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130 citation(s) found for "Ly, Shaun".

Leveraging Social Media as a Community Engagement Tool to Disseminate Study Updates in a Mixed Methods Smoking Cessation Study Including American Indian and Alaska Native Populations
Tomah, M., Land, L., Taylor, Jennifer L. , Gifford, Shaun M., Sabaque, Corinna, Rusk, A.M., McCoy, J., Patten, Christi A.

American Journal of Respiratory and Critical Care Medicine | May 11, 2025 | Volume: 211 | Issue: Supplement_1 | Pages: A3673-A3673

10.1164/ajrccm.2025.211.abstracts.a3673 Get It

Abstract RATIONALE: Community engagement is critical in the conduct of research seeking to address healthcare disparities. Indigenous peoples (American Indians and Alaskan Natives) have the highest prevalence of cigarette smoking and commercial tobacco use among all racial and ethnic groups in the United States. Including Indigenous people as partners in the research process is critical for moving interventions to improve health forward. Engagement in the research process should be considerate of the time, travel, and ease of use for research participants and advisors. Based on feedback from community members, we launched social media pages with deidentified study updates for past participants and any interested community members to receive updates on a prospective mixed methods study designed to inform a pilot smoking cessation intervention. METHODS: Facebook and Instagram were the social media platforms identified for this study. Prior themes identified from the principal investigator's previous work and results of current study informed the development of posts. Institutional Review Board approval was granted for this community engagement method. There were no recruitment activities conducted on these pages, and all information was presented in a deidentified, thematic fashion to protect research participants. There were two social media moderators monitoring interaction with social media pages. An Indigenous artist created accompanying images to enhance engagement with posts. The content covered discussions on smoking cessation identified from the primary study along with profiles highlighting team members and allies. Posts were made at non-fixed, variable intervals from May to September 2024, and were checked bi-weekly to ensure respectful conduct. RESULTS: Between May and September 2024, ten posts were shared, including three highlighting Indigenous team members and allies and seven focused on smoking cessation discussions. Instagram had more engagement when compared to Facebook. Posts that featured Indigenous team members and allies received higher interaction when compared to those on smoking cessation alone, contributing to Instagram's overall success. CONCLUSION: Instagram was the more effective platform demonstrating higher engagement and follower growth when compared to Facebook. Of note, on both platforms, posts that highlighted team members and allies resonated well, and generated the most interaction. This not only emphasizes social media as an effective tool to engage underserved populations in the research process, but also suggests that emphasizing representation and ally-ship among research teams is impactful when engaging Indigenous audiences. This outcome exemplifies the importance of integrating cultural relevance in public health messaging when discussing thoughts and attitudes surrounding smoking cessation.
Perioperative Management of Patients on Chronic Aspirin Therapy for Elective Brain Surgery: A Delphi Study
Gruenbaum, Shaun E. , Logvinov, Ilana I. , Erac, Ivana, Logvinov, Ilana, Jones, Philip M. , Logvinov, Ilana , Kulikov, Alexander , Bilotta, Federico

Journal of Neurosurgical Anesthesiology | April 30, 2025 | Volume: 38 | Issue: 1 | Pages: 53-62

10.1097/ana.0000000000001036 | PMID 40304213 Get It

Background: The perioperative management of chronic aspirin therapy in patients undergoing elective brain surgery is challenging due to the risk of bleeding and thromboembolic events. Although aspirin discontinuation reduces the bleeding risk, it can increase thrombotic complications, particularly in patients at high risk of cardiovascular complications. This Delphi study aimed to develop consensus-based guidelines to address these clinical challenges. Methods: A 2-round Delphi survey was conducted among an international panel of 42 experienced anesthesiologists and neurosurgeons. Participants assessed the risks and benefits of perioperative aspirin management, including bleeding risk, thrombotic risk, timing of cessation and resumption, and the utility of platelet function testing. Consensus was defined as ≥80% agreement in round 2. Results: Round 1 highlighted significant variability in practice patterns. In round 2, consensus was reached on several key areas. Most experts (84%) agreed that continuing aspirin increases perioperative bleeding risk in high-risk procedures, with 87% recommending discontinuing aspirin 5 to 7 days before surgery. Nearly all experts (97%) supported continuing low-dose aspirin in high-thrombotic-risk patients. Conversely, for low-thrombotic-risk patients, only 65% agreed on aspirin continuation, reflecting an ongoing debate. No consensus was reached regarding routine platelet function testing. Conclusions: This Delphi study provides experience-based recommendations for managing chronic aspirin therapy in neurosurgical patients. The panel strongly supports aspirin continuation in high-thrombotic-risk patients, with cessation 5 to 7 days before high-bleeding-risk surgeries. Individualized management is advised for low-bleeding-risk procedures and low-thrombotic-risk patients. Future research should further clarify aspirin management in these groups and explore the role of platelet function testing in neurosurgical settings.
Teclistamab for patients with heavily pretreated relapsed/refractory multiple myeloma and renal impairment
Dima, Danai , Afrough, Aimaz , Goel, Utkarsh , Grajales‐Cruz, Ariel , Khouri, Jack , Julian, Kelley , Banerjee, Rahul , Razzo, Beatrice M. , Ferreri, Christopher J. , Martinez, Mariola Alejandra Vazquez, Davis, James A. , Sannareddy, Aishwarya , Raza, Shahzad , Portuguese, Andrew J. , Gaballa, Mahmoud , Rana, Masooma , DeJarnette, Shaun, Gonzalez, Rebecca , Mikkilineni, Lekha , Hosoya, Hitomi , Ouchveridze, Evguenia, Shune, Leyla , Lin, Yi , Sborov, Douglas W. , Anderson, Larry D. , Cowan, Andrew J., Patel, Krina K. , Voorhees, Peter M. , Sidana, Surbhi , Hansen, Doris K., Susanibar-Adaniya, Sandra P. , Grajales-Cruz, Ariel F , Banerjee, Rahul , Vazquez-Martinez, Mariola A , Davis, James A , Portuguese, Andrew J , Rana, Masooma S , Lieberman-Cribbin, Alex , Chen, Anna , Herr, Megan M. , Anwer, Faiz , Sborov, Douglas W , Garfall, Alfred L , Lee, Hans C , Anderson, Larry D , Patel, Krina , Voorhees, Peter , Sidana, Surbhi , Dima, Danai , Raza, Shahzad , Hosoya, Hitomi , Julian, Kelley L , Susanibar-Adaniya, Sandra P , Pasvolsky, Oren , Vazquez‐Martinez, Mariola , Puglianini, Omar Castañeda , Ouchveridze, Evguenia, Kaur, Gurbakhash , Rossi, Adriana , Anwer, Faiz , Richard, Shambavi , Baz, Rachid , Garfall, Alfred L. , Lee, Hans C. , Hansen, Doris K. , Atrash, Shebli

