Determinants of quality of life following resection of skull base tumors: a systematic review

BackgroundSkull base tumors represent a small subset of intracranial neoplasm. Due to their proximity to critical neurovascular structures, their resection often leads to morbidity. As a result, surgical interventions can exacerbate symptoms or cause new deficits, thereby impacting the patients’ perceived quality of life (QoL). The factors influencing QoL in patients with skull base tumors remain underexplored. This systematic review aims to synthesize current research on QoL outcomes and identify potential factors influencing QoL in these patients.MethodsA systematic literature review was conducted in PubMed using the keywords “Skull Base” AND “Quality of Life.” A total of 815 studies published up to January 31, 2024, were screened. After abstract review, 656 studies were excluded, and 159 studies underwent full-text review. The wide variability in study methodologies and utilized QoL instruments made only a descriptive comparison possible.ResultsIn total, 113 studies were systematically reviewed. Publications focusing on the same tumor type or localization were compared. The majority of studies addressed tumors of the anterior skull base, with pituitary adenomas, meningiomas and vestibular schwannomas being the most commonly represented. The impact of surgery on QoL is often underestimated by caregivers and has a more profound effect on patients than expected by surgeons. A transient decline in QoL after surgery was observed across almost all studies regardless of localization and entity. Factors influencing QoL included age, gender, tumor localization, surgical approach, tumor type, extent of resection, preoperative clinical status and neurological deficits. Radiotherapy and recurrent surgeries were predictors of poorer QoL. Early psychological intervention in complex tumors appears to enhance QoL. Some successful sealing techniques, such as nasoseptal flaps and lumbar drains, affected QoL. However, variability in study methodologies reduced the validity of the findings.ConclusionThis review highlights the significant impact of skull base tumor surgery on patients’ QoL. Given the major oncological and surgical challenges presented by skull base tumors, their treatment significantly affects QoL, and gross total resection (GTR) should not always be the primary goal. Additionally, recognizing and addressing the modifiable and non-modifiable factors influencing QoL is crucial for improving patient outcomes and providing personalized care

Applied deep learning in neurosurgery: identifying cerebrospinal fluid (CSF) shunt systems in hydrocephalus patients.

BACKGROUND Over the recent decades, the number of different manufacturers and models of cerebrospinal fluid shunt valves constantly increased. Proper identification of shunt valves on X-ray images is crucial to neurosurgeons and radiologists to derive further details of a specific shunt valve, such as opening pressure settings and MR scanning conditions. The main aim of this study is to evaluate the feasibility of an AI-assisted shunt valve detection system. METHODS The dataset used contains 2070 anonymized images of ten different, commonly used shunt valve types. All images were acquired from skull X-rays or scout CT-images. The images were randomly split into a 80% training and 20% validation set. An implementation in Python with the FastAi library was used to train a convolutional neural network (CNN) using a transfer learning method on a pre-trained model. RESULTS Overall, our model achieved an F1-score of 99% to predict the correct shunt valve model. F1-scores for individual shunt valves ranged from 92% for the Sophysa Sophy Mini SM8 to 100% for several other models. CONCLUSION This technology has the potential to automatically detect different shunt valve models in a fast and precise way and may facilitate the identification of an unknown shunt valve on X-ray or CT scout images. The deep learning model we developed could be integrated into PACS systems or standalone mobile applications to enhance clinical workflows

Characterization and genomic analyses of two newly isolated Morganella phages define distant members among Tevenvirinae and Autographivirinae subfamilies

Morganella morganii is a common but frequent neglected environmental opportunistic pathogen which can cause deadly nosocomial infections. The increased number of multidrug-resistant M. morganii isolates motivates the search for alternative and effective antibacterials. We have isolated two novel obligatorily lytic M. morganii bacteriophages (vB_MmoM_MP1, vB_MmoP_MP2) and characterized them with respect to specificity, morphology, genome organization and phylogenetic relationships. MP1s dsDNA genome consists of 163,095bp and encodes 271 proteins, exhibiting low DNA (10kb chromosomal inversion that encompass the baseplate assembly and head outer capsid synthesis genes when compared to other T-even bacteriophages. MP2 has a dsDNA molecule with 39,394bp and encodes 55 proteins, presenting significant genomic (70%) and proteomic identity (86%) but only to Morganella bacteriophage MmP1. MP1 and MP2 are then novel members of Tevenvirinae and Autographivirinae, respectively, but differ significantly from other tailed bacteriophages of these subfamilies to warrant proposing new genera. Both bacteriophages together could propagate in 23 of 27M. morganii clinical isolates of different origin and antibiotic resistance profiles, making them suitable for further studies on a development of bacteriophage cocktail for potential therapeutic applications.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, COMPETE 2020 (POCI-01-0145-FEDER-006684) and the Project PTDC/BBB-BSS/6471/2014 (POCI-01-0145-FEDER-016678). RL contributed to the genome sequencing analysis, supported by the KU Leuven GOA Grant ‘Phage Biosystems’. JP acknowledges the project R-3986 of the Herculesstichting.info:eu-repo/semantics/publishedVersio

