6,016 results on '"McDermott, Michael"'
Search Results
2. Meta-analysis of [18F]FDG-PET/CT in pulmonary sarcoidosis
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Donnelly, Ryan, McDermott, Michael, McManus, Gerry, Franciosi, Alessandro N., Keane, Michael P., McGrath, Emmet E., McCarthy, Cormac, and Murphy, David J.
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- 2024
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3. The Miami Framework for ALS and related neurodegenerative disorders: an integrated view of phenotype and biology
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Benatar, Michael, Wuu, Joanne, Huey, Edward D., McMillan, Corey T., Petersen, Ronald C., Postuma, Ronald, McHutchison, Caroline, Dratch, Laynie, Arias, Jalayne J., Crawley, Anita, Houlden, Henry, McDermott, Michael P., Cai, Xueya, Thakur, Neil, Boxer, Adam, Rosen, Howard, Boeve, Bradley F., Dacks, Penny, Cosentino, Stephanie, Abrahams, Sharon, Shneider, Neil, Lingor, Paul, Shefner, Jeremy, Andersen, Peter M., Al-Chalabi, Ammar, and Turner, Martin R.
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- 2024
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4. Epigenetic reprogramming shapes the cellular landscape of schwannoma.
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Liu, S, Casey-Clyde, Tim, Cho, Nam, Swinderman, Jason, Pekmezci, Melike, Dougherty, Mark, Foster, Kyla, Chen, William, Villanueva-Meyer, Javier, Swaney, Danielle, Vasudevan, Harish, Choudhury, Abrar, Pak, Joanna, Breshears, Jonathan, Lang, Ursula, Eaton, Charlotte, Hiam-Galvez, Kamir, Stevenson, Erica, Chen, Kuei-Ho, Lien, Brian, Wu, David, Braunstein, Steve, Sneed, Penny, Magill, Stephen, Lim, Daniel, McDermott, Michael, Berger, Mitchel, Perry, Arie, Krogan, Nevan, Hansen, Marlan, Spitzer, Matthew, Gilbert, Luke, Theodosopoulos, Philip, and Raleigh, David
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Humans ,Neurilemmoma ,Epigenesis ,Genetic ,Cellular Reprogramming ,Tumor Microenvironment - Abstract
Mechanisms specifying cancer cell states and response to therapy are incompletely understood. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas, the most common tumors of the peripheral nervous system. We find schwannomas are comprised of 2 molecular groups that are distinguished by activation of neural crest or nerve injury pathways that specify tumor cell states and the architecture of the tumor immune microenvironment. Moreover, we find radiotherapy is sufficient for interconversion of neural crest schwannomas to immune-enriched schwannomas through epigenetic and metabolic reprogramming. To define mechanisms underlying schwannoma groups, we develop a technique for simultaneous interrogation of chromatin accessibility and gene expression coupled with genetic and therapeutic perturbations in single-nuclei. Our results elucidate a framework for understanding epigenetic drivers of tumor evolution and establish a paradigm of epigenetic and metabolic reprograming of cancer cells that shapes the immune microenvironment in response to radiotherapy.
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- 2024
5. Deconstructing Intratumoral Heterogeneity through Multiomic and Multiscale Analysis of Serial Sections
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Schupp, Patrick G, Shelton, Samuel J, Brody, Daniel J, Eliscu, Rebecca, Johnson, Brett E, Mazor, Tali, Kelley, Kevin W, Potts, Matthew B, McDermott, Michael W, Huang, Eric J, Lim, Daniel A, Pieper, Russell O, Berger, Mitchel S, Costello, Joseph F, Phillips, Joanna J, and Oldham, Michael C
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Cancer Genomics ,Precision Medicine ,Biotechnology ,Human Genome ,Genetics ,intratumoral heterogeneity ,clonal evolution ,tumor microenvironment ,low-grade glioma ,IDH1 ,gene coexpression ,multiomic ,single-nucleus analysis ,Oncology and carcinogenesis - Abstract
Tumors may contain billions of cells, including distinct malignant clones and nonmalignant cell types. Clarifying the evolutionary histories, prevalence, and defining molecular features of these cells is essential for improving clinical outcomes, since intratumoral heterogeneity provides fuel for acquired resistance to targeted therapies. Here we present a statistically motivated strategy for deconstructing intratumoral heterogeneity through multiomic and multiscale analysis of serial tumor sections (MOMA). By combining deep sampling of IDH-mutant astrocytomas with integrative analysis of single-nucleotide variants, copy-number variants, and gene expression, we reconstruct and validate the phylogenies, spatial distributions, and transcriptional profiles of distinct malignant clones. By genotyping nuclei analyzed by single-nucleus RNA-seq for truncal mutations, we further show that commonly used algorithms for identifying cancer cells from single-cell transcriptomes may be inaccurate. We also demonstrate that correlating gene expression with tumor purity in bulk samples can reveal optimal markers of malignant cells and use this approach to identify a core set of genes that are consistently expressed by astrocytoma truncal clones, including AKR1C3, whose expression is associated with poor outcomes in several types of cancer. In summary, MOMA provides a robust and flexible strategy for precisely deconstructing intratumoral heterogeneity and clarifying the core molecular properties of distinct cellular populations in solid tumors.
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- 2024
6. Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses
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Chen, William C, Choudhury, Abrar, Youngblood, Mark W, Polley, Mei-Yin C, Lucas, Calixto-Hope G, Mirchia, Kanish, Maas, Sybren LN, Suwala, Abigail K, Won, Minhee, Bayley, James C, Harmanci, Akdes S, Harmanci, Arif O, Klisch, Tiemo J, Nguyen, Minh P, Vasudevan, Harish N, McCortney, Kathleen, Yu, Theresa J, Bhave, Varun, Lam, Tai-Chung, Pu, Jenny Kan-Suen, Li, Lai-Fung, Leung, Gilberto Ka-Kit, Chan, Jason W, Perlow, Haley K, Palmer, Joshua D, Haberler, Christine, Berghoff, Anna S, Preusser, Matthias, Nicolaides, Theodore P, Mawrin, Christian, Agnihotri, Sameer, Resnick, Adam, Rood, Brian R, Chew, Jessica, Young, Jacob S, Boreta, Lauren, Braunstein, Steve E, Schulte, Jessica, Butowski, Nicholas, Santagata, Sandro, Spetzler, David, Bush, Nancy Ann Oberheim, Villanueva-Meyer, Javier E, Chandler, James P, Solomon, David A, Rogers, C Leland, Pugh, Stephanie L, Mehta, Minesh P, Sneed, Penny K, Berger, Mitchel S, Horbinski, Craig M, McDermott, Michael W, Perry, Arie, Bi, Wenya Linda, Patel, Akash J, Sahm, Felix, Magill, Stephen T, and Raleigh, David R
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Clinical Research ,Brain Disorders ,Brain Cancer ,Rare Diseases ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,Humans ,Biomarkers ,Gene Expression Profiling ,Meningeal Neoplasms ,Meningioma ,Neoplasm Recurrence ,Local ,Prospective Studies ,Medical and Health Sciences ,Immunology ,Biomedical and clinical sciences ,Health sciences - Abstract
Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (N = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P
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- 2023
7. Critical but commonly neglected factors that affect contrast medium administration in CT
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McDermott, Michael C., Wildberger, Joachim E., and Bae, Kyongtae T.
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- 2024
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8. Prophylactic Radiotherapy Of MInimally Symptomatic Spinal Disease (PROMISSeD): study protocol for a randomized controlled trial
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Rothrock, Robert J., Ozair, Ahmad, Avendano, Maria C., Herrera, Susana, Appel, Haley, Ramos, Suyen, Starosciak, Amy K., Leon-Ariza, Daniel S., Rubens, Muni, McDermott, Michael W., Ahluwalia, Manmeet S., Mehta, Minesh P., and Kotecha, Rupesh R.
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- 2024
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9. The importance of considering competing risks in recurrence analysis of intracranial meningioma
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Mirian, Christian, Jensen, Lasse Rehné, Juratli, Tareq A., Maier, Andrea Daniela, Torp, Sverre H., Shih, Helen A., Morshed, Ramin A., Young, Jacob S., Magill, Stephen T., Bertero, Luca, Stummer, Walter, Spille, Dorothee Cäcilia, Brokinkel, Benjamin, Oya, Soichi, Miyawaki, Satoru, Saito, Nobuhito, Proescholdt, Martin, Kuroi, Yasuhiro, Gousias, Konstantinos, Simon, Matthias, Moliterno, Jennifer, Prat-Acin, Ricardo, Goutagny, Stéphane, Prabhu, Vikram C., Tsiang, John T., Wach, Johannes, Güresir, Erdem, Yamamoto, Junkoh, Kim, Young Zoon, Lee, Joo Ho, Koshy, Matthew, Perumal, Karthikeyan, Baskaya, Mustafa K., Cannon, Donald M., Shrieve, Dennis C., Suh, Chang-Ok, Chang, Jong Hee, Kamenova, Maria, Straumann, Sven, Soleman, Jehuda, Eyüpoglu, Ilker Y., Catalan, Tony, Lui, Austin, Theodosopoulos, Philip V., McDermott, Michael W., Wang, Fang, Guo, Fuyou, Góes, Pedro, de Paiva Neto, Manoel Antonio, Jamshidi, Aria, Komotar, Ricardo, Ivan, Michael, Luther, Evan, Souhami, Luis, Guiot, Marie-Christine, Csonka, Tamás, Endo, Toshiki, Barrett, Olivia Claire, Jensen, Randy, Gupta, Tejpal, Patel, Akash J., Klisch, Tiemo J., Kim, Jun Won, Maiuri, Francesco, Barresi, Valeria, Tabernero, María Dolores, Skyrman, Simon, Broechner, Anders, Bach, Mathias Jacobsen, Law, Ian, Scheie, David, Kristensen, Bjarne Winther, Munch, Tina Nørgaard, Meling, Torstein, Fugleholm, Kåre, Blanche, Paul, and Mathiesen, Tiit
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- 2024
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10. OptImal Gamma kNife lIghTnIng sOlutioN (IGNITION) score to characterize the solution space of the Gamma Knife FIP optimizer for stereotactic radiosurgery
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Tolakanahalli, Ranjini, Wieczorek, D Jay J, Lee, Yongsook C, Tom, Martin C, Hall, Matthew D, McDermott, Michael W, Mehta, Minesh P, Kotecha, Rupesh, and Gutierrez, Alonso N
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Medical and Biological Physics ,Biomedical and Clinical Sciences ,Clinical Sciences ,Physical Sciences ,Oncology and Carcinogenesis ,Cancer ,Humans ,Radiosurgery ,Lightning ,Brain Neoplasms ,Radiotherapy Dosage ,Arteriovenous Malformations ,Radiotherapy Planning ,Computer-Assisted ,Gamma Knife ,inverse optimizer ,lightning ,stereotactic radiosurgery ,Other Physical Sciences ,Medical Physiology ,Nuclear Medicine & Medical Imaging ,Medical physiology ,Medical and biological physics - Abstract
ObjectivesThe objective of this study is to evaluate the user-defined optimization settings in the Fast Inverse Planning (FIP) optimizer in Leksell GammaPlan® and determine the parameters that result in the best stereotactic radiosurgery (SRS) plan quality for brain metastases, benign tumors, and arteriovenous malformations (AVMs).MethodsThirty patients with metastases and 30 with benign lesions-vestibular schwannoma, AVMs, pituitary adenoma, and meningioma-treated with SRS were evaluated. Each target was planned by varying the low dose (LD) and beam-on-time (BOT) penalties in increments of 0.1, from 0 to 1. The following plan quality metrics were recorded for each plan: Paddick conformity index (PCI), gradient index (GI), BOT, and maximum organ-at-risk (OAR) doses. A novel objective score matrix was calculated for each target using a linearly weighted combination of the aforementioned metrics. A histogram of optimal solutions containing the five best scores was extracted.ResultsA total of 7260 plans were analyzed with 121 plans per patient for the range of LD/BOT penalties. The ranges of PCI, GI, and BOT across all metastatic lesions were 0.58-0.97, 2.1-3.8, and 8.8-238 min, respectively, and were 0.13-0.97, 2.1-3.8, and 8.8-238 min, respectively, for benign lesions. The objective score matrix showed unique optimal solutions for metastatic lesions and benign lesions. Additionally, the plan metrics of the optimal solutions were significantly improved compared to the clinical plans for metastatic lesions with equivalent metrics for all other cases.ConclusionIn this study, FIP optimizer was evaluated to determine the optimal solution space to maximize PCI and minimize GI, BOT and OAR doses simultaneously for single metastatic/benign/non-neoplastic targets. The optimal solution chart was determined using a novel objective score which provides novice and expert planners a roadmap to generate the most optimal plans efficiently using FIP.
