Triple Therapy Group Research Articles

The effect of adding pancreatin to standard otilinium bromide and simethicone treatment in type 2 diabetes mellitus patients with irritable bowel syndrome.

This study aimed to assess the impact of adding pancreatin (a pancreatic enzyme derivative) to standard treatment on patients diagnosed with Irritable Bowel Syndrome (IBS) and Type 2 Diabetes Mellitus (T2DM). IBS and T2DM frequently coexist, leading to significant gastrointestinal symptoms and a decrease in quality of life. Gastrointestinal symptoms arising in T2DM patients present challenges in management for both clinicians and patients. Standard treatments may not fully address these symptoms. Recent studies suggest that pancreatic enzyme replacement therapy may offer additional benefits. This study investigates whether adding pancreatin to standard treatment can improve gastrointestinal outcomes in this patient population. Conducted as a prospective observational study, the research involved patients diagnosed with IBS according to Rome IV criteria and having concomitant T2DM. The patients were divided into two groups: one receiving standard dual treatment (otilinium bromide + simethicone) and the other receiving a triple therapy including a pancreatin derivative in addition to the standard treatment. Various clinical scores and measurements, including Visual Analog Scale (VAS), Bristol Stool Chart (BSC), Irritable Bowel Syndrome-Severity Scoring System (IBS-SSS), and Irritable Bowel Syndrome Quality of Life Instrument (IBS-QOL), were assessed before and after treatment. The study comprised 121 patients, with a median age of 41 years (interquartile range [IQR] 38-48), of whom approximately 70.2% were female. Fifty-eight patients (47.9%) received dual therapy, while sixty-three patients (52.1%) received triple therapy. Before treatment, both groups exhibited similar pre-treatment Bristol stool scale results: normal (39.7% and 49.2%) and constipation (37.9% and 31.7%) in the dual and triple therapy subgroups, respectively (p > 0.05). Post-treatment, the triple therapy group showed a significantly higher proportion of normal cases on the Bristol stool scale (82.5%) compared to the dual therapy group (44.8%) (p < 0.001). After treatment, the triple therapy group demonstrated statistically significant improvements in VAS score (p < 0.001), IBS-SSS (p < 0.001), and IBS-QOL (p < 0.001) compared to the dual therapy group. There were no significant differences between groups in BMI, HbA1c levels, duration of diabetes, or diabetes treatment at baseline (p > 0.05 for all parameters). The findings suggest that adding pancreatin to standard therapies significantly enhanced the quality of life for patients with both IBS and T2DM, demonstrating improvements across various symptom measurements and indicating the potential benefits of this supplementary therapy in managing gastrointestinal symptoms in this population. Further studies are warranted to explore its broader clinical implications and mechanisms of action.

Camrelizumab combined with transcatheter arterial chemoembolization and sorafenib or lenvatinib for unresectable hepatocellular carcinoma: A multicenter, retrospective study

Introduction and ObjectivesWe initiated this study to explore the efficacy of camrelizumab combined with transcatheter arterial chemoembolization (TACE) plus sorafenib or lenvatinib versus TACE plus sorafenib or Lenvatinib for unresectable hepatocellular carcinoma (HCC). Materials and MethodsFrom June 2019 to November 2022, 127 advanced HCC patients were retrospectively analyzed in this study. This consisted of 44 patients that received camrelizumab plus TACE plus sorafenib or lenvatinib (triple therapy group) and 83 patients that received TACE plus sorafenib or lenvatinib (double treatment group). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were compared between the two patient groups. ResultsOur findings demonstrated that patients received the triple therapy exhibited superior median OS (15.8 vs. 10.3 months, P=0.0011) and median PFS (7.2 vs. 5.2 months, P=0.019) compared to the double treatment group. In addition, the triple therapy group exhibited better 6-month (93.5% vs. 66.3%), 12-month (67.2% vs. 36.3%), and 24-month (17.2% vs. 7.6%) survival rates than the double treatment group. However, the ORR (43.2% vs. 28.9%, P = 0.106) and DCR (93.2% vs. 81.9%, P = 0.084) of the two groups were similar. Subgroup analysis showed that compared with the double treatment group, the triple therapy group had a better mOS for HCC with HBV (15.8 vs. 9.6 months, P = 0.0015) and tumor diameter ≥ 5cm (15.3 vs. 9.6 months, P = 0.00055). ConclusionsCamrelizumab plus TACE and sorafenib or lenvatinib may be a promising treatment approach for the clinical management of unresectable HCC patients.

