The Evolving Landscape of Leptomeningeal Cancer from Solid Tumors: A Systematic Review of Clinical Trials.

Leptomeningeal carcinomatosis (LMC) is a fatal but uncommon complication occurring in 5-15% of patients with stage IV cancer. Current treatment options are ineffective at managing leptomeningeal spread, with a median overall survival (mOS) of 2-6 months. We aimed to conduct a systematic review of the literature to identify past and future therapies for LMC from solid tumors. Forty-three clinical trials (CTs) published between 1982-2022 were identified. Of these, 35 (81.4%) were non-randomized CTs and 8 (18.6%) were randomized CTs. The majority consisted of phase I (16.3%) and phase II CTs (65.1%). Trials enrolled patients with LMC from various primary histology (n = 23, 57.5%), with one CT evaluating LCM from melanoma (2.4%). A total of 21 trials evaluated a single modality treatment. Among CTs, 23.7% closed due to low accrual. Intraventricular (ITV)/intrathecal (IT) drug delivery was the most common route of administration (n = 22, 51.2%) vs. systemic drug delivery (n = 13, 30.3%). Two clinical trials evaluated the use of craniospinal irradiation for LMC with favorable results. LMC continues to carry a dismal prognosis, and over the years, increments in survival have remained stagnant. A paradigm shift towards targeted systemic therapy with continued standardization of efficacy endpoints will help to shed light on promising treatments.

TransOrbital NeuroEndoscopic Surgery for Biopsy of the Left Cavernous Sinus: A Literature Review, Case Report, and Cadaveric Proof of Concept.

The aim of this report is to describe TransOrbital NeuroEndoscopic Surgery (TONES) as a safe alternative for obtaining a cavernous sinus (CS) biopsy. We describe this technique in a patient with a diffuse large B cell lymphoma mimicking Tolosa-Hunt's syndrome. Articles were gathered querying PubMed, Embase, and Scopus databases with terms related to a "transorbital neuroendoscopic approach." The literature search was performed by two independent authors (N.L.F. and J.R.), with inconsistencies resolved by the senior author (M.M.D.V.). After screening abstracts for relevance, full-length articles were reviewed for pertinent variables. A comparison was conducted with the illustrative case of a 69-year-old woman who presented to the emergency department with vertigo, ophthalmoplegia, and diplopia for 2 months. A brain magnetic resonance imaging revealed an infiltrative lesion at the left CS. A presumptive diagnosis of Tolosa-Hunt syndrome was made, but a confirmatory biopsy was performed using TONES. Based on our cadaveric study, literature review, and case report, the TONES approach was safe, effective for tissue diagnosis, and associated with minor morbidity and reduced hospital stay. Additional prospective studies are required to study its viability and safety in a larger group of patients.

Spinal leptomeningeal hemangioblastomatosis occurring without craniospinal surgery in von Hippel-Lindau disease.

Hemangioblastomatosis represents an unusual and malignant leptomeningeal dissemination of hemangioblastoma (HB). It has been reported in patients with sporadic HB or von Hippel-Lindau (VHL) disease. Hemangioblastomatosis had been reported following resection of a primary HB lesion in all cases except one patient with a sporadic HB. We present a patient with VHL with several HBs at the brainstem, cerebellum, pituitary stalk and retina who developed spinal hemangioblastomatosis without previous craniospinal surgery. A whole spine MRI showed the spinal dissemination from the primary lesions. The patient received craniospinal radiotherapy due to the extensive spinal leptomeningeal dissemination and multiple HBs. MRI performed 12 months after the radiotherapy showed stability of the lesions.

Smell Outcomes in Olfactory Groove Meningioma Resection Through Unilateral versus Bilateral Transcranial Approaches: A Systematic Review and Meta-analysis.

OBJECTIVE: Olfactory disturbance is a common complication that occurs following the surgical resection of olfactory groove meningiomas (OGMs). There is little evidence on the best transcranial approach that minimizes rates of postoperative olfactory disturbance. The objective of this systematic review and meta-analysis is to compare smell outcomes after OGM resection in unilateral versus bilateral transcranial approaches. METHODS: A systematic review of the literature and meta-analysis was conducted using PUBMED, SCOPUS, and EMBASE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The primary endpoint was incidence of new olfactory disturbance defined as anosmia or hyposmia, or both. Patients were classified as undergoing either a unilateral or bilateral approach. Data on presence of new postoperative olfactory deficits were used to generate standardized mean differences and 95% confidence intervals. RESULTS: Ten studies met the inclusion criteria for quantitative analysis, comprising 342 patients. A total of 216 patients underwent unilateral approaches while 126 underwent resection via bilateral approach. In the unilateral approach cohort, 17.1% experienced new postoperative olfactory disturbance following resection, compared with 19.2% of patients in the bilateral approach cohort. Forest plot did not reveal any significant difference in the incidence of new olfactory disturbance following either unilateral or bilateral approaches. CONCLUSIONS: Our data suggest that there is no significant difference between the investigated transcranial approaches and postoperative olfactory disturbances. Accordingly, our study suggests that further investigation with introduced experimental control could provide more insight into the capabilities and drawbacks of each route in relation to olfactory outcomes.