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- 2023
11. Interactive Effects of Molecular, Therapeutic, and Patient Factors on Outcome of Diffuse Low-Grade Glioma
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Hervey-Jumper, Shawn L, Zhang, Yalan, Phillips, Joanna J, Morshed, Ramin A, Young, Jacob S, McCoy, Lucie, Lafontaine, Marisa, Luks, Tracy, Ammanuel, Simon, Kakaizada, Sofia, Egladyous, Andrew, Gogos, Andrew, Villanueva-Meyer, Javier, Shai, Anny, Warrier, Gayathri, Rice, Terri, Crane, Jason, Wrensch, Margaret, Wiencke, John K, Daras, Mariza, Bush, Nancy Ann Oberheim, Taylor, Jennie W, Butowski, Nicholas, Clarke, Jennifer, Chang, Susan, Chang, Edward, Aghi, Manish, Theodosopoulos, Philip, McDermott, Michael, Jakola, Asgeir S, Kavouridis, Vasileios K, Nawabi, Noah, Solheim, Ole, Smith, Timothy, Berger, Mitchel S, and Molinaro, Annette M
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Patient Safety ,Neurosciences ,Orphan Drug ,Cancer ,Brain Cancer ,Brain Disorders ,Clinical Research ,Rare Diseases ,Precision Medicine ,Clinical Trials and Supportive Activities ,6.1 Pharmaceuticals ,Humans ,Oligodendroglioma ,Retrospective Studies ,Brain Neoplasms ,Neurosurgical Procedures ,Glioma ,Astrocytoma ,Treatment Outcome ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
PurposeIn patients with diffuse low-grade glioma (LGG), the extent of surgical tumor resection (EOR) has a controversial role, in part because a randomized clinical trial with different levels of EOR is not feasible.MethodsIn a 20-year retrospective cohort of 392 patients with IDH-mutant grade 2 glioma, we analyzed the combined effects of volumetric EOR and molecular and clinical factors on overall survival (OS) and progression-free survival by recursive partitioning analysis. The OS results were validated in two external cohorts (n = 365). Propensity score analysis of the combined cohorts (n = 757) was used to mimic a randomized clinical trial with varying levels of EOR.ResultsRecursive partitioning analysis identified three survival risk groups. Median OS was shortest in two subsets of patients with astrocytoma: those with postoperative tumor volume (TV) > 4.6 mL and those with preoperative TV > 43.1 mL and postoperative TV ≤ 4.6 mL. Intermediate OS was seen in patients with astrocytoma who had chemotherapy with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL in addition to oligodendroglioma patients with either preoperative TV > 43.1 mL and residual TV ≤ 4.6 mL or postoperative residual volume > 4.6 mL. Longest OS was seen in astrocytoma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL who received no chemotherapy and oligodendroglioma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL. EOR ≥ 75% improved survival outcomes, as shown by propensity score analysis.ConclusionAcross both subtypes of LGG, EOR beginning at 75% improves OS while beginning at 80% improves progression-free survival. Nonetheless, maximal resection with preservation of neurological function remains the treatment goal. Our findings have implications for surgical strategies for LGGs, particularly oligodendroglioma.
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- 2023
12. Diploic Bone Channel Drilling Facilitates Dissection of the Midline Dura and Protects the Superior Sagittal Sinus in Hyperostosis Frontalis Interna
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Rutkowski, Martin, Ozair, Ahmad, Niehaus, Brian, and McDermott, Michael W
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Biomedical and Clinical Sciences ,Clinical Sciences ,Neurosciences ,dural-based tumor ,hyperostosis frontalis interna ,inner table ,meningioma ,bone flap ,craniectomy ,craniotomy ,diploic bone ,hyperostosis ,superior sagittal sinus ,Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Patients with space-occupying lesions adjacent to the superior sagittal sinus (SSS) present several technical considerations. For craniotomies crossing the SSS, a two-part method allows for dissection of the epidural space and dura under direct vision after removing a more lateral parasagittal bone flap. However, when the inner table surface of the medial component of the two-part bone flap is irregular, this can be difficult. We describe a method for channel drilling of the diploic bone, which allows for the piecemeal removal of the inner table using an upbiting rongeur. This article presents the case of meningioma with documented growth and provides a technical note of this technique to facilitate safe dissection of the midline dura. A patient presented with headaches and an anterior one-third parasagittal meningioma with documented growth. She selected surgical removal for treatment. A right frontal two-part parasagittal craniotomy was recommended. The preoperative imaging showed that the frontal bone was thick, with irregularity of the inner table. Intraoperatively, a channel was drilled in the diploic space of the bone, leaving the outer table intact. This provided a thin lip of the inner table that could be dissected over a short distance and then removed with a 2-mm upbiting rongeur. This allowed for further dissection of the dura crossing the midline under direct vision and safe secondary bone piece removal. The dura was opened to the edge of the SSS, allowing full exposure of the parasagittal region and interhemispheric fissure, thus limiting retraction of the medial right frontal lobe. The bone flap was removed in two pieces without a dural tear over the midline in spite of inner table irregularities. A Simpson grade 1 removal was accomplished, including excision of the affected falx, and the postoperative course was uncomplicated. In conclusion, diploic bone channel drilling is a technique that can be used to create a thin lip of the inner table, which can be removed piecemeal for safe dissection of the midline dura crossing the midline.
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- 2023
13. A nosology of immune diseases from deep immunophenotyping
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McDermott, Michael F.
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- 2024
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14. Portfolio of published compositions and arrangements
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McDermott, Michael
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The submission consists of a critical review to support the collection of compositions found within the portfolio of published works. The portfolio of published works (six in total) is comprised of three pieces for marching band, orchestra, choir and bagpipes, two pieces for full orchestra with choir and one piece for symphonic wind band. The portfolio provides evidence of my practice-led research and the evaluation enables me to explore some of the challenges and circumstances that have arisen during the pre- and post-production stages of the works. The portfolio also examines the role of a musical director in the context of large-scale contemporary productions and the relationship between musical direction and all the various elements contained within those productions. Additionally, the portfolio highlights the contrasting challenges that present themselves during such large-scale events and seeks to demonstrate how those challenges may be approached, analysed and resolved when having to deal with varying levels of musical expertise that sometimes exist when organising events of this nature. The collected work represents an addition to existing knowledge by highlighting how some assignments introduced pioneering steps forward within the wind band movement especially when combined with other musical ensembles and instruments including the Great Highland Bagpipe. Other original features of the work include the use of the wind band in combination with other musical ensembles such as the tri-service string orchestra and rock bands, exploiting professional and amateur vocal organisations and creating music to accompany the action taking place in an arena or on stage that involved hundreds of participants carrying out completely different stage instructions. Also, employing a methodology that allowed me to persuade producers and artistic directors that some elements of the performance they had initially considered to be challenging, even unachievable, (either artistically or technically), were in fact feasible if approached from an alternative and sometimes more contemporary direction.
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- 2023
15. Development of ‘Core Outcome Sets’ for Meningioma in Clinical Studies (The COSMIC Project): protocol for two systematic literature reviews, eDelphi surveys and online consensus meetings
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Millward, Christopher P, Armstrong, Terri S, Barrington, Heather, Bell, Sabrina, Brodbelt, Andrew R, Bulbeck, Helen, Crofton, Anna, Dirven, Linda, Georgious, Theo, Grundy, Paul L, Islim, Abdurrahman I, Javadpour, Mohsen, Keshwara, Sumirat M, Koszdin, Shelli D, Marson, Anthony G, McDermott, Michael W, Meling, Torstein R, Oliver, Kathy, Plaha, Puneet, Preusser, Matthias, Santarius, Thomas, Srikandarajah, Nisaharan, Taphoorn, Martin JB, Turner, Carole, Watts, Colin, Weller, Michael, Williamson, Paula R, Zadeh, Gelareh, Najafabadi, Amir H Zamanipoor, Jenkinson, Michael D, Aldape, Kenneth, Au, Karolyn, Barnhartz-Sloan, Jill, Bi, Wenya Linda, Behling, Felix, Brastianos, Priscilla K, Brodie, Chaya, Butowski, Nicholas, Carlotti, Carlos, Castro, Ana, Cohen-Gadol, Aaron, Couce, Marta, Cusimano, Michael D, DiMeco, Francesco, Drummond, Katharine, Dunn, Ian F, Erker, Craig, Felicella, Michelle, Fountain, Daniel M, Galanis, Evanthia, Galldiks, Norbert, Giannini, Caterina, Goldbrunner, Roland, Griffith, Brent, Hashizume, Rintaro, Hanemann, C Oliver, Herold-Mende, Christel, Hnenny, Luke, Horbinski, Craig, Huang, Raymond Y, James, David, Jungk, Christine, Jungwirth, Gerhard, Kaufmann, Timothy J, Krischek, Boris, Kurz, Sylvia, Lachance, Daniel, Lafougère, Christian, Lamszus, Katrin, Lee, Ian, Liu, Jeff C, Makarenko, Serge, Malta, Tathiana, Mamatjan, Yasin, Mansouri, Alireza, Mawrin, Christian, McDermott, Michael, Moliterno-Gunel, Jennifer, Morokoff, Andrew, Munoz, David, Nassiri, Farshad, Noushmehr, Houtan, Ng, Ho-Keung, Perry, Arie, Pirouzmand, Farhad, Poisson, Laila M, Pollo, Bianca, Ragunathan, Aditya, Raleigh, David, Renovanz, Mirjam, Ricklefs, Franz, Sahm, Felix, Saladino, Andrea, Santacroce, Antonio, Schittenhelm, Jens, and Schichor, Christian
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Biomedical and Clinical Sciences ,Clinical Sciences ,Neurosciences ,Brain Disorders ,Clinical Research ,Clinical Trials and Supportive Activities ,Cancer ,Consensus ,Delphi Technique ,Humans ,Meningeal Neoplasms ,Meningioma ,Research Design ,Systematic Reviews as Topic ,Treatment Outcome ,EORTC BTG ,ICOM ,EANO ,SNO ,RANO-PRO ,BNOS ,SBNS ,BIMS ,TBTC ,International Brain Tumour Alliance ,Brainstrust ,and Brain Tumour Foundation of Canada ,clinical trial ,core outcome set ,meningioma ,Public Health and Health Services ,Other Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences ,Psychology - Abstract
IntroductionMeningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two 'Core Outcome Sets' (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma.Methods and analysisTwo systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups.Ethics and disseminationInstitutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surveys and consensus meetings. The two systematic literature reviews and two final COS will be published and freely available.Trial registration numberCOMET study ID 1508.
