Histopathology imaging and clinical data including remission status in pediatric inflammatory bowel disease.

The incidence of inflammatory bowel disease (IBD) is increasing annually. Children with IBD often suffer significant morbidity due to physical and emotional effects of the disease and treatment. Corticosteroids, often a component of therapy, carry undesirable side effects with long term use. Steroid-free remission has become a standard for care-quality improvement. Anticipating therapeutic outcomes is difficult, with treatments often leveraged in a trial-and-error fashion. Artificial intelligence (AI) has demonstrated success in medical imaging classification tasks. Predicting patients who will attain remission will help inform treatment decisions. The provided dataset comprises 951 tissue section scans (167 whole-slides) obtained from 18 pediatric IBD patients. Patient level structured data include IBD diagnosis, 12- and 52-week steroid use and name, and remission status. Each slide is labelled with biopsy site and normal or abnormal classification per the surgical pathology report. Each tissue section scan from an abnormal slide is further classified by an experienced pathologist. Researchers utilizing this dataset may select from the provided outcomes or add labels and annotations from their own institutions.

Clinical, Cultural, Computational, and Regulatory Considerations to Deploy AI in Radiology: Perspectives of RSNA and MICCAI Experts.

"Just Accepted" papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. The Radiological Society of North of America (RSNA) and the Medical Image Computing and Computer Assisted Intervention (MICCAI) Society have led a series of joint panels and seminars focused on the present impact and future directions of artificial intelligence (AI) in radiology. These conversations have collected viewpoints from multidisciplinary experts in radiology, medical imaging, and machine learning on the current clinical penetration of AI technology in radiology, and how it is impacted by trust, reproducibility, explainability, and accountability. The collective points-both practical and philosophical-define the cultural changes for radiologists and AI scientists working together and describe the challenges ahead for AI technologies to meet broad approval. This article presents the perspectives of experts from MICCAI and RSNA on the clinical, cultural, computational, and regulatory considerations-coupled with recommended reading materials-essential to adopt AI technology successfully in radiology and more generally in clinical practice. The report emphasizes the importance of collaboration to improve clinical deployment and highlights the need to integrate clinical and medical imaging data and introduces strategies to ensure smooth and incentivized integration. ©RSNA, 2024.

Fertility in the Digital Age: A Survey-Based Evaluation of Fertility App Users' Quality of Life.

This study sought to characterize fertility app use among women seen for infertility care and to investigate the association between fertility app use and quality of life. This survey-based study was conducted at an academic infertility clinic. Surveys were administered to patients who presented for a new infertility visit. One survey collected information regarding app use and the second survey was FertiQoL, an internationally validated instrument measuring quality of life in those with infertility. Descriptive statistics were used to characterize the patient population regarding app use and FertiQoL scores. Comparisons between those who did and didn't use an app were evaluated using t-tests and Cochran Armitage test for trend. 149 surveys were collected. Most (75.5%) participants reported using a fertility app. Most participants (85.1%) used a free app and nearly all (97.2%) found their app helpful. There was a significant difference (p = 0.0034) in satisfaction with one's quality of life between app users and non-app users with app users demonstrating higher satisfaction. There were no significant differences between app users and non-app users with their overall FertiQoL scores however there was a statistically significant difference (p = 0.031) in Relational sub-scores with app users displaying higher scores. While overall quality of life, measured by standardized measures, did not differ, self-perceived satisfaction with quality of life improved with more satisfaction reported in those using an app. This self-perceived satisfaction and increased quality of life surrounding relationships carries important implications, especially when one may face the stress of infertility and its treatment.

Paclitaxel-Ifosfamide-based Therapy as Salvage Treatment in Platinum-resistant Recurrent/Metastatic Head and Neck Cancer.

