Safe Strategy Research Articles

Efficacy and diabetes risk of moderate-intensity statin plus ezetimibe versus high-intensity statin after percutaneous coronary intervention

BackgroundsHigh-intensity statin is recommended for patients undergoing percutaneous coronary intervention (PCI), and ezetimibe is recommended to be added in patients not achieving low-density lipoprotein cholesterol (LDL-C) targets. Moderate-intensity statin plus ezetimibe can reduce LDL-C levels similar to high-intensity statin. The aim of this study is to examine the long-term efficacy and safety of moderate-intensity statin plus ezetimibe as the first-line strategy compared to high-intensity statin in patients undergoing PCI.MethodData was obtained from the Health Insurance Review and Assessment Service database of South Korea. Patients who underwent PCI from 2012 to 2017 were included. The primary efficacy endpoint was major adverse cardiac cerebrovascular events (MACCEs), a composite of all-cause death, revascularization, or ischemic stroke. The safety endpoint was new-onset diabetes mellitus (DM).ResultsA total of 45,501 patients received high-intensity statin (n = 38,340) or moderate-intensity statin plus ezetimibe (n = 7,161). Among propensity-score-matched 7,161 pairs, MACCEs occurred in 1,460 patients with high-intensity statin and 1,406 patients with moderate-intensity statin plus ezetimibe (33.8% vs. 31.9%, hazard ratio 0.96, 95% confidence interval 0.89–1.03, P = 0.27) at a median follow-up of 2.7 years. DM was newly diagnosed in 398 patients with high-intensity statin and 342 patients with moderate-intensity statin plus ezetimibe (12.5% vs. 10.7%; hazard ratio 0.84, 95% confidence interval 0.73–0.97, P = 0.02).ConclusionIn patients undergoing PCI, moderate-intensity statin plus ezetimibe demonstrated a similar risk of MACCEs but a lower risk of new-onset DM than high-intensity statin. Early combination treatment of moderate-intensity statin and ezetimibe may be a useful and safe lipid-lowering strategy after PCI.Graphical abstractCumulative incidence according to the first-line lipid-lowering strategy in patients undergoing percutaneous coronary intervention. Abbreviation: MACCE, major adverse cardiac cerebrovascular events; PCI, percutaneous coronary intervention.

Intimate partner violence (IPV) among sexual minority men (SMM) during the COVID-19 pandemic: A scoping review and a call for research

There is a dearth of literature documenting the impact of the COVID-19 pandemic on intimate partner violence (IPV) victimization among sexual minority men (SMM). This review examines studies conducted since the onset of the COVID-19 pandemic, focusing on the experiences and changes in IPV experiences among SMM. We conducted a comprehensive search, and article screening and selection adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only 7 studies were identified and met the eligibility, all of which utilized cross-sectional design. Studies were conducted in the U.S (n = 4), Spain (n = 1), China (n = 1), and a study using global samples (n = 1). Measurements and assessment tools for IPV victimization vary across these studies. SMM were observed to experience a relatively high rate of IPV victimization, and some reported experiencing more severe and frequent IPV victimization since the pandemic. IPV victimization was associated with multilevel factors such as younger age, substance use, mental illness, economic and structural vulnerabilities. None of the studies had examined the impact of the pandemic on help-seeking. There is a need to explore the long-term effects of the ongoing pandemic on IPV victimization among this vulnerable population. Developing safe intervention strategies and ensuring confidential access to health and supportive services are particularly urged.

Trends and inequalities in the use of deworming medication during pregnancy in Sierra Leone, 2008–2019