P145 EFFICACY AND SAFETY OF PERINDOPRIL/INDAPAMIDE/AMLODIPINE/BISOPROLOL SINGLE PILL COMBINATION IN PATIENTS WITH ESSENTIAL HYPERTENSION UNCONTROLLED ON TRIPLE THERAPY: AN INTERNATIONAL, RANDOMIZED, DOUBLE-BLIND, PHASE III TRIAL

Background and objectives: In hypertensive patients uncontrolled on triple therapy, guidelines recommend the addition of a fourth drug such as mineral corticoid receptor antagonists, or alternatively, a betablocker. They also support the use of SPCs at any step of the treatment to increase treatment adherence and BP control. Currently, no SPC of 4 drugs is available. This 4-month phase III trial aimed to demonstrate the superiority in BP reduction, ofperindopril/indapamide/amlodipine/bisoprolol (Per/Ind/Aml/Biso) SPC versus a free combination of Per/Ind/Aml in hypertensive patients uncontrolled on triple therapy at optimal doses. Methods: After a 2-month run-in period on the combination of Per/Ind/Aml at optimal doses (10/2.5/5 or 10/2.5/10 mg), patients with sustained uncontrolled essential hypertension with office SBP≥140mmHg and SBP at 24h-ambulatory blood pressure monitoring (ABPM)≥130mmHg received the quadruple SPC of Per/Ind/Aml/Biso (10/2.5/5/5 or 10/2.5/10/5 mg) or continued the same triple therapy for two additional months. Efficacy was assessed on office-SBP (primary endpoint), DBP, BP control, 24h-ABPM and home-BPM (HBPM). Results: 183 patients were randomized: 53.0% were men, mean age was 57.4±10.6 years, mean BMI was 28.2±2.6 kg/m2, and mean office SBP/DBP was 150.35±8.49/90.09±8.23mmHg. After two months, significantly greater decrease in office-SBP (-8.0mmHg, 95%CI [-11.9; -4.0]; p&lt;0.0001) was observed in the quadruple SPC group (n=80) versus the triple therapy group (n=83). Greater decrease in the 24h-systolic ABPM was achieved with the quadruple SPC therapy (-7.5mmHg, 95%CI [-10.9;-4.1]; p&lt;0.0001). Higher percentage of patients achieved 24h-ABPM and HBPM control in the SPC group 51.2% vs 20.7% (p&lt;0.0001) and 60.7% vs 25.4%, (p&lt;0.0001) respectively. After intentional 1-day SPC omission in patient volunteers (n=28), mean 24h-ABPM remained below the 130/80mmHg target, supporting the sustained efficacy of the SPC. Both treatments were well tolerated. Conclusion: The first quadruple SPC of Per/Ind/Aml/Biso demonstrated its superiority to the free combination of Per/Ind/Aml, offering a new alternative to treat effectively and safely patients with hypertension uncontrolled with a combination of Per/Ind/Aml at optimal doses.

Dual therapy based on co-formulated darunavir/ritonavir plus lamivudine for initial therapy of HIV infection: The ANDES randomized controlled trial

Tenofovir-containing antiretroviral therapy regimens may have long-term toxicity-related side effects. This study aimed to compare the virological efficacy of co-formulated darunavir/ritonavir plus lamivudine with darunavir/ritonavir plus tenofovir and emtricitabine or lamivudine. The ANDES study was a 48-week, phase 4, randomized, open-label, non-inferiority trial in treatment-naïve adults living with human immunodeficiency virus (HIV). Patients were randomized on a 1:1 basis to receive a daily oral regimen of either dual therapy based on a generic co-formulation of darunavir/ritonavir (800/100 mg) plus a generic lamivudine 300 mg pill, or triple therapy with darunavir/ritonavir plus tenofovir/emtricitabine (300/200 mg) or tenofovir/lamivudine (300/300 mg). The primary endpoint was the proportion of patients with a viral load of <50 copies/mL at week 48 in the intention-to-treat population. The US Food and Drug Administration snapshot algorithm and a non-inferiority margin of -12% were used. The secondary objective was to analyse safety in the per-protocol population. This study has been registered at ClinicalTrials.gov (NCT02770508). Between November 2015 and 31 October 2020, 336 participants were assigned at random to the triple therapy arm (n=165) or the dual therapy arm (n=171). After 48 weeks, 153 patients in the triple therapy group (93%) and 155 patients in the dual therapy group (91%) achieved virological suppression (difference -2.1%, 95% confidence interval -7.0 to 2.9). Drug-related adverse events were more common in the triple therapy group (P=0.04). Two toxicity-related events led to discontinuation in each group. Co-formulated darunavir/ritonavir plus lamivudine showed non-inferiority and a safer toxicity profile compared with the standard-of-care triple therapy regimen including tenofovir in treatment-naïve patients.

Hepatic arterial infusion chemotherapy plus targeted therapy and immunotherapy versus systemic chemotherapy for advanced intrahepatic cholangiocarcinoma: a retrospective cohort study.