Blood Advances | April 8, 2025 | Volume: 9 | Issue: 14 | Pages: 3408-3417

10.1182/bloodadvances.2025016059 | PMID 40198766 Get It

Abstract Outcomes of bispecific antibodies in patients with renal impairment (RI) are not well characterized, given the exclusion of these patients from clinical trials. Herein, we evaluated patients with relapsed/refractory multiple myeloma and RI treated with standard-of-care teclistamab. RI was defined as creatinine clearance (CrCl) <40 mL/min. CrCl <30 mL/min or dialysis dependence was defined as severe RI. Of the 384 included patients, 81 (21%) had RI, including 45 (18%) with severe RI, and 18 (5%) on dialysis. Patients with RI were more likely to be older (median age, 71 vs 67 years; P = .002) and have a higher median number of previous lines of therapy (7 vs 6; P = .04). Rates and severity of cytokine release syndrome (51% vs 59%; grade ≥3: 1.2% vs 1%) and immune effector cell–associated neurotoxicity syndrome (16% vs 13%; grade ≥3: 2.5% vs 2.6%) were similar in patients with and without RI, respectively. Patients with RI had higher baseline and day 30 post-teclistamab grade ≥3 anemia and grade ≥3 thrombocytopenia. Renal function did not worsen after teclistamab initiation in most patients with RI outside of the context of disease progression. Overall response rate (52% vs 56%; P = .61) and survival outcomes (median progression-free survival, 4.6 vs 6.5 months; P = .62) were comparable in patients with and without RI, respectively, after a median follow-up of 9.9 months. No differences in overall survival or non-relapse mortality were noted. Our findings suggest that treatment with teclistamab is feasible in patients with RI, including those on dialysis, with a similar safety and efficacy profile to patients without RI.
Suicidal Ideation, Behaviors, and Deaths in People With Ménière's Disease: A Systematic Review
McCray, Lauren R. , Farmer, Hannah G., Nguyen, Shaun A. , Nguyen, Jacqueline P. , Kil, Jonathan, Staab, Jeffrey P. , Rizk, Habib G.

Otolaryngology–Head and Neck Surgery | March 11, 2025 | Volume: 172 | Issue: 6 | Pages: 1866-1873

