Prognostic value of the 8th edition American Joint Commission Cancer nodal staging system for patients with head and neck cutaneous squamous cell carcinoma: A multi‐institutional study

a.sfakia shared this article with you from Inoreader Prognostic value of the 8th edition American Joint Commission Cancer nodal staging system for patients with head and neck cutaneous squamous cell carcinoma: A multi‐institutional study Via Head & Neck Abstract Background The 8th edition American Joint Committee on Cancer staging manual (AJCC8) introduced a separate staging system for head and neck cutaneous squamous cell carcinoma (HNcSCC) which parallels mucosal SCC and incorporates extranodal extension (ENE). This study aims to evaluate its prognostic utility. Methods Univariate analysis of 1146 patients with metastatic HNcSCC from four Australian cancer centers was performed according to both AJCC 7th (AJCC7) and the 8th editions. Results AJCC8 increased classification of 924 (80.6%) patients to either pN2a or pN3b and 341 patients (29.8%) from stage III to IV compared to AJCC7. The disease‐specific survival (DSS) was not significantly different between pN1, pN2 or pN3a categories per AJCC8. Estimates of model performance for the AJCC8 pN staging revealed modest predictive capacity (Harrell's C of 0.62 for DSS). Conclusions The risk stratification according to pN classification of AJCC8 staging system performed poorly as a prognostic indicator. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Maximum isometric tongue force in patients with obstructive sleep apnoea.

a.sfakia shared this article with you from Inoreader Maximum isometric tongue force in patients with obstructive sleep apnoea. Via http://link.springer.com/journal/405,European archives of oto-rhino-laryngology,The European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino Related Articles Maximum isometric tongue force in patients with obstructive sleep apnoea. Eur Arch Otorhinolaryngol. 2020 Oct 27;: Authors: Birk R, Stuck BA, Maurer JT, Schell A, Müller CE, Kramer B, Hoch S, Sommer JU Abstract BACKGROUND: Obstructive sleep apnea (OSA) is a sleep disorder with a prevalence of 9-38%. The underlying pathology in OSA is a collapse of the upper airway. Especially in more severely affected patients, this collapse is often located at the level of the tongue base. Therefore, various implantable systems (anchors and ligament techniques) were developed to prevent or overcome this collapse. These systems are exposed to various forces. Different models have been developed to measure these forces and data comparing forces in healthy individuals with OSA patients are rare. PURPOSE: Purpose of the study was to evaluate possible differences in tongue forces between healthy individuals and patients with OSA. METHOD: To evaluate maximum isometric tongue forces, we conducted a matched pair design study including 20 healthy individuals and 20 patients suffering from OSA. Maximum isometric tongue forces were measured in an anterior/posterior direction with the help of self-designed new device that clamps the tongue. RESULTS: We could show that the maximum isometric force does not differ significantly in healthy individuals (10.7 ± 5.2N) from patients with OSA (14.4 ± 6.3N). CONCLUSION: Currently there are no indications that maximum isometric tongue force does differ in healthy individuals and patients with OSA. Higher, as well as lower, tongue forces in patients with OSA seem not to differ from healthy subjects and therefore may not be needed to consider, in the development of tongue management devices, for OSA patients. PMID: 33111155 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Static and dynamic otolith reflex function in people with Parkinson's disease.

