Oncolytic viral therapy: a review and promising future directions.

Oncolytic viral therapy is quickly emerging as a promising subset of immunotherapy, which theoretically can target tumor cells while sparing surrounding healthy cells by harnessing the replication machinery of viruses with tropism for tumor cells, resulting in direct oncolysis, and by transforming immunologically "cold" tumor into areas that elicit the host's immune response. This review provides an overview of oncolytic viral therapy until the present day, starting with the original concept in 1912. The general mechanism of oncolytic viruses (OVs) depends on selectively integrating them into tumor cells based on genetic engineering of viral genomic material, inducing oncolysis and eliciting the host's innate immune response. Moreover, a major component of oncolytic viral therapy has been herpes simplex virus, with talimogene laherparepvec being the only FDA-approved oncolytic viral therapy for the treatment of melanomas. This review explores the characteristics, advantages, disadvantages, and therapeutic uses of several DNA and RNA viral families. A snapshot of the oncolytic viral treatments used in the most recent and advanced clinical trials is also provided. Lastly, the challenges of implementing oncolytic viral therapy are explored, both at a molecular and clinical level, with a highlight of promising future directions. In particular, the lack of an optimal delivery method based on tumor type for oncolytic viral therapy poses a significant obstacle, even in clinical studies. Intrathecal continuous delivery of OVs is a promising prospect, potentially by adapting the novel continuous irrigation and drainage IRRAflow catheter. Further exploration and testing of the IRRAflow catheter should be undertaken.

MicroRNAs' Role in Diagnosis and Treatment of Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is most commonly seen in patients over 55 years of age and often results in a loss of many productive years. SAH has a high mortality rate, and survivors often suffer from early and secondary brain injuries. Understanding the pathophysiology of the SAH is crucial in identifying potential therapeutic agents. One promising target for the diagnosis and prognosis of SAH is circulating microRNAs, which regulate gene expression and are involved in various physiological and pathological processes. In this review, we discuss the potential of microRNAs as a target for diagnosis, treatment, and prognosis in SAH.

Review of spinal dural arteriovenous fistulas: Challenges, diagnostics, management, and pathophysiology.

Spinal dural arteriovenous fistulae are rare, spinal vascular malformations that commonly present with progressive myelopathy in a specific demographic and are treatable with surgery (preferred) and/or endovascular embolization. PubMed and Google Scholar were searched with terms including but not limited to "spinal dural arteriovenous fistula", "imaging", "management" "surgery vs embolization", "outcomes", "pathogenesis" to find relevant studies, including emerging research. The purpose of this literature review is to highlight presentation, imaging characteristics, management strategies, pathophysiology, and future directions for these rare but distinct entities.

Temporal Trend of COVID-19 Clinical Severity and the Ethnic/Racial Disparity: A Report from the Maryland Study Group.

OBJECTIVES: This study aimed to evaluate the temporal trend of novel coronavirus disease 2019 (COVID-19) symptoms and severity of clinical outcomes among pregnant women over a calendar year in the State of Maryland and compare clinical outcomes between different ethnic and racial groups. STUDY DESIGN: We conducted a retrospective, multicenter observational study of the temporal trend of COVID-19 clinical presentation during pregnancy in the State of Maryland. We reviewed consecutive charts of adult pregnant females, aged 18 to 55 years, with laboratory-confirmed severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection between March 1, 2020, and February 28, 2021, and managed within the University of Maryland Medical System and Johns Hopkins Medicine. We excluded cases with insufficient data for assessing the COVID-19 diagnosis, pregnancy status, or clinical outcomes. We evaluated the evolution of COVID-19 symptoms at the time of presentation. Also, we compared COVID-19 infection rate, hospitalization rate, oxygen use, and intensive care unit (ICU) admission rates between different ethnic and racial groups. RESULTS: We included 595 pregnant women with laboratory-confirmed COVID-19 over the study period. The prevalence of respiratory and systemic symptoms decreased over time with incidence rate ratios (IRRs) of 0.91 per month (95% confidence interval [CI]: 0.88-0.95) and 0.87 per month (95% CI: 0.83-0.95), respectively. The prevalence of hospitalization, O2 requirement, and ICU admission decreased over time with IRRs of 0.86 per month (95% CI: 0.82-0.91), 0.91 per month (95% CI: 0.84-0.98), and 0.70 per month (95% CI: 0.57-0.85), respectively. The Hispanic and Black populations had a higher COVID-19 infection rate and hospitalization rate than the non-Hispanic White population (p = 0.004, < 0.001, and < 0.001, respectively). CONCLUSION: Understanding the concepts of viral evolution could potentially help the fight against pandemics like COVID-19. Moreover, this might improve the knowledge of how pandemics affect disadvantaged populations and help close the gap in health care inequities. KEY POINTS: · A trade-off between virulence and transmissibility is determined by the natural selection of viruses.. · Understanding the concepts of viral evolution can help the fight against pandemics like COVID-19.. · Evolution of SARS-CoV-2 over time resulted in decreased virulence and increased infectivity..