To improve the prognosis of advanced intrahepatic cholangiocarcinoma (iCCA), we retrospectively compared the effect and safety of combined hepatic arterial infusion chemotherapy (HAIC), targeted therapy and immunotherapy with systemic chemotherapy (SC) in unresectable iCCA patients. We retrospectively enrolled 202 advanced iCCA patients treated with SC or targeted therapy, immunotherapy, and FOLFOX-HAIC combined between March 2015 and June 2023 at our institution. 202 patients were divided into two groups based on the therapeutic regimens. Baseline characteristics and prognosis were reviewed and analyzed. After 1-to-1 propensity score matching, 76 patients were included in each group. The triple combination therapy group demonstrated longer median overall survival (OS, 20.77 vs. 14.83 months, P=0.047), progression-free survival (PFS, 9.07 vs. 6.23mo, P<0.001), intrahepatic PFS (11.03 vs. 6.73mo, P<0.001), extrahepatic PFS (11.37 vs. 7.13 months, P=0.0064), and a higher objective response rate (35.5% vs. 14.5%, P=0.003) than the SC group. Fever, thrombocytopenia, elevated ALT, elevated AST, hypoalbuminemia, and hyperbilirubinemia were more common adverse events (AEs) in the triple combination therapy group, while fatigue and anemia were more prevalent in the SC group (P<0.05). For grades 3-4 AEs, the rates of elevated ALT were higher in the triple combination group (P=0.028). Compared with SC, triple combination therapy comprising HAIC, targeted therapy and immunotherapy appears to be an effective and safe treatment for advanced iCCA.

Multiple medications and quality of life of Nigerians with primary open angle glaucoma.

To determine the impact of multiple medications on the quality of life of primary open angle glaucoma (POAG) patients on medical treatment at Guinness Eye Centre Onitsha, Nigeria. Adult patients diagnosed with POAG who were undergoing medical therapy were selected through systematic sampling. They were asked to provide information on socio-demographic background, the number and types of glaucoma medications they were using and any adverse effects encountered while using these medications. The patients' quality of life was assessed by utilizing the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) and all patients completed ocular examination. Data analysis was with Statistical Package for Social Sciences (SPSS) version 23. One hundred and seventy-one patients, aged 40-83 years, mean 59.1 ± 11.1 were studied; there were 79(46.2%) males and 92(53.8%) females. One hundred and nine (63.7%) patients were on multiple medications. Side effects of treatment increased with increasing number of medications. The mean quality of life score in monotherapy group and double therapy group were 89.3 ± 15.8 and 80.2 ± 21.1 respectively; while that in ≥ triple therapy group was 78.9 ± 18.8. This decrease in mean quality of life score with increasing number of medications was statistically significant in bivariate analysis (P < 0.01), however, multiple regression analysis showed that the number of medications did not significantly affect the quality of life scores after adjusting for confounding variables(p = 0.881). Among the patients studied, use of multiple medications, unlike visual acuity (VA) and severity of glaucoma, was not an independent predictor of quality of life.

Hepatic arterial chemotherapy infusion combined with tyrosine kinase inhibitors and PD-1 inhibitors for advanced hepatocellular carcinoma with high-risk: A propensity score matching study.

To ascertain the therapeutic efficacy and safety of FOLFOX (oxaliplatin, fluorouracil, and leucovorin)-based hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKI) and programmed cell death protein-1 inhibitors (PD-1 inhibitors) (triple therapy), as a first-line treatment in high-risk advanced hepatocellular carcinoma (aHCC with Vp4 portal vein invasion or/and tumor diameter ≥ 10cm). This retrospective multicenter study included 466 high-risk aHCC patients treated with either triple therapy (n = 245) or dual therapy (TKI and PD-1 inhibitors, n = 221). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were compared between the two groups. Propensity score matching (PSM) was performed to reduce bias between the two groups. After PSM (1:1), 194 patients in each group were analyzed. The triple-therapy group showed a longer median OS (24.6 months vs. 11.9 months; HR = 0.43, P < 0.001) and a longer median PFS (10.0 months vs. 7.7 months; HR = 0.68, P = 0.002) than the dual-therapy group. The survival rates at 6, 12, and 24 months were 94.2%, 71.0%, and 50.8% for triple therapy and 75.9%, 49.9%, and 26.8% for dual therapy. The ORR in the triple-therapy group was significantly higher (57.7% vs. 28.9%, P < 0.001). In the triple-therapy group, more patients converted to non-high-risk (68.0% vs. 36.6%, P < 0.001) and received salvage liver resection or ablation after downstaging conversion (16.5% vs. 9.2%, P = 0.033). The grade 3/4 adverse events were 59.2% and 47.4% in the triple-therapy group and dual-therapy group, respectively (P = 0.022). FOLFOX-based HAIC plus TKI and PD-1 inhibitors significantly improve survival prognosis compared with TKI plus PD-1 inhibitors. This is a potential first-line treatment for high-risk aHCC, with a relatively controlled safety profile.

