Citations

Mayo Clinic

Clear

156 citation(s) found for "Wu, Lan".

Substantial influence of psychological factors on return to sports after anterior shoulder instability surgery: a systematic review and meta‐analysis
Garcia, Ausberto Velasquez , Iida, Naoya , Marinis, Rodrigo de , Abdo, Glen , Velasquez Garcia, Ausberto , Kuroiwa, Tomoyuki , de Marinis, Rodrigo , Hsu, Kai‐Lan , Ekdahl, Max

Knee Surgery, Sports Traumatology, Arthroscopy | November 22, 2023 | Volume: 31 | Issue: 12 | Pages: 5913-5923

10.1007/s00167-023-07652-0 | PMID 37991534 Get It

Abstract Purpose This systematic review and meta‐analysis aimed to (1) determine the proportion of patients who underwent anterior shoulder instability surgery and did not return to sports for psychological reasons and (2) estimate differences in psychological readiness scores between patients who did and did not return to sports. Methods The EBSCOhost/SPORTDiscus, PubMed/Medline, Scopus, EMBASE and Cochrane Library databases were searched for relevant studies. The data synthesis included the proportion of patients who did not return to sports for psychological reasons and the mean differences in the psychological readiness of athletes who returned and those who did not return to sports. Non‐binomial data were analysed using the inverse‐variance approach and expressed as the mean difference with 95% confidence intervals. Results The search yielded 700 records, of which 13 (1093 patients) were included. Fourteen psychological factors were identified as potential causes for not returning to sports. The rates of return to sports at any level or to the preinjury level were 79.3% and 61.9%, respectively. A total of 55.9% of the patients cited psychological factors as the primary reason for not returning to sports. The pooled estimate showed that patients who returned to sports had a significantly higher Shoulder Instability‐Return to Sport After Injury score ( P < 0.00001) than those who did not, with a mean difference of 30.24 (95% CI 24.95–35.53; I 2 = 0%; n.s.). Conclusions Psychological factors have a substantial impact on the rate of return to sports after anterior shoulder instability surgery. Patients who returned to sports had significantly higher psychological readiness than those who did not return to sports. Based on these results, healthcare professionals should include psychological and functional measurements when assessing athletes’ readiness to return to sports. Level of evidence Level IV.
Comparison of clinical features between patients with anti-synthetase syndrome and dermatomyositis: results from the MYONET registry
Hum, Ryan Malcolm , Lamb, Janine A. , Oldroyd, Alexander , Wang, Guochun , Wedderburn, Lucy R, Diederichsen, Louise Pyndt , Schmidt, Jens , Danieli, Maria Giovanna , Oakley, Paula, Griger, Zoltán , Phuong, Thuy Nguyen Thi , Kodishala, Chanakya , Mercado, Mónica Vázquez-Del , Andersson, Helena , Paepe, Boél De , Maurer, Britta , McCann, Liza , Pipitone, Nicolò , McHugh, Neil , New, Robert P, Ollier, William , Krogh, Niels Steen , Lundberg, Ingrid E. , Chinoy, Hector , Registry, MYONET, D’hose, Sophie, Lu, Xin , Tian, Xiaolan , Pleštilová, Lenka, Barochová, Tereza, Kubínová, Kateřina , Gelardi, Chiara, Paladini, Alberto , Piga, Mario Andrea , Jara, Luis J. , Cruz‐Reyes, Claudia , Andrade-Ortega, Lilia, Medrano-Ramírez, Gabriel , Salazar-Páramo, Mario , Chavarría-Ávila, Efrain , Aguilar-Vázquez, Andrea, Anda, Jesús-Aureliano Robles-De , Molberg, Øyvind , Dastmalchi, Maryam, Notarnicola, Antonella , Gheorghe, Karina, Liden, Maria, Hanna, Balsam , Jalal, Awat, Hellström, Helena, Martineus, Jehns Christian, New, Paul, Platt, Hazel, Ahmed, Yasmeen , Armstrong, Raymond, Bernstein, Robert, Black, Carol M., Butler, Robin, Carty, John , Chattopadhyay, Chandra, Chelliah, E G, Clarke, Fiona, Dawes, P. T., Devlin, Joseph, Edwards, Christopher, Emery, Paul , Fordham, J. L. A., Fraser, Alexander, Gaston, Hill, Gordon, Patrick , Griffiths, Bridget , Gunawardena, Harsha , Hall, Frances, Hanna, Michael G. , Harrison, Beverley, Hay, Elaine M. , Hilton‐Jones, David, Horden, Lesley, Jones, Adrian, Kamath, Sanjeet, Kennedy, Thomas J. , Klimiuk, P S, Knights, Sally, Lambert, John, Laxminarayan, Ramasharan, Lecky, Bryan, Marks, Jeffrey M., Martin, Michael F., McGonagle, Dennis , McHugh, Neil, McKenna, Francis, McLaren, John, McMahon, Michael , McRorie, Euan , Merry, P, Miller, James , Nicholls, Anne, Ong, Voon , Over, K. E., Packham, John, Pipitone, Nicolo, Plant, Michael, Pountain, G., Pullar, T, Roberts, Mark, Scott, David A. , Shadforth, M F, Sheeran, Thomas, Srinivasan, Arul, Swinson, David, Teh, Lee‐Suan , Webley, M, Winer, Jonathan M., Wedderburn, Lucy R. , Lilleker, James B , Lamb, Janine A , Oldroyd, Alexander G S , Wedderburn, Lucy R , Griger, Zoltan , Nguyen Thi Phuong, Thuy , Kodishala, Chanakya , Vazquez-Del Mercado, Monica , De Paepe, Boel , McHugh, Neil , Vencovsky, Jiri , Lundberg, Ingrid E , Chinoy, Hector , McCann, Liza J , Bleecker, Jan De , Vencovský, Jiří , Registry, MYONET, Mann, H. , Kryštůfková, Olga , Klein, Martin , Saavedra, Miguel A , Lastra, Olga Lidia Vera , Satoh, Minoru , Petri, Marcelo H. , Rönnelid, Johan , Lan, Nguyễn Thị Ngọc , Padyukov, Leonid , Rothwell, Simon W. , Bernstein, Robert, Bowman, Simon , Bruce, Ian N , Carty, John, Denton, Christopher P. , Edwards, Christopher, Fordham, John, Isaacs, John Dudley , Isenberg, David , Kitas, George D. , Lanyon, Peter , Luqmani, Raashid Ahmed , Machado, Pedro , Marks, Jeffrey, Martin, Michael, McHugh, Neil, Miles, Sarah, Nixon, Jennifer, Ong, Voon, Packham, John, Pipitone, Nicolo, Sanders, Paul W. , Williams, Brian, Winer, Jonathan

