Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Sunday, August 7, 2022

Oncologic outcomes of salvage surgery and immune checkpoint inhibitor therapy in recurrent head and neck squamous cell carcinoma: A single‐institution retrospective study

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Survival outcomes in recurrent head and neck squamous cell carcinoma (HNSCC) are poor. This study aimed to compare survival outcomes between salvage surgery and immunotherapy in patients with recurrent advanced HNSCC.

Methods

Patients with advanced stage (stage III or IV) recurrent HNSCC following treatment with platinum-based chemotherapy were included. Survival was estimated using the Kaplan–Meier method, and Cox regression was used for multivariate logistic regression.

Results

Two-year overall survival after salvage surgery was 68.6% and after immunotherapy patients was 24.6%. Multivariate logistic regression showed that salvage surgery was associated with improved survival without statistical significance (hazard ratio [HR] 0.12, p = 0.25). Subgroup analysis of patients with oral cavity/oropharyngeal cancer noted improved survival with salvage surgery over immunotherapy (HR 0.006, p = 0.01) and decreased survival with neutrophil-to-lymphocyte ratio (NLR) > 5 (HR 6.4, p = 0.02).

Conclusion

Our retrospective single-institutional data suggest that resectable advanced stage recurrent HNSCC may have improved survival with salvage surgery in appropriately selected patients, but larger prospective studies are required.

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Characterizing the epithelial–mesenchymal transition status of circulating tumor cells in head and neck squamous cell carcinoma

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Circulating tumor cells (CTCs), in particular those undergoing an epithelial–mesenchymal transition (EMT), are a promising source of biomarkers in head and neck squamous cell carcinoma (HNSCC). Our aim was to validate a protocol using microfluidic enrichment (Parsortix platform) with flow-cytometry CTC characterization.

Method

Blood samples from 20 treatment naïve HNSCC patients underwent Parsortix enrichment and flow cytometry analysis to quantify CTCs and identify epithelial or EMT subgroups—correlated to clinical outcomes and EMT gene-expression in tumor tissue.

Results

CTCs were detected in 65% of patients (mean count 4 CTCs/ml). CTCs correlated with advanced disease (p = 0.0121), but not T or N classification. Epithelial or EMT CTCs did not correlate with progression-free or overall survival. Tumor mesenchymal gene-expression did not correlate with CTC EMT expression (p = 0.347).

Discussion

Microfluidic enrichment and flow cytometry successfully characterizes EMT CTCs in HNSCC. The lack of association between tumor and CTC EMT profile suggests CTCs may undergo an adaptive EMT in response to stimuli within the circulation.

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Excessive mechanical stress induced temporomandibular joint osteoarthritis via osteoclasts‐mediated osteogenic differentiation of BMSCs

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Bone homeostasis is a dynamic process maintained by osteoblasts and osteoclasts, which may be regulated by excessive mechanical stress (EMS).

Objectives

Our study aims to explore the relationship between osteogenic differentiation of BMSCs and EMS-activated osteoclast differentiation of RAW 264.7 cells in order to optimize orthodontic treatment.

Methods

We established the model of EMS in vivo and in vitro. In vivo, HE, Safranin-O staining, micro-CT, and immunofluorescence double-labeling were utilized to assess the changes in condylar, the distributions of osteoblasts, osteoclasts and MAPKs. In vitro, the effects of EMS-activated osteoclast differentiation exerting on osteogenic differentiation of BMSCs were observed by Western Blot, qRT-PCR and Alizarin Red staining. Furthermore, the role of MAPKs in this progress was explored by using inhibitors of MAPKs and co-culture supernatants.

Results

In vivo, EMS led to the degradation of condylar cartilage and destruction of subchondral bone, diagnosed as temporomandibular joint osteoarthritis (TMJ OA). Osteoclasts and osteoblasts were both enriched in subchondral bone, but osteoclast predominated. The expressions of p-JNK, p-ERK1/2, and p-p38 were all activated in vitro and in vivo, which were localized mainly in the Trap+ area in subchondral bone. Interestingly, only the inactivation of p-ERK1/2 in osteoclasts significantly inhibited the osteogenic differentiation of BMSCs in vitro. This revealed that p-ERK1/2 played a key role in the osteoclasts-induced osteogenic differentiation of BMSCs.

Conclusion

Our results proved that EMS led to TMJ OA, in which up-regulated p-ERK1/2 in osteoclasts was mechanosensitive and facilitated the osteogenic differentiation of BMSCs.