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- 2022
16. Supervised machine learning algorithms demonstrate proliferation index correlates with long-term recurrence after complete resection of WHO grade I meningioma.
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Nguyen, Minh P, Morshed, Ramin A, Dalle Ore, Cecilia L, Cummins, Daniel D, Saggi, Satvir, Chen, William C, Choudhury, Abrar, Ravi, Akshay, Raleigh, David R, Magill, Stephen T, McDermott, Michael W, and Theodosopoulos, Philip V
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Neurosciences ,Rare Diseases ,Brain Cancer ,Cancer ,Brain Disorders ,Prevention ,Adult ,Humans ,Middle Aged ,Meningioma ,Meningeal Neoplasms ,Retrospective Studies ,Algorithms ,World Health Organization ,Cell Proliferation ,Neoplasm Recurrence ,Local ,meningioma ,complete resection ,gross-total resection ,recurrence ,MIB-1 ,Ki-67 ,oncology ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
ObjectiveMeningiomas are the most common primary intracranial tumor, and resection is a mainstay of treatment. It is unclear what duration of imaging follow-up is reasonable for WHO grade I meningiomas undergoing complete resection. This study examined recurrence rates, timing of recurrence, and risk factors for recurrence in patients undergoing a complete resection (as defined by both postoperative MRI and intraoperative impression) of WHO grade I meningiomas.MethodsThe authors conducted a retrospective, single-center study examining recurrence risk for adult patients with a single intracranial meningioma that underwent complete resection. Uni- and multivariate nominal logistic regression and Cox proportional hazards analyses were performed to identify variables associated with recurrence and time to recurrence. Two supervised machine learning algorithms were then implemented to confirm factors within the cohort that were associated with recurrence.ResultsThe cohort consisted of 823 patients who met inclusion criteria, and 56 patients (6.8%) had recurrence on imaging follow-up. The median age of the cohort was 56 years, and 77.4% of patients were female. The median duration of head imaging follow-up for the entire cohort was 2.7 years, but for the subgroup of patients who had a recurrence, the median follow-up was 10.1 years. Estimated 1-, 5-, 10-, and 15-year recurrence-free survival rates were 99.8% (95% confidence interval [CI] 98.8%-99.9%), 91.0% (95% CI 87.7%-93.6%), 83.6% (95% CI 78.6%-87.6%), and 77.3% (95% CI 69.7%-83.4%), respectively, for the entire cohort. On multivariate analysis, MIB-1 index (odds ratio [OR] per 1% increase: 1.34, 95% CI 1.13-1.58, p = 0.0003) and follow-up duration (OR per year: 1.12, 95% CI 1.03-1.21, p = 0.012) were both associated with recurrence. Gradient-boosted decision tree and random forest analyses both identified MIB-1 index as the main factor associated with recurrence, aside from length of imaging follow-up. For tumors with an MIB-1 index < 8, recurrences were documented up to 8 years after surgery. For tumors with an MIB-1 index ≥ 8, recurrences were documented up to 12 years following surgery.ConclusionsLong-term imaging follow-up is important even after a complete resection of a meningioma. Higher MIB-1 labeling index is associated with greater risk of recurrence. Imaging screening for at least 8 years in patients with an MIB-1 index < 8 and at least 12 years for those with an MIB-1 index ≥ 8 may be needed to detect long-term recurrences.
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- 2023
17. DNA Methylation and Histone Modification in Low-Grade Gliomas: Current Understanding and Potential Clinical Targets
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Ozair, Ahmad, Bhat, Vivek, Alisch, Reid S, Khosla, Atulya A, Kotecha, Rupesh R, Odia, Yazmin, McDermott, Michael W, and Ahluwalia, Manmeet S
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Genetics ,Brain Cancer ,Neurosciences ,Rare Diseases ,Cancer ,Brain Disorders ,methylation ,methylomics ,G-CIMP ,MGMT ,DNMT ,ATRX ,CpG island ,tumor suppressor ,methyltransferases ,histone acetylation ,H3K27M ,Oncology and carcinogenesis - Abstract
Gliomas, the most common type of malignant primary brain tumor, were conventionally classified through WHO Grades I-IV (now 1-4), with low-grade gliomas being entities belonging to Grades 1 or 2. While the focus of the WHO Classification for Central Nervous System (CNS) tumors had historically been on histopathological attributes, the recently released fifth edition of the classification (WHO CNS5) characterizes brain tumors, including gliomas, using an integration of histological and molecular features, including their epigenetic changes such as histone methylation, DNA methylation, and histone acetylation, which are increasingly being used for the classification of low-grade gliomas. This review describes the current understanding of the role of DNA methylation, demethylation, and histone modification in pathogenesis, clinical behavior, and outcomes of brain tumors, in particular of low-grade gliomas. The review also highlights potential diagnostic and/or therapeutic targets in associated cellular biomolecules, structures, and processes. Targeting of MGMT promoter methylation, TET-hTDG-BER pathway, association of G-CIMP with key gene mutations, PARP inhibition, IDH and 2-HG-associated processes, TERT mutation and ARL9-associated pathways, DNA Methyltransferase (DNMT) inhibition, Histone Deacetylase (HDAC) inhibition, BET inhibition, CpG site DNA methylation signatures, along with others, present exciting avenues for translational research. This review also summarizes the current clinical trial landscape associated with the therapeutic utility of epigenetics in low-grade gliomas. Much of the evidence currently remains restricted to preclinical studies, warranting further investigation to demonstrate true clinical utility.
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- 2023
18. CDKN2A/B co-deletion is associated with increased risk of local and distant intracranial recurrence after surgical resection of brain metastases.
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Morshed, Ramin A, Nguyen, Minh P, Cummins, Daniel D, Saggi, Satvir, Young, Jacob S, Haddad, Alexander F, Goldschmidt, Ezequiel, Chang, Edward F, McDermott, Michael W, Berger, Mitchel S, Theodosopoulos, Philip V, Hervey-Jumper, Shawn L, Daras, Mariza, and Aghi, Manish K
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CDKN2A ,CDKN2B ,brain metastasis ,distant recurrence ,local recurrence ,surgery ,Genetics ,Patient Safety ,Cancer ,Neurosciences ,Human Genome ,Clinical Research ,Rare Diseases ,Brain Disorders - Abstract
BackgroundWhile genetic alterations in brain metastases (BMs) have been previously explored, there are limited data examining their association with recurrence after surgical resection. This study aimed to identify genetic alterations within BMs associated with CNS recurrence after surgery across multiple cancer types.MethodsA retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical and gene sequencing data available. Local and remote CNS recurrence were the primary study outcomes. Next-generation sequencing of the coding regions in over 500 oncogenes was performed in brain metastasis specimens. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with CNS recurrence.ResultsA total of 90 patients undergoing resection of 91 BMs composed the cohort. Genes most frequently mutated in the cohort included TP53 (64%), CDKN2A (37%), TERT (29%), CDKN2B (23%), NF1 (14%), KRAS (14%), and PTEN (13%), all of which occurred across multiple cancer types. CDKN2A/B co-deletion was seen in 21 (23.1%) brain metastases across multiple cancer types. In multivariate Cox proportional hazard analyses including patient, tumor, and treatment factors, CDKN2A/B co-deletion in the brain metastasis was associated with increased risk of local (HR 4.07, 95% CI 1.32-12.54, P = 0.014) and remote (HR 2.28, 95% CI 1.11-4.69, P = 0.025) CNS progression. Median survival and length of follow-up were not different based on CDKN2A/B mutation status.ConclusionsCDKN2A/B co-deletion detected in BMs is associated with increased CNS recurrence after surgical resection. Additional work is needed to determine whether more aggressive treatment in patients with this mutation may improve outcomes.
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- 2023
19. Dosimetric Impact of Lesion Number, Size, and Volume on Mean Brain Dose with Stereotactic Radiosurgery for Multiple Brain Metastases
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La Rosa, Alonso, Wieczorek, D Jay J, Tolakanahalli, Ranjini, Lee, Yongsook C, Kutuk, Tugce, Tom, Martin C, Hall, Matthew D, McDermott, Michael W, Mehta, Minesh P, Gutierrez, Alonso N, and Kotecha, Rupesh
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Biomedical and Clinical Sciences ,Clinical Sciences ,Cancer ,Neurosciences ,Rare Diseases ,radiosurgery ,GammaKnife ,inverse optimizer ,CyberKnife ,multiple brain metastases ,mean brain dose ,Oncology and Carcinogenesis ,Oncology and carcinogenesis - Abstract
We evaluated the effect of lesion number and volume for brain metastasis treated with SRS using GammaKnife® ICON™ (GK) and CyberKnife® M6™ (CK). Four sets of lesion sizes (10-15 mm, and >15 mm) were contoured and prescribed a dose of 20 Gy/1 fraction. The number of lesions was increased until a threshold mean brain dose of 8 Gy was reached; then individually optimized to achieve maximum conformity. Across GK plans, mean brain dose was linearly proportional to the number of lesions and total GTV for all sizes. The numbers of lesions needed to reach this threshold for GK were 177, 57, 29, and 10 for each size group, respectively; corresponding total GTVs were 3.62 cc, 20.37 cc, 30.25 cc, and 57.96 cc, respectively. For CK, the threshold numbers of lesions were 135, 35, 18, and 8, with corresponding total GTVs of 2.32 cc, 12.09 cc, 18.24 cc, and 41.52 cc respectively. Mean brain dose increased linearly with number of lesions and total GTV while V8 Gy, V10 Gy, and V12 Gy showed quadratic correlations to the number of lesions and total GTV. Modern dedicated intracranial SRS systems allow for treatment of numerous brain metastases especially for ≤10 mm; clinical evidence to support this practice is critical to expansion in the clinic.