10.1002/ohn.1216 | PMID 40062673 Get It

AbstractObjectiveTo assess relations between Ménière's disease and suicidality, measured by suicidal ideation, suicidal behaviors, and death by suicide.Data SourcesCINAHL, Cochrane Library, PubMed, PsycINFO, and SCOPUS databases were searched from inception through July 2, 2024.Review MethodsObservational studies related to suicidality in patients with Ménière's disease were included. Non‐English language papers, editorials, and studies on vestibular disorders not specified as Ménière's disease were excluded. The Risk Of Bias In Nonrandomized Studies‐of Exposure tool was used for cohort and qualitative studies, and the Joanna Briggs Institute critical appraisal checklist was used for case‐control studies.ResultsFour studies (n = 168,566) were included in our review. Two cohort studies found significantly increased adjusted hazard ratios of 2.1 (95% CI: 2.0‐2.2) for death by suicide and 7.6 (95% CI: 4.4‐13.3) for suicidal behaviors, respectively, in patients with Ménière's disease compared to the control population after their diagnosis. However, a case‐control study found no significant difference in the prevalence of suicidal ideation or behaviors prior to the date of diagnosis in patients with Ménière's disease compared to the control population (0.9% vs 0.8%; P = .44). In addition, one patient with Ménière's disease expressed suicidal ideation in the qualitative study.ConclusionPatients may experience variable responses to Ménière's disease. Thus, otolaryngologists should be mindful of the potential for suicidality in patients with Ménière's disease.
Five-Year Results With Patisiran for Hereditary Transthyretin Amyloidosis With Polyneuropathy
Wixner, Jonas , Polydefkis, Michael , Ueda, Mitsuharu , Bender, Shaun, Jay, Patrick Y. , Yureneva, Elena, group, patisiran Global OLE study, Vita, Giuseppe, Rizzo, Vincenzo , Wiesman, Janice F. , Lau, Vincent , DeLong, Douglas, May, John J., Delmont, Émilien , Pouget, Jean, Grapperon, Aude‐Marie , Campana-Salort, Emmanuelle, Coutinho, Conceição de Azevedo, Campos, Catarina Falcão de , Coelho, Teresa , Reis, Antonio Hipólito, Pérez, Javier Martínez , Silva, Ana Martins da, Alves, Cristina , Cardoso, Márcio , Valdrez, Kátia, Monte, Julia R, Novais, Marta , Guimarães, Nádia, Cardoso, Inês , Freitas, Mónica, Ferreira, Natália , Kuzume, Daisuke , Morimoto, Yuko, Gauvain, Clément , Migaud-Chervy, Maria-Claire, Deplanque, Dominique , Jozefowicz, Elsa, Théaudin-Saliou, Marie, Cauquil-Michon, Cécile, Labeyrie, Céline , Not, Adeline , Lecoq, Anne-Lise , Stephant, Maeva, Echaniz‐Laguna, Andoni , Becquemont, Laurent , Beaudonnet, Guillemette , Eliahou, Ludivine , Slama, Michel , Signaté, Aïssatou , Darche, Paola, Grimaud, Jérôme, Berthelot, Emeline, Inamo, Jocelyn , Gendre, Thierry , Arrouasse, Raphaele , Ernande, Laura , Salhi, Hayet, Choumert, Ariane , Charlin, Cyril, Megelin, Thomas, Brannagan, Thomas H., Tsang, Steven, Wajnsztajn, Fernanda, Shije, Jeffrey, Ulane, Christina, Kleyman, Inna , Weimer, Louis H., Cioroiu, Comana , Kleopa, Kleopas A. , Zamba‐Papanicolaou, Eleni , Tada, Satoshi , Nagai, Masahiro , Ando, Rina, Yamanishi, Yuki , Overcash, J. Scott , Green, Sinikka, Coskun, Derya J, Manos, Paul S. , Zepeda, Karla A, O’Riordan, William, Cortese, Andrea , Bernardo, Daniela, Paolantonio, Andrea Di , Guglielmino, Valeria , Kristen, Arnt V. , Nagel, Christian , Siepen, Fabian aus dem , Hein, Selina , Campistol, Josep M. , Marín, Lida María Rodas, Pelicano, Josep Miquel Blasco, Dávila, Lucía Galán, Cordoba, Vanesa Pytel, Sola, A. Guerrero, Feijoo, Julián García, Isla, Leopoldo Pérez de , Moreira, Carolina Lavigne , Marques, Vanessa Daccach , Beamud, Francisco Muñoz, Borrachero, Cristina, Sanz, Mónica, Oliver, E, Moreno, Juan González, Martinez, J. Michael, Descals, Cristina, Usón, Mercedes, Vega, Francisco Jose, Figuerola, Antoni, Montalà, Carles, Abreu, Aline França de , Silva, Moises Dias da, Rosa, Renata Gervais de Santa, Berensztejn, Amanda Cardoso, Guedes, Mariana de Andrade, Lautre, Andrea, Orellana, Lucas, Briseño, Maria Alejandra González-Duarte, Parra, David Rivera de la, Reyes, Jose Pablo Hernandez, Alba, Maria del Mar Saniger, Parman, Yeşim , Serbest, Nail Güven , Durmuş, Hacer , Karamürsel, Saçit , Elitok, Ali, Inan, Nermin G Sirin, Altinkurt, Emre, Polydefkis, Michael, Allen, Adriane C, Chaudhry, Vinay , Jarrett, R. J., Bressler, Neil M. , Khoshnoodi, Mohammad , Lui, Alvin T, Chung, Tae , Vista, Geno, Shah, Syed Mahmood , Hamaguchi, Hirotoshi , Oda, Tetsuya , Shimomura, Masahiro, Kim, Hee Jin, Misumi, Yohei , Nomura, Toshiya , Tateishi, Takahisa , Mauricio, Elizabeth A. , Dimberg, Elliot L., Fonder, Amie , Hobbs, Miriam, Dyck, P. James B. , Leung, Nelson , Hwa, Yi L. , Kapoor, Prashant , Kumar, Shaji , Dingli, David , Gove, Linde E., Dalia, Samir , Croy, David, Holding, Tim, Gorevic, Peter D., Su, Jen-Jen , Lin, Chao-Wen, Ajroud‐Driss, Senda , Sufit, Robert , Li, John-Michael, Freimer, Miriam , LoRusso, Samantha, Aso, Yasuhiro , Kim, Byoung‐Joon , Kim, JuHyeon, Jeon, Eun‐Seok , Seok, Jin Myoung , Park, Jae Hong , Sekijima, Yoshiki , Kato, Naga-aki, Hineno, Akiyo , Kodaira, Minori , Yoshinaga, Tsuneaki , Takasone, Ken, Miyahara, Teruyoshi, Takahashi, Yusuke , Matsumoto, Kazuhiko , Lin, Kon-Ping, Lee, Yi‐Chung , Wixner, Jonas, Pilebro, Björn, Nordh, Erik, Chermenina, Maria, Nygren, Anneli, Tournev, Ivaylo, Zhelyazkova, Sashka , Cherneva, Zheyna , Sarafov, S., Cherninkova-Gopina, Sylvia, Vorona, Elena, Huesing-Kabar, Anna, Schilling, Matthias , Kabar, Iyad , Martinez–Naharro, Ana , Chacko, Liza , Cohen, Oliver , Law, Steven , Rezk, Tamer , Quan, Dianna , Dixon, Stacy, Fridman, Vera , Low, Soon-Chai , Mezei, Michelle M. , Jack, Kristin, Wade, N. Kevin, Lopate, Glenn, Geisler, Stephanie , Sommerville, R. Brian, Florence, Julaine, Stewart, Graeme J., Taylor, Mark , Suan, Daniel, Dingli, David , Gillmore, Julian D , Lee, Yi-Chung , Karamursel, Sacit , Adams, David , Berk, John L. , Conceição, Isabel , Dispenzieri, Angela , Peltier, Amanda , Bender, Shaun , Capocelli, Kelley, Obici, Laura , group, patisiran Global OLE study, Vita, Giuseppe, Russo, Massimo , Mazzeo, Anna Teresa , Gentile, Luca, Kaku, Michelle C. , Lau, Vincent, Dalton, James, May, John, Attarian, Shahram , Verschueren, Annie , Campana-Salort, Emmanuelle, Neves, Carlos, Santos, Miguel Oliveira , Coelho, Teresa, Correia, Nuno, Perez, Javier M, Silva, Ana Martins da, Ramalho, Joana, Yamasaki, Masahiro , Morimoto, Yuko, Tard, Céline , Hachulla, É. , Lebellec, Loïc , Théaudin, Marie , Al‐Salameh, Abdallah , Algalarrondo, Vincent , Rousseau, Antoine , Planté‐Bordeneuve, Violaine , Ayache, Samar S. , Corvoisier, Philippe Le , Waters, Michael, Manos, Paul, Lozza, Alessandro , Merlini, Giampaolo , Rosti, Vittorio , Sabatelli, Mario , Bisogni, Giulia , Luigetti, Marco , Romano, Ângela , Nienhuis, Hans L. A. , Neshige, Shuichiro , Horga, Alejandro , Feijoo, Julián García, Marques, Wilson , López, Inés AL, Sanz, Monica, Martinez, Jose M Gamez, Waddington‐Cruz, Márcia , Abreu, Aline Souza de, Silva, Moises Dias da, Pinto, Marcus Vinícius , Pinto, Luiz Felipe , Barroso, Fábio , Briseno, Maria Alejandra Gonzalez Duarte, Cárdenas‐Soto, Karla , Cantú-Brito, Carlos Gerardo , Şahin, Erdi , Çakar, Arman , İNAN, NERMİN GÖRKEM ŞİRİN, Polydefkis, Michael, Jarrett, Raquel, Singh, Mandeep , Judge, Daniel P. , Lui, Alvin T, Vista, Geno, Shimomura, Masahiro, Scheid, Christof , Holtick, Udo , Oh, Jeeyoung , Kim, Hee Jin, Shin, Hyun Jin , Choi, Kyomin , Mauricio, Elizabeth A. , Cooper, Leslie T. , Gonsalves, Wilson I. , Witzig, Thomas E. , Lin, Yi , Rajkumar, S. Vincent , Gertz, Morie A. , Chao, Chi‐Chao , Lee, Ming‐Jen , Hsieh, Sung‐Tsang , Tsai, Li‐Kai , Yeh, Shin‐Joe , Yang, Chih‐Chao , Lee, Ga-Yeon , Cho, Eun Bin , Min, Ju‐Hong , Lee, Hye Lim , Kishida, Dai , Imai, Akira, Lin, Kon‐Ping, Wixner, Jonas, Suhr, Ole B. , Anan, Intissar , Nordh, Erik, Domellöf, Fátima Pedrosa , Chamova, Teodora , Schmidt, Hartmut , Tepasse, Phil‐Robin , Gillmore, Julian D. , Lachmann, Helen J. , Goh, Khean Jin , Geisler, Stephanie, Taylor, Mark, Suan, Dan

