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Seasonal Surge of Steroid-Refractory T Cell–Mediated Hepatitis in Phoenix: A Cascade of Cases and Treatment Dilemmas
MILOVANCEV, LANCE, LaBere, Brenna, Lozano-Chinga, Michelle, Dybbro, Eric, Rowland, Patrick, Wadera, Sheetal, Loutfy, Jamie, LaBere, Brenna , Chinga, Michell Lozano

Journal of Human Immunity | May 1, 2026 | Volume: 2 | Issue: CIS2026 | Pages: No page available

10.70962/cis2026abstract.184 Get It

Background T cell–mediated hepatitis is an uncommon cause of acute pediatric liver injury. Most patients respond to steroids, but management of refractory disease remains challenging. We describe four patients with non-monogenic CD8+ T cell–mediated hepatitis with close temporal presentation and variable response to therapies. All four patients had severe elevations in liver enzymes, synthetic dysfunction, hyperbilirubinemia, cytopenias, elevations in cytokines (supplemental table), and CD8+ T cell predominance on biopsy, without meeting criteria for autoimmune hepatitis. All underwent next-generation or whole-exome sequencing; no monogenic causes were elucidated. Broad infectious workup was unrevealing. Case 1 A 17-year-old male with epilepsy presented with abdominal pain and jaundice, with labs and biopsy consistent with portal and lobular hepatitis with CD8+ T cell predominance. Bone marrow aspirate (BMA) was reassuring. Hepatitis was refractory despite corticosteroids, tacrolimus, sirolimus, anakinra, intravenous immune globulin (IVIG), and anti-thymocyte globulin (ATG). Infliximab led to dramatic but incomplete improvement. He remains on steroids, tacrolimus, and infliximab, with planned hematopoietic stem cell transplantation (HSCT). Case 2 A 7-year-old female with type 1 diabetes presented with jaundice and abdominal pain, with labs and biopsy consistent with CD8+ T cell hepatitis. Steroids induced a partial response, while infliximab led to marked improvement. She transitioned to azathioprine and maintains normal liver enzymes. Case 3 A 5-year-old male with autism presented with fevers and abdominal distention, with labs and biopsy consistent with portal and lobular hepatitis with CD8+ T cell predominance. IVIG/steroids provided only a transient improvement. Tacrolimus normalized labs and enabled steroid discontinuation. Case 4 An 11-month-old healthy female presented with jaundice. Labs and biopsy were consistent with giant cell hepatitis with CD8+ T cell predominance, and no evidence of autoimmune hemolytic anemia. She was listed for liver transplantation. Partial steroid response prompted tacrolimus initiation, leading to normalization of labs and removal from transplant listing. Conclusion CD8+ T cell–mediated hepatitis may progress rapidly and be steroid refractory. Early initiation of infliximab or tacrolimus may prevent progression to liver failure. Case one represents a severe presentation with limited response; however, most avoided liver or hematopoietic stem cell transplantation. All cases presented within a three-month window, suggesting a possible infectious trigger. Tabular data are included as downloadable supplement files.
Comparison of Artificial Intelligence to Traditional Patient Education in Obstetrics and Gynecology: A Randomized Cross-Sectional Study [ID 1103]
Derakshani, Donya, Islam, N. , Yi, Johnny , Budvytyte, Laura, Mead-Harvey, Carolyn, Butterfield, Duke, Louie, Michelle, Mead‐Harvey, Carolyn , Butterfield, Duke

Obstetrics & Gynecology | April 30, 2026 | Volume: 147 | Issue: 5S | Pages: 17S-17S

