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DOTATATE (1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid [DOTA]‐octreotate) is a compound that binds somatostatin receptors seen in tumors such as meningiomas. Here, we present a case of a patient with progressive bilateral ophthalmoplegia due to meningiomatosis involving both cavernous sinuses, which was highlighted by DOTATATE imaging. Some studies have shown DOTATATE imaging is superior to contrast‐enhanced magnetic resonance imaging (MRI) in identifying extent of intraosseous meningioma growth, which has been associated with worse prognosis. DOTATATE imaging should be considered in cases of unknown diagnosis of mass lesions and lesions that are in areas not easily accessible to biopsy, such as the cavernous sinuses.

Mutant isocitrate dehydrogenase 1 ( IDH1 ) is common in gliomas, and produces D-2-hydroxyglutarate (D-2-HG). The full effects of IDH1 mutations on glioma biology and tumor microenvironment are unknown. We analyzed a discovery cohort of 169 World Health Organization (WHO) grade II–IV gliomas, followed by a validation cohort of 148 cases, for IDH1 mutations, intratumoral microthrombi, and venous thromboemboli (VTE). 430 gliomas from The Cancer Genome Atlas were analyzed for mRNAs associated with coagulation, and 95 gliomas in a tissue microarray were assessed for tissue factor (TF) protein. In vitro and in vivo assays evaluated platelet aggregation and clotting time in the presence of mutant IDH1 or D-2-HG. VTE occurred in 26–30 % of patients with wild-type IDH1 gliomas, but not in patients with mutant IDH1 gliomas (0 %). IDH1 mutation status was the most powerful predictive marker for VTE, independent of variables such as GBM diagnosis and prolonged hospital stay. Microthrombi were far less common within mutant IDH1 gliomas regardless of WHO grade (85–90 % in wild-type versus 2–6 % in mutant), and were an independent predictor of IDH1 wild-type status. Among all 35 coagulation-associated genes, F3 mRNA, encoding TF, showed the strongest inverse relationship with IDH1 mutations. Mutant IDH1 gliomas had F3 gene promoter hypermethylation, with lower TF protein expression. D-2-HG rapidly inhibited platelet aggregation and blood clotting via a novel calcium-dependent, methylation-independent mechanism. Mutant IDH1 glioma engraftment in mice significantly prolonged bleeding time. Our data suggest that mutant IDH1 has potent antithrombotic activity within gliomas and throughout the peripheral circulation. These findings have implications for the pathologic evaluation of gliomas, the effect of altered isocitrate metabolism on tumor microenvironment, and risk assessment of glioma patients for VTE.

Background Management of hydrocephalus symptoms in the setting of leptomeningeal disease (LMD) includes cerebrospinal fluid (CSF) diversion, which can in the form of ventriculoperitoneal shunting (VPS) and lumboperitoneal shunting (LPS). However, the quantifiable postoperative course following this intervention is poorly defined. Correspondingly the aim of our study was to quantitatively define and analyze the pooled metadata regarding this topic. Methods Multiple electronic databases from inception to March 2023 were searched following PRISMA guidelines. Respective cohort-level outcomes were then abstracted and pooled by means of meta-analyses and analyzed by means meta-regression, both utilizing random-effects modeling. Post-hoc bias evaluation was then performed for all outcomes. Results A total of 12 studies were identified for inclusion, describing 503 LMD patients managed by CSF diversion – 442 (88%) by VPS and 61 (12%) by LPS. Median male percentage and age at diversion were 32% and 58 years respectively, with lung and breast cancer the most common primary diagnoses. Meta-analysis demonstrated pooled incidence of symptom resolution in 79% (95% CI 68–88%) of patients after index shunt surgery, and shunt revision required in 10% (95% CI 6–15%) of cases. Pooled overall survival from index shunt surgery was 3.8 mo (95% CI 2.9–4.6 mo) across all studies. Meta-regression demonstrated that studies published later trended towards significantly shorter overall survival from index shunt surgery (co-efficient=-0.38, P = 0.023), whereas the proportion of VPS to LPS in each study did not impact survival (P = 0.89). When accounting for these biases, overall survival from index shunt surgery was re-estimated to be shorter 3.1 mo (95% CI 1.7–4.4 mo). We present an illustrative case demonstrating the course of symptom improvement, shunt revision and an overall survival of 2 weeks from index CSF diversion. Conclusion Although CSF diversion in the setting of LMD can improve hydrocephalus symptoms in the majority of patients, there is a non-negligible proportion that will require shunt revision. Postoperatively, the prognosis of LMD remains poor irrespective of shunt type, and despite possible biases within the current literature, the expected median overall survival after index surgery is a matter of months. These findings support CSF diversion as an effective palliative procedure when considering symptoms and quality of life. Further research is required to understand how postoperative expectations can be managed to respect the best wishes of patients, their family, and the treating clinical team.

