Bendok, Bernard R.

Abstract Purpose: Monitoring disease progression in patients with high-grade gliomas (HGG) is challenging due to treatment-related changes in imaging and the requirement for neurosurgical intervention to obtain diagnostic tissue. DNA junctions in HGG often amplify oncogenes, making these DNA fragments potentially more abundant in blood than monoallelic mutations. In this study, we piloted a cell-free DNA approach for disease detection in the plasma of patients with HGG by leveraging patient-specific DNA junctions associated with oncogene amplifications. Experimental Design: Whole-genome sequencing of grade 3 or 4 isocitrate dehydrogenase–mutant or wild-type astrocytomas was utilized to identify amplified junctions. Individualized qPCR assays were developed using patient-specific primers designed for the amplified junction. ctDNA levels containing these junctions were measured in patient plasma samples. Results: Unique amplified junctions were evaluated by individualized semi-qPCR assays in presurgical plasma of 18 patients, 15 with tumor-associated focal amplifications and three without tumor-associated focal amplifications. high copy-number junctions were robustly detected in the plasma of 14 of 15 (93.3%) patients with amplified junctions and none of the controls. Changes in junction abundance correlated with disease trajectory in serial plasma samples from five patients, including increased abundance of amplified junctions preceding radiographic disease progression. Conclusions: In patients with grade 3 or 4 astrocytomas who had tumor-associated amplifications, patient-specific amplified junctions were successfully detected in assayed plasma from most patients. Longitudinal analysis of plasma samples correlated with disease trajectory, including cytoreduction and progression.

Telesurgery has the potential to overcome geographical barriers in surgical care, encouraging its deployment in areas with sparse surgical expertise. Despite successful in-human experiments and substantial technological progress, the adoption of telesurgery remains slow. In this Review, we analyze the reasons for this slow adoption. First, we identify various contexts for telesurgery and highlight the vastly different requirements for their realization. We then discuss why procedures with high urgency and skill sparsity are particularly suitable for telesurgery. Last, we summarize key research areas essential for further progress. The goal of this Review is to provide the reader with a comprehensive analysis of the current state of telesurgery research and to provide guidance for faster adoption of this exciting technology.

OBJECTIVE Patients with autosomal dominant polycystic kidney disease (ADPKD) have been identified to have a significantly increased risk of developing intracranial aneurysms (IAs). These patients are diagnosed at younger ages and are also at increased risk for IA rupture. The objective of this systematic review and meta-analysis was to identify risk factors associated with IA detection during screening of asymptomatic ADPKD patients. METHODS The authors searched for studies reporting the prevalence of IA among patients with ADPKD screened using MRA, CTA, or DSA on PubMed, Embase, Google Scholar, Scopus, Web of Science, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov prior to August 2023 by using individualized standardized search strategies. Eligibility of all retrieved studies was assessed according to the PRISMA guidelines. Risk of bias of the included observational studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using a random-effects model. RESULTS Twenty-four observational studies involving 5907 patients with ADPKD were identified for quantitative analysis. The authors observed an overall prevalence of IA of 12.6%. They identified several risk factors for IA with statistically significantly increased odds for unruptured IA (UIA) detection, including female sex (18 studies, OR 1.63, 95% CI 1.37–1.94, I 2 = 0%), family history of either IA or subarachnoid hemorrhage (SAH) (12 studies, OR 2.17, 95% CI 1.68–2.81, I 2 = 0%), family history of SAH (3 studies, OR 2.67, 95% CI 1.25–5.71, I 2 = 66.0%), stage 3 or greater chronic kidney disease (CKD) (4 studies, OR 2.55, 95% CI 1.84–3.54, I 2 = 0%), and hypertension (13 studies, OR 1.41, 95% CI 1.04–1.91, I 2 = 34%). Age > 45 years, family history of ADPKD, smoking status, and presence of liver cysts did not reach statistical significance as risk factors during this meta-analysis. CONCLUSIONS The results of the authors’ meta-analysis suggest increased risk of UIA detection in screening of ADPKD patients who are female, have a family history of IA or SAH, have hypertension, or have moderate or more severe CKD. Given the increased prevalence of IA in ADPKD patients with these risk factors, these patients may stand to benefit from screening for IA early in treatment or at time of diagnosis, even if neurologically asymptomatic.

OBJECTIVE While the relationship between smoking and subarachnoid hemorrhage is well established, data regarding the probability of detecting unruptured intracranial aneurysms (UIAs) in smokers remain sparse. The aim of this systematic review and meta-analysis is to provide a comprehensive understanding of the relationship between smoking and the likelihood of identifying UIAs in healthy asymptomatic patients who underwent brain imaging for indications unrelated to UIAs. METHODS A systematic review was conducted following the PRISMA guidelines. The PubMed and Scopus databases were searched for studies published before March 2024 that reported on the presence of UIAs in healthy asymptomatic patients who had undergone brain imaging for indications unrelated to UIAs. Three independent reviewers assessed the eligibility of all retrieved studies. Risk of bias for the included observational studies was assessed using the methodological index for non-randomized studies. Data on UIA prevalence, smoking status, and patient and aneurysm characteristics were extracted. The association between smoking and the presence of UIA was studied. A prevalence proportional meta-analysis was conducted across the included studies. A meta-analysis was performed with a random-effects model by using summary statistics from the included studies. RESULTS Six studies involving 47,788 patients who had undergone brain imaging were identified for quantitative analysis. The pooled UIA prevalence in the sample was 3.07% (95% CI 2.27%–4.16%). Patients who smoked had higher rates of aneurysm detection than the patients who did not smoke (pooled prevalence of 2.96%, 95% CI 2.68%–3.27% vs 2.23%, 95% CI 2.08%–2.39%). Although the relation between the two was not statistically significant (p = 0.06), smoking was associated with higher odds for UIA detection, yielding an OR of 1.34 (95% CI 1.07–1.67) with an I 2 value of 53%. CONCLUSIONS This study suggests a potentially higher risk of UIAs in patients who smoked than in those who never smoked. However, the results of this meta-analysis revealed that smoking was not statistically associated with higher UIA detection. This result could be explained by the limited number of studies published on this topic. If these findings reach statistical significance in future larger studies, it could justify revising guidelines to include cigarette smokers in intracranial aneurysm screening.