Single Therapy Research Articles

Effect of Bacillus clausii in attenuating symptoms of DSS‐induced ulcerative colitis by modulating NFkB pathway and oxidative stress in mice

AbstractUlcerative colitis (UC) is a condition characterized by inflammation and ulcer formation in the colon and rectum due to genetic and environmental factors. It is a common condition, with a global prevalence rate exceeding 0.3%. Current treatments have limited efficacy and can cause unwanted side effects, leading to a high recurrence rate and reduced quality of life for patients. This study suggests that Bacillus clausii has a beneficial role in reducing intestinal inflammation and relieving colitis symptoms in mice. The study aimed to examine B. clausii's potential to reduce the progression and pathogenesis of dextran sulphate sodium (DSS)–induced UC. Bacillus clausii was administered to mice as a pre‐treatment, post‐treatment and adjunct treatment with sulfasalazine for 14 days. The study found that B. clausii effectively reduced the severity of colitis in mice when used preventatively. Administering B. clausii after the onset of colitis also effectively alleviated symptoms. Combining B. clausii with standard sulfasalazine as adjunct therapy was more effective in reducing intestinal inflammation than using a single therapy alone. B. clausii has shown the potential to prevent colon damage and decrease the likelihood and severity of the disease. Immunohistochemistry results revealed a decrease in the expression of pro‐inflammatory cytokines such as IL‐1β, TNF‐α and NFkB in colon tissue. Additionally, mice that received B. clausii showed a significant increase in anti‐oxidant levels and improved haematological markers. In conclusion, it must be emphasized that B. clausii possesses the potential to alleviate the symptoms of UC.

Engineering Strain-Defects to Enhance Enzymatic Therapy and Induce Ferroptosis.

The effect of mimetic enzyme catalysis is often limited by insufficient activity and a single therapy is not sufficient to meet the application requirements. In this study, a multifunctional nanozyme, MMSR-pS-PEG, is designed and fabricated by modifying poly (ethylene glycol) grafted phosphorylated serine (pS-PEG) on mesoporous hollow MnMoOx spheres, followed by loading sorafenib (SRF) into the pores. Strain engineering-induced oxygen defects endow the nanozyme with enhanced dual-enzymatic activity to mimic catalase and oxidase-like activities, which catalyze the conversion of endogenous H2O2 into oxygen and subsequently into superoxide ions in the acidic tumor microenvironment. Moreover, as an n-type semiconductor, MnMoOx generates reactive oxygen species by separating electrons and holes upon ultrasonic irradiation and simultaneously deplete glutathione by holes, thereby further augmenting its catalytic effect. As a ferroptosis inducer, SRF restrains the system xc - and indirectly inhibits glutathione synthesis, synergistically interacting with the nanozyme to stimulate ferroptosis by promoting lipid peroxidation and accumulation and the downregulation of glutathione peroxidase 4. These results provide valuable insights into the design of enzymatic therapy with high performance and highlight a promising approach for the synergism of ferroptosis and enzymatic tumor therapy.

Targeting RAF1 gene fusions with MEK inhibition in metastatic melanoma

Abstract The biological and clinical relevance of gene fusions in melanoma is unknown. Reports and preclinical data have suggested that tumor cells with specific rearrangements such as RAF1 gene fusions could be therapeutically targeted. To investigate the relevance of targeted therapy in patients with melanoma harboring RAF1 gene fusions, we reviewed records of 1268 melanoma patients with targeted sequencing data at the Dana-Farber Cancer Institute. We identified 9 cases and report here on their clinicopathologic characteristics. We describe the favorable outcome of 2 patients who received MEK inhibitor therapy, including 1 patient with a durable response. We coalesced our data with published reports of patients with RAF1 gene fusions who were treated with targeted therapy. We find that single-agent MEK inhibition has anti-tumor activity in melanoma patients harboring an RAF1 gene fusion, and we propose that patients with RAF1 gene fusions should be considered for single-agent MEK inhibitor therapy.