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- 2023
20. Dual-mode microresonators as straightforward access to octave-spanning dissipative Kerr solitons
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Weng, Haizhong, Afridi, Adnan Ali, Li, Jing, McDermott, Michael, Tu, Huilan, Barry, Liam P., Lu, Qiaoyin, Guo, Weihua, and Donegan, John F.
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Physics - Optics - Abstract
The Kerr soliton frequency comb is a revolutionary compact ruler of coherent light that allows applications, from precision metrology to quantum information technology. The universal, reliable, and low-cost soliton microcomb source is key to these applications. In this work, we thoroughly present an innovative design strategy for realizing optical microresonators with two adjacent modes, separated by approximately 10 GHz, which stabilizes soliton formation without using additional auxiliary laser or RF components. We demonstrate the deterministic generation of the single-solitons that span 1.5-octaves, i.e., near 200 THz, via adiabatic pump wavelength tuning. The ultra-wide soliton existence ranges up to 17 GHz not only suggests the robustness of the system but will also extend the applications of soliton combs. Moreover, the proposed scheme is found to easily give rise to multi-solitons as well as the soliton crystals featuring enhanced repetition rate (2 and 3 THz) and conversion efficiency greater than 10%. We also show the effective thermal tuning of mode separation for stably accessing single-soliton. Our results are crucial for the chip-scale self-referenced frequency combs with a simplified configuration., Comment: 9 pages, 5 figures, with 3 pages supplementary material
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- 2022
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21. Publisher Correction: The Miami Framework for ALS and related neurodegenerative disorders: an integrated view of phenotype and biology
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Benatar, Michael, Wuu, Joanne, Huey, Edward D., McMillan, Corey T., Petersen, Ronald C., Postuma, Ronald, McHutchison, Caroline, Dratch, Laynie, Arias, Jalayne J., Crawley, Anita, Houlden, Henry, McDermott, Michael P., Cai, Xueya, Thakur, Neil, Boxer, Adam, Rosen, Howard, Boeve, Bradley F., Dacks, Penny, Cosentino, Stephanie, Abrahams, Sharon, Shneider, Neil, Lingor, Paul, Shefner, Jeremy, Andersen, Peter M., Al-Chalabi, Ammar, and Turner, Martin R.
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- 2024
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22. Update on the Management of Brain Metastasis
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Singh, Karanvir, Saxena, Shreya, Khosla, Atulya A, McDermott, Michael W, Kotecha, Rupesh R, and Ahluwalia, Manmeet S
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Neurosciences ,Brain Cancer ,Cancer ,Brain Disorders ,Humans ,Brain Neoplasms ,Cranial Irradiation ,Neurosurgical Procedures ,Immunotherapy ,Radiosurgery ,Actionable mutations ,Brain metastases ,Systematic review ,Systemic therapy ,Targeted therapy ,Pharmacology and Pharmaceutical Sciences ,Public Health and Health Services ,Neurology & Neurosurgery ,Pharmacology and pharmaceutical sciences ,Biological psychology - Abstract
Brain metastases occur in almost one-third of adult patients with solid tumor malignancies and lead to considerable patient morbidity and mortality. The rising incidence of brain metastases has been ascribed to the development of better imaging and screening techniques and the formulation of better systemic therapies. Until recently, the multimodal management of brain metastases focused primarily on the utilization of neurosurgical techniques, with varying combinations of whole-brain radiation therapy and stereotactic radio-surgical procedures. Over the past 2 decades, in particular, the increment in knowledge pertaining to molecular genetics and the pathogenesis of brain metastases has led to significant developments in targeted therapies and immunotherapies. This review article highlights the recent updates in the management of brain metastases with an emphasis on novel systemic therapies.
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- 2022
23. A Remote Longitudinal Observational Study of Individuals at Genetic Risk for Parkinson Disease
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Jensen-Roberts, Stella, Myers, Taylor L, Auinger, Peggy, Cannon, Paul, Rowbotham, Helen M, Coker, Daniella, Chanoff, Eli, Soto, Julia, Pawlik, Meghan, Amodeo, Katherine, Sharma, Saloni, Valdovinos, Blanca, Wilson, Renee, Sarkar, Aayush, McDermott, Michael P, Alcalay, Roy N, Biglan, Kevin, Kinel, Daniel, Tanner, Caroline, Winter-Evans, Reni, Augustine, Erika F, Holloway, Robert G, Dorsey, E Ray, and Schneider, Ruth B
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Biological Sciences ,Biomedical and Clinical Sciences ,Clinical Sciences ,Genetics ,Brain Disorders ,Aging ,Parkinson's Disease ,Neurosciences ,Neurodegenerative ,Clinical Research ,Neurological ,Clinical sciences - Abstract
Background and objectivesTo recruit and characterize a national cohort of individuals who have a genetic variant (LRRK2 G2019S) that increases risk of Parkinson disease (PD), assess participant satisfaction with a decentralized, remote research model, and evaluate interest in future clinical trials.MethodsIn partnership with 23andMe, Inc., a personal genetics company, LRRK2 G2019S carriers with and without PD were recruited to participate in an ongoing 36-month decentralized, remote natural history study. We examined concordance between self-reported and clinician-determined PD diagnosis. We applied the Movement Disorder Society Prodromal Parkinson's Disease Criteria and asked investigators to identify concern for parkinsonism to distinguish participants with probable prodromal PD. We compared baseline characteristics of LRRK2 G2019S carriers with PD, with prodromal PD, and without PD.ResultsOver 15 months, we enrolled 277 LRRK2 G2019S carriers from 34 states. At baseline, 60 had self-reported PD (mean [SD] age 67.8 years [8.4], 98% White, 52% female, 80% Ashkenazi Jewish, and 67% with a family history of PD), and 217 did not (mean [SD] age 53.7 years [15.1], 95% White, 59% female, 73% Ashkenazi Jewish, and 57% with a family history of PD). Agreement between self-reported and clinician-determined PD status was excellent (κ = 0.94, 95% confidence interval 0.89-0.99). Twenty-four participants had prodromal PD; 9 met criteria for probable prodromal PD and investigators identified concern for parkinsonism in 20 cases. Compared with those without prodromal PD, participants with prodromal PD were older (63.9 years [9.0] vs 51.9 years [15.1], p < 0.001), had higher modified Movement Disorders Society-Unified Parkinson's Disease Rating Scale motor scores (5.7 [4.3] vs 0.8 [2.1], p < 0.001), and had higher Scale for Outcomes in PD for Autonomic Symptoms scores (11.5 [6.2] vs 6.9 [5.7], p = 0.002). Two-thirds of participants enrolled were new to research, 97% were satisfied with the overall study, and 94% of those without PD would participate in future preventive clinical trials.DiscussionAn entirely remote national cohort of LRRK2 G2019S carriers was recruited from a single site. This study will prospectively characterize a large LRRK2 G2019S cohort, refine a new model of clinical research, and engage new research participants willing to participate in future therapeutic trials.
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- 2022
24. Hospital Outcomes among COVID-19 Hospitalizations with Acute Ischemic Stroke: Cross-Sectional Study Results from California State Inpatient Database
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Rubens, Muni, Saxena, Anshul, Ramamoorthy, Venkataraghavan, Ahmed, Md Ashfaq, Zhang, Zhenwei, McGranaghan, Peter, Veledar, Emir, McDermott, Michael, and De Los Rios La Rosa, Felipe
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Biomedical and Clinical Sciences ,Clinical Sciences ,Stroke ,Lung ,2.4 Surveillance and distribution ,Aetiology ,Good Health and Well Being ,coronavirus ,death ,hospitalization ,ischemic stroke ,morbidity ,Neurosciences ,Psychology ,Cognitive Sciences ,Applied and developmental psychology ,Biological psychology - Abstract
Coronavirus disease 2019 (COVID-19) could be a risk factor for acute ischemic stroke (AIS) due to the altered coagulation process and hyperinflammation. This study examined the risk factors, clinical profile, and hospital outcomes of COVID-19 hospitalizations with AIS. This study was a retrospective analysis of data from California State Inpatient Database (SID) during 2019 and 2020. COVID-19 hospitalizations with age ≥ 18 years during 2020 and a historical cohort without COVID-19 from 2019 were included in the analysis. The primary outcomes studied were in-hospital mortality and discharge to destinations other than home. There were 91,420 COVID-19 hospitalizations, of which, 1027 (1.1%) had AIS. The historical control cohort included 58,083 AIS hospitalizations without COVID-19. Conditional logistic regression analysis showed that the odds of in-hospital mortality, discharge to destinations other than home, DVT, pulmonary embolism, septic shock, and mechanical ventilation were significantly higher among COVID-19 hospitalizations with AIS, compared to those without AIS. The odds of in-hospital mortality, DVT, pulmonary embolism, septic shock, mechanical ventilation, and respiratory failure were significantly higher among COVID-19 hospitalizations with AIS, compared to AIS hospitalizations without COVID-19. Although the prevalence of AIS was low among COVID-19 hospitalizations, it was associated with higher mortality and greater rates of discharges to destinations other than home.
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- 2022
25. Impact of COVID-19 on Intracranial Meningioma Resection: Results from California State Inpatient Database
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Rubens, Muni, Saxena, Anshul, Ramamoorthy, Venkataraghavan, Ahmed, Md Ashfaq, Zhang, Zhenwei, McGranaghan, Peter, Veledar, Emir, and McDermott, Michael
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Biomedical and Clinical Sciences ,Clinical Sciences ,Brain Disorders ,Patient Safety ,Neurosciences ,Good Health and Well Being ,coronavirus ,hospitalization ,intracranial meningioma resection ,morbidity ,mortality ,Oncology and Carcinogenesis ,Oncology and carcinogenesis - Abstract
PurposeTo assess the effects of COVID-19 on hospitalizations for intracranial meningioma resection using a large database.MethodsWe conducted a retrospective analysis of the California State Inpatient Database (SID) 2019 and 2020. All adult (18 years or older) hospitalizations were included for the analysis. The primary outcomes were trends in hospitalization for intracranial meningioma resection between 2019 and 2020. Secondary outcomes were Clavien-Dindo grade IV complications, in-hospital mortality, and prolonged length of stay, which was defined as length of stay ≥75 percentile.ResultsThere were 3,173,333 and 2,866,161 hospitalizations in 2019 and 2020, respectively (relative decrease, 9.7%), of which 921 and 788 underwent intracranial meningioma resection (relative decrease, 14.4%). In 2020, there were 94,114 admissions for COVID-19 treatment. Logistic regression analysis showed that year in which intracranial meningioma resection was performed did not show significant association with Clavien-Dindo grade IV complications and in-hospital mortality (OR, 1.23, 95% CI: 0.78-1.94) and prolonged length of stay (OR, 1.05, 95% CI: 0.84-1.32).ConclusionOur findings show that neurosurgery practice in the US successfully adapted to the unforeseen challenges posed by COVD-19 and ensured the best quality of care to the patients.
