Simulations of the merging cluster of galaxies Cygnus A

The archetype FR-II galaxy Cygnus A lies in a moderately rich cluster about to undergo a major merger. We study the pre-merger Cygnus cluster environment using smoothed particle hydrodynamics simulations constrained by 2Ms of Chandra observations of the hot intracluster medium. The observations constrain the total gravitating mass and concentration parameter, and the simulations provide the quiescent and merger-enhanced temperature profiles of the pre- and post merger of the cluster excluding the central active galactic nucleus. We present the first detailed model of the sub cluster north west of Cygnus A, named CygNW. We find a lower baryon fraction and higher concentration parameter for CygA than expected from known scaling relations in the literature. The model suggests the Cygnus cluster hosts a pre-merger with a progenitor mass ratio of about 1.5:1 at the virial radius. We notice that the intra cluster medium is heated as a result of the merger, but we find no evidence for a (pre-)merger shock in the interstitial region between both cluster haloes. We attribute the merger-induced heating to compression of the cluster outskirts. The smooth model obtained from our simulations is subtracted from the observed cluster state and shows residual temperature structure that is neither hydrostatic nor merger-heated cluster gas. We speculate that this residual heating may result from previous AGN activity over the last ~100 Myr

A lung function information system

Abstract A lung function information system (LFIS) was developed for the data analysis of pulmonary function tests at different locations. This system was connected to the hospital information system (HIS) for the retrieval of patient data and the storage of the lung function variables of patients to generate follow-up reports and to support financial and administrative management. The application programs were developed in such a way that high flexibility was obtained with respect to the patient-computer-technician interaction. The sampled data are stored on a disc to correct earlier decisions, perform recalculations and reanalyse the data for research purposes. When the measurements performed on a patient are authorized, the sampled data are deleted, except for when they are needed for future research. A distributed computer system was chosen to combine the benefits of a centralized system with those of several stand-alone systems. The main tasks of the central unit are to store collected data and computer programs, generate a final lung function report on laser printer and provide a connection to the HIS. In the satellite computers, which are located close to the lung function equipment, the signals and raw data are processed. Furthermore, the satellite computers were in use for program development and several research projects, and for the offline data processing of the lung function measurements from two other hospitals by means of a modem connection. The LFIS improved the quantity and quality of data acquisition. It resulted in an increased capacity of about 50% concerning spirometry, and facilitated time-consuming complex analyses. It also avoided miscalculations and mistakes in reports previously experienced with hand calculations

Reproducibility study of "Label-Free Explainability for Unsupervised Models"

Replicatio

Determinants of delay in the head and neck oncology care pathway:The next step in value-based health care

Objective Head and neck squamous cell carcinomas (HNSCC) are relatively fast-growing tumours, and delay of treatment is associated with tumour progression and adverse outcomes. The aim of this study is to identify determinants of delay in a head and neck oncology centre. Methods This cohort study with prospectively collected data investigated associations between patient (including geriatric assessment at first consultation), tumour and treatment characteristics and treatment delay. Two quality indicator intervals assessing value-based healthcare were studied: care pathway interval (CPI, interval between first visit in an HNOC and treatment initiation) and time-to-treatment initiation (TTI, interval between histopathological confirmation of HNSCC and treatment initiation), using regression analyses. Results Stage-IV tumours and initial radiotherapy were independent predictors of delay in CPI. Initial radiotherapy was associated with delay in TTI. Overall, 37% of the patients started treatment within 30 days after first consultation (67% in case of initial surgical treatment and 11.5% if treated with (chemo)radiation, p <0.001). Geriatric assessment outcomes were not associated with delay. Indicators for delay in initial surgery patients were stage-IV tumours (CPI). Conclusion The majority of HNSCC patients encounter delay in treatment initiation, specifically in patients with advanced-stage tumours or when radiotherapy is indicated

Radiologically Defined Sarcopenia as a Biomarker for Frailty and Malnutrition in Head and Neck Skin Cancer Patients