BACKGROUND: Treatment options are limited, and the prognosis is poor for patients with platinum-resistant recurrent metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). This study evaluated the efficacy and safety of a paclitaxel and ifosfamide (TI) regimen in patients with R/M HNSCC whose disease had progressed following platinum-based therapy. PATIENTS AND METHODS: In this retrospective study, we included 53 patients with R/M HNSCC who underwent at least one cycle of TI-based therapy, post platinum failure, between February 2020 and August 2023. Some patients received the TI regimen in combination with immunotherapy and/or cetuximab. Key metrics assessed included the objective response rate (ORR), disease control rate, and progression-free as well as overall survival. RESULTS: The study observed an ORR of 15.8% and a disease control rate of 36.8%. The median progression-free survival for the entire cohort was 3.3 months, and the median overall survival was 9.6 months. Notably, the combination of TI with immunotherapy yielded a higher ORR of 30.8%, compared to 14.3% with TI alone. The most prevalent grade 1-2 adverse events were anemia (81%), weight loss (68%) and hypernatremia (55%). CONCLUSION: The TI-based regimen demonstrated favorable efficacy and safety profile in treating R/M HNSCC. Enhanced outcomes may be attainable when combining it with immunotherapy. This study suggests that TI-based therapy could serve as a potential salvage option for this specific patient group.

AI Efficacy as a Function of Trainee Interpreter Proficiency: Lessons from a Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Recently, AI tools have been deployed with increasing speed in educational and clinical settings. However, the use of AI by trainees across different levels of experience has not been well studied. This study investigates the impact of AI assistance on diagnostic accuracy for intracranial hemorrhage (ICH) and large vessel occlusion (LVO) by medical students (MS) and resident trainees (RT). MATERIALS AND METHODS: This prospective study was conducted between March 2023 and October 2023. MS and RT were asked to identify ICH and LVO in 100 non-contrast head CTs and 100 head CTAs, respectively. One group received diagnostic aid simulating AI for ICH only (n = 26), the other for LVO only (n = 28). Primary outcomes included accuracy, sensitivity, and specificity for ICH / LVO detection without and with aid. Study interpretation time was a secondary outcome. Individual responses were pooled and analyzed with chi-square; differences in continuous variables were assessed with ANOVA. RESULTS: 48 participants completed the study, generating 10,779 ICH or LVO interpretations. With diagnostic aid, MS accuracy improved 11.0 points (P < .001) and RT accuracy showed no significant change. ICH interpretation time increased with diagnostic aid for both groups (P < .001) while LVO interpretation time decreased for MS (P < .001). Despite worse performance in detection of the smallest vs. the largest hemorrhages at baseline, MS were not more likely to accept a true positive AI result for these more difficult tasks. Both groups were considerably less accurate when disagreeing with the AI or when supplied with an incorrect AI result. CONCLUSIONS: This study demonstrated greater improvement in diagnostic accuracy with AI for MS compared to RT. However, MS were less likely than RT to overrule incorrect AI interpretations and were less accurate, even with diagnostic aid, than the AI was by itself. ABBREVIATIONS: ICH = intracranial hemorrhage; LVO = large vessel occlusion; MS = medical students; RT = resident trainees.

A novel IKZF1 variant in a family with autosomal dominant CVID: A case for expanding exon coverage in inborn errors of immunity.

Common variable immune deficiency (CVID) is a heterogenous group of disorders characterized by varying degrees of hypogammaglobulinemia, recurrent infections, and autoimmunity. Currently, pathogenic variants are identified in approximately 20-30% of CVID cases. Here we report a 3-generation family with autosomal dominant Common Variable Immunodeficiency (CVID) diagnosed in 9 affected individuals. Although primary immune deficiency panels and exome sequencing were non-diagnostic, whole genome sequencing revealed a novel, pathogenic c.499C > T: p.His167Tyr variant in IKZF1, a critical regulator of B cell development. Functional testing done through pericentromeric heterochromatin localization and light shift chemiluminescent electrophoretic mobility shift assay confirmed the variant's deleterious effect via a haploinsufficiency mechanism. Our findings expand the spectrum of known IKZF1 mutations and contribute to a more comprehensive understanding of CVID's genetic heterogeneity. Furthermore, this case underscores the importance of considering whole genome sequencing for comprehensive genetic diagnosis when concern for a monogenic inborn errors of immunity is high.