BackgroundIntestinal worm infections are a significant public health concern for pregnant women in low- and middle-income countries. These infections can lead to anaemia, malnutrition, and adverse pregnancy outcomes, including premature birth and low birth weight. Deworming medication during pregnancy is a safe and effective strategy to prevent these complications and improve maternal and child health. This study aims to investigate the trends and inequalities in the use of deworming medication during pregnancy among women in Sierra Leone between 2008 and 2019.MethodsThe study utilised data from the Sierra Leone Demographic Health Surveys conducted in 2008, 2013, and 2019. We used the Health Equity Assessment Toolkit developed by the World Health Organisation to calculate various measures of inequality, including difference, ratio, population attributable risk, and population attributable fraction. An inequality assessment was conducted for five stratifiers: age, economic status, level of education, place of residence, and sub-national province.ResultsThe prevalence of deworming medication during pregnancy was 43.8% in 2008, 72.4% in 2013, and 83.5% in 2019 in Sierra Leone. There was a decrease in age-related inequality from a difference of 3.7% in 2008 to −0.8% in 2019. Economic-related inequality increased from a difference of −8.5% in 2008 to −8.2% in 2019. Both population attributable fraction and population attributable risk were zero in all survey years for economic status, indicating no improvement in the setting average without economic-related inequality. Inequality in education increased from a difference of -8.9% in 2008 to −8.4% in 2019 and decreased from a difference of −2.6% in 2008 to –5.5% in 2019 for place of residence. Provincial inequality decreased from a difference of 29.5% in 2008 to 11.8% in 2019. The population attributable risk for province reveals that the setting average could have been 10.5 percentage points lower in 2008, 8.2 percentage points lower in 2013, and 5.9 percentage points lower in 2019 without provincial inequality.ConclusionThe prevalence of deworming medication use during pregnancy substantially increased from 2008 to 2019 (43.8% to 83.5%) in Sierra Leone. This suggests a positive public health trend in maternal healthcare access and education. Inequalities related to economic status and education increased slightly while age-related, place of residence and provincial inequalities decreased. This indicates an inequitable distribution of this essential healthcare intervention across these stratifiers. The government and policymakers should continue efforts to raise awareness and promote the use of deworming medication during pregnancy.

Disseminated Superficial Actinic Porokeratosis: A Systematic Treatment Review.

Disseminated superficial actinic porokeratosis (DSAP) is a disorder of keratinization characterised by small, brown plaques with elevated keratotic rims, typically occurring on sun exposed areas. DSAP poses a risk for malignant transformation, emphasising the need for effective management strategies. The aim of this study was to review the current reported management options for DSAP. This systematic review was based on a comprehensive search of databases (Cochrane, PubMed, Medline, Embase, Emcare, ProQuest, Web of Science, CINAHL) from inception to 15 March 2024. Studies reporting management of DSAP were included irrespective of study design. Of 923 citations, 61 studies were included, predominantly comprising case reports and retrospective case series. A limited number of randomized and open-label trials were identified. Various treatment modalities were reported, including topical and systemic agents, photodynamic therapy, and laser therapy. Multiple management options are available for DSAP, including topical and systemic agents, photodynamic therapy and laser treatments. However, these approaches vary in their balance between efficacy and toxicity. Currently, there is a paucity of high-quality clinical trial data to guide treatment decisions. Further studies are required to determine the most effective and safe management strategies for DSAP. PROSPEROREGISTRATION: CRD42024514558.

Implementation and Impact of a Lifting Cushion for Care Home Residents Who Have Fallen.

Falls are a global public health problem and the second leading cause of death from unintentional injury. Globally, approximately 30%-50% of people living in nursing or residential care homes fall each year. Falls have an impact on quality of life and morbidity. Prevention of falls is gold standard care. When falls do occur, implementation of safe strategies to help the person rise is required. Structured risk assessment and the use of a 'lifting' cushion are one such strategy. To evaluate the impact of the lifting cushion on management of falls and assess barriers and facilitators to staff use of the lifting cushion in 18 care homes. Two-phase study involving (i) capturing quantitative pre- and post-cushion implementation data along with comparison of means testing and (ii) theoretically underpinned qualitative semi-structured interviews to explore barriers and facilitators to cushion implementation with inductive and deductive data analysis. The cushion was used a total of 32 times out of 567 post-implementation recorded falls (6% of all falls). Barriers and facilitators to cushion use aligned to the Theoretical Domains Framework include knowledge, skills and confidence, emotion, beliefs about safety and decision processes, environmental context and resources and social influences. The lifting cushion was poorly adopted. Identified barriers to adoption would not be addressed using routine train and cascade processes. We identified facilitators that could be enhanced to promote uptake. Theoretically underpinned implementation strategies, tailored to assess determinants, are known to be more effective; however, this approach has rarely been used in care homes. We have demonstrated a structured approach to implementation of cushion use; this may be transferable to other care home practices. Cae home leaders should be aware that giving information alone will not change practice. Implementation or improvement strategies will be more effective.

