Extending the use of the Endoscopic Endonasal Sinus and Skull Base Surgery Questionnaire in a cross-sectional study:Patients with chronic rhinosinusitis versus healthy controls

Objectives There are several instruments to assess health-related quality of life (HRQoL) in chronic rhinosinusitis (CRS). Unfortunately, none of them evaluates all three health domains (physical, social and psychological) important to assess the overall well-being of the patient. The Endoscopic Endonasal Sinus and Skull Base Surgery Questionnaire (EES-Q) does assess all these elements. Initially, the EES-Q is validated to evaluate the impact of endoscopic endonasal surgery (EES) on HRQoL. The aim of this study is to assess whether EES-Q outcomes differ in patients with CRS compared with healthy individuals. Therefore, extending the use of the EES-Q for all CRS patients. Design Cross-sectional study. Setting Tertiary referral hospital. Participants One hundred patients with uncontrolled CRS (50% with nasal polyps) scheduled to receive EES. The questionnaire was completed preoperatively. Healthy control subjects (n = 100) without any history of sinusitis or a known current medical treatment at a hospital were included. Main outcome measures Mann-Whitney U test was performed to identify differences in EES-Q scores (domain scores and EES-Q score). Results The median EES-Q score in CRS patients (33.8) was significantly higher (p < 0.001) than in the control group (10.4). As well as the physical (52.5 vs. 16.4, p < 0.001), psychological (13.8 vs. 5.0, p < 0.001) and social (37.5 vs. 2.5, p < 0.001) domain scores. Conclusions With this study, we are extending the use of the EES-Q. It indicates that the EES-Q can be a valuable clinical tool to assess multidimensional HRQoL in all patients with CRS

The effect of three-dimensional visualisation on performance in endoscopic sinus surgery:A clinical training study using surgical navigation for movement analysis in a randomised crossover design

Objectives: Endoscopic imaging techniques and endoscopic endonasal surgery (EES) expertise have evolved rapidly. Only few studies have assessed the effect of three-dimensional (3D) endoscopy on endoscopic sinus surgery (ESS). The present study aimed to objectively and subjectively assess the additional value of 3D high-definition (HD) endoscopy in ESS. Design: A randomized crossover study of endoscopic surgery performance, using five ESS tasks of varying complexity, performed on Thiel embalmed human specimens. Setting: Simulated surgical environment. Participants: Thirty participants, inexperienced in ESS. Main outcome measures: Performance was assessed using video imaging, surgical navigation and questionnaires. Main outcome measures were as follows: efficiency (defined by time to task completion), distance covered inside the nose, average velocity towards target, accuracy (measured by error rate), and subjective assessment of endoscope characteristics. Results: During ESS tasks, both efficiency and accuracy did not differ significantly between 2D HD and 3D HD endoscopy. Subjectively, imaging characteristics of the 3D HD endoscope were rated significantly better. Conclusions: ESS performance of inexperienced participants was not significantly improved by the use of 3D HD endoscopy during ESS tasks, although imaging characteristics of the 3D HD endoscope were rated significantly better. Surgical field characteristics and surgical techniques are likely to influence any additional value of 3D HD endoscopy

Prospective evaluation of multidimensional health-related quality of life after endoscopic endonasal surgery for pituitary adenomas using the endoscopic endonasal sinus and skull base surgery questionnaire

Objective: Social functioning is an important factor in the evaluation of postoperative health-related quality of life (HRQoL) for pituitary adenoma patients. In a prospective cohort study multidimensional HRQoL of non-functioning (NFA) and functioning (FA) pituitary adenoma patients were evaluated following endoscopic endonasal surgery using the endoscopic endonasal sinus and skull base surgery questionnaire (EES-Q). Methods: Prospectively, 101 patients were included. The EES-Q was completed preoperatively and postoperatively (2 weeks, 3 months, 1 year). Sinonasal complaints were completed daily during the first week postoperatively. Preoperative and postoperative scores were compared. A generalized estimating equation (uni- and multivariate) analysis was performed to identify significant HRQoL changes related to selected covariates. Results: Two weeks postoperatively, physical (p &lt;.05) and social (p &lt;.05) HRQoL are worse and psychological (p &lt;.05) HRQoL improved compared with preoperatively. Three months postoperatively, psychological HRQoL (p =.01) trended back to baseline and no differences in physical or social HRQoL were reported. One year postoperatively, psychological (p =.02) and social (p =.04) HRQoL improved while physical HRQoL remained stable. FA patients report a worse HRQoL preoperatively (social, p &lt;.05) and 3 months postoperatively (social, p &lt;.02 and psychological, p &lt;.02). Sinonasal complaints peak in the first days postoperatively and gradually return to presurgical levels 3 months postoperatively. Conclusions: The EES-Q provides meaningful information on multidimensional HRQoL to improve patient-centred health care. Social functioning remains the most difficult area in which to achieve improvements. Despite the relatively modest sample size, there is some indication that the FA group continues to show a downward trend (and thus improvement) even after 3 months, when most other parameters reach stability. Level of evidence: Level II—B.</p