Rheumatology | September 11, 2023 | Volume: 63 | Issue: 8 | Pages: 2093-2100

10.1093/rheumatology/kead481 | PMID 37698987 Get It

Abstract Objectives To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations and malignancy, between adults with anti-synthetase syndrome (ASyS) and DM. Methods Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1γ/-NXP2/-SAE/-MDA5 autoantibodies, and a cohort of ASyS patients with anti-tRNA synthetase autoantibodies (anti-Jo1/-PL7/-PL12/-OJ/-EJ/-Zo/-KS) were identified. Patients with DM sine dermatitis or with discordant dual autoantibody specificities were excluded. Sub-cohorts of patients with ASyS with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron’s papules/sign, violaceous rash, shawl sign, V-sign, erythroderma, and/or periorbital rash). Results In total 1054 patients were included (DM, n = 405; ASyS, n = 649). In the ASyS cohort, 31% (n = 203) had DM-type skin involvement (ASyS-DMskin). A higher frequency of extramuscular manifestations, including Mechanic’s hands, Raynaud’s phenomenon, arthritis, interstitial lung disease and cardiac involvement differentiated ASyS-DMskin from DM (all P &lt; 0.001), whereas higher frequency of any of four DM-type rashes—heliotrope rash (n = 248, 61% vs n = 90, 44%), violaceous rash (n = 166, 41% vs n = 57, 9%), V-sign (n = 124, 31% vs n = 28, 4%), and shawl sign (n = 133, 33% vs n = 18, 3%)—differentiated DM from ASyS-DMskin (all P &lt; 0.005). Cancer-associated myositis (CAM) was more frequent in DM (n = 67, 17%) compared with ASyS (n = 21, 3%) and ASyS-DMskin (n = 7, 3%) cohorts (both P &lt; 0.001). Conclusion DM-type rashes are frequent in patients with ASyS; however, distinct clinical manifestations differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance. These findings will inform future ASyS classification criteria and patient management.
International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors
Adappa, Nithin D. , Beswick, Daniel M. , London, Nyall R. , Su, Shirley Y. , Wang, Marilene B. , Alexiev, Borislav A. , Antognoni, Paolo , Alonso‐Basanta, Michelle , Batra, Pete S., Bhayani, Mihir K. , Bell, Diana , Betz, Christian , Callejas, Claudio , Casiano, Roy R. , Chatzinakis, Vasileios , Chen, Simon , Chowdhury, Naweed I. , Citardi, Martin J. , Cohen, Marc A. , Dagan, Roi , Dalfino, Gianluca , Dassi, Camila , Almeida, John R. de , Tos, Angelo Paolo Dei , DelGaudio, John M. , Ebert, Charles S. , Eloy, Jean Anderson , Evans, James J., Fang, Christina H. , Farrell, Nyssa Fox , Ferrari, Marco , Fischbein, Nancy J. , Folbe, Adam J. , Fox, Meha G. , Lund, Valerie J. , Gallia, Gary L. , Gardner, Paul A. , Getz, Anne E., Govindaraj, Satish, Gray, Stacey T. , Gross, Bradley A. , Guo, Ruifeng , Ha, Patrick K. , Halderman, Ashleigh A. , Hanna, Ehab Y., Harvey, Richard J. , Hernandez, Stephen, Hopkins, Claire , Huang, Zhigang , Huang, Zhenxiao , Humphreys, Ian