Interventional therapy combined with tyrosine kinase inhibitors with or without immune checkpoint inhibitors as initial treatment for hepatocellular carcinoma with portal vein tumor thrombosis: a systematic review and meta-analysis

BackgroundInterventional therapy, in conjunction with tyrosine kinase inhibitors (TKIs), has shown promising outcomes for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). With the advent of immunotherapy, the combined use of immune checkpoint inhibitors (ICIs) has attracted great attention due to their potential effectiveness in advanced HCC. This study aims to compare the efficacy and safety of a triple therapy regimen (Interventional therapy, TKIs and ICIs, IT-TKI-ICI) with a dual therapy regimen (Interventional therapy and TKIs, IT-TKI) in the treatment of HCC and PVTT (HCC-PVTT).MethodsA comprehensive search was carried out in PubMed, Web of Science, Embase, Scopus, and the Cochrane Library databases. Primary outcome measures were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included tumor response rate, adverse event incidence as well as downstaging surgery rate. Statistical analysis was conducted using Revman 5.4 software.ResultsThe meta-analysis finally included 6 cohort studies. The triple therapy group demonstrated significantly prolonged OS and PFS compared to the dual therapy group. Meanwhile, the former exhibited significantly higher rates of objective response rate (ORR), disease control rate (DCR) and better downstaging effects with a higher salvage surgery rate without significantly increasing adverse events.ConclusionIn comparison to dual therapy, the triple therapy with interventional therapy, TKIs, and ICIs demonstrates superior efficacy and equivalent safety for HCC-PVTT.

Retention of triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine compared to combination methotrexate and leflunomide in rheumatoid arthritis

ObjectiveThere are various combination conventional synthetic disease-modifying-antirheumatic drug (csDMARD) treatment strategies used in rheumatoid arthritis (RA). A commonly used csDMARD combination is triple therapy with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ). Another approach is double therapy with MTX and leflunomide (LEF). We compared the real-world retention of these two treatment combinations. MethodsPatients with RA from the Ontario Best Practices Research Initiative (OBRI) who received triple or double therapy on or after OBRI enrolment were included. Retention rates were compared between these two groups. We also analyzed which medication in the combination was discontinued and the reasons for treatment discontinuation. Disease activity was assessed at baseline, 6 and 12 months after treatment initiation as well as at time of discontinuation. Risk factors for treatment discontinuation were also examined. ResultsSix hundred and ninety-two patients were included (258 triple and 434 double therapy). There were 175 (67.8%) discontinuations in the triple therapy group and 287 (66.1%) discontinuations in patients on double therapy. The median survival for triple therapy was longer (15.1 months; 95% CI: 11.2–21.2) compared to double therapy (9.6 months; 95%CI: 7.03–12.2). However, this was not statistically significant. Disease activity at 6 and 12 months, measured by 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) was lower with triple therapy (mean DAS28 at 6 months 3.4 vs. 3.9, P<0.0001 and at 12 months 3.2 vs. 3.5, P=0.0005). ConclusionPatients on triple therapy remained on treatment longer than patients on double therapy. However, this difference was not statistically significant.

Abstract 2078: The imipridone ONC212 cooperates with MEK and immune checkpoint inhibition to elicit in vivo regression of KPC mouse pancreatic tumors

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with limited therapeutic options. ONC212 is a second-generation imipridone with antitumor effects in human PDAC cell lines. ONC212 has been shown to bind to mitochondrial protease ClpP, suppress ClpX, and impair oxidative phosphorylation by decreasing ATP production. While ONC212 has been evaluated in immunocompromised mice xenografted with human pancreatic tumors, ONC212 has not been evaluated, either alone or in combination with MEK and/or immune checkpoint inhibition (ICI), in immunocompetent mice bearing notoriously aggressive KrasLSL.G12D/+; Tp53LSL.R172H/+; Pdx1Cretg/+ (KPC) murine PDAC tumors. We hypothesized that, like human PDAC cells, KPC cells would demonstrate sensitivity to ONC212 both in vitro and in vivo. Our group has previously shown that ONC212 synergizes with trametinib to induce tumor cell death in human PDAC cells. We therefore hypothesized that this combination, together with ICI, would enhance KPC tumor cell death in vivo. Methods: We determined in vitro sensitivity of the KPC cells to ONC212 alone and in combination with trametinib using CellTiter-Glo® luminescent cell viability assays. Results were analyzed after 72 hours of incubation using Compusyn and Combenefit. In vivo experiments involved C57BL/6 mice that were injected subcutaneously with 3 × 105 KPCy cells in 100 mL of PBS/matrigel. To determine the ideal ONC212 dose, we tested five different doses/dosing frequencies (50 mg/kg; 25 mg/kg; 12.5 mg/kg given by oral gavage weekly or twice weekly) in tumor-bearing (50-75 mm3) mice. Mouse weight and tumor size was measured every four days. Treatment was stopped once tumor volumes reached 3,000 mm3 or if ulceration occurred. Once the ideal dose of ONC212 was determined, a study treating KPC tumor-bearing C57BL/6 mice with ONC212, trametinib, and ICI (anti-PD-1 mAb) alone and all possible doublet/triplet combinations was performed using the same methods. Results: We found that the combination of ONC212 and trametinib exhibited synergy in the KPC cell line in vitro. Our in vivo experiments revealed that ONC212 controlled KPC tumor growth in a dose-dependent manner, however, toxicity was also noted at higher, more frequent doses. While both 25 mg/kg and 50 mg/kg twice weekly were equally effective, 25 mg/kg was better tolerated and determined to be the ideal dose. In the combination therapy study, all treatments resulted in tumor reduction, as compared to the vehicle control; however, the triple therapy group had the lowest average tumor size at day twenty. Toxicity was noted in mice receiving at least two treatments, reflected by reduced weights and mobility. Further analysis of the tumor immune microenvironment using multiplex cytokine and immunofluorescence are ongoing. Citation Format: Jasper Chan, Alexis J. Lannigan, Grace Sun, Varun V. Prabhu, Robert Edwards, Leiqing Zhang, Lanlan Zhou, Wafik S. El-Deiry, Alexander Grenander Raufi. The imipridone ONC212 cooperates with MEK and immune checkpoint inhibition to elicit in vivo regression of KPC mouse pancreatic tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2078.

