Citations

Abstract Objective . An ability to map seizure-generating brain tissue, i.e. the seizure onset zone (SOZ), without recording actual seizures could reduce the duration of invasive EEG monitoring for patients with drug-resistant epilepsy. A widely-adopted practice in the literature is to compare the incidence (events/time) of putative pathological electrophysiological biomarkers associated with epileptic brain tissue with the SOZ determined from spontaneous seizures recorded with intracranial EEG, primarily using a single biomarker. Clinical translation of the previous efforts suffers from their inability to generalize across multiple patients because of (a) the inter-patient variability and (b) the temporal variability in the epileptogenic activity. Approach . Here, we report an artificial intelligence-based approach for combining multiple interictal electrophysiological biomarkers and their temporal characteristics as a way of accounting for the above barriers and show that it can reliably identify seizure onset zones in a study cohort of 82 patients who underwent evaluation for drug-resistant epilepsy. Main results . Our investigation provides evidence that utilizing the complementary information provided by multiple electrophysiological biomarkers and their temporal characteristics can significantly improve the localization potential compared to previously published single-biomarker incidence-based approaches, resulting in an average area under ROC curve (AUC) value of 0.73 in a cohort of 82 patients. Our results also suggest that recording durations between 90 min and 2 h are sufficient to localize SOZs with accuracies that may prove clinically relevant. Significance . The successful validation of our approach on a large cohort of 82 patients warrants future investigation on the feasibility of utilizing intra-operative EEG monitoring and artificial intelligence to localize epileptogenic brain tissue. Broadly, our study demonstrates the use of artificial intelligence coupled with careful feature engineering in augmenting clinical decision making.

AbstractBackground: Biomarkers of tobacco exposure have a central role in studies of tobacco use and nicotine intake. The most significant exposure markers are nicotine itself and its metabolites in urine. Therefore, it is important to evaluate the performance of laboratories conducting these biomarker measurements.Methods: This report presents the results from a method performance study involving 11 laboratories from 6 countries that are currently active in this area. Each laboratory assayed blind replicates of seven human urine pools at various concentrations on three separate days. The samples included five pools blended from smoker and nonsmoker urine sources, and two additional blank urine samples fortified with pure nicotine, cotinine, and hydroxycotinine standards. All laboratories used their own methods, and all were based on some form of liquid chromatography/tandem mass spectrometry.Results: Overall, good agreement was found among the laboratories in this study. Intralaboratory precision was good, and in the fortified pools, the mean bias observed was < + 3.5% for nicotine, approximately 1.2% for hydroxycotinine, and less than 1% for cotinine (1 outlier excluded in each case). Both indirect and direct methods for analyzing the glucuronides gave comparable results.Conclusions: This evaluation indicates that the experienced laboratories participating in this study can produce reliable and comparable human urinary nicotine metabolic profiles in samples from people with significant recent exposure to nicotine.Impact: This work supports the reliability and agreement of an international group of established laboratories measuring nicotine and its metabolites in urine in support of nicotine exposure studies. Cancer Epidemiol Biomarkers Prev; 27(9); 1083–90. ©2018 AACR.

New techniques able to monitor the maturation of tissue engineered constructs over time are needed for a more efficient control of developmental parameters. Here, a label‐free fluorescence lifetime imaging (FLIm) approach implemented through a single fiber‐optic interface is reported for nondestructive in situ assessment of vascular biomaterials. Recellularization processes of antigen removed bovine pericardium scaffolds with endothelial cells and mesenchymal stem cells were evaluated on the serous and the fibrous sides of the scaffolds, 2 distinct extracellular matrix niches, over the course of a 7 day culture period. Results indicated that fluorescence lifetime successfully report cell presence resolved from extracellular matrix fluorescence. The recellularization process was more rapid on the serous side than on the fibrous side for both cell types, and endothelial cells expanded faster than mesenchymal stem cells on antigen‐removed bovine pericardium. Fiber‐based FLIm has the potential to become a nondestructive tool for the assessment of tissue maturation by allowing in situ imaging of intraluminal vascular biomaterials.

AimsRhabdomyosarcomas of bone are extremely rare, with fewer than 10 reported cases. A very rare subtype of spindle cell/sclerosing rhabdomyosarcoma harbouring a FUS–TFCP2 fusion and involving both soft tissue and bone locations has been reported very recently. We report only the fourth case of this unusual, clinically aggressive rhabdomyosarcoma.Material and resultsA previously well 72‐year‐old male presented with a destructive lesion of the mandible. Morphological and immunohistochemical study of a needle biopsy and the subsequent resection showed a spindle cell rhabdomyosarcoma. RNA‐seq, RT–PCR and FISH confirmed the presence of the FUS–TFCP2 fusion.ConclusionsSpindle cell rhabdomyosarcomas carrying the FUS–TFCP2 fusion are very rare rhabdomyosarcoma variants with osseous predilection. The classification and differential diagnosis of this unusual molecular variant of spindle cell/sclerosing rhabdomyosarcoma are discussed.

