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394 citation(s) found for "Iyer, P G".

A Novel Unsupervised You Only Listen Once (YOLO) Machine Learning Platform for Automatic Detection and Characterization of Prominent Bowel Sounds Towards Precision Medicine
Yerrapragada, Gayathri, Lee, Jieun , Shariff, Mohammed Naveed , Elangovan, Poonguzhali , Gopalakrishnan, Keerthy, Kaur, Avneet , Sood, Divyanshi, Rapolu, Swetha, Gohri, Jay , Panjwani, Gianeshwaree Alias Rachna , Ansari, Rabiah Aslam, Mikkilineni, Jahnavi, Asadimanesh, Naghmeh, Natarajan, T.K. , Janarthanan, Jayarajasekaran, Karuppiah, Shiva Sankari, Iyer, Vivek , Helgeson, Scott A. , Arunachalam, Shivaram P. , Shariff, Mohammad Naveed , Natarajan, Thangeswaran , Iyer, Vivek N , Arunachalam, S P , Elangovan, Poonguzhali , Helgeson, Scott A , Panjwani, Gianeshwaree Alias Rachna , Yerrapragada, Gayathri, Ansari, Rabiah Aslam, Akshintala, Venkata S.

Bioengineering | November 19, 2025 | Volume: 12 | Issue: 11 | Pages: 1271

10.3390/bioengineering12111271 | PMID 41301229 Get It

Phonoenterography (PEG) offers a non-invasive and radiation-free technique to assess gastrointestinal activity through acoustic signal analysis. In this feasibility study, 110 high-resolution PEG recordings (44.1 kHz, 16-bit) were acquired from eight healthy individuals, yielding 6314 prominent bowel sound (PBS) segments through automated segmentation. Each event was characterized using a 279-feature acoustic profile comprising Mel-frequency cepstral coefficients (MFCCs), their first-order derivatives (Δ-MFCCs), and six global spectral parameters. After normalization and dimensionality reduction with PCA and UMAP (cosine distance, 35 neighbors, minimum distance = 0.01), five clustering strategies were evaluated. K-Means (k = 5) achieved the most favorable balance between cluster quality (silhouette = 0.60; Calinski–Harabasz = 19,165; Davies–Bouldin = 0.68) and interpretability, consistently identifying five acoustic patterns: single-burst, multiple-burst, harmonic, random-continuous, and multi-modal. Temporal modeling of clustered events further revealed distinct sequential dynamics, with Single-Burst events showing the longest dwell times, random continuous the shortest, and strong diagonal elements in the transition matrix confirming measurable state persistence. Frequent transitions between random continuous and multi-modal states suggested dynamic exchanges between transient and overlapping motility patterns. Together, these findings demonstrate that unsupervised PEG-based analysis can capture both acoustic variability and temporal organization of bowel sounds. This annotation-free approach provides a scalable framework for real-time gastrointestinal monitoring and holds potential for clinical translation in conditions such as postoperative ileus, bowel obstruction, irritable bowel syndrome, and inflammatory bowel disease.
Spinal versus general anesthesia in robotic minimally invasive transforaminal lumbar interbody fusion: a comparative study on surgical outcomes
Llano, Juan P Navarro-Garcia de , Iyer, Harshvardhan , Sánchez-Garavito, Jesús E. , Safa, Adrian , Campo, Isabel Martin del , Graepel, Stephen , Patterson, Jennifer S., White, Kate E., Bojaxhi, Elird , Navarro-Ramírez, Rodrigo , Buchanan, Ian A. , Chen, Selby G. , Roberts, Andrew P, Martin Del Campo, Isabel, Iyer, Harshvardhan G , Ríos-Zermeño, Jorge , Roberts, Andrew P., ReFaey, Karim , Akinduro, Oluwaseun O. , Chen, Selby , Abode-Iyamah, Kingsley

Journal of Neurosurgery: Spine | November 17, 2025 | Volume: 44 | Issue: 1 | Pages: 99-107

