Mostrando recursos 1 - 20 de 15.385

  1. The Successful Aging After Elective Surgery Study: Cohort Description and Data Quality Procedures

    Schmitt, Eva M.; Saczynski, Jane S.; Kosar, Cyrus M.; Jones, Richard N.; Alsop, David C.; Fong, Tamara G.; Metzger, Eran; Cooper, Zara R; Marcantonio, Edward Ralph; Travison, Thomas G; Inouye, Sharon K.
    Background/Objectives Delirium is the most common complication of major elective surgery in older patients. The Successful Aging after Elective Surgery (SAGES) study was designed to examine novel risk factors and long-term outcomes associated with delirium. This report describes the cohort, quality assurance procedures, and results. Design Long-term prospective cohort study. Setting Three academic medical centers. Participants A total of 566 patients age 70 and older without recognized dementia scheduled for elective major surgery. Measurements Participants were assessed preoperatively, daily during hospitalization, and at variable monthly intervals for up to 36 months post-discharge. Delirium was assessed in hospital by trained study staff. Study outcomes included cognitive and physical function. Novel...

  2. Assessing multidimensional worry in cancer survivors

    Moye, Jennifer; Wachen, Jennifer Schuster; Mulligan, Elizabeth; Doherty, Kelly; Naik, Aanand D.
    Anxiety in cancer survivors has been characterized in numerous ways. One way is posttraumatic stress disorder (PTSD) symptoms [1]. This approach usefully captures intrusive thoughts, avoidance, and hyperarousal – focusing on cancer as a past trauma creating current symptoms. Another characterization of anxiety focuses on the fear of recurrence (FOR) [2]. FOR appears common in survivors, potentially lasting for many years post-treatment. Still, others have characterized anxiety with multidimensional scales, such as for prostate cancer [3] and breast cancer [4]. Worry differs from these in that it is future oriented; therefore, it is unlike PTSD symptoms, which are past-focused. Worry shares...

  3. Current status and recommendations for biomarkers and biobanking in neurofibromatosis

    Hanemann, C. Oliver; Blakeley, Jaishri O.; Nunes, Fabio; Robertson, Kent; Stemmer-Rachamimov, Anat; Mautner, Victor; Kurtz, Andreas; Ferguson, Michael Andrew; Widemann, Brigitte C.; Evans, D. Gareth; Ferner, Rosalie; Carroll, Steven L.; Korf, Bruce; Wolkenstein, Pierre; Knight, Pamela; Plotkin, Scott Randall
    Objective: Clinically validated biomarkers for neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis (SWN) have not been identified to date. The biomarker working group’s goals are to (1) define biomarker needs in NF1, NF2, and SWN; (2) summarize existing data on biomarkers in NF1, NF2, and SWN; (3) outline recommendations for sample collection and biomarker development; and (4) standardize sample collection and methodology protocols where possible to promote comparison between studies by publishing standard operating procedures (SOPs). Methods: The biomarker group reviewed published data on biomarkers in NF1, NF2, and SWN and on biobanking efforts outside these diseases via literature search, defined the need for biomarkers in NF,...

  4. Sleep and pulmonary outcomes for clinical trials of airway plexiform neurofibromas in NF1

    Plotkin, Scott Randall; Davis, Stephanie H.; Robertson, Kent A.; Akshintala, Srivandana; Allen, Julian; Fisher, Michael J.; Blakeley, Jaishri O.; Widemann, Brigitte C.; Ferner, Rosalie E.; Marcus, Carole L.
    Objective: Plexiform neurofibromas (PNs) are complex, benign nerve sheath tumors that occur in approximately 25%–50% of individuals with neurofibromatosis type 1 (NF1). PNs that cause airway compromise or pulmonary dysfunction are uncommon but clinically important. Because improvement in sleep quality or airway function represents direct clinical benefit, measures of sleep and pulmonary function may be more meaningful than tumor size as endpoints in therapeutic clinical trials targeting airway PN. Methods: The Response Evaluation in Neurofibromatosis and Schwannomatosis functional outcomes group reviewed currently available endpoints for sleep and pulmonary outcomes and developed consensus recommendations for response evaluation in NF clinical trials....

