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2354 citation(s) found for "Wu, Aaron".

An analysis of patient-reported outcomes among epidural steroid injection clinical trials
Khan, Adam , Ladd, Chase , Smith, Caleb J. , Douglas, A.G., Jacobsen, Sam, Otwell, Ryan, Pierce, Aaron, Relic, Aaron, Butler, Casey, Vassar, Matt, Roberts, Will , Douglas, Alexander, Jacobsen, Samuel M. , Hartwell, Micah L. , Khattab, Ahmad, Vassar, Matt B.

Regional Anesthesia & Pain Medicine | July 14, 2025 | Volume: No volume available | Issue: No issue available | Pages: rapm-2025-106861

10.1136/rapm-2025-106861 | PMID 40659444 Get It

Multicenter evaluation of blood culture contamination and blood cultures practices in US acute care hospitals: time for standardization
Fabre, Valeria , Hsu, Yea‐Jen , Carroll, Karen C. , Salinas, Alejandra , Abbo, Lilian M. , Bower, Chris , Berry, J. Michael, Degnan, Kathleen, Dhaubhadel, Pragya, Dress, Marci, Feeser, Baevin , Fisher, Mark , Flynn, Cynthia E. , Gettler, Erin , Glasser, Laurel J., Johnson, J. Kristie, Karaba, Sara M. , Kubischta, Alyssa, Landrum, B. Mark, Martinez, Marvin, Mermel, Leonard A. , Pepe, Dana , Qasba, Sonia, Rittmann, Barry , Robinson, Evan D. , Rosa, Rossana , Salinas, Jorge , Shah, Aditya , Schrank, Gregory M. , Spivak, Emily S , Stewart, Kathleen O., Wasylyshyn, Anastasia , Virk, Zunaira, Cosgrove, Sara E. , Abbo, Lilian M , Karaba, Sara M , Fabre, Valeria , Milstone, Aaron M. , Berry, Jennifer, Boyd, Sarah, Diekema, Daniel J. , Ford, Bradley , Glasser, Laurel J., Howard‐Anderson, Jessica , Kim, Justin , Mathers, Amy J. , Moehring, Rebekah W. , O’Horo, John C. , Rodriguez‐Nava, Guillermo , Ryder, Jonathan H. , Shelly, Mark , Talbot, Thomas R. , Schooneveld, Trevor Van , Gadala, Avinash

Journal of Clinical Microbiology | July 11, 2025 | Volume: 63 | Issue: 8 | Pages: No page available

10.1128/jcm.00530-25 | PMID 40643261 Get It

ABSTRACT Clinical and Laboratory Standards Institute (CLSI) recommends a blood culture contamination (BCC) threshold of <3%, with ≤1% considered optimal. However, there is not a standardized definition of BCC, and the effect of multiple definitions on BCC rates or what definitions laboratories use remain unknown. We surveyed 52 hospitals and analyzed 362,078 blood cultures (BCx) collected 1 September 2019 to 31 August 2021 from 62 intensive care units (ICUs) and 231 wards from 48 of these hospitals. We calculated and compared BCC rates using the College of American Pathologists (CAP) or CLSI criteria (both utilize a limited number of skin commensals to define BCC) and the comprehensive National Healthcare Safety Network (NHSN) commensal list. We characterized factors associated with BCC and related outcomes (central-line associated bloodstream infection [CLABSI] and vancomycin use). BCC, BCx positivity, and single BCx rates were monitored by 100%, 39%, and 21% of hospitals, respectively. Hospitals used CAP (65%), CLSI (17%), and NHSN (17%) criteria to define BCC. Mean BCC rate by CAP (CAP-BCC) was 1.38% for ICUs and 0.96% for wards. BCC rates remained similar by CLSI criteria but increased when using NHSN list. Sharing BCC data outside of the laboratory, measuring additional BCx quality indicators, and limiting central catheter-drawn BCx were associated with lower BCC rates. BCC was associated with higher CLABSI rates in ICUs. This study demonstrated variability in laboratory practices and opportunities to optimize BCx stewardship. IMPORTANCE Blood culture contamination (BCC) is associated with patient harm and unnecessary use of healthcare resources. BCC thresholds have been established; however, multiple BCC definitions exist. There is limited data on how BCC rates differ depending on the BCC definition used, what definitions laboratories most commonly use, or their approach to other blood cultures (BCx) quality indicators such as single rates or BCx positivity. A cross-sectional multicenter survey and analysis of BCx data from intensive care unit and wards revealed that most laboratories did not track single BCx or BCx positivity rates and that there was variability in how BCC was defined. Additionally, BCC rates were influenced by the definition used. BCC was associated with increased central-line associated bloodstream infection rates.
The Timing of Direct Oral Anticoagulant Usage Did Not Impact Outcomes Following Hip Arthroplasty for Femoral Neck Fractures
Chen, Xiao T. , Springer, Bryan D. , Borkar, Shalmali R. , Spaulding, Aaron , Yang, Linjun , Wyles, Cody C. , Bingham, Joshua S. , Wilke, Benjamin K. , Borkar, Shalmali , Porter, Steven B , Wilke, B K , Spaulding, Aaron , Wyles, Cody C , Bingham, Joshua S , Yang, Linjun , Porter, Steven B.

