Introduction

Ulcerative colitis (UC) has increasingly been recognized as a progressive disease. However, the benefit of starting early biologic therapy (BT) has not been established, contrary to Crohn´s disease. We aimed to assess if early intervention improves UC outcomes, particularly in preventing disease progression.

Aims & Methods

We conducted a retrospective multicenter study (11 centers) including adult UC patients who initiated BT until 2019 (minimum follow-up [FU]: 5 years). Early intervention was defined as BT initiation within ≤12 months of diagnosis. The primary outcome was UC progression at 5 and 10 years, defined as a composite of proximal extension, colonic structural changes (stenosis/ tubularization) and dysplasia/cancer. Secondary outcomes included clinical endpoints: hospitalizations, colectomy and corticosteroid use. Multivariate analysis was performed, adjusted for disease severity, extent, and prior activity.

Results

A total of 236 patients were included, with 28.8% (n=68) initiating BT within ≤12 months (mean FU after BT initiation: 8.06 ± 4.12 years).
Early intervention was associated with a reduced risk of proximal extension after BT initiation (p=0.012). In multivariable Cox regression, later BT initiation was an independent predictor of colonic structural changes at 10 years (HR 8.54; 95% CI 1.15-62.63; p=0.036). Later BT initiation independently predicted the composite outcome of progression (23.2% vs 5.9%) at 5 years (HR 5.97; 95% CI 1.42-25.13; p=0.015) and 10 years (HR 4.58; 95% CI 1.41-14.88; p=0.011). No differences in clinical outcomes were observed.
Longer disease activity before BT was also a predictor of the primary outcome at 5 years (HR 4.20; 95% CI 1.27–13.82; p=0.018) and 10 years (HR 3.60; 95% CI 1.28–10.12; p=0.015).

Conclusion

Starting BT early in the disease course may reduce the long-term risk of disease progression, reshaping the window of opportunity in UC.

References

Lujan, Rona, et al. "Early initiation of biologics and disease outcomes in adults and children with inflammatory bowel diseases: results from the Epidemiology Group of the Nationwide Israeli Inflammatory Bowel Disease Research Nucleus Cohort." Gastroenterology 166.5 (2024): 815-825.

Introduction

Chimeric antigen receptor (CAR) T cells have shown remarkable efficacy in hematological malignancies, but remain largely ineffective in solid tumors such as pancreatic ductal adenocarcinoma (PDAC). Major barriers include CAR-T cell dysfunction, poor infiltration, and limited persistence within the immunosuppressive tumor microenvironment. STING (stimulator of interferon genes) activation can remodel this environment by inducing inflammation and reversing cancer immune privilege. However, the use of STING agonists in combination with CAR-T cells is hampered by T cell-intrinsic STING signaling, which induces T cell dysfunction and apoptosis.

Aims & Methods

To overcome these limitations, we investigated the therapeutic potential of combining STING agonists with CAR-T cells genetically ablated for STING for the treatment of PDAC. Using CRISPR-Cas9-edited CAR-T cells and the STING agonist diABZI, we assessed antitumor activity in vitro using a CAR-T cell exhaustion model and in vivo using both a cell line-derived xenograft and a syngeneic mouse model.

Results

The combination of STING^KO CAR-T cells and diABZI substantially enhanced CAR-T cell function. In vitro, we observed improved tumor cell killing, increased CAR-T cell proliferation, reduced expression of exhaustion markers, and expansion of an effector-memory phenotype. These effects required genetic deletion of STING in CAR-T cells and were dependent on cancer cell-intrinsic STING signaling. Mechanistically, we identified a synergistic feedback loop, in which CAR-T cell-derived IFN-γ and TNF-α enhanced STING signaling in cancer cells, further promoting beneficial CAR-T cell states. In vivo, this combination achieved superior tumor control in both xenograft and syngeneic mouse models.

Conclusion

Our findings demonstrate that STING^KO CAR-T cells can be effectively combined with STING agonists to enhance therapeutic efficacy in immune-cold tumors such as PDAC. This strategy represents a promising approach to overcoming current barriers in CAR-T cell therapy for solid tumors.