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- 2022
26. Rationale and Design of SCOT-HEART 2 Trial: CT Angiography for the Prevention of Myocardial Infarction
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McDermott, Michael, Meah, Mohammed N., Khaing, Phyo, Wang, Kang-Ling, Ramsay, Jennifer, Scott, Gillian, Rickman, Hannah, Burt, Tom, McGowan, Ian, Fairbairn, Timothy, Bucukoglu, Marise, Bull, Russell, Timmis, Adam, van Beek, Edwin J.R., Roditi, Giles, Adamson, Philip D., Lewis, Steff, Norrie, John, McKinstry, Brian, Guthrie, Bruce, Ritchie, Lewis, Mills, Nicholas L., Dweck, Marc R., Williams, Michelle C., and Newby, David E.
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- 2024
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27. Calcified Meningiomas Demonstrate Equivocal Grade, Proliferation, and Immediate Surgical Outcomes
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Umbach, Gray, Kanungo, Ishan, Quintana, Daniel, Choudhury, Abrar, Morshed, Ramin, Villanueva-Meyer, Javier, Theodosopoulos, Philip, Magill, Stephen T., McDermott, Michael, Raleigh, David, and Goldschmidt, Ezequiel
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- 2024
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28. Adoption of high-sensitivity cardiac troponin for risk stratification of patients with suspected myocardial infarction: a multicentre cohort study
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McDermott, Michael, Kimenai, Dorien M., Anand, Atul, Huang, Zengyi, Houston, Andrew, Williams, Sophie, Evison, Felicity, Gallier, Suzy, Carenzo, Catalina, Glampson, Ben, Hasan, Madina, Robertson, Alexander, Phillips, Thomas, Davis, Cai, Sapey, Elizabeth, Mayer, Erik, Mason, Suzanne, Stammers, Matthew, and Mills, Nicholas L.
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- 2024
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29. Opportunities and challenges for the development of “core outcome sets” in neuro-oncology
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Millward, Christopher P, Armstrong, Terri S, Barrington, Heather, Brodbelt, Andrew R, Bulbeck, Helen, Byrne, Anthony, Dirven, Linda, Gamble, Carrol, Grundy, Paul L, Islim, Abdurrahman I, Javadpour, Mohsen, Keshwara, Sumirat M, Krishna, Sandhya T, Mallucci, Conor L, Marson, Anthony G, McDermott, Michael W, Meling, Torstein R, Oliver, Kathy, Pizer, Barry, Plaha, Puneet, Preusser, Matthias, Santarius, Thomas, Srikandarajah, Nisaharan, Taphoorn, Martin JB, Watts, Colin, Weller, Michael, Williamson, Paula R, Zadeh, Gelareh, Najafabadi, Amir H Zamanipoor, and Jenkinson, Michael D
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Clinical Trials and Supportive Activities ,Rare Diseases ,Neurosciences ,Clinical Research ,Cancer ,Brain Disorders ,Brain Cancer ,Evaluation of treatments and therapeutic interventions ,6.9 Resources and infrastructure (treatment evaluation) ,Generic health relevance ,Adult ,Child ,Consensus ,Delphi Technique ,Humans ,Meningeal Neoplasms ,Meningioma ,Research Design ,Treatment Outcome ,clinical trial ,core outcome set ,effectiveness ,glioma ,meningioma ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Core Outcome Sets (COS) define minimum outcomes to be measured and reported in clinical effectiveness trials for a particular health condition/health area. Despite recognition as critical to clinical research design for other health areas, none have been developed for neuro-oncology. COS development projects should carefully consider: scope (how the COS should be used), stakeholders involved in development (including patients as both research partners and participants), and consensus methodologies used (typically a Delphi survey and consensus meeting), as well as dissemination plans. Developing COS for neuro-oncology is potentially challenging due to extensive tumor subclassification (including molecular stratification), different symptoms related to anatomical tumor location, and variation in treatment options. Development of a COS specific to tumor subtype, in a specific location, for a particular intervention may be too narrow and would be unlikely to be used. Equally, a COS that is applicable across a wider area of neuro-oncology may be too broad and therefore lack specificity. This review describes why and how a COS may be developed, and discusses challenges for their development, specific to neuro-oncology. The COS under development are briefly described, including: adult glioma, incidental/untreated meningioma, meningioma requiring intervention, and adverse events from surgical intervention for pediatric brain tumors.
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- 2022
30. The safety profile of Tumor Treating Fields (TTFields) therapy in glioblastoma patients with ventriculoperitoneal shunts
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Oberheim-Bush, Nancy Ann, Shi, Wenyin, McDermott, Michael W, Grote, Alexander, Stindl, Julia, and Lustgarten, Leonardo
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Brain Cancer ,Neurosciences ,Cancer ,Hydrocephalus ,Brain Disorders ,Glioblastoma ,Humans ,Neoplasm Recurrence ,Local ,Retrospective Studies ,Ventriculoperitoneal Shunt ,Tumor Treating Fields therapy ,TTFields ,Ventriculoperitoneal shunt ,Safety ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
IntroductionTumor Treating Fields (TTFields, 200 kHz) therapy is a noninvasive, locoregional cancer treatment approved for use in newly diagnosed glioblastoma (GBM), recurrent GBM, and malignant pleural mesothelioma. GBM patients with hydrocephalus may require implantation of a ventriculoperitoneal (VP) shunt, however, the current TTFields therapy label does not include the use of VP shunts in GBM patients due to insufficient safety data. This analysis evaluates the safety of TTFields therapy use in this population.MethodsUnsolicited post-marketing global surveillance data from patients with GBM and a VP shunt (programmable/non-programmable) who received TTFields therapy between November 2012-April 2021 were retrospectively analyzed. Adverse events (AEs) were assessed using the Medical Dictionary for Regulatory Activities version 24.0.ResultsOverall, 156 patients with VP shunts were identified and included in this analysis. In total, 77% reported ≥ 1 AE; the most common TTFields therapy-related AEs were non-serious and localized, beneath-array skin AEs (43%). The incidence and categories of AEs were comparable between patients with or without VP shunts. Six patients with VP shunts experienced seven serious TTFields therapy-related AEs: skin erosion at the shunt site (n = 3); wound dehiscence at the shunt site (n = 2) and at the resection scar (n = 2). No shunt malfunctions were deemed related to TTFields therapy.ConclusionsIn the real-world setting, TTFields therapy in GBM patients with VP shunts demonstrated good tolerability and a favorable safety profile. There was no evidence that TTFields therapy disrupted VP shunt effectiveness. These results suggest TTFields therapy may be safely used in patients with VP shunts.
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- 2022
31. Zero Setup Margin Mask versus Frame Immobilization during Gamma Knife® Icon™ Stereotactic Radiosurgery for Brain Metastases
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Kutuk, Tugce, Kotecha, Rupesh, Tolakanahalli, Ranjini, Wieczorek, D Jay J, Lee, Yongsook C, Ahluwalia, Manmeet S, Hall, Matthew D, McDermott, Michael W, Appel, Haley, Gutierrez, Alonso N, Mehta, Minesh P, and Tom, Martin C
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Brain Disorders ,SRS ,brain metastases ,frame ,frameless ,mask ,radiosurgery ,zero setup margin ,Oncology and carcinogenesis - Abstract
We compared the clinical outcomes of BM treated with mask immobilization with zero-SM (i.e., zero-PTV) to standard zero-SM frame immobilization SRS. Consecutive patients with BM, 0.5−2.0 cm in maximal diameter, treated with single-fraction SRS (22−24 Gy) during March 2019−February 2021 were included. Univariable and multivariable analysis were performed using the Kaplan−Meier method and Cox proportional hazards regression. A total of 150 patients with 453 BM met inclusion criteria. A total of 129 (28.5%) lesions were treated with a zero-SM mask immobilization and 324 (71.5%) with zero-SM frame immobilization. Frame immobilization treatments were associated with a higher proportion of gastrointestinal and fewer breast-cancer metastases (p = 0.024), and a higher number of treated lesions per SRS course (median 7 vs. 3; p < 0.001). With a median follow up of 15 months, there was no difference in FFLF between the mask and frame immobilization groups on univariable (p = 0.29) or multivariable analysis (p = 0.518). Actuarial FFLF at 1 year was 90.5% for mask and 92% for frame immobilization (p = 0.272). Radiation necrosis rates at 1 year were 12.5% for mask and 4.1% for frame immobilization (p = 0.502). For BM 0.5−2.0 cm in maximal diameter treated with single-fraction SRS using 22−24 Gy, mask immobilization with zero SM produces comparable clinical outcomes to frame immobilization. The initial findings support omitting a SM when using mask immobilization with this treatment approach on a Gamma Knife® Icon™.
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- 2022
32. Comparison of Outcomes following Primary and Repeat Resection of Craniopharyngioma
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Aabedi, Alexander A, Young, Jacob S, Phelps, Ryan RL, Winkler, Ethan A, McDermott, Michael W, and Theodosopoulos, Philip V
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Biomedical and Clinical Sciences ,Clinical Sciences ,Cancer ,Clinical Research ,Patient Safety ,Evaluation of treatments and therapeutic interventions ,6.4 Surgery ,craniopharyngioma ,reoperation ,endonasal ,transcranial ,maximal safe resection ,Neurology & Neurosurgery ,Dentistry - Abstract
Introduction The management of recurrent craniopharyngioma is complex with limited data to guide decision-making. Some reports suggest reoperation should be avoided due to an increased complication profile, while others have demonstrated that safe reoperation can be performed. For other types of skull base lesions, maximal safe resection followed by adjuvant therapy has replaced radical gross total resection due to the favorable morbidity profiles. Methods Seventy-one patients underwent resection over a 9-year period for craniopharyngioma and were retrospectively reviewed. Patients were separated into primary resection and reoperation cohorts and stratified by surgical approach (endonasal vs. cranial) and survival analyses were performed based on cohort and surgical approach. Results Fifty patients underwent primary resection, while 21 underwent reoperation for recurrence. Fifty endonasal transsphenoidal surgeries and 21 craniotomies were performed. Surgical approaches were similarly distributed across cohorts. Subtotal resection was achieved in 83% of all cases. There were no differences in extent of resection, visual outcomes, subsequent neuroendocrine function, and complications across cohorts and surgical approaches. The median time to recurrence was 87 months overall, and there were no differences by cohort and approach. The 5-year survival rate was 81.1% after reoperation versus 93.2% after primary resection. Conclusion Compared with primary resection, reoperation for craniopharyngioma recurrence is associated with similar functional and survival outcomes in light of individualized surgical approaches. Maximal safe resection followed by adjuvant radiotherapy for residual tumor likely preserves vision and endocrine function without sacrificing overall patient survival.