Innovative Approaches for Breast Cancer Metastasis to the Brain.

Breast cancer metastasis is a continued concern for patients with recent development in our understanding of disease progression. In this paper, we highlight the pathophysiology behind breast cancer metastasis. Blood brain barrier disruption plays a critical component in progression. We then investigate the current treatment strategies and recommended guidelines. This focuses on radiation and medical management. Finally, we address the role of surgical intervention. The data is organized into tables and figures to highlight key components. Finally, we address emerging treatments and pre-clinical data. The paper will serve as a user-friendly guide for clinicians and researchers to help formulate a strategy to manage breast cancer metastasis patients sufficiently.

Curvularia and the Brain: Case Demonstration of Optimal Management.

Background: Curvularia is a ubiquitous fungus found in tropical climates and has been reported to grow on marijuana leaves. Rarely, it can infect humans and propagate from the nasal sinuses into the brain. Case: A 28-year-old immunocompetent patient presented with history of nasal polyps, headache, and subtle visual deficits on the right. Imaging revealed what appeared to be an invasive mass growing through the ethmoid and sphenoid sinuses into the anterior cranial fossa. Results: Otolaryngology performed an endoscopic nasal biopsy with pathology and cultures consistent for Curvularia (figure 6). A combination case with neurosurgery and otolaryngology was planned. Surgeons used a bifrontal craniotomy and endonasal approach for gross total resection. Following resection, the patient was placed on 4 weeks of amphotericin treatment followed by 12 months of voriconazole based on recommendations by infectious disease. The patient has been stable since surgery. Conclusion: Curvularia is a rare but potentially life threatening central nervous system infection that can be acquired from inhalational marijuana use. This illustrative case shows the importance of aggressive debridement followed by broad spectrum antifungal treatment to optimize outcome. With marijuana's increasing popularity, Curvalaria should be included on the differential diagnosis.

Gut microbiome and neurosurgery: Implications for treatment.

Introduction: The aim of this review is to summarize the current understanding of the gut-brain axis (GBA), its impact on neurosurgery, and its implications for future treatment. Background: An abundance of research has established the existence of a collection of pathways between the gut microbiome and the central nervous system (CNS), commonly known as the GBA. Complicating this relationship, the gut microbiome bacterial diversity appears to change with age, antibiotic exposure and a number of external and internal factors. Methods: In this paper, we present the current understanding of the key protective and deleterious roles the gut microbiome plays in the pathogenesis of several common neurosurgical concerns. Results: Specifically, we examine how spinal cord injury, traumatic brain injury and stroke may cause gut microbial dysbiosis. Furthermore, this link appears to be bidirectional as gut dysbiosis contributes to secondary CNS injury in each of these ailment settings. This toxic cycle may be broken, and the future secondary damage rescued by timely, therapeutic, gut microbiome modification. In addition, a robust gut microbiome appears to improve outcomes in brain tumour treatment. There are several primary routes by which microbiome dysbiosis may be ameliorated, including faecal microbiota transplant, oral probiotics, bacteriophages, genetic modification of gut microbiota and vagus nerve stimulation. Conclusion: The GBA represents an important component of patient care in the field of neurosurgery. Future research may illuminate ideal methods of therapeutic microbiome modulation in distinct pathogenic settings.

Neuroinflammation and subarachnoid hemorrhage: a revised look at the literature.

