Holy Cross Hospital

[This corrects the article DOI: 10.7759/cureus.57338.].

In this study, we evaluate the utility of ctDNA analysis in a large cohort of patients for whom ctDNA testing was ordered commercially with real-world application. Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for assessing post-surgical molecular residual disease (MRD) and response to treatment. A real-world data analysis was performed using commercial ctDNA testing (SignateraTM) from patients (N=795, n=5,971 plasma samples) with stage I-III colon cancer treated at multiple US institutions. The association of ctDNA detection within the MRD window, during surveillance, and the impact of ACT was correlated with patient outcomes. ctDNA-positive patients during the MRD window and surveillance showed significantly shorter DFS compared to ctDNA-negative patients (hazard ratio (HR): 9.85, P<0.0001; HR: 26.91, P<0.0001). Multivariate analysis of the MRD window revealed ctDNA-positivity as the most significant factor associated with inferior DFS (adjHR: 7.7, P<0.001). MRD-positive patients who received ACT showed improved DFS compared to patients observed post-surgery (adjHR: 6.1, FDR adj P=0.0007). No ACT benefit was observed in MRD-negative patients (adj HR: 1.20, FDR adj P=0.768). On evaluating ctDNA dynamics from MRD to surveillance, patients who remained ctDNA-positive or converted from negative to positive showed a significantly inferior DFS (HR: 34.40, P<0.0001; HR: 13.65, P<0.0001) compared to persistently ctDNA-negative patients. Postsurgical ctDNA detection is prognostic of relapse and potentially predictive of ACT benefit in patients with resectable colon cancer, which may enable personalized surveillance, intervention, and/or trial options, ultimately improving patient outcomes.

BackgroundFood Is Medicine interventions show promise for improving cardiovascular health outcomes, particularly for addressing disparities affecting Black and Hispanic populations. However, their development often lacks community co‐creation. Human‐centered design approaches can enhance the acceptability and feasibility of interventions through co‐design processes. We aimed to co‐design the THRIVE program (Adaptive Personalized Dietitian Coaching and Messaging With Produce Prescriptions to Improve Healthy Dietary Behaviors) among Black and Hispanic adults with hypertension living in healthy food priority areas in Maryland.MethodsUsing social cognitive theory and the human‐centered design double‐diamond framework, 3 iterative co‐design sessions were conducted. The first session included an orientation/listening (virtual), followed by 2 in‐person prototyping and process mapping sessions. Participants included community residents with hypertension, health care providers, local food system representatives, and community organization leaders. Data collection included detailed session notes, post‐session surveys, prototypes, and documentation of visual outputs. Content analysis identified key implementation themes.ResultsThirty‐six community stakeholders (29 female, 6 male, 17 English‐speaking, 18 Spanish‐speaking/bilingual) participated. Three primary themes emerged: (1) health care system integration, emphasizing personalized dietitian support with cultural competency; (2) food access and education, highlighting flexible produce prescription programs with practical nutrition education; and (3) community empowerment, emphasizing peer support networks. Process evaluation demonstrated high engagement, with 100% reporting valued contributions and 92% recommending similar approaches for future cardiovascular interventions.ConclusionsHuman‐centered design effectively guided community engagement in the development of a contextually tailored Food Is Medicine intervention. Integrating human‐centered design with implementation science creates more effective, equitable, and sustainable health interventions for addressing complex health challenges.