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- 2022
33. Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities
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Choudhury, Abrar, Magill, Stephen T, Eaton, Charlotte D, Prager, Briana C, Chen, William C, Cady, Martha A, Seo, Kyounghee, Lucas, Calixto-Hope G, Casey-Clyde, Tim J, Vasudevan, Harish N, Liu, S John, Villanueva-Meyer, Javier E, Lam, Tai-Chung, Pu, Jenny Kan-Suen, Li, Lai-Fung, Leung, Gilberto Ka-Kit, Swaney, Danielle L, Zhang, Michael Y, Chan, Jason W, Qiu, Zhixin, Martin, Michael V, Susko, Matthew S, Braunstein, Steve E, Bush, Nancy Ann Oberheim, Schulte, Jessica D, Butowski, Nicholas, Sneed, Penny K, Berger, Mitchel S, Krogan, Nevan J, Perry, Arie, Phillips, Joanna J, Solomon, David A, Costello, Joseph F, McDermott, Michael W, Rich, Jeremy N, and Raleigh, David R
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Biological Sciences ,Genetics ,Brain Cancer ,Cancer ,Biotechnology ,Neurosciences ,Brain Disorders ,Rare Diseases ,Orphan Drug ,Cancer Genomics ,Human Genome ,2.1 Biological and endogenous factors ,DNA Methylation ,Humans ,Meningeal Neoplasms ,Meningioma ,Neurofibromin 2 ,Proteomics ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Meningiomas are the most common primary intracranial tumors. There are no effective medical therapies for meningioma patients, and new treatments have been encumbered by limited understanding of meningioma biology. Here, we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic and single-cell approaches to show meningiomas are composed of three DNA methylation groups with distinct clinical outcomes, biological drivers and therapeutic vulnerabilities. Merlin-intact meningiomas (34%) have the best outcomes and are distinguished by NF2/Merlin regulation of susceptibility to cytotoxic therapy. Immune-enriched meningiomas (38%) have intermediate outcomes and are distinguished by immune infiltration, HLA expression and lymphatic vessels. Hypermitotic meningiomas (28%) have the worst outcomes and are distinguished by convergent genetic and epigenetic mechanisms driving the cell cycle and resistance to cytotoxic therapy. To translate these findings into clinical practice, we show cytostatic cell cycle inhibitors attenuate meningioma growth in cell culture, organoids, xenografts and patients.
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- 2022
34. Emotion Dysregulation, Help-Seeking Attitudes, and Posttraumatic Stress Disorder Symptoms: A Structural Equation Model
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Limowski, Anne R., DeJesus, Christopher R., Ward-Ciesielski, Erin F., and McDermott, Michael J.
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Objective: Most college students have experienced an adverse event in their lifetime, yet help-seeking rates remain low. This study seeks to understand psychological factors that might contribute to delays in treatment initiation among trauma-affected students. Participants: Our sample consisted of 531 undergraduate students of which 27% scored above the clinical cutoff for PTSD using the PTSD Checklist for DSM-5 (PCL-5). Methods: This cross-sectional study explored relationships among help-seeking attitudes, emotion dysregulation, and PTSD symptoms using structural equation modeling. Results: Findings demonstrated that individuals with more severe emotion dysregulation had more severe PTSD symptoms and held more negative attitudes toward seeking help. Conclusions: Individuals who are the most in need of treatment hold attitudes that may impede help-seeking. We discuss clinical implications and ways college counseling centers can maximize outreach and programming efforts to increase treatment initiation and engagement.
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- 2023
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35. Uniform or Sex-Specific Cardiac Troponin Thresholds to Rule Out Myocardial Infarction at Presentation
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Mills, Nicholas L., Strachan, Fiona E., Tuck, Christopher, Anand, Atul, Akinlade, Olawale Mathias, Barker, Stephanie, Blades, Jennifer, Boeddinghaus, Jasper, Bularga, Anda, de Bakker, Marie, Chapman, Andrew R., Doudesis, Dimitrios, Ferry, Amy V., Fujisawa, Takeshi, Georgiev, Konstantin, Kimenai, Dorien M., Lee, Kuan Ken, Lyell, Iona, Li, Ziwen, Lowry, Matthew TH., McKinlay, Lynn, McDermott, Michael, McPherson, Jean, Mendusic, Filip, Sorbie, Andrew, Souter, Grace, Schulberg, Stacey D., Taggart, Caelan, Thurston, Alexander JF., Tew, Yong Yong, Perez-Vicencio, Daniel, Wang, Yiqing, Wereski, Ryan, Williams, Kelly, Newby, David E., Fox, Keith AA., Berry, Colin, Walker, Simon, Weir, Christopher J., Ford, Ian, Gray, Alasdair, Collinson, Paul O., Apple, Fred S., Reid, Alan, Cruikshank, Anne, Findlay, Iain, Amoils, Shannon, McAllister, David A., Maguire, Donogh, Stevens, Jennifer, Norrie, John, Shah, Anoop SV., Andrews, Jack PM., Adamson, Philip D., Moss, Alastair, Anwar, Mohamed S., Hung, John, Malo, Jonathan, Fischbacher, Colin M., Croal, Bernard L., Leslie, Stephen J., Keerie, Catriona, Parker, Richard A., Walker, Allan, Harkess, Ronnie, Wackett, Tony, Weir, Christopher, Armstrong, Roma, Stirling, Laura, MacDonald, Claire, Sadat, Imran, Finlay, Frank, Harrison, Kathy, Linksted, Pamela, Lavenberg, Stephen, Lowry, Matthew T.H., Tuck, Chris, and Shah, Anoop S.V.
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- 2024
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36. RANS turbulence models for FENE-P viscoelastic fluids
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McDermott, Michael Raymond, de Boer, Greg, Wilson, Mark, Harbottle, David, and Charpentier, Thibaut
- Abstract
The development of robust turbulent viscoelastic models to predict drag reducing behaviour of polymer additives within industrial flows is highly sought after. The main objective of this thesis is to develop Reynolds Averaged Navier-Stokes (RANS) models based on the Finitely Extensible Nonlinear Elastic Peterlin (FENE-P) rheological constitutive model for the polymer chains, to predict mean features of drag reducing flows. A DNS database from multiple literature sources is collated to validate the closure models 'a priori', along with the performance of the models' mean field predictions. A new finite volume C++ computational solver is adapted in the OpenFOAM software to include the FENE-P parameters within the pre-existing turbulence class structure. A robust framework is developed for fully developed channel flow and square duct cases within foam-extend/4.0. A novel application of the groovyBC functionality is used to develop boundary conditions for the conformation tensor field. Two isotropic models (k-epsilon and k-omega) are developed in the context of fully-developed channel flow which improve upon previous models. This is achieved with a modified damping function which mimics the viscoelastic effects on the turbulent redistribution process. The non-linear terms in the constitutive equation are also greatly improved with robustness and stability, by removing friction velocity dependence and reducing complexity. The model prediction span a larger DNS data set for friction Reynolds number, Reτ₀, Weissenberg number, Wiτ₀, maximum polymer extension, L², and concentration variation, beta. An anisotropic k-epsilon-v²-f model is also developed to predict turbulent viscoelastic flow features in fully-developed channel flow and square ducts, via an extension to the Newtonian model. The non-linear closures are developed based on the premise that polymer stretching from near wall turbulent shears coincides and aligns with the mean vorticity direction, tᵢ, and redistributes energy to the wall normal direction, nᵢ, in a similar process to the Reynolds stress tensor. The predictions for the model include fully developed channel flow and square ducts, with flow features for the conformation tensor, Reynolds stresses, mean velocity (and the bending of the isolines), along with the shift of the secondary flow vorticity centre away from the wall.
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- 2022
37. Retrosigmoid Craniectomy with a Layered Soft Tissue Dissection and Hydroxyapatite Reconstruction: Technical Note, Surgical Video, Regional Anatomy, and Outcomes
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Magill, Stephen T, Lee, Young M, Rubio, Roberto R, Nguyen, Minh P, Heilman, Carl B, and McDermott, Michael W
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Biomedical and Clinical Sciences ,Clinical Sciences ,retrosigmoid ,cerebellopontine angle ,anatomy ,neuroanatomy ,CSF leak ,suboccipital ,retromastoid ,hydroxyapatite ,reconstruction ,Neurology & Neurosurgery ,Dentistry - Abstract
Introduction There are many reported modifications to the retrosigmoid approach including variations in skin incisions, soft tissue dissection, bone removal/replacement, and closure. Objective The aim of this study was to report the technical nuances developed by two senior skull base surgeons for retrosigmoid craniectomy with reconstruction and provide anatomic dissections, surgical video, and outcomes. Methods The regional soft tissue and bony anatomy as well as the steps for our retrosigmoid craniectomy were recorded with photographs, anatomic dissections, and video. Records from 2017 to 2019 were reviewed to determine the incidence of complications after the authors began using the described approach. Results Dissections of the relevant soft tissue, vascular, and bony structures were performed. Key surgical steps are (1) a retroauricular C-shaped skin incision, (2) developing a skin and subgaleal tissue flap of equal thickness above the fascia over the temporalis and sub-occipital muscles, (3) creation of subperiosteal soft tissue planes over the top of the mastoid and along the superior nuchal line to expose the suboccipital region, (4) closure of the craniectomy defect with in-lay titanium mesh and overlay hydroxyapatite cranioplasty, and (5) reapproximation of the soft tissue edges during closure. Complications in 40 cases were pseudomeningocele requiring shunt ( n = 3, 7.5%), wound infection ( n = 1, 2.5%), and aseptic meningitis ( n = 1, 2.5%). There were no incisional cerebrospinal fluid leaks. Conclusion The relevant regional anatomy and a revised technique for retrosigmoid craniectomy with reconstruction have been presented with acceptable results. Readers can consider this technique when using the retrosigmoid approach for pathology in the cerebellopontine angle.
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- 2022
38. Vascularized Pericranial Flap for Endonasal Anterior Skull Base Reconstruction
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Giurintano, Jonathan, McDermott, Michael W, and El-Sayed, Ivan H
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Biomedical and Clinical Sciences ,Clinical Sciences ,Dental/Oral and Craniofacial Disease ,Cancer ,Brain Disorders ,Anterior ,skull base ,reconstruction ,pericranial ,flap ,Neurology & Neurosurgery ,Dentistry - Abstract
Introduction As the limits of advanced skull base malignancies that can be managed through an endoscopic endonasal approach continue to be expanded, the resultant anterior skull base defects are of increasing size and complexity. In the absence of nasoseptal or turbinate flaps, the vascularized pericranial flap has been employed at our institution with excellent results. Objective The study aimed to review the outcomes of patients who underwent endonasal anterior craniofacial resection with anterior skull base reconstruction using a vascularized pericranial flap. Design Retrospective chart review of patients treated by the University of California - San Francisco minimally invasive skull base service from the years 2011 to 2017. Average duration of follow-up was 16.4 months. Setting This study was conducted at Academic tertiary referral center. Participants A total of nine patients with advanced anterior cranial base malignancies were identified who were treated with a minimally invasive, endoscopic anterior craniofacial resection from the years 2011 to 2017. Due to the nature of the resection in these patients, nasoseptal flaps and inferior/middle turbinate flaps were unavailable or insufficient for anterior skull base defect repair. Each patient underwent reconstruction of the anterior cranial base defect using an anteriorly based pericranial flap harvested by bicoronal incision, and tunneled anteriorly to the nasal cavity through a frontoethmoidal incision.