10.1097/aog.0000000000006265.45 Get It

INTRODUCTION: Online patient education materials are essential in improving access to and understanding of clinical information. Artificial intelligence (AI), specifically ChatGPT, offers a novel way to synthesize complex information and is increasingly being used for patient education, including in obstetrics and gynecology. This study compares the understandability and actionability of patient education materials about hysterectomy and uterine fibroids generated by ChatGPT with those published by the American College of Obstetricians & Gynecologists (ACOG). METHODS: In a randomized cross-sectional study, participants were allocated to one of four groups: ACOG–Fibroids, ChatGPT–Fibroids, ACOG–Hysterectomy, or ChatGPT–Hysterectomy. The ACOG groups reviewed the corresponding ACOG FAQ webpage, while the ChatGPT groups reviewed responses generated by ChatGPT to the same FAQs. Participants then completed demographic questions and the Patient Education Materials Assessment Tool (PEMAT). The primary outcome was the equivalence of PEMAT scores between ACOG and ChatGPT. RESULTS: Equivalence was not demonstrated between ChatGPT and ACOG for either topic. For fibroid material, ACOG was rated higher on both understandability (86.3 versus 82.6 points, P =.039) and actionability (65.4 versus 53.2 points, P =.003) on superiority testing. For hysterectomy content, no significant difference was observed. No interaction was found between material type and either education level or personal history of fibroids/hysterectomy. CONCLUSIONS/IMPLICATIONS: PEMAT scores for ACOG were superior to ChatGPT for fibroid content, but neither equivalent nor superior for hysterectomy content. While ChatGPT offers a responsive, iterative source of information, its understandability and actionability may depend on topic-specific factors, highlighting both the promise and limitations of AI for patient education.
Generalizable spinal cord multiple sclerosis lesion segmentation across MRI contrasts, protocols, and centers
Benveniste, Pierre‐Louis , Létourneau‐Guillon, Laurent , Araújo, David , Fetco, Dumitru , Hori, Masaaki , Kamiya, Kouhei , Messina, Steven, Audoin, Bertrand , Blezek, Daniel, Brisset, Jean‐Christophe , Charlson, Erik, Chen, Michelle , Demortière, Sarah , Edan, Gilles , Filippi, M, Kerbrat, Anne , Kirschke, J, Labauge, Pierre, Liu, Yaou, Mainero, Caterina , Medina, Nilser Laines , Reich, Daniel S. , Shepherd, Timothy M. , Smith, Seth A. , Talbott, Jason, Tauhid, Shahamat , Treaba, Constantina A. , Cohen-Adad, Julien, Fetco, Dumitru , Hori, Masaaki , Audoin, Bertrand , Bakshi, Rohit , Bannier, Elise , Blezek, Daniel , Brisset, Jean-Christophe , Callot, Virginie , Chen, Michelle , Ciccarelli, Olga , Edan, Gilles , Filippi, Massimo , Granberg, Tobias , Granziera, Cristina , Hemond, Christopher C , Keegan, B Mark , Kerbrat, Anne , Kirschke, Jan , Kollind, Shannon H , Lee, Lisa Eunyoung , McGinnis, Julian , Laines Medina, Nilser , Mühlau, Mark , Nair, Govind , O'Grady, Kristin P , Oh, Jiwon , Ouellette, Russell , Reich, Daniel S , Rocca, Maria A , Smith, Seth A , Stawiarz, Leszek , Tam, Roger , Traboulsee, Anthony , Treaba, Constantina Andrada , Valsasina, Paola , Yiannakas, Marios , Cohen-Adad, Julien , Guillon, Laurent Letourneau , Chougar, Lydia , Messina, Steven A. , Tsagkas, Charidimos , Blezek, Daniel J. , Ciccarelli, Olga , Filippi, Massimo , Keegan, B. Mark , Labauge, Pierre , Lee, Lisa Eunyoung , Nair, Govind , O’Grady, Kristin P. , Prat, Alexandre , Rocca, Maria A. , Talbott, Jason F. , Tam, Roger , Lombaert, Hervé

Multiple Sclerosis Journal | April 24, 2026 | Volume: 32 | Issue: 6 | Pages: 598-613

10.1177/13524585261427333 | PMID 42028790 Get It

Background/Objectives: Characterizing spinal cord multiple sclerosis (MS) lesions in MRI is critical for diagnosis, monitoring, and treatment evaluation. However, current automated approaches for lesion detection and segmentation are typically designed for specific MRI contrasts or acquisition sites, limiting their generalizability in real-world clinical settings where imaging protocols vary widely. This work proposes a robust multi-site, multi-contrast segmentation framework for spinal cord lesions. Methods: The segmentation model was trained and evaluated on a large-scale dataset comprising 4428 annotated images from 1849 persons with MS across 23 imaging centers, encompassing six MRI contrasts (T1w, T2w, T2*w, PSIR, STIR, and UNIT1) acquired at 1.5 tesla (T), 3 T, and 7 T. Results: Likert-type assessment performed by neuroradiologist ratings demonstrated superior generalization of the model compared to existing contrast-specific pipelines ( p < 0.01). Additional experiments evaluated robustness across spinal levels, acquisition resolutions, binarization thresholds, and quantitative evaluation on external labeled datasets. Conclusions: The proposed model can achieve accurate and reliable spinal cord MS lesion segmentation across heterogeneous MRI data, addressing a key barrier to clinical translation. The model is available in the Spinal Cord Toolbox v7.2 and higher. Code repository: https://github.com/ivadomed/seg-sc-ms-lesion-multicontrast
Advanced footwear technology versus minimalist footwear for injury prevention and performance in runners
Bruneau, Michelle , Hollander, K, Lieberman, Daniel E. , Hoo, Jennifer Soo , Saxena, Amol , Zech, Astrid , Tenforde, Adam S. , Bruneau, Michelle M , Lieberman, Daniel E , Hollander, Karsten , Kipp, Shalaya