Journal of Bone and Joint Surgery | July 10, 2025 | Volume: 107 | Issue: 16 | Pages: 1857-1866

10.2106/jbjs.24.01293 | PMID 40638713 Get It

Background: Orthopaedic surgeons routinely delay surgical management of femoral neck fractures in patients taking direct oral anticoagulants (DOACs) to decrease perioperative bleeding and associated complications. However, this practice contradicts the principles of hip fracture management, as early surgery is associated with morbidity and mortality benefits. The purpose of this study was to quantify the association of DOAC use and perioperative outcomes in patients who underwent hemiarthroplasty (HA) or total hip arthroplasty (THA) for femoral neck fractures. We hypothesized that early surgical intervention on a patient taking a DOAC medication would not lead to worse perioperative outcomes. Methods: A retrospective cohort study was conducted on 2,833 patients who underwent primary THA or HA for femoral neck fractures between December 31, 2017, and January 29, 2024, across our hospital system. The patients taking a DOAC were divided into 3 groups based on the time since the last DOAC intake: 1 day, 2 days, and ≥3 days. Propensity matching was performed 1:1, accounting for age, sex, Elixhauser Comorbidity Index, preoperative chronic kidney disease stage, preoperative hemoglobin, body mass index, and hospital type. Subanalyses utilizing linear and conditional logistic regression models were performed to assess differences in outcomes between the groups that had a DOAC withheld and the control groups. Results: The mean age of all patients was 81 ± 10 years, 1,805 patients (64%) were women, and 207 patients (7%) were taking a DOAC prior to surgery. Despite comparable preoperative and postoperative hemoglobin levels between the groups that had a DOAC withheld and the control groups (all p > 0.05), the patients who had a DOAC withheld for 1 day were more likely to receive a postoperative blood transfusion (23.1% compared with 0%; p = 0.002). This difference in transfusion rate was not observed in other cohorts. There were no differences in medical complications, reoperation, discharge disposition, or mortality between the groups that had a DOAC withheld and the matched controls at any time point. Conclusions: Delaying surgical management due to DOAC medications may be unnecessary in patients undergoing arthroplasty for femoral neck fractures. Consideration should be given to adjusting transfusion triggers to reduce unwarranted blood transfusions in patients taking a DOAC. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.
Assessment of a Deep Learning Model Trained on Permanent Pathology for the Classification of Squamous Cell Carcinoma in Mohs Frozen Sections: Lessons Learned
Choudhary, Anirudh , Nassir, Shams , Yousif, Miranda , Hughes, Alysia , Kechter, Jacob , Leibovit-Reiben, Zachary , Stockard, Alyssa , Vidal, Nahid Y. , Rios-Duarte, Jorge A, Kechter, Jacob A, Rios‐Duarte, Jorge A. , Iyer, Ravishankar K. , Leibovit‐Reiben, Zachary , Mangold, Aaron R.