Optimizing Traveler Behavior Between MADINA and JEDDA Using UPPAAL Stratego: A Stochastic Priced Timed Games Approach

This study looks at how travelers move between MADINA and JEDDA, using the UPPAAL Stratego tool to tackle the complexities of urban mobility. As cities grow, effective transportation planning becomes more challenging. Travelers have three options: car, bus, and train. The choices for car and bus travel are impacted by traffic conditions, which can vary between heavy and light, affecting both travel time and cost. We propose a detailed mathematical model that captures all possible scenarios related to these travel options, incorporating the uncertainties of real life. This allows us to simulate different traffic situations. By using UPPAAL Stratego, we evaluate three strategies: the Safe Strategy, which minimizes risk; the Fast Strategy, which aims to reduce travel time; and the Fast and Safe Strategy, which seeks a balance between speed and safety. This paper starts with an introduction to the Stochastic Priced Timed Games approach, highlighting its relevance in modeling dynamic travel environments. We then provide an overview of UPPAAL Stratego, showcasing its abilities in generating, optimizing, and comparing strategies. Next, we outline our mathematical model, explaining the assumptions, parameters, and data sources we used. Our simulation results illustrate how each strategy performs under different conditions, shedding light on traveler preferences and behaviors. The findings underscore the significance of accounting for traffic variability in travel planning and offer important insights for urban transportation policies aimed at improving the traveler experience and optimizing resource use. Additionally, we emphasize the theoretical contributions of our model by demonstrating its applicability to real-world scenarios and its potential to inform future research in urban mobility optimization. Ultimately, this research adds to the growing knowledge of smart transportation systems, demonstrating how formal mathematical modeling can address complex real-world challenges and inform future urban mobility strategies.

A safe and balanced strategy for resuming bariatric surgery in the era of COVID-19

A safe and balanced strategy for resuming bariatric surgery in the era of COVID-19

Microenvironment Self-Adaptive Nanomedicine Promotes Spinal Cord Repair by Suppressing Inflammation Cascade and Neural Apoptosis.

Despite various biomaterial-based strategies are tried in spinal cord injury (SCI), developing safe and effective microinvasive pharmacotherapy strategies is still an unmet clinical need. Stimuli-responsive nanomedicine has emerged as a promising non-invasion technology, which enhances drug delivery and promotes functional recovery following SCI. Considering the multiple progressive pathological events and the blood spinal cord barrier (BSCB) associating SCI, a microenvironment self-adaptive nanoparticle (custom-designed with rabies virus glycoprotein 29-RVG29 and hyaluronic acid-HA, RHNP) capable of consistently crossing the BSCB and selectively targeting inflammatory cells and neural cells based on different stages of SCI are developed. The data indicated that RHNP can effectively traverse the BSCB through RVG29, and adaptively modulate cellular internalization by selectively exposing either HA or RVG29 through diselenide bonds, depending on pathological reactive oxygen species (ROS) signals. Furthermore, curcumin is loaded into RHNP (RHNP-Cur) to improve motor function and coordination of hind-limbs in a traumatic SCI mouse model. This study finds that RHNP-Cur exhibited inhibitory effects on the inflammatory cascade originating from M1 microglia/macrophages and neurotoxic astrocytes, and protected neural cells from inflammation-induced apoptosis during nerve regeneration. Collectively, the work provides a microenvironment self-adaptive nanomedicine which enables efficient microinvasive treatment of SCI.

Aluminate-activated nano-SiO2 for enhancing water vapor barrier properties in polymers films: A safe and effective strategy

In this work, a series of nanocomposite films composed of polylactic acid (PLA), poly (butylene adipate-co-terephthalate) (PBAT), polybutylene succinate (PBS), nano-SiO2 activated by aluminate for different times were developed to enhance water vapor barrier properties. The physiochemical and thermal properties of the films were characterized. In addition, total and aluminum migration from the films was monitored, and non-targeted screening was performed to evaluate the potential safety of the composite films. Fourier Transform infrared spectroscopy analysis indicated that the nano-SiO2 was successfully activated by aluminate. Differential scanning calorimetry analysis indicated that incorporation of the activated nano-SiO2 slightly reduced the glass transition temperature (from 54 to 51 °C) and increased the crystallinity degree (from 6.9 % to 11.1 %) of PLA. Incorporation of 0.4 % nanofillers was found to give the highest crystallinity. Thermogravimetric analysis showed that the thermal stability of the PLA/PBAT/PBS films did not change significantly after adding the activated-nano-SiO2. However, the incorporation of these nanofillers did increase the interfacial roughness and crystallinity degree of the films, thereby reducing the water vapor permeability by around 30 %. Erucamide was detected in the composite films after exposure to food simulants, however, the films containing the nanofillers still met European Union safety standards. In summary, the nanofiller-loaded polymer films developed in this study were shown to be safe and have high water barrier properties, which means they may be suitable for application in the food, cosmetic, personal care, pharmaceutical, and agrochemical industries.

