Host-derived reactive oxygen species trigger activation of the Candida albicans transcription regulator Rtg1/3.

The signals that denote mammalian host environments and dictate the activation of signaling pathways in human-associated microorganisms are often unknown. The transcription regulator Rtg1/3 in the human fungal pathogen Candida albicans is a crucial determinant of host colonization and pathogenicity. Rtg1/3's activity is controlled, in part, by shuttling the regulator between the cytoplasm and nucleus of the fungus. The host signal(s) that Rtg1/3 respond(s) to, however, have remained unclear. Here we report that neutrophil-derived reactive oxygen species (ROS) direct the subcellular localization of this C. albicans transcription regulator. Upon engulfment of Candida cells by human or mouse neutrophils, the regulator shuttles to the fungal nucleus. Using genetic and chemical approaches to disrupt the neutrophils' oxidative burst, we establish that the oxidants produced by the NOX2 complex-but not the oxidants generated by myeloperoxidase-trigger Rtg1/3's migration to the nucleus. Furthermore, screening a collection of C. albicans kinase deletion mutants, we implicate the MKC1 signaling pathway in the ROS-dependent regulation of Rtg1/3 in this fungus. Finally, we show that Rtg1/3 contributes to C. albicans virulence in the nematode Caenorhabditis elegans in an ROS-dependent manner as the rtg1 and rtg3 mutants display virulence defects in wild-type but not in ROS deficient worms. Our findings establish NOX2-derived ROS as a key signal that directs the activity of the pleiotropic fungal regulator Rtg1/3.

Transradial approach for diagnostic cerebral angiograms in the elderly: a comparative observational study.

BACKGROUND: The transradial approach (TRA) reduces mortality, morbidity, access site complications, hospital cost, and length of stay while maximizing patient satisfaction. We aimed to assess the technical success and safety of TRA for elderly patients (aged ≥75 years). METHODS: A retrospective chart review and comparative analysis was performed for elderly patients undergoing a diagnostic cerebral angiogram performed via TRA versus transfemoral approach (TFA). Also, a second comparative analysis was performed among the TRA cohort between elderly patients and their younger counterparts. RESULTS: Comparative analysis in the elderly (TRA vs TFA) showed no significant differences for contrast dose per vessel (43.7 vs 34.6 mL, P=0.106), fluoroscopy time per vessel (5.7 vs 5.2 min, P=0.849), procedure duration (59.8 vs 65.2 min, P=0.057), conversion rate (5.8% vs 2.9%, P=0.650), and access site complications (2.3% vs 2.9%, P=1.00). Radiation exposure per vessel (18.9 vs 51.9 Gy cm2, P=0.001) was significantly lower in the elderly TRA group.The second comparison (TRA in elderly vs TRA in the young) showed no significant differences for contrast dose per vessel (43.7 vs 37.8 mL, P=0.185), radiation exposure per vessel (18.9 vs 16.5 Gy cm2, P=0.507), procedure duration (59.8 vs 58.3 min, P=0.788), access site complication (2.3% vs 1.7%, P=0.55), and conversation rate (5.8% vs 1.8%, P=0.092). A trend for prolonged fluoroscopy time per vessel (5.7 vs 4.7 min, P=0.050) was observed in the elderly TRA group. CONCLUSIONS: TRA is a technically feasible and safe option for diagnostic neurointerventional procedures in the elderly. Our small elderly cohort was not powered enough to show a significant difference in terms of access site complications between TRA and TFA.

Access-Site Complications in Transfemoral Neuroendovascular Procedures: A Systematic Review of Incidence Rates and Management Strategies.