10.3171/2025.6.spine25442 | PMID 41105976 Get It

OBJECTIVE The implementation of robotics and spinal anesthesia (SA) in spine surgery is rapidly expanding, offering significant benefits for an increasingly complex and aging patient population with degenerative spinal disease. Here, the authors present the largest cohort to date evaluating the combined use of these two techniques in minimally invasive (MIS) transforaminal lumbar interbody fusion (TLIF). METHODS The authors retrospectively analyzed surgical outcomes of a series of patients who underwent robot-assisted (RA)–MIS TLIF under SA and general anesthesia (GA) at their institution from 2018 to 2024. Primary outcomes included operative times and postoperative pain intensity. Secondary outcomes included estimated blood loss, intraoperative complications, postoperative functional status, length of stay (LOS), and discharge status. To address potential confounders, a 1:1 propensity score–matching and regression analysis was implemented. Statistical analyses were conducted using Python. RESULTS A total of 209 patients underwent RA-MIS TLIF, with 31 (14.83%) receiving SA and 178 (85.17%) GA. After propensity score matching, the SA cohort demonstrated significantly shorter median total operating room (OR) time, total procedure time, time from entering the OR to skin incision, and time from closure to leaving the OR (all p < 0.01). Additionally, postoperative pain scores were significantly lower (p < 0.01), and LOS was significantly shorter (p < 0.01) in the SA cohort. Regression analysis, adjusting for potential confounders, further supported these findings. CONCLUSIONS RA-MIS TLIF fusion under SA is a safe and effective approach that significantly reduces operative time, postoperative pain, and hospital LOS in patients undergoing surgery for degenerative lumbar spine disease.
2025 American College of Rheumatology ( ACR ) Guideline for the Treatment of Systemic Lupus Erythematosus
Sammaritano, Lisa R. , Askanase, Anca , Bermas, Bonnie L. , Dall’Era, Maria , Duarte‐García, Alí , Hiraki, Linda T. , Aranow, Cynthia , Barnado, April , Broder, Anna , Chowdhary, Vaidehi , Hersh, Aimee O. , Jules, Marimee, Kalunian, Kenneth , Smith, Benjamin J. , Smith, Natalie, Thomas, Asha , Timlin, Homa , Bartels, Christie M. , Cunha, Joanne S., DeQuattro, Kimberly , Gomes, Laís Lopes Almeida , Cuéllar‐Gutiérrez, María C. , Iyer, Priyanka , Johannemann, Andrew, Jorge, April , Kasturi, S.Psi. Taufik , Khawandi, Jana , Legge, Alexandra , Liang, Kimberly P. , Lockwood, Megan M. , Sánchez-Rodríguez, Alain , Turgunbaev, Marat, Williams, Jessica N. , Turner, Amy S. , Aranow, Cynthia , Barnado, April , Brunner, Hermine I , Chong, Benjamin F , Hersh, Aimee O , Rubinstein, Tamar B , Smith, Benjamin J , Wallace, Daniel J , Bartels, Christie M , DeQuattro, Kimberly , Figueroa-Parra, Gabriel , Garg, Shivani , Gomes, Lais Lopes Almeida , Cuéllar-Gutiérrez, María C, Jorge, April , Kasturi, Shanthini , Kawtharany, Hassan , Liang, Kimberly P , Lockwood, Megan M , Sanchez-Rodriguez, Alain , Williams, Jessica N , Turner, Amy S , Duarte-García, Alí , Sammaritano, Lisa R , Askanase, Anca , Bermas, Bonnie , Son, Mary Beth F. , Werth, Victoria P. , Chong, Benjamin F. , Izmirly, Peter , Jules, Marimee, Kamen, Diane L. , Thomas, Asha, Azzam, Muayad , Fava, Andrea , Figueroa‐Parra, Gabriel , Garg, Shivani , Kawtharany, Hassan , Mustafa, Reem A