Orthokeratology for high myopia

Purpose. With an increasing proportion of children with myopia especially in Asia, efforts have been made to reduce chances of preventable sight loss related to high myopia in the future. Orthokeratology lens has been used as one of the modalities not just to correct myopia, but also to slow down myopic progression and axial elongation. This case report reviews a patient with clinically significantly high myopia, whose refractive errors was partially corrected with orthokeratology lens and spectacle lenses. Material and Methods. A now 14-year-old patient with a history of fast progressing myopia, was prescribed and commended orthokeratology to manage myopia, while regularly monitoring her refractive errors, axial length, binocular vision status, corneal topography, and anterior eye health was monitored regularly at the author’s practice. Results. Over a two year follow up period, a partial correction of high myopia with orthokeratology lenses and residual refractive errors with additional spectacle lenses was effective in managing this patient’s myopia, as well as slowing of axial elongation. An updated pair of orthokeratology lens with a steeper back optic zone radii were prescribed to reduce superficial corneal staining and to maintain corneal health. Conclusion. Patient commitment and adherence to close monitoring of eyes in terms refractive errors, axial length, and anterior eye health, are vital in achieving a successful orthokeratology lens wear for high myopia. A dual fitting strategy consisting of orthokeratology lens and spectacle wear can be a safe management strategy that is acceptable for patients with high myopia. It would be helpful for practitioners to be able to rely on robust evidence-based guidance when determining whether lens wear can be ceased, i.e. when further axial elongation and myopic progression are no longer likely.

Antimicrobial and antibiofilm activity of human recombinant H1 histones against bacterial infections.

Histones possess significant antimicrobial potential, yet their activity against biofilms remains underexplored. Moreover, concerns regarding adverse effects limit their clinical implementation. We investigated the antibacterial efficacy of human recombinant histone H1 subtypes against Pseudomonas aeruginosa PAO1, both planktonic and in biofilms. After the in vitro tests, toxicity and efficacy were assessed in a P. aeruginosa PAO1 infection model using Galleria mellonella larvae. Histones were also evaluated in combination with ciprofloxacin (Cpx) and gentamicin (Gm). Our results demonstrate antimicrobial activity of all three histones against P. aeruginosa PAO1, with H1.0 and H1.4 showing efficacy at lower concentrations. The bactericidal effect was associated with a mechanism of membrane disruption. In vitro studies using static and dynamic models showed that H1.4 had antibiofilm potential by reducing cell biomass. Neither H1.0 nor H1.4 showed toxicity in G. mellonella larvae, and both increased larvae survival when infected with P. aeruginosa PAO1. Although in vitro synergism was observed between ciprofloxacin and H1.0, no improvement over the antibiotic alone was noted in vivo. Differences in antibacterial and antibiofilm activity were attributed to sequence and structural variations among histone subtypes. Moreover, the efficacy of H1.0 and H1.4 was influenced by the presence and strength of the extracellular matrix. These findings suggest histones hold promise for combating acute and chronic infections caused by pathogens such as P. aeruginosa.IMPORTANCEThe constant increase of multidrug-resistant bacteria is a critical global concern. The inefficacy of current therapies to treat bacterial infections is attributed to multiple mechanisms of resistance, including the capacity to form biofilms. Therefore, the identification of novel and safe therapeutic strategies is imperative. This study confirms the antimicrobial potential of three histone H1 subtypes against both Gram-negative and Gram-positive bacteria. Furthermore, histones H1.0 and H1.4 demonstrated in vivo efficacy without associated toxicity in an acute infection model of Pseudomonas aeruginosa PAO1 in Galleria mellonella larvae. The bactericidal effect of these proteins also resulted in biomass reduction of P. aeruginosa PAO1 biofilms. Given the clinical significance of this opportunistic pathogen, our research provides a comprehensive initial evaluation of the efficacy, toxicity, and mechanism of action of a potential new therapeutic approach against acute and chronic bacterial infections.