Abstract Female sex/gender is an undercharacterized variable in studies related to lung development and disease. Notwithstanding, many aspects of lung and sleep biology and pathobiology are impacted by female sex and female reproductive transitions. These may manifest as differential gene expression or peculiar organ development. Some conditions are more prevalent in women, such as asthma and insomnia, or, in the case of lymphangioleiomyomatosis, are seen almost exclusively in women. In other diseases, presentation differs, such as the higher frequency of exacerbations experienced by women with chronic obstructive pulmonary disease or greater cardiac morbidity among women with sleep-disordered breathing. Recent advances in -omics and behavioral science provide an opportunity to specifically address sex-based differences and explore research needs and opportunities that will elucidate biochemical pathways, thus enabling more targeted/personalized therapies. To explore the status of and opportunities for research in this area, the NHLBI, in partnership with the NIH Office of Research on Women’s Health and the Office of Rare Diseases Research, convened a workshop of investigators in Bethesda, Maryland on September 18 and 19, 2017. At the workshop, the participants reviewed the current understanding of the biological, behavioral, and clinical implications of female sex and gender on lung and sleep health and disease, and formulated recommendations that address research gaps, with a view to achieving better health outcomes through more precise management of female patients with nonneoplastic lung disease. This report summarizes those discussions.

Key Points Pinometostat demonstrates first evidence of DOT1L target inhibition and clinical responses in a subset of MLL-r advanced leukemia patients. The observed safety profile of pinometostat shows potential for exploration of combination therapies in leukemia.

Background: Studies assessing dysplasia’s effect on hip arthroscopy are often limited to the short term and unable to account for demographic factors that may vary between dysplastic and nondysplastic populations. Purpose: To determine the midterm failure rate and patient-reported outcomes of arthroscopic labral repair in the setting of dysplasia and make subsequent failure and outcome comparisons with a rigorously matched nondysplastic control group. Study Design: Cohort study; Level of evidence, 3. Methods: Primary arthroscopic labral repair cases at 2 centers from 2008 to 2011 were reviewed. Patients with lateral center edge angle (LCEA) <25° were matched to nondysplastic controls by age, sex, laterality, body mass index (BMI), Tönnis grade, and capsular repair per a 1:2 matching algorithm. Groups were compared with a visual analog scale (VAS) for pain, modified Harris Hip Score (mHHS), and Hip Outcome Score–Sports Specific Subscale (HOS-SSS) to determine predictors of outcome and failure. Results: Forty-eight patients with dysplasia (mean LCEA, 21.6°; range, 13.0°-24.9°; n = 25 with capsular repair) were matched to 96 controls (mean LCEA, 32.1°; range, 25°-52°; n = 50 with capsular repair) and followed for a mean of 5.7 years (range, 5.0-7.7 years). Patients achieved mean VAS improvements of 3.3 points, mHHS of 19.5, and HOS-SSS of 29.0 points ( P < .01) with no significant differences between the dysplasia and control populations ( P > .05). Five-year failure-free survival was 83.3% for patients with dysplasia and 78.1% for controls ( P = .53). No survival or outcomes difference was observed between patients with dysplasia who did or did not have capsular repair ( P ≥ .45) or when comparing LCEA <20° and LCEA 20° to 25° ( P ≥ .60). BMI ≤30 was associated with increased revision surgery risk ( P < .01). Age >35 years ( P < .05) and Tönnis grade 0 radiographs ( P < .01) predicted failure to reach minimal clinically important differences. Conclusion: With careful selection and modern techniques, patients with dysplasia can benefit significantly and durably from arthroscopic labral repair. The dysplastic cohort had outcomes and failure rates similar to those of rigorously matched controls at midterm follow-up. Subanalyses comparing LCEA <20° and LCEA 20° to 25° are presented for completeness; however, this study was not designed to detect differences in dysplastic subpopulations. BMI ≤30 was associated with increased revision risk. Age >35 years and Tönnis grade 0 radiographs predicted failure to achieve minimal clinically important differences.

AbstractIntroductionSince the introduction of wearable head‐up displays, there has been much interest in the surgical community adapting this technology into routine surgical practice.MethodsWe used the keywords augmented reality OR wearable device OR head‐up display AND surgery using PubMed, EBSCO, IEEE and SCOPUS databases. After exclusions, 74 published articles that evaluated the utility of wearable head‐up displays in surgical settings were included in our review.ResultsAcross all studies, the most common use of head‐up displays was in cases of live streaming from surgical microscopes, navigation, monitoring of vital signs, and display of preoperative images. The most commonly used head‐up display was Google Glass. Head‐up displays enhanced surgeons' operating experience; common disadvantages include limited battery life, display size and discomfort.ConclusionsDue to ergonomic issues with dual‐screen devices, augmented reality devices with the capacity to overlay images onto the surgical field will be key features of next‐generation surgical head‐up displays.

The authors present the case of a man with a papillary craniopharyngioma, first diagnosed at 47 years of age, who experienced multiple recurrences. Review of the pathologic specimen from his first resection demonstrated the BRAF V600E mutation. With his most recent recurrence following previous surgery and radiotherapy, at 52 years of age, the decision was made to initiate treatment with the BRAF V600E inhibitor dabrafenib. Imaging following initiation of dabrafenib demonstrated reduction in tumor size. He remained on dabrafenib therapy for approximately 1 year and continued to demonstrate a good clinical result. At that time the decision was made to discontinue dabrafenib therapy and follow up with serial imaging. After more than 1 year of follow-up since stopping dabrafenib, the patient has continued to do well with no radiographic evidence of tumor progression and continues to be monitored with frequent interval imaging.