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Single-position robot-assisted lateral lumbar corpectomy with minimally invasive posterior spinal fusion for traumatic burst fracture showing MRI-demonstrated indirect decompression: illustrative case
Fraipont, Genevieve , Pennington, Zach , Diaz-Aguilar, Luis Daniel , Pham, Martin H. , Fraipont, Genevieve M , Pennington, Zach , Pham, Martin H , Beyer, Ryan S.

Journal of Neurosurgery: Case Lessons | July 22, 2026 | Volume: 12 | Issue: 3 | Pages: No page available

10.3171/case26118 | PMID 42475751 Get It

BACKGROUND Ligamentotaxis-based indirect decompression using lateral approaches is well described for degenerative lumbar disease, yet its application in managing burst fractures remains underexplored. OBSERVATIONS A 72-year-old osteopenic male with an L4 burst fracture underwent a single-position robot-assisted lateral L4 corpectomy, L2–3 oblique lumbar interbody fusion, L5–S1 lateral anterior lumbar interbody fusion, and robot-assisted percutaneous segmental fixation from L2 to the ilium. Postoperative MRI demonstrated significant indirect decompression with a decrease in ligamentous buckling and restoration of the spinal canal cross-sectional area. The ligamentotaxis created by the height and lordosis restoration produced adequate decompression without resection of the ventral retropulsed fragments or posterior direct decompression. LESSONS This case illustrates that single-position lateral lumbar corpectomy can achieve indirect decompression while sparing the morbidity of an open posterior approach. To the authors’ knowledge, this is the first report with MRI evidence of indirect decompression following single-position lateral lumbar corpectomy. https://thejns.org/doi/10.3171/CASE26118
Comparison of the Type, Impact, and Resolution of Complications Following Direct Anterior Versus Posterior Approach Total Hip Arthroplasty
Perez, Sergio F. Guarin , Roberts, Heather J. , Restrepo, Diego J. , Babalola, A O, Larson, Dirk R. , Ledford, Cameron K. , Bingham, Joshua S. , Trousdale, Robert T. , Taunton, Michael J. , Guarin Perez, Sergio F , Babalola, Abraham, Pagnano, Mark W , Trousdale, Robert T , Taunton, Michael J , Sierra, Rafael J , Restrepo, Diego J. , Larson, Dirk , Bingham, Joshua S , Ledford, Cameron K , Watts, Chad D. , Sierra, Rafael J.

JBJS Open Access | July 17, 2026 | Volume: 11 | Issue: 3 | Pages: No page available

10.2106/jbjs.oa.26.00172 | PMID 42465617 Get It

Background: Prior studies have reported higher rates of periprosthetic fracture, superficial infection, and neurologic deficit with the direct anterior approach (DAA), and higher rates of dislocation with the posterior approach (PA) for total hip arthroplasty (THA). Despite these differences, the overall clinical burden of complications between approaches remains unclear. The purpose of this study was to compare the profiles, severity, impact, and resolution of 5 clinically important complications between DAA and PA THA. Methods: A retrospective review was conducted of 11,783 consecutive primary THAs performed between 2010 and 2021 across 3 centers within a single healthcare system, using either the DAA (n = 4,451) or the PA (n = 7,332). Complications assessed included dislocation, infection, periprosthetic fracture (PPFx), aseptic loosening, and neurologic deficit. Severity was graded using the Clavien-Dindo classification (I = minor, V = death). Impact was defined by reoperation burden, and outcomes were categorized as resolved or persistent. Kaplan-Meier survivorship and propensity-weighted Cox proportional hazards models were used to compare complication risk. Results: The overall 1-year risk of surgical complications did not differ between DAA and PA (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.75-1.06; p = 0.208). Dislocation occurred more frequently with PA THA than DAA THA (1.9% vs. 0.4%; HR, 5.20; 95% CI, 3.04-8.90; p < 0.001). Superficial infections were more frequent with the DAA (1.6% vs. 0.8%; HR, 2.43; 95% CI, 1.68-3.53; p < 0.001). The risk of deep infection, PPFx, aseptic loosening, and neurologic deficit did not differ significantly between approaches. Among patients with complications, the proportion classified as severe (Clavien-Dindo III–V) was similar, and adjusted analyses showed no difference in the odds of severe complications (adjusted odds ratio 1.34 for PA vs DAA; 95% CI, 0.95-1.91; p = 0.099). Complication impact and resolution were likewise comparable. Conclusion: Although the profile of complications differed between DAA and PA THA, the severity, early clinical impact, and resolution of complications appeared similar. Notably, DAA was associated with a lower risk of dislocation and a higher risk of superficial infection compared with PA THA. Level of Evidence: Level III , Retrospective Comparative Study. See Instructions for Authors for a complete description of levels of evidence.
DETERIO-LLM: enhancing traditional deterioration risk scores with clinical context and advanced reasoning
Ghanbari, Ghodsieh , Ahn, Joseph C, Kim, Eileen , Laverde, Ruth, Pope, Zach, Nemati, Shamim , Laverde, Ruth