BACKGROUND: The femoral artery is the most common access route for cerebral angiography and neurointerventional procedures. Complications of the transfemoral approach include groin hemorrhages and hematomas, retroperitoneal hematomas, pseudoaneurysms, arteriovenous fistulas, peripheral artery occlusions, femoral nerve injuries, and access-site infections. Incidence rates vary among different randomized and nonrandomized trials, and the literature lacks a comprehensive review of this subject. OBJECTIVE: To gather data from 16 randomized clinical trials (RCT) and 17 nonrandomized cohort studies regarding femoral access-site complications for a review paper. We also briefly discuss management strategies for these complications based on the most recent literature. METHODS: A PubMed indexed search for all neuroendovascular clinical trials, retrospective studies, and prospective studies that reported femoral artery access-site complications in neurointerventional procedures. RESULTS: The overall access-site complication rate in RCTs is 5.13%, while in in non-RCTs, the rate is 2.78%. The most common complication in both groups is groin hematoma followed by access-site hemorrhage and femoral pseudoaneurysm. On the other hand, wound infection was the least common complication. CONCLUSION: The transfemoral approach in neuroendovascular procedures holds risk for several complications. This review will allow further studies to compare access-site complications between the transfemoral approach and other alternative access sites, mainly the transradial approach, which is gaining a lot of interest nowadays.

Gastrointestinal stromal tumor with intracranial metastasis: case presentation and systematic review of literature.

BACKGROUND: Intracranial metastasis of Gastrointestinal Stromal Tumors (GISTs) is rare but presents unique treatment challenges. We present a case of intracranial metastasis of GIST with a systematic review of the literature. A literature search using key terms "'gastrointestinal stromal tumor' AND brain AND metastasis"" was conducted through May 2019 via Embase and Pubmed according to PRISMA guidelines. Only cases describing intradural metastases rather than calvarial or intraorbital metastases were included. CASE PRESENTATION: A 57-year-old woman with history of GIST metastatic to the liver presented with a six-week history of left facial weakness, left hearing loss, and left facial numbness, and a one-week history of headaches, gait disturbance, and dizziness. MRI revealed a contrast-enhancing dural-based left middle cranial fossa mass measuring 2.9 cm × 3.1 cm × 3.4 cm with extension into the internal auditory canal and cerebral edema. A left temporal craniotomy was performed to excise the lesion, and the patient was discharged to a rehabilitation facility at her preoperative baseline. Intraoperative pathology revealed a spindle cell neoplasm, postoperative MRI demonstrated gross total resection of the lesion, and microscopic analysis demonstrated sheets of spindled tumor cells with short ovoid, irregular, hyperchromatic nuclei and scattered large atypical nuclei without extensive necrosis. Immunohistochemical staining was positive for KIT proto-oncogene (CD117, c-KIT), and the patient was put on imatinib (400 mg/day). CONCLUSIONS: Of the 18 cases analyzed and our present case, metastasis typically involved the cerebrum with only one in infratentorial elements. The tumors in seven of the cases involved the dura, and one case metastasized to the pituitary. Eight patients died following treatment. Surgery remains the mainstay of intracranial metastatic GIST, however there are many reports of good responses to radiation or chemotherapy alone. More investigation is required to determine the best treatment course for these patients.

Molecular profiling predicts meningioma recurrence and reveals loss of DREAM complex repression in aggressive tumors.

Meningiomas account for one-third of all primary brain tumors. Although typically benign, about 20% of meningiomas are aggressive, and despite the rigor of the current histopathological classification system there remains considerable uncertainty in predicting tumor behavior. Here, we analyzed 160 tumors from all 3 World Health Organization (WHO) grades (I through III) using clinical, gene expression, and sequencing data. Unsupervised clustering analysis identified 3 molecular types (A, B, and C) that reliably predicted recurrence. These groups did not directly correlate with the WHO grading system, which classifies more than half of the tumors in the most aggressive molecular type as benign. Transcriptional and biochemical analyses revealed that aggressive meningiomas involve loss of the repressor function of the DREAM complex, which results in cell-cycle activation; only tumors in this category tend to recur after full resection. These findings should improve our ability to predict recurrence and develop targeted treatments for these clinically challenging tumors.