Assessment of the quality of online patient information resources for patients considering parastomal hernia treatment.

AIM: The aim was to examine the quality of online patient information resources for patients considering parastomal hernia treatment. METHODS: A Google search was conducted using lay search terms for patient facing sources on parastomal hernia. The quality of the content was assessed using the validated DISCERN instrument. Readability of written content was established using the Flesch-Kincaid score. Sources were also assessed against the essential content and process standards from the National Institute for Health and Care Excellence (NICE) framework for shared decision making support tools. Content analysis was also undertaken to explore what the sources covered and to identify any commonalities across the content. RESULTS: Fourteen sources were identified and assessed using the identified tools. The mean Flesch-Kincaid reading ease score was 43.61, suggesting that the information was difficult to read. The overall quality of the identified sources was low based on the pooled analysis of the DISCERN and Flesch-Kincaid scores, and when assessed against the criteria in the NICE standards framework for shared decision making tools. Content analysis identified eight categories encompassing 59 codes, which highlighted considerable variation between sources. CONCLUSIONS: The current information available to patients considering parastomal hernia treatment is of low quality and often does not contain enough information on treatment options for patients to be able to make an informed decision about the best treatment for them. There is a need for high-quality information, ideally co-produced with patients, to provide patients with the necessary information to allow them to make informed decisions about their treatment options when faced with a symptomatic parastomal hernia.

Formation of a conceptual framework during the development of a patient-reported outcome measure for early gastrointestinal recovery: phase I of the PRO-diGi study.

AIM: Patients admitted to hospital for abdominal surgery often experience gastrointestinal dysfunction. Many studies have reported outcomes following gastrointestinal dysfunction, yet there is no unified definition of recovery or a validated patient-reported outcome measure (PROM). The first stage of PROM development requires formation of a conceptual framework to identify key themes to patients. The aim of this study was to utilize semistructured interviews to identify core themes and concepts relevant to patients to facilitate development of a conceptual framework. METHOD: Adult patients admitted to hospital for major gastrointestinal, urological or gynaecological surgery, in an emergency or elective setting, were eligible to participate. Patients treated nonoperatively for small bowel obstruction were also eligible. Interviews were conducted by telephone, audio-recorded, transcribed, coded and analysed using NVivo software by two researchers and reviewed by lay members of the steering group. Interviews continued until data saturation was reached. Ethical approval was gained prior to interviews (21/WA/0231). RESULTS: Twenty nine interviews were completed (17 men, median age 64 years) across three specialties (20 gastrointestinal, six gynaecological, three urological). Two overarching themes of 'general recovery' and 'gastrointestinal symptoms' were identified. General recovery included three themes: 'life impact', 'mental impact', including anxiety, and 'physical impact', including fatigue. Gastrointestinal symptoms included three themes: 'abdominal symptoms' such as pain, 'diet and appetite' and 'expulsory function', such as stool frequency. A total of 18 gastrointestinal symptoms were identified during patient recovery-many of which lasted several weeks following discharge. CONCLUSION: This study reports a range of gastrointestinal and nongastrointestinal symptoms experienced by patients during early gastrointestinal recovery. Identified symptoms have been synthesized into a conceptual framework to enable development of a definitive PROM for early gastrointestinal recovery.

Patient preferences for treatment in steroid resistant ulcerative colitis - a discrete-choice experiment.

BACKGROUND AND AIM: Understanding treatment preferences in those patients who are not responding to corticosteroids for ulcerative colitis is important in informing treatment choices. This study aimed to assess the relative importance of treatment characteristics to patients by conducting a discrete-choice experiment. METHODS: Patients completed the questionnaire online. All data were collected between September and December 2020. Participants were shown 13 discrete-choice experiment tasks - a series of side-by-side comparisons of competing, hypothetical treatment characteristics and asked to select a preferred treatment. Survey responses were analysed using descriptive statistics and regression analyses. RESULTS: 115 patients completed the study. Patient preferences were strongest for treatments with a lower chance of side effects, this attribute had the most influence on the choice of treatment patients preferred. The second most important attribute was an improvement in maintaining remission. Conversely, route and frequency of administration were least important on the choice of treatment patients preferred. Respondents were willing to make trade offs and accept treatment benefits to compensate them for receiving a treatment with a less desirable attribute level. Participants were willing to accept a larger benefit of 45% improvement in maintenance of remission to accept a treatment with a higher probability of side effects. The benefit required was smaller with a 10% improvement in remission required to accept a treatment with a lower probability of side effects. CONCLUSION: Quantifying preferences helps to identify and prioritise treatment characteristics that are important to patients. The results highlight the importance of careful discussion of side effects, including the magnitude of risk, using visualisation tools during a patient consultation to support decisions.

