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Τρίτη 18 Οκτωβρίου 2022

Adoption of adjuvant chemotherapy in high‐risk salivary gland malignancies

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Abstract

Background

The present study characterizes national trends in the utilization of adjuvant chemotherapy to treat salivary gland malignancies.

Methods

The National Cancer Database was queried for salivary gland malignancies treated by surgery with radiation in 2004–2019. Proportions of patients receiving adjuvant chemotherapy over the study period were analyzed by linear regression. The impact of chemotherapy on overall survival was assessed using Kaplan–Meier and Cox proportional hazards analyses.

Results

Among 15 965 patients meeting inclusion criteria, 2355 (14.8%) received adjuvant chemotherapy. Chemotherapy utilization significantly increased from 4.9% to 16.5% over the study period (p < 0.001). No survival benefit was observed with adjuvant chemotherapy on propensity score-matched Kaplan–Meier analysis (HR: 0.98; 95% CI: 0.86–1.11; p = 0.72) or multivariable Cox regression (HR: 0.92; 95% CI: 0.78–1.09; p = 0.34).

Conclusions

Adjuvant chemotherapy has been increasingly utilized to treat salivary gland malignancies in recent years. Our findings highlight the importance of obtaining high-quality prospective data regarding the benefit of chemotherapy.

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Tamoxifen Alters TGF‐β1/Smad Signaling in Vocal Fold Injury

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Tamoxifen Alters TGF-β1/Smad Signaling in Vocal Fold Injury

This study investigated the effects of tamoxifen on acute vocal fold injury in a preclinical model. The antifibrotic actions of tamoxifen appear to be mediated by transforming growth factor beta 1/Smad signaling providing a novel target for intervention.


Objectives

Effective treatments for vocal fold fibrosis remain elusive. Tamoxifen (TAM) is a selective estrogen receptor modulator and was recently reported to have antifibrotic actions. We hypothesized that TAM inhibits vocal fold fibrosis via altered transforming growth factor beta 1 (TGF-β1) signaling. Both in vitro and in vivo approaches were employed to address this hypothesis.

Methods

In vitro, vocal fold fibroblasts were treated with TAM (10−8 or 10−9 M) ± TGF-β1 (10 ng/ml) to quantify cell proliferation. The effects of TAM on genes related to fibrosis were quantified via quantitative real-time polymerase chain reaction. In vivo, rat vocal folds were unilaterally injured, and TAM was administered by oral gavage from pre-injury day 5 to post-injury day 7. The rats were randomized into two groups: 0 mg/kg/day (sham) and 50 mg/kg/day (TAM). Histological changes were examined on day 56 to assess tissue architecture.

Results

TAM (10−8 M) did not affect Smad3, Smad7, Acta2, or genes related to extracellular matrix metabolism. TAM (10−8 or 10−9 M) + TGF-β1, however, significantly increased Smad7 and Has3 expression and decreased Col1a1 and Acta2 expression compared to TGF-β1 alone. In vivo, TAM significantly increased lamina propria area, hyaluronic acid concentration, and reduced collagen deposition compared to sham treatment.

Conclusions

TAM has antifibrotic potential via the regulation of TGF-β1/Smad signaling in vocal fold injury. These findings provide foundational data to develop innovative therapeutic options for vocal fold fibrosis.

Level of Evidence

NA Laryngoscope, 2022

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Early maladaptive schemas and ICD‐11 CPTSD symptoms: Treatment considerations

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Objectives

Early maladaptive schemas (EMS) can result from adverse interpersonal traumatic experiences. The ICD-11 updated the concept of disorders following traumatic experiences with the new disorder of complex post-traumatic stress disorder (CPTSD). There is now a need to develop and test interventions for CPTSD. An essential step in identifying interventions that are particularly relevant to the treatment of CPTSD is to explore psychological constructs associated more closely with CPTSD compared to PTSD. The current study explored the associations of EMS with PTSD and CPTSD.

Design

The sample consisted of 603 adults (mean age = 41.65, SD = 13.8), recruited through social media and e-mails, and who responded to an online questionnaire.

Methods

Participants completed measures of demographic, traumatic life events, EMS, PTSD and CPTSD symptoms.