M. , Hwang, Peter H. , Iloreta, Alfred Marc, Ishii, Masaru , Jafari, Aria , Kennedy, David W. , Khan, Mohemmed, Kimple, Adam J. , Kingdom, Todd T. , Knisely, Anna, Kuo, Ying‐Ju , Lamarre, Eric , Lan, Ming‐Ying , Le, Hien , Lee, Nancy Y. , Lee, Jivianne K., Lee, Victor , Levine, Corinna G. , Lin, Jin‐Ching , Lin, Derrick T., Locke, Tran B. , Luong, Amber , Magliocca, Kelly R. , Matnjani, G., Meço, Cem , Michel, Loren S. , Na'ara, Shorook, Nicolai, Piero , Nuss, Daniel W. , Nyquist, Gurston , Oakley, Gretchen M. , Omura, Kazuhiro , Orlandi, Richard R. , Otori, Nobuyoshi , Papagiannopoulos, Peter , Patel, Zara M. , Pfister, David G. , Rabinowitz, Mindy, Sanusi, Olabisi , Sargi, Zoukaa , Schafhausen, Philippe, Schlosser, Rodney J. , Sedaghat, Ahmad R. , Senior, Brent A. , Shrivastava, Raj , Sindwani, Raj , Smith, Timothy L. , Smith, Kristine A. , Solares, C. Arturo , Stamm, Aldo Cassol , Stölzel, Katharina , Sumer, Baran D. , Tajudeen, Bobby A. , Thorp, Brian D. , Tsang, Raymond K. , VanKoevering, Kyle K. , Welch, Kevin C. , Wise, Sarah K. , Witterick, Ian , Won, Tae‐Bin , Wong, Stéphanie , Woodworth, Bradford A. , Wormald, Peter‐John , Zhou, Bing , Adappa, Nithin D. , Chapurin, Nikita , Ayoub, Noel , Bitner, Benjamin F. , Chang, Michael T. , Kuan, Edward C , Wang, Eric W , Beswick, Daniel , Wang, Marilene B , Alt, Jeremiah A , Bleier, Benjamin , Callejas, Claudio , Choby, Garret , Dalfino, Gianluca , Eloy, Jean Anderson , Fang, Christina H , Farrell, Nyssa F , Ferrari, Marco , Georgalas, Christos , Grayson, Jessica W , Harvey, Richard J , Holtzman, Adam L. , Hopkins, Claire , Humphreys, Ian M , Hwang, Peter H , Jafari, Aria , Kimple, Adam J , Lal, Devyani , Lan, Ming-Ying , Luong, Amber U , Meço, Cem , Omura, Kazuhiro , Orlandi, Richard , Patel, Zara , Sedaghat, Ahmad R , Senior, Brent A , Smith, Timothy L , Smith, Kristine , Snyderman, Carl H , Tong, Charles C L , van Zele, Thibaut , Won, Tae-Bin , Woodworth, Bradford A , Yao, William C , Yeh, Chien-Fu , Zhou, Bing , Schlosser, Rodney J , Bitner, Benjamin , Guo, Ruifeng , Chang, Michael T , Su, Shirley Y , Locke, Tran Bao , Adappa, Nithin D. , Abuzeid, Waleed M. , Alt, Jeremiah A. , Bernal‐Sprekelsen, Manuel , Blay, Jean‐Yves , Bleier, Benjamin S. , Bonilla‐Velez, Juliana , Carrau, Ricardo L. , Castelnuovo, Paolo , Chandra, Rakesh Kumar , Chiu, Alexander G. , Choby, Garret , Dallan, Iacopo , El‐Sayed, Ivan H. , Fokkens, Wytske Johanna , Geltzeiler, Mathew , Grayson, Jessica W. , Gross, Bradley , Grube, Jordon G. , Hanna, Ehab Y., Ivan, Michael E , Khan, Mohemmed N., Lal, Devyani , Lechner, Matt , Lobo, Brian C. , Markovic, Svetomir N. , McKean, Erin L. , Mendenhall, William M , Phan, Jack , Psaltis, Alkis J. , Ramanathan, Murugappan , Rimmer, Ryan , Rosen, Marc R , Sreenath, Satyan B , Šurda, Pavol , Thompson, Lester D.�R. , Turner, Justin H. , Turri‐Zanoni, Mario , Udager, Aaron M , Yao, William C.

