Αρχειοθήκη ιστολογίου

Κυριακή 10 Ιουλίου 2022

Voice and communication after open partial horizontal laryngectomies: A cross‐sectional outcome study

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Abstract

Objective

The present study evaluates voice and communication after open partial horizontal laryngectomies (OPHLs), according to surgery and patient-related variables.

Methods

Fifty-eight patients were included: 18 type I OPHL, 20 type II OPHL and 20 type III OPHL. Acoustic, aerodynamic, endoscopic, perceptual and self-assessment analyses were carried out. Surgery-related variables and patient-related variables were considered for the analysis.

Results

Type I OPHL revealed the best phonatory outcomes. Type II and type III OPHL showed similar and poor results, with a highly deteriorated voice quality. A significant difference in MTP was found for patients who had both arytenoids/cricoarytenoid units preserved. Age and time from surgery showed significant correlations with voice quality after OPHLs.

Conclusions

Voice and communication outcomes after OPHLs are heterogeneous and might be influenced by several factors. Knowing variables with a substantial impact on phonatory outcomes may help clinicians in the preoperative decision-making process and the postoperative rehabilitative program.

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Deriving prognostic significance from a molecular subtype model of laryngeal carcinoma

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Abstract

Background

This study explored whether laryngeal carcinoma could be divided into different subtypes based on molecular differences using a molecular subtype-prediction model.

Methods

We extracted data from the Cancer Genome Atlas and Gene Expression Omnibus databases and then performed unsupervised cluster analysis to identify discrete molecular subtypes of laryngeal carcinoma. Significance analysis of microarrays was performed to detect differentially expressed genes for each subtype, and gene set enrichment analysis and the GenCliP3 software were used to label gene functions and identify key pathways.

Results

We categorized 126 patients into C1 and C2 molecular subtypes associated with pathologic grade. The C2 subtype appeared more aggressive, with a worse prognosis. The most significant enrichment pathway of the C2 subtype was the Hedgehog pathway, and GLI1 was a core gene.

Conclusions

Laryngeal carcinoma can be divided into two subtypes based on differences in molecular expression, which could identify key molecules associated with prognosis.

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Influence of supplement administration of omega‐3 on the subcutaneous tissue response of endodontic sealers in Wistar Rats

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Abstract

Aim

Natural substances such as omega-3 have been used in the medical field due to their numerous properties and, in particular, modulating effect on the systemic and local inflammatory processes. Thus, this study evaluated the influence of omega-3 supplementation on the subcutaneous tissue response of endodontic sealers in Wistar Rats.

Methodology

Polyethylene tubes were implanted in the subcutaneous tissue of 48 animals (one empty for control and three filled with Sealapex, AH Plus or Endofill). The animals were treated with omega-3 (TO) or water (TW). Treatments started 15 days before implantation until euthanasia. After 5, 15 and 30 days (n=8), animals were euthanized and polyethylene tubes and surrounding tissue were removed and processed for histological analysis. The inflammatory reaction was analysed by Haematoxylin and Eosin stain and immunolabeling for IL-6 and TNF-α. The collagen maturity was analysed by picrosirius red stain and calcium deposition by von Kossa stain and polarized light. Results were statistically analysed (p<0.05).

Results

Among TW sealers groups, Endofill evoked a more intense inflammatory infiltrate compared with AH Plus and control in the 30-day period (p=0.009). However, in TO sealers groups, there was no difference among the sealers and control in all periods (p>0.05). Comparing each sealer as a function of the supplementation with water or omega-3, there are differences for Endofill (p=0.001) and Sealapex (p=0.005) in the 30-day period, presenting lower inflammatory infiltrate in the animals treated with omega 3. A higher percentage of immature fibres was observed at 15 and 30 days in the TO group, compared with TW group (p<0.05). The deposition of calcium particles was observed only by Sealapex in all periods, despite the supplementation procedure.

Conclusions

Omega-3 supplementation influence the tissue reactions of endodontic sealers, modulating inflammation, the immunolabeling of IL-6 and TNF-α, the repair process and it does not interfere with calcium deposition.

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Immediate curative effects of exercise therapy in patients with myalgia of the masticatory muscles

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Abstract

Background

Exercise therapy is occasionally considered as an initial treatment for temporomandibular disorders. However, pain can be exacerbated during exercise therapy.

Objective

To investigate the immediate curative effects of exercise therapy in patients with masticatory muscle myalgia.

Methods

Fifty-nine patients with masticatory muscle myalgia were included. Therapists performed exercise therapy (stretched the painful masseter and/or cervical muscles along the direction of muscle contraction) in 10 rounds of traction, each lasting 10 seconds. The patient's pain-free maximum mouth opening distance and degree of pain (VAS value) before and immediately after exercise therapy were compared using the Wilcoxon signed rank test. Mann-Whitney U test was used for the subgroup comparisons.