A key topic for aneurysmal subarachnoid hemorrhage is neuroinflammation. Neuroinflammation can predispose to aneurysm formation and rupture. Neuroinflammation can also result from the blood breakdown products after aneurysm rupture. Recent evidence has shown that perpetual neuroinflammation can contribute to vasospasm and hydrocephalus. Targeting neuroinflammation is a novel mechanism for preventing subsequent neurologic sequalae. In this review, we highlight the pathophysiology of aneurysm formation, the neuroinflammatory surge after rupture including the involved cytokines, and ultimately tie in the contributory clinical relevance. In the last sections, we look at the pre-clinical data and novel avenues for further discovery. This paper will be a useful resource to both the clinician and scientific investigator.

CNS Lymphoma: Clinical Pearls and Management Considerations.

Primary CNS lymphoma presents unique challenges for the clinician. New evidence has emerged regarding the appropriate workup, management considerations, and treatment. In this paper, we highlight the clinical presentations, disease prognosis, and management considerations. We place specific emphasis on the decision tree for immunocompetent and immunocompromised. The key imaging characteristics are discussed. Once biopsy prove lymphoma, important management considerations are addressed. We highlight need for follow up and role for surgery verse radiation. Finally, we present emerging treatment options and pre-clinical work that will be making its way through the pipeline. This up-to-date review will serve as a key learning tool for clinicians and researchers.

Overview of Neurotrauma and Sensory Loss.

Neurotrauma can cause devastating outcomes for patients both from primary as well as secondary injury. Sensory loss following neurotrauma is often overlooked and undermanaged. To gain awareness about this important topic, we highlight key findings of visual, hearing, taste, and smell disturbances that can occur after injury. The pathways are highlighted as well as significant pathophysiology. Both primary disruption as well as secondary disruptions from ongoing inflammation are addressed. The figures are designed to be user friendly guides for the clinician to help manage these patients. In the final section, we address key management strategies and approaches. The strategies deal with multidisciplinary care as well as multimodality treatments. This review serves as a primer for early recognition of deficits and initiation of appropriate treatments.

Primer of vein of galen malformation management.

Vein of Galen Malformations offer a unique clinical challenge that can present as heart failure and hydrocephalus. The mainstay of treatment is embolization and management of systemic issues. Recently, radiation treatment has also offered some benefit. Herein we review the literature and present common findings, pathophysiology, and management strategies. This user-friendly guide can help clinicians and researchers tackle this important topic.

Recent Treatment Strategies in Alzheimer's Disease and Chronic Traumatic Encephalopathy.

Neurotrauma has been well linked to the progression of neurodegenerative disease. Much work has been done characterizing chronic traumatic encephalopathy, but less has been done regarding the contribution to Alzheimer's Disease. This review focuses on AD and its association with neurotrauma. Emerging clinical trials are discussed as well as novel mechanisms. We then address how some of these mechanisms are shared with CTE and emerging pre-clinical studies. This paper is a user-friendly resource that summarizes the emerging findings and proposes further investigation into key areas of interest. It is intended to serve as a catalyst for both research teams and clinicians in the quest to improve effective treatment and diagnostic options.

Focused ultrasound: Innovation in use for neurologic conditions.

Focused ultrasound has emerged as a key tool for neurologic disorders. In this focused review, we discuss the utility in disrupting the blood brain barrier to maximize treatment. This can facilitate creating direct coagulative lesions and aid in the administration of chemotherapy. Furthermore, it can facilitate neuromodulation when used in pulse sequencing. The current literature regarding brain tumors, essential tremor, and obsessive-compulsive disorder is reviewed. Additionally, concepts and experimental outcomes for neurodegenerative disease such as Alzheimer's is presented. Focused ultrasound as a tool is still in its infancy but the potential for adjuvant and direct therapy is promising. More clinical uses will become apparent in coming decades.

