Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Thursday, July 14, 2022

Acute toxicity in patients treated with concurrent chemoradiotherapy with proton versus intensity‐modulated radiation therapy for nonmetastatic head and neck cancers

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

We evaluated if proton therapy is associated with decreased acute toxicities compared to intensity-modulated radiation therapy (IMRT) in patients receiving concurrent chemoradiotherapy for head and neck cancers.

Methods

We analyzed 580 patients with nonmetastatic head and neck cancers. Primary endpoint was any 90-day grade ≥3 toxicity, prospectively collected and graded per CTCAEv4. Modified Poisson regression models were used.

Results

Ninety-five patients received proton and 485 IMRT. The proton group had more HPV-positive tumors (65.6 vs. 58.0%, p = 0.049), postoperative treatment (76.8 vs. 62.1%, p = 0.008), unilateral neck treatment (18.9 vs. 6.6%, p < 0.001) and significantly lower doses to organs-at-risk compared to IMRT group. Adjusted for patient and treatment characteristics, the proton group had decreased grade 2 dysgeusia (RR0.67, 95%CI 0.53–0.84, p = 0.004) and a trend toward lower grade ≥3 toxicities (RR0.60, 95%CI 0.41–0.88, p = 0.06).

Conclusions

Proton therapy was associated with significantly reduced grade 2 dysgeusia and nonstatistically significant decrease in acute grade ≥3 toxicities compared to IMRT.

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Outcomes of curative treatment for head and neck squamous cell carcinoma in very elderly adults ≥80 years old

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Head and neck cancer treatment can be difficult and advancing age is associated with greater frailty. It is unclear if curative treatment for very elderly patients is beneficial. This study compared outcomes to curative treatment in patients ≥80 aged with HNSCC to patients aged 70–79.

Methods

Retrospective study of 114 patients diagnosed with HNSCC. Overall survival (OS), Disease-Free Survival (DFS), and local-regional control (LRC) were compared and adjusted for confounders.

Results

Patients aged 70–79 had a higher median OS (35 months [95% CI, 19.58–50.42]) compared with patients aged ≥80 (19 months [11.72–26.28]; p = 0.008) but similar DFS and LRC. KPS < 90 was the stand-alone independent prognostic factor for OS (HR = 2.14 [1.05–4.38]).

Conclusion

Very elderly HNSCC patients (aged ≥80) can have favorable outcomes with curative therapy and advanced chronological age alone should not prohibit patients from receiving treatment. Performance status may be a greater predictor of survival outcome than age alone.

Level of Evidence

Level III.

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Rhinovirus persistence during the COVID‐19 pandemic – impact on paediatric acute wheezing admissions

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Rhinoviruses have persisted throughout the COVID-19 pandemic, despite other seasonal respiratory viruses (influenza, parainfluenza, respiratory syncytial virus, adenoviruses, human metapneumovirus) being mostly suppressed by pandemic restrictions, such as masking and other forms social distancing, especially during the national lockdown periods. Rhinoviruses, as non-enveloped viruses, are known to transmit effectively via the airborne and fomite route, which has allowed infection amongst children and adults to continue despite pandemic restrictions. Rhinoviruses are also known to cause and exacerbate acute wheezing episodes in children predisposed to this condition. Non-infectious causes such as air pollutants (PM2.5, PM10) can also play a role. In this retrospective ecological study, we demonstrate the correlation between UK national sentinel rhinovirus surveillance, the level of airborne particulates and the changing patterns of paedi atric emergency department presentations for acute wheezing, before and during the COVID-19 pandemic (2018-2021) in a large UK teaching hospital.

This article is protected by copyright. All rights reserved.

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Development and Characterization of an Inducible Assay System to Measure Zika Virus Capsid Interaction

alexandrossfakianakis shared this article with you from Inoreader

Abstract

The global spread of the mosquito-borne Zika virus (ZIKV) infection and its complications including Guillain-Barré syndrome and fetus microcephaly in 2015 have made ZIKV as a significant public health threat. The capsid protein plays crucial roles in ZIKV replication and thus represents an attractive therapeutic target. However, inhibitors of ZIKV capsid assembly have not been rigorously identified due to the lack of a target-based screening system. In this study, we developed a novel ZIKV capsid interaction method based on a split-luciferase complementation assay (SLCA), which can be used to measure and quantify ZIKV capsid-capsid interaction by the restored luciferase signal when capsid proteins interact with each other. Furthermore, a Tet-on inducible stable cell line was generated to screen inhibitors of capsid dimerization. By using of this system, peptides (Pep.15-24 in the N-terminal region of ZIKV capsid protein and Pep.44-58 in the α2 helix of ZIK V capsid protein) were identified to inhibit ZIKV capsid-capsid interaction. Overall, this study developed a novel inducible assay system to measure ZIKV capsid interaction and identify ZIKV capsid multimerization inhibitors, which will be applied for future discovery of ZIKV assembly inhibitors.

