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STUDY OBJECTIVES: To evaluate (determinants of) treatment success of mandibular advancement device application in a selected phenotype of patients with obstructive sleep apnea (OSA). METHODS: Ninety nonobese patients with moderate OSA (obstructive apnea-hypopnea index [OAHI] ≥ 15 and < 30 events/h) without comorbidities were prospectively included. Polysomnography was performed at baseline and with a mandibular advancement device. A drug-induced sleep endoscopy with jaw thrust was performed in 83%. RESULTS: OAHI reduction ≥ 50% was observed in 73%, OAHI reduction ≥ 50% with OAHI < 10 events/h in 70%, and complete OSA resolution (OAHI < 5 events/h) in 40%. Patients with nonpositional OSA showed a significantly higher rate of complete OSA resolution: Posttest probability increased to 67%. In patients with total disappearance of collapse at velum level and at all levels during drug-induced sleep endoscopy with jaw thrust, the drop in OAHI was impressive with an infinitively high positive likelihood ratio. However, the proportion of patients having nonpositional OSA or the drug-induced sleep endoscopy characteristics as described above was < 20%. The change in snoring disturbance based on a visual analog scale was 76% (interquartile range 40-89%, P < .001) and a statistically significant amelioration in Epworth Sleepiness Scale (especially in somnolent subjects) was observed. High adherence was reported. CONCLUSIONS: In this predefined OSA phenotype, a mandibular advancement device was effective in reduction of OAHI and in amelioration of symptoms. Stratification by nonpositional OSA and findings on drug-induced sleep endoscopy with jaw thrust increased treatment success defined as reduction in OAHI. However, the clinical relevance can be questioned because only a small number of patients demonstrated these characteristics. CITATION: Buyse B, Nguyen PAH, Leemans J, et al. Short-term positive effects of a mandibular advancement device in a selected phenotype of patients with moderate obstructive sleep apnea: a prospective study. J Clin Sleep Med. 2023;19(1):5-16. ispartof: J Clin Sleep Med vol:19 issue:1 pages:5-16 ispartof: location:United States status: published

OBJECTIVES: Tinnitus is highly prevalent, but only a few risk factors for developing tinnitus are known and little is known about factors associated with the degree of annoyance of new-onset tinnitus. Longitudinal analysis can reveal risk factors associated with the development of tinnitus and might lead to targeted prevention. The aim of this study is twofold. (1) To identify risk factors that are longitudinally associated with the odds of developing tinnitus 5 years later. (2) To identify factors that are cross-sectionally associated with tinnitus annoyance in adults with new-onset tinnitus. METHODS: Baseline, 5-year, and 10-year follow-up data of participants in the Netherlands Longitudinal Study on Hearing (NL-SH) were used. The NL-SH is a web-based prospective cohort study, which started in 2006 and includes both normal hearing and hearing-impaired adults aged 18 to 70 years at baseline. The NL-SH uses an online digit-triplet speech-in-noise test to asses speech recognition ability in noise, and online questionnaires on various aspects of life. At follow-up, participants are asked (1) if they suffer from tinnitus and (2) to rate tinnitus annoyance on a 0 to 100 numeric rating scale. We investigated whether demographic (age, sex, living arrangement, educational level), lifestyle (history of tobacco smoking, alcohol use), health (asthma, severe heart disease, hypertension, history of stroke, osteoarthritis, rheumatoid arthritis, epilepsy, multiple sclerosis, and migraine), hearing (speech recognition ability in noise, hyperacusis, and occupational noise exposure), and psychological variables (distress, somatization, depression, and anxiety) were potential risk factors for new-onset tinnitus, or associated with annoyance caused by new-onset tinnitus. Generalized estimating equations were used to longitudinally analyze the association between potential risk factors and new-onset tinnitus measured 5 years later. A multivariable association model was constructed using a forward selection procedure with p < 0.05 for model entry. Linear regression analysis was used to cross-sectionally analyze the association between potential factors and tinnitus annoyance in new-onset tinnitus. For this purpose, a multivariable association model was constructed using a forward selection procedure with p

BACKGROUND: Definitive concomitant cisplatin-based chemoradiotherapy (CRT) is the current gold standard for most patients with advanced stage head and neck squamous cell carcinoma (HNSCC) of the pharynx and larynx. Since previous meta-analysis on CRT outcomes in HNSCC have been reported, advances have been made in radiotherapy techniques and clinical management, while HPV-status has been identified as a strong confounding prognostic factor in oropharyngeal cancer. Here, we present real-world outcome data from a large multicenter cohort of HPV-negative advanced stage HNSCC treated with CRT using contemporary IMRT-based techniques.METHOD: Retrospective data were collected from a multicenter cohort of 513 patients treated with definitive concurrent platinum-based CRT with curative intent between January 2009 and August 2017. Only patients with HPV-negative advanced stage (III-IV) HNSCC were included. A prognostic model for outcome was developed based on clinical parameters and compared to TNM.RESULTS: Nearly half of the 513 patients (49%) had an oropharyngeal tumor, often locally advanced (73.3% T3-T4b) and with involvement of the regional lymph nodes (84%). Most patients (84%) received cisplatin as single agent. 66% received the planned number of cycles and 75% reached a cumulative cisplatin dose of ≥200 mg/m2. Locoregional control was achieved in 324 (63%) patients during follow-up, and no association with tumor sites was observed (p = 0.48). Overall survival at 5 year follow-up was 47%, with a better survival for laryngeal cancer (p = 0.02) compared to other sites. A model with clinical variables (gender, high pre-treatment weight loss, N2c/N3-stage and CONCLUSION: Despite advances in clinical management, more than a third of patients with HPV-negative HNSCC do not complete CRT treatment protocols due to cisplatin toxicity. A model that consists of clinical variables and treatment parameters including cisplatin dose provided the strongest association with overall survival. Since cisplatin toxicity is a major obstacle in completing definitive CRT, the development of alternative and less toxic radiosensitizers is therefore warranted to improve treatment results. The association of RT-boost technique with distant metastasis is an important finding and requires further study.

Psychoneurological symptoms are commonly reported by newly diagnosed head and neck cancer (HNC) patients, yet there is limited research on the associations of these symptoms with biomarkers of stress and inflammation. In this article, pre-treatment data of a multi-center cohort of HNC patients were analyzed using a network analysis to examine connections between symptoms (poor sleep quality, anxiety, depression, fatigue, and oral pain), biomarkers of stress (diurnal cortisol slope), inflammation markers (c-reactive protein [CRP], interleukin [IL]-6, IL-10, and tumor necrosis factor alpha [TNF-α]), and covariates (age and body mass index [BMI]). Three centrality indices were calculated: degree (number of connections), closeness (proximity of a variable to other variables), and betweenness (based on the number of times a variable is located on the shortest path between any pair of other variables). In a sample of 264 patients, poor sleep quality and fatigue had the highest degree index; fatigue and CRP had the highest closeness index; and IL-6 had the highest betweenness index. The model yielded two clusters: a symptoms—cortisol slope—CRP cluster and a IL-6—IL-10—TNF-α—age—BMI cluster. Both clusters were connected most prominently via IL-6. Our findings provide evidence that poor sleep quality, fatigue, CRP, and IL-6 play an important role in the interconnections between psychoneurological symptoms and biomarkers of stress and inflammation in newly diagnosed HNC patients.

