Prevalence of hepatitis C, hepatitis B and HIV and their therapeutic management in a French public psychiatric hospital.

INTRODUCTION: Several studies suggest that the prevalence of hepatitis C, hepatitis B and HIV are higher in psychiatric patients than in the general population; however, few French studies have been published. The aims of this study were to determine the seroprevalence of the three viruses, describe the profile of infected patients and evaluate the initiation of antiviral treatment in a population of patients hospitalized in a psychiatric hospital. METHOD: Between January and October 2020, screening for hepatitis C virus, hepatitis B virus and HIV was systematically offered to all patients admitted to the intersectoral reception and orientation unit of a psychiatric hospital. If serology was positive, viral load was automatically determined from the same blood sample. As direct-acting antivirals (DAAs) are not financed "in addition" to hospital charges, it was decided a priori to start treatment for HCV immediately before discharge. RESULTS: Between January 7 and October 1, 2020, 407 patients accepted screening. Of these patients, 17 (4.2%; 95% CI: 2.2-6.1%) were anti-HCV positive and two were anti-HIV+/anti-HCV- (0.49%). HCV RNA was detectable in 9/17 anti-HCV+ patients, with a prevalence of infection of 2.2% (CI: 0.8-3.6%). Drug use was identified in 16 anti-HCV+ patients (94%), ten with active drug use. Of the nine viraemic patients, only four received a prescription for DAA treatment at the end of hospitalization, and only one was followed up by his general practitioner with the confirmation of virological cure three months after treatment cessation. No patient tested positive for hepatitis B surface antigen, but 3% had serological markers indicating HBV past infection. The anti-HBV vaccination coverage rate was only 39% in the entire population and only 41% for patients with a history of drug use. CONCLUSION: Our study confirms that the prevalence of HCV infection is significantly higher in the psychiatric population than in the general population. By far, the main risk factor for HCV infection is drug use. This justifies the systematic performance of regular screening in this population. The way in which DAAs are financed in psychiatric hospitals seems to be a major obstacle to the initiation of treatment for chronic HCV infection during hospitalization and therefore to the elimination of HCV infection in the psychiatric population.

Atezolizumab plus bevacizumab in advanced hepatocellular carcinoma after treatment failure with multikinase inhibitors.

BACKGROUND AND AIMS: Data on the effectiveness of atezolizumab plus bevacizumab (atezo-bev) after failure of multikinase inhibitor (MKI) therapy in patients with advanced hepatocellular carcinoma are scarce. METHODS: This retrospective multicentre study included all consecutive patients treated with atezo-bev after failing one or more MKI treatments in the setting of an early access program. The primary endpoint was the objective response rate (ORR) by investigator assessment (using Response Evaluation Criteria in Solid Tumors v1.1). Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan‒Meier method. RESULTS: Fifty patients were included in this analysis. Atezo-bev was started between April 2020 and November 2021 (median follow-up, 18.21 months). The investigator-assessed ORR was 14% (95% CI 5.37-22.63%), with 7 patients displaying a tumour response, and the disease control rate was 56% (95% CI 51.21-60.8%). After starting atezo-bev, the median OS was 17.1 months (95% CI 10.58-22.01), and the median PFS was 7.99 months (95% CI 4.78-10.50). Treatment-related adverse events led to treatment discontinuation in 7 patients. CONCLUSIONS: Atezo-bev every three weeks showed clinical benefit for a proportion of patients previously treated with one or multiple lines of MKIs.

Inflammatory Bowel Disease Patients' Acceptance for Switching from Intravenous Infliximab or Vedolizumab to Subcutaneous Formulation: The Nancy Experience.