Purpose Prolonged length of stay (PLOS) can lead to resource misallocation and higher complication risks. However, there is no consensus on defining PLOS for endoscopic transsphenoidal pituitary surgery (ETPS). Therefore, we investigated the impact of varying PLOS definitions on factors associated with PLOS in patients undergoing ETPS. Methods We conducted a retrospective review of patients with pituitary adenomas who underwent ETPS at our institution from 2012 to 2023. Patients were divided into non-PLOS and PLOS groups based on varying definitions of PLOS: > median, > 4 days, > 75th percentile, and > 90th percentile. Bivariate statistical analyses were conducted using Fisher’s exact test, chi-square test, and t-tests. Univariate and multivariate logistic regression identified significant predictors for each PLOS definition. Results Our cohort ( n  = 808) had a mean age of 54.37 ± 16.06 years, 50.43% male, and a median LOS of 3 days. The 75th and 90th percentiles of LOS were 4 and 6 days, respectively. The way PLOS was defined influenced associated factors identified. Preoperative KPS score, non-private insurance, and non-home discharge disposition were associated with PLOS across all definitions used ( p  < 0.05). Increased preoperative tumor volumes and postoperative hyponatremia were associated with PLOS only when defined by the 75th and 90th percentiles ( p  < 0.05). Non-White race and low income were significantly associated with PLOS > median while intraoperative CSF leak was a significant predictor for PLOS > 90th percentile ( p  < 0.05). Conclusion Our study highlights the variability in predictors of PLOS based on its definition and emphasizes the role of non-clinical factors on LOS.

In this randomized phase II clinical trial, we evaluated the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination in patients with newly-diagnosed or recurrent WHO Grade III-IV malignant gliomas. The primary endpoints were to assess the most effective combination of vaccine and adjuvant in order to enhance the immune potency, along with safety. The combination of ATL-DC vaccination and TLR agonist was safe and found to enhance systemic immune responses, as indicated by increased interferon gene expression and changes in immune cell activation. Specifically, PD-1 expression increases on CD4+ T-cells, while CD38 and CD39 expression are reduced on CD8+ T cells, alongside an increase in monocytes. Poly-ICLC treatment amplifies the induction of interferon-induced genes in monocytes and T lymphocytes. Patients that exhibit higher interferon response gene expression demonstrate prolonged survival and delayed disease progression. These findings suggest that combining ATL-DC with poly-ICLC can induce a polarized interferon response in circulating monocytes and CD8+ T cells, which may represent an important blood biomarker for immunotherapy in this patient population.Trial Registration: ClinicalTrials.gov Identifier: NCT01204684. Autologous tumor lysate (ATL) dendritic cell (DC) vaccination can induce local and systemic anti-tumor immune responses in malignant glioma patients. In this randomized phase II clinical trial, the authors evaluate the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to ATL-DC vaccination in patients with newly-diagnosed or recurrent WHO Grade III-IV malignant gliomas.

