Wednesday, January 26, 2022

Outcomes in surgical management of sinonasal malignancy—A single comprehensive cancer center experience

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Abstract

Background

Sinonasal malignancies are a complex and diverse group of tumors. Over the past five decades, treatment advances have changed the management paradigms for these tumors. Our aim was to analyze the outcomes of patients from a comprehensive cancer center.

Materials and Methods

We retrospectively assessed 400 patients with sinonasal malignancies treated with surgery at our center between 1973 and 2015. Multiple variables were reviewed to assess the influence on 5-year outcomes.

Results

The median age was 56 years (IQR 46.8–68). Two hundred and fifty-nine (65%) were males and 141 (35%) were females. Overall survival (OS) and disease-specific survival (DSS) improved in the last analyzed decade. Orbital invasion, advanced pT-classification and pN-classification, and melanoma histology were associated with poorer outcomes.

Conclusion

Treatment outcomes for patients with sinonasal malignancy have improved over time. This is likely multifactorial with advances in surgical technique, adjuvant treatment, and patient selection. pT-classification, pN-classification, orbital invasion, and histology are predictive of survival.

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Sensitizing TRAIL response via differential modulation of anti- and pro-apoptotic factors by AZD5582 combined with ER nanosomal TRAIL in neuroblastoma

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Acta Histochem. 2022 Jan 22;124(2):151856. doi: 10.1016/j.acthis.2022.151856. Online ahead of print.

ABSTRACT

Neuroblastoma is a metastatic brain tumor particularly common in children. The cure rate is below 50% for patients of high-risk condition. Novel therapeutic agents and approaches are needed to improve the cure rate. Tumor necrosis factor-related and apoptosis-inducing ligand (TRAIL) is a promising proapoptotic factor that rapidly induces apoptosis preferentially in t ransformed and cancerous cells. Unfortunately, the common TRAIL resistance in cancers has hampered the clinical application of the ligand. Previously we prepared a novel TRAIL-armed ER derived nanosomal agent (ERN-T) that overcomes TRAIL resistance in some cancer lines when combined with a synthetic antagonist of inhibitors of apoptosis proteins (IAPs), AZD5582. However, how AZD5582 sensitizes cancer cells to ERN-T remains not well understood. In this study we continued to test the therapeutic efficacy of the combinatory therapy of ERN-T and AZD5582 on neuroblastoma, aiming to reveal the molecular mechanism underlying the synergism between AZD5582 and ERN-T. The obtained data revealed that ERN-Ts overcame TRAIL resistance and showed significant cytotoxicity on the resistant neuroblastoma line SH-SH5Y when combined with AZD5582 whilst sparing normal cells. The combination of low doses of ERN-Ts and AZD5582 induced intensive apoptosis in SH-SY5Y but not in normal skin fibroblasts (NSF s). Importantly we discovered that TRAIL sensitization in SH-SY5Y was associated with the concomitant downregulation of antiapoptotic factors cFLIP, MCL-1 and IAPs and upregulation of proapoptotic protein BAX and the death receptor 5 (DR5) by the cotreatment of ERN-T and AZD5582. In vivo study demonstrated that the combination of ERN-T and AZD5582 constituted a highly effective and safe therapy for subcutaneous SH-SY5Y xenograft neuroblastoma in nude mice. In conclusion, we identified that the concomitant regulation of both antiapoptotic and proapoptotic factors and DR5 is an essential molecular mechanism for overcoming TRAIL resistance in SH-SY5Y and the combination of ERN-T and AZD5582 potentially constitutes a novel therapeutic strategy, which is highly effective and safe for neuroblastoma.

PMID:35077998 | DOI:10.1016/j.acthis.2022.151856

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Objective evaluation of stimulation artefact removal techniques in the context of neural spike sorting

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J Neural Eng. 2022 Jan 25. doi: 10.1088/1741-2552/ac4ecf. Online ahead of print.

ABSTRACT

Objective - We present a framework to objectively test and compare stimulation artefact removal techniques in the context of neural spike sorting. Approach - To this end, we used realistic hybrid ground-truth spiking data, with superimposed artefacts from in vivo recordings. We used the framework to evaluate and compare several techniques: blanking, template subtraction by averaging, linear regression, and a multi-channel Wiener filter (MWF). Main results - Our study demonstrates that blanking and template subtraction result in a poorer spike sorting performance than linear regression and MWF, while the latter two perform similarly. Finally, to validate the conclusions found from the hybrid evaluation framework, we also performed a qualitative analysis on in vivo recordings without artificial manipulations. Significance - Our framework allows direct quan tification of the impact of the residual artefact on the spike sorting accuracy, thereby allowing for a more objective and more relevant comparison compared to indirect signal quality metrics that are estimated from the signal statistics. Furthermore, the availability of a ground truth in the form of single-unit spiking activity also facilitates a better estimation of such signal quality metrics.

PMID:35078163 | DOI:10.1088/1741-2552/ac4ecf

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Chinese guidelines for diagnosis and treatment of allergic rhinitis (2022, revision)

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Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2022 Jan 21;57:8-31. doi: 10.3760/cma.j.cn115330-20211228-00828. Online ahead of print.

NO ABSTRACT

PMID:35078291 | DOI:10.3760/cma.j.cn115330-20211228-00828

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Chemosaturation with percutaneous hepatic perfusion of melphalan for metastatic uveal melanoma

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Purpose Uveal melanoma, the most common primary ocular malignancy in adults, carries a poor prognosis: 50% of patients develop the metastatic disease with a 10–25% 1-year survival and no established standard of care treatment. Prior studies of melphalan percutaneous hepatic perfusion (M-PHP) have shown promise in metastatic uveal melanoma (mUM) patients with liver predominant disease but are limited by small sample sizes. We contribute our findings on the safety and efficacy of the procedure in the largest sample population to date. Patients and methods retrospective analysis of outcome and safety data for all mUM patients receiving M-PHP was performed. Tumour response and treatment toxicity were evaluated using RECIST 1.1 and Common Terminology Criteria for Adverse Events v5.03, respectively. Results 250 M-PHP procedures were performed in 81 patients (median of three per patient). The analysis demonstrated a hepatic disease control rate of 88.9% (72/81), a hepatic response rate of 66.7% (54/81), and an overall response rate of 60.5% (49/81). After a median follow-up of 12.9 months, median overall progression-free (PFS) and median overall survival (OS) were 8.4 and 14.9 months, respectively. There were no fatal treatment-related adverse events (TRAE). Forty-three grade 3 (29) or 4 (14) TRAE occurred in 23 (27.7%) patients with a significant reduction in such events between procedures performed in 2016–2020 vs. 2012–2016 (0.17 vs. 0.90 per patient, P
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Endoscopic Posterior Rotation Flap for Posterior Glottic Insufficiency

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