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Marinus J. Becks Rashindra Manniesing Jeroen Vister Sjoert A.H. Pegge Stefan C.A. Steens Ewoud J. van Dijk Mathias Prokop Frederick J.A. Meijer 《Journal of neuroradiology. Journal de neuroradiologie》2019,46(2):124-129
Background and purpose
To evaluate whether brain CT perfusion (CTP) aids in the detection of intracranial vessel occlusion on CT angiography (CTA) in acute ischemic stroke.Materials and methods
Medical-ethical committee approval of our hospital was obtained and informed consent was waived. Patients suspected of acute ischemic stroke who underwent non-contrast CT(NCCT), CTA and whole-brain CTP in our center in the year 2015 were included. Three observers with different levels of experience evaluated the imaging data of 110 patients for the presence or absence of intracranial arterial vessel occlusion with two strategies. In the first strategy, only NCCT and CTA were available. In the second strategy, CTP maps were provided in addition to NCCT and CTA. Receiver-operating-characteristic (ROC) analysis was used for the evaluation of diagnostic accuracy.Results
Overall, a brain perfusion deficit was scored present in 87–89% of the patients with an intracranial vessel occlusion, more frequently observed in the anterior than in the posterior circulation. Performance of intracranial vessel occlusion detection on CTA was significantly improved with the availability of CTP maps as compared to the first strategy (P = 0.023), due to improved detection of distal and posterior circulation vessel occlusions (P-values of 0.032 and 0.003 respectively). No added value of CTP was found for intracranial proximal vessel occlusion detection, with already high accuracy based on NCCT and CTA alone.Conclusion
The performance of intracranial vessel occlusion detection on CTA was improved with the availability of brain CT perfusion maps due to the improved detection of distal and posterior circulation vessel occlusions. 相似文献3.
Piotr Rozga Damian Kloska Sebastian Pawlak Malgorzata Teska-Kaminska Marlena Galazka Katarzyna Bukato Anna Pieczykolan Albert Jaworski Anna Molga-Kaczmarska Aleksandra Kopacz Bogna Badyra Neli Kachamakova-Trojanowska Olga Zolnierkiewicz Marta Targosz-Korecka Katarzyna Poleszak Michal Szymanik Bartlomiej Zerek Jerzy Pieczykolan Alicja Jozkowicz Anna Grochot-Przeczek 《International journal of cancer. Journal international du cancer》2020,147(4):1117-1130
Targeting of the TRAIL-DR4/5 pathway was proposed as a promising approach for specific induction of apoptosis in cancer cells. Clinical trials, however, showed inadequate efficiency of TRAIL as a monotherapy. It is a widely held view that the application of multifunctional molecules or combination therapy may lead to substantial improvement. Here, we demonstrate the effectiveness and safety of a novel chimeric protein, AD-O51.4, which is a TRAIL equipped with positively charged VEGFA-derived effector peptides. The study was performed in multiple cancer cell line- and patient-derived xenografts. A pharmacokinetic profile was established in monkeys. AD-O51.4 strongly inhibits tumor growth, even leading to complete long-term tumor remission. Neither mice nor monkeys treated with AD-O51.4 demonstrate symptoms of drug toxicity. AD-O51.4 exhibits a satisfactory half-life in plasma and accumulates preferentially in tumors. The cellular mechanism of AD-O51.4 activity involves both cytotoxic effects in tumor cells and antiangiogenic effects on the endothelium. The presence of DRs in cancer cells is crucial for AD-O51.4-driven apoptosis execution. The TRAIL component of the fusion molecule serves as an apoptosis inducer and a cellular anchor for the effector peptides in TRAIL-sensitive and TRAIL-resistant cancer cells, respectively. The FADD-dependent pathway, however, seems to be not indispensable in death signal transduction; thus, AD-O51.4 is capable of bypassing the refractoriness of TRAIL. AD-O51.4-driven cell death, which exceeds TRAIL activity, is achieved due to the N-terminally fused polypeptide, containing VEGFA-derived effector peptides. The high anticancer efficiency of AD-O51.4 combined with its safety has led to the entry of AD-O51.4 into toxicological studies. 相似文献