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- 2022
39. Preventing amyotrophic lateral sclerosis: insights from pre-symptomatic neurodegenerative diseases
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Benatar, Michael, Wuu, Joanne, McHutchison, Caroline, Postuma, Ronald B, Boeve, Bradley F, Petersen, Ronald, Ross, Christopher A, Rosen, Howard, Arias, Jalayne J, Fradette, Stephanie, McDermott, Michael P, Shefner, Jeremy, Stanislaw, Christine, Abrahams, Sharon, Cosentino, Stephanie, Andersen, Peter M, Finkel, Richard S, Granit, Volkan, Grignon, Anne-Laure, Rohrer, Jonathan D, McMillan, Corey T, Grossman, Murray, Al-Chalabi, Ammar, Turner, Martin R, Arias, Jalayne, Boeve, Bradley, Dave, Kuldip, Ferguson, Toby, Floeter, Mary-Kay, Rohrer, Jonathan, Gendron, Tania, Gubitz, Amelie, Kaufman, Petra, Le Ber, Isabelle, Lee, Suzee, Malaspina, Andrea, McMillan, Corey, Nicholson, Katie, Postuma, Ronald, Robinson, Richard, Ross, Christopher, Tatton, Nadine, Thakur, Neil, Turner, Martin, and Weishaupt, Jochen
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Biomedical and Clinical Sciences ,Health Sciences ,Psychology ,Neurodegenerative ,Dementia ,Genetics ,Alzheimer's Disease ,Rare Diseases ,Aging ,Prevention ,Brain Disorders ,Neurosciences ,Clinical Research ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,ALS ,Acquired Cognitive Impairment ,Biotechnology ,Detection ,screening and diagnosis ,2.1 Biological and endogenous factors ,4.1 Discovery and preclinical testing of markers and technologies ,Aetiology ,Neurological ,Alzheimer Disease ,Amyotrophic Lateral Sclerosis ,Asymptomatic Diseases ,Frontotemporal Dementia ,Humans ,Neurodegenerative Diseases ,neurodegeneration ,amyotrophic lateral sclerosis ,pre-symptomatic ,disease prevention ,First International Pre-Symptomatic ALS Workshop ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Neurology & Neurosurgery ,Biomedical and clinical sciences ,Health sciences - Abstract
Significant progress has been made in understanding the pre-symptomatic phase of amyotrophic lateral sclerosis. While much is still unknown, advances in other neurodegenerative diseases offer valuable insights. Indeed, it is increasingly clear that the well-recognized clinical syndromes of Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy and frontotemporal dementia are also each preceded by a pre-symptomatic or prodromal period of varying duration, during which the underlying disease process unfolds, with associated compensatory changes and loss of inherent system redundancy. Key insights from these diseases highlight opportunities for discovery in amyotrophic lateral sclerosis. The development of biomarkers reflecting amyloid and tau has led to a shift in defining Alzheimer's disease based on inferred underlying histopathology. Parkinson's disease is unique among neurodegenerative diseases in the number and diversity of non-genetic biomarkers of pre-symptomatic disease, most notably REM sleep behaviour disorder. Huntington's disease benefits from an ability to predict the likely timing of clinically manifest disease based on age and CAG-repeat length alongside reliable neuroimaging markers of atrophy. Spinal muscular atrophy clinical trials have highlighted the transformational value of early therapeutic intervention, and studies in frontotemporal dementia illustrate the differential role of biomarkers based on genotype. Similar advances in amyotrophic lateral sclerosis would transform our understanding of key events in pathogenesis, thereby dramatically accelerating progress towards disease prevention. Deciphering the biology of pre-symptomatic amyotrophic lateral sclerosis relies on a clear conceptual framework for defining the earliest stages of disease. Clinically manifest amyotrophic lateral sclerosis may emerge abruptly, especially among those who harbour genetic mutations associated with rapidly progressive amyotrophic lateral sclerosis. However, the disease may also evolve more gradually, revealing a prodromal period of mild motor impairment preceding phenoconversion to clinically manifest disease. Similarly, cognitive and behavioural impairment, when present, may emerge gradually, evolving through a prodromal period of mild cognitive impairment or mild behavioural impairment before progression to amyotrophic lateral sclerosis. Biomarkers are critically important to studying pre-symptomatic amyotrophic lateral sclerosis and essential to efforts to intervene therapeutically before clinically manifest disease emerges. The use of non-genetic biomarkers, however, presents challenges related to counselling, informed consent, communication of results and limited protections afforded by existing legislation. Experiences from pre-symptomatic genetic testing and counselling, and the legal protections against discrimination based on genetic data, may serve as a guide. Building on what we have learned-more broadly from other pre-symptomatic neurodegenerative diseases and specifically from amyotrophic lateral sclerosis gene mutation carriers-we present a road map to early intervention, and perhaps even disease prevention, for all forms of amyotrophic lateral sclerosis.
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- 2022
40. Evaluation of the impact of pre-operative stereotactic radiotherapy on the acute changes in histopathologic and immune marker profiles of brain metastases
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Kotecha, Rupesh, Tonse, Raees, Menendez, Miguel A Ramirez, Williams, Andre, Diaz, Zuanel, Tom, Martin C, Hall, Matthew D, Mehta, Minesh P, Alvarez, Reinier, Siomin, Vitaly, Odia, Yazmin, Ahluwalia, Manmeet S, and McDermott, Michael W
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Brain Disorders ,Cancer ,Brain Cancer ,Neurosciences ,Clinical Research ,Rare Diseases ,Biomarkers ,Brain Neoplasms ,Humans ,Necrosis ,Radiosurgery ,Retrospective Studies ,Vascular Endothelial Growth Factor A - Abstract
The unique acute effects of the large fractional doses that characterize stereotactic radiosurgery (SRS) or radiotherapy (SRT), specifically in terms of antitumor immune cellular processes, vascular damage, tumor necrosis, and apoptosis on brain metastasis have yet to be empirically demonstrated. The objective of this study is to provide the first in-human evaluation of the acute biological effects of SRS/SRT in resected brain metastasis. Tumor samples from patients who underwent dose-escalated preoperative SRT followed by resection with available non-irradiated primary tumor tissues were retrieved from our institutional biorepository. All primary tumors and irradiated metastases were evaluated for the following parameters: tumor necrosis, T-cells, natural killer cells, vessel density, vascular endothelial growth factor, and apoptotic factors. Twenty-two patients with irradiated and resected brain metastases and paired non-irradiated primary tumor samples met inclusion criteria. Patients underwent a median preoperative SRT dose of 18 Gy (Range: 15-20 Gy) in 1 fraction, with 3 patients receiving 27-30 Gy in 3-5 fractions, followed by resection within median interval of 67.8 h (R: 18.25-160.61 h). The rate of necrosis was significantly higher in irradiated brain metastases than non-irradiated primary tumors (p
- Published
- 2022
41. Nonsense mutation in the novel PERCC1 gene as a genetic cause of congenital diarrhea and enteropathy
- Author
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Marek-Yagel, Dina, Stenke, Emily, Pode-Shakked, Ben, Dunne, Cara, Crushell, Ellen, Bryce-Smith, Anthea, McDermott, Michael, O’Sullivan, Maureen J., Veber, Alvit, Krishnamurthy, Mansa, Wells, James M., Anikster, Yair, and Bourke, Billy
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- 2023
- Full Text
- View/download PDF
42. Adaptive dose-response studies to establish proof-of-concept in learning-phase clinical trials
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Ma, Shiyang and McDermott, Michael P.
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Statistics - Methodology - Abstract
In learning-phase clinical trials in drug development, adaptive designs can be efficient and highly informative when used appropriately. In this article, we extend the multiple comparison procedures with modeling techniques (MCP-Mod) procedure with generalized multiple contrast tests (GMCTs) to two-stage adaptive designs for establishing proof-of-concept. The results of an interim analysis of first-stage data are used to adapt the candidate dose-response models and the dosages studied in the second stage. GMCTs are used in both stages to obtain stage-wise p-values, which are then combined to determine an overall p-value. An alternative approach is also considered that combines the t-statistics across stages, employing the conditional rejection probability (CRP) principle to preserve the Type I error probability. Simulation studies demonstrate that the adaptive designs are advantageous compared to the corresponding tests in a non-adaptive design if the selection of the candidate set of dose-response models is not well informed by evidence from preclinical and early-phase studies.
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- 2021
43. Systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance
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Tonse, Raees, Rubens, Muni, Appel, Haley, Tom, Martin C, Hall, Matthew D, Odia, Yazmin, McDermott, Michael W, Ahluwalia, Manmeet S, Mehta, Minesh P, and Kotecha, Rupesh
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Lung Cancer ,Lung ,Brain Disorders ,Cancer ,Neurosciences ,Clinical Research ,Brain ,Discordance ,EGFR ,KRAS ,Metastasis ,Receptor ,Clinical sciences ,Oncology and carcinogenesis - Abstract
BackgroundTreatment paradigms for metastatic non-small cell lung cancer are increasingly based on biomarker-driven therapies, with the most common alteration being mutation in the epidermal growth factor receptor (EGFR). Change in expression of such biomarkers could have a profound impact on the choice and efficacy of a selected targeted therapeutic, and hence the objective of this study was to analyze discordance in EGFR status in patients with lung cancer brain metastasis (LCBM).MethodsUsing PRISMA guidelines, a systematic review was performed of series in the Medline database of biopsied or resected LCBM published before May, 2020. Key words included "lung cancer" and "brain metastasis" combined with "epidermal growth factor receptor/EGFR," and "receptor conversion/discordance or concordance." Weighted random effects models were used to calculate pooled estimates.ResultsWe identified 501 patients from 19 full-text articles for inclusion in this study. All patients underwent biopsy or resection of at least one intracranial lesion to compare to the primary tumor. On primary/LCBM comparison, the weighted pooled estimate for overall EGFR receptor discordance was 10% (95% CI 5-17%). The weighted effects model estimated a gain of an EGFR mutation in a brain metastases in patients with negative primary tumors was 7% (95% CI 4-12%). Alternatively, the weighted effects model estimate of loss of an EGFR mutation in patients with detected mutations in the primary tumor was also 7% (95% CI 4-10%). KRAS testing was also performed on both primary tumors and LCBM in a subset of 148 patients. The weighted effects estimate of KRAS-mutation discordance among LCBM compared to primary tumors was 13% (95% CI 5-27%). The weighted effects estimated of KRAS gain and loss in LCBM was 10% (95% CI 6-18%) and 8% (95% CI 4-15%), respectively. Meta-regression analysis did not find any association with any factors that could be associated with discordances.ConclusionsEGFR and KRAS mutation status discordance between primary tumor and LCBM occurs in approximately 10% and 13% of patients, respectively. Evaluation of LCBM receptor status is key to biomarker-driven targeted therapy for intracranial disease and awareness of subtype switching is critical for those patients treated with systemic therapy alone for intracranial disease.
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- 2021
44. Impact of MRI timing on tumor volume and anatomic displacement for brain metastases undergoing stereotactic radiosurgery.