Abstract 1360: TIGIT blockade combined with local radiotherapy and PD-1 blockade in a murine triple-negative breast cancer model

Abstract Background: Immune checkpoint blockades (ICB) improve outcomes of patients with some solid tumors such has melanoma and lung cancer, however the efficacy of ICB alone showed limited efficacy in many other tumors such as breast cancer. Radiation therapy is a promising combination partner of ICB as a strong immune stimulator so called in situ tumor vaccine, however it also can increase immune suppressive repertoires. TIGIT (T cell Immunoglobulin and ITIM domain) is an inhibitory receptor expressed on activated T cells and NK cells. We evaluated the effects of TIGIT blockade in addition to local RT and PD-1 blockade as a strategy to overcome therapeutic resistance of ICI in a murine breast cancer model. Materials and Methods: 4T1-Luc tumors were treated with various strategies including control, RT, anti-PD-1, anti-TIGIT, RT+anti-PD-1, RT+anti-TIGIT, anti-PD-1+anti-TIGIT, and RT+anti-PD-1+anti-TIGIT. A total of 24 Gy in 3 fractions at 1 week was delivered to the tumor at hindlimb (primary tumor) while the tumor at flank (secondary tumor) was left unirradiated. 10 mg/kg of anti-PD-1 blocking antibodies and 10 mg/kg of anti-TIGIT blocking antibodies were intraperitoneally injected for 6 times for 2 weeks. Flow cytometry, IHC staining, and ELISA were performed to assess the immunologic status after treatments. Results: The triple combination therapy (TCT) group showed the most superior growth delay of primary and secondary tumor growth among treatments. The number of metastatic lung nodule was significantly reduced by TCT as well. Plasma levels of interferon-β and interferon-γ were the highest after TCT. Moreover, TCT significantly increased the proportion of splenic CD8+ dendritic cells among myeloid cells, and effector-memory (CD44+CD62L−) cells among splenic Foxp3− non-regulatory CD4+ and CD8+ T cells. Furthermore, expression of CD226, which is an activating counter-receptor of TIGIT, on splenic CD8+ T cells was elevated by TIGIT blockade, possibly suggesting the activation of systemic immune response by addition of TIGIT blockade to local RT and PD-1 blockade. Meanwhile, TCT decreased splenic Foxp3+ regulatory T cells, as well as the expression of CD39 on splenic Foxp3+ regulatory T cells. The increase of CD8+ T cell infiltration in primary and secondary tumors was most prominent in TCT group. Conclusion: TIGIT blockade elicits systemic immune responses in a murine triple-negative breast cancer model. when combined with local RT and PD-1 blockade, which were correlated with significant delay in the growth of both irradiated and unirradiated tumors. These results suggest that TIGIT blockade could be a viable approach to increase the efficacy of RT and immune checkpoint inhibitors in breast cancer which is a relatively immunologically cold tumor. (Work supported by a grant from National Research Foundation of Korea #2023R1A2C3003782 to In Ah Kim). Citation Format: Seongmin Kim, Seung Hyuck Jeon, In Ah Kim. TIGIT blockade combined with local radiotherapy and PD-1 blockade in a murine triple-negative breast cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1360.