Previously, researchers used functional MRI to identify regional brain activations associated with sensory processing sensitivity (SPS), a proposed normal phenotype trait. To further validate SPS as a behavioral entity, to characterize it anatomically, and to test the usefulness in psychology of methodologies that assess axonal properties, the present study correlated SPS proxy questionnaire scores (adjusted for neuroticism) with diffusion tensor imaging measures. Participants (n=408) from the Young Adult Human Connectome Project that are free of neurologic and psychiatric disorders were investigated. We computed mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD) and fractional anisotropy (FA). A voxelwise, exploratory analysis showed that MD and RD correlated positively with SPS proxy scores in the right and left subcallosal and anterior ventral cingulum bundle, and the right forceps minor of the corpus callosum (peak Cohen’s D effect size = 0.269). Further analyses showed correlations throughout the entire right and left ventromedial prefrontal cortex, including the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate and arcuate fasciculus. These prefrontal regions are generally involved in emotion, reward and social processing. FA was negatively correlated with SPS proxy scores in white matter of the right premotor/motor/somatosensory/supramarginal gyrus regions, which are associated with empathy, theory of mind, primary and secondary somatosensory processing. Region of interest (ROI) analysis, based-on previous fMRI results and Freesurfer atlas-defined areas, showed small effect sizes, (+0.151 to -0.165) in white matter of the precuneus and inferior frontal gyrus. Other ROI effects were found in regions of the dorsal and ventral visual pathways and primary auditory cortex. The results reveal that in a large, diverse group of participants axonal microarchitectural differences can be identified with SPS traits that are subtle and in the range of typical behavior. The results suggest that the heightened sensory processing in people who show SPS may be influenced by the microstructure of white matter in specific neocortical regions. Although previous fMRI studies had identified most of these general neocortical regions, the DTI results put a new focus on brain areas related to attention and cognitive flexibility, empathy, emotion and low-level sensory processing, as in the primary sensory cortex. Psychological trait characterization may benefit from diffusion tensor imaging methodology by identifying influential brain systems for traits.

Kidney tubular epithelial cells (TECs) have a crucial role in the damage and repair response to acute and chronic injury. To adequately respond to constant changes in the environment, TECs have considerable bioenergetic needs, which are supported by metabolic pathways. Although little is known about TEC metabolism, a number of ground-breaking studies have shown that defective glucose metabolism or fatty acid oxidation in the kidney has a key role in the response to kidney injury. Imbalanced use of these metabolic pathways can predispose TECs to apoptosis and dedifferentiation, and contribute to lipotoxicity and kidney injury. The accumulation of lipids and aberrant metabolic adaptations of TECs during kidney disease can also be driven by receptors of the innate immune system. Similar to their actions in innate immune cells, pattern recognition receptors regulate the metabolic rewiring of TECs, causing cellular dysfunction and lipid accumulation. TECs should therefore be considered a specialized cell type - like cells of the innate immune system - that is subject to regulation by immunometabolism. Targeting energy metabolism in TECs could represent a strategy for metabolically reprogramming the kidney and promoting kidney repair.

Background It is estimated that between 12 to 25% of women who undergo an endometrial ablation for heavy menstrual bleeding (HMB) are dissatisfied after two years because of recurrent menstrual bleeding and/or cyclical pelvic pain, with around 15% of these women ultimately having a hysterectomy. The insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS) immediately after endometrial ablation may inactivate residual untreated endometrium and/or inhibit the regeneration of endometrial tissue. Furthermore, the LNG-IUS may prevent agglutination of the uterine walls preventing intrauterine adhesion formation associated with endometrial ablation. In these ways, insertion of an LNG-IUS immediately after endometrial ablation might prevent subsequent hysterectomies because of persisting uterine bleeding and cyclical pelvic pain or pain that arises de novo. Hence, we evaluate if the combination of endometrial ablation and an LNG-IUS is superior to endometrial ablation alone in terms of reducing subsequent rates of hysterectomy at two years following the initial ablative procedure. Methods/design We perform a multicentre randomised controlled trial in 35 hospitals in the Netherlands. Women with heavy menstrual bleeding, who opt for treatment with endometrial ablation and without contraindication for an LNG-IUS are eligible. After informed consent, participants are randomly allocated to either endometrial ablation plus LNG-IUS or endometrial ablation alone. The primary outcome is the hysterectomy rate at 24 months following endometrial ablation. Secondary outcomes include women’s satisfaction, reinterventions, complications, side effects, menstrual bleeding patterns, quality of life, societal costs. Discussion The results of this study will help clinicians inform women with HMB who opt for treatment with endometrial ablation about whether concomitant use of the LNG-IUS is beneficial for reducing the need for hysterectomy due to ongoing bleeding and/or pain symptoms. Trial registration Dutch Trial registration: NL7817. Registered 20 June 2019, https://www.trialregister.nl/trial/7817.

Contains fulltext : 273921.pdf (Publisher’s version ) (Open Access) BACKGROUND: T4-classified squamous cell carcinoma (SCC) of external auditory canal (EAC) can potentially involve different anatomical structures, which could translate into different treatment strategies and survival outcomes within one classification. Our aim is to evaluate the clinical added value of T4-subclasses proposed by Lavieille and by Zanoletti. METHODS: Retrospective data, including patients with primary operated cT4-classified EAC SCC, was obtained from 12 international hospitals. We subclassified according to the T4-subclasses. The treatment strategies, disease-free survival (DFS) and overall survival per subclass were calculated. RESULTS: A total of 130 T4-classified EAC SCC were included. We found commonly used treatment strategies per subclass according to Lavieille and the DFS seems also to differ per subclass. Subclass according to Zanoletti showed comparable treatment strategies and survival outcomes per subclass. CONCLUSION: Our study suggests that the subclass according Lavieille might have added value in clinical practice to improve care of T4-classified EAC SCC.

Background Several neurologic complications have been reported in close temporal association with both severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and following vaccination against SARS-CoV-2. Specifically, several cases of Guillain-Barré syndrome (GBS) have been reported in temporal relationship with COVID-19 vaccination, with two small case series describing a specific phenotype with bifacial weakness and paresthesia in the limbs. Methods We retrospectively collected patients who developed a new-onset neuromuscular disorder in the first 6 weeks after receiving a COVID-19 vaccine (either first or second dose). The patients were collected from one tertiary care centre and one secondary care centre from February to July 2021. Results We report eight patients who developed phenotypically diverse neuromuscular disorders in the weeks following COVID-19 vaccination, with a presumed immune-mediated etiology. In our case series, we report three patients with classical GBS, one patient with bifacial weakness with paresthesia variant of GBS, two patients with subacute-onset chronic inflammatory demyelinating polyneuropathy (CIDP), one patient with brachial plexopathy and one patient with subacute axonal sensorimotor polyneuropathy. Conclusions New-onset neuromuscular disorders with onset in the weeks after COVID-19 vaccination can include diverse phenotypes. A causal relationship between these disorders and the vaccine cannot be proven at present, and further epidemiological studies are needed to further investigate this association.

BACKGROUND: To investigate associations between psychological problems and the use of healthcare and informal care and total costs among head and neck cancer (HNC) patients.METHOD: Data were used of the NETherlands QUality of Life and Biomedical Cohort study. Anxiety and depression disorder (diagnostic interview), distress, symptoms of anxiety and depression (HADS), and fear of cancer recurrence (FCR) and cancer worry scale (CWS) were measured at baseline and at 12-month follow-up. Care use and costs (questionnaire) were measured at baseline, 3-, 6-, 12-, and 24-month follow-up. Associations between psychological problems and care use/costs were investigated using logistic and multiple regression analyses.RESULTS: Data of 558 patients were used. Distress, symptoms of anxiety or depression, FCR, and/or anxiety disorder at baseline were significantly associated with higher use of primary care, supportive care, and/or informal care (odds ratios (ORs) between 1.55 and 4.76). Symptoms of anxiety, FCR, and/or depression disorder at 12-month follow-up were significantly associated with use of primary care, supportive care, and/or informal care (ORs between 1.74 and 6.42). Distress, symptoms of anxiety, and FCR at baseline were associated with higher total costs.DISCUSSION: HNC patients with psychological problems make more use of healthcare and informal care and have higher costs. This is not the result of worse clinical outcomes.