Training Performance Assessment for Intracranial Aneurysm Clipping Surgery Using a Patient-Specific Mixed-Reality Simulator: A Learning Curve Study.

BACKGROUND AND OBJECTIVES The value of simulation-based training in medicine and surgery has been widely demonstrated. This study investigates the introduction and use of a new mixed-reality neurosurgical simulator in aneurysm clipping surgery, focusing on the learning curve and performance improvement. METHODS Five true-scale craniotomy head models replicating patient-specific neuroanatomy, along with a mixed-reality simulator, a neurosurgical microscope, and a set of microsurgical instruments and clips, were used in the operation theater to simulate aneurysm microsurgery. Six neurosurgical residents participated in five video-recorded simulation sessions over 4 months. Complementary learning modalities were implemented between sessions. Thereafter, three blinded analysts reported on residents' use of the microscope, quality of manipulation, aneurysm occlusion, clipping techniques, and aneurysm rupture. Data were also captured regarding training time and clipping attempts. RESULTS Over the course of training, clipping time and number of clipping attempts decreased significantly (P = .018, P = .032) and the microscopic skills improved (P = .027). Quality of manipulation and aneurysm occlusion scoring improved initially although the trend was interrupted because the spacing between sessions increased. Significant differences in clipping time and attempts were observed between the most and least challenging patient models (P = .005, P = .0125). The least challenging models presented higher rates of occlusion based on indocyanine green angiography evaluation from the simulator. CONCLUSION The intracranial aneurysm clipping learning curve can be improved by implementing a new mixed-reality simulator in dedicated training programs. The simulator and the models enable comprehensive training under the guidance of a mentor

Loop-Mediated Isothermal Amplification for Laboratory Confirmation of Buruli Ulcer Disease-Towards a Point-of-Care Test

Background As the major burden of Buruli ulcer disease (BUD) occurs in remote rural areas, development of point-of-care (POC) tests is considered a research priority to bring diagnostic services closer to the patients. Loop-mediated isothermal amplification (LAMP),a simple, robust and cost-effective technology, has been selected as a promising POC test candidate. Three BUD-specific LAMP assays are available to date, but various technical challenges still hamper decentralized application. To overcome the requirement of cold-chains for transport and storage of reagents, the aim of this study was to establish a dry-reagent-based LAMP assay (DRB-LAMP) employing lyophilized reagents. Methodology/Principal Findings Following the design of an IS2404 based conventional LAMP (cLAMP) assay suitable to apply lyophilized reagents, a lyophylization protocol for the DRB-LAMP format was developed. Clinical performance of cLAMP was validated through testing of 140 clinical samples from 91 suspected BUD cases by routine assays, i.e. IS2404 dry-reagent-based (DRB) PCR, conventional IS2404 PCR (cPCR),IS2404 qPCR, compared to cLAMP. Whereas qPCR rendered an additional 10% of confirmed cases and samples respectively, case confirmation and positivity rates of DRB-PCR or cPCR (64.84% and 56.43%;100% concordant results in both assays) and cLAMP (62.64% and 52.86%) were comparable and there was no significant difference between the sensitivity of the assays (DRB PCR and cPCR, 86.76%;cLAMP, 83.82%). Likewise, sensitivity of cLAMP (95.83%) and DRB-LAMP (91.67%) were comparable as determined on a set of 24 samples tested positive in all routine assays. Conclusions/Significance Both LAMP formats constitute equivalent alternatives to conventional PCR techniques. Provided the envisaged availability of field friendly DNA extraction formats, both assays are suitable for decentralized laboratory confirmation of BUD, whereby DRB-LAMP scores with the additional advantage of not requiring cold-chains. As validation of the assays was conducted in a third-level laboratory environment, field based evaluation trials are necessary to determine the clinical performance at peripheral health care level