BMP6 is a central cytokine in the induction of Sjögren's syndrome-associated (SS-associated) secretory hypofunction. However, the upstream initiation leading to the production of this cytokine in SS is unknown. In this study, RNA ISH on salivary gland sections taken from patients with SS indicated monocytic lineage cells as a cellular source of BMP6. RNA-Seq data on human salivary glands suggested that TLR4 signaling was an upstream regulator of BMP6, which was confirmed by in vitro cell assays and single-cell transcriptomics of human PBMCs. Further investigation showed that HSP70 was an endogenous natural TLR4 ligand that stimulated BMP6 expression in SS. Release of HSP70 from epithelial cells could be triggered by overexpression of lysosome-associated membrane protein 3 (LAMP3), a protein also associated with SS in several transcriptome studies. In vitro studies supported the idea that HSP70 was released as a result of lysosomal exocytosis initiated by LAMP3 expression, and reverse transcription PCR on RNA from minor salivary glands of patients with SS confirmed a positive correlation between BMP6 and LAMP3 expression. BMP6 expression could be experimentally induced in mice by overexpression of LAMP3, which developed an SS-like phenotype. The newly identified LAMP3/HSP70/BMP6 axis provided an etiological model for SS gland dysfunction and autoimmunity.

Elicitins are structurally conserved extracellular proteins in Phytophthora and Pythium oomycete pathogen species. They were first described in the late 1980s as abundant proteins in Phytophthora culture filtrates that have the capacity to elicit hypersensitive (HR) cell death and disease resistance in tobacco. Later, they became well-established as having features of microbe-associated molecular patterns (MAMPs) and to elicit defences in a variety of plant species. Research on elicitins culminated in the recent cloning of the elicitin response (ELR) cell surface receptor-like protein, from the wild potato Solanum microdontum, which mediates response to a broad range of elicitins. In this review, we provide an overview on elicitins and the plant responses they elicit. Wesummarize the state of the art by describing what we consider to be the nine most important features of elicitin biology.

In a study involving 51 patients with electronic-cigarette, or vaping, product use–associated lung injury in 16 states across the United States, vitamin E acetate was detected in samples of bronchoalveolar-lavage fluid from 94% of the patients but not in samples from a healthy comparator group.

The utility of ferroelectric materials stems from the ability to nucleate and move polarized domains using an electric field. To understand the mechanisms of polarization switching, structural characterization at the nanoscale is required. We used aberration-corrected transmission electron microscopy to follow the kinetics and dynamics of ferroelectric switching at millisecond temporal and subangstrom spatial resolution in an epitaxial bilayer of an antiferromagnetic ferroelectric (BiFeO₃) on a ferromagnetic electrode (La 0.7 Sr o.3 MnO₃). We observed localized nucleation events at the electrode interface, domain wall pinning on point defects, and the formation of ferroelectric domains localized to the ferroelectric and ferromagnetic interface. These results show how defects and interfaces impede full ferroelectric switching of a thin film.

Enlargement or aneurysm of the aorta predisposes to dissection, an important cause of sudden death. We trained a deep learning model to evaluate the dimensions of the ascending and descending thoracic aorta in 4.6 million cardiac magnetic resonance images from the UK Biobank. We then conducted genome-wide association studies in 39,688 individuals, identifying 82 loci associated with ascending and 47 with descending thoracic aortic diameter, of which 14 loci overlapped. Transcriptome-wide analyses, rare-variant burden tests and human aortic single nucleus RNA sequencing prioritized genes including SVIL , which was strongly associated with descending aortic diameter. A polygenic score for ascending aortic diameter was associated with thoracic aortic aneurysm in 385,621 UK Biobank participants (hazard ratio = 1.43 per s.d., confidence interval 1.32–1.54, P = 3.3 × 10 −20 ). Our results illustrate the potential for rapidly defining quantitative traits with deep learning, an approach that can be broadly applied to biomedical images. Genome-wide association analyses identify variants associated with thoracic aortic diameter. A polygenic score for ascending aortic diameter was associated with a diagnosis of thoracic aortic aneurysm in independent samples.