  5. Teaching NeuroImages: Brain mass with hilar adenopathy: The importance of histologic diagnosis

    Jordan, Justin Thomas; Yang, Hyun-Sik; Narendra, Derek; Plotkin, Scott Randall

  6. CTF meeting 2012: Translation of the basic understanding of the biology and genetics of NF1, NF2, and schwannomatosis toward the development of effective therapies

    Widemann, Brigitte C.; Acosta, Maria T.; Ammoun, Sylvia; Belzberg, Allan J.; Bernards, Andre; Blakeley, Jaishri; Bretscher, Antony; Cichowski, Karen Marie; Clapp, D. Wade; Dombi, Eva; Evans, Gareth D.; Ferner, Rosalie; Fernandez-Valle, Cristina; Fisher, Michael J.; Giovannini, Marco; Gutmann, David H.; Hanemann, C. Oliver; Hennigan, Robert; Huson, Susan; Ingram, David; Kissil, Joe; Korf, Bruce R.; Legius, Eric; Packer, Roger J.; McClatchey, Andrea I.; McCormick, Frank; North, Kathryn; Pehrsson, Minja; Plotkin, Scott Randall; Ramesh, Vijaya; Ratner, Nancy; Schirmer, Susann; Sherman, Larry; Schorry, Elizabeth; Stevenson, David; Stewart, Douglas C; Ullrich, Nicole Johnson; Bakker, Annette C.; Morrison, Helen
    The neurofibromatoses (NF) are autosomal dominant genetic disorders that encompass the rare diseases NF1, NF2, and schwannomatosis. The NFs affect more people worldwide than Duchenne muscular dystrophy and Huntington's disease combined. NF1 and NF2 are caused by mutations of known tumor suppressor genes (NF1 and NF2, respectively). For schwannomatosis, although mutations in SMARCB1 were identified in a subpopulation of schwannomatosis patients, additional causative gene mutations are still to be discovered. Individuals with NF1 may demonstrate manifestations in multiple organ systems, including tumors of the nervous system, learning disabilities, and physical disfigurement. NF2 ultimately can cause deafness, cranial nerve deficits, and...

  7. Recommendations for imaging tumor response in neurofibromatosis clinical trials

    Dombi, E.; Ardern-Holmes, S. L.; Babovic-Vuksanovic, D.; Barker, Frederick George; Connor, S.; Evans, D. G.; Fisher, Marc; Goutagny, S.; Harris, G. J.; Jaramillo, D.; Karajannis, M. A.; Korf, B. R.; Mautner, V.; Plotkin, Scott Randall; Poussaint, Tina Young; Robertson, Kent; Shih, C.-S.; Widemann, B. C.; undefined, undefined
    Objective: Neurofibromatosis (NF)-related benign tumors such as plexiform neurofibromas (PN) and vestibular schwannomas (VS) can cause substantial morbidity. Clinical trials directed at these tumors have become available. Due to differences in disease manifestations and the natural history of NFrelated tumors, response criteria used for solid cancers (1-dimensional/RECIST [Response Evaluation Criteria in Solid Tumors] and bidimensional/World Health Organization) have limited applicability. No standardized response criteria for benign NF tumors exist. The goal of the Tumor Measurement Working Group of the REiNS (Response Evaluation in Neurofibromatosis and Schwannomatosis) committee is to propose consensus guidelines for the evaluation of imaging response in clinical...

  8. Hearing and facial function outcomes for neurofibromatosis 2 clinical trials

    Plotkin, Scott Randall; Ardern-Holmes, S. L.; Barker, Frederick George; Blakeley, Jaishri O.; Evans, D. G.; Ferner, R. E.; Hadlock, Theresa A; Halpin, C.
    Objectives: Vestibular schwannomas are the hallmark of neurofibromatosis 2 (NF2), occurring in >95% of patients. These tumors develop on the vestibulocochlear nerve and are associated with significant morbidity due to hearing loss, tinnitus, imbalance, facial weakness, and risk of early mortality from brainstem compression. Although hearing loss and facial weakness have been identified as important functional outcomes for patients with NF2, there is a lack of consensus regarding appropriate endpoints in clinical trials. Methods: The functional outcomes group reviewed existing endpoints for hearing and facial function and developed consensus recommendations for response evaluation in NF2 clinical trials. Results: For hearing endpoints, the functional group endorsed...