Results

Mouth opening increased from 41 (IQR 38–43) to 46 (IQR 43–48) mm, and pain alleviation from 48 (IQR 31–56) to 21 (IQR 10–56) immediately following exercise therapy (p < 0.001 for both). None of the patients experienced pain exacerbation or reduction in mouth opening post exercise. No difference in mouth opening distance changes according to sex, painful side, painful site, and therapist were observed (p > 0.05 for all). Pain reduction was greater in patients with unilateral pain (26, IQR 12–39) than those with bilateral (13, IQR 5–25) (p = 0.019). There were no differences in the change in the degree of pain according to sex, painful site, and therapist (p > 0.05 for all).

Conclusion

Exercise therapy immediately enlarged the mouth opening distance and reduced myalgia; therefore, it could be helpful in managing masticatory muscle myalgia.

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Πέμπτη 7 Ιουλίου 2022

Pharmacokinetics, Safety, and Efficacy of Gadopiclenol in Pediatric Patients Aged 2 to 17 Years

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imageObjectives The aim of this study was to evaluate the pharmacokinetic (PK) profile, safety, and efficacy of gadopiclenol, a new high-relaxivity gadolinium-based contrast agent, in children aged 2 to 17 years. Materials and Methods Children scheduled to undergo contrast-enhanced magnetic resonance imaging of the central nervous system (CNS cohort) or other organs (body cohort) were included sequentially into 3 age groups (12–17, 7–11, and 2–6 years). Gadopiclenol was administered at the dose of 0.05 mmol/kg. A sparse sampling approach was applied, with 4 blood samples per child collected up to 8 hours postinjection. Population PK modeling was used for the analysis, including the CNS cohort and adult subjects from a previous study. Adverse events were recorded, and efficacy was assessed for all children. Results Eighty children were included, 60 in the CNS cohort and 20 in the body cohort. The 2-compartment model with linear elimination from the central compartment developed in adults was also suitable for children. Pharmacokinetic parameters were very similar between adults and children. Terminal elimination half-life was 1.82 hours for adults and 1.77 to 1.29 hours for age groups 12–17 to 2–6 years. The median clearance ranged from 0.08 L/h/kg in adults and 12–17 years to 0.12 L/h/kg in 2–6 years. The median central and peripheral volumes of distribution were 0.11 to 0.12 L/kg and 0.06 L/kg, respectively, for both adults and children. Simulations of plasma concentrations showed minor differences, and median area under the curve was 590 mg·h/L for adults and 582 to 403 mg·h/L for children. Two patients (2.5%) experienced nonserious adverse events considered related to gadopiclenol: a mild QT interval prolongation and a moderate maculopapular rash. Despite the limited number of pat ients, this study showed that gadopiclenol improved lesion detection, visualization, and diagnostic confidence. Conclusions The PK profile of gadopiclenol in children aged 2 to 17 years was similar to that observed in adults. Thus, there is no indication for age-based dose adaptation, and comparable plasma gadopiclenol concentrations are predicted to be achieved with body weight–based dosing in this population. Gadopiclenol at 0.05 mmol/kg seems to have a good safety profile in these patients and could improve lesion detection and visualization, therefore providing better diagnostic confidence.
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Severity of SARS-CoV-2 Infection in Pregnancy

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Abstract
Background
Pregnancy represents a physiological state associated with increased vulnerability to severe outcomes from infectious diseases, both for the pregnant person and developing infant. The SARS-CoV-2 pandemic may have important health consequences for pregnant individuals, who may also be more reluctant than non-pregnant people to accept vaccination.
Methods
We sought to estimate the degree to which increased severity of SARS-CoV-2 outcomes can be attributed to pregnancy using a population-based SARS-CoV-2 case file from Ontario, Canada. Due to varying propensity to receive vaccination, and changes in dominant circulating viral strains over time, a time-matched cohort study was performed to evaluate the relative risk of severe illness in pregnant women with SARS-CoV-2 compared to other SARS-CoV-2 infected women of childbearing age (10 to 49 years old). Risk of severe SARS-CoV-2 outcomes was evaluated in pregnant women and time-matched non-pregnant controls using multivariable conditional logistic regression.
Results
Compared to the rest of the population, non-pregnant women of childbearing age had an elevated risk of infection (standardized morbidity ratio (SMR) 1.28), while risk of infection was reduced among pregnant women (SMR 0.43). After adjustment for confounding pregnant women had a markedly elevated risk of hospitalization (adjusted OR 4.96, 95% CI 3.86 to 6.37) and ICU admission (adjusted OR 6.58, 95% CI 3.29 to 13.18). The relative increase in hospitalization risk associated with pregnancy was greater in women without comorbidities than in those with comorbidities (P for heterogeneity 0.004).
Conclusions
Given the safety of SARS-CoV-2 vaccines in pregnancy, risk-benefit calculus strongly favours SARS-CoV-2 vaccination in pregnant women.
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Antibody and T-cell responses 6 months after COVID-19 mRNA-1273 vaccination in patients with chronic kidney disease, on dialysis, or living with a kidney transplant

