Introduction

People who use drugs (PWUD) are an important target population for hepatitis C virus (HCV) elimination in the World Health Organization (WHO) goals, because the PWUD population contains one of the largest clusters of residual HCV infections. Case-finding and treatment of these patients in hospitals is considered a challenge, while low threshold on-site screening and therapy in addiction care might facilitate viral elimination. We studied implementation of a decentralized PWUD-HCV care model, by exploring 1) viral elimination rates, and 2) facilitators and barriers for implementation.

Aims & Methods

In a multicenter mixed-method study in addiction care centers in the Netherlands we examined HCV-related outcomes in PWUD receiving HCV treatment within addiction care. The primary outcome was viral elimination, defined as percentage of identified HCV positive patients achieving sustained virologic response (SVR). Using semi-structured interviews barriers and facilitators for implementation were identified among health professionals and policy makers of addiction care and hospitals.

Results

We found 33 PWUD HCV RNA positive. Four patients were referred to the hospital for treatment due to hepatitis B virus or HIV co-infection or other reasons. Two patients currently receive treatment, three patients were not yet fit for treatment and two were lost to follow-up before treatment could be started. On-site treatment was initiated in 22 patients. Of these patients 91% was male, mean age was 50 years (SD=13) and 36% was born in the Netherlands. All patients completed treatment with glecaprevir/pibrentasvir (n=9) or sofosbuvir/velpatasvir (n=13). All on-site and hospital treated patients reached SVR and there were no reinfections. The viral elimination rate was 79% (26/33). Themes on facilitators and barriers for implementation collected in the interviews are shown in the table.

Conclusion

This study shows the high viral elimination (79%) of decentralized care of HCV infections within addiction care and provides insight in facilitators and barriers for on-site HCV treatment. Based on these findings we recommend implementation and maintenance of decentralized HCV-addiction care models worldwide. This will lead to HCV elimination scaling-up in the Netherlands and abroad, furthering WHO goals.

References

Madden, A., Hopwood, M., Neale, J., & Treloar, C. (2018). Beyond interferon side effects: What residual barriers exist to DAA hepatitis C treatment for people who inject drugs? PLoS One, 13(11), e0207226. https://doi.org/10.1371/journal.pone.0207226
Oru, E., Trickey, A., Shirali, R., Kanters, S., & Easterbrook, P. (2021). Decentralisation, integration, and task-shifting in hepatitis C virus infection testing and treatment: a global systematic review and meta-analysis. The Lancet Global Health, 9(4), e431-e445. https://doi.org/10.1016/s2214-109x(20)30505-2
Von den Hoff, D. W., Berden, F. A. C., Atsma, F., Schellekens, A. F. A., & Drenth, J. P. H. (2022). Against All Odds? Addiction History Associated with Better Viral Hepatitis Care: A Dutch Nationwide Claims Data Study. J Clin Med, 11(4). https://doi.org/10.3390/jcm11041146
European Association for the Study of the Liver, e. e. e., Clinical Practice Guidelines Panel, C., representative, E. G. B., & Panel, m. (2020). EASL recommendations on treatment of hepatitis C: Final update of the series(). J Hepatol, 73(5), 1170-1218. https://doi.org/10.1016/j.jhep.2020.08.018

Disclosure

Daan Von den Hoff and Joost Drenth declare receipt of funds from Abbvie and Gilead; the other authors have nothing to declare.

Introduction

Watch-and-Wait is an increasingly recognized non-surgical management option for rectal cancer patients achieving a clinical complete response (cCR) following neoadjuvant therapy. This approach aims to preserve organ function by avoiding surgery, but necessitates vigilant endoscopic surveillance, to detect local tumor regrowth¹ (LTR). The specific endoscopic features associated with regrowth remain incompletely defined.

Aims & Methods

We performed a retrospective analysis of patients monitored under the Watch-and-Wait program at Karolinska University Hospital², focusing on the endoscopic characteristics of LTR. As of December 2023, 145 patients who met the criteria for clinical complete response (cCR) were included.
The neoadjuvant treatment consisted of chemoradiotherapy (CRT) in 16 patients (11%), short course radiotherapy (SCRT) + chemotherapy in 69 patients (47.6%) and SCRT alone (5 x 5 Gy) in 60 patients (41.4%). The median age of the patients was 66 years (range 29-94), with 61.4% being male. The initial tumor stage was T1/T2 in 42 patients (29%) and T3/T4 in 103 patients (71%). The nodal stage was N0 in 35 patients (24%) and N+ in 110 patients (75.9%). The median follow-up period was 29 months (range 3-102 months).
Patients were monitored with rectal digital exams, flexible endoscopy, CEA measurements, and MRI every 3 months for 2 years, and then every 6 months thereafter. During endoscopy, narrow-band imaging (NBI) and NICE classification³ was utilized.