JAMIA Open | July 16, 2026 | Volume: 9 | Issue: 4 | Pages: No page available

10.1093/jamiaopen/ooag123 | PMID 42466429 Get It

Abstract Objectives Accurate and timely prediction of physiological deterioration in hospitalized patients is essential, but existing deep learning models, which rely solely on structured electronic health record (EHR) data, generate high false-positive rates by missing crucial contextual information in clinical notes. We present DETERIO-LLM, a hybrid prediction model that selectively integrates large language models (LLMs) with a deep learning model (DETERIO) to reclassify borderline-risk alerts using narrative clinical notes. Materials and Methods This retrospective study used a cohort of 1000 inpatients (4.6% deterioration prevalence). DETERIO-LLM selectively analyzed narrative notes for alerts in the uncertainty range (scores 2.5-3.5). Performance was evaluated using sensitivity, positive predictive value (PPV), and F1 score, benchmarked against comparators including the best-established ML model, eCART. Results DETERIO-LLM significantly improved predictive precision over all comparators. At its optimal threshold, the model achieved a PPV of 30.6% and an F1 score of 37.3%, outperforming eCART. This selective integration reduced false-positive alerts by 46.5% within the uncertainty range while maintaining comparable sensitivity. Discussion This study demonstrates a practical, interpretable method for integrating LLM-derived contextual knowledge into existing structured EHR prediction workflows. By focusing LLM analysis on high-uncertainty alerts, DETERIO-LLM substantially improves clinical utility through a marked reduction in false-positive cases, which is critical for mitigating alert fatigue. Conclusion Selective LLM integration with structured EHR models offers a viable, interpretable path to improving early warning systems in clinical care by leveraging narrative context to reduce alert fatigue while enhancing predictive performance.
Placement of Triangular Titanium Implants Suprajacent to Pelvic Fixation Screws Reduces Pelvic Fixation Failure in Multilevel Spinal Fusion
Elder, Benjamin D. , Mundis, Gregory M. , Eastlack, Robert, Arrigoni, Paolo , Lee, Robert , Polly, David W. , Group, the SILVIA Investigator, Mundis, Gregory , Franke, Joerg , Polly, David , Eastlack, Robert K. , Franke, Joerg

Journal of Bone and Joint Surgery | July 16, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.2106/jbjs.25.01415 | PMID 42462059 Get It

Background: The purpose of this study was to determine whether placement of triangular titanium implants (TTI) suprajacent to S2-alar-iliac (S2AI) pelvic fixation screws during multilevel spinal fusion surgery for adult spine deformity reduces pelvic fixation failures. Methods: This prospective, multicenter, international, partially blinded randomized clinical trial included 222 patients scheduled for multilevel spinal fusion surgery with S2AI-based pelvic fixation. In the S2AI+TTI group, the mean age was 64.9 years, 54.1% were female, 3.7% were Hispanic, 5.5% were African American, and 1.8% were Asian. In the S2AI-alone group, the mean age was 64.8 years, 58.4% were female, 3.5% were Hispanic, 7.1% were African American, and 0.9% were Asian. Subjects were randomized to pelvic fixation using S2AI screws alone versus S2AI+TTI. Scheduled follow-up included a 24-month full-spine radiograph and a high-resolution computed tomography (CT) scan, which was independently interpreted. Results: The primary composite radiographic end point (S2AI screw breakage, lucency, or pullout, or posterior spinal rod breakage distal to S1) occurred less frequently in the S2AI+TTI group than in the S2AI-alone group (11.0% versus 20.4%, p = 0.0415). Except for rod-screw dissociation and rod fracture distal to S1, all components of the primary composite end point occurred less frequently in the S2AI+TTI group. TTI placement did not affect sagittal or coronal spinal alignment parameters. The rate of rod fracture throughout the spinal construct was slightly higher in the S2AI+TTI group (9.2% versus 5.3%) but the difference was not significant (p = 0.197). Conclusions: Placement of TTI suprajacent to S2AI screws reduced the rate of pelvic fixation failure in patients undergoing multilevel spinal fusion with pelvic fixation. Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.
Female Oncofertility in Colorectal Cancer: Reproductive Uncertainties and Potential Benefits of Immunotherapy
Miscia, Michele , Cipriani, Linda , Conci, Nicole , Violante, Tommaso , Notarangelo, Leonardo, Vicenti, Rossella , Cortese, Federica, Maletta, Manuela , Doglioli, Marisol , Cobellis, Luigi, Rottoli, Matteo, Seracchioli, Renato, Raimondo, Diego , Raimondo, Diego , Violante, Tommaso , Raffone, Antonio , Cobellis, Luigi , Rottoli, Matteo , Seracchioli, Renato