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Dominic Kaddu-Mulindwa Sophie Roth Aline Klees-Rollmann Klaus Fassbender Mathias Fousse 《Journal of neurovirology》2020,26(2):292-296
The development of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is often associated with neoplasia or infectious diseases as antibodies against neurons or synaptic proteins surface. A 30-year-old male patient was admitted to our department because of neurocognitive symptoms, particularly memory difficulties which had appeared a year prior and since then had been increasing. He had a medical history of smoking and hypertension. On examination, there were no focal neurological deficits. However, neuropsychological tests confirmed a lack of concentration and short-term memory impairment. Brain magnetic resonance imaging (MRI) and electroencephalography (EEG) remained unremarkable. Cerebrospinal fluid (CSF) analysis revealed a low lymphocytic pleocytosis without oligoclonal bands. Serum testing for human immunodeficiency virus (HIV) was positive with 420,000 HIV-1-RNA copies/ml. On a more detailed physical examination, a large number of purple patches were found on the entire body, which a biopsy confirmed to be Kaposi sarcoma (KS). A positive serum and CSF NMDA receptor antibody titer (serum 1:280; CSF 1:8) confirmed the diagnosis of an AIDS-associated anti-NMDA receptor encephalitis; therefore, we treated him with antiretroviral and immunosuppressive therapy. After 12 months, the KS lesions faded and the cognitive deficits improved slightly. Our case highlights that a detailed clinical examination and searching for neoplasia and/or an infection are helpful, though often neglected, tools for detecting an anti-NMDA receptor encephalitis. 相似文献
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Upneet K Sokhi Yunwei Xia Branden Sosa Kathleen Turajane Sita N Nishtala Tania Pannellini Mathias P Bostrom Alberto V Carli Xu Yang Lionel B Ivashkiv 《Journal of bone and mineral research》2022,37(3):577-594
Staphyloccocus aureus is one of the major pathogens in orthopedic periprosthetic joint infection (PJI), a devastating complication of total joint arthroplasty that often results in chronic and persistent infections that are refractory to antibiotics and require surgical interventions. Biofilm formation has been extensively investigated as a reason for persistent infection. The cellular composition, activation status, cytokine profile, and role of the immune response during persistent S. aureus PJI are incompletely understood. In this study, we used histology, multiparametric flow cytometry, and gene expression analysis to characterize the immune response in a clinically relevant orthopedic PJI model. We tested the hypothesis that persistent S. aureus infection induces feedback mechanisms that suppress immune cell activation, thereby affecting the course of infection. Surprisingly, persistent infection was characterized by strikingly high cytokine gene expression indicative of robust activation of multiple components of innate and adaptive immunity, along with ongoing severe neutrophil-dominated inflammation, in infected joint and bone tissues. Activation and expansion of draining lymph nodes and a bone marrow stress granulopoiesis reaction were also maintained during late phase infection. In parallel, feedback mechanisms involving T-cell inhibitory receptors and exhaustion markers, suppressive cytokines, and regulatory T cells were activated and associated with decreased T-cell proliferation and tissue infiltration during the persistent phase of infection. These results identify the cellular and molecular components of the mouse immune response to persistent S. aureus PJI and indicate that neutrophil infiltration, inflammatory cytokine responses, and ongoing lymph node and bone marrow reactions are insufficient to clear infection and that immune effector mechanisms are suppressed by feedback inhibitory pathways. These immune-suppressive mechanisms are associated with diminished T-cell proliferation and tissue infiltration and can be targeted as part of adjuvant immunotherapeutic strategies in combination with debridement of biofilm, antibiotics, and other therapeutic modalities to promote eradication of infection. © 2021 American Society for Bone and Mineral Research (ASBMR). 相似文献
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