BACKGROUND: Subcutaneous infliximab and vedolizumab formulations have been developed for maintenance therapy in inflammatory bowel disease. The objective of this study was to explore the inflammatory bowel disease patient's acceptance for switching from intravenous infliximab or vedolizumab to subcutaneous, as well as to describe the causes of refusal or, conversely, the factors associated with acceptance. METHODS: Patients were prospectively recruited between June 2021 and March 2022 during their infusion of infliximab or vedolizumab in the Medical Day Hospital of Nancy University Hospital. Adult patients with an established diagnosis of inflammatory bowel disease in clinical remission were eligible for inclusion in this study if they had been treated with intravenous infliximab or vedolizumab for at least six months. RESULTS: One hundred and thirty patients were included in this study. Thirty-six patients (27.7%) received vedolizumab and ninety-four patients (72.3%) received infliximab. Median duration of treatment at inclusion was 7.0 years [3.0-11.0]. In this cohort, 77.7% of patients accepted the switch from intravenous infliximab or vedolizumab to subcutaneous. The main reasons for patient's refusal for switching from intravenous to subcutaneous formulation were fear of loss of efficacy, a more spaced-out medical follow-up, increased frequency of administration, and self-administered injection. A short duration of treatment was associated with a high switch acceptance rate (odd ratio (OR) (95% confidence interval (CI)) = 0.9 (0.8-0.9); p = 0.0002). CONCLUSION: A large majority of the patients included accepted the switch of their treatment with infliximab or vedolizumab from the intravenous form to the subcutaneous form. This study identified one predictor influencing the acceptance rate in inflammatory bowel disease population: short treatment duration. Subcutaneous infliximab and vedolizumab hold potential for greater patient flexibility by self-administration, reducing travel and hospital attendance for infusion.

Impact of the Exposome on the Epigenome in Inflammatory Bowel Disease Patients and Animal Models.

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that encompass two main phenotypes, namely Crohn's disease and ulcerative colitis. These conditions occur in genetically predisposed individuals in response to environmental factors. Epigenetics, acting by DNA methylation, post-translational histones modifications or by non-coding RNAs, could explain how the exposome (or all environmental influences over the life course, from conception to death) could influence the gene expression to contribute to intestinal inflammation. We performed a scoping search using Medline to identify all the elements of the exposome that may play a role in intestinal inflammation through epigenetic modifications, as well as the underlying mechanisms. The environmental factors epigenetically influencing the occurrence of intestinal inflammation are the maternal lifestyle (mainly diet, the occurrence of infection during pregnancy and smoking); breastfeeding; microbiota; diet (including a low-fiber diet, high-fat diet and deficiency in micronutrients); smoking habits, vitamin D and drugs (e.g., IBD treatments, antibiotics and probiotics). Influenced by both microbiota and diet, short-chain fatty acids are gut microbiota-derived metabolites resulting from the anaerobic fermentation of non-digestible dietary fibers, playing an epigenetically mediated role in the integrity of the epithelial barrier and in the defense against invading microorganisms. Although the impact of some environmental factors has been identified, the exposome-induced epimutations in IBD remain a largely underexplored field. How these environmental exposures induce epigenetic modifications (in terms of duration, frequency and the timing at which they occur) and how other environmental factors associated with IBD modulate epigenetics deserve to be further investigated.

Triggering Receptors Expressed on Myeloid Cells 1 : Our New Partner in Human Oncology?

Inflammation is recognized as one of the hallmarks of cancer. Indeed, strong evidence indicates that chronic inflammation plays a major role in oncogenesis, promoting genome instability, epigenetic alterations, proliferation and dissemination of cancer cells. Mononuclear phagocytes (MPs) have been identified as key contributors of the inflammatory infiltrate in several solid human neoplasia, promoting angiogenesis and cancer progression. One of the most described amplifiers of MPs pro-inflammatory innate immune response is the triggering receptors expressed on myeloid cells 1 (TREM-1). Growing evidence suggests TREM-1 involvement in oncogenesis through cancer related inflammation and the surrounding tumor microenvironment. In human oncology, high levels of TREM-1 and/or its soluble form have been associated with poorer survival data in several solid malignancies, especially in hepatocellular carcinoma and lung cancer. TREM-1 should be considered as a potential biomarker in human oncology and could be used as a new therapeutic target of interest in human oncology (TREM-1 inhibitors, TREM-1 agonists). More clinical studies are urgently needed to confirm TREM-1 (and TREM family) roles in the prognosis and the treatment of human solid cancers.