Thirty days clinical outcomes following stent implantation with aspirin-free prasugrel monotherapy in non-ST segment elevation myocardial infarction. Interim report from ASET-Japan pilot study

Abstract Background Dual antiplatelet therapy with a P2Y12 inhibitor, in addition to aspirin, is the standard therapy after percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) to prevent ischemic cardiovascular events. The Acetyl-Salicylic Elimination Trial (ASET) pilot studies conducted in Japan in patients with NSTE-ACS investigated the safety and feasibility of a low-dose prasugrel monotherapy after PCI. Purpose To ensure the safety of the patients, enrolment in the study was implemented only after confirmation of a successful procedure. The abstract reports our interim analysis, aimed at evaluating preliminary safety and feasibility. Methods The ASET-Japan pilot study was designed to explore the feasibility and safety of a low dose of prasugrel monotherapy (3.75mg/day), without adjunctive aspirin, after optimal PCI using Everolimus eluting stent (EES) in Japanese patients with non-ST-segment elevation acute coronary syndromes. The primary endpoint in the ASET-Japan NSTE-ACS (Phase 2) is a 12-month clinical outcome. The study is currently in the follow-up phase. All the target lesions were treated with a platinum-chromium everolimus-eluting stent. The primary ischemic endpoint was the composite of cardiac death, spontaneous target vessel myocardial infarction, or definite stent thrombosis, and the primary bleeding endpoint was Bleeding Academic Research Consortium types 3 and 5 bleeding up to 12-month. If more than 3 events occurred, trial enrollment would have to be terminated by the data and safety monitoring board. Results One hundred one patients were enrolled after successful index PCI and completed a 30 days follow-up. The mean age was 69.1±12.3 years and 75.2% was male. The mean anatomical SYNTAX score was 7.9±4.7. Unstable angina (UAP) and NSTEMI were seen in 24.8% (25/101) and 75.2% (75/101) patients, respectively. According to the Braunwald classification, 8 percent of the patients were categorised as Class IA UAP, 48% as Class IB, 20% as Class IIB, 4% as Class IIIA and 20% as Class IIIB. In NSTEMI patients, the median (IQR) pre-procedural troponin value (cardiac Troponin T or I) was 2.79 (1.12 – 22.27) times the Upper Limit of Normal. According to the PRECISE DAPT score, 36.6% of patients were categorised as High Bleeding Risk (HBR) with scores above 25. At one month, the primary ischemic endpoints of cardiac death, target-vessel spontaneous MI or definite Stent thrombosis did not occur. Two patients (2.0%) had BARC type 3a bleeding. Conclusion Prasugrel monotherapy in the first 30 days following platinum-chromium everolimus-eluting stent deployment is a feasible and safe strategy in NSTE-ACS patients with simple anatomy and successful PCI.

Same-day discharge after atrial fibrillation ablation: is it equally safe?

Abstract Introduction Same-day discharge after atrial fibrillation (AF) ablation represents a paradigm shift in post-procedure care. This approach allows patients (pts) to return home on the same day after their ablation, promoting comfort and reducing hospitalization duration. Purpose To evaluate safety of same-day discharge in pts submitted to either pulsed field ablation (PFA) or cryoablation (CA). Methods Single-center retrospective study of AF pts submitted to ablation with either PFA or CA from May 2019 to November 2023. Ablation strategy consisted in pulmonary vein isolation complemented with ablation of the cavo-tricuspid isthmus in pts with history of atrial flutter. Pts were considered eligible to same-day discharge if an observation period of at least 6h was assured after the procedure. Safety was defined as 30-day major or minor complications. Chi-square tests were used for the comparison of continuous variables. Results We included 152 pts, 60 were submitted to PFA and 92 to CA, 56.6% males, median age 66±14 years, mean CHA2DS2-VASc score 2.45±1.4. Paroxysmal AF, short and long-standing persistent AF were present in 67%, 16% and 15% of pts respectively. Previous stroke was present in 8.7% of pts and 27 pts had history of heart failure. Acute success rate was 99.3%, concomitant cavo-tricuspid isthmus ablation was performed in 20% of pts, and mean procedure time was 107.5±74 min. Same-day discharge was initially considered in 70% of pts, however of these, 12 pts remained under further observation due to acute complications. No major or minor acute complications were reported in pts with same-day discharge. There were no significant differences in 30 days complications between groups. At 30 days no major complications were reported in pts with same-day discharge. One pts in which same-day discharge was halted died 4 days after ablation from hemorrhagic shock. Regarding minor complications at 30 days, 4 minor femoral hematoma were reported, 2 in each group. Conclusion In our population, same-day discharge proved to be a safe strategy if careful pts selection is assured. This practice enhances overall pt experience, marking a significant paradigm shift in AF management.