The aim of this study was to evaluate whether radiologically defined sarcopenia, or a low skeletal muscle index (SMI), could be used as a practical biomarker for frailty and postoperative complications (POC) in patients with head and neck skin cancer (HNSC). This was a retrospective study on prospectively collected data. The L3 SMI (cm2/m2) was calculated with use of baseline CT or MRI neck scans and low SMIs were defined using sex-specific cut-off values. A geriatric assessment with a broad range of validated tools was performed at baseline. POC was graded with the Clavien–Dindo Classification (with a grade of &gt; II as the cut-off). Univariate and multivariable regression analyses were performed with low SMIs and POC as the endpoints. The patients’ (n = 57) mean age was 77.0 ± 9 years, 68.4% were male, and 50.9% had stage III–IV cancer. Frailty was determined according to Geriatric 8 (G8) score (OR 7.68, 95% CI 1.19–49.66, p = 0.032) and the risk of malnutrition was determined according to the Malnutrition Universal Screening Tool (OR 9.55, 95% CI 1.19–76.94, p = 0.034), and these were independently related to low SMIs. Frailty based on G8 score (OR 5.42, 95% CI 1.25–23.49, p = 0.024) was the only variable related to POC. However, POC was more prevalent in patients with low SMIs (∆ 19%, OR 1.8, 95% CI 0.5–6.0, p = 0.356).To conclude, a low SMI is a practical biomarker for frailty and malnutrition in HNSC. Future research should be focused on interventions based on low SMI scores and assess the effect of the intervention on SMI, frailty, malnutrition, and POC.</p

The association of frailty and outcomes of geriatric assessment with acute radiation-induced toxicity in patients with head and neck cancer

BACKGROUND AND PURPOSE: Geriatric impairments and frailty are highly prevalent in patients with head and neck cancer (HNC). This study investigated the association of frailty and outcomes of geriatric assessment (GA) with radiation-induced toxicity (RIT) in patients undergoing (chemo)radiotherapy ((C)RT) for HNC. MATERIALS AND METHODS: Between October 2014 and April 2016, patients with HNC were prospectively included in OncoLifeS, an institutional data-biobank. Before treatment initiation, patients underwent GA and frailty screening (Groningen Frailty Indicator and Geriatric 8). The main outcome of this study was RIT (weight loss, mucositis, salivary gland inflammation, oral pain, sore throat, hoarseness, dry mouth, dysgeusia, dysphagia and general pain) according to the common terminology criteria of adverse events (CTCAE) version 4.0. Linear mixed models were performed, to analyse factors associated with increasing mean RIT over time during the treatment period. RESULTS: 160 patients were included. 114 (71.3%) were male and the mean age was 66.1 years. Age ≥ 65 (β = 0.03(95 %CI = 0.01;0.05), p = 0.01), regional RT (β = 0.05(95 %CI = 0.02;0.09), p = 0.004), and concurrent chemotherapy (β = 0.04(95 %CI = 0.02;0.07), p = 0.001), were independent factors associated with increasing toxicity during the 7-week treatment period, adjusted for relevant covariates. None of the single items of GA, as well as the frailty screening instruments, were associated with increasing RIT. CONCLUSION: In this study, frailty and GA were not associated with additional RIT during treatment. These results suggest that (C)RT is equally tolerated in frail and non-frail patients, with respect to acute RIT. RT could be a suitable alternative to surgery in selected frail patients

Association of Tumor Microenvironment with Biological and Chronological Age in Head and Neck Cancer