JAMA Neurology | January 13, 2025 | Volume: 82 | Issue: 3 | Pages: 228

10.1001/jamaneurol.2024.4631 | PMID 39804640 Get It

Importance There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) and on RNA interference (RNAi) therapeutics in general. This study presents the longest-term data to date on patisiran for hATTR-PN. Objective To present the long-term efficacy and safety of patisiran in adults with hATTR-PN. Design, Setting, and Participants This global open-label extension (OLE) of the APOLLO randomized clinical trial and phase 2 OLE study enrolled patients from 43 hospitals or clinical centers across 19 countries between July 2015 and August 2017, with follow-up until November 2022. Of 212 eligible patients with hATTR who completed the phase 3 APOLLO or phase 2 OLE parent studies, 211 enrolled in and 138 completed the global OLE. Intervention Patisiran, 0.3 mg/kg, intravenously once every 3 weeks for up to 5 years. Main Outcomes and Measures Outcomes evaluated at year 5 of the global OLE included disability (polyneuropathy disability [PND] score); polyneuropathy severity (Neuropathy Impairment Score [NIS]), nutritional status (modified body mass index [mBMI]), quality of life (Norfolk Quality of Life–Diabetic Neuropathy [Norfolk QOL-DN]), and Rasch-Built Overall Disability Scale (R-ODS), with no statistical hierarchy. Safety, survival probability, and mortality were also assessed. Results At the global OLE baseline, the mean (SD) age was 61.3 (12.3) years, and 156 patients (73.9%) were male. In 138 patients completing the study, PND scores remained stable or improved in 89 patients (65.0%), NISs showed a mean (SD) change of 10.9 (14.7), and mean (SD) mBMI (calculated as weight in kilograms divided by height in meters squared times serum albumin in grams per liter) increased by 46.4 (120.7) over 5 years from baseline. Norfolk QOL-DN and R-ODS scores showed mean (SD) changes of 4.1 (16.7) and –3.7 (6.2), respectively. Adverse events (AEs) leading to study withdrawal occurred in 47 patients (22.3%). Infusion-related reactions were the most common treatment-related AE (n = 34 [16.1%]). Overall, 41 patients (19.4%) died during the study. Patisiran treatment in the parent study and low familial amyloid polyneuropathy score at parent study baseline were associated with significantly improved survival. Conclusions and Relevance In the longest study of an RNAi therapeutic for any disease, patisiran treatment resulted in modest changes for patients with hATTR-PN with an acceptable safety profile. These results highlight the importance of initiating early treatment for hATTR and the potential of RNAi therapeutics in medicine. Trial Registration ClinicalTrials.gov Identifier: NCT02510261
Revisiting medical oaths: how student-driven ethical codes reflect changing values
Stein, Michael, Gruenbaum, Shaun E. , Jotkowitz, Alan, Gruenbaum, Shaun Evan, Stein, Michael

