Use of the Neurological Pupil Index to Predict Postoperative Visual Function After Resection of a Tuberculum Sellae Meningioma: A Case Report.

The Neurological Pupil index (NPi) is a standardized method for evaluating pupil reactivity that removes inter-examiner variability. Changes in the NPi can predict clinical deterioration in patients with traumatic brain injury (TBI); however, its use to predict visual impairment after the resection of parasellar meningiomas has not been described. A 71-year-old female underwent a modified expanded bifrontal craniotomy for resection of a 3.1 cm tuberculum sella meningioma that caused compression of the optic chiasm and resulted in left temporal and right superior temporal visual field deficits. Postoperatively, she lost vision in the right eye. Pupillometer measurements demonstrated an asymmetrically low NPi at that time, which improved to normal prior to partial vision recovery. The average NPi in the right pupil was 1.67 during the time of vision loss compared to 3.47 in the left pupil (p=1.7x10-10). Statistical analysis was performed with the Student's t-test and the significance level was set at p-value < 0.01. Resection of parasellar meningiomas is challenging because of the proximity of the optic apparatus. We report a case of unilateral vision loss after resection of a tuberculum sella meningioma in which the impaired eye's NPi value correlated closely with visual function. NPi values that decrease below 3 predict spikes in intracranial pressure in TBI patients; similarly, increases in the NPi value above 2.5-3 predict improvement in vision in the case reported here. By monitoring the proximal portion of the oculomotor reflex, the NPi can be a marker of visual impairment after surgery

Management of Noncatastrophic Internal Carotid Artery Injury in Endoscopic Skull Base Surgery.

Arterial injuries are the most feared complication of endoscopic skull base surgery. During resection of the middle fossa component of a large ventral skull base chondrosarcoma, arterial bleeding was encountered near the right internal carotid artery (ICA). Durable hemostasis could not be achieved with packing and the patient was taken for an emergent angiogram that revealed a pseudoaneurysm of the proximal intradural ICA. Given the presence of good collateral flow through the anterior and posterior communicating arteries, the right ICA was sacrificed by coil embolization. The patient was taken back to the operating room for closure then transferred to the intensive care unit and maintained on vasopressors for five days to ensure adequate perfusion. The right ICA was coil embolized and the patient was taken back to the operating room for closure. The patient recovered without complication. Arterial injuries, although serious, are not always catastrophic. Critical steps are immediate recognition of bleeding, vascular imaging, and vessel sacrifice if necessary

Salmonella Infection After Craniotomy.

Salmonella is an uncommon cause of meningitis, especially after neurosurgery. Here, we present a case of Salmonella meningitis after craniotomy, likely due to physical contact with a snake after surgery, with contiguous spread from the patient's hand to her wound. The purpose of this report is to serve as a reminder that patients undergoing neurosurgery should avoid contact with pets, including snakes and other reptiles, in the postoperative period and practice good hand hygiene

Patient-Specific Fetal Dose Determination for Multi-Target Gamma Knife Radiosurgery: Computational Model and Case Report.

A 42-year-old woman at 29 weeks gestation via in vitro fertilization who presented with eight metastatic brain lesions received Gamma Knife stereotactic radiosurgery (GKSRS) at our institution. In this study, we report our clinical experience and a general procedure of determining the fetal dose from patient-specific treatment plans and we describe quality assurance measurements to guide the safe practice of multi-target GKSRS of pregnant patients. To estimate fetal dose pre-treatment, peripheral dose-to-focal dose ratios (PFRs) were measured in a phantom at the distance approximating the fundus of uterus. Post-treatment, fetal dose was calculated from the actual patient treatment plan. Quality assurance measurements were carried out via the extrapolation dosimetry method in a head phantom at increasing distances along the longitudinal axis. The measurements were then empirically fitted and the fetal dose was extracted from the curve. The computed and measured fetal dose values were compared with each other and associated radiation risk was estimated. Based on low estimated fetal dose from preliminary phantom measurements, the patient was accepted for GKSRS. Eight brain metastases were treated with prescription doses of 15-19 Gy over 143 min involving all collimator sizes as well as composite sector mixed shots. Direct fetal dose computation based on the actual patient's treatment plan estimated a maximum fetal dose of 0.253 cGy, which was in agreement with surface dose measurements at the level of the patient's uterine fundus during the actual treatment. Later phantom measurements also estimated fetal dose to be in the range of 0.21-0.28 cGy (dose extrapolation curve R2 = 0.998). Using the National Council on Radiation Protection and Measurements (NCRP) population-based model, we estimate the fetal risk of secondary malignancy, which is the primary toxicity after 25 weeks gestation, to be less than 0.01%. Of note, the patient delivered the baby via scheduled cesarean section at 36 weeks without complications attributable to the GKSRS procedure. GKSRS of multiple brain metastases was demonstrated to be safe and feasible during pregnancy. The applicability of a general patient-specific fetal dose determination method was also demonstrated for the first time for such a treatment