Arthritis & Rheumatology | November 4, 2025 | Volume: 78 | Issue: 7 | Pages: 1361-1386

10.1002/art.43452 | PMID 41187097 Get It

Objective To provide evidence‐based and expert guidance for the treatment and management of non‐renal systemic lupus erythematosus (SLE); treatment and management of lupus nephritis are addressed in a separate guideline. Methods Clinical questions for treatment and management of SLE were developed in the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were developed for each PICO question, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess evidence quality and formulate recommendations. The Voting Panel achieved a consensus of ≥70% agreement on the direction (for or against) and strength (strong or conditional) of each recommendation. Results We present recommendations and ungraded, consensus‐based good practice statements for the treatment and management of SLE that are applicable to pediatric and adult patients. Recommendations emphasize uniform treatment with hydroxychloroquine, limiting duration of glucocorticoid use, and early introduction of conventional and/or biologic immunosuppressive therapies to achieve and maintain control of SLE inflammation (remission or a low level of disease activity), reduce SLE‐related morbidity and mortality, and minimize medication‐related toxicities. Conclusion This guideline presents direction regarding treatment and management of SLE and provides a foundation for well‐informed, shared clinician–patient decision‐making. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each person with SLE.
2025 American College of Rheumatology ( ACR ) Guideline for the Treatment of Systemic Lupus Erythematosus
Sammaritano, Lisa R. , Askanase, Anca , Bermas, Bonnie L. , Dall’Era, Maria , Duarte‐García, Alí , Hiraki, Linda T. , Aranow, Cynthia , Barnado, April , Broder, Anna , Chowdhary, Vaidehi , Hersh, Aimee O. , Jules, Marimee, Kalunian, Kenneth , Smith, Benjamin J. , Smith, Natalie, Thomas, Asha , Timlin, Homa , Cunha, Joanne S., DeQuattro, Kimberly , Gomes, Laís Lopes Almeida , Iyer, Priyanka , Johannemann, Andrew, Jorge, April , Kasturi, S.Psi. Taufik , Khawandi, Jana , Legge, Alexandra , Liang, Kimberly P. , Lockwood, Megan M. , Sánchez-Rodríguez, Alain , Turgunbaev, Marat, Williams, Jessica N. , Turner, Amy S. , Aranow, Cynthia , Barnado, April , Brunner, Hermine I , Chong, Benjamin F , Hersh, Aimee O , Rubinstein, Tamar B , Smith, Benjamin J , Wallace, Daniel J , Bartels, Christie M , DeQuattro, Kimberly , Figueroa-Parra, Gabriel , Garg, Shivani , Gomes, Lais Lopes Almeida , Cuéllar-Gutiérrez, María C, Jorge, April , Kasturi, Shanthini , Kawtharany, Hassan , Liang, Kimberly P , Lockwood, Megan M , Sanchez-Rodriguez, Alain , Williams, Jessica N , Turner, Amy S , Duarte-García, Alí , Sammaritano, Lisa R , Askanase, Anca , Bermas, Bonnie , Son, Mary Beth F. , Werth, Victoria P. , Chong, Benjamin F. , Izmirly, Peter , Kamen, Diane L. , Thomas, Asha, Azzam, Muayad , Bartels, Christie M. , Fava, Andrea , Figueroa‐Parra, Gabriel , Garg, Shivani , Cuéllar‐Gutiérrez, María C. , Kawtharany, Hassan , Mustafa, Reem A

Arthritis Care & Research | November 3, 2025 | Volume: 78 | Issue: 7 | Pages: 815-839