Prophylactic Anticoagulation to Prevent Left Ventricular Thrombus Following Acute Myocardial Infarction: A Systematic Review and Meta-Analysis

Clinical practice guidelines from the American Heart Association recommend consideration of prophylactic anticoagulation to prevent left ventricular thrombus (LVT) formation in anterior ST-elevation myocardial infarction (STEMI) patients. These guidelines were given a low certainty of evidence (Class IIb, Level C), relying primarily on case studies and expert consensus to inform practice. Our objective was to compare the safety and efficacy of prophylactic anticoagulation, in addition to dual antiplatelet therapy (DAPT), in the current era of timely primary percutaneous coronary intervention (pPCI). EMBASE, MEDLINE and Cochrane Library were systematically searched from January 2012 through June 2022. A total of 7,378 publications were screened, and 5 publications were eventually included in this review: 1 randomized control trial and 4 retrospective studies involving 1,461 patients. Data were pooled using a fixed effects model and reported as odds ratios (OR) with 95% confidence intervals (CI). The primary outcome of interest was the rate of LVT formation, and the secondary outcomes were the rate of major bleeding and systemic embolism. Pooled analysis showed a significantly lower rate of LVT formation (OR: 0.28 [95% CI: 0.11–0.73; p < 0.01]) and significantly higher rates of bleeding (OR: 2.85 [95% CI: 1.13–7.24; p= 0.03]) in the triple therapy (TT) group compared to DAPT. No significant difference was observed in the rate of systemic embolism between the groups (OR: 0.37 [95% CI: 0.12–1.13; p = 0.08]). In this meta-analysis, there is no conclusive evidence to either support or oppose the use of TT for LVT prevention in anterior STEMI patients treated with pPCI. Appropriately powered randomized controlled trials are warranted to further evaluate the benefits of LVT prevention against the risks of major bleeding in this population.

Survival of Women with Advanced Stage Cervical Cancer: Neo-Adjuvant Chemotherapy Followed by Radiotherapy and Hyperthermia versus Chemoradiotherapy

Aim: To investigate and compare overall survival (OS), disease-free survival (DFS) and toxicity of women who underwent either chemoradiotherapy with or without prior lymph node debulking or upfront chemotherapy followed by radiotherapy and hyperthermia (triple therapy) for locally advanced cervical cancer (LACC) to identify a potential role for triple therapy. Methods: Women with histologically proven LACC and with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2 and IIA2 to IVA were included. Cox regression analyses were used for calculating hazard ratios and to adjust for confounding variables. A multivariable logistic regression analysis was used to examine the influence of covariates on toxicity. Results: A total of 370 patients were included of whom 58% (n = 213) received chemoradiotherapy (CRT), 18% (n = 66) received node-debulking followed by chemoradiotherapy (LND-CRT) and 25% (n = 91) received triple therapy (TT). Five-year OS was comparable between the three treatment groups, with 53% (95% confidence interval 46–59%) in the CRT group, 45% (33–56%) in the LND-CRT group and 53% (40–64%) in the TT group (p = 0.472). In the adjusted analysis, 5-year OS and DFS were comparable between the three treatment groups. No chemotherapy-related differences in toxicity were observed. Conclusion: This study suggests that the toxicity and survival of TT is similar to CRT or LND-CRT.

Impact of different sequential triple oral combination therapies based selexipag on outcomes in pulmonary arterial hypertension.

While the GRIPHON study and others have confirmed the efficacy and safety of selexipag with single, dual, and initial triple combination therapy for patients with pulmonary arterial hypertension (PAH), multicenters studies concerning diverse triple oral combination therapies based on selexipag are limited. This study was conducted to evaluate the effects of various sequential triple oral combination therapies on PAH outcomes. A retrospective study was carried out involving 192 patients from 10 centers, who were receiving sequential triple oral combination therapy consisting of an endothelin receptor antagonist (ERA), a phosphodiesterase 5 inhibitor (PDE5i)/riociguat and selexipag. Clinical parameters, event-free survival, and all-cause survival were assessed and analyzed at baseline and posttreatment. Among the 192 patients, 37 were treated with ERA + riociguat + selexipag, and 155 patients received ERA + PDE5i + selexipag. Both sequential triple oral combination therapies improved the World Health Organization functional class and raised the count of low-risk parameters. As a result of the larger patients' population in the ERA + PDE5i + selexipag group, these individuals exhibited significant increases in 6-minutewalking distance(6MWD), pulmonary arterial systolic pressure,pulmonary arterial pressure, right ventricle, andeccentricity index, and significant decreases in N-terminal probrain natriuretic peptide after 6 months of treatment. Nevertheless, both sequential triple oral combination therapy groups demonstrated similar shifts in these clinical parameters between baseline and 6 months. Baseline 6MWD and mean pulmonary arterial pressure were independent predictors of survival in patients undergoing ERA + PDE5i + selexipag therapy. Importantly, no significant differences were found in 6-month event-free survival and all-cause survival between two groups. Different oral sequential triple combination therapies based on selexipag could comparably improve outcomes in patients with PAH.

Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis.