Disclosure

I.P. reports reimbursement of travel expenses from Roche and received third-party funding for scientific research from Novartis. A.G. received research support from Tabby Therapeutics and from Nanogami for work unrelated to the paper. M.S. has received research funding from Amgen, BMS/Celgene, Gilead/Kite, Janssen, Miltenyi Biotech, Molecular Partners, Novartis, Roche, Seagen and Takeda, honoraria from AbbVie, Amgen, AvenCell, BMS, CanCell Therapeutics, Gilead, Janssen, Miltenyi Biomedicine, Molecular Partners, Pfizer and Roche and was invited as speaker by AstraZeneca, BMS, Gilead/Kite, GSK, Janssen, LAWG, Novartis, Pfizer, Roche and Springer Healthcare. S. K. has received honoraria from Cymab, Plectonic, TCR2 Inc., Miltenyi, Galapagos, Novartis, BMS and GSK. S. K. is an inventor of several patents in the field of immuno-oncology. S. K. received license fees from TCR2 Inc and Carina Biotech. S.K. received research support from TCR2 Inc., Tabby Therapeutics, Catalym GmBH, Plectonic GmBH and Arcus Bioscience for work unrelated to the manuscript. The other authors have no competing interests to declare.

Introduction

Predicting choledocholithiasis in acute pancreatitis is challenging. Existing predictive models typically rely on the common bile duct (CBD) width, a parameter difficult to assess reliably. We aimed to develop a model based solely on easily available clinical and laboratory markers, excluding CBD width.

Aims & Methods

We conducted a retrospective cohort study of 348 patients treated for acute pancreatitis at the LMU University Hospital in Munich, Germany, between 2005 and 2021. A Random Forrest (RF) model was developed using the TensorFlow Decision Forests (TFDF) library with 14 clinical and laboratory features, excluding CBD width. Model performance was assessed using sensitivity, specificity, predictive values, and area under the receiver operating characteristic curve (AUC-ROC).

Results

Of 348 patients with acute biliary pancreatitis, 167 (48.0%) had CBD stones. Our model achieved a sensitivity of 92.3%, a negative predictive value (NPV) of 83.3%, and an AUC-ROC of 0.739. Compared to using CBD width ≥8 mm or bilirubin ≥4 mg/dl as predictors (as guidelines recommend), our model demonstrated superior sensitivity (92.3% vs. 79.5% vs. 30.8%, respectively) and NPV (83.3% vs. 74.3% vs. 54.8%, respectively). The rate of missed intraductal concrements was substantially lower with our model (4.3% vs. 41.4%). In subgroup analysis, our model performed better in predicting stones (AUC=0.8) than microlithiasis or sludge (AUC=0.623).

Conclusion

We developed the first machine learning-based score to predict choledocholithiasis in acute pancreatitis without relying on CBD width. The model's high sensitivity and NPV make it a promising tool for clinical decision-making, specifically for hospitals without the option of endosonography.

Disclosure

SS is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 413635475 - and the LMU Munich Clinician Scientist Program (MCSP).

Introduction

Inflammatory Bowel Disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic gastrointestinal disorder characterized by relapsing inflammation and significant psychological burden [1]. Patients with IBD often experience depression, anxiety, and reduced quality of life [2]. However, emerging research highlights posttraumatic growth (PTG)—positive psychological transformation following trauma—as a potential outcome in chronic illness [3].
PTG arises from cognitive restructuring after traumatic events, with rumination playing a key role [4]. Rumination includes intrusive rumination (unwanted, distressing thoughts) and deliberate rumination (purposeful reflection). While deliberate rumination typically fosters PTG, findings on intrusive rumination are inconsistent, with some studies reporting negative, positive, or null effects [5].

Results & Findings

A cross-sectional survey of 237 Chinese IBD patients. Intrusive rumination was negatively associated with PTG (β = -0.33; 95% CI: -0.61, -0.04), with education level impacting this effect (P for interaction < 0.05). Deliberate rumination showed a positive linear relationship with PTG (β = 0.87; 95% CI: 0.57, 1.17). Above a threshold of 17, intrusive rumination had a stronger negative impact (β = -1.01; 95% CI: -1.73, -0.30).

Summary & Discussion

This finding aligns with cognitive theories of trauma processing, which suggest that excessive intrusive thoughts may overwhelm an individual's cognitive and emotional resources, impeding adaptive meaning-making [6]. Below this threshold, intrusive rumination may serve as an initial, albeit distressing, step in cognitive processing, whereas higher levels may entrench negative thought patterns[9].This non-linear association helps reconcile conflicting findings in the literature [7]. Future research should explore whether interventions (e.g., mindfulness, cognitive restructuring) facilitate a transition toward deliberate rumination and subsequent PTG.
In contrast to intrusive rumination, deliberate rumination demonstrated a robust positive association with PTG across all models[8]. For IBD patients, who often experience fluctuating symptoms and emotional distress, facilitating deliberate cognitive processing may help them reframe their illness narrative, enhancing resilience and adaptive coping.
Individuals with lower education levels may lack the cognitive resources and flexibility needed to transform intrusive rumination into constructive meaning-making, making them more susceptible to negative emotional cycles that hinder PTG [9].

