Corilagin Ameliorates Con A-Induced Hepatic Injury by Restricting M1 Macrophage Polarization

Immune-mediated hepatic injury plays a key role in the initiation and pathogenesis of diverse liver diseases. However, treatment choice for immune-mediated hepatic injury remains limited. Corilagin, a natural ellagitannin extracted from various traditional Chinese medicines, has been demonstrated to exhibit multiple pharmacological activities, such as anti-inflammatory, anti-tumor, and hepatoprotective properties. The present study aimed to investigate the effects of corilagin on immune-mediated hepatic injury using a murine model of concanavalin A (Con A)-induced hepatitis, which is well-characterized to study acute immune-mediated hepatitis. Herein, mice were administered corilagin (25 mg/kg) intraperitoneally twice at 12 h intervals, and 1 h later, the mice were challenged with Con A (20 mg/kg body weight); serum and liver samples were collected after 12 h. The results showed that corilagin significantly increased the survival of mice and reduced serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels. In addition, corilagin markedly improved histopathological damage, hepatocyte apoptosis, and oxidative stress in the liver. The activation of M1 macrophages in the hepatic mononuclear cells was also significantly reduced compared with that in the control group. The expression of M1 macrophage-associated proinflammatory cytokines and genes, including interleukin (IL)-6, IL-12, and inducible nitric oxide synthase (iNOS), was also decreased after corilagin treatment. Finally, the results demonstrated that corilagin regulated macrophage polarization by modulating the mitogen-activated protein kinases (MAPK), nuclear factor (NF)-κB, and interferon regulatory factor (IRF) signaling pathways. Thus, the findings indicate that corilagin protects mice from Con A-induced immune-mediated hepatic injury by limiting M1 macrophage activation via the MAPK, NF-κB, and IRF signaling pathways, suggesting corilagin as a possible treatment choice for immune-mediated hepatic injury.

Open vs. Closed Sphincterotomy for Surgical Treatment of Anal Fissures

There is currently no specific evidence regarding the exact etiology of anal fissures. However, various management options were reported and validated among the relevant research. Lateral internal sphincterotomy has been validated among relevant investigations in the literature as a valid modality for managing patients with chronic anal fissures. In the present literature review, we formulated evidence based on these studies to compare open and closed techniques of this surgery according to the reported outcomes. However, evidence regarding the superiority of either of the techniques over the other is not consistent among these investigations. For instance, some studies reported that closed sphincterotomy is more favorable than the open approach and should be considered the treatment choice for chronic anal fissures. This is because the technique is associated with less frequent rates of complications, less expensive, safe, and effective. On the other hand, many other relevant studies also demonstrated that the reported outcomes for the two modalities exhibited non-significant differences. Therefore, we suggest that researchers should furtherly conduct additional investigations before drawing any conclusions in this field.

Patients Satisfaction with the Methods of Treatment used for Gallstones: A Cross-sectional Study

Background: If gallstones are not causing discomfort, there is usually no need to treat them. Many people with gallstones do not experience any symptoms for a long time. In addition, any treatment can have side effects, and operations are always associated with a certain level of risk. Gallbladder stones are treated differently than stones in the bile duct. If symptoms such as cramp-like pain (colic) occur, they can be relieved with medication. Such pain can only be prevented permanently by removing the gallbladder. An operation is also an option for people without symptoms but with very large gallstones - or with a porcelain gallbladder. The wall of the gallbladder is calcified and there is an increased risk of gallbladder cancer. Methods: This was an analytical cross-sectional study to spotlight the satisfaction levels of the Saudi Population towards the different treatment options for gallstones. The study was carried out at universities, hospitals, and malls in KSA. Data were collected from patients and the general population during a period from June to October 2021. Results: Most of the patients were highly satisfied with the treatment clarification done by the treating doctor (n= 42, 8.8%), the treatment choice for gallstones, the complications that occurred during their treatment period (n= 34, 7.1%), their condition after the end of the treatment period (n= 41, 8.6%), and the treatment method for condition (n=35, 7.3%). On the other hand, there was a proportion of participants who were not satisfied with the treatment duration (n= 39, 8.1%) and the follow-up after the end of the treatment period (n= 46, 9.6%). Conclusion: Participants are highly satisfied with treatment choice and treatment effectiveness. However, they were not satisfied with treatment duration and treatment complications.

OP242 Patient-based Evidence: A Comparison Of The Views Of Patient And Clinical Engagement Participants And Committee Members