PM&R | April 22, 2026 | Volume: 18 | Issue: S2 | Pages: No page available

10.1002/pmrj.70149 | PMID 42015394 Get It

Standardized Perioperative Protocols Are Associated With Reduced Length of Stay and Readmission in Cushing Disease: Results From the Multicenter RAPID Study
Suryadevara, Carter M. , Salcedo-Sifuentes, Jorge E., Little, Andrew S., Yuen, Kevin C. J., Mendoza, Michelle Magana, Gardner, Paul, Zenonos, Georgios, Silverstein, Julie M., Kim, Albert H., Evans, James J., Barkhoudarian, Garni, Fernandez-Miranda, Juan C., Couldwell, William T., Rennert, Robert C., Kim, Won, Kshettry, Varun R., Wu, Kyle, BENJAMIN, CAROLINA, Zada, Gabriel, Gompel, Jamie Van, Catalino, Michael P., Karsy, Michael, Rosenberg, Yaakov, Mamelak, Adam N, Agrawal, Nidhi , Pacione, Donato , Karsy, Michael , Van Gompel, Jamie, Karsy, Michael , Salcedo-Sifuentes, Jorge E. , Little, Andrew S. , Yuen, Kevin C.J. , Zenonos, Georgios A, Silverstein, Julie , Kim, Albert H , Evans, James J., Barkhoudarian, Garni , Fernandez‐Miranda, Juan C. , Couldwell, William T. , Rennert, Robert C , Kshettry, Varun R. , Zada, Gabriel , Chicoine, Michael , Gompel, Jamie J. Van , Catalino, Michael Paul, Agrawal, Nidhi

Neurosurgery | April 21, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1227/neu.0000000000003992 | PMID 42012163 Get It

BACKGROUND AND OBJECTIVES: Perioperative protocols facilitate earlier discharge without compromising safety in nonfunctioning pituitary adenomas, but no large multicenter studies in the United States have investigated protocols regarding Cushing disease (CD). We sought to characterize perioperative protocols and how their implementation influences clinical outcomes in patients with CD. METHODS: A retrospective analysis was conducted using data from the Registry of Adenomas of the Pituitary and Related Disorders consortium comprising 13 US academic pituitary centers. Institutions were surveyed regarding perioperative procedures for patients undergoing transsphenoidal tumor resection for CD. The impacts of institutional procedures and approaches to implementation on length of stay (LOS) and unplanned 90-day readmission were evaluated. RESULTS: Thirteen institutions contributed survey responses and clinical data for a total of 832 patients meeting inclusion criteria. Ten (76.9%) institutions reported having a postoperative protocol, 9 (69.2%) used a formal document to outline their protocol, and 3 (23.1%) had protocols implemented into hospital policy. Mean LOS was significantly reduced in centers with an established protocol (3.14 vs 3.42 days, P = .032), and more so with a formal document (3.10 vs 3.48 days, P = .001) or hospital policy (2.72 vs 3.36 days, P < .001). Patients treated after protocol implementation experienced shorter LOS ( P < .001). Other factors associated with reduced LOS were presence of a separate CD pathway, intraoperative checklist specific to pituitary surgery, non-narcotic pain regimen, Foley removal order, dedicated outpatient advanced practice provider follow-up, and target discharge date ≤2 days. Intraoperative checklist ( P = .045), non-narcotic pain regimen ( P = .048), nasal packing ( P = .005), and 1-day target discharge date ( P = .032) were important factors against readmission. Compared with microscopic surgery, endoscopic surgery was associated with shorter LOS but increased readmission odds. CONCLUSION: This is the first multicenter study to illustrate that implementation of perioperative protocols is associated with a reduction in LOS and readmission risk in patients with CD.
ADLM Guidance Document on Incorporating Gender Diversity in Pathology and Laboratory Medicine
Thomas, Tiffany, Winston‐McPherson, Gabrielle , Amarillo, Pérez, Berry, Alisha D. , Davidge‐Pitts, Caroline , Devaraj, Sridevi, Goldstein, Zil, Karon, Brad S. , Katzman, Brooke M. , Khalifa, Mahmoud A. , Stockley, Tracy L, Stoffel, Michelle , Davidge-Pitts, Caroline , Luu, Hung S , Nichols, James H , Stoffel, Michelle R , Greene, Dina , Krasowski, Matthew D , Amarillo, Ina, Devaraj, Sridevi , Goldstein, Zil , Luu, Hung S. , Nichols, James H. , Stockley, Tracy , Greene, Dina N. , Krasowski, Matthew D.

