Immuno-related cardio-vascular adverse events associated with immuno-oncological treatments: an under-estimated threat for cancer patients.

Immunotherapy represents an emergent and heterogeneous group of anticancer treatments harnessing the human immune-surveillance system, including immune-checkpoint inhibitor monoclonal antibodies (mAbs), Chimeric Antigen Receptor T Cells (CAR-T) therapy, cancer vaccines and lymphocyte activation gene-3 (LAG-3) therapy. While remarkably effective against several malignancies, these therapies, often in combination with other cancer treatments, have showed unforeseen toxicity, including cardiovascular complications. The occurrence of immuno-mediated adverse (irAEs) events has been progressively reported in the last 10 years. These irAEs present an extended range of severity, from self-limiting to life-threatening conditions. Although recent guidelines in CardioOncology have provided important evidence in managing cancer treatments, they often encompass general approaches. However, a specific focus is required due to the particular etiology, unique risk factors, and associated side effects of immunotherapy. This review aims to deepen the understanding of the prevalence and nature of cardiovascular issues in patients undergoing immunotherapy, offering insights into strategies for risk stratification and management.

Changes of intracardiac flow dynamics measured by HyperDoppler in patients with aortic stenosis.

Aims: Assessment of intracardiac flow dynamics has recently acquired significance due to the development of new measurement methods based on echocardiography. Recent studies have demonstrated that cardiac abnormalities are associated with changes in intracardiac vortical flows. Yet, no previous study assessed the impact of aortic stenosis (AS) on intracardiac vortices. This study aims to explore the clinical potential of additional information provided by quantifying intracardiac flow dynamics in patients with AS. Methods and results: One hundred and twenty patients with severe AS, sixty patients with concentric ventricular remodelling (VR), and hundred controls (CTRL) were prospectively included and underwent non-invasive evaluation of intracardiac flow dynamics. In addition to standard echocardiography, fluid dynamics were assessed by means of HyperDoppler. Vortex depth (P < 0.001), vortex length (P = 0.003), vortex intensity (P < 0.001), and vortex area (P = 0.049) were significantly increased in AS compared with CTRL. In addition, mean energy dissipation was significantly higher in AS compared with CTRL (P < 0.001) and VR (P = 0.002). At receiver operating characteristic analysis, vortex depth showed the best discrimination capacity for AS (P < 0.001). Conclusion: Changes in fluid dynamics-based HyperDoppler indices can be reliably assessed in patients with AS. Significant changes in vortex depth and intensity can selectively differentiate AS from both concentric remodelling and healthy CTRLs, suggesting that the assessment of intracardiac flow dynamics may provide complementary information to standard echocardiography to better characterize patients' subsets.

The Role of Coronary Imaging in Chronic Total Occlusions: Applications and Future Possibilities.

Chronic total occlusions (CTOs) represent a challenging scenario in coronary artery disease (CAD). The prevalence of CTOS in patients undergoing coronary angiography underscores the need for effective diagnostic and therapeutic strategies. Coronary angiography, while essential, offers limited insights into lesion morphology, vessel course, and myocardial viability. In contrast, coronary imaging techniques-including optical coherence tomography (OCT), intravascular ultrasound (IVUS), and coronary computed tomography angiography (CCTA)-provide comprehensive insights for each stage of CTO percutaneous coronary intervention (PCI). OCT facilitates the assessment of plaque morphology and stent optimization, despite low evidence and several limitations in CTO-PCI. IVUS offers deeper penetration, allowing managing proximal cap scenarios and guiding subintimal navigation. CCTA provides a non-invasive, three-dimensional view of coronary anatomy, enabling the precise evaluation of myocardial mass at risk and detailed procedural planning. Despite their individual limitations, these imaging modalities have enhanced the success rates of CTO-PCI, thus reducing procedural and long-term complications and improving patient outcomes. The future of CTO management lies in further technological advancements, including hybrid imaging, artificial intelligence (AI) integration, and improved fusion imaging. These innovations promise to refine procedural precision and personalize interventions, ultimately improving the care of patients with complex coronary artery disease.

Percutaneous coronary revascularization versus medical therapy in chronic coronary syndromes: An updated meta-analysis of randomized controlled trials.