Population Pharmacokinetics of Sacituzumab Govitecan in Patients with Metastatic Triple-Negative Breast Cancer and Other Solid Tumors.

BACKGROUND AND OBJECTIVE: Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of an antibody with affinity for Trop-2 coupled to SN-38 via hydrolyzable linker. SG is approved for patients with metastatic triple-negative breast cancer (mTNBC) who have received two or more prior chemotherapies (at least one in a metastatic setting) and for patients with pretreated hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. METHODS: In these analyses, the pharmacokinetics of SG, free SN-38, and total antibody (tAB) were characterized using data from 529 patients with mTNBC or other solid tumors across two large clinical trials (NCT01631552; ASCENT, NCT02574455). Three population pharmacokinetic models were constructed using non-linear mixed-effects modeling; clinically relevant covariates were evaluated to assess their impact on exposure. Models for SG and tAB were developed independently whereas free SN-38 was sequentially generated via a first-order release process from SG. RESULTS: Pharmacokinetics of the three analytes were each described by a two-compartment model with estimated body weight-based scaling exponents for clearance and volume. Typical parameter estimates for clearance and steady-state volume of distribution were 0.133 L/h and 3.68 L for SG and 0.0164 L/h and 4.26 L for tAB, respectively. Mild-to-moderate renal impairment, mild hepatic impairment, age, sex, baseline albumin level, tumor type, UGT1A1 genotype, or Trop-2 expression did not have a clinically relevant impact on exposure for any of the three analytes. CONCLUSIONS: These analyses support the approved SG dosing regimen of 10 mg/kg as intravenous infusion on days 1 and 8 of 21-day cycles and did not identify a need for dose adjustment based on evaluated covariates or disease characteristics.

Targeted phasing of 2-200 kilobase DNA fragments with a short-read sequencer and a single-tube linked-read library method.

In the human genome, heterozygous sites refer to genomic positions with a different allele or nucleotide variant on the maternal and paternal chromosomes. Resolving these allelic differences by chromosomal copy, also known as phasing, is achievable on a short-read sequencer when using a library preparation method that captures long-range genomic information. TELL-Seq is a library preparation that captures long-range genomic information with the aid of molecular identifiers (barcodes). The same barcode is used to tag the reads derived from the same long DNA fragment within a range of up to 200 kilobases (kb), generating linked-reads. This strategy can be used to phase an entire genome. Here, we introduce a TELL-Seq protocol developed for targeted applications, enabling the phasing of enriched loci of varying sizes, purity levels, and heterozygosity. To validate this protocol, we phased 2-200 kb loci enriched with different methods: CRISPR/Cas9-mediated excision coupled with pulse-field electrophoresis for the longest fragments, CRISPR/Cas9-mediated protection from exonuclease digestion for mid-size fragments, and long PCR for the shortest fragments. All selected loci have known clinical relevance: BRCA1, BRCA2, MLH1, MSH2, MSH6, APC, PMS2, SCN5A-SCN10A, and PKI3CA. Collectively, the analyses show that TELL-Seq can accurately phase 2-200 kb targets using a short-read sequencer.

Assessing the Performance of Artificial Intelligence Models: Insights from the American Society of Functional Neuroradiology Artificial Intelligence Competition.