10.1002/acr.25690 | PMID 41182321 Get It

Objective To provide evidence‐based and expert guidance for the treatment and management of non‐renal systemic lupus erythematosus (SLE); treatment and management of lupus nephritis are addressed in a separate guideline. Methods Clinical questions for treatment and management of SLE were developed in the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were developed for each PICO question, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess evidence quality and formulate recommendations. The Voting Panel achieved a consensus of ≥70% agreement on the direction (for or against) and strength (strong or conditional) of each recommendation. Results We present recommendations and ungraded, consensus‐based good practice statements for the treatment and management of SLE that are applicable to pediatric and adult patients. Recommendations emphasize uniform treatment with hydroxychloroquine, limiting duration of glucocorticoid use, and early introduction of conventional and/or biologic immunosuppressive therapies to achieve and maintain control of SLE inflammation (remission or a low level of disease activity), reduce SLE‐related morbidity and mortality, and minimize medication‐related toxicities. Conclusion This guideline presents direction regarding treatment and management of SLE and provides a foundation for well‐informed, shared clinician–patient decision‐making. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each person with SLE.
Comparative Outcomes of Brachyury Vaccine vs. Imatinib in Advanced Chordoma: A Mayo Clinic Experience
Llano, Juan P Navarro-Garcia de , Iyer, Harshvardhan , Hoffman, Holly , Seetharam, ­Mahesh , Attia, Steven , Navarro-Garcia de Llano, Juan P , Iyer, Harshvardhan G , Hoffman, Harry C , Akinduro, Oluwaseun O.

Cancers | October 31, 2025 | Volume: 17 | Issue: 21 | Pages: 3493

10.3390/cancers17213493 | PMID 41228286 Get It

Background/Objectives: Chordoma, a rare slow-growing malignant bone tumor, remains therapeutically challenging due to its invasive nature. We examined institutional outcomes comparing imatinib and brachyury-directed vaccines. Methods: We used data from three sites of our quaternary care academic institution to analyze demographics, time to progression, overall survival, and adverse events in chordoma patients treated with imatinib or enrolled in a brachyury vaccine trial. Results: We included a total of 52 patients (8 in the brachyury vaccine cohort and 44 in the imatinib cohort) in the analysis. As expected, sacrococcygeal location was the most predominant in both cohorts: 62.5% in the brachyury cohort and 45.5% in the imatinib cohort. No demographic differences were present between the cohorts. ECOG was similar in both groups (p = 0.796). The primary outcome, time to progression (TTP), was shorter in the brachyury compared to the imatinib cohort (5.6 vs. 13 months, p = 0.0589), almost reaching statistical significance. Overall survival (OS) was comparable, 211 vs. 212 months for the brachyury and imatinib cohorts, respectively (p = 0.277). Although the brachyury vaccine cohort presented a higher incidence of adverse events than the imatinib cohort (75% vs. 31.8%, p = 0.021), the severity was milder. Conclusions: Imatinib showed longer disease control than the brachyury vaccine, though overall survival was similar. Future studies and deeper molecular insights are essential to develop better therapies and improve patient quality of life.
Leveraging Artificial Intelligence for the Diagnosis of Systemic Sclerosis Associated Pulmonary Arterial Hypertension: Opportunities, Challenges, and Future Perspectives
Jain, Samiksha , Kaur, Avneet , Qadeer, Abdul , Ghosh, Victor , Thota, Shivani, Banala, Mallareddy , Lee, Jieun , Yerrapragada, Gayathri, Poonguzhali, E. , Shariff, Mohammed Naveed , Natarajan, T.K. , Janarthanan, Jayarajasekaran, Kala, Jayavinamika Jayapradhaban, Richard, Samuel, Vommi, Saai Poornima, Karuppiah, Shiva Sankari, Muthyala, Anjani, Iyer, Vivek , Helgeson, Scott A. , Mitra, Dipankar , Arunachalam, Shivaram P. , Natarajan, Thangeswaran , Jayapradhaban Kala, Jayavinamika, Iyer, Vivek N , Arunachalam, S P , Helgeson, Scott A , Shariff, Mohammad Naveed , Qadeer, Abdul , Thota, Shivani

Advances in Respiratory Medicine | October 17, 2025 | Volume: 93 | Issue: 5 | Pages: 47