INTRODUCTION: Coronary artery disease (CAD) is a main cause of morbidity and mortality. The effectiveness of coronary revascularization in chronic coronary syndromes (CCS) is still debated. Our recent study showed the superiority of coronary revascularization over optimal medical therapy (OMT) in reducing cardiovascular (CV) mortality and myocardial infarction (MI). The recent publication of the ORBITA-2 trial suggested superiority of percutaneous coronary revascularization (PCI) in reducing angina and improving quality of life. Therefore, we aimed to provide an updated meta-analysis evaluating the impact of PCI on both clinical outcomes and angina in CCS. METHODS: Relevant studies were screened in PubMed/Medline until 08/01/2024. Randomized controlled trials (RCTs) comparing PCI to OMT in CCS were selected. The primary outcome was CV death. Secondary outcomes were MI, all-cause mortality, stroke, major bleeding and angina severity. RESULTS: Nineteen RCTs involving 8616 patients were included. Median follow-up duration was 3.3 years. Revascularization significantly reduced CV death (4.2% vs. 5.5%; OR = .77; 95% CI .62-.96, p = .02). Subgroup analyses favoured revascularization in patients without chronic total occlusions (CTOs) (p = .052) and those aged <65 years (p = .02). Finally, a follow-up duration beyond 3 years showed increased benefit of coronary revascularization (p = .04). Secondary outcomes analyses showed no significant differences, except for a lower angina severity in the revascularization group according to the Seattle Angina Questionnaire (SAQ) (p = .04) and to the Canadian Cardiovascular Society (CCS) classification (p = .005). CONCLUSIONS: PCI compared to OMT significantly reduces CV mortality and angina severity, improving quality of life in CCS patients. This benefit was larger without CTOs, in patients aged <65 years and with follow-up duration beyond 3 years.

Effects of sacubitril-valsartan on aging-related cardiac dysfunction.

Heart failure (HF) remains a huge medical burden worldwide, with aging representing a major risk factor. Here, we report the effects of sacubitril/valsartan, an approved drug for HF with reduced EF, in an experimental model of aging-related HF with preserved ejection fraction (HFpEF). Eighteen-month-old female Fisher 344 rats were treated for 12 weeks with sacubitril/valsartan (60 mg/kg/day) or with valsartan (30 mg/kg/day). Three-month-old rats were used as control. No differential action of sacubitril/valsartan versus valsartan alone, either positive or negative, was observed. The positive effects of both sacubitril/valsartan and valsartan on cardiac hypertrophy was evidenced by a significant reduction of wall thickness and myocyte cross-sectional area. Contrarily, myocardial fibrosis in aging heart was not reduced by any treatment. Doppler echocardiography and left ventricular catheterization evidenced diastolic dysfunction in untreated and treated old rats. In aging rats, both classical and non-classical renin-angiotensin-aldosterone system (RAAS) were modulated. In particular, with respect to untreated animals, both sacubitril/valsartan and valsartan showed a partial restoration of cardioprotective non-classical RAAS. In conclusion, this study evidenced the favorable effects, by both treatments, on age-related cardiac hypertrophy. The attenuation of cardiomyocyte size and hypertrophic response may be linked to a shift towards cardioprotective RAAS signaling. However, diastolic dysfunction and cardiac fibrosis persisted despite of treatment and were accompanied by myocardial inflammation, endothelial activation, and oxidative stress.

Challenge of concomitant thymoma resection and myocardial revascularization: A Case Report.

Myocardial revascularization in patients presenting with an anterior mediastinal mass poses considerable challenges. In this report, we outline two cases involving patients with anterior mediastinal masses who underwent surgical resection alongside concurrent myocardial revascularization. One patient underwent coronary artery bypass graft surgery, while the other was treated by percutaneous coronary intervention with drug-eluting stent placement. Both patients fully recovered from the relative procedures and were discharged within two weeks post-surgery, ultimately diagnosed with thymoma. The concomitant intervention offered the advantage of promptly addressing both conditions, and it was performed safely through a collaborative multidisciplinary effort.