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Abstract
Background
The immune response to COVID-19 vaccination is inferior in kidney transplant recipients (KTR), and to a lesser extent in patients on dialysis or with chronic kidney disease (CKD). We assessed the immune response 6 months after mRNA-1273 vaccination in kidney patients and compared this to controls.
Methods
152 participants with CKD stages G4/5 (eGFR <30  mL/min/1.73m2), 145 participants on dialysis, 267 KTR, and 181 controls were included. SARS-CoV-2 Spike S1-specific IgG antibodies were measured by fluorescent bead-based multiplex-immunoassay, neutralizing antibodies to ancestral, Delta and Omicron (BA.1) variants by plaque reduction, and T-cell responses by IFN-γ release assay.
Results
At 6 months after vaccination S1-specific antibodies were detected in 100% of controls, 98.7% of CKD G4/5 patients, 95.1% of dialysis patients, and 56.6% of KTR. These figures were comparable to the respons e rates at 28 days, but antibody levels waned significantly. Neutralization of the ancestral and Delta variant was detected in most participants, whereas neutralization of Omicron was mostly absent. S-specific T-cell responses were detected 6 months in 75.0% of controls, 69.4% of CKD G4/5 patients, 52.6% of dialysis patients, and 12.9% of KTR. T-cell responses at 6 months were significantly lower than responses at 28 days.
Conclusions
Although seropositivity rates at 6 months were comparable to that at 28 days after vaccination, significantly decreased antibody levels and T-cell responses were observed. The combination of low antibody levels, reduced T-cell responses, and absent neutralization of the newly-emerging variants indicates the need for additional boosts or alternative vaccination strategies in KTR.
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Strategies for Evaluating Anosmia Therapeutics in the COVID-19 Era

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jamanetwork.com

Two studies in this issue of JAMA Otolaryngology–Head & Neck Surgery evaluate the use of nasal theophylline, a phosphodiesterase inhibitor that may promote neural olfactory signaling and recovery for postviral olfactory dysfunction (OD). The first, a dose-modification Research Letter by Lee et al was conducted in patients with non-COVID-19–related hyposmia or anosmia secondary to viral infection and confirmed by the objective University of Pennsylvania Smell Identification Test. This open-label, dose-escalation trial provides an educational description of how to evaluate the appropriate dose for an emerging pharmacologic intervention. Specifically, the authors identified 400 mg of theophylline twice daily as a tolerated dosage. This was calculated as an equivalent oral dose of 20 mg. A phase 2 pilot study by Gupta et al was desig ned using this valuable information. Patients with suspected COVID-19–related OD completed the University of Pennsylvania Smell Identification Test and were randomized to either theophylline or placebo nasal irrigations for 6 weeks. This study was inconclusive regarding the clinical benefit of theophylline nasal irrigations, although there was suggested improvement by subjective assessments. The authors acknowledge several limitations, including small sample size, the virtual nature of the study design and subsequent inability to conduct endoscopic nasal examinations, lack of information regarding participant COVID-19 vaccination status, lack of polymerase chain reaction–confirmed COVID-19 infection, and short-term participant follow-up. These acknowledgments are justified, and many can be overcome in subsequent studies with adequate funding and time. However, the heterogeneous nature of COVID-19 and associated research make this area of work particularly challenging. Herein, we propose several approaches to improve the rigor of OD research in the COVID-19 era.
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Efficacy and Safety of Saline Nasal Irrigation Plus Theophylline for COVID-19–Related Olfactory Dysfunction

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jamanetwork.com

This randomized clinical trial evaluates the efficacy and safety of theophylline added to saline nasal irrigation compared with placebo for COVID-19–related olfactory dysfunction.
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Safety of High-Dose Nasal Theophylline Irrigation in the Treatment of Postviral Olfactory Dysfunction

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jamanetwork.com

This case series aims to determine the maximum tolerable dose of theophylline delivered via high-volume, low-pressure nasal saline irrigation for treatment of postviral olfactory dysfunction.
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