Intravascular lithotripsy in the management of underexpanded stents

Abstract Introduction Stent underexpansion significantly heightens the risk of major adverse cardiac events (MACE), and available treatment options for this condition remain limited. Intravascular Lithotripsy (IVL) technology disrupts superficial and deep calcium by using localized pulsative sonic pressure waves, emerges as a promising tool for underexpanded stents. Methods Following PRISMA guidelines, we systematically explored PubMed, SCOPUS, and Cochrane databases up to September 3, 2023, for studies evaluating IVL's safety and efficacy in treating underexpanded stents. We gathered angiographic (QCA) and intracoronary imaging (OCT or IVUS) data, examining the stent's minimal diameter stenosis (MDS), minimal lumen diameter (MLD), minimal stent area (MSA), and minimal lumen area (MLA) pre- and post-IVL application. Procedural success constituted the efficacy endpoint, while peri-procedural complications, in-hospital-30-days and long-term mortality, and MACE were safety endpoints Results This meta-analysis comprised 21 studies including 669 patients and 673 treated lesions in underexpanded stent. The mean age was 73.2 ± 2.1 years, with an overall IVL procedural success rate of 93% [(95% Confidence Interval (CI): 88%-96%, I2=29%), while the in-hospital-30-days and long-term mortality incidence were 1% (95% CI: 1%-3%, I2=0%) and 3% (95% CI: 2%-6%, I2=0), respectively. The 30-days target lesion revascularization (TLR) was approximately 6% (95% CI: 3%-12%, I2=50%). There was a significant increase in the MDS [Standardized Mean Difference (SMD): +50.52%, 95% CI: 39.4-61.6, I2=94%)] and in MSA (SMD: +3.52, 95% CI: 2.47 to -4.58, I2=83%) immediately after IVL application. It was observed a significant increase in MLD (SMD: +1.54, 95% CI: 1.09 to 1.98, I2=95%) and in the MLA (SMD: +3.64, 95% CI: 2.62-4.66, I2=5%). Major procedural and device related complications were 3% (95% CI: 1%-6%, I2=0%) and 1% (95% CI: 0%-2%, I2=85%) respectively. Notably low rates were observed for stent thrombosis (0%, 95% CI: 0%-2%, I2=0%), dissections (1%, 95% CI: 1%-4%, I2=0%), perforations (1%, 95% CI: 1%-3%, I2=0%) and no-reflow (0%, 95% CI: 0%-1%, I2=0%). Conclusions IVL demonstrates promise as a safe and effective strategy for underexpanded stent treatment, characterized by low rates of periprocedural complications. Future prospective studies are now warranted to compare IVL to other lesion preparation strategies.30day All-Cause Mortality after IVL use.Minimum Stent Diameter after IVL use.

Shortened versus standard duration of dual antiplatelet treatment after percutaneous coronary intervention in patients with and without chronic kidney disease: a systematic review and meta-analysis

Abstract Background Impaired renal function is an established risk factor for recurrent cardiac events. The severity of chronic kidney disease (CKD) is related with an increased risk for both ischemic and bleeding complications. As a result, the clinical implications of antithrombotic therapies may be different in patients with CKD as compared to those without. Recently, shortened duration of DAPT, namely one to three months, after percutaneous coronary intervention (PCI) has been proven as a safe and feasible strategy in various different clinical scenarios, like in high-bleeding risk patients, in acute coronary syndromes and complex PCI. However, it remains debatable whether DAPT should be shortened in patients with high ischemic and bleeding risk, such as those with CKD. Purpose The aim of our systematic review and meta-analysis is to explore the safety and efficacy of shortened therapy (1-3 months; S–DAPT) in patients without and without CKD undergoing PCI. Methods Three major databases (MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus) were screened for eligible randomized – controlled trials, or subgroup or post – hoc analyses of them. The studies should compare shortened (S–DAPT) with longer (>3 months) DAPT (L–DAPT) in patients undergoing PCI, and include data on CKD presence. The endpoints were Net Adverse Clinical Events (NACE) and Major Adverse Cardiac Events (MACE) and should be evaluated at 12 months. NACE and MACE were used as per trial defined. The effect of different DAPT regimens was assessed by calculating the risk ratio (RR) with 95% confidence interval (CI) using random-effects model (Mantel-Haenzel). Results A total of eight studies and 56,660 patients were included in our analysis; a notable proportion of patients (9.7%, N=5,466) suffered from CKD. Our analysis showed an overall benefit of S-DAPT in NACE (RR: 0.88, 95%CI: 0.81 – 0.95), which was consistent in patients with and without CKD (p-interaction=0.58). (Figure 1) No significant difference regarding MACE was observed between S-DAPT and L-DAPT (RR: 0.98, 95%CI: 0.90 – 1.06) in both patients with and without CKD (p-interaction=0.19). (Figure 2) Conclusions Our analysis showed an overall benefit of S-DAPT in NACE without any difference in MACE, with similar findings among patients with and without CKD. Thus, DAPT shortening could be a feasible and safe approach when it is required, even in patients with impaired renal function. Further randomized controlled trials focusing on patients with CKD are required for validating the previous results and exploring further benefits of abbreviated duration of DAPT.Net adverse clinical eventsMajor adverse cardiac events