Antibody Opsonization of a TLR9 Agonist-Containing Virus-like Particle Enhances In Situ Immunization.

The immunologic and therapeutic effects of intratumoral (IT) delivery of a novel virus-like particle as a lymphoma immunotherapy were evaluated in preclinical studies with human cells and a murine model. CMP-001 is a virus-like particle composed of the Qß bacteriophage capsid protein encapsulating an immunostimulatory CpG-A oligodeoxynucleotide TLR9 agonist. In vitro, CMP-001 induced cytokine production, including IFN-α from plasmacytoid dendritic cells, but only in the presence of anti-Qß Ab. In vivo, IT CMP-001 treatment of murine A20 lymphoma enhanced survival and reduced growth of both injected and contralateral noninjected tumors in a manner dependent on both the ability of mice to generate anti-Qß Ab and the presence of T cells. The combination of IT CMP-001 with systemic anti-PD-1 enhanced antitumor responses in both injected and noninjected tumors. IT CMP-001 alone or combined with anti-PD-1 augmented T cell infiltration in tumor-draining lymph nodes. We conclude IT CMP-001 induces a robust antitumor T cell response in an anti-Qß Ab-dependent manner and results in systemic antitumor T cell effects that are enhanced by anti-PD-1 in a mouse model of B cell lymphoma. Early-phase clinical evaluation of CMP-001 and anti-PD-1 combination therapy in lymphoma will begin shortly, based in part on these results.

Intraperitoneal CMP-001: A Novel Immunotherapy for Treating Peritoneal Carcinomatosis of Gastrointestinal and Pancreaticobiliary Cancer.

BACKGROUND: The treatment options for patients with peritoneal carcinomatosis (PC) of gastrointestinal and pancreaticobiliary origins are limited. The virus-like particle, CMP-001, composed of the Qß bacteriophage capsid protein encapsulating a CpG-A oligodeoxynucleotide, activates plasmacytoid dendritic cells (pDCs) and triggers interferon alpha (IFNα) release, leading to a cascade of anti-tumor immune effects. METHODS: To evaluate the ability of CMP-001 to trigger an immune response in patients with PC, peritoneal cells were isolated and stimulated ex vivo with CMP-001. Both IFNα release and percentage of pDC were quantified using enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. To evaluate the anti-tumor response in vivo, murine PC models were generated using mouse cancer cell lines (Panc02 and MC38) in immunocompetent mice treated with intraperitoneal CMP-001 or saline control. Survival was followed, and the immunophenotype of cells in the peritoneal tumor microenvironment was evaluated. RESULTS: The pDCs accounted for 1% (range 0.1-3.9%; n = 17) of the isolated peritoneal cells. Ex vivo CMP-001 stimulation of the peritoneal cells released an average of 0.77 ng/ml of IFNα (range, 0-4700 pg/ml; n = 14). The IFNα concentration was proportional to the percentage of pDCs present in the peritoneal cell mixture (r = 0.6; p = 0.037). In murine PC models, intraperitoneal CMP-001 treatment elicited an anti-tumor immune response including an increase in chemokines (RANTES and MIP-1ß), pro-inflammatory cytokines (IFNγ, interleukin 6 [IL-6], and IL-12), and peritoneal/tumor immune infiltration (CD4+/CD8+ T and natural killer [NK] cells). The CMP-001 treatment improved survival in both the Panc02 (median, 35 vs 28 days) and the MC38 (median: 57 vs 35 days) PC models (p < 0.05). CONCLUSIONS: As a novel immunotherapeutic agent, CMP-001 may be effective for treating patients with PC.

Developing a core outcome set for fistulising perianal Crohn's disease.

