Objectives:
A retrospective cohort study of endoscopic endonasal approaches (EEA) to intracranial pathology through a suprasellar approach with nasoseptal flap reconstructions was used to determine ...the pediatric age groups viable for nasoseptal flap reconstruction based on preoperative radio anatomic analysis of computed tomography (CT) scans and surgical outcomes.
Study Design:
A total of 16 pediatric patients who underwent EEA with nasoseptal flap reconstruction of a suprasellar defect were retrospectively analyzed for defect size and potential flap coverage using preoperative maxillofacial CT for radioanatomic analysis.
Methods:
Measurements included potential nasoseptal flap dimensions and dimensions required to reconstruct a suprasellar defect. Measurements and surgical outcomes were compared with determine if the flap size would be sufficient to cover said defects in two pediatric age groups: those older than10 years (average age 14 years) and those younger than 10 years (average age 6 years).
Results:
Of all patients encountered in this cohort, the only postoperative CSF leak was identified in the population older than 10 years. Intraoperatively, this was a technical error and flap coverage was adequate. Average potential flap length and width are sufficient to cover the average suprasellar defect length and width in both age groups.
Conclusion:
Although the previous literature has suggested nasoseptal flap coverage may be inadequate in younger patients, our measurements and postoperative outcomes show that the nasoseptal flap is a reliable option in the reconstruction of suprasellar defects in pediatric patients of all ages.
Abstract
Subsets of pediatric cancers, including high grade glioma (pHGG), have high rates of uniquely long telomeres, associated with ATRX gene mutations and alternative lengthening of telomeres ...(ALT). Ultimately, these cancers may benefit from a therapy stratification approach. In order to identify and further characterize pediatric brain tumors with telomere lengthening (TL), we determined the intratelomeric content in silico from paired WGS of 918 tumors from CBTTC Pediatric Brain Tumor Atlas (PBTA). The results were highly concordant with experimental assays to determine ALT in a subset of 45 pHGG tumors from the set. Overall, 13% of the PBTA cohort had telomere lengthening. We confirmed the highest rate of TL (37%) in the pHGG cohort (37/100 tumors; 30/82 patients). There was no statistical difference in age, gender or survival in subset analysis. As expected, the patient pHGG tumors with telomere lengthening were enriched for ATRX mutations (60%, q= 1.76e-3). However, 6 tumors without ATRX mutation also had normal protein expression, suggesting a different mechanism of inactivation or TL. The pHGG tumors with telomere lengthening had increased mutational burden (q=8.98e-3) and included all known pHGG cases (n=6) in the cohort with replication repair deficiencies. Of interest, the second highest rate of telomere lengthening was 9 subjects (24%) in the craniopharyngioma cohort. None of the craniopharyngioma tumors had ATRX mutations or low ATRX expression, and 55% of those with TL had CTNNB1 mutations. Finally, lower rates of telomere lengthening were found in medulloblastoma (10%), ependymoma (10%), low grade astrocytoma (8%) and ganglioglioma (7/47, 15%).
Abstract
PURPOSE: Pediatric high grade glioma (pHGG) remains a fatal disease. Increasing the number of patient derived tumor models and reagents will encourage research in pHGG and support the ...translation of basic science research discoveries. This work describes a recent multi-institution initiative to provide such a resource. METHODS: pHGG tumors with associated clinical data were prospectively collected and sequenced through the Children’s Brain Tumor Tissue Consortium (CBTTC) and Pediatric Brain Tumor Atlas (PBTA) with data deposited into PedcBioPortal for easy access and visualization. Primary tumor was dissociated and cultured to create both adherent and glioma stem cell lines analyzed by targeted and WGS/RNA sequencing. A tissue microarray (TMA) of primary pHGG tumors was created and examined by immunohistochemistry. RESULTS: The pHGG set included 81 collection events (70 patients, 54% at diagnosis, median age of 11 yrs, 52% female, 43% hemispheric). Analysis of somatic mutations and copy number alterations of known glioma genes were of expected distribution (36% H3.3, 47% TP53, 24% ATRX and 7% BRAF V600E variants). There were rare germline variants in mismatch repair genes with resultant tumor hyper-mutation. At least one established adherent and/or suspension glioma stem cell line was generated from 22 (31%) patients and validated by targeted sequencing for driver pHGG mutations. A subset of lines had WGS and RNAseq profiling which computationally clustered with their parental primary tumors. The lines’ cell biology makeup and in vivo tumor formation was also evaluated. A pHGG TMA (n=77), including 37 (53%) of the sequenced pHGG tumors, showed concordance with mutation status when stained for ATRX, H3.3 K27M and TP53. CONCLUSION: The CBTTC and PBTA have created a freely available integrated resource of characterized pHGG primary tumors, corresponding cell lines and archival fixed tissue to advance translational research for pHGG.