Results

Overall, results suggest that participants with CPTSD present with higher schema elevations across all schemas compared to those with PTSD or no diagnosis. Secondly, the schemas of emotional deprivation, abandonment/instability, social isolation/alienation, defectiveness/shame, enmeshment/undeveloped self, subjugation, emotional inhibition and insufficient self-control/self-discipline were significantly associated with the symptom clusters of CPTSD. Finally, results indicate that different schemas form significant associations with the individual symptom clusters of CPTSD.

Conclusions

Although results require replication in clinical samples, initial findings suggest that specific EMS may be important psychological correlates of CPTSD symptoms. Wider treatment considerations of these findings are discussed.

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Long-term Traffic-related Air Pollutant Exposure and Amyotrophic Lateral Sclerosis Diagnosis in Denmark: A Bayesian Hierarchical Analysis

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imageBackground: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Limited evidence suggests ALS diagnosis may be associated with air pollution exposure and specifically traffic-related pollutants. Methods: In this population-based case–control study, we used 3,937 ALS cases from the Danish National Patient Register diagnosed during 1989–2013 and matched on age, sex, year of birth, and vital status to 19,333 population-based controls free of ALS at index date. We used validated predictions of elemental carbon (EC), nitrogen oxides (NOx), carbon monoxide (CO), and fine particles (PM2.5) to assign 1-, 5-, and 10-year average exposures pre-ALS diagnosis at study participants' present and historical residential addresses. We used an adjusted Bayesian hierarchical conditional logistic model to estimate individual pollutant associations and joint and average associations for traffic-related pollutants (EC, NOx, CO). Results: For a standard deviation (SD) increase in 5-year average concentrations, EC (SD = 0.42 µg/m3) had a high probability of individual association with increased odds of ALS (11.5%; 95% credible interval [CrI] = –1.0%, 25.6%; 96.3% posterior probability of positive association), with negative associations for NOx (SD = 20 µg/m3) (–4.6%; 95% CrI = 18.1%, 8.9%; 27.8% posterior probability of positive association), CO (SD = 106 µg/m3) (–3.2%; 95% CrI = 14.4%, 10.0%; 26.7% posterior probability of positive association), and a null association for nonelemental carbon fine particles (non-EC PM2.5) (SD = 2.37 µg/m3) (0.7%; 95% CrI = 9.2%, 12.4%). We found no association between ALS and joint or average traffic pollution concentrations. Conclusions: This study found high probability of a positive association between ALS diagnosis and EC concentration. Further work is needed to understand the role of traffic-related air pollution in ALS pathogenesis.
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Long-term Exposure to Oxidant Gases and Mortality: Effect Modification by PM2.5 Transition Metals and Oxidative Potential

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imageBackground: Populations are simultaneously exposed to outdoor concentrations of oxidant gases (i.e., O3 and NO2) and fine particulate air pollution (PM2.5). Since oxidative stress is thought to be an important mechanism explaining air pollution health effects, the adverse health impacts of oxidant gases may be greater in locations where PM2.5 is more capable of causing oxidative stress. Methods: We conducted a cohort study of 2 million adults in Canada between 2001 and 2016 living within 10 km of ground-level monitoring sites for outdoor PM2.5 components and oxidative potential. Ox exposures (i.e., the redox-weighted average of O3 and NO2) were estimated using a combination of chemical transport models, land use regression models, and ground-level data. Cox proportional hazards models were used to estimate associations between 3-year moving average Ox and mortality outcomes across strata of transition metals and sulfur in PM2.5 and three measures of PM2.5 oxidative potential adjusting for possible confounding factors. Results: Associations between Ox and mortality were consistently stronger in regions with elevated PM2.5 transition metal/sulfur content and oxidative potential. For example, each interquartile increase (6.27 ppb) in Ox was associated with a 14.9% (95% CI = 13.0, 16.9) increased risk of nonaccidental mortality in locations with glutathione-related oxidative potential (OPGSH) above the median whereas a 2.50% (95% CI = 0.600, 4.40) increase was observed in regions with OPGSH levels below the median (interaction P value
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