Results

Out of the 145 patients, 28 (19.3%) experienced LTR as of December 2023. The median time from the completion of radiotherapy to regrowth was 9 months (range 3-20 months). Regrowth was detected intraluminally by endoscopy in 23 patients (82.1%), while in 5 patients (17.9%), regrowth was detected on MRI but was not visible intraluminally.
The most common endoscopic features of regrowth included a NICE 3 pattern (n=16) and contact bleeding (n=16). Additional findings included polypoid tissue (n=13), ulceration (n=10), irregular surface (n=9), fibrin cover (n=9), stenosis (n=6), and submucosal nodules (n=5).

Conclusion

As regrowth occurs in at least one of five patients and most commonly with intraluminal findings, this study highlights the importance of meticulous endoscopic follow-up. Contact bleeding and NICE type 3 lesions observed with narrow-band imaging (NBI) were key endoscopic findings in patients with tumor regrowth, while polypoid lesions were observed in less than 50%. Combining endoscopic assessment with other modalities, such as MRI, is essential, as regrowth may be undetectable endoscopically in a proportion of patients.

References

1. Cerdan-Santacruz C, Vailati BB, Sao Juliao GP, Habr-Gama A, Perez RO. Local tumor regrowth after clinical complete response following neoadjuvant therapy for rectal cancer: what happens when organ preservation falls short. Tech Coloproctol 2023;27(1):1-9. DOI: 10.1007/s10151-022-02654-5.
2. Nilsson PJ, Ahlberg M, Kordnejad S, Holm T, Martling A. Organ preservation following short-course radiotherapy for rectal cancer. BJS Open 2021;5(5). DOI: 10.1093/bjsopen/zrab093.
3. Hamada Y, Tanaka K, Katsurahara M, et al. Utility of the narrow-band imaging international colorectal endoscopic classification for optical diagnosis of colorectal polyp histology in clinical practice: a retrospective study. BMC Gastroenterol 2021;21(1):336. DOI: 10.1186/s12876-021-01898-z.

Disclosure

Stephan Haas (SLH) has received speaker's honoraria from Santax Medico, Tillotts Pharma, Lilly, Mediahuset, and Johnson & Johnson.

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

Intestinal point-of-care ultrasound, as standardized by the International Bowel Ultrasound Group (IBUS), has emerged as a valuable tool for diagnosing, monitoring, and managing patients with Inflammatory Bowel Disease (IBD). While IBUS emphasizes a structured intestinal assessment, some European centers adopt a more comprehensive approach, combining intestinal ultrasound with a complete abdominal examination.
The Karolinska Centre for Digestive Health, a tertiary referral institution providing specialized care to approximately 4,500 patients with IBD, established a dedicated Gastrointestinal Ultrasound Unit in October 2023. This unit offers advanced diagnostic services to both hospitalized patients and those treated on an outpatient basis.

Aims & Methods

This retrospective study aimed to assess the prevalence of secondary extraintestinal findings in IBD patients undergoing comprehensive abdominal ultrasound between October 4, 2023, and March 4, 2025. All patients underwent ultrasound assessments that included both intestinal and abdominal imaging. Patients referred for indications unrelated to intestinal ultrasound (IUS), as well as those undergoing repeat examinations, were excluded from the analysis to ensure data consistency.
All examinations were performed by a single gastroenterologist with 25 years of ultrasound experience. In cases where secondary extraintestinal findings were identified, patients’ electronic medical records were reviewed to determine whether these findings represented new diagnoses or previously known conditions.

Results

The study included 348 patients with IBD, 201 (58%) females and 147 (42%) males, with a mean age of 42.4 years. Among these, 260 (75%) were referred internally by our IBD Outpatient Clinic, 47 (13%) by the Gastroenterology Ward, 33 (10%) by private outpatient clinics, and the remainder from other healthcare sites. IUS revealed evidence of intestinal inflammation in 144 patients (42%), while findings were normal in 204 patients (58%).
Furthermore, 150 patients presented with a total of 195 secondary extraintestinal findings, of which 113 (58%) represented newly identified pathologies. Among all secondary findings, the majority, 104 (53%), were related to the hepatobiliary system, including 33 newly diagnosed cases of hepatic steatosis and 17 new cases of cholecystolithiasis. One patient demonstrated ultrasound features suggestive of primary sclerosing cholangitis (PSC) and is currently undergoing further evaluation. Additional findings involved the reproductive system (29/15%), urinary system (15/7%), spleen (32/16%), and pancreas (5/2%). Various other intra-abdominal findings were also identified (37/18%). Notably, one patient presented with a suspicious mass in the right iliac fossa, and another demonstrated ultrasound findings suggestive of a prostatic tumor; both cases were referred for further oncologic evaluation. Additionally, three patients were newly diagnosed with intraductal papillary mucinous neoplasm (IPMN), which was subsequently confirmed via magnetic resonance imaging, and all were enrolled in the national IPMN surveillance protocol.