The Journal of Applied Laboratory Medicine | April 18, 2026 | Volume: 11 | Issue: 4 | Pages: 887-926

10.1093/jalm/jfag071 | PMID 42383916 Get It

Abstract Background The first international clinical standards of care for the gender-diverse population were formulated in the late 1970s. In the last 15 years, multiple subspecialty societies within the United States have developed clinical care guidelines for those with gender dysphoria, including gender-affirming hormone therapy (GAHT) and surgical treatments. To date, there are no pathology- and laboratory medicine–specific recommendations in the United States for the gender-diverse population. Content This document outlines pathology- and laboratory medicine–specific recommendations for providing optimal care to the gender-diverse population, with a predominant focus on the adult population. The scope of this document focuses on the following 5 topics: (a) reference intervals and interpretation of laboratory tests impacted by use of GAHT (testosterone for transgender men; estradiol with or without antiandrogens for transgender women), focusing on those stably on GAHT for 6 months or longer; (b) transfusion medicine considerations for the gender-diverse patient population, (c) consideration of gender diversity in autopsy and death investigation, (d) interpretation of histology from tissues that are impacted by GAHT and surgical procedures; and (e) pathology and laboratory medicine informatics challenges and opportunities. Summary A relatively small group of laboratory tests is significantly impacted by GAHT. The histology of some tissues shows changes attributable to GAHT or to nonhormonal medical procedures. Autopsy and transfusion medicine practices for the gender-diverse population currently lack standardization, although this is evolving. The landscape of pathology informatics related to gender diversity is complicated by varying electronic health record and laboratory informatics systems functionality.
Abstract LB324: The impact of the Community Living Lab learning health system on the prostate cancer knowledge, attitudes, beliefs, and cues to action of Black men
Odedina, Folakemi T., Bolajoko, Opeyemi , Wimberly, Quincy A., Lee, Daniel W. , Willis, Floyd B. , Moultrie, Toshiko, Ford, Wayne , Green, Derry , Merriweather, Arnold, Fudge, Michelle, Wimberly, Quincy , Fudge, Michelle

Cancer Research | April 17, 2026 | Volume: 86 | Issue: 8_Supplement | Pages: LB324-LB324