SKA2 regulated hyperactive secretory autophagy drives neuroinflammation-induced neurodegeneration

High levels of proinflammatory cytokines induce neurotoxicity and catalyze inflammation-driven neurodegeneration, but the specific release mechanisms from microglia remain elusive. Here we show that secretory autophagy (SA), a non-lytic modality of autophagy for secretion of vesicular cargo, regulates neuroinflammation-mediated neurodegeneration via SKA2 and FKBP5 signaling. SKA2 inhibits SA-dependent IL-1β release by counteracting FKBP5 function. Hippocampal Ska2 knockdown in male mice hyperactivates SA resulting in neuroinflammation, subsequent neurodegeneration and complete hippocampal atrophy within six weeks. The hyperactivation of SA increases IL-1β release, contributing to an inflammatory feed-forward vicious cycle including NLRP3-inflammasome activation and Gasdermin D-mediated neurotoxicity, which ultimately drives neurodegeneration. Results from protein expression and co-immunoprecipitation analyses of male and female postmortem human brains demonstrate that SA is hyperactivated in Alzheimer's disease. Overall, our findings suggest that SKA2-regulated, hyperactive SA facilitates neuroinflammation and is linked to Alzheimer's disease, providing mechanistic insight into the biology of neuroinflammation

A path forward in the debate over health impacts of endocrine disrupting chemicals

Several recent publications reflect debate on the issue of “endocrine disrupting chemicals” (EDCs), indicating that two seemingly mutually exclusive perspectives are being articulated separately and independently. Considering this, a group of scientists with expertise in basic science, medicine and risk assessment reviewed the various aspects of the debate to identify the most significant areas of dispute and to propose a path forward. We identified four areas of debate. The first is about the definitions for terms such as “endocrine disrupting chemical”, “adverse effects”, and “endocrine system”. The second is focused on elements of hormone action including “potency”, “endpoints”, “timing”, “dose” and “thresholds”. The third addresses the information needed to establish sufficient evidence of harm. Finally, the fourth focuses on the need to develop and the characteristics of transparent, systematic methods to review the EDC literature. Herein we identify areas of general consensus and propose resolutions for these four areas that would allow the field to move beyond the current and, in our opinion, ineffective debate

Advancements in Life Cycle Human Exposure and Toxicity Characterization

BACKGROUND: The Life Cycle Initiative, hosted at the United Nations Environment Programme, selected human toxicity impacts from exposure to chemical substances as an impact category that requires global guidance to overcome current assessment challenges. The initiative leadership established the Human Toxicity Task Force to develop guidance on assessing human exposure and toxicity impacts. Based on input gathered at three workshops addressing the main current scientific challenges and questions, the task force built a roadmap for advancing human toxicity characterization, primarily for use in life cycle impact assessment (LCIA). OBJECTIVES: The present paper aims at reporting on the outcomes of the task force workshops along with interpretation of how these outcomes will impact the practice and reliability of toxicity characterization. The task force thereby focuses on two major issues that emerged from the workshops, namely considering near-field exposures and improving dose-response modeling. DISCUSSION: The task force recommended approaches to improve the assessment of human exposure, including capturing missing exposure settings and human receptor pathways by coupling additional fate and exposure processes in consumer and occupational environments (near field) with existing processes in outdoor environments (far field). To quantify overall aggregate exposure, the task force suggested that environments be coupled using a consistent set of quantified chemical mass fractions transferred among environmental compartments. With respect to dose-response, the task force was concerned about the way LCIA currently characterizes human toxicity effects, and discussed several potential solutions. A specific concern is the use of a (linear) dose-response extrapolation to zero. Another concern addresses the challenge of identifying a metric for human toxicity impacts that is aligned with the spatiotemporal resolution of present LCIA methodology, yet is adequate to indicate health impact potential. CONCLUSIONS: Further research efforts are required based on our proposed set of recommendations for improving the characterization of human exposure and toxicity impacts in LCIA and other comparative assessment frameworks. https://doi.org/10.1289/EHP3871

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries