Enabling mRNA medicine for brain tumors

mRNA is a new class of drugs that has the potential to revolutionize the treatment of brain tumors. Thanks to the COVID-19 mRNA vaccines and numerous therapy-based clinical trials, it is now clear that lipid nanoparticles (LNPs) are a clinically viable means to deliver RNA therapeutics. However, LNP-mediated mRNA delivery to brain tumors remains elusive. Over the past decade, numerous studies have shown that tumor cells communicate with each other via small extracellular vesicles, which are around 100 nm in diameter and consist of lipid bilayer membrane similar to synthetic lipidbased nanocarriers. We hypothesized that rationally designed LNPs based on extracellular vesicle mimicry would enable efficient delivery of RNA therapeutics to brain tumors without undue toxicity. We synthesized LNPs using four components similar to the formulation used in the mRNA COVID19 vaccines (Moderna and Pfizer): ionizable lipid, cholesterol, helper lipid and polyethylene glycol (PEG)-lipid. For the in vitro screen, we tested ten classes of helper lipids based on their abundance in extracellular vesicle membranes, commercial availability, and large-scale production feasibility while keeping rest of the LNP components unchanged. The transfection kinetics of GFP mRNA encapsulated in LNPs and doped with 16 mol% of helper lipids was tested using GL261, U87 and SIM-A9 cell lines. Several LNP formations resulted in stable transfection (upto 5 days) of GFP mRNA in all the cell lines tested in vitro. The successful LNP candidates (enabling >80% transfection efficacy) were then tested in vivo to deliver luciferase mRNA to brain tumors via intrathecal administration in a syngeneic glioblastoma (GBM) mouse model, which confirmed luciferase expression in brain tumors in the cortex. LNPs were then tested to deliver Cre recombinase mRNA in syngeneic GBM mouse model genetically modified to express tdTomato under LoxP marker cassette that enabled identification of LNP targeted cells. mRNA was successfully delivered to tumor cells (70-80% transfected) and a range of different cells in the tumor microenvironment, including tumor-associated macrophages (80-90% transfected), neurons (31- 40% transfected), neural stem cells (39-62% transfected), oligodendrocytes (70-80% transfected) and astrocytes (44-76% transfected). Then, LNP formulations were assessed for delivering Cas9 mRNA and CD81 sgRNA (model protein) in murine syngeneic GBM model to enable gene editing in brain tumor cells. Sanger sequencing showed that CRISPR-Cas9 editing was successful in ~94% of brain tumor cells in vivo. In conclusion, we have developed a library of safe LNPs that can transfect GBM cells in vivo with high efficacy. This technology can potentially be used to develop novel mRNA therapies for GBM by delivering single or multiple mRNAs and holds great potential as a tool to study brain tumor biology.

Neurooncology: 2021 update.

This article briefly presents 10 topics that were selected by the author as 'top 10 discoveries' published in 2020 in the broader field of neurooncological pathology including neurosciences as well as clinical neurooncology of interest for neurooncological pathology. The selected topics concern new information on the molecular characteristics of gliomas (infratentorial IDH-mutant diffuse astrocytomas, pediatric low-grade gliomas, infant-type high-grade gliomas, hypermutation in gliomas), the immunological aspects of the brain tumor microenvironment (TME), the impact of the TME on preclinical glioma models, and the importance of lymphatic drainage on brain tumor surveillance. Furthermore, important papers were published on two 'new' genetic syndromes predisposing to medulloblastoma, on liquid biopsy-based diagnosis of central nervous system (CNS) tumors, and on the 'microbiome' in glioblastomas (and other cancers). In the last part of this review, a dozen of papers are given as examples of papers that did not make it to the top 10 list of the author, underscoring the subjective component in the selection process. Acknowledging that 2020 will be remembered as the year in which the world changed because of the COVID-19 pandemic, some of the consequences of this pandemic for neurooncological pathology are briefly discussed as well. Hopefully, this review forms an incentive to appreciate the wealth of information provided by the papers that were used as building blocks for the present manuscript.

Impact of Covid19 Infection in Patients with Cancer

Background: coronaviral pandemic (COVID-19) induced by severe acute coronaviral syndrome 2 has imminent consequences for COVID-19 patients. To determine the effect of this pandemic on oncological treatment, Netherlands cancer patients performed a national study . Method(s): From 11 April 2020 to 11 Jan 2021, the oncological care perspective was discussed by an online study. The survey included 20 questions on four topics: patient characteristics, hospital engagement, COVID-19 and COVID-19 problems. Result(s): A total of 2418 (64.53%) patients were female and the remainder (57.5%) were <50 years of age. The most prevalent cancer diagnosis were haematological malignancies (26.1%), breast cancer (22.8%) and other cancers (19.2%). Depending on their illness environment, 34.7% of patients had incurable conditions while 21.6% and 31.8% had curable or healed diseases. The (expected) result of their illness was 'unknown' for 11.9% of patients. According to outpatient environment, 1691 (45.1%) patients have been oncologically examined and have taken follow-up, contrasted with 529 (14.1%) and 1527 (40.8%) patients presently or pending for therapy. Conclusion(s): This is the first research exploring cancer patients' experiences after the COVID-19 pandemic in Iraq. The research indicates the major effect of COVID-19 on oncological treatment, showing the need for psycho-oncological assistance during this pandemic.Copyright © 2020 Ubiquity Press. All rights reserved.

Federated Learning for Healthcare Domain - Pipeline, Applications and Challenges

Federated learning is the process of developing machine learning models over datasets distributed across data centers such as hospitals, clinical research labs, and mobile devices while preventing data leakage. This survey examines previous research and studies on federated learning in the healthcare sector across a range of use cases and applications. Our survey shows what challenges, methods, and applications a practitioner should be aware of in the topic of federated learning. This paper aims to lay out existing research and list the possibilities of federated learning for healthcare industries.© 2022 Copyright held by the owner/author(s).

Postoperative surveillance in cranial and spinal tumor neurosurgery: when is this warranted?

OBJECTIVE: The outbreak of COVID-19 and the sudden increase in the number of patients requiring mechanical ventilation significantly affected the management of neurooncological patients. Hospitals were forced to reallocate already scarce human resources to maximize intensive care unit (ICU) capacities, resulting in a significant postponement of elective procedures for patients with brain and spinal tumors, who traditionally require elective postoperative surveillance on ICU or intermediate care wards. This study aimed to characterize those patients in whom postoperative monitoring is required by analyzing early postoperative complications and associated risk factors. METHODS: All patients included in the analysis experienced benign or malignant cerebral or intradural tumors and underwent surgery between September 2017 and May 2019 at University Hospital Münster, Germany. Patient data were generated from a semiautomatic, prospectively designed database. The occurrence of adverse events within 24 hours and 30 days postoperatively-including unplanned reoperation, postoperative hemorrhage, CSF leakage, and pulmonary embolism-was chosen as the primary outcome measure. Furthermore, reasons and risk factors that led to a prolonged stay on the ICU were investigated. By performing multivariable logistic regression modeling, a risk score for early postoperative adverse events was calculated by assigning points based on beta coefficients. RESULTS: Eight hundred eleven patients were included in the study. Eleven patients (1.4%) had an early adverse event within 24 hours, which was either an unplanned reoperation (0.9%, n = 7) or a pulmonary embolism (0.5%, n = 4) within 24 hours. To predict the incidence of early postoperative complications, a score was developed including the number of secondary diagnoses, BMI, and incision closure time, termed the SOS score. According to this score, 0.3% of the patients were at low risk, 2.5% at intermediate risk, and 12% at high risk (p < 0.001). CONCLUSIONS: Postoperative surveillance in cranial and spinal tumor neurosurgery might only be required in a distinct patient collective. In this study, the authors present a new score allowing efficient prediction of the likelihood of early adverse events in patients undergoing neurooncological procedures, thus helping to stratify the necessity for ICU or intermediate care unit beds. Nevertheless, validation of the score in a multicenter prospective setting is needed.

Tumor agnostic comparison of immunohistochemistry and next-generation sequencing in detecting ALK fusions and assessment of ALK tyrosine kinase inhibitor efficacy

Background: Reliable methods to identify anaplastic lymphoma kinase (ALK) fusions are critical to matching patients to ALK tyrosine kinase inhibitors (TKIs) therapy, on or off trial. Various methods including FISH have been used, but immunohistochemistry (IHC) and next-generation sequencing (NGS) are most commonly employed. Evaluating the concordance of IHC and NGS is key, particularly in non-lung cancers where data is sparse. Method(s): NGS+ (MSK-IMPACT DNA hybrid capture NGS and/or RNA anchored multiplex PCR) and/or IHC+ (clone: D5F3) patients with cancers of any histology were identified as ALK+. ALK IHC was scored as negative (0), equivocal (e: 1+, 2+) or positive (3). Concordance of ALK detection (number of NGS+ and IHC+/total number of patients with NGS and IHC) was calculated. For patients with metastatic disease treated with any ALK TKI in the first-line (1L) setting, progression-free survival (PFS) was reported. Result(s): 347 ALK+ solid tumor patients were identified. As expected, the majority (96%, n=336) had lung cancer, however, 11 patients with 11 unique non-lung cancer histologies were found (3 gastrointestinal, 2 gynecologic, 1 breast, 1 thyroid, 1 primary brain tumor, 1 DLBCL, 1 PEComa, and 1 CUP). 57% had EML4-ALK fusions;36 non-EML4 ALK rearrangements were identified, including four novel fusions (PEKHA7-ALK, ZFPM2-ALK, TRIM24-ALK, ALK-MYO3B). ALK was evaluated by IHC alone in 83 patients (23.9%). The concordance rate between NGS and IHC was 85%. Among discordant cases, 11% (n=28) were IHC+/NGS-, 24% (n=63) were IHCe/NGS-, 3% (n=8) were IHCe/NGS+, and 0.4% (n=1) was IHC-/NGS+. The most frequent ALK TKIs were alectinib (n= 87, 58%) and crizotinib (n= 56, 38%). PFS on 1L ALK TKIs for patients with IHC+/NGS+ (n=134), IHC-/NGS+(n=1), IHC+/NGS- (n=8), IHCe/NGS+ (n=4), IHCe/NGS- (n=1) was 26 months, 26 months, 39 months, 41 months, 9 months respectively. Conclusion(s): In a population including multiple tumor types, NGS and IHC were highly concordant in ALK fusion detection. ALK TKI benefit may be observed in cases with discordant testing, in which only one assay detects a putative ALK fusion. Legal entity responsible for the study: The authors. Funding(s): NIH Cancer Center grant: P30CA008748. Disclosure: M.G. Kris: Financial Interests, Personal, Research Grant: Boehringer Ingelheim, National Lung Cancer Partnership, Pfizer, PUMA, Stand up to Cancer;Financial Interests, Personal, Advisory Role: Ariad, AstraZeneca, Bind Bioscience, Boehringer Ingelheim, Chug Pharma, Clovis, Covidien, Daiichi Sankyo, Esanex, Genentech;Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Novartis, Millenium, Pfizer, Roche. A. Drilon: Financial Interests, Personal, Advisory Board: Ignyta/Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millennium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, BeiGene, BerGenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem Oncology, MORE Health, AbbVie, 14ner/Elevation Oncology, Remedica Ltd, ArcherDX, Monopteros, Novartis, EMD Serono, Melendi, Liberum, Repare RX, Amgen, Janssen, EcoR1, Monte Rosa;Financial Interests, Personal, Other, CME: Medscape, Onclive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice, PeerView Institute, Paradigm Medical Communications, WebMD, MJH Life Sciences, Med Learning, Imedex, Answers in CME, Medscape, Clinical Care Options, AiCME;Financial Interests, Personal, Other, CME, Consulting: Axis;Financial Interests, Personal, Other, Consulting: Nuvalent, Merus, EPG Health, mBrace, Harborside Nexus, Ology, TouchIME, Entos, Treeline Bio, Prelude, Applied Pharmaceutical Science, Inc;Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, Remedica Ltd, RV More;Financial Interests, Personal, Stocks/Shares: Treeline Biosciences;Financial Interests, Personal, Royalties: Wolters Kluwer;Financial Interests, Personal, Other, stocks: mBrace;Financial Interests, Institutional, Funding, Research funding: Pfizer, Exelixis, GlaxoSmithKline, Teva, Taiho, PharmaMar;Finan ial Interests, Personal, Funding, Research: Foundation Medicine;Non-Financial Interests, Personal, Member: ASCO, AACR, IASLC;Other, Personal, Other, Food/Beverage: Merck, PUMA, Merus;Other, Personal, Other, Other: Boehringer Ingelheim. All other authors have declared no conflicts of interest.Copyright © 2023 European Society for Medical Oncology

An Efficient Deep Learning based Approach for the Detection of Brain Tumors

Deep learning has stretched out its roots even more in our daily lives. As a society, we are witnessing small changes in lifestyle such as self-driving cars, Google Assistant, Netflix recommendations, and spam email detection. Similarly, deep learning is also evolving in healthcare, and today many doctors often use it more comfortably. Using deep learning models we can detect severe brain tumors with the help of MRI scans, in fact in the Covid era, deep learning evolved majorly to detect the disease with the help of Lung X-Rays. Magnetic Resonance Imaging (MRI) is used when a person has a brain tumor to detect it. Brain tumors can fall into any category, and MRI scans of these millions of people are needed to determine if they have the disease and if so, which category they belong to. Determining the type of brain tumor can be a rigid task and deep learning models play an important role here. For the proposed deep learning model, we have implemented convolution neural networks (CNN) through which our model has achieved a testing accuracy of 96.5%. Also, along with this, the libraries of Keras and Tensorflow have been explored by the authors in this research. © 2022 IEEE.

Going Virtual During Covid with the NCI-Connect Cares (Coping, Advocacy, Resources, Education, Support) Group for Rare Brain and Spine Tumor (RBST) Patients and their Families

Background/Purpose: RBST patients have limited supportive care resources and feel secluded as few healthcare providers have expertise in these diseases. The NCI-CONNECT specialized clinic for adults with RBSTs created a multidisciplinary approach with a genetic counselor, knowledgeable healthcare team, and group sessions with a health and wellness counselor (CARES). The CARES sessions created an educational and supportive space for patients to share their unique experiences. We report the adaptation of the CARES group that evolved from in-person to virtual during COVID. Method(s): Patients with RBSTs and their families attended weekly (1 h) groups at their clinic appointments. The CARES group leaders (A.A, S.S) led wellness/coping presentations (15-20 min) and a guided discussion on the topic. In 2021, the COVID pandemic shifted the group to monthly virtual meetings, and educational content was shared via a closed-Facebook group and NCI-CONNECT website. Six groups included presenters within Neuro-Oncology, shortened prerecorded presentations (10 min) allowing for more engagement opportunities, and a coping activity concluded the meeting. Emailed survey feedback was requested (5 out of 13 completed). Result(s): On average, six patients attended each group. Topics included mindfulness, distress, relational challenges, body image, and an educational series on symptom management. All presentations can be found on the NCI-CONNECT website. Patients reported enjoyment in the ability to connect with others, with 80% preferring monthly virtual meetings. Open-ended comments noted that hearing other patients' stories created connections patients expressed they needed. Conclusions and Implications: The virtual CARES group created an accessible space for RBST patients to build relationships and gain support to manage the uncertainties of coping with a rare disease during a time of physical isolation. Patient responses capture the need to continue the group further. Future work will focus on expanding the group based on patient needs and building metrics to understand the overall group benefits in a virtual world.

Central Nervous System Distribution of the Ataxia-Telangiectasia Mutated Kinase Inhibitor AZD1390: Implications for the Treatment of Brain Tumors

Effective drug delivery to the brain is critical for the treatment of glioblastoma (GBM), an aggressive and invasive primary brain tumor that has a dismal prognosis. Radiation therapy, the mainstay of brain tumor treatment, works by inducing DNA damage. Therefore, inhibiting DNA damage response (DDR) pathways can sensitize tumor cells to radiation and enhance cytotoxicity. AZD1390 is an inhibitor of ataxia-telangiectasia mutated kinase, a critical regulator of DDR. Our in vivo studies in the mouse indicate that delivery of AZD1390 to the central nervous system (CNS) is restricted due to active efflux by P-glycoprotein (P-gp). The free fraction of AZD1390 in brain and spinal cord were found to be low, thereby reducing the partitioning of free drug to these organs. Coadministration of an efflux inhibitor significantly increased CNS exposure of AZD1390. No differences were observed in distribution of AZD1390 within different anatomic regions of CNS, and the functional activity of P-gp and breast cancer resistance protein also remained the same across brain regions. In an intracranial GBM patient-derived xenograft model, AZD1390 accumulation was higher in the tumor core and rim compared with surrounding brain. Despite this heterogenous delivery within tumor-bearing brain, AZD1390 concentrations in normal brain, tumor rim, and tumor core were above in vitro effective radiosensitizing concentrations. These results indicate that despite being a substrate of efflux in the mouse brain, sufficient AZD1390 exposure is anticipated even in regions of normal brain. SIGNIFICANCE STATEMENT Given the invasive nature of glioblastoma (GBM), tumor cells are often protected by an intact blood-brain barrier, requiring the development of brain-penetrant molecules for effective treatment. We show that efflux mediated by P-glycoprotein (P-gp) limits central nervous system (CNS) distribution of AZD1390 and that there are no distributional differences within anatomical regions of CNS. Despite efflux by P-gp, concentrations effective for potent radiosensitization are achieved in GBM tumor-bearing mouse brains, indicating that AZD1390 is an attractive molecule for clinical development of brain tumors.Copyright © 2022 American Society for Pharmacology and Experimental Therapy. All rights reserved.

The COVID-19 Pandemic Experience for Patients with Central Nervous System (CNS) Tumors: Differences in Patient- Reported Outcomes (PROs) and Practice Recommendations

Background/Purpose: The COVID-19 pandemic and associated mitigation procedures have significantly altered daily life in ways that may disproportionately affect patients with CNS tumors. This study aimed to explore differences in symptom burden and interference, mood disturbance, and health-related quality of life in the CNS tumor patient population during the COVID-19 pandemic, compared to a normative sample of pre-pandemic data. Method(s): Data from the Neuro-Oncology Branch (NOB) Natural History Study, including demographic and clinical data, as well as PROs including PROMIS Anxiety and Depression Short-Forms, EQ- 5D-3L, MDASI-Brain Tumor/Spine Tumor, and NeuroQOL-Cognition Function, were collected and compared across groups ('NOB normative sample' and 'COVID year' patients) using one-sample proportion tests. Result(s): 178 COVID year CNS tumor patients (55% male, 82% Caucasian, median age 45 years) were compared with 678 NOB normative sample patients with similar demographic and clinical characteristics. Symptom burden remained comparably high during the COVID year compared to the NOB normative sample with the most common moderate-severe symptoms being fatigue (31% vs. 35%), difficulty remembering (28% vs. 24%), drowsiness (22% vs. 25%), disturbed sleep (20% vs. 22%), and distress (20% for both). However, a significantly greater proportion of COVID year assessments endorsed moderate-severe depression on the PROMIS compared to the NOB normative sample (17% vs. 12%, p = 0.023, Cohen's h = 0.22) and moderate-severe depression/anxiety on the EQ-5D-3L was also more prevalent (53% vs. 43%, p = 0.009, Cohen's h = 0.28). There were no other significant differences in PROs between groups. Conclusions and Implications: These findings demonstrated that while objective symptom burden for CNS tumor patients was unchanged, there was an increase in depression reported during the COVID-19 pandemic. Future work should investigate potential pandemic-era interventions for screening, targeting, and improving both mood disturbance and other disease-specific symptoms to improve symptom burden and quality of life.

Feasibility and preliminary efficacy of a virtual reality intervention targeting distress and anxiety in primary brain tumor patients at the time of clinical evaluation: Study protocol for a phase 2 clinical trial.

BACKGROUND: Primary brain tumor (PBT) patients experience higher levels of distress and anxiety than other solid tumor patients, particularly at the time of clinical evaluation when uncertainty about disease status is high ("scanxiety"). There is promising evidence supporting use of virtual reality (VR) to target psychological symptoms in other solid tumor patients, though PBT patients have not been studied extensively in this context. The primary aim of this phase 2 clinical trial is to establish the feasibility of a remote VR-based relaxation intervention for a PBT population, with secondary aims designed to determine preliminary efficacy of improving distress and anxiety symptoms. METHODS: PBT patients (N = 120) with upcoming MRI scans and clinical appointments who meet eligibility will be recruited to participate in a single arm trial conducted remotely through the NIH. Following completion of baseline assessments, participants will complete a 5-min VR intervention via telehealth using a head-mounted immersive device while under supervision of the research team. Following the intervention, over the course of 1 month patients can use VR at their discretion with follow-up assessments done immediately post-VR intervention, as well as 1 week and 4 weeks later. Additionally, a qualitative phone interview will be conducted to assess patient satisfaction with the intervention. DISCUSSION: Use of immersive VR is an innovative interventional approach to target distress and scanxiety symptoms in PBT patients who are at high risk for experiencing these symptoms leading into their clinical appointments. Findings from this study may inform design of a future multicenter randomized VR trial for PBT patients and may aid in development of similar interventions for other oncology populations. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04301089), registered 9 March 2020.

The impact of the COVID-19 pandemic on the number of brain tumor surgeries in Poland: A national database study.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has greatly affected the treatment of most medical conditions. In particular, the treatment of seriously ill patients had to be adjusted due to the limited availability of in-hospital procedures. OBJECTIVES: The aim of this study was to evaluate the effects of COVID-19-related changes on neuro-oncological surgeries in the Polish medical system. MATERIAL AND METHODS: Data from the period of 2010-2020 were collected from National Health Insurance database for 2 diagnosis-related groups: A11 (complex intracranial procedures) and A12 (large intracranial procedures). The total number of procedures and diagnoses per year, trend changes and changes in procedures grouped by medical type were analyzed, including resections/biopsies, malignant/stable (nonmalignant) lesions, elective/acute procedures, and length of stay. RESULTS: Mean yearly numbers of 7177 (standard deviation (SD) = 760) procedures and 5934 (SD = 1185) diagnoses were recorded. Both numbers were growing up to 9.1% per year until 2018. From 2018, a 3.1% decrease in the number of procedures was observed, with a significantly larger decrease of 10.5% observed in 2020 (p < 0.001). The number of diagnoses decreased in 2019 by 2.7%, and by 9.2% in 2020 (p = 0.706), with a statistically significant change in the annual growth rate (p = 0.044). The number of resections decreased by 11.5% in 2020 (p = 0.204), with a significant change in the annual growth rate (p < 0.001). The number of biopsies decreased by 2.5% in 2020 (p = 0.018), with the annual decrement in 2019/2020 also being significant (p = 0.004). Decreases were observed in 2019 and 2020 for the number of malignant (0.5% and 6.3%, respectively) and nonmalignant (5.4% and 12.9%, respectively) tumors (p = 0.233 and p = 0.682 for absolute values, and p = 0.008 and p = 0.004 for the annual growth rates, respectively). The number of acute procedures in 2020 further decreased by 9.8% from 5.5% decrease in 2019 (p = 0.004), and the number of elective procedures decreased by 11.8% (p = 0.009). The annual growth rates for both acute and elective procedures were statistically significant (p < 0.001 and p < 0.001). CONCLUSIONS: The decrease in the number of neuro-oncological surgeries appeared to be much lower than the 20% decrease observed for general oncological surgeries in Poland during the COVID-19 pandemic. This seems to have resulted from postponing the treatment of less critical cases (i.e., nonmalignant and elective) and focusing on the treatment of the most precarious patients.

Mind-body and creative arts therapies for people with aphasia: a mixed-method systematic review

Background: In the context of aphasia rehabilitation, there is a perceived need for interventions with a reduced linguistic demand targeting well-being. Mind-body and creative arts approaches are holistic and person-centred approaches, primarily relying on means other than verbal exchanges and promoting self-regulation strategies. Aim(s): This mixed-method systematic review aimed to evaluate the availability, feasibility and effectiveness of mind-body and creative arts therapies in promoting well-being for people with aphasia. Eight databases were searched using subject headings and keywords. Full-text screening, critical appraisal and data extraction were conducted independently by two reviewers. A segregated synthesis approach was used (i.e., Revised Effect Direction Plot technique and Thematic Synthesis approach). Findings are presented in a narrative and visual form. Main Contribution: Twenty-two studies were included (Mind-body: n = 11;Creative arts: n = 11). Heterogeneity of study design and quality, intervention type, procedures and dosage, outcomes, and level of offered communication support were identified. Improvements were noted across a wide range of well-being outcomes with more consistent positive results for anxiety and communication. One hundred and twenty-eight findings were extracted and synthesised in three broad themes: positive impact on self, empowering multifaceted experience, and relevance of needs-centred adjustments. Conclusion(s): Provisional findings about the benefits of mind-body and creative arts interventions on aspects of well-being for some individuals with aphasia were identified. However, findings are complex and need to be interpreted cautiously. Facilitators and barriers to these therapies are highlighted with related recommendations for practice. This review poses a demand for further research in the field, implementing rigorous methodology and aphasia-specific support to facilitate inclusion and engagement.Copyright © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Immunotherapy-responsive recurrent extensive white matter disease without neuronal or glial surface antibodies: A case report

Background: Acute disseminated encephalomyelitis (ADEM) is classically considered as a monophasic immune-mediated demyelinating disorder. A relapse can occur in children but extremely rare in adults. Case-report: A 57-year-old man presented with fulminant ADEM-like episode without proceeding viral illness. Neurological deficits rapidly developed associated with extensive demyelinating brain lesions with vasogenic edema. After the initiation of aggressive immunotherapy, his symptoms resolved, but he relapsed twice during 26-month observation period;one was a mild episode characterized by rapidly evolving MRI lesions without development of symptoms, and the other was a fulminant ADEM-like episode similar to the first one. The second fulminant episode occurred only 2 days after getting a flu shot despite no clinical or radiological relapse when he received COVID-19 vaccinations. The patient's symptoms and extensive brain MRI lesions improved after the initiation of aggressive immunotherapy at the early stage. No autoantibodies against neuronal surface (such as GABA A receptor) or glial surface antigens (aquaporin 4, or myelin oligodendrocyte glycoprotein) were identified in either serum or CSF. Conclusion(s): Extensive white matter lesions can occur without neuronal or glial surface antibodies, recurrent fulminant ADEM-like episode can develop even in an adult patient, and flu shot may provoke fulminant ADEM-like episode.Copyright © 2022

Lactoferrin for Mental Health: Neuro-Redox Regulation and Neuroprotective Effects across the Blood-Brain Barrier with Special Reference to Neuro-COVID-19.

Overall mental health depends in part on the blood-brain barrier, which regulates nutrient transfer in-and-out of the brain and its central nervous system. Lactoferrin, an innate metal-transport protein, synthesized in the substantia nigra, particularly in dopaminergic neurons and activated microglia is vital for brain physiology. Lactoferrin rapidly crosses the blood-brain barrier via receptor-mediated transcytosis and accumulates in the brain capillary endothelial cells. Lactoferrin receptors are additionally present on glioma cells, brain micro-vessels, and neurons. As a regulator of neuro-redox, microglial lactoferrin is critical for protection/repair of neurons and healthy brain function. Iron imbalance and oxidative stress are common among patients with neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, dementia, depression, and multiple sclerosis. As an endogenous iron-chelator, lactoferrin prevents iron accumulation and dopamine depletion in Parkinson's disease patients. Oral lactoferrin supplementation could modulate the p-Akt/PTEN pathway, reduce Aß deposition, and ameliorate cognitive decline in Alzheimer's disease. Novel lactoferrin-based nano-therapeutics have emerged as effective drug-delivery systems for clinical management of neurodegenerative disorders. Recent emergence of the Coronavirus disease-2019 (COVID-19) pandemic, initially considered a respiratory illness, demonstrated a broader virulence spectrum with the ability to cross the blood-brain barrier and inflict a plethora of neuropathological manifestations in the brain - the Neuro-COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are widely reported in Parkinson's disease, Alzheimer's disease, dementia, and multiple sclerosis patients with aggravated clinical outcomes. Lactoferrin, credited with several neuroprotective benefits in the brain could serve as a potential adjuvant in the clinical management of Neuro-COVID-19.

Utility of multidisciplinary meetings in paediatric and adolescent oncofertility

Study objective: Multidisciplinary meetings (MDMs) are increasingly implemented in complex care based on the principle that they lead to evidence-based treatment recommendations, foster adherence to clinical guidelines, induce better team performance and improve medical care. In oncofertility, the uncertain outcomes of fertility preservation procedures in children contribute to the complexity of decision-making. There is limited published information on the influence of MDMs on paediatric and adolescent oncofertility care. Aim(s): To describe the implementation, characteristics & outcomes of multidisciplinary meetings (MDMs) in a paediatric oncofertility setting. Method(s): A retrospective medical records review of oncofertility MDMs held between April 2020 and March 2021 at the Royal Children's Hospital Melbourne. Inductive content analysis of the reasons for MDM was undertaken. MDM documentation was scored out of 24, according to a Victorian Paediatric Integrated Cancer Service quality assurance checklist for MDMs, (1)) which included consent for MDM, nature of attendees, quality of discussion and documentation. Result(s): Of the 169 oncology patients treated at the Royal Children's Hospital between 1st April 2020 and 31st March 2021, MDMs were required for 40 patients (23.7%). The median number of clinical attendees was 10, and included craft groups from both paediatric and adult centres (oncology, oncofertility, gynaecology, clinical ethics, endocrinology, paediatric surgery, anaesthetics, haematology, fertility specialists and reproductive scientists). Fifty-four percent (n=22) of MDMs were for male patients (median age 8.4 [0.1-16.5] years) and 46% for females (n=18, median age 8.1[0.4-16.3] years). The commonest diagnoses presented at MDM were brain tumours (27.5%), leukemia (25%), and non malignant conditions (19.5%). Approximately 77% of all MDM patients were going to receive treatment that put them at high infertility risk and 62.5% had co-morbidities. MDMs included the following themes (i) likelihood of successful parenthood: disease progression, prognosis, neurocognitive decline;(ii) certainty or otherwise of planned treatment and infertility risks;(iii) mitigation of anaesthetic and surgical risks;(iv) ethical concerns;(v) organizational capacity and logistics in the face of covid restrictions or high dependent care between centres (vi) child and family of risks, expectations and their values regarding fertility preservation. In 87.5% of cases, it was deemed permissible to offer fertility preservation. The median score for the MDMs derived from the quality assurance checklist was 16. Conclussion: MDMs acted as a valuable educational and communication tool improving situational awareness, building shared mental models, assisting with risk mitigation and oncofertility planning.Copyright © 2023

Impact of Covid-19 pandemic on neuro-oncology multidisciplinary tumor board in the pre-vaccine era: the Normandy experience.