Abstract Circulating tumor DNA (ctDNA) is a non-invasive biomarker increasingly used to detect residual or recurrent disease and to monitor patient response to therapy. However, there is a need for more sensitive tests that can achieve earlier detection of disease. The NeXT Personal® Dx (NPDx) ctDNA MRD test uses paired tumor and normal whole genome sequencing (WGS) to design a bespoke panel of up to ∼1800 variants and relies on advanced noise suppression to achieve ultrasensitive detection down to ∼1 part per million (PPM) of ctDNA (1x10-6 tumor fraction) with high analytical specificity (&amp;gt;99.9%). Here, we describe the real world performance for a set of cancer patients (&amp;gt;15 cancer types) profiled using the NPDx test. For this study we have included 1693 plasma timepoints from 700 patients (range of 1 to 21 timepoints per patient), with the highest proportion of patients having breast, lung or colorectal cancer. The plasma timepoints have a median LOD of 1.93 PPM (IQR:1.55-2.78 PPM). Notably 41.6% of MRD+ samples were detected at low traces of ctDNA below 100 PPM, in the ultrasensitive range; moreover, a majority (50.4%) of the ultrasensitive detections are at or below 15 PPM, further highlighting the impact of a highly sensitive assay for MRD profiling. We also examined performance in specific challenging situations. NPDx tests performed well with challenging FFPE tumor samples (low tumor DIN &amp;lt;=3 indicating some sample degradation or low tumor fraction &amp;lt;=30%), achieving low LODs (median = 2.97 and 2.56 PPM, respectively). The WGS-based panel design allowed NPDx to achieve ultrasensitivity on low TMB tumors (&amp;lt;=2 mutation/MB, median LOD = 2.90 PPM) through utilization of variants from intergenic regions (95% MRD panel variants were from non-exonic regions) that would largely be unavailable to exome-based tests. Testing was performed across a wide range of cell free DNA (cfDNA) inputs (range 2-30 ng, median = 14 ng). Even with low cfDNA inputs (&amp;lt;=3ng, 5.25% of cohort), NPDx still achieved a low median LOD of 2.63 PPM. Two case studies demonstrate the impact of ultrasensitive MRD testing with patients. A 50-year-old woman with stage 1B endometrial cancer was monitored using NPDx following hysterectomy and brachytherapy, and ctDNA was detected in the ultrasensitive range (&amp;lt;50 PPM in this case). Reflex imaging revealed a new nodule leading to additional therapy and ctDNA clearance. In a second case, a woman in her 70s with stage 1 HER2+ breast cancer who underwent standard lumpectomy and adjuvant treatment was found with persistent low levels of ctDNA (between 25-30 PPM) detected with NPDx over a period of five months. Reflex imaging revealed a new nodule leading to additional radiation therapy, with plans for chemotherapy. These cases illustrate how NPDx's ultrasensitive detection capabilities can impact patient management in a real world setting. Citation Format: Rachel Marty Pyke, Steven Dea, Fábio C.P. Navarro, Charles W. Abbott, Sherif El-Refai, Yi Chen, Janet Lai, Gabor Bartha, John M. Lyle, Jason Harris, Georges Azzi, Sean M. Boyle, Richard O. Chen. Impact of an ultrasensitive ctDNA test on MRD detection in real world clinical patient testing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4549.

Proton pump inhibitors (PPI) are widely used medications for gastrointestinal disorders. Recent research suggests a potential association between long-term PPI use and increased cardiovascular (CV) risk, creating a complex clinical dilemma. This review critically evaluates the current evidence for this association, considering the limitations of observational studies and the lack of definitive confirmation from randomized controlled trials.This review delves into the reported association between PPIs and adverse CV events, examining proposed mechanisms such as drug interactions, electrolyte imbalances induced by PPIs and their potential impact on cardiac and vascular function. Evidence suggests these mechanisms converge, with varying influence depending on patient populations.Clinicians require a risk-benefit analysis for each patient considering their CV risk profile. Alternative gastrointestinal therapies should be explored for high-bleeding risk patients. Medications with lower cytochrome-P450 interaction potential may be preferable among essential PPI users. Elucidating the specific mechanisms by which PPIs might influence CV health, assessing long-term vascular effects and investigating interactions with newer anticoagulant medications are crucial for future research.

Background:The SENZA-PDN study evaluated high-frequency 10-kHz spinal cord stimulation (SCS) for the treatment of painful diabetic neuropathy (PDN). Over 24 months, 10-kHz SCS provided sustained pain relief and improved health-related quality of life. This report presents additional outcomes from the SENZA-PDN study, focusing on diabetes-related pain and quality of life outcomes.Methods:The SENZA-PDN study randomized 216 participants with refractory PDN to receive either conventional medical management (CMM) or 10-kHz SCS plus CMM (10-kHz SCS + CMM), allowing crossover after six months if pain relief was insufficient. Postimplantation assessments at 24 months were completed by 142 participants with a permanent 10-kHz SCS implant, comprising 84 initial and 58 crossover recipients. Measures included the Brief Pain Inventory for Diabetic Peripheral Neuropathy (BPI-DPN), Diabetes-Related Quality of Life (DQOL), Global Assessment of Functioning (GAF), and treatment satisfaction.Results:Over 24 months, 10-kHz SCS treatment significantly reduced pain severity by 66.9% (P < .001; BPI-DPN) and pain interference with mood and daily activities by 65.8% (P < .001; BPI-DPN). Significant improvements were also observed in overall DQOL score (P < .001) and GAF score (P < .001), and 91.5% of participants reported satisfaction with treatment.Conclusions:High-frequency 10-kHz SCS significantly decreased pain severity and provided additional clinically meaningful improvements in DQOL and overall functioning for patients with PDN. The robust and sustained benefits over 24 months, coupled with high participant satisfaction, highlight that 10-kHz SCS is an efficacious and comprehensive therapy for patients with PDN.

