Πέμπτη 22 Σεπτεμβρίου 2022

Longitudinal Effects of Base of Tongue Concurrent Chemoradiation Therapy in a Pre‐Clinical Model

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Longitudinal Effects of Base of Tongue Concurrent Chemoradiation Therapy in a Pre-Clinical Model

We present a clinically relevant animal model quantifying the effects of concurrent chemoradiation therapy (CCRT) on tongue strength and elasticity over time. This study demonstrates an increasing difference in tongue strength over time between control animals and those exposed to CCRT. Tongue elasticity was not significantly affected by CCRT, suggesting that changes in strength may not be caused by fibrosis during the time period studied.


Background/Objectives

Base of tongue (BOT) dysfunction is common following oropharyngeal concurrent chemoradiation therapy (CCRT). We present a clinically relevant animal model quantifying the effects of CCRT on tongue strength and elasticity over time.

Methods

Fifty-three male and 53 female Sprague–Dawley rats were randomized to control or experimental groups. Experimental animals received cisplatin, 5-fluorouracil, and 5 fractions of 7 Gy directed to the BOT. Controls received no intervention. At 2 weeks, 5 months, or 10 months after CCRT, animals underwent non-survival surgery to measure twitch and tetanic tongue strength, which were analyzed using multivariate linear mixed effects models. Tongue displacement, a surrogate for tongue elasticity, was also determined via stress–strain testing and analyzed via a multivariate linear mixed effects model.

Results

Reporting the combined results of both sexes, the estimated experimental group mean peak twitch forces became more divergent over time compared to controls, being 8.3% lower than controls at 2 weeks post-CCRT, 15.7% lower at 5 months, and 31.6% lower at 10 months. Estimated experimental group mean peak tetanic forces followed a similar course and were 2.9% lower than controls at 2 weeks post CCRT, 20.7% lower at 5 months, and 27.0% lower at 10 months. Stress–strain testing did not find CCRT to have a significant effect on tongue displacement across experimental timepoints.

Conclusions

This study demonstrates an increasing difference in tongue strength over time between controls and animals exposed to CCRT. Tongue elasticity was not significantly affected by CCRT, suggesting that changes in strength may not be caused by fibrosis.

Level of Evidence

NA Laryngoscope, 2022

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Cetuximab-Based vs Carboplatin-Based Chemoradiotherapy for Patients With Head and Neck Cancer

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jamanetwork.com

This cohort study compares survival with cetuximab-based and carboplatin-based chemoradiotherapy in locally advanced head and neck squamous cell carcinoma.
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Validation of Pain Catastrophizing Scale on Breast Cancer Survivor

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Abstract

Introduction

Pain Catastrophizing Scale (PCS) is the most used scale to measure pain catastrophizing. In breast cancer survivors (BCS), pain catastrophizing is related to upper-limbs dysfunction and disability. This study aimed to assess the internal consistency, internal structure and convergent validity of the Spanish version of the PCS in Spanish BCS

Material and Methods

BCS were recruited from the service of Medical Oncology of the University Clinical Hospital Virgen de la Victoria, in Málaga (Spain). The psychometric properties were evaluated with analyses factor structure by maximum likelihood extraction (MLE), internal consistency, and construct validity by confirmatory factor analysis (CFA).

Results

Factor structure was three-dimensional, and one item was removed due to cross-loading. The new 12-items PCS showed a high internal consistency for the total score (α=0.91) and a good homogeneity, and CFA revealed a satisfactory fit. PCS showed an acceptable correlation with FACS (r=0.53, p<0.01)

Conclusion

PCS is a valid and reliable instrument to evaluate pain catastrophizing in Spanish BCS. This tool may help clinicians in the management of pain by assessing pain and by measuring the effect of interventions.

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Perspectives from recent advances of Helicobacter pylori vaccines research

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Abstract

Background

Helicobacter pylori (H. pylori) infection is the main factor leading to some gastric diseases. Currently, H. pylori infection is primarily treated with antibiotics. However, with the widespread application of antibiotics, H. pylori resistance to antibiotics has also gradually increased year by year. Vaccines may be an alternative solution to clear H. pylori.

Aims

By reviewing the recent progress on H. pylori vaccines, we expected it to lead to more research efforts to accelerate breakthroughs in this field.

Materials & Methods

We searched the research on H. pylori vaccine in recent years through PubMed®, and then classified and summarized these studies.

Results

The study of the pathogenic mechanism of H. pylori has led to the development of vaccines using some antigens, such as urease, catalase, and heat shock protein (Hsp). Based on these antigens, whole-cell, subunit, nucleic acid, vector, and H. pylori exosome vaccines have been tested.

Discussion

At present, researchers have developed many types of vaccines, such as whole cell vaccines, subunit vaccines, vector vaccines, etc. However, although some of these vaccines induced protective immunity in mouse models, only a few were able to move into human trials. We propose that mRNA vaccine may play an important role in preventing or treating H. pylori infection. The current study shows that we have developed various types of vaccines based on the virulence factors of H. pylori. However, only a few vaccines have entered human clinical trials. In order to improve the efficacy of vaccines, it is necessary to enhance T-cell immunity.

Conclusion

We should fully understand the pathogenic mechanism of H. pylori and find its core antigen as a vaccine target.

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Τετάρτη 21 Σεπτεμβρίου 2022

Ad5‐nCoV booster and Omicron variant breakthrough infection following two doses of inactivated vaccine elicit comparable antibody levels against Omicron variants

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Abstract

Background

Little information is available for antibody levels against SARS-CoV-2 variants of concern induced by Omicron breakthrough infection and a third booster with an inactivated vaccine (InV) or Ad5-nCoV in people with completion of two InV doses.

