Conventional Treatment Research Articles

DEX Immunotherapy Pharmaco-Biotechnological Advances in Multimodal Therapy for Cancer

This article reviews the synergy between pulsed dendritic cell exosome (DEX) immunotherapy and chemotherapy in cancer treatment. DEX exosomes, which act as immune system modulators, enhance chemotherapy efficacy by modifying the tumor microenvironment and activating an immune response targeted against tumor cells. This combination not only amplifies cancer cell destruction but also protects healthy cells, thus reducing systemic adverse effects of chemotherapy. The article highlights preclinical and clinical advances demonstrating the effectiveness of this combined strategy, showing promising results in tumors resistant to conventional treatments. Despite the benefits, challenges such as the high production cost of exosomes and the need to optimize treatment protocols for different cancer types are identified. Additionally, future research directions are presented, focusing on improving personalized treatments through genetically modified exosomes. In conclusion, the combination of DEX and chemotherapy has the potential to revolutionize cancer treatment, enhancing both treatment tolerance and clinical efficacy.

Recent Advances in the Translational Application of Immunotherapy with Pulsed Dendritic Cell-Derived Exosomes (DEX)

This article explores recent advances in immunotherapy using exosomes derived from dendritic cells (DEXs), highlighting their potential as an innovative option in cancer treatment. DEXs have demonstrated the ability to activate robust and sustainable immune responses, overcoming the limitations of conventional therapies. Their low toxicity profile and capacity to induce long-term immunological memory position them as a viable alternative, especially for patients who do not respond to traditional treatments. The article analyzes the mechanisms of action of DEXs and details their optimized production using advanced pulsing techniques. Clinical trials in melanoma, lung cancer, and other resistant tumors underscore their efficacy and the potential for combining them with conventional treatments, thereby improving tolerance and increasing effectiveness by minimizing adverse reactions. Additionally, the article reviews the epicutaneous administration of DEXs, a strategy that enhances immune response while improving patient experience. The adaptability of DEXs to different types and stages of cancer makes them a fundamental tool in personalized oncology. The question is no longer whether this therapy is effective, but rather when and which low-cost implementation option will be chosen for clinical use, consolidating DEXs as an innovative and validated therapeutic line integrated into protocols that promote more precise and safer treatments with greater effectiveness.

Treatment of gingival enlargement caused by orthodontic treatment

The aim of this study was to assess the healing process of gingival enlargement in adolescents with and without fixed orthodontic appliances using conventional scalpel treatments over a 3-month follow-up period. 20 patients with gingival enlargement were divided into two groups. The control group, without fixed orthodontic appliances, received mechanical treatment through conventional scalpel. Test group, comprising patients with fixed orthodontic appliances, was treated using conventional scalpel. Follow-up visits were conducted on days 1 and 90. Clinical periodontal parameters, including plaque index, gingival index, bleeding on probing, probing pocket depth, and gingival overgrowth index, were compared across groups at different time intervals from baseline. All groups exhibited statistically significant reductions in clinical periodontal parameters during the study period (P < 0.05). Test group, treated with conventional scalpel, showed the fastest and most consistent improvements in the healing process compared to baseline. Conventional scalpel therapy proved to be an effective method for treating gingival enlargement, with no reported discomfort or pain during or after the procedure. Given the challenges patients with fixed orthodontic appliances face in maintaining oral hygiene, they should be scheduled for more frequent follow-ups and given thorough home-care instructions.

Multidisciplinary management of severe hyperemesis gravidarum complicated by cannabinoid and opioid use: A case report on the complex interplay of hyperemesis gravidarum, opioids and treatment challenges

Hyperemesis gravidarum (HG) presents a significant management challenge in pregnancy due to its debilitating effects on maternal health and fetal outcomes. This case report details the presentation and management of a 34-year-old primigravida at 17 weeks and 4 days gestation with severe HG. The patient’s history includes significant gastrointestinal procedures, a prior child with lissencephaly, and continued opioid use during pregnancy. Her symptoms were refractory to conventional treatments and further complicated by cannabinoid use. A multidisciplinary approach involving gastroenterology, surgery, obstetrics, pharmacists, and dietitians was employed, resulting in significant improvement. This case highlights the importance of a comprehensive care strategy in managing refractory HG complicated by substance use.

Intranasal liposomal angiotensin-(1-7) administration reduces inflammation and viral load in the lungs during SARS-CoV-2 infection in K18-hACE2 transgenic mice.