OBJECTIVE: Lack of standardised outcomes hampers effective analysis and comparison of data when comparing treatments in fistulising perianal Crohn's disease (pCD). Development of a standardised set of outcomes would resolve these issues. This study provides the definitive core outcome set (COS) for fistulising pCD. DESIGN: Candidate outcomes were generated through a systematic review and patient interviews. Consensus was established via a three-round Delphi process using a 9-point Likert scale based on how important they felt it was in determining treatment success culminating in a final consensus meeting. Stakeholders were recruited nationally and grouped into three panels (surgeons and radiologists, gastroenterologists and IBD specialist nurses, and patients). Participants received feedback from their panel (in the second round) and all participants (in the third round) to allow refinement of their scores. RESULTS: A total of 295 outcomes were identified from systematic reviews and interviews that were categorised into 92 domains. 187 stakeholders (response rate 78.5%) prioritised 49 outcomes through a three-round Delphi study. The final consensus meeting of 41 experts and patients generated agreement on an eight domain COS. The COS comprised three patient-reported outcome domains (quality of life, incontinence and a combined score of patient priorities) and five clinician-reported outcome domains (perianal disease activity, development of new perianal abscess/sepsis, new/recurrent fistula, unplanned surgery and faecal diversion). CONCLUSION: A fistulising pCD COS has been produced by all key stakeholders. Application of the COS will reduce heterogeneity in outcome reporting, thereby facilitating more meaningful comparisons between treatments, data synthesis and ultimately benefit patient care.

B-CLL cells acquire APC- and CTL-like phenotypic characteristics after stimulation with CpG ODN and IL-21.

CpG oligodeoxynucleotides (CpG) and IL-21 are two promising agents for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). Recently, we reported that the combination of CpG and IL-21 (CpG/IL-21) can induce granzyme B (GrB)-dependent apoptosis in B-CLL cells. Here, we demonstrate that treatment of B-CLL cells with CpG and IL-21 results in the development of antigen-presenting cell (APC)-like cells with cytotoxic features. These properties eventually give rise to B-CLL cell apoptosis, independently of their cytogenetic phenotype, whereas normal B-cell survival is not negatively affected by CpG/IL-21. APC- and CTL-typical molecules found to be up-regulated in CpG/IL-21-stimulated B-CLL cells include GrB, perforin, T-bet, monokine-induced by IFN-γ and IFN-γ-inducible protein 10 (IP-10), as well as molecules important for cell adhesion, antigen cross-presentation and costimulation. Also induced are molecules involved in GrB induction, trafficking and processing, whereas the GrB inhibitor Serpin B9 [formerly proteinase inhibitor-9 (PI-9)] is down-modulated by CpG/IL-21. In conclusion, CpG/IL-21-stimulated B-CLL cells acquire features that are reminiscent of killer dendritic cells, and which result in enhanced immunogenicity, cytotoxicity and apoptosis. Our results provide novel insights into the aberrant immune state of B-CLL cells and may establish a basis for the development of an innovative cellular vaccination approach in B-CLL.

Chemoimmunotherapy for relapsed/refractory and progressive 17p13-deleted chronic lymphocytic leukemia (CLL) combining pentostatin, alemtuzumab, and low-dose rituximab is effective and tolerable and limits loss of CD20 expression by circulating CLL cells.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analog refractory disease or TP53 dysfunction still have limited treatment options and poor survival. Alemtuzumab-containing chemoimmunotherapy regimens can be effective but frequently cause serious infections. We report a Phase II trial testing the efficacy and tolerability of a short-duration regimen combining pentostatin, alemtuzumab, and low-dose high-frequency rituximab designed to decrease the risk of treatment-associated infections and to limit the loss of CD20 expression by CLL cells. The study enrolled 39 patients with progressive CLL that was either relapsed/refractory (n = 36) or previously untreated with 17p13 deletion (17p13-) (n = 3). Thirteen (33%) patients had both 17p13- and TP53 mutations predicted to be dysfunctional, and eight patients had purine analog refractory CLL without TP53 dysfunction. Twenty-six (67%) patients completed therapy, with only five (13%) patients having treatment-limiting toxicity and no treatment-related deaths. Twenty-two (56%) patients responded to treatment, with 11 (28%) complete responses (four with incomplete bone marrow recovery). Median progression-free survival was 7.2 months, time to next treatment was 9.1 months, and overall survival was 34.1 months. The majority of deaths (82%) were caused by progressive disease, including transformed diffuse large B-cell lymphoma (n = 6). Correlative studies showed that low-dose rituximab activates complement and natural killer cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that pentostatin, alemtuzumab, and low-dose high-frequency rituximab is a tolerable and effective therapy for CLL and that low-dose rituximab therapy can activate innate immune cytotoxic mechanisms without substantially decreasing CD20 expression.