a.sfakia shared this article with you from Inoreader Static and dynamic otolith reflex function in people with Parkinson's disease. Via http://link.springer.com/journal/405,European archives of oto-rhino-laryngology,The European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino Related Articles Static and dynamic otolith reflex function in people with Parkinson's disease. Eur Arch Otorhinolaryngol. 2020 Oct 28;: Authors: Hawkins KE, Chiarovano E, Paul SS, MacDougall HG, Curthoys IS Abstract PURPOSE: Parkinson's disease (PD) is a neurodegenerative disorder with possible vestibular system dysfunction. This study reports the transient and sustained functions of the otoliths and their reflex pathways in PD compared to healthy controls (HC) and determines if otolith function relates to previous fall history. METHODS: Forty participants with PD and 40 HC had their otolith function assessed. Transient saccular and utricular-mediated reflexes were assessed by cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs, respectively) elicited by air-conducted stimulus (clicks) and bone-conducted vibration (light tendon hammer taps). Static otolith function was assessed by the Curator Subjective Visual Vertical (SVV) test. RESULTS: Compared to HC, the PD group had significantly more absent cVEMP responses to both clicks (47.5% vs. 30%, respectively, p = 0.03) and taps (21.8% vs. 5%, respectively, p = 0.002). Only the PD group had bilaterally absent tap cVEMPs, this was related to previous falls history (p < 0. 001). In both groups, click oVEMPs were predominantly absent, and tap oVEMPs were predominantly present. The PD group had smaller tap oVEMP amplitudes (p = 0.03) and recorded more abnormal SVV responses (p = 0.01) and greater error on SVV compared to HC, p < 0.001. SVV had no relationship with VEMP responses (p = 0.14). CONCLUSIONS: PD impacts on cVEMP reflex pathways but not tap oVEMP reflex pathways. Bone-conducted otolith stimuli (taps) are more robust than air-conducted sound stimuli (clicks) for both o and cVEMPs. A lack of association between SVV and VEMP responses suggest that static and dynamic otolith functions are differentially affected in PD. PMID: 33112983 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Combination of copanlisib with cetuximab improves tumor response in cetuximab-resistant patient-derived xenografts of head and neck cancer.

a.sfakia shared this article with you from Inoreader Combination of copanlisib with cetuximab improves tumor response in cetuximab-resistant patient-derived xenografts of head and neck cancer. Via Oncotarget,Albany, N.Y. : Impact Journals,http://www.impactjournals.com/oncotarget/ Related Articles Combination of copanlisib with cetuximab improves tumor response in cetuximab-resistant patient-derived xenografts of head and neck cancer. Oncotarget. 2020 Oct 13;11(41):3688-3697 Authors: Klinghammer K, Politz O, Eder T, Otto R, Raguse JD, Albers A, Kaufmann A, Tinhofer I, Hoffmann J, Keller U, Keilholz U Abstract Despite recent advances, the treatment of head and neck squamous cell carcinoma (HNSCC) remains an area of high unmet medical need. HNSCC is frequently associated with either amplification or mutational changes in the PI3K pathway, making PI3K an attractive target particularly in cetuximab-resistant tumors. Here, we explored the antitumor activity of the selective, pan-class I PI3K inhibitor copanlisib with predominant activity towards PI3Kα and δ in monotherapy and in combination with cetuximab using a mouse clinical trial set-up with 33 patient-derived xenograft (PDX) models with known HPV and PI3K mutational status and available data on cetuximab sensitivity. Treatment with copanlisib alone resulted in moderate antitumor activity with 12/33 PDX models showing either tumor stabilization or regression. Combination treatment with copanlisib and cetuximab was superior to either of the monotherapies alone in the majority of the models (21/33), and the effect was particularly pronounced in cetuximab-resistant tumors (14/16). While no correlation was observed between PI3K mutation status and response to either cetuximab or copanlisib, increased PI3K signaling activity evaluated through gene expression profiling showed a positive correlation with response to copanlisib. Together, these data support further investigation of PI3K inhibition in HNSCC and suggests gene expression patterns associated with PI3K signaling as a potential biomarker for predicting treatment responses. PMID: 33110476 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A novel format for recombinant antibody-interleukin-2 fusion proteins exhibits superior tumor-targeting properties in vivo.