Conclusion

A considerable proportion of patients with IBD were found to have previously unknown extraintestinal abdominal pathologies, underscoring the essential role of comprehensive ultrasound examination that combines both intestinal and abdominal assessment. Fortunately, only a minority of these findings resulted in changes to patient management.

Disclosure

Francesca Bresso has acted as national and/or local principal investigator for clinical trials for Janssen, Ferring, and AbbVie. Charlotte Hedin served as a speaker and/or advisory board member for AstraZeneca, AbbVie, Dr. Falk Pharma and the Falk Foundation, Galapagos, Janssen, Pfizer, Ferring, Takeda, and Tillotts Pharma and received grant support from Tillotts Pharma and Takeda. Stephan L. Haas has served as a speaker for Takeda, Santax Medico, Tillotts Pharma, Johnson & Johnson, and Mediahuset. The rest of the authors have nothing to declare.

Introduction

Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking drug indicated for Crohn's disease (CD), is administered intravenously at Weeks 0, 2, and 6, then every 8 weeks (Q8W). Dose escalation to every 4 weeks (Q4W) may recapture response to treatment in ~50% of patients with inadequate/loss of response. Factors associated with VDZ dose escalation from Q8W to Q4W and real-world outcomes remain underexplored.

Aims & Methods

Adults with moderate to severe CD initiating VDZ Q8W maintenance therapy were prospectively followed in a Canadian patient support program (2015-2023). Two cohorts were included: 1) patients escalated to Q4W during maintenance therapy any time after week 14 infusion (Q8W>Q4W maintenance) and 2) patients maintained on Q8W treatment for ≥2 years without dose escalation (Q8W maintenance). Baseline characteristics were summarized as median (range) and frequency (%) and compared between cohorts. Rates of clinical remission (Harvey-Bradshaw Index [HBI]<5) were described stratifying by prior biologic experience. Associations between baseline factors and clinical remission 3 months after Q4W dose escalation were assessed using Wilcoxon rank sum test and Fisher’s exact test. Treatment persistence at 12 and 24 months after treatment initiation and dose escalation were evaluated in the Q8W>Q4W cohort using Kaplan-Meier survival analysis.

Results

250 patients were included in the Q8W>Q4W maintenance cohort (39% bio-naïve), and 116 in the Q8W maintenance cohort (51% bio-naïve). In both cohorts, median age at treatment initiation was 50 years and baseline HBI score was 10. In the Q8W>Q4W maintenance cohort, median disease duration prior to initiation of treatment was 14 years (0-69) and median follow-up duration was 22 months (7-60). In the Q8W cohort, median disease and follow-up duration were 8 years (0-50) and 35 months (27-46), respectively. At 14 weeks post-treatment initiation, rates of remission in the Q8W>Q4W maintenance cohort were 47% (bio-naïve) and 22% (bio-experienced), and in the Q8W cohort 61% (bio-naïve) and 48% (bio-experienced) (Table 1). Among patients in the Q8W>Q4W maintenance cohort not in remission at the time of dose escalating, 33% achieved remission 3 months after dose escalation to Q4W. Disease duration at baseline was shorter in these patients than in those who did not achieve remission (8 months [0-52] vs. 16 months [0-69], p=0.007). In the Q8W>Q4W maintenance cohort, 12- and 24-month treatment persistence after treatment initiation was 91% and 64% (bio-naïve) and 94% and 67% (bio-experienced), respectively. After dose escalation, 12- and 24-month treatment persistence was 66% and 59% (bio-naïve) and 69% and 53% (bio-experienced) (Table 1).

Conclusion

Patients with CD who underwent VDZ Q8W>Q4W dose escalation achieved lower rates of clinical remission than those remaining on Q8W treatment, and one third achieved clinical remission 3 months after dose escalating. Baseline disease duration was significantly associated with remission among those escalating to Q4W.