10.1158/1538-7445.am2026-lb324 Get It

Abstract Background: Black men experience the highest burden of prostate cancer (CaP) incidence and mortality in the United States. The reasons documented for the significant burden of CaP in Black communities include health systems, care process, and individual/personal level factors, such as cultural factors, psychosocial factors, decision making/preferences, comprehension, past experience, and perceived behavioral control. The Community Living Lab (CoLLab) Learning Health System (LHS) was established within three American Legion Posts (ALP) in Northeast Florida to address these factors. Study Objective: This clinical trial study evaluated the impact of the CoLLab LHS on the knowledge, attitudes, beliefs, and cues to action of Black men who received Resources, Education, Amenities, and Community Health (REACH) services at the ALPs. Methods: The design was guided by the Intervention Mapping Framework and the Social Ecological Model. CoLLab REACH services were made available to participants through trusted community infrastructures. Services integrated include CaP resources and materials, social determinant of health navigation, healthy grocery distribution, cancer advocacy programs, and research participation. Participants were recruited at three ALPs and were asked to visit their respective CoLLab LHS site at least twice a month and up to 24 times over one year to use any of the services. The impact was measured using baseline and quarterly surveys assessing CaP awareness, knowledge, attitude, health beliefs, perceived control, intentions, and cues to action. Descriptive statistics were used to compare participants' information at baseline and at 3-month follow-up. Results: A total of 173 participants were included in this analysis; 57.9% were ≥ 60 years, and 92.2% were US-born Black men. Prostate cancer knowledge increased from baseline to 3-month follow-up. The median score rose from 4±1.29 at baseline, with the mean increasing to 4.24±1.10. Attitudes towards Cap screening declined marginally from 12.58±2.15 to 12.27±2.40. Health beliefs showed a clear upward shift, with the mean increasing from 22.86±3.0 at baseline to 23.20±2.82 after 3 months of intervention. Additionally, cues to action also improved, with the mean increasing from 2.78±1.67 to 3.25±1.45. Only the cues-to-action index showed a statistically significant difference (p = 0.018), with higher scores observed after 3 months of intervention. Conclusion: Across the four core constructs—prostate cancer knowledge, testing attitudes, health beliefs, and cues to action—outcomes at follow-up demonstrated modest but consistent improvements compared to those of baseline, alongside slightly reduced variability for most domains. Overall, the evaluation showed that CoLLab REACH services improved knowledge, enhanced stronger health beliefs, and significantly increased cues to action, while testing attitudes remained comparatively stable. Citation Format: Folakemi T. Odedina, Opeyemi Oreoluwa Bolajoko, Quincy A. Wimberly, Daniel W. Lee, Floyd B. Willis, Toshiko Moultrie, Wayne Ford, Derry Green, Arnold J. Merriweather, Michelle Fudge. The impact of the Community Living Lab learning health system on the prostate cancer knowledge, attitudes, beliefs, and cues to action of Black men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB324.
Microsurgical management of tentorial dural arteriovenous fistula: an analysis from the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR)
Hallak, Hana , Connor, Michelle, Lanzino, Giuseppe, Kim, Louis, Levitt, Michael R., Samaniego, Edgar, Amin-Hanjani, Sepideh, Alaraj, Ali, Starke, Robert M., Abla, A, Koch, Matthew, Sheehan, Jason P., Gross, Bradley A., Satomi, J, Tada, Yoshiteru , Dijk, J. Marc C. van , Potgieser, Adriaan R. E., Bulters, Diederik O., Du, Rose, Lawton, Michael, Abecassis, Isaac Josh, Osbun, Joshua W., Zipfel, Gregory J., Bulters, Diederik , van DijK, J Marc C , Bulters, Diederik O , Lanzino, Giuseppe , Kim, Louis J. , Levitt, Michael R. , Hayakawa, M. , Amin-Hanjani, Sepideh , Alaraj, Ali , Starke, Robert M. , Koch, Matthew J. , Dagra, Abeer , Sheehan, Jason P. , Derdeyn, Colin P. , Gross, Bradley , Du, Rose , Lawton, Michael T. , Osbun, Joshua W , Zipfel, Gregory J.

Journal of Neurosurgery | April 17, 2026 | Volume: No volume available | Issue: No issue available | Pages: 1-12