Contains fulltext : 246727.pdf (Publisher’s version ) (Open Access) Background: This study assessed the course of fear of cancer recurrence (FCR) in patients newly diagnosed with head and neck cancer (HNC), identified FCR trajectories and factors associated with FCR trajectories. Methods: Six hundred and seventeen HNC patients from the NET-QUBIC cohort study completed the Cancer Worry Scale-6 at diagnosis, 3 and 6 months post-treatment. FCR trajectories were identified using Latent Class Growth Analysis. Associations were explored between FCR trajectories and baseline demographic and medical variables, coping and self-efficacy. Results: Overall, FCR decreased slightly between baseline and 3 months post-treatment and remained stable up to 6 months. Two FCR trajectories were identified: "high stable" (n = 125) and "low declining" (n = 492). Patients with high stable FCR were younger, reported more negative adjustment, passive coping, and reassuring thoughts, and less avoidance. Conclusions: The majority of HNC patients have low declining FCR after diagnosis, but one in five patients experience persistent high FCR up to 6 months post-treatment. 12 p.

Incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing globally and the human papillomavirus (HPV) has been linked to this increase. This study aimed to present a comprehensive overview of OPSCC trends in incidence rates by age group and investigate differences in risk factors profile. Netherlands Cancer Registry data from 1989-2018 were analyzed to calculate the annual percentage change (APC) over European standardized incidence rates by gender and age group using joinpoint regression software. Smoking, alcohol drinking and HPV-status were available for 2015-2018. During 1989-2018, 13 048 cases of OPSCC were reported with a male-to-female ratio of 2.1:1. The overall incidence rate increased by 5.4% (APC) annually from 1989 to 1996 but slowed thereafter by 1.2%. Significant declines were found in patients of 35-44 years (APCs -3.7%). Adults aged 45-59 years displayed significant increases from 1989 to 2001, followed by a significant decline. In patients >= 60 years, the incidence rates increased overall, with APC for women being consistently higher than men. The data on HPV status was available for 69% of the patients, of whom 47% were HPV+. Smoking and alcohol consumption were more prevalent, that is 75 and 76 % respectively. The declining trends of OPSCC for Dutch people aged 35-44 years from 1989 to 2018 and for those aged 45-59 years from 2002 onwards are inconsistent to trends reported elsewhere in the developed countries. The prevalence of smoking and drinking alcohol was quite high in all age groups, whereas the proportion of HPV-positivity was relatively low.

Background: Superficial white matter (SWM) alterations correlated with cognitive decline have been described in Alzheimer’s disease (AD). Objective: The study aims to extend the investigation of the SWM alterations to AD and non-AD neurodegenerative dementia (ND) and explore the relationship with cerebrospinal fluid (CSF) biomarkers and clinical data. Methods: From a database of 323 suspected dementia cases, we retrospectively recruited 55 ND with abnormal amyloid-β42 (AD) and 38 ND with normal amyloid-β42 (non-AD) and collected clinical data, CSF biomarkers, and magnetic resonance images. Ten healthy controls (HC) were recruited for imaging and Mini-Mental State Examination (MMSE). Diffusion tensor imaging (DTI) measurements were performed in the lobar SWM regions and Kruskal Wallis tests were used for among-group comparison. Spearman’s correlation tests were performed between DTI measures, CSF biomarkers, and clinical data. Results: AD and non-AD showed significant differences in the DTI measures across the SWM compared to HC. Significant differences between AD and non-AD were detected in the left parietal lobe. DTI measures correlated with amyloid-β42 and MMSE diffusely in the SWM, less extensively with total-tau and phosphorylated tau, and with disease duration in the parietal lobe bilaterally. Conclusion: Widespread SWM alterations occur in both AD and non-AD ND and AD shows appreciably more severe alterations in the parietal SWM. Notably, the alterations in the SWM are strongly linked not only to the cognitive decline but also to the diagnostic CSF biomarkers. Further studies are encouraged to evaluate the DTI measures in the SWM as in vivo non-invasive biomarkers in the preclinical phase.

There has been an increasing trend in oral squamous cell carcinoma (OSCC) in patients under 45 years of age. The aim of this study was to evaluate the burden of OSCC in the Netherlands between 1989 and 2018 among young adults (age 20 34 years) when compared to adults (age 35-44 years), and to describe the burden in older groups as well, utilizing cancer registry data to characterize incidence patterns by age, sex, and risk factors. A total of 18,963 cases of OSCC were reported. The overall incidence rate, as measured by annual percentage change (APC), increased significantly from 1989 to 2010 by 1.3% per year (95% confidence interval (CI) 0.9-1.7%) but decreased thereafter by -0.9% (95% CI -2.5% to 0.7%). Annual incidence increased significantly by 2.4% (95% CI 1.1-3.8%) for patients aged 20-34 years, while it decreased for those aged 35-44 years by -0.9% (95% CI -1.7% to 0.0%). In patients older than 60 years, incidence rates increased overall (60-74 years: APC 1.8%, 95% CI 1.5-2.1%; >= 75 years: APC 1.5%, 95% CI 1.2-1.9%). Overall, 66.5% of patients were smokers and 65.3% were alcohol consumers. The marked differences in incidence within the young age subgroups warrants further investigation to elucidate any likely disparity in biological process and clinical outcomes in these populations.

Contains fulltext : 290942.pdf (Publisher’s version ) (Open Access) OBJECTIVES: This study aimed to evaluate dynamics of antibody levels after exposure to SARS-CoV-2 for 12 months in Dutch non-vaccinated hairdressers and hospitality staff. METHODS: In this prospective cohort study, blood samples were collected every 3 months for 1 year and analyzed using a qualitative total antibody enzyme-linked immunosorbent assay (ELISA) and a quantitative immunoglobulin (Ig)G antibody ELISA. Participants completed questionnaires, providing information on demographics, health, and work. Differences in antibody levels were evaluated using Mann-Whitney U and Wilcoxon signed-rank tests. Beta coefficients (β) and 95% confidence intervals (CIs) were calculated using linear regression. RESULTS: Ninety-five of 497 participants (19.1%) had ≥1 seropositive measurement before their last visit using the qualitative ELISA. Only 2.1% (2/95) seroreverted during follow-up. Of 95 participants, 82 (86.3%) tested IgG seropositive in the quantitative ELISA too. IgG antibody levels significantly decreased in the first months (P

Background Accurate segmentation of head and neck squamous cell cancer (HNSCC) is important for radiotherapy treatment planning. Manual segmentation of these tumors is time-consuming and vulnerable to inconsistencies between experts, especially in the complex head and neck region. The aim of this study is to introduce and evaluate an automatic segmentation pipeline for HNSCC using a multi-view CNN (MV-CNN). Methods The dataset included 220 patients with primary HNSCC and availability of T1-weighted, STIR and optionally contrast-enhanced T1-weighted MR images together with a manual reference segmentation of the primary tumor by an expert. A T1-weighted standard space of the head and neck region was created to register all MRI sequences to. An MV-CNN was trained with these three MRI sequences and evaluated in terms of volumetric and spatial performance in a cross-validation by measuring intra-class correlation (ICC) and dice similarity score (DSC), respectively. Results The average manual segmented primary tumor volume was 11.8±6.70 cm3 with a median [IQR] of 13.9 [3.22-15.9] cm3. The tumor volume measured by MV-CNN was 22.8±21.1 cm3 with a median [IQR] of 16.0 [8.24-31.1] cm3. Compared to the manual segmentations, the MV-CNN scored an average ICC of 0.64±0.06 and a DSC of 0.49±0.19. Improved segmentation performance was observed with increasing primary tumor volume: the smallest tumor volume group (3) scored a DSC of 0.26±0.16 and the largest group (>15 cm3) a DSC of 0.63±0.11 (p Conclusion An automatic segmentation pipeline was evaluated for primary HNSCC on MRI. The MV-CNN produced reasonable segmentation results, especially on large tumors, but overestimation decreased overall performance. In further research, the focus should be on decreasing false positives and make it valuable in treatment planning.