BACKGROUND AND PURPOSE: Artificial intelligence (AI) models in radiology are frequently developed and validated using datasets from a single institution and are rarely tested on independent, external datasets, raising questions about their generalizability and applicability in clinical practice. The American Society of Functional Neuroradiology (ASFNR) organized a multi-center AI competition to evaluate the proficiency of developed models in identifying various pathologies on NCCT, assessing age-based normality and estimating medical urgency. MATERIALS AND METHODS: In total, 1201 anonymized, full-head NCCT clinical scans from five institutions were pooled to form the dataset. The dataset encompassed normal studies as well as pathologies including acute ischemic stroke, intracranial hemorrhage, traumatic brain injury, and mass effect (detection of these-task 1). NCCTs were also assessed to determine if findings were consistent with expected brain changes for the patient's age (task 2: age-based normality assessment) and to identify any abnormalities requiring immediate medical attention (task 3: evaluation of findings for urgent intervention). Five neuroradiologists labeled each NCCT, with consensus interpretations serving as the ground truth. The competition was announced online, inviting academic institutions and companies. Independent central analysis assessed each model's performance. Accuracy, sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic (ROC) curves were generated for each AI model, along with the area under the ROC curve (AUROC). RESULTS: 1177 studies were processed by four teams. The median age of patients was 62, with an interquartile range of 33. 19 teams from various academic institutions registered for the competition. Of these, four teams submitted their final results. No commercial entities participated in the competition. For task 1, AUROCs ranged from 0.49 to 0.59. For task 2, two teams completed the task with AUROC values of 0.57 and 0.52. For task 3, teams had little to no agreement with the ground truth. CONCLUSIONS: To assess the performance of AI models in real-world clinical scenarios, we analyzed their performance in the ASFNR AI Competition. The first ASFNR Competition underscored the gap between expectation and reality; the models largely fell short in their assessments. As the integration of AI tools into clinical workflows increases, neuroradiologists must carefully recognize the capabilities, constraints, and consistency of these technologies. Before institutions adopt these algorithms, thorough validation is essential to ensure acceptable levels of performance in clinical settings.ABBREVIATIONS: AI = artificial intelligence; ASFNR = American Society of Functional Neuroradiology; AUROC = area under the receiver operating characteristic curve; DICOM = Digital Imaging and Communications in Medicine; GEE = generalized estimation equation; IQR = interquartile range; NPV = negative predictive value; PPV = positive predictive value; ROC = receiver operating characteristic; TBI = traumatic brain injury.

A Guideline for Open-Source Tools to Make Medical Imaging Data Ready for Artificial Intelligence Applications: A Society of Imaging Informatics in Medicine (SIIM) Survey.

In recent years, the role of Artificial Intelligence (AI) in medical imaging has become increasingly prominent, with the majority of AI applications approved by the FDA being in imaging and radiology in 2023. The surge in AI model development to tackle clinical challenges underscores the necessity for preparing high-quality medical imaging data. Proper data preparation is crucial as it fosters the creation of standardized and reproducible AI models while minimizing biases. Data curation transforms raw data into a valuable, organized, and dependable resource and is a fundamental process to the success of machine learning and analytical projects. Considering the plethora of available tools for data curation in different stages, it is crucial to stay informed about the most relevant tools within specific research areas. In the current work, we propose a descriptive outline for different steps of data curation while we furnish compilations of tools collected from a survey applied among members of the Society of Imaging Informatics (SIIM) for each of these stages. This collection has the potential to enhance the decision-making process for researchers as they select the most appropriate tool for their specific tasks.

Multi-harmonic near-infrared-ultraviolet dual-comb spectrometer.

Dual-comb spectroscopy in the ultraviolet (UV) and visible would enable broad bandwidth electronic spectroscopy with unprecedented frequency resolution. However, there are significant challenges in generation, detection, and processing of dual-comb data that have restricted its progress in this spectral region. In this work, we leverage robust 1550 nm few-cycle pulses to generate frequency combs in the UV-visible. We combine these combs with a wavelength multiplexed dual-comb spectrometer and simultaneously retrieve 100 MHz comb-mode-resolved spectra over three distinct harmonics at 386, 500, and 760 nm. The experiments highlight the path to continuous dual-comb coverage spanning 200-750 nm, offering extensive access to electronic transitions in atoms, molecules, and solids.

