I/MDA5, TRIF, and STING signaling pathways

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Abstract

SARS-CoV-2 is a poor inducer of innate antiviral immunity, and the underlying mechanism still needs further investigation. Here, we reported that SARS-CoV-2 NSP7 inhibited the production of type I and III IFNs by targeting the RIG-I/MDA5, TLR3-TRIF, and cGAS-STING signaling pathways. SARS-CoV-2 NSP7 suppressed the expression of IFNs and IFN-stimulated genes induced by poly (I:C) transfection and infection with Sendai virus or SARS-CoV-2 virus-like particles. NSP7 impaired type I and III IFN production activated by components of the cytosolic dsRNA-sensing pathway, including RIG-I, MDA5, and MAVS, but not TBK1, IKKε, and IRF3-5D, an active form of IRF3. In addition, NSP7 also suppressed TRIF- and STING-induced IFN responses. Mechanistically, NSP7 associated with RIG-I and MDA5 prevented the formation of the RIG-I/MDA5−MAVS signalosome and interacted with TRIF and STING to inhibit TRIF-TBK1 and STING-TBK1 complex formation, thus reducing the subsequent IRF3 phosphorylation and nu clear translocation that are essential for IFN induction. In addition, ectopic expression of NSP7 impeded innate immune activation and facilitated virus replication. Taken together, SARS-CoV-2 NSP7 dampens type I and III IFN responses via disruption of the signal transduction of the RIG-I/MDA5−MAVS, TLR3-TRIF, and cGAS-STING signaling pathways, thus providing novel insights into the interactions between SARS-CoV-2 and innate antiviral immunity.

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Friends or foes: The mononuclear phagocyte system in ischemic stroke

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Friends or foes: The mononuclear phagocyte system in ischemic stroke

Pathophysiological effects of mononuclear phagocyte system MPS in ischemic stroke.


Abstract

Ischemic stroke (IS) is a major cause of disability and death in adults, and the immune response plays an indispensable role in its pathological process. After the onset of IS, an inflammatory storm, with the infiltration and mobilization of the mononuclear phagocyte system (MPS), is triggered in the brain. Microglia are rapidly activated in situ, followed by waves of circulating monocytes into the ischemic area. Activated microglia and monocytes/macrophages are mainly distributed in the peri-infarct area. These cells have similar morphology and functions, such as secreting cytokines and phagocytosis. Previously, the presence of the MPS was considered a marker of an exacerbated inflammatory response that contributes to brain damage. However, recent studies have suggested a rather complicated role of the MPS in IS. Here, we reviewed articles focusing on various functions of the MPS among different phases of IS, including recruitment, polarization, phagocytosis, angiogenesis, and in teraction with other types of cells. Moreover, due to the characteristics of the MPS, we also noted clinical research addressing alterations in the MPS as potential biomarkers for IS patients for the purposes of predicting prognosis and developing novel therapeutic strategies.
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The risk of acute myocardial infarction among patients with laboratory-confirmed invasive pneumococcal disease: a self-controlled case series study

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Abstract
Background
Major cardiovascular events, including acute myocardial infarction (AMI), have been reported among patients with certain viral and bacterial infections. Yet, whether invasive pneumococcal disease (IPD) increases the risk of AMI remains unclear. We examined whether laboratory-confirmed IPD was associated with the risk of AMI.
Methods
We conducted a self-controlled case series analysis among adult Tennessee residents with evidence of a first AM I hospitalization (2003-2019). Patient follow-up started 1 year prior to the earliest AMI and continued through the date of death, 1 year after AMI or end of study (12/2019). Periods for AMI assessment included the 7 to 1 days before IPD-specimen collection (pre IPD detection), day 0 through day 7 after IPD-specimen collection (current IPD), the 8 to 28 days after IPD-specimen collection (post IPD), and a control period (all other follow-up time). We used conditional Poisson regression to calculate incidence rate ratios and 95% confidence intervals (CI) for each risk period compared to control periods using within-person comparisons.
Results
We studied 324 patients hospitalized for AMI with a laboratory-confirmed IPD within 1 year before or after the AMI hospitalization. The incidence of AMI was significantly higher during the pre-IPD detection period (IRR:10.29; CI:6.33-16.73) and current IPD (IRR: 92.95; CI:72.17-119.71) periods, but non-significantly elevated in the post -IPD risk period (IRR: 1.83; CI:0.86-3.91) compared to control periods. An elevated AMI incidence was also observed in the post-IPD control period (29 to 364 days after IPD) [IRR: 2.95; CI:2.01-4.32].
Conclusions
Hospitalizations with AMI were strongly associated with laboratory-confirmed IPD.
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Prevalence of ocular candidiasis and Candida endophthalmitis in patients with candidemia: A systematic review and meta-analysis

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Abstract
Background
Infectious diseases and ophthalmology professional societies have disagreed regarding ocular screening in patients with candidemia. This study aimed to summarize the current evidence on the prevalence of ocular candidiasis (OC) and Candida endophthalmitis (CE) according to the standardized definitions.
Methods
A literature search was conducted from the 1990s through October 16th, 2022, using PubMed, Emb ase, and SCOPUS. Pooled prevalence of ocular complications was derived from generalized linear mixed models. (PROSPERO CRD42022326610)
Results
A total of 70 and 35 studies were included in the meta-analysis for OC and concordant CE (chorioretinitis with vitreous involvement), respectively. This study represented 8,599 patients with candidemia who underwent ophthalmologic examination. The pooled prevalence [95% confidence interval] of OC, overall CE, concordant CE, and discordant CE were 10.7% [8.4%-13.5%], 3.1% [2.1%-4.5%], 1.8% [1.3%-2.6%], and 7.4% [4.5%-12%] of patients screened, respectively. Studies from Asian countries had significantly higher concordant CE prevalence of patients screened [95% CI] of 3.6% [2.9% - 4.6%] compared to studies from European countries of 1.4% [0.4% - 5%] and American countries of 1.4% [0.9% - 2.2%], p-value <0.01. Presence of total parenteral nutrition and C. albicans were associated with CE with p ooled odds ratios [95% CI] of 6.92 [3.58–13.36] and 3.02 [1.67–5.46], respectively.
Conclusion
Prevalence of concordant CE overall and among Asian countries was two-times and four-times higher than the prevalence previously reported by American Academy of Ophthalmology of < 0.9%, respectively. There is an urgent need to study optimal screening protocols and to establish joint recommendations by the Infectious Diseases and Ophthalmology Societies.
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The Long Outer-Hair-Cell RC Time Constant: A Feature, Not a Bug, of the Mammalian Cochlea

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AbstractThe cochlea of the mammalian inner ear includes an active, hydromechanical amplifier thought to arise via the piezoelectric action of the outer hair cells (OHCs). A classic problem of cochlear biophysics is that theRC (resistance-capacitance) time constant of the hair-cell membrane appears inconveniently long, producing an effective cut-off frequency much lower than that of most audible sounds. The longRC time constant implies that the OHC receptor potential —and hence its electromotile response—decreases by roughly two orders of magnitude over the frequency range of mammalian hearing, casting doubt on the hypothesized role of cycle-by-cycle OHC-based amplification in mammalian hearing. Here, we review published data and basic physics to show that t he "RC problem " has bee...
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