Hepatic arterial infusion chemotherapy (HAIC) has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma (uHCC). HAIC-based treatment showed great potential for treating uHCC. However, large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking. To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors, programmed cell death of protein 1 (PD-1) and its ligand (PD-L1) blockers (triple therapy) under real-world conditions. Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis. Study-level pooled analyses of hazard ratios (HRs) and odds ratios (ORs) were performed. This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades (AIPB) at Sun Yat-sen University Cancer Center from January 2018 to April 2023. Propensity score matching (PSM) was performed to balance the bias between the groups. The Kaplan-Meier method and cox regression were used to analyse the survival data, and the log-rank test was used to compare the suvival time between the groups. A total of 13 randomized controlled trials were included. HAIC alone and in combination with sorafenib were found to be effective treatments (P values for ORs: HAIC, 0.95; for HRs: HAIC + sorafenib, 0.04). After PSM, 176 HCC patients were included in the analysis. The triple therapy group (n = 88) had a longer median overall survival than the AIPB group (n = 88) (31.6 months vs 14.6 months, P < 0.001) and a greater incidence of adverse events (94.3% vs 75.4%, P < 0.001). This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC. Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.

Combination of radiotherapy and Anlotinib enhances benefit from immunotherapy to liver metastasis and abscopal tumor from lung cancer

Many studies have shown that liver metastasis can weaken the efficacy of immunotherapy. Immunotherapy combined with radiotherapy or anti-angiogenic therapy has been proven to have synergistic anti-tumor effects. So we devote to explore whether the combination of the three therapies can exert effective anti-tumor effects on liver metastasis. The clinical information of 118 patients with liver metastasis were collected to compare the intrahepatic progression-free survival between immunotherapy and immunotherapy combined with other treatments. We used Lewis lung cancer (LLC) cell to establish a mouse liver metastasis tumor model and record tumor burden and survival. Tumor-infiltrating immune cells detected by flow cytometry. RNA sequencing was performed and the proportion of immune cells were analyzed by TIMER2.0 database. Compared with immunotherapy group, the combination therapy group showed a trend for longer median intrahepatic progression-free survival. Radiotherapy combined with PD-1 inhibitor and Anlotinib can inhibit liver metastasis and subcutaneous tumor growth and prolong the survival compared with other groups in vivo. Compared with the anti-PD-1 treatment group, triple therapy can increase CD4+T, CD8+T, and IFN-γ+CD8+T cells and decrease infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) in tumors. PPAR signaling pathway were significantly activated and CD8+T and dendritic cells (DC) were increased in the triple therapy group compared to the PD-1 inhibitor combined with Anlotinib group. Radiotherapy combined with PD-1 inhibitor and Anlotinib can effectively exert anti-tumor efficacy and reshape the tumor immune microenvironment by increasing the infiltration of anti-tumor immune cells and reducing the infiltration of immunosuppressive immune cells.

Bailout inclisiran-based triple lipid-lowering therapy reduces plaque lipid content in stable coronary artery disease patients

Abstract Background Low-density lipoprotein cholesterol (LDL-C) has a causal role in atherosclerotic cardiovascular disease. Genetic studies and variability in individual response to lipid-lowering therapies suggest combining hypolipidaemic medications with different mechanisms of action. Purpose The aim of this study was to evaluate the effect of triple inclisiran-based hypolipidaemic therapy in patients not reaching LDL-C target on maximum statin/ezetimibe treatment. Methods This prospective study enrolled 37 stable coronary artery disease patients admitted for elective percutaneous coronary intervention after 4-6 weeks on maximum tolerated statin and/or ezetimibe therapy during run-in period. Afterwards, patients with LDL-C level &amp;gt;1.8 mmol/l at the time of inclusion were assigned to receive add-on inclisiran (triple therapy group). In all participants near-infrared spectroscopy (NIRS) was performed at baseline and after 15 months for atherosclerotic plaque evaluation in the segment of interest, defined as 20-50% lesion in the proximal or middle third of a coronary artery. Statistical analysis was carried out with SPSS Statistics software. Results Average LDL-C level among screened patients was 2.81 (±1.17) mmol/l. In 19 patients LDL-C level remained &amp;gt;1.8 mmol/l on maximally tolerated statin and/or ezetimibe treatment, and after 15 months of triple therapy mean LDL-C reached 1.81 (±1.02) mmol/l with a significant LDL-C percentage change of 35.59% (95%CI -47.31 to -9.18, P=0.006) in this group. 17 patients continued statin/ezetimibe as mono or dual treatment and at 15-month follow-up mean LDL-C level comprised 1.67 (±0.61) mmol/l among these participants. According to NIRS data, maximum lipid-core burden index within 4 mm (maxLCBI4 mm) was significantly reduced by 28.85 (95%CI -189.39 to 17.64, P=0.041) in triple therapy group and by 114.72 in mono or dual therapy group (-194.76 to 23.01, P=0.004), with no statistically significant difference established between both groups (P=0.494). Conclusions Triple therapy demonstrated significant atherosclerotic plaque lipid content reduction along with LDL-C level lowering in patients with insufficient effectiveness of statin/ezetimibe treatment.