Enhancing regional control in p16-negative oropharyngeal cancer: A propensity score-matched analysis of upfront neck dissection and definitive chemoradiotherapy.

BACKGROUND: The presence of p16 and neck disease is important predictors of prognosis for oropharyngeal squamous cell carcinoma (OPSCC). Patients who are p16-negative and have clinically node-positive (cN+) disease generally have worse oncologic outcomes. This study aimed to investigate whether upfront neck dissection (UFND) could provide potential benefits for patients with cN+ p16-negative OPSCC. METHODS: Through this retrospective study, 76 patients with cN+ p16-negative OPSCC were analyzed, those who received either definite concurrent chemoradiotherapy (CCRT group) or UFND followed by chemoradiotherapy (UFND group). The primary endpoints were regional recurrence-free survival (RRFS), disease-specific survival (DSS), and overall survival (OS). Factors associated with survival were evaluated by univariate and multivariate analysis. Survival between the two groups was compared by propensity score-matched analysis. RESULTS: Matched 23 patients in each group through propensity analysis, the UFND group showed a significantly better 5-year RRFS (94.1% vs 61.0%, p = 0.011) compared to the CCRT group. Univariate analysis revealed that UFND was the sole factor associated with regional control (hazard ratio [HR] = 0.110; 95% CI, 0.014-0.879; p = 0.037). Furthermore, the study found that the CCRT group was associated with a higher dose of radiotherapy and exhibited a significantly higher risk of mortality due to pneumonia. CONCLUSION: The study indicated that UFND followed by CCRT may be a potential treatment option for patients with cN+ p16-negative OPSCC, as it can reduce the risk of regional recurrence. Additionally, the study highlights that definite CCRT is connected to a larger dose of radiotherapy and a higher risk of fatal pneumonia. These findings could be beneficial in informing clinical decision-making and improving treatment outcomes for patients with OPSCC.

The association of patient and disease characteristics with the overtreatment of low-risk prostate cancer from 2010 to 2016.

BACKGROUND: Although active surveillance is the preferred management for low-risk prostate cancer (PCa), some men remain at risk of overtreatment with definitive local therapy. We hypothesized that baseline characteristics may be associated with overtreatment and represent a potential source of health disparities. We therefore examined the associations of patient and disease characteristics with the surgical overtreatment of low-risk PCa. METHODS: We identified men aged 45-75 years with cT1 cN0 cM0 prostate adenocarcinoma with biopsy Gleason score 6 and PSA < 10 ng/ml from 2010-2016 in the National Cancer Database (NCDB) and who underwent radical prostatectomy (RP). We evaluated the associations of baseline characteristics with clinically insignificant PCa (iPCa) at RP (i.e., "overtreatment"), defined as organ-confined (i.e., pT2) Gleason 3 + 3 disease, using multivariable logistic regression. RESULTS: We identified 36,088 men with low-risk PCa who underwent RP. The unadjusted rate of iPCa decreased during the study period, from 54.7% in 2010 to 40.0% in 2016. In multivariable analyses adjusting for baseline characteristics, older age (OR 0.98, 95% CI 0.97-0.98), later year of diagnosis (OR 0.62, 95% CI 0.57-0.67 for 2016 vs. 2010), Black race (OR 0.85, 95% CI 0.79-0.91), treatment at an academic/research program (OR 0.82, 95% CI 0.73-0.91), higher PSA (OR 0.91, 95% CI 0.90-0.92), and higher number of positive biopsy cores (OR 0.87, 95% CI 0.86-0.88) were independently associated with a lower risk of overtreatment (iPCa) at RP. Conversely, a greater number of biopsy cores sampled (OR 1.01, 95% CI 1.01-1.02) was independently associated with an increased risk of overtreatment (iPCa) at RP. CONCLUSIONS: We observed an ~27% reduction in rates of overtreatment of men with low-risk PCa over the study period. Several patient, disease, and structural characteristics are associated with detection of iPCa at RP and can inform the management of men with low-risk PCa to reduce potential overtreatment.