Journal of Clinical Medicine | July 16, 2026 | Volume: 15 | Issue: 14 | Pages: 5549

10.3390/jcm15145549 | PMID 42513463 Get It

Early-onset colorectal cancer is increasing, making reproductive health an increasingly relevant survivorship issue. While immune checkpoint inhibitors have altered the management of deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) colorectal cancer, their implications for reproductive-age women remain insufficiently defined. We performed a focused narrative review, structured in line with the SANRA framework, to clarify this specific clinical domain. Immunotherapy may reshape female oncofertility counseling through two distinct mechanisms: direct reproductive uncertainty, including established endocrine toxicities and hypothesized, but currently unproven, direct gonadal effects; and indirect pathway-modifying effects, such as the potential avoidance of pelvic radiotherapy or radical surgery in selected patients with locally advanced dMMR/MSI-H rectal cancer. Anatomical organ preservation should not be automatically equated with functional fertility preservation. The key clinical message is that reproductive counseling should not be restricted to historically gonadotoxic chemotherapy. Instead, early multidisciplinary guidance should explicitly distinguish CRC-specific evidence from extrapolated or theoretical concerns, integrate fertility preservation strategies when clinically feasible, and address pelvic and sexual health, contraception, washout, endocrine follow-up, and future pregnancy planning. Until prospective CRC-specific reproductive data become available, immunotherapy should not be presented as either reproductively neutral or fertility-preserving.
Modifiable Risk Factors and Attributable Ischemic Heart Disease Mortality in US States, 1990-2023
Benziger, Catherine P., Stark, Benjamin A., Johnson, Catherine O., Roth, Gregory A., Collaborators, GBD 2023 US IHD, Abohashem, Shady, Ahmed, Syed Anees, Al-Aly, Ziyad, Alsabri, Mohammed A., Antony, Catherine M., Aravkin, Aleksandr Y., Areda, Demelash, Bell, Michelle L., Brauer, Michael, Chi, Gerald, Criqui, Michael H., Dai, Xiaochen, Doshi, Ojas Prakashbhai, Doshi, Rajkumar Prakashbhai, E’mar, Abdel Rahman, Elhadi, Muhammed, Göbölös, Laszlo, Haile, Demewoz, Hebert, Jeffrey J., Hemmati, Mehdi, Ibrahim, Ramzi, Kankam, Samuel Berchi, Kantar, Rami S., Khubchandani, Jagdish, Kim, Min Seo, Kimokoti, Ruth W., Kisa, Adnan, Kokkorakis, Michail, Kumar, Ashish, Liu, Xuefeng, Lv, Lei, Mahmoudi, Morteza, Manla, Yosef, Martinez-Piedra, Ramon, Marzouk, Sammer, Mensah, George A., Mestrovic, Tomislav, Miller, Ted R., Mokdad, Ali H., Mougin, Vincent, Mustafa, Ahmad, Nassar, Mahmoud, Natto, Zuhair S., Nugen, Fred, Parikh, Romil R., Pasovic, Maja, Patil, Shankargouda, Puvvula, Jagadeesh, Ramasamy, Shakthi Kumaran, Rashid, Ahmed Mustafa, Root, Kevin T., Sawhney, Monika, Schuermans, Art, Shariff, Mariam, Shuval, Kerem, Simegn, Gizeaddis Lamesgin, Singh, Rohit, Stafford, Lauryn K., Taiba, Jabeen, Tanwar, Manoj, Teramoto, Masayuki, Thirunavukkarasu, Sathish, Tran, Thang Huu, Uppal, Dipan, Vinayak, Manish, Yuce, Deniz, Murray, Christopher J. L., Moran, Andrew E., Kimokoti, Ruth W , Liu, Xuefeng , Nassar, Mahmoud , Singh, Rohit , Tanwar, Manoj , Yu, Hairui , Taiba, Jabeen , Benziger, Catherine P. , Stark, Benjamin, Johnson, Catherine O., Roth, Gregory A. , Collaborators, GBD, Abohashem, Shady , Al‐Aly, Ziyad , Antony, Catherine M, Aravkin, Aleksandr Y. , Areda, Demelash, Bräuer, Michael , Chi, Gerald , Criqui, Michael H. , Doshi, Ojas Prakashbhai , Doshi, Rajkumar , E’mar, Abdel Rahman, Elhadi, Muhammed, Göbölös, László , Haile, Demewoz , Hébert, Jeffrey J. , Hemmati, Mehdi , Ibrahim, Ramzi , Kankam, Samuel Berchi , Kantar, Rami S. , Khubchandani, Jagdish , Kısa, Adnan , Kokkorakis, Michail , Lv, Lei , Mahmoudi, Morteza , Manla, Yosef , Martínez, Ramón , Marzouk, Sammer , Mensah, George A. , Meštrović, Tomislav , Miller, Ted R. , Mokdad, Ali H. , Mougin, Vincent , Mustafa, Ahmad , Nassar, Mahmoud, Nugen, Fred , Pasovic, Maja , Puvvula, Jagadeesh , Rashid, Ahmed Mustafa , Root, Kevin T., Sawhney, Monika, Schuermans, Art , Shariff, Mariam , Shuval, Kerem , Simegn, Gizeaddis Lamesgin , Stafford, Lauryn K , Teramoto, Masayuki , Thirunavukkarasu, Sathish, Uppal, Dipan , Vinayak, Manish , Yuce, Deniz, Murray, Christopher J. L., Moran, Andrew Edward