Non-pharmacological interventions to improve sleep quality and quantity for hospitalized adult patients-co-produced study with surgical patient partners: systematic review.

BACKGROUND: Hospitalized patients experience sleep disruption with consequential physiological and psychological effects. Surgical patients are particularly at risk due to surgical stress and postoperative pain. This systematic review aimed to identify non-pharmacological interventions for improving sleep and exploring their effects on sleep-related and clinical outcomes. METHODS: A systematic literature search was performed in accordance with PRISMA guidelines and was preregistered on the Open Science Framework (doi: 10.17605/OSF.IO/EA6BN) and last updated in November 2023. Studies that evaluated non-pharmacological interventions for hospitalized, adult patients were included. Thematic content analysis was performed to identify hypothesized mechanisms of action and modes of administration, in collaboration with a patient partner. Risk of bias assessment was performed using the Cochrane Risk Of Bias (ROB) or Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tools. RESULTS: A total of 59 eligible studies and data from 14 035 patients were included; 28 (47.5%) were randomized trials and 26 included surgical patients (10 trials). Thirteen unique non-pharmacological interventions were identified, 17 sleep measures and 7 linked health-related outcomes. Thematic analysis revealed two major themes for improving sleep in hospital inpatients: enhancing the sleep environment and utilizing relaxation and mindfulness techniques. Two methods of administration, self-administered and carer-administered, were identified. Environmental interventions, such as physical aids, and relaxation interventions, including aromatherapy, showed benefits to sleep measures. There was a lack of standardized sleep measurement and an overall moderate to high risk of bias across all studies. CONCLUSIONS: This systematic review has identified several sleep interventions that are likely to benefit adult surgical patients, but there remains a lack of high-quality evidence to support their routine implementation.

Rituximab infusion induces NK activation in lymphoma patients with the high-affinity CD16 polymorphism.

Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity involving FcγRIIIa (CD16) likely contributes to the clinical efficacy of rituximab. To assess the in vivo effects of CD16 polymorphisms on rituximab-induced NK activation, blood was evaluated before and 4 hours after initiation of the initial dose of rituximab in 21 lymphoma subjects. Rituximab induced NK activation and a drop in circulating NK-cell percentage in subjects with the high-affinity [158(VF/VV)] but not the low-affinity [158(FF)] CD16 polymorphism. There was no correlation between NK-cell activation or NK-cell percentage and polymorphisms in CD32A, C1q, or CH50. We conclude that NK activation occurs within 4 hours of rituximab infusion in subjects with the high-affinity CD16 polymorphism but not those with the low-affinity CD16 polymorphism. This finding may help explain the superior clinical outcome seen in the subset of high-affinity CD16 polymorphism lymphoma patients treated with single-agent rituximab.

Granzyme B produced by human plasmacytoid dendritic cells suppresses T-cell expansion.

Human plasmacytoid dendritic cells (pDCs) are crucially involved in the modulation of adaptive T-cell responses in the course of neoplastic, viral, and autoimmune disorders. In several of these diseases elevated extracellular levels of the serine protease granzyme B (GrB) are observed. Here we demonstrate that human pDCs can be an abundant source of GrB and that such GrB(+) pDCs potently suppress T-cell proliferation in a GrB-dependent, perforin-independent manner, a process reminiscent of regulatory T cells. Moreover, we show that GrB expression is strictly regulated on a transcriptional level involving Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), and STAT5 and that interleukin-3 (IL-3), a cytokine secreted by activated T cells, plays a central role for GrB induction. Moreover, we find that the immunosuppressive cytokine IL-10 enhances, while Toll-like receptor agonists and CD40 ligand strongly inhibit, GrB secretion by pDCs. GrB-secreting pDCs may play a regulatory role for immune evasion of tumors, antiviral immune responses, and autoimmune processes. Our results provide novel information about the complex network of pDC-T-cell interactions and may contribute to an improvement of prophylactic and therapeutic vaccinations.

Patient preferences and current practice for adults with steroid-resistant ulcerative colitis: POPSTER mixed-methods study.