10.3171/2025.11.jns251185 | PMID 41996712 Get It

OBJECTIVE Dural arteriovenous fistulas (dAVFs) are rare cerebrovascular anomalies. Tentorial dAVFs (TDAVFs) have more aggressive features, making them prone to symptomatic presentations and hemorrhage. TDAVFs are heterogenous and require tailored surgical approaches. Presented is a multicenter analysis of TDAVF surgical outcomes. METHODS The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) consortium compiled data on dAVFs from 16 international centers from 1990 to 2021 retrospectively. Microsurgical treatment success was defined as angiographically confirmed complete obliteration of the fistula or discontinuation of cortical venous drainage (CVD) in high-grade TDAVFs. TDAVF subtypes and tailored surgical approaches were reviewed. RESULTS Of 1360 patients in CONDOR, 161 had TDAVFs and 27% (44/161) of these patients underwent surgical management, with the majority (52% [23/44]) receiving surgery as a salvage treatment following failed embolization. The mean age (SD) of this cohort was 56 (15) years, and 68% (30/44) were male. In total, 91% (40/44) of surgically treated patients presented with aggressive symptoms: 64% (28/44) presented with hemorrhage and 27% (12/44) with nonhemorrhagic neurological deficit (NHND). The median (IQR) duration from symptom onset to diagnosis was 1 (1–4) day. The median time (IQR) between diagnosis and surgery was 15 (3–80) days. Surgical approaches varied across the cohort, with the retrosigmoid being the most common (44% [18/41]), followed by the midline suboccipital (24% [10/41]) and occipital (15% [6/41]) approaches. Perioperative complications occurred in 11% (5/44) of cases, as well as permanent neurological deficits in 2% (1/44). Surgical success was achieved in 90% of patients (38/42). During the mean 3-year follow-up, 2 patients experienced a recurrence of their fistula including representation of CVD (2/38 [5%]) and 1 patient had a new NHND (1/43 [2%]). Shorter symptom duration was significantly associated with success (15.6 vs 181.5 days, p = 0.001). Primary versus salvage microsurgery showed no difference in outcomes. Both patients with recurrent fistula were effectively treated with Gamma Knife radiosurgery. CONCLUSIONS Resection is safe and durable for the treatment of TDAVF not otherwise amenable to embolization. It can achieve a high degree of success with a low rate of perioperative complications and permanent neurological deficits, benefits far exceeding the risks associated with TDAVF natural history or management with less effective modalities.
Ketamine Use in Critically Ill Patients: Insights into Depressive Symptoms and Hemodynamic Changes
Patel, Vrutti , Sujanyal, Saurabh Ashok , Raavi, Lekhya , Blumenfeld, Sophia G. , Saleem, Faiz , Bateh, Said , Hanson, Abby , Jena, Anek , Isha, Shahin , Pietrzak, Katheleen A. Rottman, Ojard, Michelle, Shah, Sadia Z. , Sanghavi, Devang , Anna, Shapiro, Sujanyal, Saurabh , Rottman Pietrzak, Katheleen A, Ojard, Michelle M , Huespe, Ivan Alfredo , Moreno Franco, Pablo , Edwards, Michael A. , Chauhan, Mohit , Sanghavi, Devang K , Shahin, Isha , Kunze, Katie L. , Johnson, Patrick W. , Pietrzak, Katheleen A., Huespe, Iván , Franco, Pablo Moreno , Chauhan, Mohit

Journal of Intensive Care Medicine | April 16, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1177/08850666261438474 | PMID 41989186 Get It