Anatomy of the inferior orbital fissure: Implications for endoscopic cranial base surgery

Considering many approaches to the skull base confront the inferior orbital fissure (IOF) or sphenomaxillary fissure, the authors examine this anatomy as an important endoscopic surgical landmark. In morphometric analyses of 50 adult human dry skulls from both sexes, we divided the length of the IOF into three segments (anterolateral, middle, posteromedial). Hemotoxylin- and eosin-stained sections were analyzed. Dissections were performed using transnasal endoscopy in four formalin-fixed cadaveric cranial specimens (eight sides); three endoscopic approaches to the IOF were performed.IOF length ranged from 25 to 35 mm (mean 29 mm). Length/width of the individual anterolateral, middle, and posteromedial segments averaged 6.46/5, 4.95/3.2, and 17.6/ 2.4 mm, respectively. Smooth muscle within the IOF had a consistent elationship with several important anatomical landmarks. The maxillary introstomy,total ethmoidectomy approach allowed access to the posteromedial segment of the fissure. The endoscopic modified, medial maxillectomy approach allowed access to the middle and posterior-medial segment. The Caldwell-Luc approach allowed complete exposure of the IOF. The IOF serves as an important anatomic landmark during endonasal endoscopic approaches to the skull base and orbit. Each of the three segments provides a characteristic endoscopic corridor, unique to the orbit and different fossas surrounding the fissure.Fil: de Battista, Juan Carlos. University of Cincinnati; Estados Unidos. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Anatomia Normal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zimmer, Lee A.. University of Cincinnati; Estados UnidosFil: Theodosopoulos, Philip V.. University of Cincinnati; Estados UnidosFil: Froelich, Sebastien C.. University of Cincinnati; Estados UnidosFil: Keller, Jeffrey T.. University of Cincinnati; Estados Unidos. Mayfield Clinic; Estados Unido

PATH-38. ROSETTE-FORMING GLIONEURONAL TUMOR IS DEFINED BY FGFR1 ACTIVATING ALTERATIONS WITH FREQUENT ACCOMPANYING PI3K AND MAPK PATHWAY MUTATIONS