JAMA Cardiology | July 15, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1001/jamacardio.2026.2435 | PMID 42455550 Get It

Importance Ischemic heart disease (IHD), the leading cause of death in the US, is predominantly due to modifiable risk factors. Estimates of IHD mortality attributable to risk factors provide evidence for health policy decision-making. Objective To estimate the burden of IHD death attributable to risk factors in the US from 1990-2023. Design, Setting, and Participants The Global Burden of Disease Study 2023 (GBD 2023) used vital records and a broad set of epidemiologic data to estimate IHD death rates, risk factor exposure, and relative risk curves for risk-outcome pairs for 1990-2023 for the general population. Data analysis was performed from October 2024 to December 2025. Exposure Twelve metabolic, behavioral, and environmental risk factors. Main Outcomes and Measures The primary outcomes were IHD death rates per 100 000 persons, counts, and attributable risks from 1990-2023 by age, sex, and US state. Estimates include 95% uncertainty intervals (UI). IHD death rates were estimated using ensemble modeling methods. Risk exposures were estimated using bayesian meta-regression methods. Relative risks were estimated following the Burden of Proof framework. Results In 2023, there were 473 000 IHD deaths (95% UI, 414 000-510 000) in the US, a decrease of 58.7% (95% UI, 56.8%-61.0%) in age-standardized rate since 1990. Between 2010 and 2023, there was a 19.0% decrease (95% UI, 15.0%-22.9%) for males and a 24.5% decrease (95% UI, 20.3%-29.7%) for females in IHD death rates. High systolic blood pressure (SBP), dietary risks, and high low-density lipoprotein cholesterol (LDL-C) were the leading risk factors for IHD deaths in 2023, accounting for 47.2% (95% UI, 36.4%-57.0%), 38.6% (95% UI, 17.2%-56.8%), and 28.5% (95% UI, 19.3%-39.6%) of IHD deaths, respectively. Increased exposure to several risk factors substantially increased their attributable burden for IHD deaths in 2023, with high fasting plasma glucose (FPG) increasing 38.8% (95% UI, 11.5%-81.1%) and high body mass index (BMI) increasing 54.5% (95% UI, 41.8%-66.3%) since 1990. Smoking and particulate matter pollution had the greatest decrease in attributable IHD mortality since 1990, at 33.3% (95% UI, 23.6%-41.7%) and 74.9% (95% UI, 46.7%-88.8%), respectively. Conclusion and Relevance Per the results of this systematic analysis of GBD 2023, a total of 88.7% (95% UI, 83.4%-92.5%) of IHD deaths were attributable to modifiable risk factors in the US in 2023, with high SBP, dietary risks, and high LDL-C being the greatest contributors. High BMI and high FPG showed the largest attribution increases, while exposure to other risks did not increase significantly for the population.
SpaceXray: Feasibility and Diagnostic Capabilities of On-Orbit Medical Radiography
Gifford, Sheyna E. , Pohlen, Michael , Wang, Adam S. , Lerner, David J. , Wadhwa, Anna , Cairnie, Michael, Walter, Jeanne, Karim, Karim S. , Tilley, Steven , Karnick, Amol , Rosenberg, Marissa A , Petersen, Lonnie G , Gifford, Sheyna E. , Pohlen, Michael , Lerner, David J. , Wadhwa, Anna , Cairnie, Michael, Walter, Jeanne, Karim, Karim S. , Tilley, Steven