There is often a mismatch between the chronological and biological age of head and neck squamous cell carcinoma (HNSCC) patients. Treatment is based on chronological age, while biological age seems to be a better prognosticator for treatment toleration. This study investigated whether tumor characteristics are associated with chronological and biological age. The relation with survival was also assessed. Prospectively collected data from 164 newly diagnosed HNSCC patients enrolled in the OncoLifeS database were analyzed. Biological age was assessed by a multidomain geriatric assessment. Several immunological markers were tested by immunohistochemistry on tissue microarray sections from the tumor. Disease-free survival (DFS), adjusted for chronological- and biological age, was assessed by univariable and bivariable analyses. In biologically old patients, a lower infiltration of CD163+ macrophages (p = 0.036) as well as CD4+ (p = 0.019) and CD8+ (p = 0.026) lymphocytes was found in the tumor microenvironment. Chronological older patients showed significantly lower PD-L1 combined positive scores (p = 0.030). Advanced tumor stage and perineural growth were related to a worse DFS. None of the immunological markers showed a significant association with DFS. Biological age might have a stronger influence on tumor microenvironment than chronological age. These findings should initiate clinical studies investigating the response to specific treatment regimens (e.g., immunotherapy) according to the biological age.</p

Association of Tumor Microenvironment with Biological and Chronological Age in Head and Neck Cancer

There is often a mismatch between the chronological and biological age of head and neck squamous cell carcinoma (HNSCC) patients. Treatment is based on chronological age, while biological age seems to be a better prognosticator for treatment toleration. This study investigated whether tumor characteristics are associated with chronological and biological age. The relation with survival was also assessed. Prospectively collected data from 164 newly diagnosed HNSCC patients enrolled in the OncoLifeS database were analyzed. Biological age was assessed by a multidomain geriatric assessment. Several immunological markers were tested by immunohistochemistry on tissue microarray sections from the tumor. Disease-free survival (DFS), adjusted for chronological- and biological age, was assessed by univariable and bivariable analyses. In biologically old patients, a lower infiltration of CD163+ macrophages (p = 0.036) as well as CD4+ (p = 0.019) and CD8+ (p = 0.026) lymphocytes was found in the tumor microenvironment. Chronological older patients showed significantly lower PD-L1 combined positive scores (p = 0.030). Advanced tumor stage and perineural growth were related to a worse DFS. None of the immunological markers showed a significant association with DFS. Biological age might have a stronger influence on tumor microenvironment than chronological age. These findings should initiate clinical studies investigating the response to specific treatment regimens (e.g., immunotherapy) according to the biological age.</p

Geriatric assessment of patients treated for cutaneous head and neck malignancies in a tertiary referral center:Predictors of postoperative complications

Introduction: As cutaneous head and neck malignancies are highly prevalent especially in older patients, the risk of surgical complications is substantial in this potentially vulnerable population. The objective of this study was to evaluate the value of geriatric assessment of this population with respect to postoperative complications. Methods: Patients were prospectively included in OncoLifeS, a databiobank. Before surgery, patients underwent a geriatric assessment including multiple validated screening tools for frailty, comorbidity, polypharmacy, nutrition, functional status, social support, cognition and psychological status. Postoperatively, complications (Clavien-Dindo ≥ grade II) were registered. Uni- and multivariable logistic regression analyses were performed yielding odds ratios (ORs) and 95% confidence intervals (95%CIs). Results: 151 patients undergoing surgery for cutaneous head and neck malignancies were included in this study (mean age 78.9 years, 73.5% male). In a multivariable analysis, frailty measured by the Geriatric 8 (G8) (OR = 6.34; 95%CI:1.73–23.25) was the strongest independent predictor of postoperative complications, among other predictors such as major treatment intensity (OR = 2.73; 95%CI:1.19–6.26) and general anesthesia (OR = 4.74; 95%CI:1.02–22.17), adjusted for age and sex. Conclusion: Frailty, measured by G8, is the strongest predictor of postoperative complications in patients undergoing surgery for cutaneous head and neck malignancies in addition to treatment intensity and type of anesthesia. Geriatric screening on multiple domains is recommended for patients with cutaneous malignancies undergoing head and neck surgery is recommended, as this population includes old patients and frequently suffers postoperative complications