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Study Question: What are outcome and procedural differences when using the semi-automated closed Gavi® device versus the manual open Cryotop® method for vitrification of pronuclear (2PN) stage oocytes within an IVF program?, Summary Answer: A semi-automated closed vitrification method gives similar clinical results as compared to an exclusively manual, open system but higher procedure duration and less staff convenience., What Is Known Already: A semi-automated closed vitrification device has been introduced to the market, however, little evaluation of its performance in a clinical setting has been conducted so far., Study Design, Size, Duration: This prospective, randomised, open non-inferiority trial was conducted at three German IVF centers (10/2017-12/2018). Randomization was performed on day of fertilization check, stratified by center and by indication for vitrification (surplus 2PN oocytes in the context of a fresh embryo transfer (ET) cycle or 'freeze-all' of 2PN oocytes)., Participant/material, Setting, Methods: The study population included subfertile women, aged 18-40 years, undergoing IVF or ICSI treatment after ovarian stimulation, with 2PN oocytes available for vitrification. The primary outcome was survival rate of 2PN oocytes at first warming procedure in a subsequent cycle and non-inferiority of 2PN survival was to be declared if the lower bound 95% CI of the mean difference in survival rate excluded a difference larger than 9.5%; secondary, descriptive outcomes included embryo development, pregnancy and live birth rate, procedure time and staff convenience., Main Results and the Role of Chance: The randomised patient population consisted of 149 patients, and the per-protocol population (patients with warming of 2PN oocytes for culture and planned ET) was 118 patients. The survival rate was 94.0% (±13.5) and 96.7% (±9.7) in the Gavi® and the Cryotop® group (weighted mean difference -1.6%, 95% CI -4.7 to 1.4, P = 0.28), respectively, indicating non-inferiority of the Gavi® vitrification/warming method for the primary outcome. Embryo development and the proportion of top-quality embryos was similar in the two groups, as were the pregnancy and live birth rate. Mean total procedure duration (vitrification and warming) was higher in the Gavi® group (81 ± 39 min vs 47 ± 15 min, mean difference 34 min, 95% CI 19 to 48). Staff convenience assessed by eight operators in a questionnaire was lower for the Gavi® system. The majority of respondents preferred the Cryotop® method because of practicality issues., Limitations, Reason for Caution: The study was performed in centers with long experience of manual vitrification, and the relative performance of the Gavi® system as well as the staff convenience may be higher in settings with less experience in the manual procedure. Financial costs of the two procedures were not measured along the trial., Wider Implications of the Findings: With increasing requirements for standardization of procedures and tissue safety, a semi-automated closed vitrification method may constitute a suitable alternative technology to the established manual open vitrification method given the equivalent clinical outcomes demonstrated herein., Study Funding/competing Interests: The trial received no direct financial funding. The Gavi® instrument, Gavi® consumables and staff training were provided for free by the distributor (Merck, Darmstadt, Germany) during the study period. The manufacturer of the Gavi® instrument had no influence on study protocol, study conduct, data analysis, data interpretation or manuscript writing. J.H. has received honoraria and/or non-financial support from Ferring, Merck and Origio. G.G. has received honoraria and/or non-financial support from Abbott, Ferring, Finox, Gedeon Richter, Guerbet, Merck, MSD, ObsEva, PregLem, ReprodWissen GmbH and Theramex. The remaining authors have no competing interests., Trial Registration Number: ClinicalTrials.gov NCT03287479., Trial Registration Date: 19 September 2017., Date of First Patient’s Enrolment: 10 October 2017., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Fluorescence-guided surgery (FGS) allows surgeons to have improved visualization of tumor tissue in the operating room, enabling maximal safe resection of malignant brain tumors. Over the past two decades, multiple fluorescent agents have been studied for FGS, including 5-aminolevulinic acid (5-ALA), fluorescein sodium, and indocyanine green (ICG). Both non-targeted and targeted fluorescent agents are currently being used in clinical practice, as well as under investigation, for glioma visualization and resection. While the efficacy of intraoperative fluorescence in studied fluorophores has been well established in the literature, the effect of timing on fluorophore administration in glioma surgery has not been as well depicted. In the past year, recent studies of 5-ALA use have shown that intraoperative fluorescence may persist beyond the previously studied window used in prior multicenter trials. Additionally, the use of fluorophores for different brain tumor types is discussed in detail, including a discussion of choosing the right fluorophore based on tumor etiology. In the following review, the authors will describe the temporal nature of the various fluorophores used in glioma surgery, what remains uncertain in FGS, and provide a guide for using fluorescence as a surgical adjunct in brain tumor surgery., Competing Interests: CH is a consultant for NX Development Corporation (NXDC) and Synaptive Medical. NXDC, a privately held company, markets Gleolan (5-ALA, aminolevulinic acid hydrochloride). Gleolan is an optical imaging agent approved for the visualization of malignant tissue during glioma surgery. CH is a consultant for NXDC and receives royalty payments for the sale of Gleolan, has also received speaker fees by Carl Zeiss and Leica. FA has received speaker's fees from Carl Zeiss Meditec, Oberkochen, Germany. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schupper, Rao, Mohammadi, Baron, Lee, Acerbi and Hadjipanayis.)