International Forum of Allergy & Rhinology | September 2, 2023 | Volume: 14 | Issue: 2 | Pages: 149-608

10.1002/alr.23262 | PMID 37658764 Get It

Abstract Background Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology‐based topics spanning the field. Methods In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence‐Based Review with Recommendations, Evidence‐Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses format, and completed sections underwent a thorough and iterative consensus‐building process. The final document underwent rigorous synthesis and review prior to publication. Results The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology‐based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. Conclusion As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.
Surgical treatment of inferior pole fractures of the patella: a systematic review
Chang, Chih‐Hsun, Kuan, Fa‐Chuan , Hong, Chih‐Kai , Su, Wei‐Ren, Hsu, Kai‐Lan , Hsu, Kai-Lan , Shih, Chien‐An , Su, Wei‐Ren

Journal of Experimental Orthopaedics | June 1, 2023 | Volume: 10 | Issue: 1 | Pages: No page available

10.1186/s40634-023-00622-y | PMID 37261559 Get It

AbstractPurposeThis study aimed to comprehensively review the existing evidence concerning surgical treatment of inferior pole fractures of the patella and to report the outcomes and complications of different fixation techniques.MethodThis systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Searches of PubMed, Scopus, and Web of Science were conducted in March 2023. Studies were screened against predecided inclusion and exclusion criteria. The extracted data included fracture characteristics, surgical techniques, and radiographic and functional outcomes. The Methodological Index for Non‐Randomized Studies (MINORS) quality assessment tool was used to assess the eligible literature. The primary outcome was postoperative range of motion of different surgical methods, and the secondary outcomes were other clinical results and complications.ResultsA total of 42 studies satisfied all the inclusion criteria and were deemed suitable for review. Fourteen case–control studies and 28 case series were selected, for a total of 1382 patients with a mean age of 51.0 years (range = 11–90). The follow‐up period ranged from 6 to 300 months. The surgical techniques were categorized based on the device used as follows: (1) rigid fixation device; (2) tensile fixation device; (3) mixed device; and (4) extra‐patella device.ConclusionRegarding the outcomes following surgical treatment of inferior pole fractures of the patella, the postoperative range of motion (ROM) of each technique ranged from 120° to 135°, with the exception of that involving the patellotibial wire which had poorer outcomes. The lowest functional score was also found in those using the patellotibial wire. Complications after surgery are rare, but approximately half of the patients required additional surgery for implant removal, particularly those whose initial surgery involved rigid fixation devices. It's worth noting that bony fragment excision is no longer recommended, and the combined use of multiple surgical devices is now more common.