Innovative Glucagon-Based Therapies for Obesity

Abstract Obesity poses a significant global health challenge, with an alarming rise in prevalence rates. Traditional interventions, including lifestyle modifications, often fall short of achieving sustainable weight loss, ultimately leading to surgical interventions, which carry a significant burden and side effects. This necessitates the exploration of effective and relatively tolerable pharmacological alternatives. Among emerging therapeutic avenues, glucagon-based treatments have garnered attention for their potential to modulate metabolic pathways and regulate appetite. This paper discusses current research on the physiological mechanisms underlying obesity and the role of glucagon in energy homeostasis. Glucagon, traditionally recognized for its glycemic control functions, has emerged as a promising target for obesity management due to its multifaceted effects on metabolism, appetite regulation, and energy expenditure. This review focuses on the pharmacological landscape, encompassing single and dual agonist therapies targeting glucagon receptors (GcgRs), glucagon-like peptide-1 receptors (GLP-1Rs), glucose-dependent insulinotropic polypeptide receptors (GIPRs), amylin, triiodothyronine, fibroblast growth factor 21 (FGF21), and peptide tyrosine tyrosine. Moreover, novel triple-agonist therapies that simultaneously target GLP-1R, GIPR, and GcgR show promise in augmenting further metabolic benefits. This review paper tries to summarize key findings from preclinical and clinical studies, elucidating the mechanisms of action, safety profiles, and therapeutic potential of glucagon-based therapies in combating obesity and its comorbidities. Additionally, it explores ongoing research endeavors, including phase III trials, aimed at further validating the efficacy and safety of these innovative treatment modalities.

Relative Benefit of Dual Versus Single Antiplatelet Therapy Among Patients With Atrial Fibrillation on Oral Anticoagulation According to Time After ACS and PCI: Insights From the AUGUSTUS Trial.

In the AUGUSTUS trial (An Open-Label, 2 x 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs Vitamin K Antagonist and Aspirin vs Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention), the combination of dual antiplatelet therapy plus oral anticoagulation increased the risk of bleeding without reducing ischemic events compared with a P2Y12 inhibitor plus oral anticoagulation among patients with atrial fibrillation and acute coronary syndrome or elective percutaneous coronary intervention. However, AUGUSTUS enrolled patients up to 14 days after acute coronary syndrome or percutaneous coronary intervention, and there may be a benefit to dual antiplatelet therapy plus oral anticoagulation early after an ischemic event. In this secondary analysis of AUGUSTUS, we divided patients into groups based on whether they were enrolled <6 days (early) or ≥6 days (later) after their index acute coronary syndrome or percutaneous coronary intervention, and tested the interaction between time from the index event to enrollment and randomized treatment (apixaban versus vitamin K antagonist and aspirin versus placebo) on 30-day and 6-month clinical outcomes using Cox proportional hazards models. Among 4605 patients enrolled in AUGUSTUS with data available on time from the index event to enrollment, the median time from the index event to enrollment was 6 (range, 0-14) days. There were no significant interactions between time from the index event and aspirin versus placebo on clinical outcomes at 30 days or 6 months, though patients with time from the index event <6 days had a nominally significant reduction in death or ischemic events at 30 days with aspirin (hazard ratio, 0.55 [95% CI, 0.30-0.99]), whereas patients with time from the index event ≥6 days did not (hazard ratio, 0.88 [95% CI, 0.54-1.43]; interaction P=0.23). There were no significant interactions between time from the index event and apixaban versus vitamin K antagonist on clinical outcomes. Among patients with atrial fibrillation with acute coronary syndrome or undergoing percutaneous coronary intervention, there was no difference in the relative benefit of apixaban versus vitamin K antagonist or aspirin versus placebo when patients were enrolled early versus later after their index event. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.

Imaging treatment efficacy of repeated photodynamic therapy in glioblastoma using chemical exchange transfer saturation MRI.

To observe the tumor responses during photodynamic therapy in a murine glioblastoma model using chemical exchange saturation transfer (CEST) MRI and to compare the treatment effectiveness between single photodynamic therapy (sPDT) and repeated PDT (rePDT). After tumor cell implantation in NSG mouse brain(n = 27), mice were subjected to four PDT sessions (rePDT), sPDT after the administration of 5-aminolevulinic acid 6 h before each session, and a non-PDT session (control). A 630-nm LED light was used to effectuate PDT. After 24 h for each PDT session, T2-weighted and CEST MRI were performed over 7 days. We observed that rePDT resulted in a continuous suppression of tumors according to T2-weighted images; thus, the tumor volume was the smallest among three groups on Day 7. Both CEST contrasts at 3.5 ppm (amide proton transfer, APT) and 3.5 ppm (relayed nuclear Overhauser enhancement, rNOE) in the rePDT group were significantly lower (p < 0.05) than those in the control group starting from Day 5, which corresponds to lower protein and cellularity in tumors in the rePDT group, respectively. CEST contrast decreased by 17.9% at 3.5 ppm and 11.3% at 3.5 ppm for rePDT group. This was validated by histology, where we observed moderatecorrelations between APTwith cell proliferation (R = 0.730, p < 0.01) and cell apoptosis (R = 0.715, p < 0.05) and moderate correlation between rNOE with cellularity (R = 0.796, p < 0.01). rePDT has a better effect in tumor growth suppression when compared with sPDT, and CEST could be a robust and noninvasive mean to assess the molecular changes related to treatment efficacy.