IntroductionThe Scottish Medicines Consortium (SMC) conducts early health technology assessment (HTA) of new medicines on behalf of NHSScotland. Evidence from patients and carers on end-of-life and orphan medicines is gathered during Patient and Clinician Engagement (PACE) meetings. The output is a consensus statement describing a medicine's added value from the perspective of patients/carers and clinicians, which is used by SMC committee members in decision-making. This study compared the importance of factors in the PACE statement to PACE participants and committee members.MethodsA survey of ninety-eight PACE participants (consisting of forty-two patient group (PG) representatives and fifty-six clinicians) investigated the importance of quality of life (QoL) themes (family/carer impact, health benefits, tolerability, psychological benefit, hope, normal life, treatment choice and convenience) identified from an earlier thematic analysis of PACE statements. The findings from PG representatives and clinicians were compared, and the overall results were further compared with those from a previous survey of committee members (n = 26).ResultsAmong PACE participants who responded (twenty-six PG representatives and fourteen clinicians), 100 percent rated ‘health benefits’ and ‘ability to take part in normal life’ as important / very important. ‘Convenience of administration’ and ‘treatment choice’ received the lowest rating with fifteen percent and nineteen percent respectively of PG representatives versus seven percent of clinicians rating each as very important. ‘Hope for the future’ received the most diverse response with fifty-eight percent of PG representatives and fourteen of clinicians rating this as very important.In general, PACE participants rated importance of QoL themes higher than committee members (n = 21) but the rank order was similar. Differences between the proportion of PACE participants and committee members who rated themes important/very important was greatest for ‘treatment choice’ (sixty-seven percent versus twenty percent respectively) and ‘hope for the future’ (eighty-two percent versus fifty-three percent).ConclusionsThe findings demonstrate some alignment between PACE participants’ and committee members’ responses, supporting the value of the PACE output in decision-making. Areas for further research are highlighted.

Current Clinical Practice and Decision-Making in Multiple Myeloma Treatment in the United States of America: A Real-World Survey

Introduction: With each successive line of therapy (LOT), treatment choice for patients with multiple myeloma (MM) becomes increasingly complicated due to existing regimens and the lack of consensus on the standard of care for relapsed/refractory disease. There is a need for more real-world (RW) information on current MM treatments and clinical practices. More insight into the complexity of treatment choices for MM, increasing with each LOT, is also needed to better understand and inform patient treatment as their MM progresses. We aimed to examine current clinical practice and decision-making in the RW setting in MM. Methods: Data were derived from the Adelphi MM Disease Specific Programme™, a point-in-time survey of hematologists and hemato-oncologists conducted in the United States of America between August 2020 and July 2021, collating descriptive information on MM treatment patterns and decision-making from first-line (1L) to fourth-line therapy and beyond (4L+). Physicians completed online patient record forms for their next 8 consulting patients who had a confirmed diagnosis of MM and were actively receiving 1L-4L+ treatment (ie, a quota of ≥2 patients on each LOT). Results: A total of 63 physicians were included in the interim analysis, reporting patients who ever received, or are on at the time of data collection, a specific LOT. Data were provided for 259 patients with 1L treatment, 186 with second-line (2L), 120 with third-line (3L), 60 with 4L, and 2 with fifth-line treatment. Of the patients included in the study, 66% were male with a mean age of 67.7 years (standard deviation 8.16 years); 59% of patients used Medicare for their health insurance and 32% of patients had commercial insurance. The majority of patients received triplet regimens in each LOT (1L: 72%, 2L: 72%, 3L: 68%, 4L: 43%). The top 5 triplet regimens are shown in Table 1. Regimens including cluster of differentiation (CD)38-targeted treatments were used across all LOTs, with the most frequent use seen in earlier relapsed/refractory settings (1L: 8%, 2L: 45%, 3L: 26%, 4L: 19%). Retreatment with the same drug class occurred in 53% of patients treated with a proteasome inhibitor, 50% of patients treated with immunomodulatory drugs, and 4% of patients treated with CD38-targeted treatment. Disease progression/relapse was the most frequent reason for treatment cessation across all LOTs among patients who used either mono, doublet, triplet, or quad regimens (1L: n=92 [48%], 2L: n=72 [61%], 3L: n=37 [63%], 4L: n=2 [100%]). For all LOTs, the leading factors influencing physicians' treatment choice were good clinical data regarding overall survival (OS) (1L: 59%, 2L: 65%, 3L: 52%, 4L: 48%) followed by better efficacy overall (1L: 48%, 2L: 53%, 3L: 45%, 4L: 41%). In 3L, high overall response rate was also important (24%). Good clinical data regarding OS was the most frequent factor influencing choice of triplet regimens at 1L, 2L, and 3L (56%, 62%, and 50%, respectively), whereas manageable side effects profile was the leading factor driving choice of triplet regimen at 4L+ (43%). Other factors that influenced treatment choice included long-term safety, transplant eligibility, and effective use of the treatment as part of a combination therapy. Conclusion: We provide valuable RW data on current treatment patterns and decision-making in MM. Interim analyses revealed a trend for use of triplet therapies across all LOTs, high retreatment rate with the same drug class, and the importance of survival data and clinical efficacy as key factors influencing physician selection of treatment. Additional analyses will be conducted as physicians complete their patient reporting for the study to identify unmet needs and opportunities for new treatment strategies in MM. Funding: GlaxoSmithKline (Study 209997). Figure 1 Figure 1. Disclosures Ribbands: Adelphi Real World, paid employee: Current Employment. Gorsh: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Boytsov: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Luke: Adelphi Real World, paid employee: Current Employment. Lambert: Adelphi Real World, paid employee: Current Employment. Hogea: GlaxoSmithKline, paid employee: Current equity holder in publicly-traded company, Ended employment in the past 24 months.