BACKGROUND: Corticosteroids are a mainstay of the treatment of moderately severe relapses of ulcerative colitis, yet almost 50% of patients do not respond fully to these and risk prolonged steroid use and side effects. There is a lack of clarity about the definitions of steroid resistance, the optimum choice of treatment, and patient and health-care professional treatment preferences. OBJECTIVES: The overall aim of this research was to understand how steroid-resistant ulcerative colitis is managed in adult secondary care and how current practice compares with patient and health-care professional preferences. DESIGN: A mixed-methods study, including an online survey, qualitative interviews and discrete choice experiments. SETTING: NHS inflammatory bowel disease services in the UK. PARTICIPANTS: Adults with ulcerative colitis and health-care professionals treating inflammatory bowel disease. RESULTS: We carried out a survey of health-care professionals (n = 168), qualitative interviews with health-care professionals (n = 20) and patients (n = 33), discrete choice experiments with health-care professionals (n = 116) and patients (n = 115), and a multistakeholder workshop (n = 9). The interviews with and survey of health-care professionals showed that most health-care professionals define steroid resistance as an incomplete response to 40 mg per day of prednisolone after 2 weeks. The survey also found that anti-tumour necrosis factor drugs (particularly infliximab) are the most frequently offered drugs across most steroid-resistant (and steroid-dependent) patient scenarios, but they are less frequently offered to thiopurine-naive patients. Patient interviews identified several factors influencing their treatment choices, including effectiveness of treatment, recommendations from health-care professionals, route of administration and side effects. Over time, depending on the severity and duration of symptoms and, crucially, as medical treatment options become exhausted, patients are willing to try alternative treatments and, eventually, to undergo surgery. The discrete choice experiments found that the probability of remission and of side effects strongly influences the treatment choices of both patients and health-care professionals. Patients are less likely to choose a treatment that takes longer to improve symptoms. Health-care professionals are willing to make difficult compromises by tolerating greater safety risks in exchange for therapeutic benefits. The treatments ranked most positively by patients were infliximab and tofacitinib (each preferred by 38% of patients), and the predicted probability of uptake by health-care professionals was greatest for infliximab (62%). LIMITATIONS: The survey and the discrete choice experiments with patients and health-care professionals are limited by their relatively small sample sizes. The qualitative studies are subject to selection bias. The timing of the different substudies, both before and during the COVID-19 pandemic, is a potential limitation. CONCLUSIONS: We have identified factors influencing treatment decisions for steroid-resistant ulcerative colitis and the characteristics to consider when choosing treatments to evaluate in future randomised controlled trials. The findings may be used to improve discussions between patients and health-care professionals when they review treatment options for steroid-resistant ulcerative colitis. FUTURE WORK: This research highlights the need for consensus work to establish an agreed definition of steroid resistance in ulcerative colitis and a greater understanding of the optimal use of tofacitinib and surgery for this patient group. A randomised controlled trial comparing infliximab with tofacitinib is also recommended. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 41. See the NIHR Journals Library website for further project information.

Steroids are one of the main treatments for ulcerative colitis; however, steroids work well for only about 50% of people who take them. There are many other treatments that can be given when steroids do not work, but evidence is limited about how these treatments are best used. To carry out better research about the best treatment options and to improve clinical practice in the future, this study aimed to find out how adults with steroid-resistant ulcerative colitis are managed in hospital and why patients and health-care professionals prefer different treatments. The study combined various methods of research, including an online survey of health-care professionals (n = 168), interviews with health-care professionals (n = 20) and patients (n = 33), a survey of health-care professionals (n = 116) and patients (n = 115) to ask them about treatment preferences, and a multistakeholder workshop (n = 9). The interviews with and survey of health-care professionals found that most health-care professionals define steroid resistance as an incomplete response to 40 mg per day of prednisolone after 2 weeks. The survey also found that the most frequently offered drugs are anti-tumour necrosis factor drugs (particularly infliximab). Patient interviews found that several factors influenced treatment choices, including effectiveness of treament, guidance from health-care professionals, route of administration and side effects. Patients were willing to try alternative treatments and surgery over time. The survey found that a higher level of remission and a lower chance of side effects strongly influenced treatment choices. Patients are less likely to choose a treatment that takes longer to improve symptoms. Health-care professionals are willing to make difficult compromises by tolerating greater safety risks in exchange for therapeutic benefits. Infliximab and tofacitinib were ranked most positively by patients, and the predicted uptake by health-care professionals was greatest for infliximab. The results of this study help improve understanding of why people choose certain treatments, improve decision-making in partnership and inform the design of future research.