Detection by fluorescence of pituitary neuroendocrine tumour (PitNET) tissue during endoscopic transsphenoidal surgery using bevacizumab-800CW (DEPARTURE trial):study protocol for a non-randomised, non-blinded, single centre, feasibility and dose-finding trial

INTRODUCTION: Achieving gross total resection and endocrine remission in pituitary neuroendocrine tumours (PitNET) can be challenging, especially in PitNETs with cavernous sinus (CS) invasion, defined as a Knosp grade of 3 or 4. A potential target to identify PitNET tissue is vascular endothelial growth factor A (VEGF-A), which expression is known to be significantly higher in PitNETs with CS invasion.METHODS AND ANALYSIS: The aim of this non-randomised, non-blinded, single centre, feasibility and dose-finding phase 1 trial is to determine the feasibility of intraoperative fluorescence imaging detection of PitNET tissue during endoscopic transsphenoidal surgery using the VEGF-A targeting optical agent bevacizumab-800CW (4, 5, 10 or 25 mg). Nine to fifteen patients with a PitNET with a Knosp grade of 3 or 4 will be included. Secondary objectives are: (1) To identify the optimal tracer dose for imaging of PitNET tissue during transsphenoidal surgery for further development in a phase 2 fluorescence molecular endoscopy trial. (2) To quantify fluorescence intensity in vivo and ex vivo with multidiameter single-fibre reflectance, single-fibre fluorescence (MDSFR/SFF) spectroscopy. (3) To correlate and validate both the in vivo and ex vivo measured fluorescence signals with histopathological analysis and immunohistochemical staining. (4) To assess the (sub)cellular location of bevacizumab-800CW by ex vivo fluorescence microscopy. Intraoperative, three imaging moments are defined to detect the fluorescent signal. The tumour-to-background ratios are defined by intraoperative fluorescence in vivo measurements including MDSFR/SFF spectroscopy data and by ex vivo back-table fluorescence imaging. After inclusion of three patients in each dose group, an interim analysis will be performed to define the optimal dose.ETHICS AND DISSEMINATION: Approval was obtained from the Medical Ethics Review Board of the University Medical Centre Groningen. Results will be disseminated through national and international journals. The participants and relevant patient support groups will be informed about the results.TRIAL REGISTRATION NUMBER: NCT04212793.</p

Intrinsic factors and the embryonic environment influence the formation of extragonadal teratomas during gestation

Background: Pluripotent cells are present in early embryos until the levels of the pluripotency regulator Oct4 drop at the beginning of somitogenesis. Elevating Oct4 levels in explanted post-pluripotent cells in vitro restores their pluripotency. Cultured pluripotent cells can participate in normal development when introduced into host embryos up to the end of gastrulation. In contrast, pluripotent cells efficiently seed malignant teratocarcinomas in adult animals. In humans, extragonadal teratomas and teratocarcinomas are most frequently found in the sacrococcygeal region of neonates, suggesting that these tumours originate from cells in the posterior of the embryo that either reactivate or fail to switch off their pluripotent status. However, experimental models for the persistence or reactivation of pluripotency during embryonic development are lacking. Methods: We manually injected embryonic stem cells into conceptuses at E9.5 to test whether the presence of pluripotent cells at this stage correlates with teratocarcinoma formation. We then examined the effects of reactivating embryonic Oct4 expression ubiquitously or in combination with Nanog within the primitive streak (PS)/tail bud (TB) using a transgenic mouse line and embryo chimeras carrying a PS/TB-specific heterologous gene expression cassette respectively. Results: Here, we show that pluripotent cells seed teratomas in post-gastrulation embryos. However, at these stages, induced ubiquitous expression of Oct4 does not lead to restoration of pluripotency (indicated by Nanog expression) and tumour formation in utero, but instead causes a severe phenotype in the extending anteroposterior axis. Use of a more restricted T(Bra) promoter transgenic system enabling inducible ectopic expression of Oct4 and Nanog specifically in the posteriorly-located primitive streak (PS) and tail bud (TB) led to similar axial malformations to those induced by Oct4 alone. These cells underwent induction of pluripotency marker expression in Epiblast Stem Cell (EpiSC) explants derived from somitogenesis-stage embryos, but no teratocarcinoma formation was observed in vivo. Conclusions: Our findings show that although pluripotent cells with teratocarcinogenic potential can be produced in vitro by the overexpression of pluripotency regulators in explanted somitogenesis-stage somatic cells, the in vivo induction of these genes does not yield tumours. This suggests a restrictive regulatory role of the embryonic microenvironment in the induction of pluripotency

Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign

Abstract: In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M ⊙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87’s spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded

Evaluation of the psychometric properties of the endoscopic endonasal sinus and skull base surgery questionnaire (EES-Q) in a prospective cohort study