  9. Achieving consensus for clinical trials: The REiNS International Collaboration

    Plotkin, Scott Randall; Blakeley, J. O.; Dombi, Eva; Fisher, Michael J.; Hanemann, C. O.; Walsh, Karin S; Wolters, P. L.; Widemann, Brigitte C.
    The neurofibromatoses (NF)—including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis—are related tumor-suppressor syndromes characterized by a predisposition to multiple tumor types and other disease manifestations, which often result in functional disability, reduced quality of life, pain, and, in some cases, malignancy. With increasing knowledge of the biology and pathogenesis of NF, clinical trials with targeted agents directed at NF tumors have become available. Most clinical trials for patients with NF have used designs and endpoints similar to oncology trials. However, differences in the disease manifestations and natural history of NF (compared to cancers) require the development of new designs...

  10. Update from the 2011 International Schwannomatosis Workshop: From genetics to diagnostic criteria

    Plotkin, Scott Randall; Blakeley, Jaishri O.; Evans, D. Gareth; Hanemann, C. Oliver; Hulsebos, Theo J.M.; Hunter-Schaedle, Kim; Kalpana, Ganjam V.; Korf, Bruce; Messiaen, Ludwine; Papi, Laura; Ratner, Nancy; Sherman, Larry S.; Smith, Miriam J.; Stemmer-Rachamimov, Anat; Vitte, Jeremie; Giovannini, Marco
    Schwannomatosis is the third major form of neurofibromatosis and is characterized by the development of multiple schwannomas in the absence of bilateral vestibular schwannomas. The 2011 Schwannomatosis Update was organized by the Children’s Tumor Foundation ( and held in Los Angeles, CA, from June 5–8, 2011. This article summarizes the highlights presented at the Conference and represents the “state-of-the-field” in 2011. Genetic studies indicate that constitutional mutations in the SMARCB1 tumor suppressor gene occur in 40–50% of familial cases and in 8–10% of sporadic cases of schwannomatosis. Tumorigenesis is thought to occur through a four-hit, three-step model, beginning with a...

  11. Clinical Reasoning: A case of multiple intracerebral hemorrhages

    Wendell, L. C.; Freeman, S. H.; Plotkin, Scott Randall; Sims, John R

  12. A high-throughput kinome screen reveals serum/glucocorticoid-regulated kinase 1 as a therapeutic target for NF2-deficient meningiomas

    Beauchamp, Roberta L.; James, Marianne; DeSouza, Patrick A.; Wagh, Vilas; Zhao, Wen-Ning; Jordan, Justin Thomas; Stemmer-Rachamimov, Anat; Plotkin, Scott Randall; Gusella, James Francis; Haggarty, Stephen John; Ramesh, Vijaya
    Meningiomas are the most common primary intracranial adult tumor. All Neurofibromatosis 2 (NF2)-associated meningiomas and ~60% of sporadic meningiomas show loss of NF2 tumor suppressor protein. There are no effective medical therapies for progressive and recurrent meningiomas. Our previous work demonstrated aberrant activation of mTORC1 signaling that led to ongoing clinical trials with rapamycin analogs for NF2 and sporadic meningioma patients. Here we performed a high-throughput kinome screen to identify kinases responsible for mTORC1 pathway activation in NF2-deficient meningioma cells. Among the emerging top candidates were the mTORC2-specific target serum/glucocorticoid-regulated kinase 1 (SGK1) and p21-activated kinase 1 (PAK1). In NF2-deficient...

  13. TLR9 Differentiates Rapidly from Slowly Progressing Forms of Idiopathic Pulmonary Fibrosis

    Trujillo, G.; Meneghin, A.; Flaherty, K. R.; Sholl, Lynette Marie; Myers, J. L.; Kazerooni, E. A.; Gross, B. H.; Oak, S. R.; Coelho, A. L.; Evanoff, H.; Day, E.; Toews, G. B.; Joshi, A. D.; Schaller, M. A.; Waters, B.; Jarai, G.; Westwick, J.; Kunkel, S. L.; Martinez, F. J.; Hogaboam, C. M.
    Idiopathic pulmonary fibrosis is a generally progressive disorder with highly heterogeneous disease progression. The most common of the idiopathic interstitial pneumonias, idiopathic pulmonary fibrosis is characterized by a steady worsening of lung function and gas exchange cause by diffuse alveolar damage and severe fibrosis. We examined clinical features of patients with idiopathic pulmonary fibrosis to classify them as exhibiting rapid or slowly progressive over the first year of follow-up. We identified differences between the two groups in order to investigate the mechanism of rapid progression. Previous work from our laboratory has demonstrated that Toll-like receptor 9, a pathogen recognition receptor,...