A Qualitative Service Evaluation of the Introduction of Single Session Therapy for Families in a Child and Adolescent Mental Health Service in England, United Kingdom.

This service evaluation details the process of introducing Single Session Therapy (SST) with families to a Child and Adolescent Mental Health Service in the United Kingdom. SST is a model of short-term psychotherapy intervention which can be applied to family contexts to provide timely mental health support. This service evaluation had two objectives: (1) Review the existing evidence base and literature for SST. (2) Evaluate the implementation of a new SST treatment pathway in CAMHS, including patient experiences and satisfaction with the service. SQUIRE Guidelines are used to report on this new knowledge of healthcare. This evaluation used qualitative methods to evaluate the impact of the new service. The team also used existing frameworks within the Trust, namely discharge data, which is collected routinely as part of service evaluation. This evaluation suggests positive support for this model, and that many families appreciate and value the opportunity to build on strengths and work toward their goals as families. This project outcome appears to support some of Talmon's (1990) findings that the most commonly attended number of sessions is one, and that of those who attended only one session, many perceived the session as useful. Waiting times for our service are extremely long. The pace and structure around goals and solutions could feel both galvanising, as some reported, but others felt it was an insufficient response to the severity of their difficulties. More high-quality research is needed before judgments can be made around the cost-effectiveness or efficacy of SST over existing approaches in the United Kingdom. While implementing SST should not be used to justify reduction in existing interventions, it offers a positive additional service for young people experiencing mental health difficulties and their families.

Liposomes and Their Therapeutic Applications in Enhancing Psoriasis and Breast Cancer Treatments

Psoriasis and breast cancer are two examples of diseases where associated inflammatory pathways within the body’s immune system are implicated. Psoriasis is a complex, chronic and incurable inflammatory skin disorder that is primarily recognized by thick, scaly plaques on the skin. The most noticeable pathophysiological effect of psoriasis is the abnormal proliferation of keratinocytes. Breast cancer is currently the most diagnosed cancer and the leading cause of cancer-related death among women globally. While treatments targeting the primary tumor have significantly improved, preventing metastasis with systemic treatments is less effective. Nanocarriers such as liposomes and lipid nanoparticles have emerged as promising drug delivery systems for drug targeting and specificity. Advances in technologies and drug combinations have emerged to develop more efficient lipid nanocarriers to include more than one drug in combinational therapy to enhance treatment outcomes and/or relief symptoms for better patients’ quality of life. Although there are FDA-approved liposomes with anti-cancer drugs for breast cancer, there are still unmet clinical needs to reduce the side effects associated with those nanomedicines. Hence, combinational nano-therapy may eliminate some of the issues and challenges. Furthermore, there are no nanomedicines yet clinically available for psoriasis. Hence, this review will focus on liposomes encapsulated single and/or combinational therapy to augment treatment outcomes with an emphasis on the effectiveness of combinational therapy within liposomal-based nanoparticulate drug delivery systems to tackle psoriasis and breast cancer. This review will also include an overview of both diseases, challenges in delivering drug therapy and the roles of nanomedicines as well as psoriasis and breast cancer models used for testing therapeutic interventions to pave the way for effective in vivo testing prior to the clinical trials.

X-ray-triggered fenton-like nanocomposites for passive-activation and non-spontaneous chemodynamic therapy

Currently, many studies focused on the TME-regulating strategies to address the unsatisfactory therapeutic effect of single chemodynamic therapy (CDT). However, most of TME-regulating strategies were nonspecific, the CDT agents with spontaneous CDT activity would result in augmented killing effect not only in tumor but also in normal tissues. Furthermore, CDT efficiency was subject to attenuation due to the gradually exhausted active sites in CDT agents. Herein, the passive-activation and non-spontaneous CDT strategy was proposed by constructing a completely X-ray-triggered CDT agent (F-SCNPs) to target the therapeutic dilemma between the augmented CDT efficacy and high tumor specificity. In this study, the designed F-SCNPs can launch Fe2+ sites generation to initiate CDT activity only when they were exposed to X-ray, which were totally different from the traditional CDT agents including other stimuli-responsive CDT agents that always spontaneously exert CDT activity no matter they had accepted the stimuli or not. The X-ray-activated feature of F-SCNPs endowed their tumor specificity with less affect by nonspecific TME-regulating strategies. Meanwhile, X-ray can promote the Fe2+/Fe3+ cycling of F-SCNPs to enhance the •OH yield. This X-ray-mediated nanosystem with remarkable synergistic therapy of CDT and radiotherapy provided a promising avenue for high-efficiency and precise cancer treatments.