a.sfakia shared this article with you from Inoreader A novel format for recombinant antibody-interleukin-2 fusion proteins exhibits superior tumor-targeting properties in vivo. Via Oncotarget,Albany, N.Y. : Impact Journals,http://www.impactjournals.com/oncotarget/ Related Articles A novel format for recombinant antibody-interleukin-2 fusion proteins exhibits superior tumor-targeting properties in vivo. Oncotarget. 2020 Oct 13;11(41):3698-3711 Authors: Ongaro T, Gouyou B, Stringhini M, Corbellari R, Neri D, Villa A Abstract The targeted delivery of interleukin-2 to the tumor is gaining attention as an avenue to potentiate the action of T and NK cells at the site of disease. We have previously described the fusion of the L19 antibody, specific to the EDB domain of fibronectin, with human interleukin-2, using a non-covalent homodimeric diabody format. Here, we describe four novel formats for the L19-IL2 fusion, featuring different arrangements of antibody and IL2. A comparative quantitative biodistribution analysis in tumor-bearing mice using radioiodinated proteins revealed that the novel format (L19L19-IL2, with the antibody in single-chain diabody format) exhibited the best biodistribution results. In vitro assays on peripheral blood mononuclear cells showed a decrease activation of regulatory T cells when single IL2 domain was used. In vivo, both L19-IL2 and L19L19-IL2 inhibited tumor growth in immunocompetent mouse models of cancer. T-cell analysis revealed similar levels of CD4+ and FoxP3+ c ells, with an expansion of the CD8+ T cell in mice treated with L19-IL2 and L19L19-IL2. The percentage of CD4+ regulatory T cells was markedly decreased with L19L19-IL2 combined with a mouse-specific PD-1 blocker. Collectively, these data indicate that the new L19L19-IL2 format exhibits favorable tumor-homing properties and mediates a potent anti-cancer activity in vivo. PMID: 33110477 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Evaluation of cancer-derived myocardial impairments using a mouse model.

a.sfakia shared this article with you from Inoreader Evaluation of cancer-derived myocardial impairments using a mouse model. Via Oncotarget,Albany, N.Y. : Impact Journals,http://www.impactjournals.com/oncotarget/ Related Articles Evaluation of cancer-derived myocardial impairments using a mouse model. Oncotarget. 2020 Oct 13;11(41):3712-3722 Authors: Miyagawa Y, Nukaga S, Mori T, Fujiwara-Tani R, Fujii K, Mori S, Goto K, Kishi S, Sasaki T, Nakashima C, Ohmori H, Kawahara I, Luo Y, Kuniyasu H Abstract Myocardial damage in cancer patients is emphasized as a cause of death; however, there are not many murine cachexia models to evaluate cancer-derived heart disorder. Using the mouse cachexia model that we established previously, we investigated myocardial damage in tumor-bearing mice. In cachexic mice, decreased heart weight and myocardial volume, and dilated left ventricular lumen, and atrophied cardiomyocytes were noted. The cardiomyocytes also showed accumulated 8-hydroxydeoxyguanosine, decreased leucine zipper and EF-hand-containing transmembrane protein-1, and increased microtubule-associated protein light chain3-II. Levels of tumor necrosis factor-α and high-mobility group box-1 proteins in the myocardium were increased, and nuclear factor κB, a signaling molecule associated with these proteins, was activated. When rat cardiomyoblasts (H9c2 cells) were treated with mouse cachexia model ascites and subjected to flux analysis, both oxidative phosphorylation and glycolys is were suppressed, and the cells were in a quiescent state. These results are in good agreement with those previously reported on cancerous myocardial damage. The established mouse cachexia model can therefore be considered useful for analyzing cancer-derived myocardial damage. PMID: 33110478 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Melatonin increases overall survival of prostate cancer patients with poor prognosis after combined hormone radiation treatment.