Radiology | July 14, 2026 | Volume: 320 | Issue: 1 | Pages: No page available

10.1148/radiol.260258 | PMID 42446357 Get It

By acquiring the first human and equipment radiographs in space, this study demonstrated the feasibility of on-orbit radiography and expanded diagnostic capabilities for crew health and hardware evaluation.
Lessons Learned from Nonoperative Management of Greater Trochanter Fractures After Total Hip Arthroplasty
Wang, P S, Labott, Josh R, Perez, Sergio F Guarin, Restrepo, Diego J, Hannon, Charles P, Abdel, Matthew P, Sierra, Rafael J, Sierra, Rafael J. , Abdel, Matthew P. , Hannon, Charles P. , Perez, Sergio F. Guarin , Restrepo, Diego J. , Wang, Pai-Han , Guarin Perez, Sergio F , Restrepo, Diego J. , Hannon, Charles P , Abdel, Matthew P , Sierra, Rafael J , Labott, Joshua R.

JBJS Open Access | July 13, 2026 | Volume: 11 | Issue: 3 | Pages: No page available

10.2106/jbjs.oa.26.00168 | PMID 42428036 Get It

Background: Greater trochanteric (GT) fractures after total hip arthroplasty (THA) are typically managed nonoperatively. However, outcome data for patient counseling remain limited. We evaluated the nonoperative results, focusing on fracture union rates and the presence of persistent limp in relation with fracture location, displacement magnitude, and direction. Methods: We retrospectively reviewed 82 postoperative GT fractures not associated with trochanteric osteolysis following primary THA performed between 1984 and 2020. The mean follow-up was 9 years. Fracture location was classified relative to the contralateral lesser trochanter as tip, waist, or base. Initial displacement, migration, final displacement, and bony union were assessed radiographically. Clinical outcomes included the presence of a persistent limp and Harris Hip Score. Multivariable analyses were performed to identify factors associated with nonunion and limp. Results: Fractures were classified as tip (n = 32), waist (n = 29), or base (n = 21). The mean initial displacement was 8.9 mm, with 43% displaced >10 mm. Initial displacement was significantly lower in base fractures (4.8 mm) compared with tip (10.1 mm) or waist (10.8 mm) fractures (p < 0.05). The mean final displacement was 14.6 mm. 45% of fractures achieved complete bony union, and 38% of patients demonstrated a persistent limp. In multivariable analysis, greater final displacement (>12 mm), and tip and waist fractures were independently associated with nonunion. Posterior fracture displacement was significantly associated with persistent limp. Conclusions: Outcomes following nonoperative management of GT fractures after THA depend on fracture morphology and displacement characteristics. Tip and waist fractures and fractures with final displacement >12 mm have a higher risk of nonunion, whereas posterior and superior displacement is associated with persistent limp. Greater than 20 mm of displacement is associated with both limp and nonunion. These findings may assist surgeons in counseling patients and in identifying fracture patterns at higher risk for adverse outcomes of nonoperative management. Level of Evidence: Level III (Prognostic Study). See Instructions for Authors for a complete description of levels of evidence.
Plasma Phosphorylated Tau 217 in Participants at Risk for Chronic Traumatic Encephalopathy
