bluuebunny/crossref_metadata_2025_split huggingface dataset:
A RANDOMISED TRIAL TO OPTIMISE OUTCOMES IN PATIENTS WITH BRAIN METASTASES (AROMA): TRIAL PROPOSAL
Authors: Ho Andrew , Pakzad-Shahabi Lillie , Chen Jiarong , Williams Matthew 
Published: September 2023

Abstract

AIMS
Brain metastases carry significant morbidity and mortality. The survival of patients with metastatic disease has improved due to systemic therapy advances conferring greater extracranial control. Optimal intracranial local control is probably surgical resection or stereotactic radiosurgery. However, there is a cohort for whom this is inappropriate, either for disease or patient fitness reasons. Traditionally, treatment has included whole brain radiotherapy although this has not been convincingly shown to improve survival or quality of life.
AROMA is a single-arm phase II study investigating the feasibility of delivering a novel radiotherapy technique and measuring quality of life.

METHOD
We have developed a modern technique to deliver dose-escalated internal PTV (DE-iPTV) in patients with metas- tases too large for SRS. Our previously-published planning study demonstrates dosimetric improvements in 5 fractions versus WBRT, with higher lesion dose and lower normal tissue dose. It is delivered using a standard linear accelerator.
In AROMA, patients for whom their oncologist would normally consider WBRT instead receive DE-iPTV. QoL measures (EQ5D-3L, Barthel, PS) are collected weekly for 8 weeks then monthly to 6 months. There is an MRI at 6 weeks post-radiotherapy. We are also collecting retrospective observational data on participating centres’ WBRT cohort.

RESULTS
The primary outcome is completion of treatment and completion of QoL at 8 weeks. Secondary outcomes include lesional response, survival, QoL and steroid use.

CONCLUSIONS
AROMA is a phase II study looking at the feasibility of DE-iPTV for patients with brain metastases not suitable for SRS or neurosurgery. It is currently in the design and setup phase.
AN EVALUATION OF THE USE OF TARGETED GENE PANELS TO IDENTIFY TARGETED TREATMENTS IN PATIENTS WITH BRAIN TUMOURS
Authors: Hussain Sana , Hughes Jane , Collinson Fi , Short Susan 
Published: September 2023

Abstract

AIMS
• To assess the impact of undertaking targeted gene panel testing in brain tumour patients outside clinical studies
• To assess if novel treatments have impacted management decisions and/or prognosis
Testing for specific mutations in brain tumours may give opportunities for using targeted drugs. It is not well established how much patients benefit from this approach since routine panel testing has not been widely applied.

METHOD
We reviewed patients who had a known brain tumour and were referred to the early phase research clinic at St James’s for consideration of further treatment in the 6-month period [08/2022 – 02/2023]. We identified ten patients and reviewed their records in detail. Ad hoc testing was done on 6 patients, and SPARTA trial screening on 4 patients.

RESULTS
There were 7 males, 3 females with a mean age of 42 years (24-59). 3 were eligible for clinical trials using agents targeting mutations in the FGFR gene or RET fusion positive status (for the FIGHT 209 and TAPISTRY trials respectively). In 3 patients, there were no targetable mutations. One patient died whilst awaiting results and another is currently under palliative care. Two patients have outstanding molecular data. The data are too early to be able to assess effects on disease trajectory in any patient.

CONCLUSIONS
These data confirm that gene panel testing may suggest novel treatment options in a subset of brain tumour patients and support efforts to ensure that potentially suitable patients have access to appropriate molecular pathology and genomic testing.
SPATIAL DISTRIBUTION AND FUNCTIONAL RELEVANCE OF FGFR1 AND FGFR2 EXPRESSION FOR GLIOBLASTOMA TUMOUR INVASION
Authors: Begum Ayesha , Alshahrany Nawal , Jimenez-Pascual Ana , Siebzehnrubl Florian 
Published: September 2023

Abstract

AIMS
Glioblastoma (GBM) is the most common brain tumour in adults. The GBM microenvironment is made up of heterogeneous GBM cell populations, but how microenvironmental signalling pathways contribute to GBM het- erogeneity and specific GBM pathological features remains incompletely understood. Here, we compare expression of fibroblast growth factor receptors (FGFRs) within the tumour core and the invasion front, specifically investigating the functional relevance of FGFR1 and FGFR2 for in GBM invasion in vitro and in vivo.

METHOD
Quantification of the relative expression levels of FGFR1 and FGFR2 was determined in GBM primary patient- derived cell lines and xenograft models. Additional transcriptional profiling using RNA sequencing identified potential gene-regulatory networks involved in FGFR1-driven GBM tumour invasion.

RESULTS
We found FGFR1 distributed across the tumour mass and expressed in invasive GBM cells, while FGFR2 expression is confined to the tumour mass only. Loss of FGFR1, but not FGFR2, significantly reduced cell migration in vitro and tumour invasion in human GBM xenografts. Comparative analysis of RNA-sequencing data of FGFR1 and FGFR2 knockdown GBM cells revealed a FGFR1-specific gene regulatory network associated with tumour invasion.

CONCLUSIONS
Differential expression of FGFR1 and FGFR2 on invasive GBM cells identified FGFR1 is functionally relevant for tumour invasion in GBM. New gene candidates linked to FGFR1-mediated GBM invasion have been revealed and warrant further investigation to identify how FGFR1 regulates GBM invasion.
PREDICTING INPATIENT LENGTH OF STAY FOR PATIENTS UNDERGOING NEURO-ONCOLOGICAL OPERATIONS: A MACHINE LEARNING PERSPECTIVE FROM A 10-YEAR STUDY AT A NATIONAL TERTIARY NEUROSURGICAL CENTRE
Authors: Snowdon Ella , Biswas Sayan , MacArthur Joshua , Sarkar Ved , Tetlow Callum , George K Joshi 
Published: September 2023

Abstract

AIMS
Length of stay (LOS) following neuro-oncological (NO) operations is essential information for both clinicians, patients and hospital administrators. This study aimed to analyse the LOS of patients following the most common NO surgeries over time and subsequently create a machine learning (ML) algorithm to predict LOS.

METHOD
Retrospective case series analysis of all NO operations at a tertiary neurosurgical centre from 2012 to 2022. A total of 4700 patients were identified and classified based on 40 operation types. 3 regression ML models were developed to predict the inpatient LOS: XGBoost Regressor, Huber Regressor and Support Vector Machine. Models were trained using 25 stratified KFold cross-validation with an 80:20 train-test split. All models were evaluated via model coverage score, mean absolute error (MAE), mean squared error (MSE) and root mean squared error (RMSE) metrics. All analysis was conducted in R and Python.

RESULTS
The average patient age was 53.5±15.7 years, with a mean overall LOS of 160.7hrs. The most common operation was an excision of lesion of brain with 2735 operations. The operation with the longest average LOS was extirpation of lesion of meninges of spinal cord at 268.9hrs, with the shortest being biopsy of lesion of brain at 48.1hrs. The best performing model was the XGBoost Regressor with a mean coverage score=0.885 [0.966, 0.803], RMSE=0.784, MAE=0.594, MSE=0.615.

CONCLUSIONS
ML models can accurately predict LOS and have potential for use in clinical practice to help clinical decision making. Further studies are needed to validate these models on prospective data and additional predictor variables.
STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES FROM GASTROINTESTINAL PRIMARIES: ANALYSIS OF OUTCOMES
Authors: Lynch Sophie , Al-Salihi Omar , Manik Vishal , Qureshi Asad , Hassan Sheila , Forner Samantha , Durve Meeta , Chia Kazumi 
Published: September 2023

Abstract

AIMS
Brain metastases from gastrointestinal primaries are uncommon with poor reported outcomes following SRS. We evaluated clinical outcomes for patients diagnosed with metastatic brain tumours from a gastrointestinal primary treated with stereotactic radiosurgery (SRS).

METHOD
A single institutional retrospective review of patients treated with LINAC-based SRS at our institution between 2017 and 2022. Median survival was calculated from the time of SRS.

RESULTS
A total of 24 patients were treated with primary malignancy locations as follows: 10 colon, 7 rectum and 7 oesophageal. Median survival was 6.4 months for the overall cohort and 4.5 months for colon, 6.1 months for rectum and 14 months for oesophagus. 44% and 14% of patients had undergone surgical resection with colorectal cancer (CRC) and oesophageal cancer respectively. Median survival in CRC patients receiving SRS post-operatively was 6.8 months compared with 11.5 months for patients with non-gastrointestinal primaries. Time from diagnosis of the primary malignancy to diagnosis of brain metastases showed an inverse correlation with survival: 48 months colon, 21 months rectum and 13 months oesophagus. Compared to oesophageal patients, CRC patients were more likely to have extra-cranial disease at the time of SRS (57% vs. 18%).

CONCLUSIONS
Survival after SRS to brain metastases from gastrointestinal primaries is poor, but we demonstrate important differences in outcome depending on the location of the primary malignancy. Oesophageal cancer patients had the best survival with colon cancer patients having the worst. Although our findings are likely to influenced by patient selection bias, these differences are worthy of further investigation.
SURVIVAL OVER A DECADE IN A CASE OF GLIOBLASTOMA
Authors: Shawki Omar , Shaikh Salman , Mukherjee Soumya , El-Maghraby Hussien , Dardis Ronan 
Published: September 2023

Abstract

AIMS
Glioblastoma multiforme is the most aggressive type of primary brain tumours, but there is a small percentage of patients who have a long-term survival and some exceptional cases who survive decades after surgical removal of tumour along with adjuvant therapy.

METHOD
In 2011, a 40-year-old man, presented with headaches & confusion and underwent gliolan guided resection of a right frontal glioblastoma WHO grade IV. He received 30# of 60Gy Radiotherapy with TMZ. Chemotherapy was continued with interval scans in 2016 and 2018 showing stable disease. MRI scan in October 2022 showed contrast enhancing foci for which redo surgery was eventually performed 5 months later. The repeat histology is pending. 12 years after the primary diagnosis, the patient is clinically well.

RESULTS
Only a very handful cases of glioblastoma show prolonged survival of over 10 years. The long-survival for glioblastoma multiforme can be linked to age, surgical resection, molecular profile and good performance score before surgery.

CONCLUSIONS
These extremely rare scenarios of prolonged survival in glioblastoma serves as a motivation to continue incessant research in this field with the hope of improving life expectancy in grade 4 tumours.
PROGNOSTIC FACTORS IN NON-SMALL CELL LUNG CANCER METASTATIC TO THE BRAIN
Authors: Shelley Daniel , Gkogkou Pinelopi 
Published: September 2023

Abstract

AIMS
To identify prognostic factors significantly associated with overall survival in patients with non-small cell lung cancer (NSCLC) metastatic to the brain. To identify whether intracranial or extracranial factors had greater influence on overall survival in this cohort.

METHOD
Retrospective review of 21 patients from a single UK centre with NSCLC metastatic to the brain was undertaken. Hazard ratios were obtained from the Cox proportional hazards model, and survival curves plotted via the Kaplan-Meier method.

RESULTS
On univariate analysis, higher Karnofsky Performance Status (KPS) was significantly associated with improved overall survival compared to lower (HR 0.112; 95% CI 0.029 – 0.438) as was stable primary disease relative to progressive primary disease (HR 0.088; 95% CI 0.017 – 0.459). Surgical resection of primary disease was also associated with longer overall survival relative to no resection (HR 0.2713; 95% CI 0.075 – 0.980). Local treatment to brain metastases with either surgery or stereotactic radiosurgery prolonged overall survival relative to no local metastatic treatment (HR 0.1422; 95% CI 0.031 – 0.656). Notable variables not significantly associated with overall survival include number, size and location of metastases as markers of intracranial metastatic burden.

CONCLUSIONS
Primary disease activity (p = 0.004), KPS (p = 0.002), surgical resection of thoracic disease (p = 0.046) and treatment modality of brain metastasis (p = 0.012) were significant prognostic covariates in this cohort of 21 patients. Extracranial disease and patient factors appear to have greater prognostic significance than intracranial metastatic burden in this patient population.
SIX YEARS OF NEURO-NAVIGATION ASSISTED BRAIN TUMOUR SURGERY: PROGRESS AND CHALLENGES
Authors: Ugwuanyi Ugochukwu , Salawu Morayo , Ayogu Obinna , Jubrin Paul 
Published: September 2023

Abstract

AIMS
To report a six-year experience with computerized neuro-navigation assistance in our neuro-oncology surgeries and services.

METHOD
Retrospective review of all consecutive cases involving computer-assisted neuro-navigation diagnostic and resective brain tumour operation over a six-year period (January 2016-December 2021). Main study parameters: Clinical diagnostic procedures, operations, histological diagnosis, adjuvant treatments. Data were analysed using simple descriptive statistics, and results were presented accordingly.

RESULTS
Total number of cases 111, Males 70 and Females 41 (M: F = 1.7:1). Age ranges from 8 months to 80 years. The commonest presentation was headache, nausea, and vomiting. Pre-op diagnosis: Intra axial tumours 70/111 (63%), Extra axial tumours 41/111 (36%). Operations: Resection/Debulking of tumour 86/111(77,4%), with complete EOR of 65/86 (75%). Diagnostic Biopsy 68/111(61%) with target precision of 100%. Common Histology were Gliomas 50/111(45%), Meningiomas 41/111 (36.9%), and Metastatic 15/111 (13.5%). Adjuvant treatments and follow-ups were advised accordingly.

CONCLUSIONS
With computerized neuro-navigation assistance, a wider spectrum of brain tumours were more confidently operated, and adjuvant treatments were easily deployed in line with a precise histological diagnosis for improved neuro-oncology services. But this success was at a huge cost of adopting measures to overcome some inevitable challenges.
What Do We Measure When We Measure Affective Polarization across Countries?
Authors: Tichelbaecker Thomas , Gidron Noam , Horne Will , Adams James 
Published: September 2023

Abstract
Measures of affective polarization—that is, dislike and hostility across party lines—have been developed and validated in the context of America’s two-party system. Yet increasingly, affective polarization is examined comparatively. We address this issue by introducing a novel dataset that measures aspects of partisan affect in 10 countries with diverse party systems. We detect associations between partisan affect toward out-parties versus affect toward out-parties’ supporters, but their strength varies across countries. We discuss measurement reasons for this variation and consider the implications of our findings for the emerging comparative affective polarization literature.
Old paradigms and new concepts in familial Mediterranean fever (FMF): an update 2023
Authors: Ben-Chetrit Eldad 
Published: September 2023

Abstract
Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent attacks of fever and polyserositis. Its first description as a new entity was published by Siegal in 1945. Colchicine has been the treatment of choice for this disease since 1972. Significant progress has been made over the years in understanding FMF’s clinical features, diagnosis, mode of inheritance, pathogenesis and therapeutic approach. However, many old paradigms related to FMF have proven inaccurate, leading to the emergence of new concepts that provide more precise insights. The term ‘FMF’ is no longer appropriate as the disease is found beyond the Mediterranean basin. The concept of diagnosis based only upon clinical ground proved to be wrong. The paradigm that MEFV mutations in FMF lead to loss of function of the encoded peptide pyrin turned out to be a gain of function mutation. Finally, the concept that as a genetic disease FMF should be treated for life was found to be inaccurate for the subpopulation of the heterozygote patients. Thus, the breakthroughs of identifying the gene associated with the disease (MEFV) and the deciphering of its pathogenesis revolutionized our old paradigms and replaced them with new and more precise insights.
Patterns and determinants of response to novel therapies in juvenile and adult-onset polyarthritis
Authors: Triaille Clément , Quartier Pierre , De Somer Lien , Durez Patrick , Lauwerys Bernard R , Verschueren Patrick , Taylor Peter C , Wouters Carine 
Published: September 2023

Abstract
Biologic and targeted synthetic DMARDs (b/tsDMARDs) have revolutionized the management of multiple rheumatic inflammatory conditions. Among these, polyarticular JIA (pJIA) and RA display similarities in terms of disease pathophysiology and response pattern to b/tsDMARDs. Indeed, the therapeutic efficacy of novel targeted drugs is variable among individual patients, in both RA and pJIA. The mechanisms and determinants of this heterogeneous response are diverse and complex, such that the development of true ‘precision’-medicine strategies has proven highly challenging. In this review, we will discuss pathophysiological, patient-specific, drug-specific and environmental factors contributing to individual therapeutic response in pJIA in comparison with what is known in RA. Although some biomarkers have been identified that stratify with respect to the likelihood of either therapeutic response or non-response, few have proved useful in clinical practice so far, likely due to the complexity of treatment–response mechanisms. Consequently, we propose a pragmatic, patient-centred and clinically based approach, i.e. personalized instead of biomarker-based precision medicine in JIA.
Mechanisms of Alveolar Type 2 Epithelial Cell Death During Acute Lung Injury
Authors: Qi Xiaofeng , Luo Yali , Xiao Mengyong , Zhang Qiuju , Luo Jing , Ma Linna , Ruan Linfeng , Lian Nini , Liu Yongqi 
Published: September 2023