Journal of Medical Ethics | December 18, 2024 | Volume: 51 | Issue: 10 | Pages: 679-683

10.1136/jme-2024-110460 | PMID 39694800 Get It

Background Medical oaths and ethical codes play a crucial role in guiding physicians through their professional responsibilities. This study extends prior research on ethical codes created by students at the Medical School for International Health (MSIH) by analysing codes from the years 2007 to 2022. Objective The objective of this study is to evaluate changes in the ethical principles emphasised by MSIH students over time and to compare these with previous cohorts. Methods Ethical codes from MSIH classes (2007–2022) were analysed using the framework developed by Baker. This framework categorises oaths into four sections: preamble, covenant, code of duties to patients and peroration. The focus was primarily on the code of duties to patients. Quantitative analysis was used to assess the prevalence of specific ethical principles. Results The study found an increased emphasis on principles such as ‘respect for patients’ and ‘cultural competence/sensitivity’, while traditional values like ‘benevolence’ and ‘honesty’ were mentioned less frequently. New themes, including ‘patient autonomy’ and ‘cultural competence’, emerged, reflecting a shift towards patient-centred care and justice, though emerging issues like artificial intelligence ethics were not addressed. Conclusions MSIH students’ ethical codes have evolved to emphasise patient respect and cultural competence. The findings suggest a maturation in the ethical perspectives of medical students, though gaps remain in addressing contemporary challenges. Future studies should explore how ethical codes can incorporate emerging issues in healthcare.
Smart Driving Technology for Non-Invasive Detection of Age-Related Cognitive Decline
Serhan, Peter , Victor, Shaun , Pérez, Óscar Osorio , Karam, Kevin Abi , Elghoul, Anthony Ziad, Ransdell, Madison , Al-Hindawi, Firas , Geda, Yonas E. , Chahal, Geetika, Eagan, Danielle E., Tsow, Francis , Forzani, Erica , Abi Karam, Kevin, Elghoul, Anthony, Geda, Yonas E , Perez, Oscar Osorio, Wu, Teresa

Sensors | December 18, 2024 | Volume: 24 | Issue: 24 | Pages: 8062

10.3390/s24248062 | PMID 39771798 Get It

Alzheimer’s disease (AD) and Alzheimer’s Related Dementias (ADRD) are projected to affect 50 million people globally in the coming decades. Clinical research suggests that Mild Cognitive Impairment (MCI), a precursor to dementia, offers a critical window of opportunity for lifestyle interventions to delay or prevent the progression of AD/ADRD. Previous research indicates that lifestyle changes, including increased physical exercise, reduced caloric intake, and mentally stimulating activities, can reduce the risk of MCI. Early detection of MCI is challenging due to subtle and often unnoticed cognitive decline and is traditionally monitored through infrequent clinical tests. In this research, the Smart Driving System, a novel, unobtrusive, and economical technology to detect early stages of neurodegenerative diseases, is presented. The system comprises a multi-modal biosensing array (MMS) and AI algorithms, including driving performance and driver’s biometrics, offering insights into a driver’s cognitive function. This publication is the first work reported towards the ultimate goal of developing the Smart Driving Device and App, integrating it into vehicles, and validating its effectiveness in detecting MCI through comprehensive pilot studies.
Predictors and Characterization of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) in Patients with Multiple Myeloma Receiving Teclistamab
Afrough, Aimaz , Dong, Wenli , Richards, Tiffany, Vazquez‐Martinez, Mariola , Sannareddy, Aishwarya , Goel, Utkarsh , Gaballa, Mahmoud , Rana, Masooma S, Ferreri, Christopher J. , Shune, Leyla , DeJarnette, Shaun, Ouchveridze, Evguenia, Forsberg, Peter A. , Hosoya, Hitomi , Mikkilineni, Lekha , Rossi, Adriana, Eberwein, Erin , Blue, Brandon , Sborov, Douglas W. , Voorhees, Peter M. , Patel, Krina K. , Sidana, Surbhi , Cowan, Andrew J. , Khouri, Jack , Davis, James A. , Sidana, Surbhi , Davis, James A , Hosoya, Hitomi , Pasvolsky, Oren , Feng, Lei , Davis, James A, Dima, Danai , Grajales‐Cruz, Ariel , Banerjee, Rahul , Lieberman-Cribbin, Alex , Julian, Kelley , Ouchveridze, Evguenia, Susanibar-Adaniya, Sandra P. , Portuguese, Andrew J. , Kaur, Gurbakhash , Rossi, Adriana , Herr, Megan M. , Lin, Chenyu , Raza, Shahzad , Lin, Yi , McGuirk, Joseph P. , Atrash, Shebli , Anwer, Faiz , Hansen, Doris K. , Anderson, Larry D. , Richard, Shambavi , Garfall, Alfred L. , Lee, Hans C.