Epilepsy in Loeys-Dietz Syndrome: The Rare Concurrence of a Connective Tissue and Neuronal Migration Disorder

We present a 7-year-old girl who presented to our emergency department in active status epilepticus. Seizures responded to standard antiepileptic medications; however, baseline work-up for seizure etiology remained unremarkable. Her new-onset seizures were further investigated via EEG and MRI brain, which revealed focal epileptiform discharges and periventricular nodular heterotopia, respectively. Concurrently, the clinical evaluation revealed extensive marfanoid features, and a personal history of eczema and asthma. Her family history was pertinent for aortic valve disease, asthma, and tall stature. Given the peculiar skeletal features, allergic propensities and coexistent weighty family history, a molecular genetic panel analysis for Marfan Syndrome and Loeys-Dietz Syndrome (LDS) were sought. Genetic testing revealed an underlying heterozygous variant in the TGFBR-1 gene; thereby confirming the presence of LDS. The child had responded well to single antiepileptic agent therapy and was discharged in good condition with regular outpatient cardiac and neurology follow-up. This is a unique case reported of a child with genetically diagnosed LDS concurring with an underlying neuronal migration disorder, manifesting in an acute, severe, and lifethreatening fashion.

Cyclosporin for the treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN): a systematic review of observational studies and clinical trials focusing on single therapy, combination therapy, and comparative assessments.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, severe, and potentially life-threatening skin and mucous membrane disorders. They are characterized by widespread skin and mucosal detachment and necrosis, and are classified based on the percentage of total body surface area (TBSA) affected. Given the severe and often life-threatening nature of these conditions, the identification and implementation of effective treatments is crucial. Notably, cyclosporin has demonstrated efficacy in managing these challenging conditions. A systematic search was carried out through the PubMed, Scopus, Embase, Web of Science, and Cochrane Library databases until May 2024. Additionally, a manual search was conducted through the reference lists of the included studies to minimize the risk of missing reports. Overall, 17 studies involving 4761 patients were included in our analysis. The majority of the included studies suggested favorable outcomes for the use of cyclosporin in SJS/TEN patients. The use of cyclosporin was associated with improved survival rates, early arrest of disease progression, faster re-epithelialization, reduced length of hospital stays, and lower rates of multi-organ failure. However, a few studies did not find a survival advantage with cyclosporin and even reported an increased risk of mortality, as well as an increased TBSA detachment and risk of infection. Most studies indicate positive outcomes with cyclosporin treatment in SJS/TEN patients. This is likely due to cyclosporin's immunomodulatory properties, which may help attenuate the severe inflammatory response associated with these conditions.

Association between preprocedural thromboembolic or bleeding events under oral anticoagulation therapy and mid-term outcomes after percutaneous left atrial appendage closure

Abstract Background Currently, no consensus has been established on the most effective antithrombotic therapy to prevent thromboembolic and bleeding events in patients undergoing percutaneous left atrial appendage closure (LAAC). Methods We retrospectively investigated the incidence of device-related thrombosis (DRT), thromboembolic events, and bleeding events in patients who underwent LAAC from September 2019 to October 2022. After categorizing patients into groups based on preprocedural thromboembolic or bleeding events under oral anticoagulation (OAC) therapy, we compared the incidence of DRT and prognosis according to the postprocedural antithrombotic therapy. Results In patients who received the conventional antithrombotic therapy (OAC with and without single antiplatelet therapy for 45 days after LAAC and dual-antiplatelet therapy from 45 days to 6 months followed by single antiplatelet therapy), preprocedural thromboembolic events despite OAC were independently associated with DRT or postprocedural thromboembolic events at the 3-year follow-up (hazard ratio [HR] 4.55; 95% confidence interval [CI] 1.32–15.6; P = 0.016), whereas preprocedural bleeding events were independently associated with postprocedural bleeding events (HR 8.01, 95% CI 1.45–58.3; P = 0.036). Continuation of OAC for 12 months among patients who developed preprocedural thromboembolic events during OAC significantly decreased the incidence of DRT or postoperative thromboembolic events (P = 0.002) with no increase in the bleeding events (P = 0.522). Conclusions Preprocedural thromboembolic and bleeding events can predict adverse events after LAAC with conventional antiplatelet-based antithrombotic therapy. Patients who develop thromboembolic events under continuous OAC may benefit from continuous OAC for 1 year after LAAC.