Objective:Evidence from adult literature shows the involvement of cortical grey matter areas of the frontoparietal lobe and the white matter bundle, the superior longitudinal fasciculus (SLF) in motor planning. This is yet to be confirmed in children.Method:A multimodal study was designed to probe the neurostructural basis of childhood motor planning. Behavioural (motor planning), magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) data were acquired from 19 boys aged 8–11 years. Motor planning was assessed using the one and two colour sequences of the octagon task. The MRI data were preprocessed and analysed using FreeSurfer 6.0. Cortical thickness and cortical surface area were extracted from the caudal middle frontal gyrus (MFG), superior frontal gyrus (SFG), precentral gyrus (PcG), supramarginal gyrus (SMG), superior parietal lobe (SPL) and the inferior parietal lobe (IPL) using the Desikan–Killiany atlas. The DWI data were preprocessed and analysed using ExploreDTI 4.8.6 and the white matter tract, the SLF was reconstructed.Results:Motor planning of the two colour sequence was associated with cortical thickness of the bilateral MFG and left SFG, PcG, IPL and SPL. The right SLF was related to motor planning for the two colour sequence as well as with the left cortical thickness of the SFG.Conclusion:Altogether, morphology within frontodorsal circuity, and the white matter bundles that support communication between them, may be associated with individual differences in childhood motor planning.

Question What is the cost-effectiveness of respiratory physiotherapy interventions for people with chronic obstructive pulmonary disease? Design Systematic review of full economic evaluations alongside clinical trials published between 1997 and 2021. Reviewers independently screened studies for inclusion, extracted data and assessed methodological quality. Participants People with chronic obstructive pulmonary disease. Intervention Respiratory physiotherapy interventions as defined in the respiratory physiotherapy curriculum of the European Respiratory Society. Outcome measures Costs expressed in monetary units, effect sizes expressed in terms of disease-specific quality of life (QOL), quality-adjusted life years (QALYs) or monetary units. Results This review included 11 randomised trials with 3,261 participants. The interventions were pulmonary rehabilitation, airway clearance techniques, an integrated disease-management program and an early assisted discharge program, including inpatient respiratory physiotherapy. Meta-analysis was considered irrelevant due to the extensive heterogeneity of the reported interventions. A total of 45 incremental cost-effectiveness ratios (ICERs) were extracted. Regardless of the economic perspectives, 67% of all QOL-related ICERs and 71% of all QALY-related ICERs were situated in the north-east or south-east quadrants of the cost-effectiveness plane. Six studies could be seen as cost-effective when compared with a specified cost-effectiveness threshold per QALY gained. Conclusion Respiratory physiotherapy interventions focusing on exercise training in combination with enhancing physical activity levels are likely to be cost-effective in terms of costs per unit QOL gained and QALYs. Some uncertainty still exists on the various estimates of cost-effectiveness due to differences in the content and intensity of the type of interventions, outcome measures and comparators. Registration PROSPERO CRD42018088699.

Evaluation of the management and survival in patients treated for temporal bone squamous cell carcinoma (TBSCC) in a tertiary referral centre.Forty-nine patients underwent primary treatment for TBSCC. Thirty-six patients underwent a lateral temporal bone resection (LTBR) or subtotal temporal bone resection (STBR). Overall survival (OS) and disease-specific survival (DSS) analysis were assessed.Five-year OS of the 49 patients was 39%. Five-year OS of the 36 patients who underwent LTBR or STBR was 46%. Tumour-free margins were achieved in all patients with T1 and T2 disease, in 59% patients with T3 tumours and 0% patients with T4 disease. Five-year DSS was 85% for all T1/T2 tumours, 53% for T3 tumours and 0% for T4 tumours. Clear resection margins was the only significant predictor of DSS in our cohort.The mainstay of treatment for TBSCC is temporal bone resection with tumour free resection margins, with or without adjuvant radiotherapy. Survival is negatively influenced by non-radical resection. T1 and T2 tumours can be managed safely with LTBR. More advanced disease requires a more extensive resection, with a higher likelihood of non-radical resections and decreased survival rates.Il trattamento chirurgico del carcinoma a cellule squamose dell’osso temporale: fattori predittivi di sopravvivenza.Valutazione della gestione e sopravvivenza in pazienti trattati per carcinoma a cellule squamose dell’osso temporale (TBSCC) in un centro di riferimento terziario.Quarantanove pazienti sono stati sottoposti a trattamento primario per TBSCC. Trentasei pazienti sono stati sottoposti a resezione ossea temporale laterale (LTBR) o resezione ossea temporale subtotale (STBR). Sono state eseguite analisi della sopravvivenza globale (OS) e della sopravvivenza specifica per la malattia (DSS).l’OS a cinque anni di tutti i 49 pazienti è stata del 39%. L’OS a cinque anni di tutti i 36 pazienti sottoposti a LTBR o STBR è stata del 46%. Margini liberi da tumore sono stati raggiunti in tutti i pazienti con malattia T1 e T2, nel 59% dei pazienti con tumori T3 e nello 0% pazienti con malattia T4. Il DSS a cinque anni era dell’85% per tutti i tumori T1 / T2, del 53% per i tumori T3 e dello 0% per i tumori T4. I margini di resezione chiari erano l’unico predittore significativo di sopravvivenza specifica per malattia nella nostra coorte.Il cardine del trattamento per TBSCC è la resezione dell’osso temporale con margini di resezione senza tumore, con o senza radioterapia adiuvante. La sopravvivenza è influenzata negativamente dalla resezione irradicale. I tumori T1 e T2 possono essere gestiti in sicurezza con LTBR. Una malattia più avanzata richiede una resezione più estesa, con una maggiore probabilità di resezioni irradicali e tassi di sopravvivenza ridotti.