Methods

Plasma was collected from InV pre-vaccinated Omicron infected patients (OIPs), unvaccinated OIPs between 0-22 days, and healthy donors (HDs) 14 days or 6 months after the second doses of an InV and 14 days after a homogenous booster or heterologous booster of Ad5-nCoV. Anti-Wuhan-, Anti-Delta-, and Anti-Omicron-receptor binding domain (RBD)-IgG titers were detected using enzyme-linked immunosorbent assay.

Results

InV pre-vaccinated OIPs had higher anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers compared to unvaccinated OIPs. Anti-Wuhan-RBD-IgG titers sharply increased in InV pre-vaccinated OIPs 0-5 days post-infection (DPI), while the geometric mean titers (GMTs) of anti-Delta- and anti-Omicron-RBD-IgG were 3.3- and 12.0-fold lower. Then, the GMT of anti-Delta- and anti-Omicron-RBD-IgG increased to 35112 and 28186 during 11-22 DPI, about 2.6- and 3.2-fold lower, respectively, than the anti-Wuhan-RBD-IgG titer. The anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers declined over time in HDs after two doses of an InV, with 25.2-, 5.6-, and 4.5-fold declination, respectively, at 6 months relative to the titers at 14 days after the second vaccination. Anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers elicited by a heterologous Ad5-nCoV booster were significantly higher than those elicited by an InV booster, comparable to those in InV pre-vaccinated OIPs.

Conclusion

InV and Ad5-nCoV booster could improve humoral immunity against Omicron variants. Of these, the Ad5-nCoV booster is a better alternative.

This article is protected by copyright. All rights reserved.

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Two stage, hybrid endovascular and open surgical approach to treat difficult carotid body tumors

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Abstract

Objective

Present the feasibility, applicability, clinical effectiveness, and results of complicated Shamblin II or III carotid body tumors treated with a two-stage hybrid surgical approach.

Materials and Methods

Retrospective, observational, cross-sectional, descriptive study of the successful treatment of 16 cases of difficult Shamblin II or III carotid body tumors, consisting of a two-stage surgical approach. We conducted a retrospective, observational, cross-sectional, descriptive study of a series of patients with complicated Shamblin II or III carotid body tumors, which we treated with a two-stage hybrid surgical procedure, in which we first placed a carotid endoprosthesis and 45 days later performed surgical resection of the tumor, following our originally published technique. This study was conducted from February, 2007 to November, 2019, in a third level care centre.

Results

We treated 16 patients with a mean age of 50.5 years. All resided at more than 2000 meters above sea level. In all 16 a complete resection was performed. The average duration of surgery was 103.9 min, the average intraoperative bleeding was 69 ml. There were three cases of neuropraxia. The ansa cervicalis nerve had to be sectioned in three cases and there was permanent upper laryngeal nerve injury in two cases. There were no permanent cerebrovascular injuries from placement of the endoprostheses. One patient developed transient cerebral ischaemia (TIA) with no long-term sequelae. There were two cases of asymptomatic late occlusion of the endoprostheses. The average initial volume of the tumors was 54.4 cc. The average tumor volume 35 days after implant of the endoprosthesis was 30.9 cc.

Symptoms

Presence of tumors in the neck in all cases and two cases of dysphagia.

Conclusion

This two-stage hybrid technique allowed for the complete resection of difficult Shamblin II or III carotid body tumors, with one case of TIA and two with permanent upper laryngeal nerve injuries and without mortality.

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Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection

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Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection

The human frontal cortex of SAD, FAD, and APOEch is characterized by specific astrocyte phenotypes which define the integrity of Gliovascular unit. ApoE3ch mutation in an E280A carrier might be related to the promotion of astrocytic and gliovascular homeostatisis despite the massive load of Aβ. This study provides new insights into the potential relevance of the gliovascular unit in the development and protection of AD.


Abstract

In response to brain insults, astrocytes become reactive, promoting protection and tissue repair. However, astroglial reactivity is typical of brain pathologies, including Alzheimer's disease (AD). Considering the heterogeneity of the reactive response, the role of astrocytes in the course of different forms of AD has been underestimated. Colombia has the largest human group known to have familial AD (FAD). This group carries the autosomal dominant and fully penetrant mutation E280A in PSEN1, which causes early-onset AD. Recently, our group identified an E280A carrier who did not develop FAD. The individual was homozygous for the Christchurch mutation R136S in APOE3 (APOEch). Remarkably, APOE is the main genetic risk factor for developing sporadic AD (SAD) and most of cerebral ApoE is produced by astroglia. Here, we characterized astrocyte properties related to reactivity, glutamate homeostasis, and structural integrity of the gliovascular unit (GVU), as factors that could underlie the pathogenesis or protection of AD. Specifically, through histological and 3D microscopy analyses of postmortem samples, we briefly describe the histopathology and cytoarchitecture of the frontal cortex of SAD, FAD, and APOEch, and demonstrate that, while astrodegeneration and vascular deterioration are prominent in SAD, FAD is characterized by hyperreactive-like glia, and APOEch displays the mildest astrocytic and vascular alterations despite having the highest burden of Aβ. Notably, astroglial, gliovascular, and vascular disturbances, as well as brain cell death, correlate with the specific astrocytic phenotypes identified in each condition. This study provides new insights into the potential relevance of the gliovasculature in the development and protection of AD. To our knowledge, this is the first study assessing the components of the GVU in human samples of SAD, FAD, and APOEch.

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