International Epidemiology of Carbapenemase-Producing Escherichia coli
Boutzoukas, Angelique E , Komarow, Lauren , Chen, Liang , Hanson, Blake , Liu, Zhengyin , Mendoza, Soraya Salcedo, Ordóñez, Karen , Wang, Minggui , Ge, Lizhao , Giri, Abhigya, Hill, Carol , Baum, Keri, Kreiswirth, Barry N. , Patel, Robin , Arias, César A. , Chambers, Henry F. , Fowler, Vance G. , Investigators, Multi-Drug Resistant Organism Network, Souha, S Kanj, Jean, Francois Jabbour, Fujie, Zhang, Judith, J Lok, Robert, A Salata, Martin, Stryjewski, Valentina, Di Castelnuovo, Jose, Millan Oñate Gutierrez, Eric, Cober, Susan, Richter, Deverick, J Anderson, Beth, Evans, Carol, Hill, Heather, Reich, Keri, Baum, Rebekka, Arias, Vance, G Fowler, Karen, Ordoñez, Jesse, T Jacob, Li, Linghua , Barry, Neil, Samit, Desai, Erica, Herc, Ezequiel, Cordova, Maria, R Ponisio, Samuel, Vichez, Marisa, Laëtitia , Sandra, Valderrama, Jairo, Figueroa, Cesar, A Arias, An, Qiang , Diane, Panesso, Kirsten, R., Truc, Thanh, Jiachun, Su, Jiang, Jianping , Ming-gui, Wang, Xu, Xiaogang , Yang, Yang , Jose, M Munita, Maria, Spencer, Thamer, Alenazi, Robert, Alain, Steven, Hersch, Susan, Davies, Charles, Huskins, Kerry, G, Robin, Patel, Suzannah, Schmidt-Malan, Sara, Revolinski, Glenn, Wortmann, Robert, C Kalayjian, Greg, Weston, Belinda, Ostrowsky, Gopi, Patel, Daniel, E Furst, Angela, Kim, Julia, Garcia-Diaz, Soraya, Salcedo, John, Jeffy, Zhengyin, Liu, Andrew, Henderson, David, Louis, Qing, Xie, Keith, S Kaye, Gao, Hainv , Yu, Yunsong , Mary, Waters, Bettina, C Fries, Brandon, Eilertson, Kean, Lee Chew, Nares, Smitasin, Paul, Ananth Tambyah, Jason, Christopher, Anton, Peleg, Marcel, L. Saint, Lan-juan, LI , Lauren, Komarow, Lizhao, Ge, Scott, Evans, Todd, McCarty, Henry, Fitjerald , Omai, B Garner, Lilian, M Abbo, David, van Duin, Ebbing, Lautenbach, Jennifer, Harrington, Yohei, Doi, Darren, W Logan, Blake, Hanson, Jinnethe, Reyes, Maria, Virginia Villegas Botero, Lorena, Diaz, Federico, P., Ritu, Banerjee, Sorabh, Dhar, Michael, Joy S, Zhiyong, Zong, Stryjewski, Martín E. , Villegas, María Virginia , Wang, Minggui , Evans, Scott R , Patel, Robin , van Duin, David , Pérez, Federico , Jiang, Jianping , Boutzoukas, Angelique , Chen, Liang , Villegas, Maria Virginia , Kanj, Souha S. , Paterson, David L. , Evans, Scott , Bonomo, Robert A. , Kreiswirth, Barry N , Arias, César A. , Fowler, Vance G. , Investigators, Multi-Drug Resistant Organism Network, Souha, S Kanj, Fujie, Zhang, Jose, Millan-Onate, Eric, Cober, Barry, N Kreiswirth, Claudia, Manca, Marisa, L Sanchez, An, Q Dinh, Kirsten, Rydell, Hu, Fupin , Maria, Spencer-Sandino, Robert, A Bonomo, Steven, H Marshall, Susan, D Rudin, Glenn, Wortmann, Gopi, Patel, Zhengyin, Liu, David, L Paterson, Qing, Xie, Marimuthu, Kalisvar , Anton, Peleg, Henry, F Chambers, Ebbing, Lautenbach, Jennifer, H Han, Lorena, Diaz, Federico, Perez, Ritu, Banerjee, Zhiyong, Zong