To effectively reduce the health impact of coronavirus disease (COVID-19), it is essential to adopt comprehensive strategies to protect individuals from severe acute respiratory syndrome. In that sense, much effort has been devoted to the discovery and repurposing of effective antiviral and anti-inflammatory molecules. The endogenous peptide angiotensin-(1-7) [Ang-(1-7)] has been recently proposed as a promising anti-inflammatory agent to control respiratory infections. Liposomes also emerged as a safe and effective drug carrier system for local drug delivery to the lungs. In this context, the aim of this study was to develop a liposomal formulation of Ang-(1-7) [LAng (1-7)] and investigate its impact on animal survival as well as its antiviral and anti-inflammatory efficacies after intranasal administration in transgenic K18-hACE2 mice infected with SARS-CoV-2. The liposomal formulation was prepared by the ethanol injection method, exhibiting a mean diameter of 100 nm and a polydispersity index of 0.1. Following treatment of infected mice every 12 hours for 5 days, LAng (1-7) extended animal survival compared to the control groups that received either empty liposomes, free Ang-(1-7), or phosphate-buffered saline. Furthermore, the treatment with LAng (1-7) significantly decreased the viral load, as well as IL-6 and tumor necrosis factor levels in the lungs. Conventional treatment with remdesivir by parenteral route used as a positive control promoted similar effects, leading to improved survival rates and reduced viral load in the lungs without significant effects on IL-6 level. In conclusion, liposomal Ang-(1-7) emerges as a promising formulation to improve the treatment and decrease the severity of respiratory infections, such as COVID-19.

Effect of single parenteral administration of marbofloxacin on bacterial load and selection of resistant Enterobacteriaceae in the fecal microbiota of healthy pigs

BackgroundAntimicrobial resistance (AMR) is a global concern impacting both humans, animals and their environment. The use of oral antimicrobials in livestock, particularly in pigs, has been identified as a driver in the selection of AMR bacteria. The aim of the present study was to evaluate the effects of a single intramuscular (IM) dose of marbofloxacin (8 mg/kg) on Enterobacteriaceae and E. coli populations, as well as on fluoroquinolone resistance within the fecal microbiota of pigs. Twenty healthy pigs, 60-days old, were divided into two groups: a treated group (n = 13) and a control group (n = 7) and were monitored over a 28-day experimental period. Fecal samples were collected from all animals for the isolation of E. coli and Salmonella strains. The minimum inhibitory concentration (MIC) of marbofloxacin for the isolates recovered on MacConkey agar supplemented with 1 or 4 µg/mL of marbofloxacin and for some generic E. coli isolates (recovered from MacConkey agar not supplemented with marbofloxacin) was determined using the broth microdilution method. Genomic DNA was extracted from the confirmed bacterial strains and sequenced using the Sanger method to identify mutations in the quinolone resistance determining regions (QRDRs) of the gyrA and parC genes.ResultsThe single IM administration of marbofloxacin resulted in a significant decrease in Enterobacteriaceae and E. coli fecal populations from days 1 to 3 post- treatment. No Salmonella isolates were detected in either group, and no marbofloxacin-resistant E. coli isolates were identified. The MIC of the selected generic E. coli strains (n = 100) showed an increase to up to 0.5 µg/mL between days 1 and 3 post-treatment but remained below the clinical breakpoint of marbofloxacin resistance (4 µg/mL). Sequencing of these isolates revealed no mutations in gyrA and parC genes.ConclusionsThe present study showed that this dosing regimen of marbofloxacin significantly decreases the fecal shedding of Enterobacteriaceae and E. coli populations in pigs, while limiting the selection of marbofloxacin-resistant E. coli isolates. These findings warrant validation in sick pigs to support the selective use of this antibiotic solely in cases of clinical disease, thereby minimizing the reliance on conventional (metaphylactic) group treatments in pigs.

Biologics in congenital ichthyosis: are they effective?

Congenital ichthyoses (CI) comprise a heterogeneous group of genetic diseases requiring lifelong treatment and having a major effect on quality of life. Conventional treatments reduce scaling and skin discomfort; however, they usually have little or no effect on erythema and pruritus. The identification of cytokine alterations in CI raised the possibility of repurposing available biologics. Several case reports in the literature report successes using different biologics. We aimed to report the effects of biologics in real life. This was a retrospective, observational, international multicenter study of patients with CI treated with at least one biologic for a minimum of 3 months. The effect of the biologics was evaluated using an Investigator Global Assessment-Change (IGA-C) scale. A comprehensive literature search was performed in parallel. A total of 98 patients were included, with a mean age of 19.7 years and both sexes equally represented. Patients with Netherton syndrome (NS) or congenital ichthyosiform erythroderma (CIE) represented the majority of patients (30% and 21.4%, respectively). Most patients (84.7%) had a severe or very severe form of CI. The most frequently used biologics were inhibitors targeting interleukin-17 (IL-17), IL-12/IL-23, or the IL-4 receptor. The mean duration of treatment was 22+20.1 months. There were 45 responders (45.9%), including 18 patients (18.3%) who were good responders; all had an erythrodermic CI subset and received one of the three main biologics. In 2 NS and CIE, IL-12/IL-23 and IL-4 receptor inhibitors tended to be most effective. Review of the literature revealed a shorter mean duration of use of biologics (11.5+8.5 months) and higher percentage of responders (85.7%), suggesting reporter bias. This series identified subsets of CI that may respond to biologics and will aid in designing future clinical trials of biologics for CI.