Blood | December 6, 2024 | Volume: 144 | Issue: Supplement 1 | Pages: 3337-3337

10.1182/blood-2024-206357 Get It

Background: Teclistamab (Tec) received regulatory approval for the treatment of relapsed refractory multiple myeloma (RRMM) based on the MajesTEC-1 study. The risk of CRS and ICANS with Tec is well established with a manufacturer's recommendation of inpatient observation for 48-hours for CRS/ICANS monitoring after the initial 3 step up doses. There are limited real-world data on the characteristics of and risk factors for CRS and ICANS with Tec. Such data could inform management of Tec patients (pts), including patient selection for inpatient or outpatient step-up dosing. Methods: RRMM pts treated with standard-of-care Tec across 13 U.S. academic institutions were included in this analysis. The follow-up data cutoff was 30 April 2024. CRS and ICANS classification was based on the American Society for Transplantation and Cellular Therapy consensus grading criteria. Multivariable logistic regression models were fitted to estimate the effects of covariates on CRS and ICANS events, with a particular focus on grade ≥2 CRS, any-grade ICANS, and the combination of CRS grade ≥2 and/or any-grade ICANS. Results: 385 pts were included in the analysis, with a median of 6 lines of prior therapy. Median age was 68 years (range 31-92), 88 patients (25% of pts with available data) had ECOG ≥2, and 301 pts (78%) would have been ineligible for MajesTEC-1. 48 (33%) of 145 evaluable pts with a baseline bone marrow (BM) prior to Tec had >50% BM plasma cells, 139 pts (36%) had extramedullary disease (EMD) (either paraskeletal or true-EMD) and 5 pts (1%) had plasma cell leukemia prior to start of Tec. 224 pts (59%) received Tec with an accelerated step-up dosing regimen, defined as having at least one step-up dose interval of ≥ 2 days. 220 pts (57%) developed any-grade CRS [Grade 1: 46% (N=179), grade 2: 10% (N=37), grade 3: 0.8% (N=3), grade 4: 0.3% (N=1)]. Median time to CRS from start of Tec was 3 days (range, 0-15). Fifty-four pts (14%) developed any-grade ICANS [Grade 1: 7% (N=26), Grade 2: 5% (N=18), grade 3: 3% (N=10), grade 4: none]. There were no grade 5 CRS or ICANS events. Median time to onset of ICANS from start of Tec was 4 days (range, 0-25). There was one case of hemophagocytic lymphohistiocytosis in the entire cohort. 38% of pts received tocilizumab and 17% of pts received corticosteroids. In univariate analysis (UVA), baseline platelet <50, triple-class refractory, penta-refractory status, and EMD prior to start of Tec were associated with increased risk for CRS grade ≥2 (p-values <0.1) and incorporated in MVA. Baseline platelet <50, age >60, ECOG ≥2, Hgb <8 g/dL, BM plasma cells >50%, and ferritin or CRP in the upper quartile were associated with increased risk for any-grade ICANS in UVA (p-values <0.1). Baseline platelet <50, ECOG ≥2, Hgb <8 g/dL, BM plasma cells >50%, ferritin or CRP in the upper quartile, and prior BCMA exposure were associated with increased risk of CRS grade ≥2 and/or any-grade ICANS in UVA (p-values <0.1). Accelerated step-up dosing, renal impairment (CrCl < 30 mL/min) and baseline LDH in the upper quartile were not associated with an increased risk of either CRS or ICANS in UVA. Baseline BM plasma cells >50% was excluded from multivariable analysis (MVA) due to high number of missing data, since most pts (62%) did not undergo BM biopsy prior to start of Tec. In MVA, risk factors for CRS grade ≥2 included baseline platelet <50 at the start of Tec treatment (OR: 2.35, 95% CI 1.08-5.08; p=0.03) and penta-refractory disease (OR: 2.48, 95% CI 1.13-5.45; p=0.02). Risk factors for any-grade ICANS included platelet <50 (OR: 4.18, 95% CI 1.88-9.28; p=0.0004), age >60 (OR: 7.54, 95% CI 1.63-34.89; p=0.01) and CRP in the upper quartile (OR: 2.51, 95% CI 1.16-5.43; p=0.02). Risk factors for CRS grade ≥2 and/or any-grade ICANS included platelet <50 (OR: 2.65, 95% CI 1.42-4.94; p=0.002) and ECOG ≥2 (OR: 2.07, 95% CI 1.19-3.61; p=0.01). Conclusions: This real-world analysis of RRMM pts treated with Tec revealed comparable rates CRS and ICANS relative to the MajesTEC-1 study, and these were mostly limited to grade 1/2. MVA demonstrated a significantly higher risk of CRS grade ≥2 and/or any-grade ICANS in pts with baseline platelet <50 and/or ECOG ≥2, the former may reflect BM disease burden. These results may help identify pts who are at higher risk for IEC related toxicities with Tec that would warrant inpatient monitoring during initial step-up dosing. OP, AA, & LF: co-first authors. AG, HCL & JK: co-senior authors
Outcomes of Elderly Patients with Relapsed Refractory Multiple Myeloma (RRMM) Treated with Teclistamab: A Multicenter Study from the U.S. Multiple Myeloma Immunotherapy Consortium
Dong, Wenli , Richards, Tiffany, Davis, James A. , Afrough, Aimaz , Vazquez‐Martinez, Mariola , Sannareddy, Aishwarya , Goel, Utkarsh , Khouri, Jack , Curet, Frances N. Cervoni, Gaballa, Mahmoud , Rana, Masooma S, Ferreri, Christopher J. , Shune, Leyla , DeJarnette, Shaun, Ouchveridze, Evguenia, Hosoya, Hitomi , Mikkilineni, Lekha , Rossi, Adriana, Schrum, Daniel , Sborov, Douglas W. , Voorhees, Peter M. , Alsina, Melissa , Freeman, Ciara L. , Sidana, Surbhi , Cowan, Andrew J. , Anderson, Larry D. , Patel, Krina K. , Sidana, Surbhi , Anderson, Larry D , Davis, James A , Hosoya, Hitomi , Pasvolsky, Oren , Dima, Danai , Feng, Lei , Banerjee, Rahul , Lieberman-Cribbin, Alex , Julian, Kelley , Ouchveridze, Evguenia, Susanibar-Adaniya, Sandra P. , Portuguese, Andrew J. , Kaur, Gurbakhash , Rossi, Adriana , Herr, Megan M. , Lin, Chenyu , Raza, Shahzad , Lin, Yi , Atrash, Shebli , McGuirk, Joseph P. , Anwer, Faiz , Garfall, Alfred L. , Hansen, Doris K. , Richard, Shambavi , Lee, Hans C. , Grajales‐Cruz, Ariel