V-A ECMO weaning with pump-controlled retrograde trial off (PCRTO) approach: an illustration of safety, benefits and feasibility

Abstract Introduction Weaning cardiogenic shock patients off V-A ECMO is a crucial but difficult step in the management of these patients. Conventional weaning strategies reduce the ECMO flow to approximately 1 L/min, yet this still entails significant unloading of the cardiopulmonary circulation. Background The PCRTO technique enables controlled retrograde flow of oxygenated blood from the patient’s arterial side into the right ventricle, resulting in an incremental increase of 0.5 L/min in right ventricular preload. This process challenges and evaluates the entire cardiopulmonary system (Figure). Methods We prospectively examined the use of the Pump-Controlled Retrograde Trial Off (PCRTO) approach (-0.5 L/min) compared to conventional ECMO weaning (+1 L/min) in a cross over study including 14 V-A ECMO patients across three quaternary high-output cardiogenic shock centers. Both the conventional and the PCRTO-technique are performed under continuous cardiac echo and PA-catheter guidance. Results After achieving adequate anticoagulation levels (Xa>0.3), no thrombotic or other complications were observed, confirming 100% safety of this technique. Table 1 provides an overview of our PCRTO-cohort and their evaluation after conventional versus PCRTO weaning. In 43% (6/14) of our cohort, conventional weaning strategies determined feasibility of ECMO-device weaning, while ultimately failing with PCRTO due to e.g. right ventricular failure or oxygenation failure. In contrast, 4/14 patients who failed the conventional weaning showed a positive weaning potential with PCRTO, potentially enabling patients to be liberated from bridging to durable ventricular assist devices or heart transplant. Conclusions In conclusion, PCRTO is a safe weaning strategy that increases the likelihood of successful weaning in critically ill V-A ECMO patients by challenging oxygenation/ventilation and cardiac circulation through increased right ventricular preload and reduced left ventricular afterload. Here, PCRTO ultimately led to a different destination scenario in 78,5% of our patient cohort compared to conventional V-A ECMO weaning alone. PCRTO may provide a standardised, reproducible approach to ECMO assessment and liberation which will be useful for future clinical trials in this population.

Combined SK and K2P channel block cardioverts atrial fibrillation in 82% of cases, doubling the efficacy of single channel block

Abstract Background Inhibiting the atrial-selective SK and K2P channels represents a promising strategy for cardioverting atrial fibrillation (AF), but its efficacy has not been evaluated in a large human cohort. Objectives This study employed in-silico trials in 1000 virtual patients (i.e., clinical trials conducted in a population of virtual human subjects through modelling and simulation) to estimate the efficacy and safety of three pharmacological interventions: single and combined SK and K2P channel block. Methods A large cohort of 1000 virtual patients was developed based on human data, to cover the electrophysiological, anatomical and structural variability encountered in clinical practice. The subset of virtual patients with AF maintenance underwent pharmacological cardioversion (Figure). Results Sustained AF was observed in 654 (65%) virtual patients. In this cohort, cardioversion efficacies of 33% (213 of 654), 43% (278 of 654) and 82% (534 of 654) were obtained for single SK, single K2P and combined channel block, respectively (Figure). The cardioversion efficacy was proportional to an increase in tissue refractoriness (increase of 45.2±43.0, 71.0±55.3 and 133.0±48.4 ms in the atrial refractory period) and depended on the ionic current profile. Virtual patients cardioverted by SK channel block presented lower K2P densities (0.008±0.002 vs. 0.006±0.002 S/mF; non-cardioverted vs. cardioverted virtual patients, respectively). Similarly, a lower SK density favoured the success of K2P channel inhibition (1.87±0.24 vs. 1.46±0.5 S/mF; non-cardioverted vs. cardioverted virtual patients, respectively). Both ionic currents had a crucial role on atrial repolarization, and thus, a synergism resulted from the polypharmacological strategy (i.e., higher efficacy than the additive effects of single channel block). All three interventions, including the multi-channel block, preserved the atrial electrophysiological function (i.e., conduction velocity and calcium transient dynamics) and thus, the atrial contractile properties (safety). Conclusion In-silico trials identify the polypharmacological SK+K2P channel block as an effective and safe strategy for AF management.