Quantification methods based on the acquisition of diffusion magnetic resonance imaging (dMRI) with multiple diffusion weightings (e.g., multi-shell) are becoming increasingly applied to study the in-vivo brain. Compared to single-shell data for diffusion tensor imaging (DTI), multi-shell data allows to apply more complex models such as diffusion kurtosis imaging (DKI), which attempts to capture both diffusion hindrance and restriction effects, or biophysical models such as NODDI, which attempt to increase specificity by separating biophysical components. Because of the strong dependence of the dMRI signal on the measurement hardware, DKI and NODDI metrics show scanner and site differences, much like other dMRI metrics. These effects limit the implementation of multi-shell approaches in multicenter studies, which are needed to collect large sample sizes for robust analyses. Recently, a post-processing technique based on rotation invariant spherical harmonics (RISH) features was introduced to mitigate cross-scanner differences in DTI metrics. Unlike statistical harmonization methods, which require repeated application to every dMRI metric of choice, RISH harmonization is applied once on the raw data, and can be followed by any analysis. RISH features harmonization has been tested on DTI features but not its generalizability to harmonize multi-shell dMRI. In this work, we investigated whether performing the RISH features harmonization of multi-shell dMRI data removes cross-site differences in DKI and NODDI metrics while retaining longitudinal effects. To this end, 46 subjects underwent a longitudinal (up to 3 time points) two-shell dMRI protocol at 3 imaging sites. DKI and NODDI metrics were derived before and after harmonization and compared both at the whole brain level and at the voxel level. Then, the harmonization effects on cross-sectional and on longitudinal group differences were evaluated. RISH features averaged for each of the 3 sites exhibited prominent between-site differences in the frontal and posterior part of the brain. Statistically significant differences in fractional anisotropy, mean diffusivity and mean kurtosis were observed both at the whole brain and voxel level between all the acquisition sites before harmonization, but not after. The RISH method also proved effective to harmonize NODDI metrics, particularly in white matter. The RISH based harmonization maintained the magnitude and variance of longitudinal changes as compared to the non-harmonized data of all considered metrics. In conclusion, the application of RISH feature based harmonization to multi-shell dMRI data can be used to remove cross-site differences in DKI metrics and NODDI analyses, while retaining inherent relations between longitudinal acquisitions. ispartof: Neuroimage vol:259 ispartof: location:United States status: accepted

The prognostic impact of human papillomavirus (HPV) in oropharyngeal cancer is generally acknowledged, and HPV‐status is assessed routinely in clinical practice. Paradoxically, while the oral cavity seems the predilection site for productive HPV‐infections, figures on HPV‐attribution in oral cavity squamous cell carcinoma (OCSCC) differ widely, and prognostic impact is uncertain. Major obstacles are the lack of reproducible assays to detect HPV in nonoropharyngeal cancers, the relatively small cohorts studied and consequently the shortfall of convincing data. In our study, we used a validated, nucleic acid‐based workflow to assess HPV‐prevalence in a consecutive cohort of 1016 OCSCCs, and investigated its prognostic impact. In parallel, we analyzed p16‐immunohistochemistry (p16‐IHC) as surrogate marker for transforming HPV‐infection and independent prognosticator. All OCSCC‐patients diagnosed between 2008 and 2014 at two Dutch university medical centers were included (N = 1069). Formalin‐fixed, paraffin‐embedded (FFPE)‐samples of 1016 OCSCCs could be retrieved. Punch biopsies were taken from the tumor area in the FFPE‐blocks and tested for HPV. P16‐IHC was performed on 580 OCSCCs, including all HPV‐positive tumors. From 940 samples (92.5%), nucleic acids were of sufficient quality for HPV‐testing. In total, 21 (2.2%) OCSCCs were HPV DNA‐positive. All HPV DNA‐positive tumors were E6 mRNA‐positive and considered as true HPV‐positive. There was no difference in survival between HPV‐positive and HPV‐negative OCSCCs. In total, 46 of 580 (7.9%) OCSCCs were p16‐immunopositive, including all HPV‐positive tumors. Survival was comparable in p16‐positive and p16‐negative OCSCCs. To conclude, HPV‐prevalence is very low in OCSCC and neither HPV‐status nor p16‐status affects outcome. Based on these data, determining HPV‐status in OCSCC seems irrelevant for clinical management., What's new? While human papillomavirus (HPV)‐infection is prognostic for oropharyngeal squamous cell carcinoma (OCSCC), its role and prognostic impact in OCSCC remain uncertain. In the present study, nucleic acid‐based HPV‐testing of a cohort of 1016 tumor samples collected from OCSCC patients diagnosed between 2008 and 2014 reveals very low HPV‐prevalence in OCSCC. In addition, no difference was found in survival between HPV‐positive and HPV‐negative tumors. The findings indicate that HPV is uncommon in OCSCC and, when present, has no impact on survival, providing new and important insight into the ongoing debate regarding the role of HPV in OCSCC.

Emotion regulation is related to recovery after mild traumatic brain injury (mTBI). This longitudinal tractography study examined white matter tracts subserving emotion regulation across the spectrum of mTBI, with a focus on persistent symptoms. Four groups were examined: (a) symptomatic (n = 33) and (b) asymptomatic (n = 20) patients with uncomplicated mTBI (i.e., no lesions on computed tomography [CT]), (c) patients with CT‐lesions in the frontal areas (n = 14), and (d) healthy controls (HC) (n = 20). Diffusion and conventional MRI were performed approximately 1‐ and 3‐months post‐injury. Whole‐brain deterministic tractography followed by region of interest analyses was used to identify forceps minor (FM), uncinate fasciculus (UF), and cingulum bundle as tracts of interest. An adjusted version of the ExploreDTI Atlas Based Tractography method was used to obtain reliable tracts for every subject. Mean fractional anisotropy (FA), mean, radial and axial diffusivity (MD, RD, AD), and number of streamlines were studied per tract. Linear mixed models showed lower FA, and higher MD, and RD of the right UF in asymptomatic patients with uncomplicated mTBI relative to symptomatic patients and HC. Diffusion alterations were most pronounced in the group with frontal lesions on CT, particularly in the FM and UF; these effects increased over time. Within the group of patients with uncomplicated mTBI, there were no associations of diffusion measures with the number of symptoms nor with lesions on conventional MRI. In conclusion, mTBI can cause microstructural changes in emotion regulation tracts, however, no explanation was found for the presence of symptoms., This diffusion MRI study examined frontal tracts supporting emotion regulation in patients with mild traumatic brain injury (mTBI). Asymptomatic patients with uncomplicated (i.e., no lesions on computed tomography [CT]) mTBI showed changes in the microstructure of the right uncinate fasciculus (UF), whereas symptomatic patients did not. Microstructural changes were most pronounced in patients with frontal lesions on CT, particularly in the forceps minor and UF. In uncomplicated mTBI, tract microstructure was not related to the number of symptoms or lesions on conventional MRI.

© 2022 The AuthorsSurvivors of head and neck cancer can experience long-term consequences of the cancer and subsequent treatments even after the cancer has resolved. Increasingly clinicians are aware of the social, psychological, financial, and emotional impacts of these cancers, in addition to the support required for the physical symptoms. This review provides recommendations on the long-term management and support required for survivors of head and neck cancer in the European healthcare setting.