Introduction: Primary Biliary Cholangitis (PBC) is an autoimmune liver disease characterized by the immune-mediated destruction of small and medium intrahepatic bile ducts. The disease is distinguished by the presence of the anti-mitochondrial antibody (AMA) in 90-95% of patients. Case Description/Methods: A 20-year-old primigravida at 28.3 weeks gestation was initially admitted to an outside hospital 8 days prior to transfer due to 20 days of nausea, emesis, and dehydration without abdominal pain, fever, chills, or diarrhea. At that time admission findings included acute kidney injury, leukocytosis, and hypokalemia (K 2.6), along with markedly elevated total bilirubin (3.7), aspartate aminotransferase (1251), alanine aminotransferase (1890), and alkaline phosphatase (170) with an unremarkable right upper quadrant ultrasound. Further work-up revealed low IgG levels (547), positive antinuclear antibodies (ANA) (1:160), and positive anti-centromere antibodies. Serological tests for viral hepatitis and other infections were negative.Given the positive ANA, autoimmune hepatitis was also considered, prompting transfer to a tertiary center for comprehensive evaluation. Rheumatology service was consulted to evaluate the presence of underlying systemic sclerosis given the abnormal antibodies findings. Upon evaluation at the hospital, the patient was asymptomatic. She reported regular follow-up with an obstetrician. Denied any family history of autoimmune disease, over-the-counter medications, new medications, or herbal supplements. A transthoracic echocardiogram was performed, which showed a normal ejection fraction and normal right systolic ventricular pressure and no valvulopathy. After rheumatology evaluation, anti-mitochondrial M2 antibodies came back elevated with negative anti-smooth muscle antibodies. The patient was started on ursodiol for pruritus with further improvement of the symptoms and liver enzyme levels and was discharged to follow up with outpatient hepatology. Discussion: Positive anti-centromere antibodies (ACA) in the context of abnormal liver tests cannot be overstated, as it strongly correlates with the presence of primary biliary cholangitis (PBC) and may aid in early disease diagnosis. It is important to have a multidisciplinary approach in managing patients with autoimmune diseases and interpreting such tests, facilitating timely diagnosis and optimized patient care (see Table 1). Table 1. - Antibody profile showing and positive ANA 1:640, Anti Centromere and Anti Mitochondrial M2 Antibody Test Result ANA Present 1:640 Anti Centromere Ab Positive Anti Mitochondrial M2 Positive Actin IgG Anti Smooth Muscle Ab Negative Anti Ds DNA Anti SSA Anti SSB Anti Smith Anti-RNP Anti SMRNP Anti Ribosomal P Antibody Anti Scleroderma 70 Anti JO1 Ab Anti Chromatin Antibody Negative

Gastric cancers rarely metastasize to the bones. If they do, they have a very poor prognosis. We here present a case study of a 56-year-old man who, within a year, rapidly declined and died. He was first revealed to have an erosion found on an esophageal gastroduodenoscopy (EGD), which was later proven to be a poorly differentiated gastric adenocarcinoma. He then proceeded to have a thoracic trans-hiatal esophagogastrostomy with gastric pull-up to resect this cancer. At this point in time, the review of systems and CT scans of the abdomen and pelvis were negative. A few months later, he started having back pain and was diagnosed with metastatic disease of the bones through a CT scan. Although detecting gastric cancer at an early stage is rare, it is shown to have a better prognosis. It is, therefore, very important to reflect on the possibility of engaging in earlier screening to detect gastric cancers at an earlier stage to minimize the risk of invasions of other organs, especially for those who have other risk factors such as obesity and tobacco use. We believe it is prudent to ensure close follow-up with any patient with early gastric cancer to potentially detect recurrence or metastasis in a timely fashion.