Modern heart failure treatment is superior to conventional treatment across the left ventricular ejection spectrum: Real-life data from the Swedish Heart Failure Registry 2013-2020

Abstract Background Heart failure (HF) is a clinical syndrome characterized by high mortality and morbidity. In 2016, Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), was recommended as a new treatment option for HF in patients with HFrEF. In the 2021 European Society of Cardiology guidelines for treatment of HFrEF patients Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were introduced because they demonstrated significantly reduced HF events or cardiovascular (CV) mortality. Since ARNI and SGLT2i were introduced to treat HF, its therapeutic regimen has modernized from previous treatment with beta-blocker (BB) and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) with mineralocorticoid receptor antagonist (MRA) as added-on in HF with reduced ejection fraction (HFrEF). Purpose This study is aimed to compare effectiveness of modern therapy including ARNI and SGLT2i with conventional heart failure treatment. Conventional HF treatment includes (BB, ACEi/ARB, with or without MRA) and modern heart failure treatment (BB, ACEi/ARB, MRA, SGLT2i or BB, ARNI, MRA with/without SGLT2i) in real-world. Methods This observational study (2013-2020), using the Swedish HF Registry, involved 20,849 HF patients. Patients received either conventional (BB, ACEi/ARB, with/without MRA, n=20,140) or modern (BB, ACEi/ARB, MRA, SGLT2i or BB, ARNI, MRA with/without SGLT2i, n=709) treatment at the index visit. The endpoints were all-cause and cardiovascular (CV) mortality. Results Modern HF therapy was associated with a significant 28% reduction in all-cause mortality compared to conventional HF treatment (adjusted HR [aHR]: 0.72 (95% CI 0.54 - 0.96), p=0.024), and had 33% reduced all-cause mortality (aHR: 0.67 (95% CI 0.48 - 0.94), p=0.019) within 2 years of index registration. Similarly, modern HF therapy was associated with a significant 62% reduction in CV mortality compared to conventional HF treatment (aHR: 0.38 (95% CI 0.21 - 0.68), p=0.0013). In addition, we found a 58% reduced CV mortality (aHR 0.42 (95% CI 0.22 - 0.79), p=0.0067) within 2 years of index registration. In the propensity score 1:1 matched cohort in which ARNI was included in the matching procedure, i.e., no ARNI was used in any of the two treatment groups and the effect of SGLT2i was the target assessment. The results were associated with a statistically significant risk reduction of 42% in all-cause mortality in the modern HF treatment group compared to the conventional treatment group (aHR: 0.58 (95% CI 0.36 - 0.94), p=0.028), and a 49% (aHR: 0.51 (95% CI 0.29 - 0.89), p=0.018) risk reduction within 2 years of index registration. Conclusion This study demonstrates that modern HF therapy in a real-world Swedish HF population is associated with a statistically significant risk reduction in all-cause and CV mortality, regardless of EF, sex, age, eGFR, and etiology of HF compared to conventional HF therapy.Central Illustration

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.

Unravel novel therapeutic targets in heart failure and associated pulmonary hypertension

