Gliomas, particularly glioblastoma (GBM), represent the most prevalent and aggressive tumors of the central nervous system (CNS). Despite recent treatment advancements, patient survival rates remain low. The diagnosis of GBM traditionally relies on neuroimaging methods such as magnetic resonance imaging (MRI) or computed tomography (CT) scans and postoperative confirmation via histopathological and molecular analysis. Imaging techniques struggle to differentiate between tumor progression and treatment-related changes, leading to potential misinterpretation and treatment delays. Similarly, tissue biopsies, while informative, are invasive and not suitable for monitoring ongoing treatments. These challenges have led to the emergence of liquid biopsy, particularly through blood samples, as a promising alternative for GBM diagnosis and monitoring. Presently, blood and cerebrospinal fluid (CSF) sampling offers a minimally invasive means of obtaining tumor-related information to guide therapy. The idea that blood or any biofluid tests can be used to screen many cancer types has huge potential. Tumors release various components into the bloodstream or other biofluids, including cell-free nucleic acids such as microRNAs (miRNAs), circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), proteins, extracellular vesicles (EVs) or exosomes, metabolites, and other factors. These factors have been shown to cross the blood-brain barrier (BBB), presenting an opportunity for the minimally invasive monitoring of GBM as well as for the real-time assessment of distinct genetic, epigenetic, transcriptomic, proteomic, and metabolomic changes associated with brain tumors. Despite their potential, the clinical utility of liquid biopsy-based circulating biomarkers is somewhat constrained by limitations such as the absence of standardized methodologies for blood or CSF collection, analyte extraction, analysis methods, and small cohort sizes. Additionally, tissue biopsies offer more precise insights into tumor morphology and the microenvironment. Therefore, the objective of a liquid biopsy should be to complement and enhance the diagnostic accuracy and monitoring of GBM patients by providing additional information alongside traditional tissue biopsies. Moreover, utilizing a combination of diverse biomarker types may enhance clinical effectiveness compared to solely relying on one biomarker category, potentially improving diagnostic sensitivity and specificity and addressing some of the existing limitations associated with liquid biomarkers for GBM. This review presents an overview of the latest research on circulating biomarkers found in GBM blood or CSF samples, discusses their potential as diagnostic, predictive, and prognostic indicators, and discusses associated challenges and future perspectives. 

Circulating Liquid Biopsy Biomarkers in Glioblastoma: Advances and Challenges

Liquid biopsy: creating opportunities in brain space

Postpartum hemorrhage is a relatively common and highly morbid complication of the postpartum period that often requires management by specialized providers at tertiary care facilities. Critical care transport teams may be tasked with transporting postpartum patients who are already experiencing postpartum hemorrhage, but they should also be aware that other peripartum patients may be at risk for developing postpartum hemorrhage while in the process of transport. As such, it is imperative that transport providers understand the signs, symptoms, causes, and complications of postpartum hemorrhage as well as the options for intervention and treatment. This article reviews the current clinical evidence regarding resuscitation and medical management strategies that transport teams should be familiar with as well as more advanced and invasive management techniques they may encounter and be expected to monitor during transport, such as balloon tamponade and aortic balloon occlusion. 

Management of Postpartum Hemorrhage in Critical Care Transport

Artificial Intelligence Applications to Detect Pediatric Brain Tumor Biomarkers

Purpose of review The purpose of this review is to discuss the value of blood and CSF biomarkers in primary CNS tumors. Recent findings Several analytes can be assessed with liquid biopsy techniques, including circulating tumor cells, circulating cell-free tumor DNA, circulating cell-free RNA, circulating proteins and metabolites, extracellular vesicles and tumor-educated platelets. Among diffuse gliomas of the adult, ctDNA in blood or CSF has represented the most used analyte, with the detection of molecular alterations such as MGMT promoter, PTEN, EGFRVIII, TERT promoter mutation and IDH R132H mutation. In general, CSF is enriched for ctDNA as compared with plasma. The use of MRI-guided focused ultrasounds to disrupt the blood–brain barrier could enhance the level of biomarkers in both blood and CSF. The detection of MYD88 L265P mutation with digital droplet PCR and the detection of ctDNA with next generation sequencing represent the best tools to diagnose and monitoring CNS lymphomas under treatment. In meningiomas, the low concentration of ctDNA is a limiting factor for the detection of driver mutations, such as NF2, AKTs, SMO, KLF4, TRAF7, SMARCB1, SMARCE1, PTEN, and TERT; an alternative approach could be the isolation of ctDNA through circulating extracellular vesicles. Liquid biopsies are being used extensively for diagnosis and surveillance of diffuse midline gliomas, in particular with the detection of the driver mutation H3K27M. Last, specific methylome patterns in CSF may allow the distinction of glioblastomas from CNS lymphomas or meningiomas. Summary This review summarizes the current knowledge and future perspectives of liquid biopsy of blood and CSF for diagnosis and monitoring of primary CNS tumors. 