The Immune Landscape of Human Pancreatic Ductal Carcinoma: Key Players, Clinical Implications, and Challenges.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadliest cancer worldwide with an overall survival rate, all stages combined, of still <10% at 5 years. The poor prognosis is attributed to challenges in early detection, a low opportunity for radical resection, limited response to chemotherapy, radiotherapy, and resistance to immune therapy. Moreover, pancreatic tumoral cells are surrounded by an abundant desmoplastic stroma, which is responsible for creating a mechanical barrier, preventing appropriate vascularization and leading to poor immune cell infiltration. Accumulated evidence suggests that PDAC is impaired with multiple "immune defects", including a lack of high-quality effector cells (CD4, CD8 T cells, dendritic cells), barriers to effector cell infiltration due to that desmoplastic reaction, and a dominance of immune cells such as regulatory T cells, myeloid-derived suppressor cells, and M2 macrophages, resulting in an immunosuppressive tumor microenvironment (TME). Although recent studies have brought new insights into PDAC immune TME, its understanding remains not fully elucidated. Further studies are required for a better understanding of human PDAC immune TME, which might help to develop potent new therapeutic strategies by correcting these immune defects with the hope to unlock the resistance to (immune) therapy. In this review, we describe the main effector immune cells and immunosuppressive actors involved in human PDAC TME, as well as their implications as potential biomarkers and therapeutic targets.

Reliability in villous tumors staging between preoperative MRI and histopathological examination.

PURPOSE: This study aimed to assess the reliability of rectal villous tumors staging between rectal MRI and histological examination used as the Gold Standard and to investigate causes for discrepancies. METHODS: The rectal 1.5 T MR scans of 40 patients followed for a histologically proven rectal villous adenoma were retrospectively included. Two independent experienced radiologists staged each tumor according to the TNM classification and described the occurrence of retraction of the rectal wall or spiculations within the associated mesorectum. A third radiologist collected tumor's morphological characteristics. RESULTS: Among the 40 villous tumors studied, 25 (63%) were non-invasive and 15 (37%) were invasive. The mean volume of tumors with spiculations and retraction was significantly greater (p < 0.05) compared to tumors without these characteristics. Spiculations and retraction of the rectal wall were observed regardless of the definitive histological stage and did not represent a malignancy criterion. A weak interobserver reliability [Gwet's AC2: 0.31 (0.04-0.57)] in T-staging was observed between the two readers. Reader 1 showed a high reliability [Gwet's AC2: 0.90 (0.81-0.99)] in T-staging between Histopathological examination and preoperative MRI. In the opposite, reader 2 showed a weak reliability [Gwet's AC2: 0.31 (0.03-0.58)] in T-staging. He overstaged all tumors (100%) with spiculations (p < 0.05). CONCLUSION: MRI understaged rectal villous adenoma and was unable to detect degenerative criteria, along with slight Interobserver agreement. The typical worrisome signs of rectal tumor, such as retractions and spiculations, occurred in all stages and were responsible for misstaging in most cases, in particular bulky tumors.

Impact of a medical interview on the decision to switch from originator infliximab to its biosimilar in patients with inflammatory bowel disease.

BACKGROUND: To lighten the burden on health-care spending, switching from the infliximab originator to a biosimilar in patients with inflammatory bowel disease (IBD) is advocated. However, the uptake of biosimilars lacks initiatives aimed at educating patients. AIMS: To explore the impact of a gastroenterologist's interview on IBD patients' acceptance for switching from infliximab bio-originator Remicade® to its biosimilar CT-P13 Inflectra®. METHODS: After the interview of 138 included patients, 120 properly responded to a self-administered questionnaire to collect consent about the switch and relevant data. French national IBD patients' association (Association François Aupetit) provided an information sheet on biosimilars. RESULTS: 93 (67.0%) out of 138 and 82 (68.3%) out of 120 patients switched treatment. 114 (79.8%) had never heard about biosimilars. Paradoxically, having heard about biosimilars was associated with a poorer chance to switch (Odds Ratio OR [95% CI] = 0.13 [0.02-0.72]). On the contrary, the more satisfied about generics, the more patients accepted the switch (OR [95% CI] = 1.31 [1.01-1.69]). There were 1.47 (Relative Risk RR [95% CI] = 1.47 [1.07-2.01]) times more chance to agree to the switch if the interview modified the patient's opinion on biosimilars. CONCLUSION: This study confirms that an organized information provided to the patient is a contributive way to enhance patient's acceptance of biosimilars in IBD.