Blood | December 5, 2024 | Volume: 144 | Issue: Supplement 1 | Pages: 934-934

10.1182/blood-2024-205989 Get It

Background: Teclistamab (Tec), a first-in-class BCMA bispecific T-cell antibody, received regulatory approval for the treatment of RRMM based on the MajesTEC-1 study [Moreau et al, NEJM, 2022] which demonstrated an overall response rate (ORR) of 63% and median progression free survival (PFS) of 11.3 months. However, less than 15% (N=24) of patients (pts) enrolled in MajestTEC-1 were ≥75 years, an age cohort that is often underrepresented in clinical trials and comprises approximately one third of MM pts at diagnosis [SEER 22 2017-2021]. In this multicenter retrospective study, we report the real-world safety and efficacy of a large cohort of elderly (≥75 years) RRMM pts treated with Tec. Methods: Pts with RRMM who received standard-of-care Tec across 13 U.S. academic institutions were included in the study. The follow-up data cutoff was 30 April 2024. Pts were divided by age into two groups: age <75 years (<75 group) and age ≥75 years (≥75 group). High-risk cytogenetic abnormalities (HRCA) were defined as the presence of del(17p), t(4;14), t(14;16) and/or gain or amplification of 1q21. Disease response and progression was evaluated using IMWG criteria. Time-to-event analyses were evaluated using the Kaplan-Meier method. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) assessment was based on the American Society for Transplantation and Cellular Therapy consensus grading. Results: Among 385 pts, 83 (22%) were in the ≥75 group (median age 78, range 75-92) and 302 (78%) in the <75 group (median age 65, range 31-74). Compared to pts in the <75 group, those in the ≥75 group were more often white (78% vs. 63%, p=0.009). Both the ≥75 and <75 age groups had a median of 6 prior lines of therapy, a similar proportion with ECOG ≥2 at start of Tec (29% vs. 24%, respectively; p=0.37), and a high proportion of pts with triple-class-refractory disease (77% vs. 85%, p=0.06) and pts who would have been ineligible MajesTEC-1 (73% vs. 80%, p=0.20). In contrast, pts in the ≥75 group had a lower incidence of adverse MM risk factors compared to the <75 group, including HRCA (44.6% vs. 57.9%, p=0.03), ultra high-risk (≥2 HRCA) MM (12% vs. 24%, p=0.02), extramedullary disease (22% vs. 40%, p=0.02), hemoglobin <8 g/dL (10% vs. 21%, p=0.02) or albumin <3 g/dL (6% vs. 19%, p=0.04) at the time of starting Tec. Moreover, a lower proportion of pts in the ≥75 group had prior autologous stem cell transplantation (43% vs. 72%, p<0.0001) or prior BCMA-directed therapy (33% vs. 55%, p=0.0003). The median time from diagnosis to start of Tec was longer for pts in the ≥75 group (7.21 years vs. 5.81 years, p=0.02). There was no significant difference in rates of any-grade CRS (52% vs. 59%, p=0.27), CRS grade 2-4 (10% vs. 11%, p=0.74) or any-grade ICANS (19% vs. 13%, p=0.12) between the ≥75 and <75 age groups, respectively. Four pts in the entire cohort developed CRS grade 3-4, one of whom was in the ≥75 group. Ten pts developed grade 3 ICANS (none grade 4), three of whom were in the ≥75 group. There was no significant difference between the ≥75 group and <75 group in ORR (62% vs. 53%, p=0.17) and ≥very good partial response (VGPR) rate (53% vs. 44%, p=0.14). After a median follow-up period of 9.9 months (95% CI 9.6-10.6 months), the median PFS in the ≥75 group was 10.7 months (95% CI 6.6-NR) vs. 5.2 months (95% CI 6.6-NR) in the <75 group (p=0.005). At the time of data cut-off, the median overall survival (OS) for pts in the ≥75 group had not been reached (95% CI NR - NR) compared to 16.1 months (95% CI 14.0 - NR) in the <75 group (p=0.048). In multivariable analysis for the entire cohort, age ≥75 was not significantly associated with either PFS (HR 0.87, 95% CI 0.54-1.39; p=0.55) or OS (HR 0.60, 95% CI 0.30-1.19; p=0.15). Conclusions: This analysis of a large cohort of RRMM pts treated with Tec in the real-world setting demonstrates comparable efficacy and safety outcomes in elderly (aged ≥75 years) pts to those reported in the overall study population of MajesTEC-1. The adverse baseline disease characteristics and inferior efficacy in pts <75 years age compared to ≥75 years likely reflect patient selection and prescribing patterns in the early era of access to commercial BCMA bispecific therapy with Tec. In multivariable analysis there was no significant impact of age ≥75 on survival outcomes. OP, DD & LF: co-first authors. KKP, HCL & AGC: co-senior authors
Outcomes of Teclistamab (Tec) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) with Prior Exposure to BCMA-Directed Therapy (BCMA-DT): A Multicenter Study from the U.S. Multiple Myeloma Immunotherapy Consortium
Vazquez‐Martinez, Mariola , Davis, James A. , Goel, Utkarsh, Afrough, Aimaz , Sannareddy, Aishwarya , Razzo, Beatrice M. , Khouri, Jack , Rana, Masooma , DeJarnette, Shaun, Gaballa, Mahmoud , Avila, Gabriel De, Ouchveridze, Evguenia, Richards, Tiffany, Hosoya, Hitomi , Mikkilineni, Lekha , Schrum, Daniel , Castaneda, Omar, Rossi, Adriana, Forsberg, Peter A. , Lin, Yi, Sborov, Douglas W. , Shain, Kenneth H. , Voorhees, Peter M. , Sidana, Surbhi , Patel, Krina K. , Cowan, Andrew J. , Anderson, Larry D. , Ferreri, Christopher J. , Shune, Leyla , Sidana, Surbhi , Anderson, Larry D , Davis, James A , Hosoya, Hitomi , Dima, Danai , Goel, Utkarsh , Pasvolsky, Oren , Banerjee, Rahul , Grajales‐Cruz, Ariel , Lieberman-Cribbin, Alex , Julian, Kelley , Portuguese, Andrew J. , Susanibar-Adaniya, Sandra P. , Raza, Shahzad , Herr, Megan M. , Ouchveridze, Evguenia, Kaur, Gurbakhash , Puglianini, Omar Castañeda , Rossi, Adriana , Lin, Chenyu , Atrash, Shebli , Richard, Shambavi , Garfall, Alfred L. , Hansen, Doris K. , Lee, Hans C. , Anwer, Faiz