Abstract
Diffuse alveolar epithelial cell (AEC) death occurs extensively during acute lung injury (ALI). Due to the limited proliferative capacity of alveolar type 1 epithelial (AT1) cells, the differentiation and regenerative capacity of alveolar type 2 epithelial (AT2) cells are required to restore the barrier function of AECs. However, during lung injury, AT1 cells are particularly susceptible to injury, and ATII cells die in the presence of severe or certain types of injury. This disruption ultimately results in a hindrance to the ability of AT2 cells to proliferate and differentiate into AT1 cells in time to repair the extensively damaged AECs. Therefore, understanding the mechanism of injury death of AT2 cells may be beneficial to reverse the above situation. This article reviews the main death modes of AT2 cells, including apoptosis, necrosis, necroptosis, pyroptosis, autophagic cell death, and ferroptosis. It compares the various forms of death, showing that various cell injury death modes have unique action mechanisms and partially overlapping pathways. Studying the mechanism of AT2 cell death is helpful in screening and analyzing the target pathway of AEC barrier function recovery. It opens up new ideas and strategies for preventing and treating ALI.
The nuts and bolts of multimodal anaesthesia in the 21st century: a primer for clinicians
Authors: Lersch Friedrich , Correia Paula Cruz , Hight Darren , Kaiser Heiko A. , Berger-Estilita Joana 
Published: September 2023

Purpose of review
This review article explores the application of multimodal anaesthesia in general anaesthesia, particularly in conjunction with locoregional anaesthesia, specifically focusing on the importance of EEG monitoring. We provide an evidence-based guide for implementing multimodal anaesthesia, encompassing drug combinations, dosages, and EEG monitoring techniques, to ensure reliable intraoperative anaesthesia while minimizing adverse effects and improving patient outcomes.

Recent findings
Opioid-free and multimodal general anaesthesia have significantly reduced opioid addiction and chronic postoperative pain. However, the evidence supporting the effectiveness of these approaches is limited. This review attempts to integrate research from broader neuroscientific fields to generate new clinical hypotheses. It discusses the correlation between high-dose intraoperative opioids and increased postoperative opioid consumption and their impact on pain indices and readmission rates. Additionally, it explores the relationship between multimodal anaesthesia and pain processing models and investigates the potential effects of nonpharmacological interventions on preoperative anxiety and postoperative pain.

Summary
The integration of EEG monitoring is crucial for guiding adequate multimodal anaesthesia and preventing excessive anaesthesia dosing. Furthermore, the review investigates the impact of combining regional and opioid-sparing general anaesthesia on perioperative EEG readings and anaesthetic depth. The findings have significant implications for clinical practice in optimizing multimodal anaesthesia techniques (Supplementary Digital Content 1: Video Abstract, http://links.lww.com/COAN/A96).
Office-based anesthesia: a contemporary update on outcomes, incentives, and controversies
Authors: Young Steven , Osman Brian , Shapiro Fred E. 
Published: September 2023

Purpose of review
The volume of office-based surgery (OBS) has surged over the last 25–30 years, however patients with increasing comorbidities are being considered for procedures in office locations. This review focuses on office-based surgery outcomes, financial incentives driving this change, and controversies.

Recent findings
Healthcare economics appear to drive the push towards OBS with improved reimbursements, but there are rising out-of-pocket costs impacting patients. Plastic surgery has low complications, but procedures like buttock augmentation are associated with mortality. In ophthalmology, emerging controversial literature investigates the impact of anesthesia type on and whether anesthesia providers impact ophthalmology outcomes. Dental anesthesia continues to suffer occasional wrong-sided surgeries. Vascular interventions are being driven towards offices due to reimbursements, and may be safely performed. Meta-analyses of ear, nose, and throat in-office surgeries have low complication rates.

Summary
The reported safety supports the proper selection of patients for the proper procedure in the right location. Anesthesiologists need to develop and implement safe and efficient systems to optimize patient outcomes in outpatient office settings. Further research and uniform standardized outcomes tracking are needed in the emerging specialties performing office-based surgery.