Abstract Background Heart Failure (HF) is a complex clinical syndrome with poor prognosis. Pulmonary hypertension (PH) often complicates HF but can hardly be addressed therapeutically. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with HF. Whether SGLT2i positively impact on HF-associated PH is poorly understood. Omics offer great promise in the discovery of novel biomarkers and therapeutic targets for HF and PH. Aims We investigated novel markers associated with HF and PH, as well as how these biomarkers vary in response to HF-modyfing therapies, including SGLT2i. We also explored the impact of SGLT2i, compared with conventional anti-HF therapy, on HF-associated PH and right ventricular function. Methods Seventy-four patients with HF and reduced ejection fraction (HFrEF) with/without diabetes were divided into a gliflozin (G)-group receiving 10 mg/day empagliflozin or dapagliflozin, and a control (C)-group receiving conventional anti-HF therapy. Resting echocardiography, analyses on senescence markers [leucocyte telomere length (LTL), mitochondrial DNA copy number (mtDNAcn)], as well as measurement of two microRNAs (miRNA-21 and miRNA-92, recently implicated in response to treatment in HFpEF patients), were performed. Shotgun proteomic analyses were conducted on peripheral blood mononuclear cells. Results Compared to group C, group G had a significantly higher ejection fraction (EF, 42±13 vs 33±8, p=0.001), reduced left ventricular filling pressures (11±3 vs 15±5, p=0.001), reduced pulmonary artery systolic pressure (PAPs, 31±11 vs 46±15, p=0.001), better right ventricular-pulmonary artery coupling index (0.64±0.31 vs 0.44±0.22, p=0.002), increased LTL (Figure 1 A), higher mtDNAcn (Figure 1 B), reduced miRNA-21 levels (Figure 1 C) and no significant changes of miRNA-92 (Figure 1 D). Functional proteomic analysis showed that, compared with the C-group, the protein cargo from the G-group was able to trigger several biological pathways, showing a significant activation of T lymphocytes immune response (p-value=9.67x10-06, z-score=2.21) chemotaxis of monocytes (p-value=9.39x10-07, z-score=2.0), leukocytes (p-value=9.67x10-10, z-score=2.0)and phagocytes (p-value)=3.10x10-10, z-score=2.03) (Figure 2). Compared with the C-group, the G-group showed a downregulation of activin signaling pathway (z-score=-2.12), which is a novel therapeutic target in pulmonary arterial hypertension (PAH). Conclusions In HF patients, SGLT2i therapy is associated with improved left ventricular function and improved pulmonary hemodynamics. Activin is overactive in HF patients and its serum levels may be reduced by SGLT2i. SGLT2i may preserve LTL and mtDNA-cn as well as modulate the expression of specific miRNA implied in the regulation of endothelial function. SGLT2i may represent an additional therapeutic tool in patients with HF-associated PH, an area with no approved treatment options beyond traditional HF therapy.Figure 1:genomic analysesFigure 2:proteomic analyses

Assessing the predictive value of intraductal carcinoma of the prostate (IDC-P) in determining abiraterone efficacy for metastatic hormone-sensitive prostate cancer (mHSPC) patients.

This study explored the value of intraductal carcinoma of the prostate (IDC-P) in predicting the efficacy of abiraterone treatment in metastatic hormone-sensitive prostate cancer (mHSPC) patients. A retrospective study of 925 patients who underwent prostate biopsies to detect IDC-P was conducted, with participants divided into two cohorts. The first cohort of 165 mHSPC patients receiving abiraterone treatment was analyzed to compare therapeutic effectiveness between IDC-P positive and negative cases. Utilizing propensity score matching (PSM) to reduce bias, outcomes such as PSA response, progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival were assessed. Additionally, the second cohort of 760 mHSPC patients compared the efficacy of abiraterone with conventional hormone therapy, focusing on differences between IDC-P positive and negative individuals. After PSM, our first cohort included 108 patients with similar baseline characteristics. Among them, 50% (54/108) were diagnosed with IDC-P, with 22.2% (12/54) having IDC-P pattern 1 and 77.8% (42/54) with IDC-P pattern 2. While no notable difference was seen in PSA responses between IDC-P positive and negative patients, IDC-P presence linked to worse clinical outcomes (PSA-PFS: 18.6 months vs. not reached [NR], p = 0.009; rPFS: 23.6 months vs. NR, p = 0.020). Further analysis showed comparable outcomes for IDC-P pattern 1 but significantly worse prognosis for IDC-P pattern 2 (PSA-PFS: 18.6 months vs. NR, p = 0.002; rPFS: 22.4 months vs. NR, p = 0.010). Subgroup analysis revealed IDC-P pattern 2 consistently predicted poorer outcomes across patient subgroups. Remarkably, both IDC-P positive and negative patients gained more from androgen deprivation therapy with abiraterone than conventional treatment, with IDC-P negative patients showing a more significant survival advantage, supported by better hazard ratios (0.47 and 0.66). This study found that IDC-P, especially pattern 2, predicts poor prognosis in mHSPC patients on abiraterone therapy. Also, abiraterone's advantage over hormone therapy is reduced in cases with IDC-P compared to those without.