  14. Chemotherapy for locally advanced and metastatic pulmonary carcinoid tumors

    Chong, Curtis Robert; Wirth, Lori Julin; Nishino, Mizuki; Chen, Aileen Betty; Sholl, Lynette Marie; Kulke, Matthew H; McNamee, Ciaran; Janne, Pasi Antero; Johnson, Bruce Evan
    Objectives The optimal management of locally advanced and metastatic pulmonary carcinoid tumors remains to be determined. Materials and methods A retrospective review was conducted on patients with typical and atypical pulmonary carcinoid tumors treated at our institutions between 1990 and 2012. Results 300 patients were identified with pulmonary carcinoid, (80 patients with atypical carcinoid), of whom 29 presented with metastatic disease (16 atypical). Of evaluable patients, 26 (41%) with stages I–III atypical carcinoid tumors recurred at a median time of 3.7 years (range, 0.4–32), compared to 3 (1%) patients with typical carcinoid (range, 8–12.3). 39 patients were treated with chemotherapy, including 30 patients with metastatic...

  15. Multi-institutional Oncogenic Driver Mutation Analysis in Lung Adenocarcinoma: The Lung Cancer Mutation Consortium Experience

    Sholl, Lynette Marie; Aisner, Dara L.; Varella-Garcia, Marileila; Berry, Lynne D.; Dias-Santagata, Dora; Wistuba, Ignacio I.; Chen, Heidi; Fujimoto, Junya; Kugler, Kelly; Franklin, Wilbur A.; Iafrate, Anthony John; Ladanyi, Marc; Kris, Mark G.; Johnson, Bruce Evan; Bunn, Paul A.; Minna, John D.; Kwiatkowski, David Joseph
    Introduction Molecular genetic analyses of lung adenocarcinoma have recently become standard of care for treatment selection. The Lung Cancer Mutation Consortium was formed to enable collaborative multi-institutional analyses of 10 potential oncogenic driver mutations. Technical aspects of testing, and clinicopathologic correlations are presented. Methods Mutation testing in at least one of 8 genes (EGFR, KRAS, ERBB2, AKT1, BRAF, MEK1, NRAS, PIK3CA) using SNaPshot, mass spectrometry, Sanger sequencing +/− PNA and/or sizing assays, along with ALK and/or MET FISH were performed in 6 labs on 1007 patients from 14 institutions. Results 1007 specimens had mutation analysis performed, and 733 specimens had all 10 genes analyzed. Mutation...

  16. Combined Use of ALK Immunohistochemistry and FISH for Optimal Detection of ALK-Rearranged Lung Adenocarcinomas

    Sholl, Lynette Marie; Weremowicz, Stanislawa; Gray, Stacy; Wong, Kwok-Kin; Chirieac, Lucian Radu; Lindeman, Neal I.; Hornick, Jason L.
    INTRODUCTION ALK gene rearrangements occur in ~5% of lung adenocarcinomas (ACA), leading to ALK overexpression and predicting response to targeted therapy. Fluorescence in situ hybridization (FISH) is the gold standard for detection of ALK rearrangements in lung ACA but requires specialized equipment and expertise. Immunohistochemistry (IHC) for ALK protein overexpression is a promising screening modality, with reports of newer antibodies showing excellent sensitivity and specificity for ALK-rearranged lung ACA. METHODS In this study, we analyze ALK IHC (5A4 clone) in 186 cases from our clinical service and compare with ALK FISH and EGFR and KRAS mutation status. RESULTS Twelve cases had concordant ALK protein overexpression...