INTRODUCTION: The COVID19 pandemic had a strong impact on the healthcare system, particularly in oncology. Brain tumor are usually revealed by acute and life threatening symptoms. We wanted to evaluate the possible consequences of the COVID19 pandemic in 2020 on the activity of neuro-oncology multidisciplinary tumor board in a Normandy region (France). METHODS: A descriptive, retrospective, multicenter study was conducted in the four referent centers (two universitary hospitals and two cancer centers). The main objective was to compare the average number of neuro-oncology patients presented per multidisciplinary tumor board per week between a pre-COVID19 reference period (period 1 from December 2018 to December 2019) and the pre-vaccination period (period 2 from December 2019 to November 2020). RESULTS: Across Normandy, 1540 cases were presented in neuro-oncology multidisciplinary tumor board in 2019 and 2020. No difference was observed between period 1 and 2: respectively 9.8 per week versus 10.7, P=0.36. The number of cases per week also did not significantly differ during the lockdown periods: 9.1/week versus 10.4 during the non-lockdown periods, P=0.26. The only difference observed was a higher proportion of tumor resection during the lockdown periods: 81.4% (n=79/174) versus 64.5% (n=408/1366), P=0.001. CONCLUSION: The pre-vaccination era of the COVID19 pandemic did not impact the activity of neuro-oncology multidisciplinary tumor board in the Normandy region. The possible consequences in terms of public health (excess mortality) due to this tumor location should now be investigated.

Impact of COVID-19 pandemic on neuropathology service: Experience at one Canadian center.

The COVID-19 pandemic has had a significant impact on medical services. Many countries postponed nonemergent procedures to preserve hospital resources for the unprecedented situation. Surgical backlogs caused by the COVID-19 pandemic have been evaluated by different groups. However, the impact of this pandemic on pathology and specifically neuropathology (NP) services has received limited attention. In this study, we reviewed all NP reports of the London Health Sciences Centre from January 2018 (2 years before the pandemic declaration) until the end of the year 2021. Demographic information and pathology details were collected. For tumors, site, histopathology types, and WHO grading were analyzed. In nontumoral specimens, pathological diagnoses were compared in pre- and postpandemic time. The total number of NP samples reached its lowest in April 2020, corresponding to the first Ontario provincial lockdown, and fluctuated throughout the studied period. Among the different types of NP surgical specimens, muscle and epilepsy-related specimens showed a more significant reduction, compared to neoplastic specimens. In 2020, the proportion of tumor specimens from patients older than 40 years of age increased. Similarly, the proportion of high-grade glioma and brain metastasis diagnoses also increased. Lastly, we observed a marked increase in biopsies for temporal arteritis and other inflammatory lesions.

Advances in mRNA nanomedicines for malignant brain tumor therapy

Nowadays, malignant brain tumors are still mostly lethal diseases with poor prognosis and a clinical median survival rate of fewer than 2 years after therapeutic intervention. It is difficult to achieve complete remission of brain tumors due to blood-brain barrier (BBB) and a lack of efficient drug delivery systems to targeted transportation of brain tumor medicines. Nanoparticle delivery systems have shown merits including stability and high carrier capacity for the transportation of different drugs to treat brain tumors. The application of mRNA nanomedicines brings in great promise not only in COVID-19, but also for malignant brain tumor immunotherapy. The appropriate delivery system facilitates mRNA delivery efficiency and enhances the immune response successfully, for optimal treatment outcomes on malignant brain tumors. Herein, we do an updated review on the development of mRNA nanomedicines for malignant brain cancer treatment. We focus on how to design mRNA-loaded nanoparticle-based delivery systems with optimized pharmacokinetics and pharmacodynamics for efficient therapy of brain cancers. In addition, we point out the challenges and solutions for further development of mRNA nanomedicines for brain cancer therapy. We hope this review would stimulate interest among researchers with different backgrounds and expedite the translation from bench to bedside for the mRNA nanomedicines. © 2022 The Authors