Optimisation of cone beam CT radiotherapy imaging protocols using a novel 3D printed head and neck anthropomorphic phantom

Objective.This study aimed to optimise Cone Beam Computed Tomography (CBCT) protocols for head and neck (H&N) radiotherapy treatments using a 3D printed anthropomorphic phantom. It focused on precise patient positioning in conventional treatment and adaptive radiotherapy (ART).Approach.Ten CBCT protocols were evaluated with the 3D-printed H&N anthropomorphic phantom, including one baseline protocol currently used at our centre and nine new protocols. Adjustments were made to milliamperage and exposure time to explore their impact on radiation dose and image quality. Additionally, the effect on image quality of varying the scatter correction parameter for each of the protocols was assessed. Each protocol was compared against a reference CT scan. Usability was assessed by three Clinical Scientists using a Likert scale, and statistical validation was performed on the findings.Main results. The work revealed variability in the effectiveness of protocols. Protocols optimised for lower radiation exposure maintained sufficient image quality for patient setup in a conventional radiotherapy pathway, suggesting the potential for reducing patient radiation dose by over 50% without compromising efficacy. Optimising ART protocols involves balancing accuracy across brain, bone, and soft tissue, as no single protocol or scatter correction parameter achieves optimal results for all simultaneously.Significance.This study underscores the importance of optimising CBCT protocols in H&N radiotherapy. Our findings highlight the potential to maintain the usability of CBCT for bony registration in patient setup while significantly reducing the radiation dose, emphasizing the significance of optimising imaging protocols for the task in hand (registering to soft tissue or bone) and aligning with the as low as reasonably achievable principle. More studies are needed to assess these protocols for ART, including CBCT dose measurements and CT comparisons. Furthermore, the novel 3D printed anthropomorphic phantom demonstrated to be a useful tool when optimising CBCT protocols.

Clinical Observation of the Therapeutic Effects of Wenzhong Hewei Formula in Treating Spleen and Stomach Qi Deficiency Syndrome in Internal Medicine Diseases

Objective: To observe the clinical efficacy and safety of Wenzhong Hewei Formula in treating spleen and stomach qi deficiency syndrome in internal medicine diseases. Methods: Sixty patients with spleen and stomach qi deficiency syndrome admitted to the hospital from April 2022 to June 2023 were randomly divided into observation and control groups, with 30 patients in each group. The control group received conventional internal medicine treatment, while the observation group was additionally treated with Wenzhong Hewei Formula on the basis of conventional treatment. Both groups were treated for 4 weeks. Results: The total effective rate of treatment in the observation group was higher than that of the control group (P < 0.05). After treatment, the traditional Chinese medicine syndrome scores of both groups were significantly lower than before treatment, with the observation group showing a more pronounced reduction (P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion: Wenzhong Hewei Formula can effectively improve clinical symptoms in patients with spleen and stomach qi deficiency syndrome, enhance clinical efficacy, and have a high level of safety, making it worthy of clinical promotion.

Early improvement in left ventricular microvascular flow post sonothrombolysis is associated with better left ventricular systolic function in st elevation myocardial infarction patients

Abstract Background/Introduction Acute coronary syndromes are the main cause of death worldwide and the timely application of proper therapy is critical for patient outcome. However, even when state of the art treatment is implemented, significant no-reflow phenomenon may occur. In this scenario, sonothrombolysis, which consists of a continuous infusion of an ultrasound-enhancing agent associated with high-energy intermittent ultrasound impulses, may restore cardiac microcirculation and improve left ventricular (LV) systolic function. Purpose We aimed to evaluate LV segmental microvascular flow, LV mechanics and function in patients with ST-elevation myocardial infarction (STEMI) after sonothrombolysis therapy and evaluate whether an early (immediately post percutaneous coronary intervention – PCI or PCI+Sonothrombolysis) improvement in myocardial microvascular flow could predict better LV systolic function at 1-month. Methods STEMI patients receiving conventional treatment (PCI with or without previous fibrinolytic therapy) were randomized to sonothrombolysis (therapy group - TG) or conventional treatment (control group - CG). This study included 143 patients (interim analysis) who compose the HUBBLE I databank (High-intensity Ultrasonic impulses and microbuBBles to Limit the Extent of acute myocardial infarction I) and were randomized from two clinical trials (NCT04732091 and NCT02410330): CG, N=74 and TG, N=69 patients. There were 25 patients treated previously with fibrinolytic therapy (14 in CG and 11 in TG) and the percentage of left anterior descending artery as culprit vessel was similar between groups (59 vs. 54%, P=0.482). Sonothrombolysis was initiated after patient admission to the emergency room and continued after PCI for a total of 50 minutes. Echocardiography was carried out immediately after PCI or PCI+Sonothrombolysis and at 1-month for assessing LV ejection fraction (LVEF) and perfusion score index (PSI) in contrasted imaging and global longitudinal strain (GLS) in 2D imaging, that was presented in [module]. Results Demographic characteristics, cardiovascular risk factors and echocardiographic variables immediately after PCI or PCI+Sonothrombolysis were similar between groups (P>0.05). At 1-month follow up, TG presented higher LVEF (46.4±10.5 vs. 50.9±11.1%, P=0.018) and GLS (13.0±3.6 vs. 14.9±4.3%, P=0.008) and lower PSI (1.56±0.4 vs. 1.39±0.3, P=0.007) and number of segments with perfusion defects (5.8±3.7 vs. 4.6±3.3, P=0.050) compared with CG. There was a negative correlation between early PSI and 1-month LVEF (r=-0.701, p<0.0001). Conclusions The preliminary data indicates that sonothrombolysis can be an effective adjuvant treatment in STEMI patients previously treated or not with fibrinolytic therapy, contributing to a better myocardial microvascular flow and LV systolic performance. Early myocardial microvascular reperfusion improvement can predict whether cardiac function will improve in this setting.