Background: Fluorescence-guided surgery (FGS) using 5-aminolevulic acid (5-ALA) is a widely used strategy for delineating tumor tissue from surrounding brain intraoperatively during high-grade glioma (HGG) resection. 5-ALA reaches peak plasma levels ~4 h after oral administration and is currently approved by the FDA for use 2-4 h prior to induction to anesthesia. Objective: To demonstrate that there is adequate intraoperative fluorescence in cases undergoing surgery more than 4 h after 5-ALA administration and compare survival and radiological recurrence to previous data. Methods: Retrospective analysis of HGG patients undergoing FGS more than 4 h after 5-ALA administration was performed at two institutions. Clinical, operative, and radiographic pre- and post-operative characteristics are presented. Results: Sixteen patients were identified, 6 of them female (37.5%), with mean (SD) age of 59.3 ± 11.5 years. Preoperative mean modified Rankin score (mRS) was 2 ± 1. All patients were dosed with 20 mg/kg 5-ALA the morning of surgery. Mean time to anesthesia induction was 425 ± 334 min. All cases had adequate intraoperative fluorescence. Eloquent cortex was involved in 12 cases (75%), and 13 cases (81.3%) had residual contrast enhancement on postoperative MRI. Mean progression-free survival was 5 ± 3 months. In the study period, 6 patients died (37.5%), mean mRS was 2.3 ± 1.3, Karnofsky score 71.9 ± 22.1, and NIHSS 3.9 ± 2.4. Conclusion: Here we demonstrate that 5-ALA-guided HGG resection can be performed safely more than 4 h after administration, with clinical results largely similar to previous reports. Relaxation of timing restrictions could improve procedure workflow in busy neurosurgical centers, without additional risk to patients., Competing Interests: CH is a consultant for NX Development Corporation (NXDC) and Synaptive Medical. NXDC, a privately held company, markets Gleolan (5-ALA, aminolevulinic acid hydrochloride). Gleolan is an optical imaging agent approved for the visualization of malignant tissue during glioma surgery. CH is a consultant for NXDC and receives royalty payments for the sale of Gleolan. CH receives financial compensation as a consultant and lecturer for Synaptive (manufacturer of the 3D Synaptive MODUS V device). He has also received speaker fees by Carl Zeiss and Leica. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Maragkos, Schüpper, Lakomkin, Sideras, Price, Baron, Hamilton, Haider, Lee, Hadjipanayis and Robin.)

Background: Tuberculous spondylitis (Pott's disease), a common extrapulmonary manifestation of tuberculosis (TB), typically presents with back pain, tenderness, paraparesis/paraplegia, and various constitutional symptoms. Due to radiological similarities between Pott's disease and lung cancer, some lung cancer patients may initially be erroneously diagnosed and treated for TB, allowing for extensive progression of their cancer., Case Description: A 28-year-old male presented with a chronic dry cough, weight loss, and 2 months of increased back pain accompanied by bilateral lower extremity weakness. Magnetic resonance imaging revealed an epidural collection causing compression of the spinal cord at the T5-T6 level. The initial diagnosis was Mycobacterium tuberculosis /Pott's disease. A thoracic T4-T8 decompression fusion was performed; however, pathologic examination of the tissue revealed adenocarcinoma. Postoperatively, after the patient experienced several episodes of acute respiratory distress and a tension pneumothorax, lung imaging confirmed multiple tumor infiltrates along with lung cancer extending into the thoracic vertebrae. Pelvic studies also confirmed the presence of pelvic metastases. The patient passed away 3 weeks following surgery., Conclusion: In this case report, a 28-year-old male was treated for thoracic Pott's disease that proved to be metastatic lung adenocarcinoma. To avoid such misdiagnoses in the future, physicians should better differentiate spinal TB from other malignancies that may affect the spine. This study underscores the importance of obtaining at least a chest X-ray in any patient with suspected Pott's disease, irrespective of age, to help rule out lung cancer or other pathologies., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Surgical Neurology International.)

Purpose: The rationale for 'professional education and development' (PED) courses is to support general practitioners, enabling them to access a range of theoretical and practical skills within a supportive schema. It aims to identify whether and how a regional PED course has had a beneficial impact upon participants., Methods: The study comprised a qualitative investigation of participants' assessed coursework portfolios. The content of each portfolio gives individual accounts of the impact of the course on personal and practice development. Permission to access extant portfolios was obtained from 16 recent alumni of the course. The anonymous written material was analysed by the research team for recurring discourses and themes using a thematic framework analysis., Results: Seven major thematic categories were extrapolated from the data: leadership, resilience, quality improvement, change management, development of new services, educational expertise, and patient safety. In each category, we found evidence that the course enabled development of practitioners by enhancing knowledge and skills which had a positive impact upon their self-perceived effectiveness and motivation., Conclusion: Extended specialty training is on the horizon but such courses may still serve a valuable purpose for current trainees and the existing general practitioners workforce which will be responsible for leading the shift towards community-based service delivery.

Although laughter forms an important part of human non-verbal communication, it has received rather less attention than it deserves in both the experimental and the observational literatures. Relaxed social (Duchenne) laughter is associated with feelings of wellbeing and heightened affect, a proximate explanation for which might be the release of endorphins. We tested this hypothesis in a series of six experimental studies in both the laboratory (watching videos) and naturalistic contexts (watching stage performances), using change in pain threshold as an assay for endorphin release. The results show that pain thresholds are significantly higher after laughter than in the control condition. This pain-tolerance effect is due to laughter itself and not simply due to a change in positive affect. We suggest that laughter, through an endorphin-mediated opiate effect, may play a crucial role in social bonding.