The Association of a Peritoneal Interposition Flap With Lymphocele Formation After Pelvic Lymph Node Dissection During Robotic-assisted Laparoscopic Radical Prostatectomy: A Systematic Review and Meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to evaluate the association of a peritoneal interposition flap (PIF) with lymphocele formation following robotic-assisted laparoscopic radical prostatectomy (RALP) with pelvic lymph node dissection. METHODS: We conducted a systematic search of MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials through August 30, 2023, to identify randomized and nonrandomized studies comparing RALP with pelvic lymph node dissection with and without PIF. A random effects meta-analysis was then performed to evaluate the associations of PIF with 90-day postoperative outcomes. RESULTS: Five randomized controlled trials (RCTs) and four observational studies, including a total of 2941 patients, were included. The use of PIF was associated with a reduced risk of 90-day symptomatic lymphocele formation after RALP when examining only RCTs (pooled odds ratios [OR] 0.44, 95% CI 0.28-0.69; I2 =3%) and both RCTs and observational studies (OR 0.35, 95% CI 0.22-0.56; I2 =17%). Similarly, use of PIF was associated with a reduced risk of 90-day any lymphocele formation (OR 0.40, 95% CI 0.28-0.56, I2 =39%). There were no statistically significant differences in postoperative complications between the two groups (OR 0.89; 95% CI 0.69-1.14; I2 =20%). CONCLUSION: Use of the PIF is associated with an approximately 50% reduced risk of symptomatic and any lymphocele formation within 90-days of surgery, and it is not associated with an increase in postoperative complications.

How Can We Identify Extraprostatic Extension (EPE) Before Surgery? The Use of a Preoperative Prostate MRI EPE Scoring System to Assess Postprostatectomy Locally Advanced Prostate Cancer.

Background: Distinguishing between organ-confined disease and extraprostatic extension (EPE) is crucial for the treatment of patients with prostate cancer. EPE is associated with an increased risk of biochemical recurrence, positive surgical margins, and metastatic disease. An MRI-based EPE scoring system was developed by Mehralivand in 2019; however, it has not been adopted in the Urology community. The purpose of this study is to evaluate the association of MRI-based EPE scoring with the pathologic EPE (pEPE) after radical prostatectomy. Methods: We conducted a retrospective review on a prospectively collected database of male patients who underwent a prostate MRI with EPE scoring by a trained genitourinary radiologist and subsequent robotic radical prostatectomy at our institution from September 2020 to December 2022. The associations between MRI EPE (mEPE) score and the presence of EPE on surgical pathology (pEPE) were examined using multivariable logistic regression. Results: A total of 194 patients met inclusion criteria with a median age of 63 years and prostate specific antigen (PSA) 7 ng/mL. Among those with mEPE score 3, 96% had pEPE. Those patients with an mEPE score ≥2 had an increased risk of pEPE compared with those with mEPE score 0 (odds ratio 3.79; 95% confidence interval 1.28-11.3) Furthermore, those with an mEPE score 3 were significantly more likely to have pEPE compared with those with mEPE score 0, 1 and 2 independently. Conclusion: MRI EPE is a straightforward tool that strongly correlates with the presence of pEPE. If validated prospectively, this scoring system could assist in counseling patients regarding nerve-sparing approach.

Postradical prostatectomy prostate-specific antigen outcomes after 6 versus 18 months of perioperative androgen-deprivation therapy in men with localized, unfavorable intermediate-risk or high-risk prostate cancer: Results of part 2 of a randomized phase 2 trial.

BACKGROUND: Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.3% of patients (n = 24 of 118). Herein, the authors report the results of part 2. METHODS: For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL). RESULTS: Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms. CONCLUSIONS: In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.

Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis.

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.