Biosynthesis of pH-Responsive Mesoporous Silica Nanoparticles from Cucumber Peels for Targeting 3D Lung Tumor Spheroids.

Lung adenocarcinoma is considered to be one of the primary causes of cancer-related deaths globally. Conventional treatments, such as chemotherapy and radiation therapy taken together, have not significantly lowered mortality rates. Repositioning of authorized anticancer medications supported by nanotechnology has therefore emerged as an effective strategy to close such gaps. In this context, mesoporous silica nanoparticles (MSNs) were biosynthesized from cucumber peels and were loaded with doxorubicin, a common anticancer drug to form doxorubicin-bound mesoporous silica nanoparticles (DMSNs). The study addresses a sustainable method for turning waste materials into MSNs, which can be used to create multifunctional nanosystems. The therapeutic module (DMSNs) was designed specifically to target 2D monolayer cells and 3D tumor spheroids of lung adenocarcinoma cancer. The DMSNs demonstrated notable antiproliferative activity and effective intracellular localization in addition to being biocompatible and innately fluorescent. Subsequent investigations revealed significant antibacterial activity against Staphylococcal infection, which is primarily prevalent in lung cancer patients. Thus, the developed MSNs held promising potential for anticancer drug delivery systems and have antibacterial potential to treat bacterial infections in patients with lung cancer. Furthermore, the cucumber peel-mediated synthesis of MSNs could also aid in the management of food waste and promote the adoption of the waste-to-health paradigm for sustainable solutions.

The implementation of modern guideline-directed medical therapy among hospitalized patients with heart failure with reduced ejection fraction: real-world experience from two tertiary cardiac centers

Abstract Background According to the 2021 ESC HF Guidelines (GLs), the conventional triple therapy (TT) (RASi+βB+MRA) of HFrEF has been supplemented with the SGLT2 inhibitor dapa- and empagliflozin as the fourth pillar of the foundational quadruple therapy (QT) recommended for all HFrEF patients. Aim To assess the changes in the implementation of GDMT and investigate its impact on the prognosis among hospitalized HFrEF patients in light of the 2021 HF GLs. Patients and methods A retrospective data analysis of a consecutive cohort of HFrEF patients hospitalized due to HF between 01/01/2019 and 31/12/2023 at two tertiary cardiac centers was performed. Patients were classified into two groups: those hospitalized before and those after the publication of the 2021 ESC HF GLs (27/08/2021). Differences in the implementation of the drug therapy were analysed using the Chi-square test. 1-year all-cause mortality (ACM) was compared using Kaplan-Meier method and log-rank test. The independent predictors of the 1-year ACM were investigated with uni-, and multivariate Cox-regression analysis. Results A total cohort of 560 patients (male: 76%, age: 63 [51-72] years, coronary artery disease: 46%, diabetes: 38%, atrial fibrillation: 44%, LVEF: 25 [20-30]%, eGFR: 57 [43-74]mL/min/1.73m²; NT-proBNP: 5574 [2529-10960]pg/mL) was treated with a high proportion of TT (80%) and with QT (TT + SGLT2i) in 34% at discharge. After the publication of the 2021 ESC HF GLs, the proportion of patients on these SGTL2is improved (10% vs 57%, p<0.001; in the group before vs. after the publication of the GLs), resulting in an increased proportion of patients on QT (10% vs. 52%, p<0.001). There was no significant difference between groups regarding the use of TT (6% vs. 3%) or QT (1% vs. 3%) at target doses. The 1-year ACM was more favourable for those receiving QT (non-QT and non-TT: 41% vs. TT: 16% vs. QT: 11%, p<0.001). According to the multivariate Cox-regression analysis, older age, and more advanced left ventricular systolic dysfunction proved to be negative independent predictors of 1-year ACM, while "de novo" diagnosis of HFrEF and the application of TT/QT (adjusted HR: 0.303, 95% CI: 0.207-0.445, p<0.001) resulted in better outcomes. Conclusions The 2021 ESC HF GLs have led to a breakthrough regarding the modern drug treatment recommended for all patients in HFrEF. Our results demonstrated that the introduction of SGLT2is and the use of QT was feasible even in the everyday practice among complex, multimorbid HFrEF patients requiring hospitalization and the implementation of TT/QT was accompanied by a better prognosis.