Blood and cerebrospinal fluid biomarkers in neuro-oncology

To evaluate the safety and efficacy of combining yttrium-90 radioembolization (Y90-RE) with immune checkpoint inhibitor therapy, consecutive advanced unresectable hepatocellular carcinoma (HCC) patients treated between 2016 and 2022 with atezolizumab/bevacizumab or nivolumab within three-months pre- and post-Y90-RE were retrospectively evaluated. Tumor response and treatment-related clinical/laboratory adverse events (AE) were assessed at 1 and 6 months, as well as differences in clinical and laboratory variables and median overall survival (OS) from initial treatment (whether it was Y90-RE or systemic therapy) between the two cohorts. A total of 19 patients (10 atezolizumab/bevacizumab; 9 nivolumab), comprising 84% males with median age 69 years, met the inclusion criteria. Compared to the atezolizumab/bevacizumab group, there were less males (100% vs. 67%; p = 0.02) and more ECOG ≥ 2 patients in the nivolumab group (0% vs. 33%; p = 0.02). Baseline characteristics or incidence of 6-month post-treatment any-grade AE (60% vs. 56%; p = 0.7), grade ≥ 3 AE (0% vs. 11%; p = 0.3), objective response (58% total, 60% vs. 56%; p = 0.7), and complete response (16% total; 10% vs. 22%; p = 0.8) were similar between the atezolizumab/bevacizumab and the nivolumab cohorts. Median OS was 12.9 months for the whole cohort, 16.4 months for nivolumab, and 10.7 months for atezolizumab/bevacizumab. Among patients with advanced unresectable HCC, the utilization of Y90-RE concurrently or within 90 days of nivolumab or atezolizumab/bevacizumab immunotherapy, appears to be well-tolerated and with a low incidence of severe AE.

Safety and Efficacy of Concurrent Atezolizumab/Bevacizumab or Nivolumab Combination Therapy with Yttrium-90 Radioembolization of Advanced Unresectable Hepatocellular Carcinoma

Resuscitative endovascular balloon occlusion of the aorta (REBOA) has emerged over the past decade as a technique to control life-threatening hemorrhage and treat hemorrhagic shock, being increasingly used to treat noncompressible traumatic torso hemorrhage. Reports during this time also support the use of the REBOA device for an expanding range of indications including non-traumatic abdominal hemorrhage, postpartum hemorrhage, placenta accreta spectrum disorder (PAS), and cardiopulmonary resuscitation (CPR). The strongest available evidence supports REBOA as a lifesaving adjunct to definitive surgical management in trauma and as a method to help prevent hysterectomy in select patients with postpartum hemorrhage or PAS. In comparison with initial descriptions of complete REBOA inflation, techniques for partial REBOA inflation have been introduced to achieve hemodynamic stability while minimizing adverse events relating to reperfusion injuries. Fluoroscopy-free REBOA has been described in various settings, including trauma, obstetrics, and out-of-hospital cardiac arrest. As use of REBOA expands outside of the trauma setting and into non-traumatic abdominal hemorrhage, obstetrics, and CPR, it is imperative for radiologists to become familiar with this technology, its proper placement, and its potential adverse sequela.

REBOA: Expanding Applications from Traumatic Hemorrhage to Obstetrics and Cardiopulmonary Resuscitation, From the AJR Special Series on Emergency Radiology.

Glioblastoma (GBM) is a common and deadly brain tumor with late diagnoses and poor prognoses. Machine learning (ML) is an emerging tool that can create highly accurate diagnostic and prognostic prediction models. This paper aimed to systematically search the literature on ML for GBM metabolism and assess recent advancements. A literature search was performed using predetermined search terms. Articles describing the use of an ML algorithm for GBM metabolism were included. Ten studies met the inclusion criteria for analysis: diagnostic (n = 3, 30%), prognostic (n = 6, 60%), or both (n = 1, 10%). Most studies analyzed data from multiple databases, while 50% (n = 5) included additional original samples. At least 2536 data samples were run through an ML algorithm. Twenty-seven ML algorithms were recorded with a mean of 2.8 algorithms per study. Algorithms were supervised (n = 24, 89%), unsupervised (n = 3, 11%), continuous (n = 19, 70%), or categorical (n = 8, 30%). The mean reported accuracy and AUC of ROC were 95.63% and 0.779, respectively. One hundred six metabolic markers were identified, but only EMP3 was reported in multiple studies. Many studies have identified potential biomarkers for GBM diagnosis and prognostication. These algorithms show promise; however, a consensus on even a handful of biomarkers has not yet been made.

/pdf/assessing-metabolic-markers-in-glioblastoma-using-machine-284rcqiy.pdf

Assessing Metabolic Markers in Glioblastoma Using Machine Learning: A Systematic Review

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Papers

Safety and Efficacy of Concurrent Atezolizumab/Bevacizumab or Nivolumab Combination Therapy with Yttrium-90 Radioembolization of Advanced Unresectable Hepatocellular Carcinoma

REBOA: Expanding Applications from Traumatic Hemorrhage to Obstetrics and Cardiopulmonary Resuscitation, From the AJR Special Series on Emergency Radiology.

Assessing Metabolic Markers in Glioblastoma Using Machine Learning: A Systematic Review