Clinical Infectious Diseases | May 8, 2023 | Volume: 77 | Issue: 4 | Pages: 499-509

10.1093/cid/ciad288 | PMID 37154071 Get It

Abstract Background Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of patients from several countries with CP-Ec isolates obtained from a prospective cohort. Methods Patients with CP-Ec were enrolled from 26 hospitals in 6 countries. Clinical data were collected, and isolates underwent whole-genome sequencing. Clinical and molecular features and outcomes associated with isolates with or without metallo-β-lactamases (MBLs) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after the index culture. Results Of the 114 CP-Ec isolates in Consortium on resistance against carbapenems in Klebsiella and other Enterobacterales-2 (CRACKLE-2), 49 harbored an MBL, most commonly blaNDM-5 (38/49, 78%). Strong regional variations were noted with MBL-Ec predominantly found among patients in China (23/49). Clinically, MBL-Ec were more often from urine sources (49% vs 29%), less often met criteria for infection (39% vs 58%, P = .04), and had lower acuity of illness when compared with non–MBL-Ec. Among patients with infection, the probability of a better DOOR outcome for a randomly selected patient with MBL-Ec as compared with non–MBL-Ec was 62% (95% CI: 48.2–74.3%). Among infected patients, non–MBL-Ec had increased 30-day (26% vs 0%; P = .02) and 90-day (39% vs 0%; P = .001) mortality compared with MBL-Ec. Conclusions Emergence of CP-Ec was observed with important geographic variations. Bacterial characteristics, clinical presentations, and outcomes differed between MBL-Ec and non–MBL-Ec. Mortality was higher among non-MBL isolates, which were more frequently isolated from blood, but these findings may be confounded by regional variations.
Healthcare call center efficiency improvement using a simulation approach to achieve the organization’s target
Jiang, Lan , Huang, Yu-Li , Jiang, Lan

International Journal of Healthcare Management | March 23, 2023 | Volume: 17 | Issue: 2 | Pages: 379-388

10.1080/20479700.2023.2190250 Get It

Oral IRAK-4 Inhibitor CA-4948 Is Blood-Brain Barrier Penetrant and Has Single-Agent Activity against CNS Lymphoma and Melanoma Brain Metastases
Roemeling, Christina A. Von , Doonan, Bently P. , Klippel, Kelena , Schultz, Daniel , Hoang-Minh, Lan , Trivedi, Vrunda , Li, Chenglong , Russell, Rylynn A. , Kanumuri, Raju S. , Sharma, Abhisheak , Mitchell, Duane A. , von Roemeling, Christina A , Tun, Han W , Mitchell, Duane A , Doonan, Bently , Tun, Han W.

Clinical Cancer Research | February 7, 2023 | Volume: 29 | Issue: 9 | Pages: 1751-1762

10.1158/1078-0432.ccr-22-1682 | PMID 36749885 Get It

Abstract Purpose: An ongoing challenge in cancer is the management of primary and metastatic brain malignancies. This is partly due to restrictions of the blood-brain barrier and their unique microenvironment. These challenges are most evident in cancers such as lymphoma and melanoma, which are typically responsive to treatment in systemic locations but resistant when established in the brain. We propose interleukin-1 receptor-associated kinase-4 (IRAK-4) as a potential target across these diseases and describe the activity and mechanism of oral IRAK-4 inhibitor CA-4948. Experimental Design: Human primary central nervous system lymphoma (PCNSL) and melanoma brain metastases (MBM) samples were analyzed for expression of IRAK-4 and downstream transcription pathways. We next determined the central nervous system (CNS) applicability of CA-4948 in naïve and tumor-bearing mice using models of PCNSL and MBM. The mechanistic effect on tumors and the tumor microenvironment was then analyzed. Results: Human PCNSL and MBM have high expression of IRAK-4, IRAK-1, and nuclear factor kappa B (NF-κB). This increase in inflammation results in reflexive inhibitory signaling. Similar profiles are observed in immunocompetent murine models. Treatment of tumor-bearing animals with CA-4948 results in the downregulation of mitogen-activated protein kinase (MAPK) signaling in addition to decreased NF-κB. These intracellular changes are associated with a survival advantage. Conclusions: IRAK-4 is an attractive target in PCNSL and MBM. The inhibition of IRAK-4 with CA-4948 downregulates the expression of important transcription factors involved in tumor growth and proliferation. CA-4948 is currently being investigated in clinical trials for relapsed and refractory lymphoma and warrants further translation into PCNSL and MBM.
Alcohol abstinence partially restores peripheral mucosal-associated invariant T cells in patients with alcoholic hepatitis
Li, Wei , Lin, Edward L. , Liangpunsakul, Suthat , Rane, Susimita, Chalasani, Sai, Puri, Puneet , Kamath, Patrick S. , Shah, Vijay H. , Katz, Barry P., Radaeva, Svetlana , Crabb, David W. , Chalasani, Naga , Yu, Qigui, Lin, Edward, Lan, Jie , Sanyal, Arun J. , Yu, Qigui