Dermatologic Surgery | July 9, 2025 | Volume: 52 | Issue: 1 | Pages: 31-35

10.1097/dss.0000000000004758 | PMID 40631753 Get It

BACKGROUND There is a scarcity of artificial intelligence models trained on frozen pathology. One way to expand the clinical utility of models trained on permanent pathology is by applying them to frozen sections and fine-tune based on weaknesses. OBJECTIVE To qualitatively evaluate a deep learning model trained on permanent pathology to classify squamous cell carcinoma on Mohs surgery frozen sections to learn model shortcomings and inform retraining and fine-tuning. MATERIALS AND METHODS The authors trained a model for classification of tumor on 746 skin biopsy slides and tested it on 15 Mohs surgery frozen sections. The authors estimated performance metrics and compared the regions of interest generated by the model with the original H&E slides. RESULTS The model achieved an AUC-ROC of 0.985 and 0.796 for tumor classification in permanent pathology and in frozen sections, respectively. Regions of interest for frozen sections with scarce tumor areas were inaccurate, focusing on normal tissue for slides classified as false negative, or highlighting structures different from tumor (e.g., inflammation, muscle, and nerves) for slides classified as true positive. CONCLUSION Deep anatomical structures more commonly present in Mohs frozen pathology might represent data out-of-distribution for models trained on permanent pathology, potentially leading to inadequate model outputs.
The Angiography Pattern of Buerger’s Disease: Challenges and Recommendations
Fazeli, Bahare , Poredoš, Pavel , Stephen, Edwin , Bashar, Abul Hasan Muhammad , Kozak, Matija, Catalano, M. , Salman, Mussaad Mohammaed Al, Altarazi, Louay, Dimakakos, Evangelos , Erer, Dilek , Farkas, Katalin , Fokou, Marcus , Ionac, Mihai , Iwai, Takehisa , Karahan, Oğuz , Kashani, Daniel , Kota, Albert Abhinay , Kröger, Knut , Kubat, Emre , Premkumar, Prabhu , Marcoccia, Antonella , Pandey, Sandeep Raj , Patel, Malay , Pécsvárady, Zsolt, Polat, Adıl , Ravari, Hassan , Selvaraj, Dheepak, Sharebiani, Hiva , Stanek, Agata , Taha, Wassila , Taheri, Hossein , Yuwono, Hendro Sudjono , Zor, Mustafa Hakan , Stephen, Edwin , Bashar, Abul Hasan Muhammad , Catalano, Mariella , Dimakakos, Evangelos , Farkas, Katalin , Ionac, Mihai , Karahan, Oguz , Kashani, Daniel , Kota, Albert , Kubat, Emre , Kumar, Prabhu Prem , Marcoccia, Antonella , Polat, Adil , Ravari, Hassan , Sharebiani, Hiva , Stanek, Agata , Liew, Aaron , Antignani, Pier Luigi , Desai, Sanjay, Hüssein, Emad , Małecki, Rafał , Schernthaner, G. , Szuba, Andrzej

Journal of Clinical Medicine | July 8, 2025 | Volume: 14 | Issue: 14 | Pages: 4841