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Kutuk, Tugce, Tolakanahalli, Ranjini, Williams, Andre, Tom, Martin C, Vadhan, Jason D, Appel, Haley, Hall, Matthew D, Wieczorek, D Jay J, Davis, Stephen, McDermott, Michael W, Ahluwalia, Manmeet S, Mehta, Minesh P, Gutierrez, Alonso N, and Kotecha, Rupesh
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Brain Disorders ,Rare Diseases ,Neurosciences ,Clinical Research ,Brain Cancer ,Biomedical Imaging ,MRI timing ,SRS ,brain metastasis ,radiosurgery ,tumor dynamics ,Oncology and carcinogenesis - Abstract
BackgroundThe objective of this study was to evaluate the impact of the time interval between planning imaging and stereotactic radiosurgery (SRS) delivery on tumor volumes and spatial anatomic displacements of brain metastases (BM).MethodsConsecutive patients diagnosed with BM treated with SRS over a 3-year period were evaluated. Only patients who underwent an institutionally standardized diagnostic MRI (MRI-1) and a treatment planning MRI (MRI-2) were included. The impact of histology, inter-scan time interval, lesion location, tumor volume, and diameter were evaluated on final lesion diameter, volume, anatomic displacement, and ultimate need for change in management (ie, expanding margins, rescanning).Results101 patients (531 lesions) with a median inter-scan time interval of 8 days (range: 1-42 days) met the inclusion criteria. The median percentage increase in BM diameter and volume were 9.5% (IQR: 2.25%-24.0%) and 20% (IQR: 0.7%-66.7%). Overall, 147 lesions (27.7%) in 57 patients (56.4%) required a change in management. There was a statistically significant relationship between initial tumor diameter (cm) and change in management (OR: 2.69, 95% CI: 1.93-3.75; P < .001). Each day between MRI-1 and MRI-2 was associated with a change in management with an OR of 1.05 (95% CI: 1.03-1.07; P < .001).ConclusionsChanges in tumor diameter, volume, and spatial position occur as a function of time. Planning imaging for SRS is recommended to occur in close temporal proximity to treatment; for those with delays, a larger setup margin may need to be used to ensure tumor coverage and account for positional changes.
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- 2021
45. Temozolomide-induced hypermutation is associated with distant recurrence and reduced survival after high-grade transformation of low-grade IDH-mutant gliomas
- Author
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Yu, Yao, Villanueva-Meyer, Javier, Grimmer, Matthew R, Hilz, Stephanie, Solomon, David A, Choi, Serah, Wahl, Michael, Mazor, Tali, Hong, Chibo, Shai, Anny, Phillips, Joanna J, Wainer, Bruce H, McDermott, Michael, Haas-Kogan, Daphne, Taylor, Jennie W, Butowski, Nicholas, Clarke, Jennifer L, Berger, Mitchel S, Molinaro, Annette M, Chang, Susan M, Costello, Joseph F, and Bush, Nancy Ann Oberheim
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Brain Disorders ,Neurosciences ,Brain Cancer ,Cancer ,Rare Diseases ,Orphan Drug ,Clinical Research ,Brain ,Brain Neoplasms ,Glioma ,Humans ,Mutation ,Neoplasm Recurrence ,Local ,Temozolomide ,hypermutation ,IDH-mutant ,low-grade glioma ,temozolomide ,tumor mutational burden ,IDH-mutant ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundChemotherapy improves overall survival after surgery and radiotherapy for newly diagnosed high-risk IDH-mutant low-grade gliomas (LGGs), but a proportion of patients treated with temozolomide (TMZ) will develop recurrent tumors with TMZ-induced hypermutation. We aimed to determine the prevalence of TMZ-induced hypermutation at recurrence and prognostic implications.MethodsWe sequenced recurrent tumors from 82 patients with initially low-grade IDH-mutant gliomas who underwent reoperation and correlated hypermutation status with grade at recurrence and subsequent clinical outcomes.ResultsHypermutation was associated with high-grade disease at the time of reoperation (OR 12.0 95% CI 2.5-115.5, P = .002) and was identified at transformation in 57% of recurrent LGGs previously exposed to TMZ. After anaplastic (grade III) transformation, hypermutation was associated with shorter survival on univariate and multivariate analysis (HR 3.4, 95% CI 1.2-9.9, P = .024), controlling for tumor grade, subtype, age, and prior radiotherapy. The effect of hypermutation on survival after transformation was validated in an independent, published dataset. Hypermutated (HM) tumors were more likely to develop discontiguous foci of disease in the brain and spine (P = .003). To estimate the overall incidence of high-grade transformation among low-grade IDH-mutant tumors, data from a phase II trial of TMZ for LGG were analyzed. Eight-year transformation-free survival was 53.8% (95% CI 42.8-69.2), and 61% of analyzed transformed cases were HM.ConclusionsTMZ-induced hypermutation is a common event in transformed LGG previously treated with TMZ and is associated with worse prognosis and development of discontiguous disease after recurrence. These findings impact tumor classification at recurrence, prognostication, and clinical trial design.
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- 2021
46. Factors associated with unplanned readmissions and costs following resection of brain metastases in the United States
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Tonse, Raees, Townsend, Alexandra, Rubens, Muni, Siomin, Vitaly, McDermott, Michael W, Tom, Martin C, Hall, Matthew D, Odia, Yazmin, Ahluwalia, Manmeet S, Mehta, Minesh P, and Kotecha, Rupesh
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Prevention ,Patient Safety ,Neurosciences ,Brain Disorders ,Health Services ,Good Health and Well Being ,Brain Neoplasms ,Cohort Studies ,Craniotomy ,Cross-Sectional Studies ,Databases ,Factual ,Female ,Humans ,Male ,Patient Readmission ,Postoperative Complications ,Risk Factors ,United States - Abstract
The purpose of this study was to critically analyze the risk of unplanned readmission following resection of brain metastasis and to identify key risk factors to allow for early intervention strategies in high-risk patients. We analyzed data from the Nationwide Readmissions Database (NRD) from 2010-2014, and included patients who underwent craniotomy for brain metastasis, identified using ICD-9-CM diagnosis (198.3) and procedure (01.59) codes. The primary outcome of the study was unplanned 30-day all-cause readmission rate. Secondary outcomes included reasons and costs of readmissions. Hierarchical logistic regression model was used to identify the factors associated with 30-day readmission following craniotomy for brain metastasis. During the study period, 44,846 index hospitalizations occurred for patients who underwent resection of brain metastasis. In this cohort, 17.8% (n = 7,965) had unplanned readmissions within the first 30 days after discharge from the index hospitalization. The readmission rate did not change significantly during the five-year study period (p-trend = 0.286). The median per-patient cost for 30-day unplanned readmission was $11,109 and this amounted to a total of $26.4 million per year, which extrapolates to a national expenditure of $269.6 million. Increasing age, male sex, insurance status, Elixhauser comorbidity index, length of stay, teaching status of the hospital, neurological complications and infectious complications were associated with 30-day readmission following discharge after an index admission for craniotomy for brain metastasis. Unplanned readmission rates after resection of brain metastasis remain high and involve substantial healthcare expenditures. Developing tools and interventions to prevent avoidable readmissions could focus on the high-risk patients as a future strategy to decrease substantial healthcare expense.
- Published
- 2021
47. Machine Learning for Myocardial Infarction Compared With Guideline-Recommended Diagnostic Pathways
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Boeddinghaus, Jasper, Doudesis, Dimitrios, Lopez-Ayala, Pedro, Lee, Kuan Ken, Koechlin, Luca, Wildi, Karin, Nestelberger, Thomas, Borer, Raphael, Miró, Òscar, Martin-Sanchez, F. Javier, Strebel, Ivo, Rubini Giménez, Maria, Keller, Dagmar I., Christ, Michael, Bularga, Anda, Li, Ziwen, Ferry, Amy V., Tuck, Chris, Anand, Atul, Gray, Alasdair, Mills, Nicholas L., Mueller, Christian, Richards, A. Mark, Pemberton, Chris, Troughton, Richard W., Aldous, Sally J., Brown, Anthony F.T., Dalton, Emily, Hammett, Chris, Hawkins, Tracey, O’Kane, Shanen, Parke, Kate, Ryan, Kimberley, Schluter, Jessica, Barker, Stephanie, Blades, Jennifer, Chapman, Andrew R., Fujisawa, Takeshi, Kimenai, Dorien M., McDermott, Michael, Newby, David E., Schulberg, Stacey D., Shah, Anoop S.V., Sorbie, Andrew, Soutar, Grace, Strachan, Fiona E., Taggart, Caelan, Vicencio, Daniel Perez, Wang, Yiqing, Wereski, Ryan, Williams, Kelly, Weir, Christopher J., Berry, Colin, Reid, Alan, Maguire, Donogh, Collinson, Paul O., Sandoval, Yader, Smith, Stephen W., Wussler, Desiree, Muench-Gerber, Tamar, Glaeser, Jonas, Spagnuolo, Carlos, Huré, Gabrielle, Gehrke, Juliane, Puelacher, Christian, Gualandro, Danielle M., Shrestha, Samyut, Kawecki, Damian, Morawiec, Beata, Muzyk, Piotr, Buergler, Franz, Buser, Andreas, Rentsch, Katharina, Twerenbold, Raphael, López, Beatriz, Martinez-Nadal, Gemma, Adrada, Esther Rodriguez, Parenica, Jiri, and von Eckardstein, Arnold
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- 2024
- Full Text
- View/download PDF
48. Long term management of patients with cryopyrin-associated periodic syndromes (CAPS) : focus on rilonacept (IL-1 Trap)
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Church, Leigh D, Savic, Sinisa, and McDermott, Michael F
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- 2008
49. Pathophysiology: How COVID-19 Impacts the Pancreas and Peripheral Insulin Resistance
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Low Wang, Cecilia C., Seggelke, Stacey A., McDermott, Michael T., Reusch, Jane E. B., Poretsky, Leonid, Series Editor, and Myers, Alyson K., editor
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- 2023
- Full Text
- View/download PDF
50. Far Lateral Craniotomy Closure Technique for Preservation of Suboccipital Musculature
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Ali, Muhammad Salman, Magill, Stephen T, and McDermott, Michael W
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Biomedical and Clinical Sciences ,Clinical Sciences ,Dental/Oral and Craniofacial Disease ,Rare Diseases ,Musculoskeletal ,far lateral ,transcondylar ,muscle atrophy ,modified far lateral ,extreme lateral ,technique ,Neurology & Neurosurgery ,Dentistry - Abstract
The far lateral approach is used for accessing pathology at the craniovertebral junction but can be complicated by postoperative suboccipital muscle atrophy. In addition to significant cosmetic deformity, this atrophy can lead to head and neck pain and potentially could contribute to cranio-cervical instability. To address this issue, the senior author began using a single myocutaneous flap without a muscle cuff and securing it directly to the bone using predrilled holes in the bone that resemble a chevron. The method is described and illustrated with an example case. Results from seven consecutive cases are reported since the technique was adopted. Muscle atrophy was measured by calculating area at the level of the occipital condyle and compared with the contralateral side. No significant differences were noted. In conclusion, we have found this to be an excellent closure technique and wanted to present our initial results for consideration by other skull base surgeons.
- Published
- 2021
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