Miner, A, Zetterberg, Henrik, Blennow, Kaj, Groh, Jenna R., Singh, Alpana, Dieckhoff, Kari, Tripodis, Yorghos, Adler, Charles H., Balcer, Laura J. , Bernick, C L, Peskind, Elaine, Asken, Breton M., Tanner, Jeremy A., Rabinovici, Gil D., Banks, Sarah J., Barr, William B., Wethe, Jennifer V., Cantu, Robert C., Dodick, David W., Mez, Jesse, Palmisano, J, Martin, Brett, Stein, Thor D., McKee, Ann C., Cummings, Jeffrey L., Shenton, Martha E., Reiman, E Bieto, Rc, Stern, Ashton, Nicholas J., Alosco, Michael L., Chen, Kewei, Protas, Hillary, Su, Yi, Boker, Connie, Au, Rhoda, Farrer, Lindsay, Helm, Robert, Kowall, Neil, Mercier, Gustavo, Otis, James, Weller, Jason, Bragg, Tahlia, Simkin, Irene, Trujillo-Rodriguez, Diana, Amerongen, Suzan van , Andino, Alondra, Conneely, Shannon, Diamond, Courtney, Fagle, Tessa, Haller, Olivia, Hunt, Tennyson, Gullotti, Nicole, Kossow, Bailey, Kugelmass, Carrie, Mariani, Megan, Mayville, Brian, McLaughlin, Kathleen, Nanna, Mary, DiPopolo, Marty, Platt, Taylor, Rice, Fiona, Sestak, Madison, McClean, Michael, Annis, Douglas, Chaisson, Christine, Dixon, Diane, Finney, Carolyn, Gallagher, Kerrin, Hartlage, Kaitlin , Lu, Jun, Ojo, E O, Pine, Brittany, Ramachandran, Janani, Baucom, Zachary, Tuz‐Zahra, Fatima , Yhang, Eukyung , Bouix, Sylvain, Fitzsimmons, Jennifer, Lin, Alexander P., Koerte, Inga K., Pasternak, Ofer, Arciniega, Hector , Billah, Tashrif , Bonke, Elena, Breedlove, Katherine M. , Carrington, Holly, Coello, Eduardo , Coleman, Michael J., John, Omar , Jung, Leonard, Liao, Huijun, Loy, Maria, Rizzoni, Elizabeth, Schulz, V. D., Silva, Annelise, Vessey, Brynn, Wiegand, Tim L.T, Miller, Jason, Ritter, Aaron , Sabbagh, Marwan, Cruz, Raelynn de la, Durant, Jan, Golceker, Morgan, Harmon, Nicolette, Kaylegian, Jaeson, Long, Rachelle, Nance, Christine, Sandoval, Priscilla, Staples, Miranda, Clark, Emma F., Serrano, Andrew, Geda, Yonas, Duffy, Amy, Falk, Bryce, Howard, Marci, Montague, Michelle , Osgood, Thomas, Babcock, Debra, Bellgowan, Patrick, GOLDBERG, JUDITH, Joseph, Binu , Kirov, Ivan, Lui, Yvonne, Marmar, Charles, Wisniewski, T R, Al-Kharafi, Alhassan, George, Allan, Hasanaj, Lisena, Martin, Sammie, Riley, Edward, Runge, William, Serrano, Liliana , Iliff, Jeffrey, Li, Gail, Janssen, D, Meabon, James, Piantino, Juan, Schindler, Abigail, Thomas, Ronald, Colasurdo, Elizabeth , Shofer, Jane, Marcus, Daniel S., Gurney, Jenny , Greenwald, Richard, Johnson, Keith A., Singh, Alpana , Singh, Alpana , Miner, Annalise E., Zetterberg, Henrik , Blennow, Kaj , Groh, Jenna R. , Singh, Alpana, Tripodis, Yorghos , Adler, Charles H. , Bernick, Charles , Peskind, Elaine R. , Asken, Breton M. , Rabinovici, Gil D. , Banks, Sarah J. , Barr, William , Wethe, Jennifer V. , Cantu, Robert C. , Dodick, David W. , Mez, Jesse , Stein, Thor D. , McKee, Ann C. , Cummings, Jeffrey L. , Shenton, Martha E. , Reiman, Eric M. , Ashton, Nicholas J. , Alosco, Michael L. , Protas, Hillary , Au, Rhoda, Weller, Jason , Trujillo‐Rodriguez, Diana , Fagle, Tessa, Mariani, Megan, McLaughlin, Kathleen , Pulukuri, Surya Vamsi , Sestak, Madison, McClean, Michael D , Annis, Douglas, Finney, Carolyn, Lu, Jun, Pine, Brittany, Ramachandran, Janani , Baucom, Zachary, Bouix, Sylvain , Koerte, Inga K , Pasternak, Ofer , Bonke, Elena M. , Carrington, Holly , Coleman, Michael J. , Liao, Huijun, Schulz, Vivian, Wiegand, Tim L. T. , II, Robert W. Turner , Marek, Kenneth , Geda, Yonas E. , Howard, Marci, Montague, Michelle, Babcock, Debra, Bellgowan, Patrick S.F. , Kirov, Ivan, George, Allan, Meabon, James S. , Piantino, Juan , Thomas, Ronald G. , Colasurdo, Elizabeth A. , Shofer, Jane, Marcus, Daniel S., Johnson, Keith A.