OBJECTIVES: The patients' perspective on health has become increasingly important when assessing treatment outcomes. Recently, the Endoscopic Endonasal Sinus and Skull Base Surgery Questionnaire (EES-Q) was developed to determine the impact of endoscopic endonasal surgery on health-related quality of life (HRQoL). The aim of this study was to evaluate the test-retest reliability, construct validity, and responsiveness of the EES-Q. DESIGN: Prospective cohort study. SETTING: University Medical Center Groningen, tertiary referral hospital, the Netherlands. PARTICIPANTS: One hundred patients who underwent endoscopic endonasal surgery because of sinus or anterior skull base pathology. MAIN OUTCOME MEASURES: Test-retest reliability, construct validity and responsiveness. RESULTS: The EES-Q domains exhibited good test-retest reliability (ICC > 0.90). Construct validity was corroborated by significant positive and negative correlations between the EES-Q and the SNOT-22 and postoperative health status (p < 0.01) respectively. The correlation between the social EES-Q domain and the ability to move and perform usual activities (EQ-5D-3L) was significant positive (p < 0.01). In patients with paranasal sinus pathology, the EES-Q was responsive to clinical change (Cohen's d = 0.6). CONCLUSION: The EES-Q is a reliable and acceptable responsive disease-specific HRQoL instrument. The expected construct validity of the EES-Q is supported by the results in this study. Inconveniences in social functioning had the greatest negative impact on postoperative health status rating. This reflects the importance of a multidimensional HRQoL assessment after EES. The results indicate that the EES-Q is a promising disease-specific tool for the HRQoL assessment after endoscopic endonasal sinus or anterior skull base surgery. This article is protected by copyright. All rights reserved

Calculating nasoseptal flap dimensions:a cadaveric study using cone beam computed tomography

We hypothesize that three-dimensional imaging using cone beam computed tomography (CBCT) is suitable for calculating nasoseptal flap (NSF) dimensions. To evaluate our hypothesis, we compared CBCT NSF dimensions with anatomical dissections. The NSF reach and vascularity were studied. In an anatomical study (n = 10), CBCT NSF length and surface were calculated and compared with anatomical dissections. The NSF position was evaluated by placing the NSF from the anterior sphenoid sinus wall and from the sella along the skull base towards the frontal sinus. To visualize the NSF vascularity in CBCT, the external carotic arteries were perfused with colored Iomeron. Correlations between CBCT NSFs and anatomical dissections were strongly positive (r > 0.70). The CBCT NSF surface was 19.8 cm(2) [16.6-22.3] and the left and right CBCT NSF lengths were 78.3 mm [73.2-89.5] and 77.7 mm [72.2-88.4] respectively. Covering of the anterior skull base was possible by positioning the NSF anterior to the sphenoid sinus. If the NSF was positioned from the sella along the skull base towards the frontal sinus, the NSF reached partially into the anterior ethmoidal sinuses. CBCT is a valuable technique for calculating NSF dimensions. CBCT to demonstrate septum vascularity in cadavers proved to be less suitable. The NSF reach for covering the anterior skull base depends on positioning. This study encourages preoperative planning of a customized NSF, in an attempt to spare septal mucosa. In the concept of minimal invasive surgery, accompanied by providing customized care, this can benefit the patients' postoperative complaints

Development of the Endoscopic Endonasal Sinus and Skull Base Surgery Questionnaire

Background: The patients' perspective of health outcomes has become important input for assessing treatment effects. However, existing endoscopic endonasal surgery (EES) instruments are not fully aligned with the concept of health-related quality of life (HRQoL). A prospective cohort study was therefore conducted to develop a suitable quality-of-life tool to assess nasal morbidity after EES: the Endoscopic Endonasal Sinus and Skull Base Surgery Questionnaire (EES-Q). Methods: The study included 300 patients: 207 with sinus pathology and 93 with anterior skull base pathology. The EES-Q was administered prior to surgery and postoperatively (2 weeks, 3 months, and 1 year). Psychometric instrument properties were tested and relevant health domains were formulated. Seventy-two items were generated by the conventional psychometric approach. An exploratory factor analysis was used to test construct validity. The optimal number of factors to retain was determined by using the eigenvalues-greater-than-1 rule and scree plot. Orthogonal varimax rotation was used to enhance interpretability. Internal consistency was assessed using the Cronbach alpha. Results: The factor analysis yielded a 3-factor solution, representing physical, psychological, and social functioning. The final version of the instrument consisted of 30 items with a high internal consistency (>0.80) for all 3 HRQoL domains. Conclusions: The EES-Q is a comprehensive, multidimensional, disease-specific instrument. A distinguishing characteristic is that, apart from the physical and psychological domains, the EES-Q also encompasses a social domain. Understanding different HRQoL aspects in patients undergoing EES may help caregivers restore, improve, or preserve the patient's health through individualized care, which depends on identifying their specific needs. (C) 2017 ARS-AAOA, LLC

BRAF V600E is associated with higher incidence of second cancers in adults with Langerhans cell histiocytosis

In this retrospective study, BRAF mutation status did not correlate with disease extent or (event-free) survival in 156 adults with Langerhans cell histiocytosis. BRAF V600E was associated with an increased incidence of second malignancies, often comprising hematological cancers, which may be clonally related.</p