10.3390/arm93050047 | PMID 41149139 Get It

Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is a life-threatening vascular complication of SSc, marked by high morbidity and mortality. Early diagnosis remains a major challenge due to nonspecific symptoms and the limitations of conventional tools such as echocardiography (ECHO), pulmonary function tests (PFTs), and serum biomarkers. This review evaluates the emerging role of artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), in improving the diagnostic landscape of SSc-PAH. A comprehensive literature search was conducted across PubMed, Scopus, IEEE Xplore, Embase and Google Scholar to identify studies involving AI applications in SSc, pulmonary arterial hypertension (PAH), and their intersection. Evidence indicates that AI models can assist interpretation across modalities, including heart sounds, ECGs, chest X-rays (CXRs), ECHOs, CT pulmonary angiography (CTPA), and omics-based biomarkers. While several models show encouraging diagnostic performance, their accuracy varies by dataset and modality, and most require external validation against right heart catheterization (RHC)-confirmed cohorts. Integrating multimodal data through AI frameworks may enhance early recognition and individualized risk stratification; however, these tools remain exploratory. Future work should emphasize harmonized hemodynamic definitions, transparent validation protocols, and SSc-specific datasets to ensure clinical applicability and reproducibility.
Reduced-Dose Chest CTA for the Detection of Pulmonary Arteriovenous Malformations in Pediatric Patients With Hereditary Hemorrhagic Telangiectasia
Saadeh, Zaid , Demirel, Nadir , Koo, Chi Wan , Oo, Daniel W. , Tandon, Yasmeen K. , Thorne, Jamison E. , Zhou, Zhongxing , Yu, Lifeng , Hull, Nate C., Oo, Daniel, Horst, Kelly K. , Iyer, Vivek , Larson, Nicholas B. , McCollough, Cynthia H. , Yu, Lifeng , Hull, Nathan C.

Journal of Computer Assisted Tomography | October 15, 2025 | Volume: 50 | Issue: 2 | Pages: 254-262

10.1097/rct.0000000000001804 | PMID 41091128 Get It

Objectives: To determine the feasibility of reduced-dose chest computed tomographic angiography (CTA) with convolutional neural network (CNN) denoising for detecting pulmonary arteriovenous malformations (pAVMs) in children with hereditary hemorrhagic telangiectasia (cwHHT). Methods: Fifteen cwHHT underwent a chest CTA (ie, a controlled “study” dose). Noise was inserted to simulate a quarter dose (QD) exam. Images were reconstructed using iterative reconstruction (IR) and our self-trained CNN denoising model. For each case, 3 sets of images were created: study dose (SD)+IR, QD+IR, and QD+CNN. Two thoracic radiologists independently scored each set to assess quality, spatial resolution, artifacts, and the presence of pAVMs using 4-level ordinal scales. Quantitative assessments of image quality were performed using contrast-to-noise ratios (CNRs) with comparisons made between the experimental conditions. Results: Thirteen of the 15 patients recruited with hereditary hemorrhagic telangiectasia (mean age: 9.3±4.5 y) were positive for pAVM by transthoracic contrast echocardiography. The sensitivities using QD+CNN were 0.85 and 1.00 for readers 1 and 2, respectively. This was compared with 0.69 and 0.84 using QD+IR versus 0.85 and 0.92 for SD+IR. Inter-reader agreement for pAVM detection utilizing QD+CNN was moderate and resulted in kappa=0.59 ( P =0.012). The subjective assessments for QD+CNN were comparable to the SD technique. Regression analysis of reader scores revealed improved quality in QD+CNN versus QD+IR ( P =0.001). Similarly, the QD+CNN condition demonstrated the highest CNRs. Conclusions: Reduced-dose chest CTA with CNN denoising provides a level of sensitivity comparable to standard dose CTA and high CNRs for the detection of pAVMs in cwHHT.
State-of-the-Art Review of Current Technology in Pressure Injury Early Detection
Bogie, Kath M. , Sonenblum, Sharon Eve , Newton, David , Vargo, Deanna M., Ronin, Jamie, Hester, Amy , Gillespie, Carroll, Tescher, Ann, Iyer, Vignesh , Brienza, David M. , Tzen, Yi-Ting , Delmore, Barbara , M Bogie, Kath , Sonenblum, Sharon Eve , Newton, David , Iyer, Vignesh , Brienza, David , Delmore, Barbara