10.3390/jcm14144841 | PMID 40725544 Get It

In 2023, the VAS international working group on Buerger’s Disease (BD) recommended two diagnostic criteria based on a prior Delphi study: “definitive” and “suspected”. The “definitive” criteria are history of smoking, typical angiography, and typical histopathological features. All three features are mandatory to confirm a “definitive” diagnosis of BD. The conundrum is—what features should be considered typical of BD angiography? According to this review, segmental occlusion of infrapopliteal arteries, corkscrew collaterals that appear to continue the occluded arterial segment (Martorell’s sign) or bypass the segmental occlusion, absence of atherosclerotic plaque or aneurysm could differentiate BD from ASO. Hence, for “typical” BD angiography, these manifestations should certainly be considered. However, data for differentiating angiography patterns of BD from the small- and medium-sized vasculitis including Behcet’s disease, scleroderma, hepatitis associated vasculitis, and anti-phospholipid syndrome are limited. Further studies for investigating the angiography pattern in BD patients in early and late presentation of BD, particularly in the patients with long-term follow up, are highly recommended.
Outcomes of Patients With Embolic Stroke of Undetermined Source Treated With Antiplatelet Agents or Anticoagulation
Siegler, James E. , Badillo‐Goicoechea, Elena , Penckofer, Mary , Eklund, Kelsey , Yaghi, Shadi , Stretz, Christoph , Lineback, Christina , Stamm, Brian , Peter, Shani , D’Souza, Marissa , Conyers, Frank, Khasiyev, Farid , Kerrigan, Deborah , Lewis, Skylar, Ali, Hamid , Nour, Hassan Aboul , Sharma, Richa, Glover, Patrick , Thompson, Sean, Alshaer, Qasem , Thottempudi, Neeharika, Melkumova, Emiliya , Chionatos, Rafail , Daniel, Jean-Philippe Auguste, Frankel, Michael , Dumitrașcu, Oana , Parikh, Parth , Doolittle, Charles, Yahnke, Ian, Sathya, Anvitha , Kang, Jieun , Kirchhoffer, Kaitlyn, Bowman, Anna, Smith, M. J., Asabere, Aaron, Shahrivari, Mahan, Sheibani, Nazanin , Krishnaiah, Balaji , Gaudio, Elizabeth, Rothstein, Aaron , Alvi, Muhammad M. , Annam, Saketh , Amankwah, Curtis , Kam, Wayneho , Abburi, Nandini , Rojas-Soto, Diana , Molaie, Amir , Khezri, Nicole, Zubair, Adeel , Abbasi, Mehdi , Coevering, Russell J. Van , Nedelcu, Simona , Herpich, Franziska , Chahien, Dalia, Sehgal, Siddharth, Liebeskind, David S. , Linares, Guillermo , Zha, Alicia , Sarkar, Monica , Xi, Romi, Nelson, Ashley, Qdais, Ahmad Abu, Kasab, Sami Al , Singh, Eesha , Patel, Vivek , Mehndiratta, Prachi , DeMarco, Alexis, Cucchiara, Brett , Omran, Setareh Salehi , Dubinski, Michael , Ackerman, Jiyoun, Thon, Jesse , Brown, Samantha , Siegler, James E , Goicoechea, Elena Badillo , Lineback, Christina M , Conyers, F Garrett , Aboul-Nour, Hassan , Sharma, Richa , Nahab, Fadi B , Glover, Patrick , Alshaer, Qasem N , de Havenon, Adam H , Melkumova, Emiliya , Chionatos, Rafail A , Jillella, Dinesh V , Frankel, Michael R , Dumitrascu, Oana M , Sathya, Anvitha , Smith, Matthew M , Brorson, James R , Elangovan, Cheran , Krishnaiah, Balaji , Sloane, Kelly L , Rothstein, Aaron , Alvi, Muhammad M , Kam, Wayneho , Abburi, Nandini , Farooqui, Mudassir , Molaie, Amir , Zubair, Adeel , Abbasi, Mehdi , Van Coevering, Russell J , Nedelcu, Simona , Liebeskind, David S. , Linares, Guillermo , Zha, Alicia , Abu Qdais, Ahmad , Al Kasab, Sami , Aziz, Yasmin , Mehndiratta, Prachi , Sharrief, Anjail , Cucchiara, Brett L , Salehi Omran, Setareh , Nguyen, Thanh N , Thon, Jesse , Yaghi, Shadi , Stretz, Christoph , Penckofer, Mary , Khasiyev, Farid , Brown, Samantha J , Eklund, Kelsey , Stamm, Brian , Daniel, Jean-Philippe Auguste , D'Souza, Marissa , Sharma, Richa , Thottempudi, Neeharika , Havenon, Adam de , Culbertson, Collin J , Jillella, Dinesh , Daniel, Jean-Philippe Auguste, Ro, Jennifer , Brown, Samantha, Doolittle, Charles, Brorson, James R. , Asabere, Aaron, Elangovan, Cheran , Chen, Lucia , Aziz, Yasmin , Nguyen, Thanh N. , Ackerman, Jiyoun

