Bi, Yan

Background & Aims: Multi-target stool DNA (mt-sDNA) is an established stool-based colorectal cancer screening test, yet long-term performance is not well-described. We evaluated follow-up colonoscopy rates & quality, neoplasia yield, and repeat-testing adherence over 10 years with an integrated screening program. Methods: We assembled a retrospective cohort of mt-sDNA tests (September 2014–July 2025) within a multi-site health system. A validated large-language-model pipeline extracted colonoscopy, pathology, and quality endpoints from free-text reports. Detection outcomes (adenoma detection rate, advanced neoplasia, modified advanced adenoma, sessile serrated lesion (SSL), and negative exams) were calculated among high-quality exams; adenocarcinoma, bowel preparation adequacy, and cecal intubation rate (CIR) used all screening exams. We assessed colonoscopy completion ≤1 year after positive mt-sDNA, follow-up colonoscopy findings, findings by time-to-colonoscopy, and adherence to repeat mt-sDNA after negative result. Results: Among 148,624 tests in 110,410 individuals, positivity was 13.6%. Of 19,506 positives, 65.1% completed colonoscopy within 12 months (median 82 days). Colonoscopy after a positive mt-sDNA had high yield: advanced adenoma diagnosis was 30.7%; adenocarcinoma was 1.3%. Of patients who had colonoscopy within 3 years of a negative mt-sDNA test, 45.2% had adenoma/serrated lesion, 9.3% had advanced adenoma and 0.5% had colon cancer. Adenoma detection rate after positive mt-sDNA (>50%) exceeded specialty society quality benchmarks and increased over time; Longer intervals (>6 months) to colonoscopy after a positive test were associated with higher advanced adenoma (trend P=0.001).After an initial negative mt-sDNA, only 35.3% were screened again by mt-sDNA testing within 3 years. Conclusions: Over a decade,mt-sDNA screening achieved high colonoscopy qualitybut revealed critical gaps in the care cascade. One-third of positive tests lacked timely follow-up and nearly two-thirds of negative tests were not repeated on schedule, suggesting opportunities for system-level interventions.

INTRODUCTION: A deeper understanding of the factors influencing survival in patients with pancreatic ductal adenocarcinoma (PDAC) is essential for optimizing treatment strategies. This study investigates the independent association of body composition parameters with overall survival in patients with PDAC. METHODS: This retrospective multisite cohort study included patients diagnosed with PDAC. Diagnostic computed tomography scans were retrieved, and body composition was evaluated using a validated deep learning-based segmentation algorithm that measured tissue volume and density in a 20 cm vertical abdominal section. RESULTS: A total of 1,666 patients with PDAC were included, 938 male (56.3%) and median age 69 years (interquartile range 61–76). In the subgroup of patients who underwent surgical resection (n = 509), myosteatosis (intramuscular infiltration of adipose tissue; hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.16–2.11, P = 0.004), sarcopenic obesity (HR 1.75, 95% CI 1.06–2.91, P = 0.03), and less subcutaneous adipose tissue (HR 1.09, 95% CI 1.03–1.16, P = 0.002) were associated with higher mortality. In patients receiving palliative systemic therapy (n = 439), lower skeletal muscle density (HR 1.43, 95% CI 1.03–1.99, P = 0.03) was associated with higher mortality. In patients who did not undergo tumor-targeted treatment (n = 718), less visceral adipose tissue (HR 1.04, 95% CI 1.01–1.08, P = 0.02) was associated with higher mortality. DISCUSSION: Body composition parameters, derived from computed tomography scans at the time of PDAC diagnosis, particularly low skeletal muscle density, sarcopenic obesity, and low adipose tissue, are independently associated with overall survival in patients with PDAC. Evaluating body composition at diagnosis could enhance clinical decision-making and enable more personalized treatment strategies.

Postoperative pancreatic fistula (POPF) is a critical complication following pancreatic surgeries, marked by leakage of pancreatic fluid due to anastomotic or pancreatic duct failure. Recent advancements have refined its definition, risk classification and management strategies. This review emphasises discussing new definitions, classification updates, predictive factors (both pancreatic and non-pancreatic), comparisons of surgical techniques and therapeutic advancements. Emerging trials and innovations, such as robotic-assisted surgery and personalised stents, are also addressed. The evolving understanding of POPF underscores the need for holistic and patient-centred surgical strategies.