The safety of standardized management of suspected cardiovascular immune-related events in patients treated by immunecheckpoints inhibitors

Abstract Background Immune checkpoint inhibitors (ICIs) treatment carries a risk of immune-related adverse events (irAEs), including cardiovascular (CV) events. Current guidelines recommend troponin testing to detect early CV irAEs, especially myocarditis, prompting hospital admission. However, high volumes might hinder hospital admission for all suspected CV irAEs patients. Purpose To assess the safety of standardized management in outpatients with suspected irAEs. Methods A prospective single-center cohort study was conducted, including all adults referred to our unit for suspected CV irAEs. Patients exhibiting CV symptoms, receiving double ICIs, or showing ECG changes were referred to cardiology or intensive care based on severity. Patients with no CV symptoms or ECG changes, on single ICI therapy, and no other immune disorder were assessed in a day stay within 8 working days. Patients underwent serial serum testing, ECG, transthoracic echocardiogram, and cardiac magnetic resonance imaging (cMRI) and were assessed by a multidisciplinary team (MDT) including cardiology and internal medicine specialists. Coronary artery imaging and endomyocardial biopsy were performed when deemed necessary (Figure 1). The primary endpoint was CV mortality at 30 days after referral. Secondary endpoints included identifying factors associated with the diagnosis of CV irAEs at referral. Events were adjudicated by a panel of experts (FC, MM, SH) who reviewed the MDT's weekly meeting conclusions. Results 175 patients were enrolled from March 2022 to October 2023; 40 (22.89%) were male, median age 61 (IQR 48.0-72.0) years. 146 (83.4%) were seen in the outpatient clinic. No CV deaths occurred within the initial 30 days. 95 patients (54.1%) had CV irAEs at referral, including 72 (41.1%) with myocarditis; 10 (5.7%) with acute coronary syndromes; 9 (5.1%) with pericarditis; 7 (4.0%) with heart failure; 4 (2.3%) with high-degree conduction or ventricular arrhythmias; and 1 (0.6%) with Tako-Tsubo. 8 (4.6%) had a combination of CV irAEs. The majority of patients admitted to the hospital had CV irAEs (24, 82.7%). On multivariable regression analysis(Figure 2), CV or muscle symptoms(OR 2.677 [CI 1.207-5.937], p=0.015), prior CV disease history(OR 3.668 [CI 1.486-9.057], p=0.0048), and abnormal ECG (OR 2.855 [CI 1.074-7.589], p=0.035) remained associated with CV irAEs at referral. Including global longitudinal strain (GLS) in the model, we identified prior CV disease history. (OR 7.011 [CI 2.217-22.167], p=0.0009) and GLS &amp;lt;16% (OR 2.774 [CI 1.07-7.17], p=0.035) as significant. Conclusions We demonstrate the safety of a standardized outpatient management approach for most patients referred for suspected CV irAEs, mainly triggered by asymptomatic elevation of troponin. No patient experienced CV death at 30 days. When suspecting a CV irAEs, CV or muscle symptoms, previous history of CV disease, and abnormal ECG should prompt speedy assessment given the higher likelihood of CV irAEsFigure 1

Clinical characteristics and predictors of adverse cardiovascular events from the australia-new zealand spontaneous coronary artery dissection (ANZ-SCAD) registry

Abstract Background Spontaneous coronary artery dissection (SCAD) is an increasingly recognised cause of acute coronary syndrome (ACS), predominantly affecting women. Our understanding of SCAD remains incomplete with limited prospective data on determinants of major adverse cardiovascular events (MACE). Purpose We aimed to describe the clinical characteristics of patients with SCAD from a large, multicentre SCAD registry. We aimed to identify the predictors of MACE (defined as the composite of all-cause death, non-fatal myocardial infarction, stroke, heart failure, and revascularisation). Methods Observational, multi-centre prospective and retrospective cohort study recruiting patients with SCAD from 23 hospitals in Australia and New Zealand. Patients aged=&amp;gt;18 years with SCAD and an ACS were eligible for inclusion. Prospectively recruited patients gave their informed consent with a waiver of consent for retrospectively recruited patients. All invasive coronary angiography imaging was adjudicated by an independent core laboratory to confirm the diagnosis of SCAD. Cox proportional hazard analysis was used to evaluate the association between MACE and SCAD recurrence with predefined clinical variables. Results From a total 487 patients recruited, 423 (132 prospective and 291 retrospective) patients with SCAD confirmed on core laboratory review were included for analysis. Mean age was 52.4±10.7 years, 89.7% were female and 73.1% were Caucasian. Percutaneous coronary intervention (PCI) was performed in 10.6% of patients. On discharge, 64% of conservatively managed patients were on dual antiplatelet therapy (DAPT). At 15 (interquartile range 5-36) months median follow-up, the accumulated MACE rate was 6.6%. On multivariate analysis, percutaneous coronary intervention (PCI) was associated with a higher risk of MACE [hazard ratio (HR) 3.50, 95% confidence interval (CI) 1.56-7.89, p=0.002], while discharge on at least one antiplatelet medication was associated with a lower risk of MACE (HR 0.13, 95% CI, 0.05-0.36, p&amp;lt;0.001). In patients managed conservatively (n=353), discharge on at least one antiplatelet medication (n=337) was associated with lower MACE (HR 0.27, 95% CI 0.1-0.73, p=0.01), with no difference between single and dual antiplatelet therapy (DAPT) (p=0.74). In patients managed conservatively and on DAPT (n=226), aspirin and clopidogrel was associated with a lower risk of MACE (HR 0.31, 95% CI 0.10-0.93, p=0.038) compared with DAPT consisting of aspirin and ticagrelor (HR 3.25, 95%CI 1.07-9.85 p=0.038) on multivariate analysis. Conclusion Patients with SCAD are at significant risk of MACE. In conservatively managed patients treated with DAPT, aspirin and clopidogrel was independently associated with a lower risk of MACE than aspirin and ticagrelor