Advances in Skin & Wound Care | October 14, 2025 | Volume: 38 | Issue: 10 | Pages: E128-E137

10.1097/asw.0000000000000358 | PMID 41085249 Get It

OBJECTIVE: To review currently available devices on pressure injury (PI) early detection, summarize challenges and opportunities to clinical implementation, and propose evaluation standards for device categories. DATA SOURCES: PubMed and US Food and Drug Administration (FDA) databases. STUDY SELECTION: Published in English from peer-reviewed journals with full text available. Excluded if opinion statements, lack of empirical data, or unrelated to project’s objective. DATA EXTRACTION: For both clinical device and research equipment: measurement mechanisms, measurement types, outcome/output, FDA classification, and indications for use. Addition data were extracted for clinical devices: instruction for use, end user, order requirement, and billable code. DATA SYNTHESIS: The 4 clinical devices are ultrasound, long-wave infrared thermography, subepidermal moisture assessment, and nearinfrared spectroscopy. The 3 research devices are laser Doppler flowmetry, laser speckle contrast imaging, and colorimetry. CONCLUSIONS: The measurement mechanisms of all devices are unique and different from each other. One commonality is that they could measure the nonvisual signs of PI (eg, inflammation, edema, ischemia, and hypoxia) except colorimeter. Some clinical devices are promising to assist with early identification of PIs, especially in individuals with dark skin tones. Currently, there is no reimbursement available for early detection of PI. Current evidence did not support replacing the standard skin assessment of visual inspection and palpation with the devices reviewed, rather using validated devices to augment the current practice standard. This is especially recommended for individuals identified as high risk for a PI on admission to a facility.
Expert Practice Patterns for Screening, Diagnosis, and Management of Barrett’s Esophagus in the United States
Iyer, Prasad G. , Clarke, John O. , Kamal, A. N. , Wang, Fangfang, Kamal, Afrin N , Clarke, J , Wang, Fangfang, Kahn, Allon

Journal of Clinical Gastroenterology | October 10, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1097/mcg.0000000000002259 | PMID 41071183 Get It