a.sfakia shared this article with you from Inoreader Melatonin increases overall survival of prostate cancer patients with poor prognosis after combined hormone radiation treatment. Via Oncotarget,Albany, N.Y. : Impact Journals,http://www.impactjournals.com/oncotarget/ Related Articles Melatonin increases overall survival of prostate cancer patients with poor prognosis after combined hormone radiation treatment. Oncotarget. 2020 Oct 13;11(41):3723-3729 Authors: Zharinov GM, Bogomolov OA, Chepurnaya IV, Neklasova NY, Anisimov VN Abstract BACKGROUND: The antitumor and immunomodulating activities of melatonin are widely known. These activities are based upon the multifactorial mechanism of action on various links of carcinogenesis. In the present paper, the long-term results of the clinical use of melatonin in the combined treatment of patients with prostate cancer of various risk groups were evaluated. MATERIALS AND METHODS: A retrospective study included 955 patients of various stages of prostate cancer (PCa) who received combined hormone radiation treatment from 2000 to 2019. Comprehensive statistical methods were used to analyze the overall survival rate of PCa patients treated with melatonin in various prognosis groups. RESULTS: The overall survival rate of PCa patients with favorable and intermediate prognoses treated or not treated with melatonin was not statistically significantly different. In the poor prognosis group, the median overall survival in patients taking the drug was 153.5 months versus 64.0 months in patients not using it (p < 0.0001). The 5-year overall survival rates in the research and control groups were 66.8 ± 1.9 and 53.7 ± 2.6 (p < 0.0001) respectively. In a multivariate analysis, melatonin administration proved to be an independent prognostic factor and reduced the risk of death of PCa patients by more than twice (p < 0.0001). CONCLUSIONS: The multicomponent antitumor effect of melatonin is fully realized and clearly demonstrated in treatment of PCa patients with poor prognosis with a set of unfavorable factors of the tumor progression. PMID: 33110479 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Efavirenz induces DNA damage response pathway in lung cancer.

a.sfakia shared this article with you from Inoreader Efavirenz induces DNA damage response pathway in lung cancer. Via Oncotarget,Albany, N.Y. : Impact Journals,http://www.impactjournals.com/oncotarget/ Related Articles Efavirenz induces DNA damage response pathway in lung cancer. Oncotarget. 2020 Oct 13;11(41):3737-3748 Authors: Marima R, Hull R, Dlamini Z, Penny C Abstract The cell-cycle related genes are potential gene targets in understanding the effects of efavirenz (EFV) in lung cancer. The present study aimed at investigating the expression changes of cell-cycle related genes in response to EFV drug treatment in human non-small cell lung carcinoma (A549) and normal lung fibroblast (MRC-5) cells. The loss in nuclear integrity in response to EFV was detected by 4', 6-diamidino-2-phenylindole (DAPI) staining. Gene expression profiling was performed using human cell cycle PathwayFinder RT2 Profiler™ PCR Array. The expression changes of 84 genes key to the cell cycle pathway in humans following EFV treatment was examined. The R2 PCR Array analysis revealed a change in expression of selected gene targets (including MAD2L2, CASP3, AURKB). This change in gene expression was at least a two-fold between test (EFV treated) and the control. RT-qPCR confirmed the PCR array data. In addition to this, the ATM signaling pathway was shown to be upregulat ed following EFV treatment in MRC-5 cells. In particular, ATM's upstream activation resulted in p53 upregulation in normal lung fibroblasts. Interestingly, the p53 signaling pathway was activated irrespective of the repressed ATM pathway in A549 cells as revealed by the Ingenuity Pathway Analysis (IPA). These EFV effects are similar to those of ionizing radiation and this suggests that EFV has anti-tumour properties. PMID: 33110481 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A Comprehensive Review on DNA Gyrase Inhibitors.