One-year clinical outcome of aspirin-free prasugrel monotherapy following stent implantation in patients with chronic coronary syndrome: insight from ASET-JAPAN study

Abstract Background Single antiplatelet therapy with a potent P2Y12 inhibitor without aspirin after coronary stent implantation may provide an adequate balance between ischemic and bleeding risks in selected patients. The 3-month follow-up of the Acetyl-Salicylic Elimination Trial (ASET)-Japan pilot study demonstrated the feasibility and safety of Prasugrel monotherapy without aspirin after successful percutaneous coronary intervention (PCI) in selected patients with chronic coronary syndrome (CCS). Purpose The current study aimed to evaluate the 1-year clinical outcome in the ASET-Japan. Methods The ASET-Japan pilot study was designed to demonstrate the feasibility and safety of the approved dose of prasugrel monotherapy in Japan without aspirin after optimal PCI with a platinum-chromium everolimus-eluting stent in CCS population. After successful procedure, all patients were treated with a locally approved maintenance dose of 3.75 mg/day of Prasugrel monotherapy up to 3-month. After 3-month, the choice of antiplatelet therapy was left to the discretion of the investigators. Patients were followed up to 1 year. The target lesion-related endpoint was a composite of cardiac death, spontaneous target-vessel myocardial infarction (MI) &amp;gt;48 h after the index PCI or clinical-driven target lesion revascularisation. Patient-Oriented Composite Endpoint (POCE) was defined as a composite of all cause mortality, any stroke, any MI and any revascularisation. Spontaneous MI was defined according to Forth universal definition. The event rate was estimated by the Kaplan-Meier method. The event was adjudicated by an independent clinical event committee. Results A total of 208 patients were enrolled in the study. The average anatomical SYNTAX score was 7.96 (±4.6). After procedure, prasugrel monotherapy was immediately initiated. After 3-month, Prasugrel monotherapy was continued in 88.6% up to 1-year. Aspirin monotherapy was prescribed to 10 patients (5.0%), while 6 patients (3.0%) were on DAPT at 1-year. All-cause mortality rate was 1.49%, with no occurrence of cardiovascular death. Revascularisation occurred in 4.0% (n=8) with no occurrence of TLR, while one patient (0.5%) underwent a clinical driven target vessel revascularisation. In summary, 7 out of 8 revascularisations were non-target vessel revascularisation (6 clinically-driven non-TVR). Spontaneous non TV-MI occured in 0.5% (n=1) of patients. There was no definite/probable stent thrombosis up to 1 year. The target lesion related endpoint rate at 1-year was 0%, whereas 1-year POCE rate was 7.0% (n=14). Conclusion Discontinuation of Aspirin and Prasugrel monotherapy at a low maintenance dose of 3.75 mg/day following an angiographically successful stent deployment was feasible and safe in selected patients with CCS and low SYNTAX score. This safety profile is confirmed at 1 year while the investigators, in their large majority and at their own discretion, had maintained the prasugrel treatment.