Neurology | July 3, 2025 | Volume: 105 | Issue: 3 | Pages: No page available

10.1212/wnl.0000000000213876 | PMID 40609061 Get It

International Delphi Consensus on Medial Meniscal Root Tears Shows High Agreement on Diagnosis, Treatment, and Rehabilitation but Lack of Agreement on Treatment of Asymptomatic Tears
Chahla, Jorge , Chahla, Jorge, García, José Rafael , Tollefson, Luke V. , Dzidzishvili, Lika , Gerhold, Cameron , Krych, Aaron J. , LaPrade, Robert F., Group, Meniscus Root International Expert, Bassett, Ashley J., Bernholt, David L., Bhatia, Sanjeev, Bøe, Berte, Brown, Charles H., Chung, Kyu Sung, Cohen, Moisés, Engebretsen, Lars, Familiari, Filippo, Faucett, Scott C., Feucht, Matthias J., Furumatsu, Takayuki, Geeslin, Andrew G., Getgood, Alan M.J., Hiranaka, Takaaki, Inderhaug, Eivind, Iñiguez, C. Magaly, Johnson, Darren L., Kim, Jin Goo, Kim, Sung‐Hwan, Kodama, Yuya, Kon, Elizaveta, Kopf, Sebastian, LaPrade, Christopher M., Larson, Christopher M., Lee, Dhong Won, Lind, Martin, Logan, Catherine A., López‐Torres, Irene I., Lording, Timothy, Maestu, Rodrigo, Moatshe, Gilbert, Monson, Jill K., Murray, Iain R., Musahl, Volker, Vyhmeister, Roberto Negrin, Okazaki, Yuki, Parker, David, Petersen, Wolf, Riboh, Jonathan C., Seil, Romain, Servien, Elvire, Sonnery‐Cottet, Bertrand, Spalding, Tim, Stevenson, Ciara, Stuart, Michael J., Tanaka, Miho J., Tapasvi, Sachin, Tuca, Maria, Wal, Wybren A. van der, Verma, Nikhil N., Bormann, Richard PB. von, Yanke, Adam B., Krych, Aaron J., Kopf, Sebastian , Krych, Aaron J , Chahla, Jorge A , Chahla, Jorge, Allende, Felicitas , LaPrade, Robert F., Group, Meniscus Root International Expert, Bassett, Ashley J., Bernholt, David L., Bhatia, Sanjeev, Bøe, Berte, Brown, Charles H., Chung, Kyu Sung, Cohen, Moisés, Engebretsen, Lars, Familiari, Filippo, Faucett, Scott C., Feucht, Matthias J., Furumatsu, Takayuki, Geeslin, Andrew G., Getgood, Alan M.J., Hiranaka, Takaaki, Inderhaug, Eivind, Iñiguez, C. Magaly, Johnson, Darren L., Kim, Jin Goo, Kim, Sung‐Hwan, Kodama, Yuya, Kon, Elizaveta , LaPrade, Christopher M., Larson, Christopher M., Lee, Dhong Won, Lind, Martin, Logan, Catherine A., López‐Torres, Irene I., Lording, Timothy, Maestu, Rodrigo, Moatshe, Gilbert, Monson, Jill K., Murray, Iain R., Musahl, Volker, Vyhmeister, Roberto Negrin, Okazaki, Yuki, Parker, David, Petersen, Wolf, Riboh, Jonathan C., Seil, Romain, Servien, Elvire, Sonnery‐Cottet, Bertrand, Spalding, Tim, Stevenson, Ciara, Stuart, Michael J., Tanaka, Miho J., Tapasvi, Sachin, Tuca, Maria, Wal, Wybren A. van der, Verma, Nikhil N., Bormann, Richard PB. von, Yanke, Adam B., Krych, Aaron J.