JAMA Network Open | July 13, 2026 | Volume: 9 | Issue: 7 | Pages: e2622966

10.1001/jamanetworkopen.2026.22966 | PMID 42440317 Get It

Importance In vivo biomarkers for detecting neuropathologies from repetitive head impacts (RHI), including chronic traumatic encephalopathy (CTE), are needed. Objective To evaluate the utility of plasma phosphorylated tau 217 (p-tau217), assess its performance as a beta-amyloid (Aβ) biomarker in participants with RHI exposure at risk for CTE, and explore concordance with CTE neuropathology in a postmortem subsample. Design, Setting, and Participants This longitudinal, multicenter, case-control study used data from the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of CTE (DIAGNOSE CTE) Research Project, collected from September 2016 to October 2023. Participants were former American football players (case participants) and asymptomatic men unexposed to RHI (control participants). A subsample had available neuropathologic data. Exposures RHI, traumatic encephalopathy syndrome (TES) diagnoses, and levels of CTE certainty. Main Outcomes and Measures Plasma p-tau217 (classified as positive [≥0.63 pg/mL], intermediate [0.40-0.62 pg/mL], and negative [&amp;lt;0.40 pg/mL]), Aβ–positron emission tomography (PET; 18 F-florbetapir; with Aβ-positive defined as a standardized uptake value ratio [SUVR] ≥1.10), and tau-PET ( 18 F-flortaucipir). TES diagnoses were assigned by multidisciplinary consensus conference. Analyses of postmortem brains controlled for age, race, and APOE ε4 status. Results Among 231 participants (mean [SD] age, 57.75 [8.25] years), 177 were former football players (117 professional and 60 college) and 54 were unexposed participants. Former football players had higher baseline mean (SD) p-tau217 concentrations than unexposed participants (0.35 [0.26] pg/mL vs 0.27 [0.14] pg/mL; P = .008), although this was driven by a higher proportion of Aβ-PET–positive participants among former players. Plasma p-tau217 increased over time across the sample (B = 0.207 [95% CI, 0.117-0.298]; P &amp;lt; .001), with no significant time × exposure group interactions. Among football players, p-tau217 showed no time × group interactions with TES diagnosis, TES-CTE certainty, or RHI metrics. Higher p-tau217 concentration correlated with higher global Aβ-PET SUVR (B = 0.058 [95% CI, 0.053-3.501; P = .01), with a few discordant cases (5 participants were p-tau217–negative and Aβ-PET–positive; 7 participants were p-tau217–positive and Aβ-PET–negative). P-tau217 had similar areas under the curve for projecting Aβ-PET positivity as cerebrospinal fluid (CSF) p-tau181/Aβ42 and CSF Aβ40/42 measures (p-tau217: AUC, 0.88 [95% CI, 0.80-0.96]; CSF p-tau181/Aβ42: AUC, 0.89 [95% CI, 0.79-1.00]; CSF Aβ40/42: AUC, 0.85 [95% CI, 0.72-0.98]). Among 9 brain donors, 6 had CTE (stages II-IV; none with Alzheimer disease). Seven had negative or intermediate p-tau217, concordant with Aβ-PET. Two p-tau217 outliers with stage III CTE had normal concentrations upon additional testing. Conclusions and Relevance The findings of this study suggest that plasma p-tau217 concentration is unlikely to be useful for the detection of CTE, but it does show utility for ruling out Aβ pathology in participants at risk for CTE.