Objective: Patients with chronic pancreatitis commonly experience abdominal pain, anxiety, depression, reduced mobility, and difficulty performing daily activities or maintaining employment. These factors contribute to diminished quality-of-life and high healthcare utilization. This study aims to explore the relationship between specific quality-of-life domains among patients with chronic pancreatitis. Methods: A 55-item online survey was administered to patients with the diagnosis of chronic pancreatitis at 3 Mayo Clinic sites from December 26, 2023, to December 26, 2024. The survey included validated questions assessing demographic, clinical, and quality-of-life metrics using EuroQol 5-Dimension 5-Level instrument—a standardized assessment tool that evaluates 5 key health dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Results: Of the 298 patients with chronic pancreatitis who completed the survey, employed patients had decreased odds of reporting problems with mobility (odds ratio [OR] = 0.45, P < .05), self-care (OR = 0.26, P < .01), usual activities (OR = 0.47, P < .05), and anxiety/depression (OR = 0.41, P < .05). Similarly, older patients had decreased odds of reporting problems with self-care (OR = 0.91, P < .01), usual activities (OR = 0.96, P < .01), pain/discomfort (OR = 0.96, P < .01) and anxiety/depression (OR = 0.92, P < .01). However, Medicare patients had greater odds of reporting problems with self-care (OR = 5.54, P < .01) and pain/discomfort (OR = 2.58, P < .05). Conclusions: Chronic pancreatitis impacts multiple dimensions of quality-of-life beyond pain. The EuroQol 5-Dimension 5-Level tool enables comprehensive assessment of physical and mental health. Our findings highlight key associations between patient characteristics and quality-of-life domains, supporting the need for individualized, deficit-targeted interventions. These results also suggest a potential role for vocational rehabilitation in promoting functional recovery and enhancing overall well-being in individuals with chronic pancreatitis.

ABSTRACTTissue‐specific gene manipulation using Cre/loxP or Flp/frt recombination systems is a cornerstone of genetically engineered mouse models. In this study, we aim to develop a novel hepatocyte‐specific, tamoxifen‐inducible Flp mouse line. BAC (bacterial artificial chromosome)‐Alb(albumin)‐FlpER2(estrogen receptor ligan binding domain) was developed by inserting IRES‐FlpER2 cDNA between the translation stop codon and 3′‐UTR of the mouse albumin gene in a bacterial artificial chromosome. Upon tamoxifen induction in mice crossed with reporter lines, western blotting, immunohistochemistry, immunofluorescence staining, and X‐gal staining (5‐bromo‐4‐chloro‐3‐indolyl‐β‐D‐galactopyranoside Staining) were used to verify the recombination efficiency and specificity of this mouse model. Recombination was highly efficient and specific in hepatocytes, with no recombination detected in intrahepatic cholangiocytes or other organs in this mouse model. We generated a new tamoxifen‐induced hepatocyte‐specific mouse model with highly efficient recombination specifically in hepatocytes, and this model can be used to generate tumor model lines.

Objectives: New methods are needed to detect pancreatic ductal adenocarcinoma (PDAC) earlier to improve outcomes. We previously reported that a panel of protein N-glycosylation traits (NGTs) discriminated PDAC from healthy controls with an area under the curve (AUC) of 0.81–0.88. However, it remained unclear whether this panel accurately differentiates PDAC from other benign pancreatic disorders. Our study aims to evaluate the performance of the NGT panel in combination with CA19-9 in a diverse cohort, including PDAC cases, healthy controls, and controls with benign pancreatic disorders. Methods: Protein N-glycosylation profiles were determined in plasma samples using an in-house developed mass spectrometry assay. CA19-9 levels were measured using a routine immunoassay test. Results of total plasma NGTs and CA19-9 were evaluated separately as well as in combination. Logistic regression was performed to calculate odds ratios (ORs), AUC, sensitivity, and specificity to determine the performance of NGTs and CA19-9 in distinguishing PDAC from controls. Results: In total, 221 individuals were included: 45 (20.4%) with PDAC, and 176 (79.6%) controls (53 healthy and 123 with benign pancreatic disease). The AUC for differentiating PDAC from the total control cohort based on the combination of the NGT panel and CA19-9 was 0.94 (95% CI, 0.90–0.97), with a sensitivity of 0.89 (95% CI, 0.78–0.98) and specificity of 0.86 (95% CI, 0.81–0.91). Comparison of PDAC cases with healthy controls only resulted in an AUC of 0.96 (95% CI, 0.93–0.99), with a sensitivity of 0.84 (95% CI, 0.73–0.93) and specificity of 0.98 (95% CI, 0.94–1.00). Conclusions: Both plasma NGTs and CA19-9 distinguish PDAC from a diverse control cohort. The accuracy further improves when these readouts are combined, showing promise for future early detection methods.