Lipoprotein (a) and lipidemic parameters in PCSK-9 inhibitor patients. Experience from a specialized centre in Greece

Abstract Background Previous studies have reported an association between Proprotein Convertase Subtilsin-kexin type 9 (PCSK-9) inhibition and levels of lipoprotein a [Lp (a)], having a possible effect on the cardiovascular benefit achieved by their use. The purpose of this study was to investigate the effect of PCSK-9 inhibitor use in Lp (a) and other lipidemic parameter levels in the population of a specialized Lipids Clinic during a follow up period of 24 months. Methods We enrolled 143 (80 males, mean age 60 years old) patients who were on PSCK-9 inhibitor treatment from the outpatient lipid clinic of our hospital. Information were obtained regarding the presence of coronary artery disease (CAD) and CAD risk factors. CAD was present in 72 patients (63%), Familial Hypercholesterolaemia (FH) in 97 patients (85%) and 20 (18%) patients suffered from statin intolerance. Patients were on triple lipid lowering therapy (statin plus ezetimibe plus PCSK-9 inhibitors) except for those with statin intolerance who were either on dual therapy (ezetimibe plus PCSK-9 inhibitors, N=8) or single PCSK-9 inhibitors therapy (N=10). Lp (a) levels and lipid parameters such as Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Triglycerides (TG) were measured at baseline, 3 months, 12 months and 24 months of treatment. Additionally, patients were categorized according to baseline Lp (a) levels in two groups, Group 1 (&amp;lt;70mg/dl) (N=62), Group 2 (≥70 mg/dl) (N=26). A comparison of the response in lipid parameters between these two groups was performed. Results Mean value for Lp (a) in the whole population was 54mg/dl, 48mg/dl, 44mg/dl, and 45mg/dl at baseline, 3, 12 and 24 months, respectively. T test analysis revealed a significant reduction in Lp (a) levels after 12 months (P&amp;lt;0.05) There was also a significant reduction in LDL levels at all time points (165mg/dl to 78mg/dl, 85mg/dl, 78mg/dl respectively, P&amp;lt;0.05), a reduction in triglyceride levels at 3 and 12 months (125mg/dl to 110mg/dl, 108mg/dl respectively, P&amp;lt;0.05) and an increase in HDL levels after 12 months (50mg/dl to 53mg/dl, P&amp;lt;0.05). Moreover, in Group 1, the response in LDL levels was higher after 12 months of treatment with PCSK-9 inhibitors (158mg/dl to 69mg/dl, P&amp;lt;0.05) compared to Group 2 (155mg/dl to 86mg/dl), indicating that high levels of Lp (a) seem to define the response to treatment. Colclusions Besides the detrimental effect in LDL levels, PCSK-9 inhibition has an impact on HDL and TG levels. Lp (a) was also reduced indicating an additional important effect of this inhibition. While higher levels of Lp (a) seem to correlate with poorer response to treatment, our findings enhance the already known importance of Lp (a) as a prognostic factor.

Clopidogrel versus aspirin monotherapy for secondary prevention after percutaneous coronary intervention - a nationwide population-based study

Abstract Background After percutaneous coronary intervention (PCI), patients are maintained on single antiplatelet therapy (SAPT) for secondary cardiovascular prevention after completing the guideline-recommended duration of DAPT for a period of time. We sought to compare the efficacy and safety of clopidogrel versus aspirin monotherapy for secondary prevention in patients who undergoing PCI in a population-based cohort study using the database from the National Health Insurance Service (NHIS) in Korea. Methods Of those who underwent PCI from 2009 to 2020, 133,343 patients were selected for analysis. (aspirin 65,802 patients, clopidogrel 67,653 patients). To balance between aspirin and clopidogrel users for the comparison of efficacy and safety, we applied the inverse probability of treatment weighting (IPTW) of propensity score method. The primary effectiveness outcome was major cardiovascular events (MACEs) as the composite of cardiovascular death, myocardial infarction (MI) or stroke. The primary safety outcome was any bleeding. We divided the short DAPT user (&amp;lt; 6 months of DAPT in patients with CCS or &amp;lt; 12 months of DAPT in patients with ACS) and long DAPT user (≥ 6 months of DAPT in patients with CCS or ≥ 12 months of DAPT in patients with ACS) by DAPT duration. Results After IPTW matching, overall the mean age of participants was 63.8±16.3 and the median SAPT duration was 3.3 (1.3 – 6.2). During period, the overall primary effectiveness outcome occurred in 4.1% in aspirin group and 2.8% in clopidogrel group (hazard ratio [HR], 0.684; 95% CI, 0.656 – 0.712; p-value &amp;lt;0.0001) (Figure 1-A). the overall primary safety outcome occurred in 2.4% in aspirin group and 2.1% in clopidogrel group (HR, 0.945; 95% CI, 0.899 – 0.994; p-value, 0.0287) (Figure 1-B). In short DAPT group, clopidogrel reduced the risk of MACE (HR, 0.761; 95% CI, 0.715 – 0.811; p-value, &amp;lt;0.0001) but did not reduce the risk of bleeding (HR, 0.973; 95% CI, 0.893 – 1.056; p-value, 0.5067) comaped with aspirin. However, in the long DAPT group, clopdiogrel reduced both MACE (HR, 0.633; 95% CI, 0.600 – 0.669; p-value &amp;lt;0.0001) and bleeding risk (HR, 0.931; 95% CI, 0.873 – 0.992; p-value, 0.028) compared with aspirin. (Figure 2) Conclusion Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after PCI reduced the risk of MACEs and bleeding. As shown in randomized controlled trials, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future clinical adverse events in real-world bid database.