Pregnancy alters interleukin-1 beta expression and antiviral antibody responses during severe acute respiratory syndrome coronavirus 2 infection.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2, the disease-causing pathogen of the coronavirus disease 2019 pandemic, has resulted in morbidity and mortality worldwide. Pregnant women are more susceptible to severe coronavirus disease 2019 and are at higher risk of preterm birth than uninfected pregnant women. Despite this evidence, the immunologic effects of severe acute respiratory syndrome coronavirus 2 infection during pregnancy remain understudied. OBJECTIVE: This study aimed to assess the impact of severe acute respiratory syndrome coronavirus 2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to severe acute respiratory syndrome coronavirus 2 among pregnant and nonpregnant women. STUDY DESIGN: Immune responses to severe acute respiratory syndrome coronavirus 2 were analyzed using samples from pregnant (n=33) and nonpregnant (n=17) women who tested either positive (pregnant, 22; nonpregnant, 17) or negative for severe acute respiratory syndrome coronavirus 2 (pregnant, 11) at Johns Hopkins Hospital. We measured proinflammatory and placental cytokine messenger RNAs, neonatal Fc receptor expression, and tetanus antibody transfer in maternal and cord blood samples. In addition, we evaluated antispike immunoglobulin G, antispike receptor-binding domain immunoglobulin G, and neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 in serum or plasma collected from nonpregnant women, pregnant women, and cord blood. RESULTS: Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection expressed more interleukin-1 beta, but not interleukin 6, in blood samples collected within 14 days vs >14 days after performing severe acute respiratory syndrome coronavirus 2 test. Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection also had reduced antispike receptor-binding domain immunoglobulin G titers and were less likely to have detectable neutralizing antibody than nonpregnant women. Although severe acute respiratory syndrome coronavirus 2 infection did not disrupt neonatal Fc receptor expression in the placenta, maternal transfer of severe acute respiratory syndrome coronavirus 2 neutralizing antibody was inhibited by infection during pregnancy. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of coronavirus disease 2019 treatment in pregnancy. In addition, the long-term implications of placental inflammation for neonatal health require greater consideration.

Spinal Cord Injury: A Review of Current Management Considerations and Emerging Treatments.

Traumatic spinal cord injuries can have devastating outcomes for patients. In this focused review, we discuss the epidemiology of spinal cord injuries, associated neurologic exam findings, and primary and secondary injury progression. We then delve into the emerging treatment approaches and relevance to improving outcomes. The disease is multifactorial and has many management considerations. This concise user-friendly resource can help guide clinicians caring for these patients. Also, it points to the need for continued scientific discovery and improved pharmaceutical and device innovations.

Dysregulated immunity in SARS-CoV-2 infected pregnant women.

IMPORTANCE: The effects of SARS-CoV-2 infection on immune responses during pregnancy have not been systematically evaluated. OBJECTIVE: To assess the impact of SARS-CoV-2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to SARS-CoV-2 among pregnant and non-pregnant women. DESIGN: Immune responses to SARS-CoV-2 were analyzed using samples from pregnant and non-pregnant women who had either tested positive or negative for SARS-CoV-2. We measured, proinflammatory and placental cytokine mRNAs, neonatal Fc receptor (FcRn) receptor expression, and tetanus antibody transfer in maternal and cord blood samples. Additionally, we measured anti-spike (S) IgG, anti-S-receptor binding domain (RBD) IgG, and neutralizing antibody (nAb) responses to SARS-CoV-2 in serum or plasma collected from non-pregnant women, pregnant women, and cord blood. SETTING: Johns Hopkins Hospital (JHH). PARTICIPANTS: Pregnant women were recruited through JHH outpatient obstetric clinics and the JHH Labor & Delivery unit. Non-pregnant women were recruited after receiving outpatient SARS-CoV-2 testing within Johns Hopkins Health System, USA. Adult non-pregnant women with positive RT-PCR results for SARS-CoV-2, within the age range of 18-48 years, were included in the study. EXPOSURES: SARS-CoV-2. MAIN OUTCOMES AND MEASURES: Participant demographic characteristics, antibody titers, cytokine mRNA expression, and FcRn receptor expression. RESULTS: SARS-COV-2 positive pregnant women expressed more IL1ß , but not IL6 , in blood samples collected within 14 days versus > 14 days after a confirmed SARS-CoV-2 test, with similar patterns observed in the fetal side of placentas, particularly among asymptomatic pregnant women. Pregnant women with confirmed SARS-CoV-2 infection also had reduced anti-S-RBD IgG titers and were less likely to have detectable nAb as compared with non-pregnant women. Although SARS-CoV-2 infection did not disrupt FcRn expression in the placenta, maternal transfer of nAb was inhibited by SARS-CoV-2 infection during pregnancy. CONCLUSIONS AND RELEVANCE: SARS-CoV-2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of COVID-19 therapeutics in pregnancy. The long-term implications of placental inflammation for neonatal health also requires greater consideration.