Background Ketamine has demonstrated efficacy in treatment-resistant depression, primarily in psychiatric or outpatient populations. Its use in ICU patients remains underexplored, with limited data beyond case reports and small series. This study evaluated the association between subanesthetic ketamine infusions and improvement in depressive symptoms and hemodynamic changes in ICU patients. Methods We conducted a retrospective study of adults admitted to the ICU who received IV ketamine (0.3-0.75 mg/kg over 40 min on three consecutive days) for depressive symptoms. Changes in depressive symptoms were assessed using routine clinical documentation by physicians, nurses, and occupational and physical therapists. Hemodynamic parameters (blood pressure and heart rate) were recorded before and up to 120 min after infusion. The primary outcome was to evaluate depressive symptoms while the secondary outcome was to assess hemodynamic changes post transfusion. Results Thirty-four patients met criteria, including 18 solid organ transplant recipients. Median age was 59 years; 61.8% were male. Ketamine was associated with improvement in apparent sadness (90.0% vs 52.2%, P < .05) and reported sadness (95.0% vs 59.1%, P < .05). In transplant recipients, improvement in apparent sadness remained significant (80.0% vs 41.7%, P < .05). Hemodynamic parameters remained stable; heart rate increased transiently at 15-30 min post-infusion, returning to baseline by 60-90 min. Adverse effects observed were anxiety (12.5%), restlessness and/or agitation (10.4%), and dissociation (8.16%). Conclusion Subanesthetic ketamine improved specific depressive symptoms in critically ill ICU patients without significant hemodynamic instability. These findings support its potential as a rapid-acting antidepressant in the ICU, warranting further prospective trials.
Evaluation of Regorafenib in Newly Diagnosed and Recurrent Glioblastoma: GBM AGILE Phase II/III Bayesian Randomized Platform Trial
Wen, Patrick Y. , Berry, Donald A. , Buxton, Meredith , Colman, Howard , Groot, John de , Lim, Michael, Mellinghoff, Ingo K. , Perry, James, Weller, M, Blondin, Nicholas A., Butt, Omar H. , Damek, Denise M., Fuente, Macarena I. de la , Drappatz, Jan, Dunbar, Erin, Giglio, Pierre , Hyddmark, Emma Viktoria, Iwamoto, Fabio, Jaeckle, Kurt A. , Kim, Lyndon, Kling, Heather M., Lee, Eudocia Q., Mantica, Megan , Mikkelsen, Tom, Newton, Herbert B. , Walbert, Tobias , Weathers, Shiao‐Pei , Lassman, Andrew B. , Group, for the GBM AGILE Regorafenib Study, Alexander, Brian, Anker, Lars , Berry, Nicholas , Cloughesy, Tim, Connelly, Jennifer , Detry, Michelle A. , Fitzgerald, Mark, Gordon, Gary, Graves, Todd, Hu, Jethro , Hyddmark, Emma Maria Viktoria, Johnson, Adam, Kalabic, Marija, Lesser, Glenn J., Marion, Joe , Owen, Scott, Perry, James R, Peters, Katherine B., Powell, Ashley, Saunders, Christina T., Tanner, Kirk, Untch, Sarah, Wilcox, Emma, Yung, W. K. Alfred, Lim, Michael , Buxton, Meredith , de Groot, John , Mellinghoff, Ingo K , Weller, Michael , De La Fuente, Macarena , Lee, Eudocia Q , Mantica, Megan , Nabors, Louis Burt , Newton, Herbert B , Olson, Jeffrey J. , Schiff, David , Walbert, Tobias , Weathers, Shiao-Pei , Cloughesy, Timothy F , Lassman, Andrew B , Berry, Donald , Colman, Howard , Blondin, Nicolas, Drappatz, Jan , Iwamoto, Fabio M., Lee, Eudocia Q. , Mikkelsen, Tom , Nabors, Burt , Newton, Herbert B. , Cloughesy, Timothy F. , Anderson, Mark D., Cavenee, Webster K. , Connelly, Jennifer , Ellingson, Benjamin M. , Galanis, Evanthia , Gordon, Gary, Graber, Jerome J. , Khasraw, Mustafa , Lesser, Glenn J. , McGlothlin, Anna , Peters, Katherine B. , Saunders, Christina T. , Sulman, Erik P. , Tanner, Kirk, Yung, W.K. Alfred

Journal of Clinical Oncology | April 14, 2026 | Volume: 44 | Issue: 18 | Pages: 1676-1686

10.1200/jco-25-01137 | PMID 41980234 Get It

PURPOSE GBM AGILE (ClinicalTrials.gov identifier: NCT03970447 ) is a phase II/III Bayesian adaptive platform registration trial testing multiple arms against a common control; the primary end point is overall survival (OS). Regorafenib, a multikinase inhibitor, showed OS benefit in recurrent (RD) glioblastoma in the phase II REGOMA trial and entered GBM AGILE as the first investigational arm. METHODS Patient subtypes included in the regorafenib arm of GBM AGILE were newly diagnosed unmethylated (NDU) and RD glioblastoma. Prospective defined sets of subtypes, or arm signatures, were NDU, RD, and all (NDU + RD). As the first investigational arm in GBM AGILE, regorafenib was equally randomized to the control arm. Treatment in the control arm is temozolomide + radiotherapy (in newly diagnosed) or lomustine (in RD). Efficacy was assessed by OS hazard ratio (HR), arm/control, and demonstrated when the Bayesian probability of benefit (HR <1.00) was ≥98%. Analysis was performed monthly for limited efficacy, which occurs when the Bayesian predictive power is <25% for all signatures, and determines stopping enrollment. Follow-up continued for 12 months after accrual stopped. RESULTS When the predictive power was <25% in all predefined signatures for regorafenib, accrual stopped for limited efficacy. The final analysis did not demonstrate OS improvement in the regorafenib arm in RD nor NDU glioblastoma. Median HRs were 1.05 (NDU), 1.07 (RD), and 1.07 (all) with final probabilities of benefit (HR <1.00) of 0.421 (NDU), 0.312 (RD), and 0.296 (all). Regorafenib was associated with increased toxicity relative to control. CONCLUSION GBM AGILE did not show superiority of regorafenib over control in RD (lomustine) or NDU (temozolomide + radiotherapy) glioblastoma, yet caused increased toxicities. Regorafenib has been removed from National Comprehensive Cancer Network guidelines as a treatment option for RD.