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Thursday, August 4, 2022

COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection during Delta-dominant and Omicron-dominant periods in Japan: a multi-center prospective case-control study (FASCINATE study)

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Although several COVID-19 vaccines initially showed high efficacy, there have been concerns due to waning immunity and the emergence of variants with immune escape capacity.
Methods
A test-negative design case-control study was conducted in 16 healthcare facilities in Japan during the Delta-dominant period (August-September 2021) and the Omicron-dominant period (January-March 2022). Vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection was calculated for 2 doses for the Delta-dominant period and 2 or 3 doses for the Omicron-dominant period, compared to unvaccinated individuals.
Results
The analysis included 5795 individuals with 2595 (44.8%) cases. Among vaccinees, 2242 (55.8%) received BNT162b2 and 1624 (40.4%) received mRNA-1273 at manufacturer-recommended intervals. During the Delta-dominant period, VE was 88% (95% CI: 82-93) 14 days-3 months after dose 2 and 87% (95% CI: 38-97) 3-6 months a fter dose 2. During the Omicron-dominant period, VE was 56% (95% CI: 37-70) 14 days-3 months since dose 2, 52% (95% CI: 40-62) 3-6 months after dose 2, 49% (95% CI: 34-61) 6 + months after dose 2, and 74% (95% CI: 62-83) 14 + days after dose 3. Restricting to individuals at high risk of severe COVID-19 and additional adjustment for preventive measures (i.e. mask-wearing/high-risk behaviors) yielded similar estimates, respectively.
Conclusions
In Japan where most are infection-naïve and strict prevention measures are maintained regardless of vaccination status, 2-dose mRNA vaccines provided high protection against symptomatic infection during the Delta-dominant period and moderate protection during the Omicron-dominant period. Among individuals who received an mRNA booster dose, VE recovered to a high level.
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Extracorporeal hemoadsorption with the CytoSorb device as a potential therapeutic option in severe intoxications: Review of the rationale and current clinical experiences

alexandrossfakianakis shared this article with you from Inoreader
Extracorporeal hemoadsorption with the CytoSorb device as a potential therapeutic option in severe intoxications: Review of the rationale and current clinical experiences

Extracorporeal hemoadsorption with the CytoSorb device as a potential therapeutic option in severe intoxications: review of the rationale and current clinical experiences.


Abstract

What is known and objective

Many severe intoxications occur with substances with no specific antidote, which is why methods of extracorporeal elimination represent a particularly useful and even critical component in their management. The purpose of this review is to summarize the accumulating evidence and clinical results from the application of CytoSorb hemoadsorption therapy in patients with severe intoxications.

Comment

The technology represents a promising technique with an increasing number of publications in a variety of severe intoxication scenarios suggesting that early intervention might provide rapid substance removal with subsequent overall clinical improvement.

What is new and conclusion

Given the tremendous challenges in performing prospective, randomized trials in this field, the strong safety profile of the device and the high acuity of these life-threatening situations, CytoSorb should be considered as a therapeutic option in severe intoxications, particularly when direct antidotes are not available. However, further clinical data are desirable to provide precise recommendations.

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Prognostic capacity of the transcriptional expression of lactate dehydrogenase A in patients with head and neck squamous cell carcinoma

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

To analyze the relationship between the transcriptional expression of lactate dehydrogenase A (LDHA) and the disease control in patients with a head and squamous cell carcinoma (HNSCC).

Methods

We determined the transcriptional expression of LDHA in 110 HNSCC patients treated with surgery.

Results

Five-year disease-free survival for patients with a high transcriptional expression of LDHA (n = 51) was 39.2% (95% confidence interval [CI]: 25.3%–53.1%), and for patients with a low expression (n = 59), it was 63.6% (95% CI: 51.1%–76.1%) (p = 0.004). According to the results of a multivariate analysis, patients with a high transcriptional expression of LDHA had a 3.4-fold increased risk of tumor recurrence. Patients with a high transcriptional expression of LDHA tended to show a higher intensity of immunohistochemical expression of LDHA at the tumor cells (p = 0.086).

Conclusion

In HNSCC patients treated with surgery, a high transcriptional expression of LDHA was associated with a significant decrease in disease-free survival.

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Epstein-Barr Virus–Positive Plasma Cell Neoplasm of Nasal Cavity in an Immunocompetent Adult

alexandrossfakianakis shared this article with you from Inoreader

jamanetwork.com

This case report describes patient in their 40s with a medical history of sleep apnea and diabetes and no history of immunosuppression who presented with left-sided nasal obstruction for 1 year and was found to have an Epstein-Barr virus–positive plasmacytoma.
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