Abstract BACKGROUND Rosette-forming glioneuronal tumor (RGNT) is an uncommon CNS tumor originally described in the fourth ventricle characterized by a low-grade glial neoplasm admixed with a rosette-forming neurocytic component. METHODS We reviewed clinicopathologic features of 42 patients with RGNT. Targeted next-generation sequencing was performed, and genome-wide methylation profiling is underway. RESULTS The 20 male and 22 female patients had a mean age of 25 years (range 3–47) at time of diagnosis. Tumors were located within or adjacent to the lateral ventricle (n=16), fourth ventricle (15), third ventricle (9), and spinal cord (2). All 31 tumors assessed to date contained FGFR1 activating alterations, either in-frame gene fusion, kinase domain tandem duplication, or hotspot missense mutation in the kinase domain (p.N546 or p.K656). While 7 of these 31 tumors harbored FGFR1 alterations as the solitary pathogenic event, 24 contained additional pathogenic alterations within PI3-kinase or MAP kinase pathway genes: 5 with additional PIK3CA and NF1 mutations, 4 with PIK3CA mutation, 3 with PIK3R1 mutation (one of which also contained focal RAF1 amplification), 5 with PTPN11 mutation (one with additional PIK3R1 mutation), and 2 with NF1 deletion. The other 5 cases demonstrated anaplastic features including hypercellularity and increased mitotic activity. Among these anaplastic cases, 3 harbored inactivating ATRX mutations and two harbored CDKN2A homozygous deletion, in addition to the FGFR1 alterations plus other PI3-kinase and MAP kinase gene mutations seen in those RGNT without anaplasia. CONCLUSION Independent of ventricular location, RGNT is defined by FGFR1 activating mutations or rearrangements, which are frequently accompanied by mutations involving PIK3CA, PIK3R1, PTPN11, NF1, and KRAS. Whereas pilocytic astrocytoma and ganglioglioma are characterized by solitary activating MAP kinase pathway alterations (e.g. BRAF fusion or mutation), RGNT are genetically more complex with dual PI3K-Akt-mTOR and Ras-Raf-MAPK pathway activation. Rare anaplastic examples may show additional ATRX and/or CDKN2A inactivation

Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas

BACKGROUND. Long-term prognosis of WHO grade II low-grade gliomas (LGGs) is poor, with a high risk of recurrence and malignant transformation into high-grade gliomas. Given the relatively intact immune system of patients with LGGs and the slow tumor growth rate, vaccines are an attractive treatment strategy. METHODS. We conducted a pilot study to evaluate the safety and immunological effects of vaccination with GBM6-AD, lysate of an allogeneic glioblastoma stem cell line, with poly-ICLC in patients with LGGs. Patients were randomized to receive the vaccines before surgery (arm 1) or not (arm 2) and all patients received adjuvant vaccines. Coprimary outcomes were to evaluate safety and immune response in the tumor. RESULTS. A total of 17 eligible patients were enrolled — 9 in arm 1 and 8 in arm 2. This regimen was well tolerated with no regimen-limiting toxicity. Neoadjuvant vaccination induced upregulation of type-1 cytokines and chemokines and increased activated CD8+ T cells in peripheral blood. Single-cell RNA/T cell receptor sequencing detected CD8+ T cell clones that expanded with effector phenotype and migrated into the tumor microenvironment (TME) in response to neoadjuvant vaccination. Mass cytometric analyses detected increased tissue resident–like CD8+ T cells with effector memory phenotype in the TME after the neoadjuvant vaccination. CONCLUSION. The regimen induced effector CD8+ T cell response in peripheral blood and enabled vaccine-reactive CD8+ T cells to migrate into the TME. Further refinements of the regimen may have to be integrated into future strategies

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

The effect of ω-fatty acids on mrna expression level of PPARγ in patients with gastric adenocarcinoma

Background: The antineoplastic role of peroxisome proliferator-activated receptor gamma (PPARγ) ligandshas previously been demonstrated in several gastric cancer cell lines. Activation of PPARγ by polyunsaturated fatty acids (PUFAs) inhibits growth and proliferationof tumor cells. In this double-blind clinical study, we evaluate the effect of PUFAs on PPARγ mRNA expression in patients with gastric adenocarcinoma. Materials and Methods: A total of 34 chemotherapy-naive patients diagnosed with gastric adenocarcinoma were enrolled in the present study. According to treatment strategies, all subjects were divided into two groups, the first group (17 individuals) received cisplatin without supplements and the second group (17 individuals) received cisplatin plus orally administered PUFAs supplements for 3 weeks. The gastric biopsy samples were obtained from all participants before and after treatment, and PPARγ mRNA expression levels were evaluated by quantitative real-time polymerase chain reaction using validated reference genes. Results: Our findings revealed that PPARγ mRNA expression is significantly upregulated in group II afterreceiving cisplatin plus orally administered PUFAs supplements for three weeks (p < 0.0001), whereas PPARγ mRNA expression did not show significant alteration in group I after receiving cisplatin alone. Conclusion: The results of the study evidence that PPARγ may act as a potential target for the therapy of human gastric adenocarcinoma