The Journal of Immunology | January 2, 2023 | Volume: 200 | Issue: Supplement_1 | Pages: 166.64-166.64

10.4049/jimmunol.200.supp.166.64 Get It

Abstract Alcoholic hepatitis (AH) develops in a small percentage of heavy drinkers. The adaptive immune system of AH patients is hyper-activated, yet dysregulated and ineffective against infectious diseases. Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that are found in liver, intestinal mucosa, and peripheral blood and contribute to protection against infectious diseases. To determine whether MAIT cells were dysregulated in heavy drinkers and the effect of alcohol abstinence on MAIT cell recovery, we compared peripheral MAIT cells between AH patients and heavy drinkers without liver disease (HDC) at baseline and 6- and 12-month followup. At baseline, AH patients had severely reduced frequency of MAIT cells than HDC and healthy donor controls (HC), whereas MAIT cell frequency was not significantly different between HDC and HC. In addition, MAIT cells in AH patients expressed higher levels of the activation markers (CD69, CD38, and HLA-DR) as well as the immune checkpoint inhibitor PD-1. Multiplex immunoassays showed that plasma levels of several cytokines related to MAIT cell activation were elevated in AH patients (IFN-s, IL-7, IL-15, IL-17, IL-18, and IL-23, and TNF-a). In AH patients, the frequency MAIT cells and CD38-expressing MAIT cells correlated with levels of several cytokines and AST. At followup, AH patients had increased MAIT cell frequency and decreased MAIT cell activation with cessation of alcohol. However, abstinent AH patients still had higher levels of CD38-expressing MAIT cells than HDC at 6-month followup. Conclusion Blood MAIT cells were severely reduced and were dysregulated in AH patients and alcohol abstinence partially reversed abnormalities in MAIT cell frequency and phenotype.
Classifying the Large Vestibular Aqueduct: Morphometry to Audiometry
Deep, Nicholas L. , Carlson, Matthew L. , Driscoll, Colin L. W., Lohse, Christine M. , Lane, John I. , Ho, Mai‐Lan , Ho, Mai-Lan , Hoxworth, Joseph M.

Otology & Neurotology | December 12, 2022 | Volume: 44 | Issue: 1 | Pages: 47-53

10.1097/mao.0000000000003748 | PMID 36509439 Get It

Objective Large vestibular aqueduct (LVA) is the most common inner ear dysplasia identified in patients with hearing loss. Our objective was to systematically quantify LVA morphologies and correlate imaging findings with established audiometric outcomes. Study Design Retrospective review. Setting Tertiary referral center. Patients Patients with large vestibular aqueduct identified radiographically, with or without hearing loss. Intervention(s) Diagnostic only. Main Outcome Measure(s) Vestibular aqueduct (VA) width at midpoint, width at external aperture, and length were measured on cross-sectional imaging. Morphology was classified as type I (borderline), type II (tubular), or type III (funneled). Audiometric endpoints included air/bone conduction, pure tone averages, and air-bone gaps at 250 and 500 Hz. Statistical associations were evaluated using linear regression models, adjusted for age at first audiogram and sex. Results One hundred seventeen patients (197 ears) were included, with mean age at first audiogram of 22.2 years (standard deviation, 21.7 yr). Imaging features associated with poor audiometric outcomes were increasing VA width at midpoint and external aperture, decreasing VA length, dilated extraosseous endolymphatic sac, cochleovestibular malformations, and increasing VA type (III > II > I). Conclusions Quantitative LVA measurements and a standardized morphologic classification system aid in prediction of early audiometric endpoints.