OBJECTIVES: To estimate the effects of musculoskeletal rehabilitation interventions on movementevoked pain and to explore the assessment methods/protocols used to evaluate movement-evoked pain in adults with musculoskeletal pain. DESIGN: Systematic review with meta-analysis. LITERATURE SEARCH: Three electronic databases (PubMed, Web of Science, and Scopus) were searched. STUDY SELECTION CRITERIA: Randomized controlled trials investigating musculoskeletal rehabilitation interventions for movement-evoked pain in adults with musculoskeletal pain were included. DATA SYNTHESIS: Meta-analysis was conducted for outcomes with homogeneous data from at least 2 trials. The mean change in movementevoked pain was the primary outcome measure. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. RESULTS: Thirty-eight trials were included, and 60 different interventions were assessed. There was moderate-certainty evidence of a beneficial effect of exercise therapy compared to no treatment (standardized mean difference [SMD], -0.65; 95% confidence interval [CI]: -0.83, -0.47; P

Objectives: Quantitative Sensory Testing (QST) is used to test somatosensory functioning in patients with low back pain (LBP) and most performed on people with chronic LBP in secondary/tertiary health care facilities. Studies using QST-testing on LBP populations in primary care are scarce. Central Sensitization Inventory (CSI) measures central sensitization (CS)-related symptoms and studies investigating the differences between QST-testing and participants with LBP with a positive and negative score on the CSI questionnaire are also rare. This case-control study investigates differences of an extensive QST-measurement between patients with acute, chronic LBP and healthy controls in primary care. Secondary aim is to investigate differences of an extensive QST-measurement between "CS" and "no-CS" group. Methods: Participants with LBP were recruited from November 2016 to October 2019. Demographic and clinical information was collected and a standardized QST-protocol was taken. Data-analysis involved determining differences between groups. Results: Data of 100 participants with LBP and 50 healthy controls were analyzed. Heat pain thresholds, pressure pain threshold, conditioned pain modulation local and remote were significantly moderately to relatively strongly affected by acute, chronic LBP and healthy controls (P

Head and neck cancer (HNC) and its treatment often negatively impact swallowing function. The aim was to investigate the course of patient-reported swallowing problems from diagnosis to 3, 6, 12, and 24 months after treatment, in relation to demographic, clinical, and lifestyle factors.Data were used of the Netherlands Quality of Life and Biomedical Cohort Study in head and neck cancer research (NET-QUBIC). The primary outcome measures were the subscales of the Swallowing Quality of Life Questionnaire (SWAL-QOL). Linear mixed-effects models (LMM) were conducted to investigate changes over time and associations with patient, clinical, and lifestyle parameters as assessed at baseline.Data were available of 603 patients. There was a significant change over time on all subscales. Before treatment, 53% of patients reported swallowing problems. This number increased to 70% at M3 and decreased to 59% at M6, 50% at M12, and 48% at M24. Swallowing problems (i.e., longer eating duration) were more pronounced in the case of female, current smoking, weight loss prior to treatment, and stage III or IV tumor, and were more prevalent at 3 to 6 months after treatment. Especially patients with an oropharynx and oral cavity tumor, and patients receiving (C)RT following surgery or CRT only showed a longer eating duration after treatment, which did not return to baseline levels.Half of the patients with HNC report swallowing problems before treatment. Eating duration was associated with sex, smoking, weight loss, tumor site and stage, and treatment modality, and was more pronounced 3 to 6 months after treatment.

OBJECTIVE: To evaluate the effect of an informative 360-degree virtual reality (VR) video on preoperative anxiety before visiting a one-stop clinic for abnormal uterine bleeding.STUDY DESIGN: A randomized controlled trial was performed in a teaching hospital in the Netherlands. A total of 83 women scheduled for a first consultation at the one-stop clinic between April 2017 and September 2017 were included in the analysis. All women received a standard information leaflet about the clinic. 40 women were randomized to receive a 360-degree VR-video of the clinic in addition. The primary outcome was change in the Visual Analogue Scale for Anxiety (VAS-A), measured at baseline (before randomization) and in the waiting room (before visit, after randomization). Anxiety assessed with the State-Trait Anxiety Inventory (STAI-S) was a secondary outcome. Other secondary outcomes included anxiety during the visit and the opinion of the women about the provided information.RESULTS: Only 27 out of the 40 women actually watched the VR-video. Women in the VR-group who actually watched the video reported lower levels of anxiety at baseline compared to women in the VR-group who did not watch the video. In the intention-to-treat analysis, there was no difference in change in anxiety between the VR-group and the control group (mean difference VAS-A = 0.07, 95% CI -0.96 to 1.10; mean difference STAI-S = 1.97, 95% CI -1.82 to 5.77). In the per-protocol analysis, women in the VR-group reported lower anxiety scores in the waiting room. However, the change in anxiety scores between baseline and waiting room was comparable in both groups. 31% of the women who watched the VR-video reported that the video resulted in a reduction of anxiety, 69% reported that the video is of added value and 65% would use a VR-video again in future.CONCLUSIONS: Adding the informative 360-degree VR-video to conventional information did not result in a reduction of anxiety prior to visiting the one-stop clinic. However, the majority of women who watched the video felt that it was of added value. Remarkable was that women who reported higher anxiety at baseline seemed less willing to watch the video.

Purpose The aim of the present study is to investigate the prevalence of body image distress among head and neck cancer (HNC) patients after treatment and to examine its association with sociodemographic and clinical factors, health-related quality of life (HRQOL), HNC symptoms, sexuality, self-compassion, and psychological distress. Second, we aim to explore daily life experiences of HNC patients regarding body image. Methods A cross-sectional survey among HNC patients investigated the prevalence of body image distress based on the Body Image Scale. Multivariable logistic regression analysis was applied to study associations with sociodemographic and clinical factors, HRQOL (EORTC QLQ-C30), HNC symptoms (QLQ-HN43), sexuality (FSFI-6; IIEF-5), self-compassion (SCS-SF), and psychological distress (HADS). Qualitative data from a body image writing intervention was used to explore experiences in daily life related to body image. Results Body image distress was prevalent in 13–20% (depending on cut-off scores) of 233 HNC patients. Symptoms of depression (p p p = 0.001), problems with wound healing (p = 0.013), and larger extent of surgery (p = 0.014) were associated with having body image distress. This model explained 67% of variance. Writing interventions of 40 HNC patients showed that negative body image experiences were related to appearance and function, with social functioning problems described most often. Conclusion Prevalence of body image distress in HNC patients, using different cut-off scores, is 13–20%. Younger patients, patients after extensive surgery, and patients who had wound healing problems are most at risk. There is a significant association between body image distress and depressive symptoms and social functioning.

Background: Due to the heat and moisture exchanger's (HME) breathing resistance, laryngectomized patients cannot always use an (optimal) HME during physical exercise. We propose a novel HME cassette concept with adjustable “bypass,” to provide adjustment between different breathing resistances within one device. Methods: Under standardized conditions, the resistance and humidification performance of a high resistance/high humidification HME (XM) foam in a cassette with and without bypass were compared to a lower resistance/lesser humidification HME (XF) foam in a closed cassette. Results: With a bypass in the cassette, the resistance and humidification performance of XM foam were similar to those of XF foam in the closed cassette. Compared to XM foam in the closed cassette, introducing the bypass resulted in a 40% resistance decrease, whereas humidification performance was maintained at 80% of the original value. Conclusions: This HME cassette prototype allows adjustment between substantially different resistances while maintaining appropriate humidification performances.

Purpose We aimed to examine whether pre-treatment, post-treatment and change in health-related quality of Life (HRQoL) is associated with survival, in patients with head and neck cancer (HNC). Methods We included 948 newly diagnosed HNC patients treated with primary or adjuvant (chemo)radiotherapy with curative intent. The EORTC QLQ-C30 questionnaire was assessed pre-treatment and at 6 weeks, 6 months and 12 months post-treatment. Multivariable Cox regression analyses were performed to examine whether HRQoL at all time points and changes in HRQoL over time were associated with survival, after adjusting for demographic, clinical and lifestyle-related variables. Results Higher HRQoL scores were significantly associated with improved 5-year overall survival at all time points, except for the subscale global QoL at 6 weeks. Changes in HRQoL at 6 weeks post-treatment compared to pre-treatment were not significantly associated with survival. Changes in physical (HR: 0.88 95% CI: 0.82–0.96) and emotional functioning (HR: 0.90 95% CI: 0.85–0.96) from pre-treatment to 6 months post-treatment and changes in global QOL, and physical, emotional, and social functioning from pre-treatment to 12 months post-treatment were significantly associated with survival. Conclusion Higher HRQoL reported pre-treatment and post-treatment (6 weeks, 6 months and 12 months) are significantly associated with improved survival, as well as changes in HRQoL at 6 and 12 months compared to pre-treatment. Our results highlight the value of monitoring HRQoL and to identify those patients that report decreased or deteriorated HRQOL. This may help to further improve cancer care in a timely and efficient manner.