Effect of catheter ablation vs medical therapy on cardiovascular outcomes in hypertrophic cardiomyopathy with atrial fibrillation

Abstract Background Atrial fibrillation (AF) increases the risks of stroke and mortality. AF ablation in patients with heart failure (HF) was associated with a lower risk of death and hospitalisation for worsening HF. Whether AF ablation is beneficial to improve cardiovascular outcomes in patients with concomitant hypertrophic cardiomyopathy (HCM) and AF remains unclear. Objective To investigate whether AF ablation is more effective than conventional medical therapy for improving outcomes in HCM. Methods 2,281 patients with HCM and AF undergoing catheter ablation or medical therapy (antiarrhythmic drugs or rate control drugs) in 2005–2015 were identified from the Korean National Health Insurance Service database. The primary composite outcome of death from cardiovascular causes, ischaemic stroke, hospitalization for worsening HF, or acute myocardial infarction was compared between catheter ablation and medical therapy using propensity score overlap weighting. The time-at-risk was counted from the first medical therapy, and catheter ablation was analysed as a time-varying exposure. Results Of the included (41.1% female; median age: 66 years), 145 (6.1%) underwent catheter ablation for AF during the study period. During a mean follow-up of 3.1 (IQR 1.3–5.8) years, a total of 831 composite outcomes occurred including 292 cardiovascular deaths and 401 strokes. Catheter ablation, compared with medical therapy, was associated with lower risks of the primary composite outcome (weighted incidence rate: 3.84 vs. 6.43 per 100 person-years; weighted HR 0.61, 95% CI 0.38–0.96) and ischaemic stroke (weighted HR 0.43, 95% CI 0.19–0.97). The association between ablation and a lower risk of composite outcome was more pronounced in cases of ablation success whereas no significant difference was observed in cases of ablation failure. Conclusions In patients with AF and HCM, catheter ablation was associated with a lower risk of adverse cardiovascular outcomes than medical therapy.

Safety and effectiveness of sodium-glucose co-transporter 2 inhibitors in active cancer patients with heart failure: results of the observational TOSCA trial

Abstract Background Sodium-glucose co-transporter 2 inhibitors (SGLT2i) currently represent a pillar of heart failure (HF) treatment. However, cancer patients have not been included in landmark randomized controlled trials (RCTs), and data on safety and effectiveness in this population are lacking. Purpose Purpose of present study was to evaluate safety and effectiveness of SGLT2i in active cancer patients with HF. Methods TOSCA is a multi-centre observational trial including patients (≥ 18 years) with active cancer (diagnosis < 3 years) receiving SGLT2i for HF treatment. Patients were enrolled in two (prospective and retrospective) cohorts. The primary endpoint was safety (incidence of known and unexpected side effects). The secondary endpoint was effectiveness (ejection fraction (EF) increase, New York Heart Association (NYHA) class change, HF-related events). Exploratory endpoints included drug-drug interactions with anticancer and supportive care drugs, treatment of cancer therapy-related cardiac dysfunction (CTRCD), and changes in NT-proBNP. Results Eighty-three pts were enrolled (59 prospective - 24 retrospective). Median age was 71 (range 44-92) yrs, M/F 48/52%. The main cancer sites were breast, gastrointestinal tract, and hematological malignancies. Most cases (62%) received an active treatment (mainly chemotherapy) while on SGLT2i. Prevalent aetiology was drug-induced HF (37%) with reduced EF as the prevalent clinical presentation (39%). Prescribed agents were dapagliflozin in 60% and empagliflozin in 40% of cases on top of conventional guideline-directed medical therapy, with a median treatment duration of 3 (range 3-25) months. The incidence of urinary tract infection was 2.5%. No cases of genital infection, hypoglycemia, diabetic ketoacidosis, acute renal injury, thrombosis, and bone fractures were reported. Mean overall EF slightly increased (44.1% vs. 46.6%), and NYHA class improved (class improvement in 16%). Unplanned cardiology visits (1.2%), i.v. diuretics (1.2%), coronary angiography (5%), emergency access (2.5%), and new HF episodes (3.7%) rates were low. SGLT2i appeared effective in 31 cases of CTRCD. A relative reduction in mean NT-proBNP levels (2748 vs 1125pg/mL) was observed. No drug-drug interactions were reported. Conclusions SGLT2i appear to be safe and effective in active cancer patients with HF, with potential cardioprotective effect. No new safety warnings were recorded.