Abstract 13589: Prophylactic Anticoagulation to Prevent Left Ventricular Thrombus Following Myocardial Infarction: A Systematic Review and Meta-Analysis

Introduction: Left ventricular thrombus (LVT) complicates an estimated 12% of anterior STEMI. The current standard of care for STEMI patients includes primary PCI and dual antiplatelet therapy (DAPT). Guidelines from the American Heart Association recommend consideration of prophylactic anticoagulation to prevent LVT in select high-risk patients following STEMI. These guidelines have a low certainty of evidence (level C), with most studies published prior to the current era of primary PCI and DAPT. Therefore, an updated review is needed in this area. Methods: Electronic databases, including EMBASE, MEDLINE and CENTRAL were systematically searched from January 2012 to June 2022. We included primary studies that used PCI as the lone revascularization strategy for STEMI. Studies were included if they compared the incidence of LVT in patients receiving prophylactic anticoagulation and DAPT with those receiving DAPT alone. Results: 7,378 studies were screened, with 4 studies eventually included in this review. One study was a randomized control trial and three were retrospective cohort studies. Pooled analysis using a fixed-effects model showed LVT was significantly less common in the triple therapy (TT) group compared to the DAPT group (OR = 0.38; 95% CI = 0.17-0.86; p = 0.02). However, using a random-effects model, there was no significant difference in LVT between the TT and DAPT group (OR = 0.42; 95% CI = 0.04-4.67; p = 0.33). Conclusions: Based on the current state of knowledge, there is no compelling evidence to either support or oppose prophylactic anticoagulation in STEMI. An appropriately powered clinical trial is warranted due to the need for more robust data in this area.

A retrospective study of people with familial hypercholesterolaemia in a Belgian lipid clinic

Background Familial hypercholesterolaemia (FH) is a genetic disease characterised by hypercholesterolaemia and premature cardiovascular events. Early diagnosis and treatment can reduce the cardiovascular burden. We describe the characteristics of patients with heterozygous FH followed in a tertiary hospital in Belgium. Methods We retrospectively studied a population of 321 patients with definite heterozygous FH who visited the UZ Leuven lipid clinic at least once between 1 January 2016 and 31 December 2020. Data are represented as mean ± SD. Results The age at time of diagnosis of FH was 39 ± 18 years. Patients with atherosclerotic disease (secondary prevention) were older (p < .001), more often male (p < .001), had a higher body mass index (p < .001), prevalence of (pre)diabetes (p < .001) and hypertension (p < .001) and had lower levels of low-density lipoprotein-cholesterol (LDL-C) (p < .001) than individuals without atherosclerotic disease (primary prevention). The average LDL-C in both primary (109 ± 53 mg/dL) and secondary (81 ± 63 mg/dL) prevention did not meet the targets of LDL-C as proposed by the 2019 ESC/EAS guidelines for the management of dyslipidaemias. However, LDL-C levels in the subgroup of patients treated with PCSK9 inhibition therapy, and especially in the triple therapy group (combination of statin, ezetimibe and PCSK9 inhibitor), were markedly lower (p < .001). Conclusions In this Belgian population, people with heterozygous FH remain undertreated. Reaching treatment targets in FH seems possible, although this requires combination treatment (with PCSK9-targeted therapy) in most patients. Earlier diagnosis of FH, more extensive lipid-lowering treatment and reimbursement options and a more holistic approach are needed to lower LDL-C and cardiovascular risk in patients with FH.

Treatment of Helicobacter pylori infection 14-day concomitant quadruple therapy versus triple therapy: A parallel double-blind randomized controlled trial.

Successful Helicobacter pylori (Hp) eradication with the traditional 7-day course of proton pump inhibitor triple therapy is declining. Prolonging therapy to 14 days is associated with better eradication rates. Most learned societies recommend concomitant quadruple therapy (QC) as a first-line alternative therapy for this bacterial infection. The aim of this study is to compare the efficacy and safety of triple therapy (TT) and QC for the eradication of Hp infection. A parallel double-blind randomized controlled trial was conducted. The diagnosis of Hp infection was made by pathological examination of gastric biopsies. Patients were randomly assigned to two treatment groups: either QC (esomeprazole 80 mg, amoxicillin 2000 mg, clarithromycin 1000 mg, and metronidazole 1000 mg daily) or triple therapy (esomeprazole 80 mg, amoxicillin 2000 mg, and clarithromycin 1000 mg daily in divided doses) for 14 days. The efficacy of the treatment is defined by Hp eradication attested by a negative breath test performed 6 weeks after the completion of treatment. Treatment outcomes were compared using the chi-square test, while binary logistic regression identified predictors of treatment failure. Ninety-two patients were included. Forty-two patients belonged to the QC group and 50 to the TT group. No significant difference was noted between the two groups concerning the rate of Hp eradication either by intention to treat (81% vs. 72% respectively, p = 0.31) or per protocol (81.6% vs. 76.1% respectively, p = 0.54). Likewise, there was no difference between the two groups in terms of tolerance to treatment (59.5% for QC vs. 58% for TT, p = 0.88). No factor has been associated with treatment failure. There was no significant difference in the rate of HP eradication between the QC and the 14-day triple therapy. Neither regimen should be used topically because of their low eradication rates.