Arthroscopy | July 3, 2025 | Volume: 41 | Issue: 11 | Pages: 4683-4698

10.1016/j.arthro.2025.06.028 | PMID 40614908 Get It

Purpose To develop an expert consensus statement on the diagnosis, management, and rehabilitation of medial meniscal root tears (MMRTs) using a modified Delphi technique. Methods A working group developed statements on MMRT diagnosis, nonoperative management, surgical indications, surgical management, alignment, and rehabilitation using modified Delphi techniques. Fifty‐six experts were surveyed over 3 rounds to reach consensus, with agreement measured on a 5‐point Likert scale. Statements were included, revised, or excluded on the basis of predefined thresholds (≥75% agreement, <20% disagreement). Experts suggested revisions or new statements in the first 2 rounds, and final consensus statements were included. Results All 56 experts completed 3 survey rounds. Experts agreed that root tears may occur with no known history of trauma, typically in older patients, and that it should be diagnosed with an magnetic resonance imaging. In symptomatic patients with MMRTs without advanced osteoarthritis should be repaired using an anatomic transtibial pull‐out technique (performing a pie‐crusting technique can be helpful for visualization). Nonoperative management is advised for patients with advanced osteoarthritis. High tibial osteotomy may be considered for significant varus malalignment during MMRT repair. The only statement without consensus was the management of asymptomatic MMRTs with mild medial compartment cartilage wear, indicating ongoing debate. Conclusions Overall, 98% of statements reached consensus. There is agreement that magnetic resonance imaging is the gold standard for diagnosis. Symptomatic MMRTs without advanced osteoarthritis should be repaired early using an anatomic transtibial pull‐out technique. End‐stage knee osteoarthritis warrants nonoperative management of MMRTs, and a structured postoperative protocol with limited weightbearing and range of motion is essential after repair. No agreement was reached on managing asymptomatic MMRTs in patients without significant medial compartment degeneration. Meniscal centralization sutures may help in cases of substantial extrusion, but their routine use is debated. Level of Evidence Level V, consensus of expert opinion.
Pneumocystis Pneumonia in Cirrhosis: An Underrecognized Fungal Infection in a Vulnerable Host
Pulsipher, Aaron M. , Barnhill, Michele , Vikram, Holenarasipur R. , Gotway, Michael B. , Cartin‐Ceba, Rodrigo , Zhou, Kevin , Thompson, Emily , Aqel, Bashar , Ham, Kealy R., Thompson, Emily R , Aqel, Bashar A. , Ham, Kealy , Vikram, Holenarasipur R. , Gotway, Michael B , Pulsipher, Aaron M , Limper, Andrew H.

Journal of Fungi | July 3, 2025 | Volume: 11 | Issue: 7 | Pages: 500

10.3390/jof11070500 | PMID 40985382 Get It

Pneumocystis pneumonia (PCP) is a serious fungal infection affecting immunocompromised hosts. Decompensated cirrhosis leads to cirrhosis-associated immune dysfunction (CAID), a form of impaired cellular immunity that may predispose patients to opportunistic infections such as PCP. We conducted a retrospective review of 727 patients with proven or probable PCP from 2017 to 2025. Of these, 33 had decompensated cirrhosis. These patients were stratified into two groups: Cirrhosis Only (n = 16) and Cirrhosis with Additional Immunocompromising Conditions (n = 17). Among the patients with cirrhosis, the overall mortality was 48%, with the 90-day mortality reaching 57.6% (95% CI: 39.2–74.5%). Compared with those without cirrhosis, the patients with cirrhosis had a higher risk of mortality (OR: 4.08, 95% CI: 2.01–8.30, p < 0.001), increased intensive care unit (ICU) admission (87% vs. 42%, p < 0.001), and greater need for renal replacement therapy (54.6% vs. 7.5%, p < 0.001). These findings suggest that decompensated cirrhosis alone may represent a sufficient and underrecognized risk factor for PCP, with a high associated mortality. Given the preventable nature of this infection, future studies are needed to assess the incidence, define the risk, and investigate the role of prophylaxis in this vulnerable population.
Targeting the IL-36 receptor with spesolimab mitigates residual inflammation and prevents generalized pustular psoriasis flares
Krueger, James G. , Sarkar, Mrinal K. , Lebwohl, Mark , Gordon, Kenneth B. , Bogle, Rachael , Cole, C. , Coon, Anthony, Burden, A. David , Zheng, Min , Mangold, Aaron R. , Anadkat, Milan J. , Barker, Jonathan N., Tang, Ming , Becker, Kolja , Delić, Denis , Thoma, Christian , Mangold, A R , Sarkar, Mrinal K , Morita, Akimichi , Wasikowski, Rachael, Langley, Richard G B , Warren, Richard Bruce , Mostaghimi, Arash , Strober, Bruce E , Barker, Jonathan N., Merola, Joseph F. , Tsoi, Lam C. , Gudjonsson, Johann E