Empagliflozin: unlocking new potentials in heart failure decongestion

Abstract Background Managing acute heart failure (AHF) remains a formidable challenge in cardiology, primarily due to the limitations of conventional decongestive therapies. This study explores the efficacy of Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, in decongestion management for AHF. Methods Conducted in a tertiary care setting, this prospective cohort study involved 450 patients, divided equally into an Empagliflozin group and a control group receiving standard care. The study assessed changes in body weight, clinical congestion scores, hematocrit levels, and NT-proBNP levels as primary outcomes over a period of 90 days. Safety and adverse events related to Empagliflozin were also monitored. Results Empagliflozin led to a significant reduction in body weight (mean difference at Day 15: −1.95 kg, P<0.0001), and clinical congestion scores (mean difference at Day 15: −0.35, P=0.0050). Hematocrit levels increased significantly (mean increase at Day 15: 1.65%, P<0.0001), and NT-proBNP levels showed a more substantial decrease in the Empagliflozin group compared to the placebo. Safety profiles were consistent with previous studies, showing no significant increase in adverse events. Conclusion Empagliflozin demonstrates a substantial improvement in decongestion management in AHF patients, offering a promising alternative to traditional therapies. The findings indicate potential broader applications in heart failure management and support the need for updated clinical guidelines incorporating Empagliflozin as a therapeutic option in AHF.

Post-PCI anticoagulation with unfractionated heparin in acute coronary syndrome: insight from the STOPDAPT-3 trial

Abstract Background The guidelines recommend the post-procedural anticoagulation should be discontinued after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) except for the specific indications.(1) However, these guideline recommendations were not well supported by data, and therefore, post-PCI parental anticoagulation has been commonly implemented in patients with ACS in the previous studies.(2-5) Purpose To clarify the preference and clinical situations of post-PCI unfractionated heparin (UFH) in ACS patients and to explore the influence of post-PCI UFH on cardiovascular and bleeding outcomes. Methods STOPDAPT-3 trial is a randomized controlled trial to demonstrate the efficacy and safety of the aspirin-free prasugrel monotherapy strategy compared to the conventional dual antiplatelet therapy after PCI in patients with high-bleeding risk or ACS.(6) Data on periprocedural heparin use and its doses were vigorously collected. The current study population was the ACS patients enrolled in the STOPDAPT-3 without use of mechanical circulatory support devices. The two co-primary endpoints were the bleeding outcome defined as the BARC 3 or 5 criteria and the cardiovascular outcome defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Outcomes were assessed at 30 days from index PCI. Results Among 4088 ACS study patients, 2339 (57.2%) patients received post-PCI UFH. Median dose of UFH was 7.1 (IQR 6.0-8.8) units/kg/hour and the median duration was 25 (IQR 24-48) hours. As many as 57.7% of patients received 10000 units/day of heparin after PCI irrespective of body weight. STEMI patients more frequently received post-PCI UFH compared to NSTE-ACS (72.3% and 38.8%, P<0.001) and the patients with intraprocedural adverse angiographic findings such as thrombus, slow-flow, no-reflow, or final TIMI flow <=2 also more frequently received post-PCI UFH than those without (67.6% and 47.5%, P<0.001). Post-PCI UFH was associated with a significantly increased risk of bleeding endpoint (4.75% and 2.52%, adjusted HR 1.69 [95%CI 1.15-2.46], P=0.007) and a numerically increased risk of cardiovascular endpoint (3.16% and 1.72%, adjusted HR 1.56 [95%CI 0.98-2.46], P=0.06). Even in the patients with intraprocedural adverse angiographic findings, post-PCI UFH did not show a clear benefit for cardiovascular endpoint (3.15% and 1.72%, adjusted HR 1.73 [95%CI 0.88-3.41]. P=0.11). Conclusion(s) Post-PCI anticoagulation with UFH was frequently implemented in ACS patients enrolled in the latest large Japanese clinical trial. Post-PCI UFH use was associated with harm in terms of bleeding without a benefit in reducing cardiovascular events.