This article is protected by copyright. All rights reserved.

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Dynamics of nasopharyngeal tract phageome and association with disease severity and age of patients during three waves of COVID‐19

alexandrossfakianakis shared this article with you from Inoreader

Abstract

In December 2019, several patients were hospitalized and diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which subsequently led to a global pandemic. To date, there are no studies evaluating the relationship between the respiratory phageome and the SARS-CoV-2 infection. The current study investigated the phageome profiles in the nasopharyngeal swabs collected from 55 patients during the three different waves of COVID-19 in the Campania Region (Southern Italy). Data obtained from the taxonomic profiling show that phage families belonging to the order Caudovirales have a high abundance in the patient samples. Moreover, the severity of the COVID-19 infection seems to be correlated with the phage abundance.

This article is protected by copyright. All rights reserved.

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Wednesday, July 13, 2022

Predicting Progression of Oral Lesions to Malignancy Using Machine Learning

alexandrossfakianakis shared this article with you from Inoreader

Objective

To use large-scale electronic health record (EHR) data to develop machine learning models predicting malignant transformation of oral lesions.

Methods

A multi-institutional health system database was used to identify a retrospective cohort of patients with biopsied oral lesions. The primary outcome was malignant transformation. Chart review and automated system database queries were used to identify a range of demographic, clinical, and pathologic variables. Machine learning was used to develop predictive models for progression to malignancy.

Results

There were 2192 patients with a biopsied oral lesion, of whom 1232 had biopsy proven oral dysplasia. There was malignant transformation in 34% of patients in the oral lesions dataset, and in 54% of patients in the dysplasia subset. Multiple machine learning-based models were trained on the data in two experiments, (a) including all patients with biopsied oral lesions and (b) including only patients with biopsy-proven dysplasia. In the first experiment, the best machine learning models predicted malignant transformation among the biopsied oral lesions with an area under the curve (AUC) of 86%. In the second experiment, the random forest model predicted malignant transformation among lesions with dysplasia with an AUC of 0.75. The most influential features were dysplasia grade and the presence of multiple lesions, with smaller influences from other features including anemia, histopathologic description of atypia, and other prior cancer history.

Conclusion

With diverse features from EHR data, machine learning approaches are feasible and allow for generation of models that predict which oral lesions are likely to progress to malignancy.

Level of Evidence

3 Laryngoscope, 2022

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Outcomes for Organ Preservation with Chemoradiation Therapy for T4 Larynx and Hypopharynx Cancer

alexandrossfakianakis shared this article with you from Inoreader
Outcomes for Organ Preservation with Chemoradiation Therapy for T4 Larynx and Hypopharynx Cancer

Limited data exists on the non-surgical management of stage T4 larynx and hypopharynx cancer patients who are not surgical candidates or refuse surgery. This study aims to investigate the clinical and functional outcomes of non-surgical management of T4 larynx and hypopharynx cancer patients. The outcomes reported in this study will provide guidance for those who have unresectable disease or refuse surgery for advanced laryngeal and hypopharyngeal cancer patients.


Objective

Limited data is available to guide non-surgical management of Stage T4 larynx and hypopharynx cancer patients who have inoperable disease or refuse surgery. We aim to review the nonoperative management of T4 laryngeal and hypopharyngeal cancer and report the long-term therapeutic and functional outcomes.

Methods

We reviewed the nonoperative management of T4 laryngeal (n = 44) and hypopharyngeal (n = 53) cancer from 1997 to 2015 and performed a univariate analysis (UVA).

Results

The 2-/5-year OS rates were 73%/38% for larynx patients and 52%/29% for hypopharynx patients. Locoregional failure (LRF) occurred in 25% and 19% of larynx and hypopharynx patients, respectively. On UVA of the larynx subset, N3 nodal status and non-intensity-modulated radiation therapy were negatively associated with OS; treatment with radiation therapy alone impacted disease-free survival; and age >70 was associated with LRF. On UVA of the hypopharynx subset, only T4b status significantly impacted OS. In the larynx and hypopharynx groups, 68% and 85% received a percutaneous endoscopic gastrostomy (PEG) tube and 32% and 40% received a tracheostomy tube, respectively. At the last follow-up visit, 66% of our larynx cohort had neither tracheostomy or PEG placed and 40% of our hypopharynx cohort had neither.

Conclusion

We report better than previously noted outcomes among T4 larynx and hypopharynx patients who have unresectable disease or refuse surgery.

Level of Evidence

Level 4 Laryngoscope, 2022

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