Purpose To develop a European White Paper document on oropharyngeal dysphagia (OD) in head and neck cancer (HNC). There are wide variations in the management of OD associated with HNC across Europe. Methods Experts in the management of specific aspects of OD in HNC across Europe were delegated by their professional medical and multidisciplinary societies to contribute to this document. Evidence is based on systematic reviews, consensus-based position statements, and expert opinion. Results Twenty-four sections on HNC-specific OD topics. Conclusion This European White Paper summarizes current best practice on management of OD in HNC, providing recommendations to support patients and health professionals. The body of literature and its level of evidence on diagnostics and treatment for OD in HNC remain poor. This is in the context of an expected increase in the prevalence of OD due to HNC in the near future. Contributing factors to increased prevalence include aging of our European population (including HNC patients) and an increase in human papillomavirus (HPV) related cancer, despite the introduction of HPV vaccination in various countries. We recommend timely implementation of OD screening in HNC patients while emphasizing the need for robust scientific research on the treatment of OD in HNC. Meanwhile, its management remains a challenge for European professional associations and policymakers.

Purpose Mucoepidermoid carcinoma (MEC) of the head and neck is a prevalent malignant salivary gland tumour with a reported good outcome. The aim of this study was to report the outcome in our centre. Methods A retrospective chart analysis with survival analyses was performed combined with fluorescence in situ hybridization (FISH) analysis to assess CRTC1/3 MAML 2 fusion gene presence. Results Sixty-four cases of MEC were identified. Median age at presentation was 51.4 years with a predominance for parotid gland involvement. Five, 10- and 20- year disease-free survival was 98%, 90% and 68%, respectively. Overall survival was 94%, 90% and 64%, respectively. Local recurrence was seen up to 14 years after primary diagnosis; distant metastases were diagnosed up to 17 years later. The overall recurrence rate was less than 20 per cent. CRTC1/3 MAML 2 fusion gene presence showed no survival benefit. Conclusion MEC of the head and neck has a favorable outcome with the exception of high-grade MEC. PNI and nodal involvement are not rare. CRTC1/3 MAML 2 fusion gene presence showed no survival benefit. The tendency for late onset of loco-regional and distant recurrence should not be underestimated.

Contains fulltext : 231712.pdf (Publisher’s version ) (Open Access) BACKGROUND: Oncokompas is a web-based self-management application that supports cancer survivors to monitor their health-related quality of life (HRQOL) and symptoms, and to obtain personalised feedback and tailored options for supportive care. In a large randomised controlled trial among survivors of head and neck cancer, colorectal cancer, and breast cancer and (non-)Hodgkin lymphoma, Oncokompas proved to improve HRQOL, and to reduce several tumour-specific symptoms. Effect sizes were however small, and no effect was observed on the primary outcome patient activation. Therefore, this study aims to explore which subgroups of cancer survivors may especially benefit from Oncokompas. MATERIALS AND METHODS: Cancer survivors (n = 625) were randomly assigned to the intervention group (access to Oncokompas, n = 320) or control group (6 months waiting list, n = 305). Outcome measures were HRQOL, tumour-specific symptoms, and patient activation. Potential moderators included socio-demographic (sex, age, marital status, education, employment), clinical (tumour type, stage, time since diagnosis, treatment modality, comorbidities), and personal factors (self-efficacy, personal control, health literacy, Internet use), and patient activation, mental adjustment to cancer, HRQOL, symptoms, and need for supportive care, measured at baseline. Linear mixed models were performed to investigate potential moderators. RESULTS: The intervention effect on HRQOL was the largest among cancer survivors with low to moderate self-efficacy, and among those with high personal control and those with high health literacy scores. Cancer survivors with higher baseline symptom scores benefitted more on head and neck (pain in the mouth, social eating, swallowing, coughing, trismus), and colorectal cancer (weight) specific symptoms. DISCUSSION: Oncokompas seems most effective in reducing symptoms in head and neck cancer and colorectal cancer survivors who report a higher burden of tumour-specific symptoms. Oncokompas seems most effective in improving HRQOL in cancer survivors with lower self-efficacy, and in cancer survivors with higher personal control, and higher health literacy.

Purpose To investigate the course of health-related quality of life (HRQOL) from diagnosis to 2 years follow-up among patients with oropharyngeal cancer (OPSCC), in relation to human papilloma virus (HPV) status. Methods This study included 270 OPSCC patients. Age, sex, tumor sublocation, tumor stage, HPV status, treatment modality, comorbidity, smoking, and alcohol use were retrieved from medical records. HPV status was positive when p16 and HPV DNA tests were both positive. HRQOL was assessed using the EORTC QLQ-C30/QLQ-H&N35 pretreatment and at 6 weeks, 6, 12, 18, and 24 months after treatment. To compare the course of HRQOL between patients with an HPV-positive versus HPV-negative tumor, linear and logistic mixed models were used. Results Patients with an HPV-positive tumor (29%) were more often male, diagnosed with a tumor of the tonsil or base of the tongue, treated with single treatment, had fewer comorbidities, were less often current smokers and had lower alcohol consumption. Adjusted for confounders, the course of global quality of life, physical, role, and social functioning, fatigue, pain, insomnia, and appetite loss was significantly different: patients with an HPV-positive tumor scored better before treatment, worsened during treatment, and recovered better and faster at follow-up, compared to patients with an HPV-negative tumor. The course of emotional functioning and oral pain was also significantly different between the two groups, but with other trajectories. Conclusion The course of HRQOL is different in patients with an HPV-positive tumor versus an HPV-negative tumor, adjusted for sociodemographic, clinical, and lifestyle confounders.

Contains fulltext : 229418.pdf (Publisher’s version ) (Open Access) BACKGROUND: Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is a rare disease, which is commonly classified with the modified Pittsburgh classification. Our aim was to evaluate the predictive performance of this classification in relation to disease-free survival (DFS). METHODS: We examined retrospective data from a nationwide Dutch cohort study including patients with primary EAC SCC. These data were combined with individual patient data from the literature. Using the combined data, the predictive performances were calculated using the c-index. RESULTS: A total of 381 patients were included, 294 for clinical and 281 for the pathological classification analyses. The c-indices of the clinical and the pathological modified Pittsburgh classification predicting DFS were 0.725 (0.668-0.782) and 0.729 (0.672-0.786), respectively. CONCLUSION: The predictive performance of the modified Pittsburgh classification system as such appears to be acceptable to predict the DFS of EAC SCC. Other factors need to be added to a future model to improve the predicted performance.

This EHNS–ESMO–ESTRO Clinical Practice Guideline provides key recommendations for managing SCCHN. It covers clinical and pathological diagnosis, staging and risk assessment, treatment and follow-up. Opportunities for personalised medicine in SCCHN are also discussed. All recommendations were compiled by a multidisciplinary group of experts from different institutions and countries. Recommendations are based on available clinical evidence and the collective expert opinion of the authors.