Temporal trends in antithrombotic therapy following transcatheter aortic valve implantation in denmark

Abstract Background A number of randomized clinical trials have examined the use of antithrombotic therapy after transcatheter aortic valve implantation (TAVI), and guidelines have changed over time. Yet, data from clinical practise patterns are lacking and it is important to evaluate adherence to guideline recommendations over time. Purpose This study aims to evaluate the temporal use of antithrombotic therapy after TAVI in Denmark. Methods A nationwide Danish cohort of patients undergoing first-time TAVI from 2008 to 2017 were identified from Danish nationwide registries. Patients were categorized into four groups according to data on prescription filling of antithrombotic therapy within a three-months period post-TAVI: i) No antithrombotic therapy, ii) single antiplatelet therapy (SAPT), iii) dual antiplatelet therapy (DAPT), or iv) anticoagulant therapy. The use of antithrombotic therapy post-TAVI was examined for each year from 2008 to 2017. Results We identified 3187 patients undergoing first-time TAVI, among whom 120 (3.8%) did not receive any antithrombotic therapy, 715 (22.4%) were prescribed SAPT, 1244 (39.0%) were on DAPT, and 1108 (34.8%) were treated with anticoagulant therapy at three months post-TAVI. Patients without antithrombotic therapy were more often men (64.2%) and were more likely to have a history of malignancy (23.3%) compared with the other treatment groups. Patients who received oral anticoagulation had a higher burden of atrial fibrillation (75.7%). The proportion of patients with atrial fibrillation remained stable over time. During the first decade of TAVI, there was a shift in the antithrombotic treatment pattern: no therapy was ranging from 1.1% to 6.6%, SAPT from 19.1% to 29.4%, while DAPT decreased from 51.0% to 31.2% and anticoagulant therapy increased from 21.6% to 39.8% (Figure 1). Conclusion During the first decade of TAVI, antithrombotic therapy patterns post-TAVI changed substantially, such that the use of dual antiplatelet therapy decreased over time, while the use of anticoagulant therapy increased. Since atrial fibrillation remained stable over time, the increase in anticoagulant therapy is most likely due to changes in guidelines for management of atrial fibrillation in 2010. These findings show the evolving treatment patterns in the first decade of TAVI, which reflects the recommendations from clinical trials and guidelines for the management of antithrombotic therapy for patients with TAVI.

Effectiveness of combined physical exercise and cognitive training in older adults with cognitive impairment: A systematic review and meta-analysis

Falls among cognitively impaired older adults are a global concern. The aim of this study was to assess the efficacy of combining physical exercise and cognitive training to improve balance among older adults. A systematic search of databases, including Embase, Medline-OVID, CINAHL-EBSCOhost, and Central-Cochrane Library, was conducted from March 9 to April 6, 2023. The search used keywords based on the PICO question, where the population was older adults with cognitive impairment. Compared to a single therapy, the intervention involved a combination of muscle strengthening and cognitive therapy, with the outcome of falls or balance. Inclusion criteria were randomized controlled trials (RCTs) in any setting. Studies with participants under 60 years old and lacking baseline clinical assessments were excluded. EndNote 20 was used as a reference manager tool, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 flow diagram was used to map out the number of identified records. Two investigators worked independently, and the Jadad scale was used for critical appraisal. The PROSPERO registration number is CRD42023454876. A fixed-effects meta-analysis was performed using an inverse-variance method. Four articles met the inclusion criteria, three of which were included in the meta-analysis. Studies were from Europe, New Zealand, and the Philippines, with a total sample of 255 participants and mean ages of 65.9–87.5 years. The studies used combined physical and cognitive training in one group. Results showed a significant moderate effect size (effect size (ES): 2.29; standardized mean difference (SMD): 0.41; p&lt;0.05; heterogeneity (I2): 0%) indicating no heterogeneity. In conclusion, the combined intervention displayed the potential to improve balance for cognitively impaired older adults.

PO0425: Low-Dose Rate Brachytherapy with Permanent Implants as Single Therapy in High-Risk Localized Prostate Cancer in a Single Center

PO0425: Low-Dose Rate Brachytherapy with Permanent Implants as Single Therapy in High-Risk Localized Prostate Cancer in a Single Center