Zika virus infection of the placenta alters extracellular matrix proteome.

Zika virus (ZIKV) infection has been associated with fetal abnormalities by compromising placental integrity, but the mechanisms by which this occurs are unknown. Flavivirus can deregulate the host proteome, especially extracellular matrix (ECM) proteins. We hypothesize that a deregulation of specific ECM proteins by ZIKV, affects placental integrity. Using twelve different placental samples collected during the 2016 ZIKV Puerto Rico epidemic, we compared the proteome of five ZIKV infected samples with four uninfected controls followed by validation of most significant proteins by immunohistochemistry. Quantitative proteomics was performed using tandem mass tag TMT10plex™ Isobaric Label Reagent Set followed by Q Exactive™ Hybrid Quadrupole Orbitrap Mass Spectrometry. Identification of proteins was performed using Proteome Discoverer 2.1. Proteins were compared based on the fold change and p value using Limma software. Significant proteins pathways were analyzed using Ingenuity Pathway (IPA). TMT analysis showed that ZIKV infected placentas had 94 reviewed differentially abundant proteins, 32 more abundant, and 62 less abundant. IPA analysis results indicate that 45 of the deregulated proteins are cellular components of the ECM and 16 play a role in its structure and organization. Among the most significant proteins in ZIKV positive placenta were fibronectin, bone marrow proteoglycan, and fibrinogen. Of these, fibrinogen was further validated by immunohistochemistry in 12 additional placenta samples and found significantly increased in ZIKV infected placentas. The upregulation of this protein in the placental tissue suggests that ZIKV infection is promoting the coagulation of placental tissue and restructuration of ECM potentially affecting the integrity of the tissue and facilitating dissemination of the virus from mother to the fetus.

Decreased CSTB, RAGE, and Axl Receptor Are Associated with Zika Infection in the Human Placenta.

Zika virus (ZIKV) compromises placental integrity, infecting the fetus. However, the mechanisms associated with ZIKV penetration into the placenta leading to fetal infection are unknown. Cystatin B (CSTB), the receptor for advanced glycation end products (RAGE), and tyrosine-protein kinase receptor UFO (AXL) have been implicated in ZIKV infection and inflammation. This work investigates CSTB, RAGE, and AXL receptor expression and activation pathways in ZIKV-infected placental tissues at term. The hypothesis is that there is overexpression of CSTB and increased inflammation affecting RAGE and AXL receptor expression in ZIKV-infected placentas. Pathological analyses of 22 placentas were performed to determine changes caused by ZIKV infection. Quantitative proteomics, immunofluorescence, and western blot were performed to analyze proteins and pathways affected by ZIKV infection in frozen placentas. The pathological analysis confirmed decreased size of capillaries, hyperplasia of Hofbauer cells, disruption in the trophoblast layer, cell agglutination, and ZIKV localization to the trophoblast layer. In addition, there was a significant decrease in CSTB, RAGE, and AXL expression and upregulation of caspase 1, tubulin beta, and heat shock protein 27. Modulation of these proteins and activation of inflammasome and pyroptosis pathways suggest targets for modulation of ZIKV infection in the placenta.

SARS-Cov-2: Biology, Detection, Macrophage Mediated Pathogenesis and Potential Treatments.

The respiratory disease caused by the Coronavirus infectious disease 2019 (COVID19) has spread rapidly since December 2019 in Wuhan, China. This new strain of Coronavirus is similar to the SARS Corona virus and has been termed SARS-CoV-2. Both viruses have emerged from bats and adapted to humans. On March 11, 2020 COVID19 was declared Pandemic by the WHO and as of May 1, 2020 COVID19 disease continues to grow rapidly with 3,400,595 cases and 239,583 deaths world-wide. This review describes the biology of SARSCOV2, Detection, Macrophage-Mediated Pathogenesis and Potential Treatments.