Background We investigated the added value of combining information from direction-encoded color (DEC) maps with high-resolution structural magnetic resonance imaging scans (T1-weighted images [T1WIs]) to improve the identification of regions of interest (ROIs) for fiber tracking during preoperative planning for patients with brain tumors. Methods The dataset included 42 patients with gliomas and 10 healthy subjects from the Human Connectome Project. For identification of the ROIs, we combined the structural information from high-resolution T1WIs and the directional information from DEC maps. To test our hypothesis, we examined the interrater and intrarater agreement. Results We identified specific ROIs to extract the main white matter bundles. The directional information from the DEC maps combined with the T1WIs (T1WI–DEC maps) had significantly facilitated ROI identification in patients with brain tumors, especially patients in whom the tracts had been displaced by the mass effect of the tumor. Fiber tracking using the combined T1WI–DEC maps showed significantly greater inter- and intrarater agreement compared with using either T1WI or DEC maps alone. Conclusion Combining the information from diffusion-derived color-encoded maps with high-resolution anatomical details from structural imaging (T1WI–DEC map), especially in patients with brain tumors, could be useful for accurate identification of the ROIs.

At the Photo Injector Test facility at DESY in Zeuthen (PITZ), an RD platform for electron FLASH and very high energy electron radiation therapy and radiation biology is being prepared (FLASHlab@PITZ). The beam parameters available at PITZ are worldwide unique. They are based on experiences from 20 + years of developing high brightness beam sources and an ultra-intensive THz light source demonstrator for ps scale electron bunches with up to 5 nC bunch charge at MHz repetition rate in bunch trains of up to 1 ms length, currently 22 MeV (upgrade to 250 MeV planned). Individual bunches can provide peak dose rates up to 10

Thresholding of low-weight connections of diffusion MRI-based brain networks has been proposed to remove false-positive connections. It has been previously established that this yields more reproducible scan-rescan network architecture in healthy subjects. In patients with brain disease, network measures are applied to assess inter-individual variation and changes over time. Our aim was to investigate whether thresholding also achieves improved consistency in network architecture in patients, while maintaining sensitivity to disease effects for these applications.We applied fixed-density and absolute thresholding on brain networks in patients with cerebral small vessel disease (SVD, n = 86; ≈24 months follow-up), as a clinically relevant exemplar condition. In parallel, we applied the same methods in healthy young subjects (n = 44; scan-rescan interval ≈4 months) as a frame of reference. Consistency of network architecture was assessed with dice similarity of edges and intraclass correlation coefficient (ICC) of edge-weights and hub-scores. Sensitivity to disease effects in patients was assessed by evaluating interindividual variation, changes over time, and differences between those with high and low white matter hyperintensity burden, using correlation analyses and mixed ANOVA.Compared to unthresholded networks, both thresholding methods generated more consistent architecture over time in patients (unthresholded: dice = .70; ICC: .70-.78; thresholded: dice = .77; ICC: .73-.83). However, absolute thresholding created fragmented nodes. Similar observations were made in the reference group. Regarding sensitivity to disease effects in patients, fixed-density thresholds that were optimal in terms of consistency (densities: .10-.30) preserved interindividual variation in global efficiency and node strength as well as the sensitivity to detect effects of time and group. Absolute thresholding produced larger fluctuations of interindividual variation.Our results indicate that thresholding of low-weight connections, particularly when using fixed-density thresholding, results in more consistent network architecture in patients with longer rescan intervals, while preserving sensitivity to disease effects.

In cerebral small vessel disease (cSVD), whole brain MRI markers of cSVD-related brain injury explain limited variance to support individualized prediction. Here, we investigate whether considering abnormalities in brain tracts by integrating multimodal metrics from diffusion MRI (dMRI) and structural MRI (sMRI), can better capture cognitive performance in cSVD patients than established approaches based on whole brain markers. We selected 102 patients (73.7 ± 10.2 years old, 59 males) with MRI-visible SVD lesions and both sMRI and dMRI. Conventional linear models using demographics and established whole brain markers were used as benchmark of predicting individual cognitive scores. Multi-modal metrics of 73 major brain tracts were derived from dMRI and sMRI, and used together with established markers as input of a feed-forward artificial neural network (ANN) to predict individual cognitive scores. A feature selection strategy was implemented to reduce the risk of overfitting. Prediction was performed with leave-one-out cross-validation and evaluated with the R2 of the correlation between measured and predicted cognitive scores. Linear models predicted memory and processing speed with R2 = 0.26 and R2 = 0.38, respectively. With ANN, feature selection resulted in 13 tract-specific metrics and 5 whole brain markers for predicting processing speed, and 28 tract-specific metrics and 4 whole brain markers for predicting memory. Leave-one-out ANN prediction with the selected features achieved R2 = 0.49 and R2 = 0.40 for processing speed and memory, respectively. Our results show proof-of-concept that combining tract-specific multimodal MRI metrics can improve the prediction of cognitive performance in cSVD by leveraging tract-specific multi-modal metrics.

To investigate if network thresholding and raw data harmonization improve consistency of diffusion MRI (dMRI)-based brain networks while also increasing precision and sensitivity to detect disease effects in multicentre datasets.Brain networks were reconstructed from dMRI of five samples with cerebral small vessel disease (SVD; 629 patients, 166 controls), as a clinically relevant exemplar condition for studies on network integrity. We evaluated consistency of network architecture in age-matched controls, by calculating cross-site differences in connection probability and fractional anisotropy (FA). Subsequently we evaluated precision and sensitivity to disease effects by identifying connections with low FA in sporadic SVD patients relative to controls, using more severely affected patients with a pure form of genetically defined SVD as reference.In controls, thresholding and harmonization improved consistency of network architecture, minimizing cross-site differences in connection probability and FA. In patients relative to controls, thresholding improved precision to detect disrupted connections by removing false positive connections (precision, before: 0.09-0.19; after: 0.38-0.70). Before harmonization, sensitivity was low within individual sites, with few connections surviving multiple testing correction (k = 0-25 connections). Harmonization and pooling improved sensitivity (k = 38), while also achieving higher precision when combined with thresholding (0.97).We demonstrated that network consistency, precision and sensitivity to detect disease effects in SVD are improved by thresholding and harmonization. We recommend introducing these techniques to leverage large existing multicentre datasets to better understand the impact of disease on brain networks.

Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio , as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay.

Introduction: The aim was to analyse prognosticators in acinic cell carcinoma (AciCC) in two head and neck referral centers in Amsterdam, the Netherlands. Materials and methods: Eighty- nine cases of AciCC treated between 1979 and 2016 were retrospectively reviewed. Five, − 10 -and 20- year estimates of survival were executed as well as univariate analysis of prognosticators. Results: The majority of AciCC were T1-T2; 89%. Two percent had nodal disease (2%). The most affected organ was the parotid gland (84%) with a female preponderance (67%). Mean age was 52 years with most cases diagnosed in the fourth to sixth decade. The majority of patients received adjuvant radiotherapy. Elective neck dissection (END) in the N0 neck showed no metastases. High grade transformation (HGT) was found in 21% of cases. Median follow up was 101.9 months. Median time to recurrence was 26 months. Nine patients developed distant metastases (DM) of whom 6 had HGT-AciCC. Median survival with DM was 7 months. Five,- ten -and twenty- year estimates were 84%, 81% and 81% for recurrence free survival respectively. Negative clinical features were advanced stage disease and tumour size > 2.6 cm. Negative histological features were a high mitotic rate, HGT, close and involved surgical margins and necrosis. Conclusion: AciCC- HGT excluded- of the head and neck has an excellent prognosis and shows acceptable long term results. END can be considered as part of the standard treatment due to the relative high incidence of HGT- AciCC and low accuracy of cytology.