Journal of Clinical Investigation | July 1, 2025 | Volume: 135 | Issue: 17 | Pages: No page available

10.1172/jci188530 | PMID 40591420 Get It

Refinement of day 28 treatment response criteria for acute GVHD: a collaboration study of the JSTCT and MAGIC
Akahoshi, Yu , Inamoto, Yoshihiro , Spyrou, Nikolaos , Diniz, Márcio A. , Ayuk, Francis , Choe, Hannah , Doki, Noriko , Eto, Tetsuya, Etra, Aaron , Holler, Ernst , Kawakita, Toshiro , Tanaka, Takashi , Vášová, Ingrid, Ishimaru, Fumihiko , Fukuda, Takahiro, Chen, Yi‐Bin , Nakamura, Ryotaro , Ferrara, James L.M. , Kanda, Yoshinobu , Diniz, Marcio A , Doki, Noriko , Hexner, Elizabeth , Hogan, William J , Tanaka, Takashi , Yoshihara, Satoshi , Ishimaru, Fumihiko , Chen, Yi-Bin , Kanda, Junya , Nakamura, Ryotaro , Atsuta, Yoshiko , Levine, John E , Teshima, Takanori , Akahoshi, Yu , Nakasone, Hideki , Asada, Noboru , Eto, Tetsuya , Hexner, Elizabeth O. , Hiramoto, Nobuhiro , Hogan, William J. , Kataoka, Keisuke , Tanaka, Masatsugu , Uchida, Naoyuki , Levine, John E.

Blood Advances | July 1, 2025 | Volume: 9 | Issue: 18 | Pages: 4640-4653

10.1182/bloodadvances.2025016233 | PMID 40590886 Get It

Abstract Overall response (OR) that combines complete (CR) and partial responses (PR) is the conventional end point for acute graft-versus-host disease (GVHD) trials. Because PR includes heterogeneous clinical presentations, reclassifying PR could produce a better end point. Patients in the primary treatment cohort from the Japanese Society for Transplantation and Cellular Therapy (JSTCT) were randomly divided into training and validation sets. In the training set, a classification and regression tree algorithm generated day 28 refined response (RR) criteria based on symptoms at treatment and day 28. We then evaluated RR for primary and second-line treatments, using the area under the receiver operating characteristic curve (AUC) and negative predictive value (NPV) for 6-month nonrelapse mortality as performance measures. RR considered patients with grade 0/1 at day 28 without additional treatment as responders. RR for primary treatment produced higher AUCs than OR with small improvement of NPVs in both validation sets: JSTCT (AUC, 0.73 vs 0.69 [P &lt; .001]; NPV, 92.0% vs 89.6% [P &lt; .001]) and the Mount Sinai Acute GVHD International Consortium (MAGIC; AUC, 0.71 vs 0.68 [P = .032]; NPV, 90.9% vs 89.8% [P = .009]). RR for second-line treatment produced similar AUCs but much higher NPVs than OR in both validation sets of JSTCT (AUC, 0.64 vs 0.63 [P = .775]; NPV, 74.5% vs 66.0% [P &lt; .001]) and MAGIC (AUC, 0.67 vs 0.64 [P = .105]; NPV, 86.8% vs 76.1% [P = .004]). Classifying persistent but mild skin symptoms as responses and residual lower gastrointestinal GVHD as nonresponses were major drivers in improving the prognostic performance of RR. Our externally validated day 28 RR would serve as a better end point than conventional criteria in future first- and second-line treatment trials.