References

N/A

Disclosure

AHS: Advisory Board Membership/Consultant: Abbvie, Amgen, BioJAMP, BMS, Celltrion, Fresenius Kabi, Janssen, McKesson, Mylan Pharmaceuticals, Organon, Pendopharm, Roche, Pfizer, Sandoz, Takeda, Viatris, Speakers’ Bureau: Abbvie, Amgen, Ferring, Fresenius Kabi, Janssen, Organon, Pfizer, Sandoz, Takeda, Research Grants: Abbvie, Arena, Celgene/BMS, Genentech, Janssen, Roche, Takeda.
EJB: Participation in advisory boards or speaker services: Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Pendopharm, Jamp, Fresenius, Kabi, Bausch Health, Celltrion, Eli Lilly, BMS, Grant/Research: Janssen, Abbvie, Any other investment or relationship that could be judged by a reasonable and knowledgeable participant to have the potential to influence the content of the training activity, Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Pendopharm, Jamp, Fresenius, Kabi, Bausch Health, Celltrion, BMS.
JFL: AbbVie, BMS, Janssen, Frenesius-Kabi, Pfizer, Sandoz, Takeda. AHS: Advisory Board Membership/Consultant: Abbvie, Amgen, BioJAMP, BMS, Celltrion, Fresenius Kabi, Janssen, McKesson, Mylan Pharmaceuticals, Organon, Pendopharm, Roche, Pfizer, Sandoz, Takeda, Viatris, Speakers’ Bureau: Abbvie, Amgen, Ferring, Fresenius Kabi, Janssen, Organon, Pfizer, Sandoz, Takeda, Research Grants: Abbvie, Arena, Celgene/BMS, Genentech, Janssen, Roche, Takeda.
PW: Personal fees from AbbVie, Ferring, Biogen, and Janssen
MJA, AW, RW: were employees of Takeda Canada Inc. at the time of the study.
RM, JW, CP: were employees of Pentavere Research Group Inc. at the time of the study.
LPB: Consulting from AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HACPharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant, and Vectivbio; grants from Takeda, Fresenius Kabi, and Celltrion; and lecture fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, and Medac.
BB: Advisor/Speaker: Ferring, Janssen, Abbvie, Takeda, Pfizer, BMS, Merck, Sandoz, Organon, Lifelabs, Celltrion. Advisor: Alimentiv, Gilead, Iterative Health, AMT, Celgene, Merck, Amgen, Pendopharm, Eli Lilly, BMS, Fresenius Kabi, Mylan, Viatris, Bausch Health, Celltrion Healthcare, BioJamp Pharma, Eupraxia. Research support: Janssen, Abbvie, GSK, BMS, Amgen, Genentech, Merck. Stock Options: Qu Biologic.

Introduction

Cirrhosis is characterized by structural and functional hepatic alterations. The associated metabolic imbalances and psycho-neurological factors contribute to the high prevalence of sexual disorders and erectile dysfunction among affected patients. The aim of our study was to identify factors associated with sexual dysfunction in cirrhotic patients.

Aims & Methods

We conducted a prospective cross-sectional study, collecting data from patients followed for cirrhosis at the gastroenterology department of Charles Nicolle Hospital in Tunis over a one-year period. Female sexual function was assessed using the FSFI questionnaire. Female sexual dysfunction was defined by an FSFI score below 26 (or below 20 in post menopausal women). Male sexual function was evaluated using the IIEF-15 questionnaire. Male sexual dysfunction was identified by an IIEF-15 score below 42.9. Erectile dysfunction was confirmed by an IIEF-5 score
below 26. An analytical statistical study was conducted, highlighting factors associated with sexual dysfunction in both female and male patient groups.

Results

We included 55 cirrhotic patients (24 women and 31 men), with a sex ratio (M/F) of 1.29 and a mean age at inclusion of 59.11 ± 12.16 years. Female sexual dysfunction was observed in 70.8% of female patients. Male sexual dysfunction was found in 61.3% of patients. Erectile dysfunction was reported in 74.1% of men. Our study showed that the factors associated with female sexual dysfunction were: low economic status (p = 0.007), the presence of arterial hypertension (p = 0.026), and hepatic disease severity attested by Child-Pugh class B/C and MELD score >15 (p = 0.049 and p = 0.018, respectively). In male patients, a higher prevalence of sexual dysfunction was found among smokers patients (p = 0.045; OR = 0.18; 95% CI [0.03; 1.05]) and them who consumed alcohol (p = 0.042; OR = 0.19; 95% CI [0.04; 0.94]). In multivariate analysis, only alcohol consumption was independently associated with male sexual dysfunction (p = 0.041; OR = 9.187). MELD score >15

Conclusion

In conclusion, our study highlights the high frequency of sexual disorders in cirrhotic patients and identifies several associated factors, notably the severity of liver disease, socioeconomic
status, and certain comorbidities. For these reasons, screening and appropriate management of sexual dysfunction is essential in cirrhotic patients especialy with advanced disease or comorbidities.