Coupling CoIr Nanoalloys with MXene by Lewis Acidic Molten Salt Etching for Wide-pH-Environment Hydrogen Evolution Reaction.

Metal/MXene-based materials show broad prospects in energy conversation through the strong metal-support interaction (SMSI). However, the difficulty and harshness of synthesis heavily limit their further application. Herein, using Lewis acidic molten salt to etch MAX as a precursor of MXene, a more convenient and safer strategy is designed to in situ construct the MXene-supported CoIr nanoalloy (CoIr/MXene) catalyst through Ti─O─M bond. The special layered structure and oxygen-containing functional group of MXene regulate the SMSI upon CoIr nanoalloys. Moreover, the contact angle and in situ Raman test results exhibit good interface hydrophilicity of MXene, enhancing the water adsorption on interfaces, and accelerating the mass transfer process. As a result, CoIr/MXene shows high hydrogen evolution reaction (HER) performance, which only needs overpotentials of 34 and 50mV to drive a current density of 10mA cm-2 in alkaline and acidic media, respectively, with excellent stability. Especially, in alkaline media, CoIr/MXene possesses 6 times higher HER mass activity (4.297 A mgIr -1) than commercial Pt/C catalysts (0.686 A mgPt -1) at the potential of 50mV, indicating larger active site density and intrinsic activity for CoIr/MXene. This work expands the application of the molten salt assist etching strategy and provides new insight for the development of metal/MXene-based catalysts.

Vitamin C improved anxiety and depression like behavior induced by chronic unpredictable mild stress in adolescent rats by influencing on oxidative stress balance, neurotransmitter systems, and inflammatory response

ABSTRACT Objectives: Stress is an adaptive response to different events in daily life that could strain physically, emotionally, or psychologically. Adolescence is an important developmental period due to physical, psychological, and social maturation. The aim of our study is to state whether chronic unpredictable mild stress (CUMS) during adolescence in male rats can cause anxiety and depression in adulthood and whether vitamin C (Vit C) can prevent this problem or not. Methods: For this purpose, we performed behavioral tests, including open field test, elevated plus maze, and forced swimming test. In addition, we investigated the metabolism of serotonin, the level of inflammation, oxidative stress and brain-derived neurotrophic factor (BDNF) in the brain cortex tissue of animals. Results: Results indicated that CUMS exacerbates mood-related behaviors by affecting the brain oxidative stress balance, inflammatory response, and serotonin metabolism. Moreover, we found that CUMS-Vit C co-treatment could significantly reverse CUMS-induced complications by restoration of the mentioned biochemical parameters. Discussion: Taken together, we would like to suggest the use of Vit C supplementation as a safe, inexpensive, and effective strategy for the management of CUMS.

Novel Phenoxyalkanoic Acid Derivatives as Free Fatty Acid Receptor 4 Agonists for Treating Type 2 Diabetes Mellitus

Diabetes mellitus (DM) is a common metabolic disease that poses a severe threat to human health. Despite a range of therapeutic approaches, there remains a lack of effective and safe therapies with the existing drugs. Therefore, there is an urgent need to develop novel, effective, and safe therapeutic strategies for DM. Free fatty acid receptor 4 (FFAR4), also known as GPR120, is a member of the G protein-coupled receptor family, which has received considerable attention as an attractive new therapeutic target for treating DM. In the present study, based on the structure of TUG-891, which has excellent activity and selectivity, a series of novel FFAR4 agonists was designed by replacing the phenylpropanoic acid β position carbon atom with an oxygen atom, while replacing the linking oxymethylene with an amide-linking group. The target compounds were evaluated for FFAR4 agonistic activity, and the preferred compounds were evaluated for selectivity, oral glucose tolerance in normal ICR mice, antidiabetic activity in diet-induced obese (DIO) mice, pharmacokinetic properties in ICR mice and molecular modeling studies. The results showed that compound 10f possessed excellent FFAR4 agonistic activity and selectivity, significantly improved glucose tolerance in normal ICR mice, lowered blood glucose and promoted insulin secretion in a dose-dependent manner in DIO mice, and showed favorable pharmacokinetic properties. These results indicate that compound 10f may be a promising compound that deserves further structure–activity relationship and pharmacological studies for the development of antidiabetic drugs.