Goals: This study aimed to assess perspectives and practices among expert gastroenterologists regarding the screening, diagnosis, and management of BE. Background: Significant variability in the management of Barrett’s esophagus (BE) persists among physicians despite the development and dissemination of several clinical practice guidelines. Study: An online survey was conducted with 38 expert gastroenterologists specializing in BE management. The 38-question survey evaluated demographics, medical management, and attitudes toward endoscopic treatment, with responses analyzed for trends and variations. Results: Of the 38 experts, 34 (89%) responded. Respondents were primarily male (85%), with 82% affiliated with academic hospitals and 53% clinically focused on BE. Half discussed BE risks during initial consultations for gastroesophageal reflux disease (GERD). Most (61.8%) agreed BE should be considered in women with chronic GERD, and 88.2% regularly used narrow-band imaging (NBI). However, 44% were neutral or disagreed with diagnosing BE based solely on community gastroenterologist biopsies, and acceptance of Wide-Area Transepithelial Sampling with 3D Analysis (WATS-3D) for Barrett’s esophagus diagnosis and surveillance was limited. Fifty-three percent recommended ablation for nondysplastic BE. Fifty-two percent recommended indefinite daily PPI therapy after complete eradication of intestinal metaplasia (CEIM), regardless of symptoms. When encountering cardia intestinal metaplasia after endoscopic eradication, 38% recommended ablation, while 47% continued surveillance. Conclusion: This study highlights substantial variations in the management of BE among expert gastroenterologists, despite the existence of updated guidelines. Identifying these discrepancies is crucial for optimizing care. Further efforts are needed to standardize practices and enhance the implementation of evidence-based guidelines in clinical settings.
Discovery and Validation of Molecular Biomarkers for Differentiation of Nondysplastic Barrett’s Esophagus from High-grade Dysplasia and Esophageal Adenocarcinoma
Matchett, Caroline L. , Taylor, William R. , Berger, Calise K. , Anderson, Caryn E., Passe, Melissa, Lansing, Ramona, Wang, Panwen , Chalmers, Collin E., Foote, Patrick H. , Eckel‐Passow, Jeanette E. , Codipilly, Don C. , Leggett, Cadman L. , Ramirez, Francisco C. , Wolfsen, Herbert C. , Eluri, Swathi , Konda, Vani J. , Iyer, Prasad G. , Slettedahl, Seth W , Taylor, William R , Berger, Calise K , Anderson, Caryn E , Passe, Melissa A , Lansing, Ramona M , Wang, Panwen , Chalmers, Collin E , Foote, Patrick H , Eckel-Passow, Jeanette E , Sun, Zhifu , Mahoney, Douglas W , Codipilly, Don Chamil , Leggett, Cadman L , Ramirez, Francisco C , Kahn, Allon , Wolfsen, Herbert C , Eluri, Swathi , Konda, Vani , Trindade, Arvind J , Iyer, P G , Kisiel, John B , Slettedahl, Seth W. , Sun, Zhifu , Mahoney, Douglas W. , Kahn, Allon , Trindade, Arvind J. , Kisiel, John B.

Cancer Prevention Research | October 8, 2025 | Volume: 19 | Issue: 1 | Pages: 49-60

10.1158/1940-6207.capr-25-0215 | PMID 41059926 Get It

Abstract Aberrant DNA methylation and copy-number alterations (CNA) drive Barrett’s esophagus progression to esophageal adenocarcinoma; however, their combined utility for early detection is unclear. We aimed to identify and validate methylated DNA markers (MDM) and CNAs to distinguish esophageal adenocarcinoma/high-grade dysplasia (HGD) from nondysplastic Barrett’s esophagus (NDBE). In this multiphase, multicenter study, we discovered and validated MDMs and quantified CNAs utilizing whole-genome methylation sequencing of esophageal brushings. DNA biomarkers identified from discovery were further validated in independent patients with paired esophageal brushing and swallowed capsule sponge samples. MDMs were filtered against a reduced representation bisulfite sequencing dataset obtained from independent tissue samples to advance only concordant candidates. CNA burden was quantified using ichorCNA-derived aneuploidy scores (AS). Two hundred MDMs discovered in HGD (N = 18) and esophageal adenocarcinoma (N = 18) versus NDBE brushing samples (N = 18) were tested in independent samples (N = 146). A 52-MDM panel achieved a cross-validated AUC of 0.88 [95% confidence interval (CI), 0.82–0.95]; the addition of AS improved discrimination of HGD/esophageal adenocarcinoma from NDBE to 0.91 (95% CI, 0.86–0.97) AUC. At 80% specificity, the combined model detected 93% of esophageal adenocarcinoma and 88% of HGD cases. In paired capsule sponge samples, a 58-MDM panel achieved a cross-validated AUC of 0.77 (95% CI, 0.66–0.88); a combined 58-MDM and AS model achieved AUC 0.80 (95% CI, 0.7–0.9). MDMs and AS discerned HGD/esophageal adenocarcinoma from normal esophagus/NDBE in endoscopic brushing and capsule sponge samples. This approach may improve Barrett’s esophagus surveillance. Prevention Relevance: This study demonstrates that combining epigenetic and genomic biomarkers across minimally invasive sampling methods can accurately distinguish HGD/esophageal adenocarcinoma from nondysplastic Barrett’s esophagus, offering promising, less invasive strategies to improve BE surveillance and enable endoscopic therapy for esophageal adenocarcinoma prevention and treatment.