  17. Adam8 Limits the Development of Allergic Airway Inflammation in Mice

    Knolle, M. D.; Nakajima, T.; Hergrueter, A.; Gupta, K.; Polverino, Francesca; Craig, V; Fyfe, S. E.; Zahid, M.; Permaul, Perdita; Cernadas, Manuela; Montano, Giancarlo Vengco; Tesfaigzi, Y.; Sholl, Lynette Marie; Kobzik, Lester; Israel, Elliot; Owen, Caroline Ann
    To determine whether a disintegrin and a metalloproteinase-8 (Adam8) regulates allergic airway inflammation (AAI) and airway hyper-responsiveness (AHR), we compared AAI and AHR in wild type (WT) versus Adam8−/− mice in different genetic backgrounds sensitized and challenged with ovalbumin (OVA) or house dust mite protein extract (HDM). OVA- and HDM-treated Adam8−/− mice had higher lung leukocyte counts, more airway mucus metaplasia, greater lung levels of some TH2 cytokines, and higher methacholine-induced increases in central airway resistance than allergen-treated WT mice. Studies of OVA-treated Adam8 bone marrow chimeric mice confirmed that leukocyte-derived Adam8 predominantly mediated Adam8’s anti-inflammatory activities in murine airways....

  18. Intrathymic cyst: Clinical and radiological features in surgically resected cases

    Araki, Tetsuro; Sholl, Lynette Marie; Gerbaudo, Victor H.; Hatabu, Hiroto; Nishino, Michiya
    AIM To investigate radiological and clinical characteristics of pathologically proven cases of intrathymic cysts. MATERIALS AND METHODS The study population consisted of 18 patients (five males, 13 females; median age 56 years) with pathologically confirmed intrathymic cysts who underwent thymectomy and had preoperative chest computed tomography (CT) available for review. The patient demographics, clinical presentation, and preoperative radiological diagnoses were reviewed. CT images were evaluated for shape, contour, location of the cysts and the presence of adjacent thymic tissue, mass effect, calcifications, and septa. The size and CT attenuations of the cysts were measured. RESULTS The most common CT features of intrathymic cysts included oval...

  19. Clinical, Pathologic, and Biologic Features Associated with BRAF Mutations in Non-Small Cell Lung Cancer

    Cardarella, S.; Ogino, Atsuko; Nishino, Michiya; Butaney, M.; Shen, Jeanne; Lydon, C.; Yeap, Beow Yong; Sholl, Lynette Marie; Johnson, Bruce Evan; Janne, Pasi Antero
    Purpose BRAF mutations are found in a subset of non-small cell lung cancers (NSCLCs). We examined the clinical characteristics and treatment outcomes of patients with NSCLC harboring BRAF mutations. Experimental Design Using DNA sequencing, we successfully screened 883 NSCLC patients for BRAF mutations between 7/1/09 and 7/16/12. Baseline characteristics and treatment outcomes were compared between patients with and without BRAF mutations. Wild type controls consisted of NSCLC patients without a somatic alteration in BRAF, KRAS, EGFR, and ALK. In vitro studies assessed the biological properties of selected non-V600E BRAF mutations identified from NSCLC patients. Results Of 883 tumors screened, 36 (4%) harbored BRAF mutations (V600E:...

  20. Clinicopathologic Features and Long-term Outcomes of NUT Midline Carcinoma

    Bauer, Daniel Evan; Mitchell, C. M.; Strait, K. M.; Lathan, Christopher Scott; Stelow, E. B.; Luer, S. C.; Muhammed, S.; Evans, A. G.; Sholl, Lynette Marie; Rosai, J.; Giraldi, E.; Oakley, R. P.; Rodriguez-Galindo, C; London, Wendy B; Sallan, Stephen Earl; Bradner, James Elliott; French, Christopher Alexander
    Purpose NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer characterized by rearrangement of the NUT gene. Research advances have provided opportunities for targeted therapy in NMC, yet the clinical features of this rare disease have not been systematically characterized. We report on a large population of such patients to identify the disease characteristics and treatments, correlate them with outcome, and to consider clinical recommendations. Experimental Design A clinical database was established using retrospective demographic and outcomes data available on all known cases of NMC. Questionnaires were completed by treating physicians. Pathologic, demographic, and clinical variables were assessed for 63 patients, the...

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