Defining standards in colorectal optimisation: a Delphi study protocol to achieve international consensus on key standards for colorectal surgery prehabilitation.

INTRODUCTION: Prehabilitation in colorectal surgery is evolving and may minimise postoperative morbidity and mortality. With many different healthcare professionals contributing to the prehabilitation literature, there is significant variation in reported primary endpoints that restricts comparison. In addition, there has been limited work on patient-related outcome measures suggesting that patients with colorectal cancer needs and issues are being overlooked. The Defining Standards in Colorectal Optimisation Study aims to achieve international consensus from all stakeholders on key standards to provide a framework for reporting future prehabilitation research. METHODS AND ANALYSIS: A systematic review will identify key standards reported in trials of prehabilitation in colorectal surgery. Standards that are important to patients will be identified by a patient and public involvement (PPI) event. The longlist of standards generated from the systematic review and PPI event will be used to develop a three-round online Delphi process. This will engage all stakeholders (healthcare professionals and patients) both nationally and internationally. The results of the Delphi will be followed by a face-to-face interactive consensus meeting that will define the final standards for prehabilitation for elective colorectal surgery. ETHICS AND DISSEMINATION: The University of Glasgow College of Medical, Veterinary and Life Sciences Ethics Committee has approved this protocol, which is registered as a study (200190120) with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of the standards developed by all stakeholders will increase the potential for comparative research that advances understanding of the clinical application of prehabilitation. PROSPERO REGISTRATION NUMBER: CRD42019120381.

Direct and indirect immune effects of CMP-001, a virus-like particle containing a TLR9 agonist.

BACKGROUND: CMP-001, also known as vidutolimod, is a virus-like particle containing a TLR9 agonist that is showing promise in early clinical trials. Our group previously demonstrated that the immunostimulatory effects of CMP-001 are dependent on an anti-Qß antibody response which results in opsonization of CMP-001 and uptake by plasmacytoid dendritic cells (pDCs) that then produce interferon (IFN)-α. IFN-α then leads to an antitumor T-cell response that is responsible for the in vivo efficacy of CMP-001. Here, we explore mechanisms by which the initial effects of CMP-001 on pDCs activate other cells that can contribute to development of an antitumor T-cell response. METHODS: Uptake of CMP-001 by various peripheral blood mononuclear cell (PBMC) populations and response to anti-Qß-coated CMP-001 were evaluated by flow cytometry and single-cell RNA sequencing. Purified monocytes were treated with anti-Qß-coated CMP-001 or recombinant IFN-α to evaluate direct and secondary effects of anti-Qß-coated CMP-001 on monocytes. RESULTS: Monocytes had the highest per cell uptake of anti-Qß-coated CMP-001 with lower levels of uptake by pDCs and other cell types. Treatment of PBMCs with anti-Qß-coated CMP-001 induced upregulation of IFN-responsive genes including CXCL10, PDL1, and indoleamine-2,3-dioxygenase (IDO) expression by monocytes. Most of the impact of anti-Qß-coated CMP-001 on monocytes was indirect and mediated by IFN-α, but uptake of anti-Qß-coated CMP-001 altered the monocytic response to IFN-α and resulted in enhanced expression of PDL1, IDO, and CD80 and suppressed expression of CXCL10. These changes included an enhanced ability to induce autologous CD4 T-cell proliferation. CONCLUSIONS: Anti-Qß-coated CMP-001 induces IFN-α production by pDCs which has secondary effects on a variety of cells including monocytes. Uptake of anti-Qß-coated CMP-001 by monocytes alters their response to IFN-α, resulting in enhanced expression of PDL1, IDO and CD80 and suppressed expression of CXCL10. Despite aspects of an immunosuppressive phenotype, these monocytes demonstrated increased ability to augment autologous CD4 T-cell proliferation. These findings shed light on the complexity of the mechanism of action of anti-Qß-coated CMP-001 and provide insight into pathways that may be targeted to further enhance the efficacy of this novel approach to immunotherapy.

Monocytes Exposed to Immune Complexes Reduce pDC Type 1 Interferon Response to Vidutolimod.