Blood | December 5, 2024 | Volume: 144 | Issue: Supplement 1 | Pages: 897-897

10.1182/blood-2024-203409 Get It

Background: Tec is a BCMA-directed bispecific antibody (BsAb) approved for RRMM after ≥4 prior lines of therapy (LOT) based on the MajesTEC-1 trial. However, patients who had previously received a BCMA-DT were excluded from MajesTEC-1. Herein, we evaluated outcomes of RRMM patients with prior exposure to BCMA-DT treated with standard-of-care Tec. Methods: This was a multicenter retrospective cohort study. We compared variables between different groups using Chi-squared and Kruskal-Wallis tests, and assessed progression free survival (PFS) and overall survival (OS) using Kaplan Meier and Cox proportional hazards model. We used the maximally selected rank statistics method to determine the optimal cut-off point for continuous variables to find the most significant difference in PFS among different groups. Results: A total of 385 patients were included in this study. 193 patients had received a prior BCMA-DT, of whom 77%, 22%, and 1% had received 1, 2, and 3 prior anti-BCMA agents, respectively. In patients who had received a prior BCMA-DT, 35% were aged ≥70 years, 24% had ECOG performance status (PS) ≥2, 61% had high-risk FISH, 32% had extramedullary disease (EMD) at Tec initiation, and 42% were penta-refractory. Compared to the cohort without prior BCMA-DT (n=192), patients who were treated with prior BCMA-DT were more likely to have high risk FISH (61% vs 49%, p=0.02), and higher median number of prior LOT (7 vs 5, p <0.001). The specific types of prior BCMA-DTs with the respective overall response rate (ORR) to the most recent prior BCMA-DT were: antibody drug conjugate only (ADC, n=47, ORR 43%), chimeric antigen receptor T-cell therapy only (CAR T, n=99, ORR 86%), BsAb only (n=6, ORR 100%), ADC + CAR T (n=36, ORR 56%), and other ADC/CAR T/BsAb combinations (n=5, ORR 60%). Median follow up was 9.9 (95% CI:9.5-10.6) months. Patients with prior receipt of BCMA-DT had a lower ORR (51.4% vs 61.5%; p=0.012) and ≥very good partial response rate (39.4% vs 52.6%, p=0.009), but similar ≥complete response rate (22.3% vs 24%; p=0.78) to Tec compared to those without prior BCMA-DT. Moreover, patients with prior BCMA-DT had worse median PFS compared to patients without prior BCMA-DT (prior BCMA-DT: 4.6 months, 95% CI: 2.7-7.5; without prior BCMA-DT: 8.2 months, 95% CI: 5.7-12.2; p=0.017). On multivariable analysis incorporating prior BCMA-DT, age, cytogenetics, EMD, and ECOG PS, receipt of prior BCMA-DT was not independently associated with PFS (HR 1.25, 95% CI 0.95-1.64, p=0.1). The estimated 1-year OS rate was 58.9% (95% CI: 51.64-67.2) for the prior BCMA-DT group vs 65.1% (95% CI: 58.1-73.1) for the group without prior BCMA-DT, p=0.16. For the prior BCMA-DT cohort, response rates to Tec were numerically higher in patients who received CAR T (ORR 51.2%) followed by ADC (ORR 45.5%), and bispecific (ORR 30%) as their most recent prior BCMA-DT (p=0.39). No significant difference in PFS was noted when stratifying patients by number of prior BCMA-DTs, types of all prior BCMA-DTs received, type of most recent prior BCMA-DT, or depth of response to most recent BCMA-DT. Patients who responded to Tec had a numerically longer median time from most recent BCMA-DT exposure to Tec initiation compared to non-responders: 10.5 vs 7.5 months, p=0.48. We found that the optimal cut-off for time from last BCMA-DT exposure to Tec initiation was 8.7 months. Patients with > 8.7 months between last exposure to prior BCMA-DT and Tec initiation had a superior median PFS with Tec (8.1 months, 95% CI: 4.6-11.7) compared to patients with < 8.7 months from last exposure to prior BCMA-DT (2.5 months, 95% CI: 1.1-5.7), p=0.001. The toxicity profile for patients with prior BCMA-DT was similar to those who had not received a prior BCMA-DT. Grade ≥2 CRS occurred in 8.7% vs 13% (p=0.18), and grade ≥2 ICANS in 7.7% vs 6.7%, (p=0.85) of patients with and without prior BCMA-DT, respectively. Patients in the prior BCMA-DT cohort were more likely to have grade 3 thrombocytopenia in the first 30 days after Tec initiation (10.7% vs 6.6%; p=0.08). Conclusion: This is the largest study to date of any BCMA-directed BsAb among BCMA-exposed patients. Receipt of prior BCMA-DT was associated with a trend toward worse PFS, although not statistically significant, and lower likelihood of attaining an overall response. Waiting >9 months between sequencing BCMA therapies may be associated with improved PFS. D.D., M.A.V.M., J.A.D: co first authors; F.A., C.F., L.S.: co senior authors