AbstractA deeper understanding of pathophysiology, from the initiation of tumors of epithelial cells to the outcomes associated with it, is imperative to test potential interventions for these diseases. However, few models can accomplish this because of the complexity of origin cells and their transformation. We established an epithelial cell original tumor mouse model by conditional KrasG12D activation and tumor suppressor gene p53 deletion specifically in epithelial cells of the whole body using Cytokeratin 19 (CK19) promoter via Cre‐ERT mediation. Multiple tumors derived from epithelial cells developed in this novel model. This model can recapitulate the progress of intestinal, pancreatic, liver, lung, and subcutaneous tumors which derive from epithelial cells. This model is suitable for studying the pathophysiology of tumors derived from epithelial cells and may have the potential to test interventions.

INTRODUCTION: The increasing prevalence of clarithromycin (CLA)-resistant Helicobacter pylori (H. pylori) strains poses a significant challenge in the management of H. pylori infections. This systematic review and meta-analysis investigates the diagnostic accuracy of polymerase chain reaction (PCR) in identifying CLA-resistant H. pylori strains in stool. METHODS: A comprehensive literature search was conducted using PubMed, Embase, and Cochrane databases from database inception to April 30, 2023. Eligible studies evaluated the effectiveness of PCR stool tests in detecting CLA-resistant H. pylori strains in adults (>18-year-old). Studies of pediatric populations, alternative methods to PCR or stool samples, and reference tests other than gastric biopsy were excluded. The bivariate random-effects model was used to pool diagnostic accuracy from the included studies. RESULTS: The analysis of 11 prospective diagnostic studies with a total of 866 patients showed a pooled sensitivity of 0.97 (95% CI: 0.9–0.99) and a pooled specificity of 0.98 (95% CI: 0.81–1.00). Subgroup analysis based on the used technique demonstrated consistent findings without notable variations. The diagnostic odds ratio was calculated at 1843.92 (95% CI: 134.28–25,321.3). The positive likelihood ratio was determined as 51.02 (95% CI: 4.61–564.5), while the negative likelihood ratio was found to be 0.03 (95% CI: 0.01–0.1). DISCUSSION: PCR testing for clarithromycin-resistant H. pylori was highly sensitive and specific across studies with proven reliability in clinical practice, particularly in outpatient settings. Their implementation offers cost-effectiveness and the potential for tailored treatment strategies, holding promise for improved patient outcomes.

Clostridioides difficile infection (CDI) is one of the most common and severe nosocomial infections worldwide. It can also affect healthy individuals in the community. The incidence of CDI has been on the rise globally for the past decade, necessitating a proactive approach to combat its spread; new strategies are being developed to enhance diagnostic accuracy and optimize treatment outcomes. Implementing the 2-step testing has increased diagnostic specificity, reducing the usage of CD-specific antibiotics with no concomitant increase in surgical complication rates. In 2021, the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) shifted its preference for initial treatment to fidaxomicin over vancomycin and metronidazole due to its lower recurrence rate. It also prioritized fidaxomicin for the treatment of recurrent CDI. There are new developments on the frontiers of fecal microbiota therapies, with RBX2660 and SER-109 approved recently by the FDA for prevention, with other microbiome-based therapies in various development and clinical trials. This review offers providers an updated and practical guide for CDI management.

Background: Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium. Methods: PRECEDE is a multi-institutional international collaboration that has undertaken an observational prospective cohort study. Individuals (aged 18–90 years) are enrolled into 1 of 7 cohorts based on family history and pathogenic germline variant (PGV) status. From April 1, 2020, to November 21, 2022, a total of 3,402 participants were enrolled in 1 of 7 study cohorts, with 1,759 (51.7%) meeting criteria for the highest-risk cohort (Cohort 1). Cohort 1 HRIs underwent germline testing and pancreas imaging by MRI/MR-cholangiopancreatography or endoscopic ultrasound. Results: A total of 1,400 participants in Cohort 1 (79.6%) had completed baseline imaging and were subclassified into 3 groups based on familial PC (FPC; n=670), a PGV and FPC (PGV+/FPC+; n=115), and a PGV with a pedigree that does not meet FPC criteria (PGV+/FPC–; n=615). One HRI was diagnosed with stage IIB PC on study entry, and 35.1% of HRIs harbored pancreatic cysts. Increasing age (odds ratio, 1.05; P <.001) and FPC group assignment (odds ratio, 1.57; P <.001; relative to PGV+/FPC–) were independent predictors of harboring a pancreatic cyst. Conclusions: PRECEDE provides infrastructure support to increase access to clinical surveillance for HRIs worldwide, while aiming to drive early PC detection advancements through longitudinal standardized clinical data, imaging, and biospecimen captures. Increased cyst prevalence in HRIs with FPC suggests that FPC may infer distinct biological processes. To enable the development of PC surveillance approaches better tailored to risk category, we recommend adoption of subclassification of HRIs into FPC, PGV+/FPC+, and PGV+/FPC– risk groups by surveillance protocols.