Vidutolimod, also known as CMP-001, is a virus-like particle composed of the Qß bacteriophage coat protein encasing a TLR9 agonist. Vidutolimod injected intratumorally is showing promise in early phase clinical trials based on its ability to alter the tumor microenvironment and induce an anti-tumor immune response. We previously demonstrated that the in vivo efficacy of vidutolimod is dependent on the presence of anti-Qß antibodies that enhance opsonization and uptake of vidutolimod by TLR9-expressing plasmacytoid dendritic cells (pDCs). Here, we evaluated the effect of immune complexes, including anti-Qß-coated vidutolimod, on induction of Type 1 Interferon production by peripheral blood mononuclear cells in response to vidutolimod and soluble TLR9 agonists. Immune complexes, including but not limited to anti-Qß-coated vidutolimod, indirectly suppressed TLR9-mediated Type 1 Interferon production by pDCs in a monocyte-dependent manner. These findings indicate that anti-Qß-coated vidutolimod has effects in addition to those mediated by TLR9 that could have important clinical implications for understanding the mechanism of action of this exciting new approach to in situ immunization and cancer immunotherapy.

Patient Views Around Their Hernia Surgery: A Worldwide Online Survey Promoted Through Social Media.

Introduction: Hernias are one of the most common surgical diagnoses, and general surgical operations are performed. The involvement of patients in the decision making can be limited. The aim of this study was to explore the perspectives of patients around their hernia and its management, to aid future planning of hernia services to maximise patient experience, and good outcomes for the patient. Methods: A SurveyMonkey questionnaire was developed by patient advocates with some advice from surgeons. It was promoted on Twitter and Facebook, such as all found "hernia help" groups on these platforms over a 6-week period during the summer of 2020. Demographics, the reasons for seeking a hernia repair, decision making around the choice of surgeon, hospital, mesh type, pre-habilitation, complications, and participation in a hernia registry were collected. Results: In total, 397 questionnaires were completed in the study period. The majority of cases were from English speaking countries. There was a strong request for hernia specialists to perform the surgery, to have detailed knowledge about all aspects of hernia disease and its management, such as no operation and non-mesh options. Chronic pain was the most feared complication. The desire for knowledge about the effect of the hernia and surgery on the sexual function in all age groups was a notable finding. Pre-habilitation and a hernia registry participation were well-supported. Conclusions: Hernia repair is a quality of life surgery. Whether awaiting surgery or having had surgery with a good or bad outcome, patients want information about their condition and treatment, such as the effect on aspects of life, such as sex, and they wish greater involvement in their management decisions. Patients want their surgery by surgeons who can also manage complications of such surgery or recommend further treatment. A large group of "hernia surgery injured" patients feel abandoned by their general surgeon when complications ensue.

Development and evaluation of a patient decision aid for patients considering ongoing medical or surgical treatment options for ulcerative colitis using a mixed-methods approach: protocol for DISCUSS study.

INTRODUCTION: Approximately 20%-30% of patients with ulcerative colitis (UC) require surgery, the majority of these being elective due to chronic symptoms refractory to medical treatment. The decision for surgery is difficult and dependent on patient preferences. Current resources for patients considering surgery have been found not to meet minimum international standards. The overall aim of the 'DISCUSS' study is to develop and evaluate a new patient decision aid (PtDA) for patients considering surgery for UC created in line with international minimum standards. METHODS AND ANALYSIS: This is a prospective mixed-methods study of adults (18+ years) who are considering surgical intervention for UC across two regional centres in Yorkshire, UK. This study is in three stages. In stage 1 we will develop the PtDA and its content via systematic reviews and a patient questionnaire. In stage 2 we will assess the face validity of the PtDA using mixed-methods on key stakeholders using both semistructured interviews and questionnaires, following which the PtDA will be refined. In stage 3 we will assess the acceptability of using the PtDA in clinical practice. This will use a mixed-methods approach on clinicians and patients who are considering undergoing elective surgery. Questionnaires including the Preparation for Decision-Making Scale, a measure of anxiety and decisional conflict will be analysed at two timepoints using paired sample t-tests and CIs. Interviews with patients and clinicians will be analysed using thematic analysis. ETHICS AND DISSEMINATION: Research ethics approval from North East-Tyne & Wear South Research Ethics Committee (Ref: 19/NE/0073) and Health Research Authority approval (Ref: 257044) have been granted. Results will be published in open access peer-reviewed journals, presented in conferences and distributed through the Crohn's and Colitis UK charity. External endorsement will be sought from the International Patient Decision Aid Standards Collaboration inventory of PtDAs. PROSPERO REGISTRATION NUMBER: CRD42018115513, CRD42019126186, CRD42019125193.