a.sfakia shared this article with you from Inoreader A Comprehensive Review on DNA Gyrase Inhibitors. Via Infectious disorders drug targets,http://goo.gl/XqkpND Related Articles A Comprehensive Review on DNA Gyrase Inhibitors. Infect Disord Drug Targets. 2020 Jan 01;: Authors: Chitra SR, Ramalakshmi N, Kumar SA, Manimegalai P Abstract The newly emerging infectious organisms, the global crisis in antibiotic resistance, and the threat of bioterrorism create an urgent need to discover novel antimicrobial agents. In order to develop novel antimicrobial agents, the mechanism of infectious disease must be better understood. DNA Gyrase is a bacterial enzyme that plays an important role in the replication of DNA and transcription process. It is not present in higher eukaryotes making it a perfect target for developing new antibacterial agents. This review describes the role of DNA gyrase inhibitors in preventing various diseases. In this review, we outline the synthesis and pharmacological action of various novel DNA gyrase inhibitors. DNA gyrase inhibitors were used to treat tuberculosis, bacterial, fungal infections and malaria. DNA gyrase inhibitors mainly act by preventing the supercoiling of DNA strands. PMID: 33109068 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Unraveling Pathophysiological Mechanisms of Parkinson's Disease: Contribution of CSF Biomarkers.

a.sfakia shared this article with you from Inoreader Unraveling Pathophysiological Mechanisms of Parkinson's Disease: Contribution of CSF Biomarkers. Via pubmed: misdiagnosis of alzh... Related Articles Unraveling Pathophysiological Mechanisms of Parkinson's Disease: Contribution of CSF Biomarkers. Biomark Insights. 2020;15:1177271920964077 Authors: Farotti L, Paolini Paoletti F, Simoni S, Parnetti L Abstract Diagnosis of Parkinson's disease (PD) relies on clinical history and physical examination, but misdiagnosis is common in early stages. Identification of biomarkers for PD may allow for early and more precise diagnosis and provide information about prognosis. Developments in analytical chemistry allow for the detection of a large number of molecules in cerebrospinal fluid (CSF), which are known to be associated with the pathogenesis of PD. Given the pathophysiology of PD, CSF α-synuclein species have the strongest rationale for use, also providing encouraging preliminary results in terms of early diagnosis. In the field of classical Alzheimer's disease (AD) biomarkers, low CSF Aβ42 levels have shown a robust prognostic value in terms of development of cognitive impairment. Other CSF biomarkers including lysosomal enzymes, neurofilament light chain, markers of neuroinflammation and oxidative stress, although promising, have not proved to be reliable for diagnostic and prognos tic purposes yet. Overall, the implementation of CSF biomarkers may give a substantial contribution to the optimal use of disease-modifying drugs. PMID: 33110345 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Current Practices in Endotracheal Tube Size Selection for Adults

a.sfakia shared this article with you from Inoreader Current Practices in Endotracheal Tube Size Selection for Adults Via The Laryngoscope Objectives/Hypothesis Intubation with inappropriately sized endotracheal tubes (ETT) can cause long‐term tracheal and laryngeal injuries often requiring surgical intervention. Although tracheal size has been demonstrated to vary based on height and sex, it is unclear whether these guidelines are regularly implemented in patients undergoing endotracheal intubation. The objective of this study is to determine the rate of appropriate ETT size selection in patients undergoing intubation and assess provider decision making in ETT size selection. Study Design Retrospective cohort study. Methods The study population was all patients who underwent endotracheal intubation over a two‐week period at a tertiary academic medical center. Data were collected on patient age, gender, height, BMI, comorbidities, ETT size, duration of intubation, bronchoscopies, and type of practitioner who performed the intubation. A height‐based nomogram for ETT size selection was used to determine the recommended ETT size for each patient. Results One hundred five patients met the inclusion criteria. 22% of patients were intubated with an inappropriately large tube, defined as 1.0 mm larger than the recommended size. Women were more likely to be intubated with an inappropriately large ETT (OR = 13.58, P = .001), as were patients with height less than 160 cm (OR = 141, P = .001). Other factors related to disease severity, anticipation for bronchoscopy, and BMI were not risk factors for the use of inappropriately large ETT. Conclusions Although there is compelling evidence that height is a strong predictor of tracheal morphology and appropriate ETT size, height‐based guidelines have yet to be universally adopted for ETT size selection. Laryngoscope, 2020 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.