Conclusion

In conclusion, a nonlinear relationship between intrusive rumination and PTG in patients with IBD was found. When intrusive rumination exceeded a threshold of 17, it was negatively correlated with PTG. Additionally, deliberate rumination was positively associated with PTG, highlighting its potential as a facilitator of psychological growth.

References

1. Barberio B, Zamani M, Black CJ, et al. Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2021;6(5):359-370.
2. Tedeschi RG, Calhoun LG. The Posttraumatic Growth Inventory: measuring the positive legacy of trauma. J Trauma Stress. 1996;9(3):455-471.
3. Joseph S, Murphy D, Regel S. An affective-cognitive processing model of post-traumatic growth. Clin Psychol Psychother. 2012;19(4):316-325.
4. Allen N, Hevey D, Cogley C, et al. A meta-analysis of the association between event-related rumination and posttraumatic growth: the event-related rumination inventory and the posttraumatic growth inventory. J Trauma Stress. 2022;35(6):1575-1585. https://doi.org/10.1002/jts.22875
5. Jones SR, Fernyhough C. Rumination, reflection, intrusive thoughts, and hallucination-proneness: towards a new model. Behav Res Ther. 2009;47(1):54-59.
6. Hill EM, Watkins K. Women with ovarian cancer: Examining the role of social support and rumination in posttraumatic growth, psychological distress, and psychological well-being. J Clin Psychol Med Settings. 2017;24(1):47-58
7. Tedeschi RG, Shakespeare-Finch J, Taku K, et al. Posttraumatic growth: Theory, research, and applications. Routledge. 2018.
8. Niemeyer H, Bieda A, Michalak J, et al. Education and mental health: Do psychosocial resources matter? SSM Popul Health. 2019;7:100392.

Disclosure

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction

The legal responsibility of nurses is a key element in the healthcare sector, especially in complex areas such as digestive endoscopy. This role requires advanced technical skills and a deep understanding of legal implications. Nurses must follow protocols, ethical standards, and laws to ensure patient safety and prevent complications. Despite adherence to protocols, unusual complications can occur. Nurses have an autonomous position of guarantee towards the patient, based on their professional autonomy, which implies an essential task of health protection.

Results & Findings

The systematic literature review examined documented clinical cases in the field of digestive endoscopy, consulting clinical databases for situations where nursing responsibility was crucial. Precise data were obtained to provide specifics on nursing responsibility in endoscopy. However, from the analysis of collected clinical cases and available data, it emerges that about 50%-60% of the responsibilities are attributable to non-compliance with good care practices. Ineffective communication, both within the healthcare team and with patients, represents about 20%-30% of the issues in particularly complex contexts. Finally, suboptimal management of a complex environment, including organizational and technological factors, contributes to the remaining 10%-20% of difficulties.

Summary & Discussion

The results of this review highlight the importance of nursing responsibility in digestive endoscopy. The main cause of liability is the failure to adhere to good care practices, indicating the need to improve training and adherence to protocols. Ineffective communication represents a significant portion of the issues, emphasizing the importance of developing effective communication skills. Finally, suboptimal management of complex environments requires attention to organizational and technological factors to improve the quality of care.

Conclusion

From the clinical cases considered, common issues emerge, including the failure to apply good practices, inadequate consideration of the complex environment in which nurses work, and communication difficulties. These factors impact the quality of care and highlight the need to invest in tools and training. Focusing on effective communication strategies and appropriate protocols could improve nursing responsibility.

References

Endoscopia digestiva e responsabilità dell'infermiere-http//www.Nurse24.it;Endoscopia digestiva e responsabilità dell'infermiere-http//wwwDocsity.com;Survey Nazionale di Anote-Anigea -infermiere online;Irti G, L'infermiere di endoscopia oggi: compiti e responsabilità. Ipasvi Roma 2000; studio centrato sulla letteratura della responsabilità in endoscopia –http//tesi.univpm.it