The impact of sinonasal malignancies (SNMs) on quality of life (QOL) at presentation is poorly understood. The Sinonasal Outcome Test (SNOT-22) and University of Washington Quality of Life (UWQOL) ...are validated QOL instruments with distinctive subdomains. This study aims to identify factors impacting pretreatment QOL in SNM patients to personalize multidisciplinary management and counseling.
Patients with previously untreated SNMs were prospectively enrolled (2015-2022) in a multicenter observational study. Baseline pretreatment QOL instruments (SNOT-22, UWQOL) were obtained along with demographics, comorbidities, histopathology/staging, tumor involvement, and symptoms. Multivariable regression models identified factors associated with reduced baseline QOL.
Among 204 patients, presenting baseline QOL was significantly reduced. Multivariable regression showed worse total SNOT-22 QOL in patients with skull base erosion (p = 0.02). SNOT-rhinologic QOL was worse in women (p = 0.009), patients with epistaxis (p = 0.036), and industrial exposure (p = 0.005). SNOT extranasal QOL was worse in patients with industrial exposure (p = 0.016); worse SNOT ear/facial QOL if perineural invasion (PNI) (p = 0.027). Squamous cell carcinoma pathology (p = 0.037), palate involvement (p = 0.012), and pain (p = 0.017) were associated with worse SNOT sleep QOL scores. SNOT psychological subdomain scores were significantly worse in patients with palate lesions (p = 0.022), skull base erosion (p = 0.025), and T1 staging (p = 0.023). Low QOL was more likely in the presence of PNI on UW health (p = 0.019) and orbital erosion on UW overall (p = 0.03). UW social QOL was worse if palatal involvement (p = 0.023) or PNI (p = 0.005).
Our findings demonstrate a negative impact on baseline QOL in patients with SNMs and suggest sex-specific and symptom-related lower QOL scores, with minimal histopathology association. Anatomical tumor involvement may be more reflective of QOL than T-staging, as orbital and skull base erosion, PNI, and palate lesions are significantly associated with reduced baseline QOL.
I provide a unique example of a transgenerational maternal effect in anti-predator behavior, which takes the form of a "warning" that female fall field crickets, Gryllus pennsylvanicus, transmit to ...their offspring about wolf spiders. Experimental exposure of gravid crickets to a wolf spider Hogna helluo demonstrated that their offspring exhibit greater anti-predator immobility in response to Hogna chemical cues than do offspring of non-exposed females. These "forewarned" crickets exhibit greater survival in the presence of Hogna than those not forewarned. Accordingly, gravid crickets from areas with significant Hogna populations produce offspring that are more responsive to Hogna cues than those from nearby Hogna-free areas. However, the production of defensive traits may be costly, and such costs may be avoided when the defense is facultative rather than obligatory. One potential cost of maternally-induced anti-predator behavior is foraging rate. A trade-off may occur if "forewarned" offspring from Hogna-exposed mothers forage less, potentially limiting the growth and reproduction of offspring. However, I found that the predator-naïve offspring of gravid female G. pennsylvanicus exposed to the risk of predation from either the wolf spider Hogna helluo or Rabidosa spp. in the laboratory exhibited a foraging rate similar to offspring from non-exposed mothers. My research suggests that transgenerational maternal effects may be more common than presently realized, especially when the predatory environment experienced by females predicts that of their offspring.
F Modified Storm, Jay
Sportscar (USA),
11/2009, Letnik:
67, Številka:
11
Magazine Article
Running in the fourth heat gave the F Mod drivers some time to see the developing lines created by previous competitors and take one last look at the course if they hustled through the midday ...course walk.
YEAR OF THE MODIFIEDS Avard, David; Baruth, Mark; Brown, Paul ...
Sportscar (USA),
11/2011, Letnik:
69, Številka:
11
Magazine Article
... only two male drivers went farther before their fi rst loss, and young Garfi eld hasn't lost yet. The Gumout All-Star Motorhead Shootout evoked distant memories of the Identical Car Challenge ...back when British Leyland was the first sponsor of the Solo National Championships.
Return to Lincoln Airpark Avard, David; Cashmore, Jeff; Darby, Darren ...
Sportscar (USA),
11/2010, Letnik:
68, Številka:
11
Magazine Article
... for those who came last year, yep, up 48th Street from I-80, or those staying at the hotel cluster on the east side have discovered the loop road around the north end of the airport; then east ...on Mathis to the event site. SCCA staffer Eric Prill in E Modified won only the second trophy ever under the South Texas Border Region flag (the first was in 1978), while two Gulf Coast Region drivers, Eric Trigg in A Stock and Roberta Wetzel in BSL, tripled their region's trophy count - the region had claimed one only once in the previous 37 years. ... runs saw Garfield assume the lead, while 2009 winner Joey Montelo moved up to the second position.
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