How Patients Feel with Telemedicine Devices as an Enabling Factor for Personalised Medicine: A Preliminary Study.

Telemonitoring tools have become essential in today's healthcare, representing fundamental resources for chronic disease home management supporting early detection of clinical worsening with great reduction of hospitalization costs. Therefore the investigation of the patient compliance is a key enabling point. We aim to assess how patients with chronic coronary syndromes evaluate a telemonitoring device meant for ongoing health monitoring. Twenty-six patients used the device for a week and subsequently filled out a well-designed questionnaire. The survey questions were about the device's ease of use, satisfaction levels, perceived effectiveness, and its influence on the patients' healthcare experiences. This study emphasizes the significance of focusing on patient needs in telemedicine and the importance of addressing these concerns to improve telehealth interventions.

Full-Moon Coronary Calcification as Detected With Computed Tomography Angiography in Chronic Total Occlusion Percutaneous Coronary Intervention.

"Full moon" is a central calcification that occludes the entire vessel on coronary computed tomography angiography (CCTA). We examined the association of full moon calcification as identified by CCTA, on clinical and procedural outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We studied patients who underwent elective CTO-PCI in 2 European centers and had preprocedural CCTA. The primary end point was the inability to cross the lesion and/or the need for extensive debulking techniques. Secondary end points were procedural success, in-hospital cardiac mortality, the need for extensive debulking techniques, myocardial infarction, major adverse cardiac events (defined as in-hospital death, myocardial infarction, and clinically driven target vessel revascularization), and stent thrombosis. Secondary procedural end points included procedural time, fluoroscopy time, number of guidewires and balloons, stent length, number and diameter, and contrast volume. Multivariable logistic regression analysis was performed, identifying potential covariates related to the primary outcome according to knowledge and previous studies. Subsequently, a stepwise selection approach was performed to select factors with the greatest predictive value. Of 140 patients included, 28 (20%) had a full moon calcified CTO plaque. Patients in the full moon group were older and had more cardiovascular risk factors. There was not significant difference in the need for retrograde approach and anterograde dissection and reentry techniques between the full moon group and the other groups (32.1% vs 37.5%, p = 0.59 and 0% vs 1.7%, p = 0.47, respectively). Patients in the full moon group had greater incidence of the primary outcome than did those who did not have full moon morphology (53.5% vs 12.5%, p <0.001). On multivariable analysis that included chronic kidney failure and previous coronary artery bypass surgery, full moon calcification was associated with greater incidence of the primary end point (odds ratio 6.5, 95% confidence interval 2.1 to 20.5, p = 0.001). Moreover, less procedural success (71.4% vs 87.5%, p = 0.03), greater incidence of coronary perforations (14.2% vs 3.5%, p <0.02), and greater procedural (172.5 [118.0 to 237.5] vs 144.0 [108.50 to 174.75], p = 0.02) and fluoroscopic time (62.6 [38.1 to 83.0] vs 42.8 [29.5 to 65.7], p = 0.03) were observed in the full moon group. Overall major adverse cardiac events did not differ between the 2 groups (1 patient in the full moon group vs 1 patient in the non-full moon group; 3.5% vs 0.8%, p = 0.29). In conclusion, full moon calcification on CCTA was independently associated with procedural complexity and adverse outcomes in CTO-PCI.

Mechanisms of Cardiovascular Calcification and Experimental Models: Impact of Vitamin K Antagonists.

Cardiovascular calcification is a multifactorial and complex process involving an array of molecular mechanisms eventually leading to calcium deposition within the arterial walls. This process increases arterial stiffness, decreases elasticity, influences shear stress events and is related to an increased risk of morbidity and mortality associated with cardiovascular disease. In numerous in vivo and in vitro models, warfarin therapy has been shown to cause vascular calcification in the arterial wall. However, the exact mechanisms of calcification formation with warfarin remain largely unknown, although several molecular pathways have been identified. Circulating miRNA have been evaluated as biomarkers for a wide range of cardiovascular diseases, but their exact role in cardiovascular calcification is limited. This review aims to describe the current state-of-the-art research on the impact of warfarin treatment on the development of vascular calcification and to highlight potential molecular targets, including microRNA, within the implicated pathways.

Underlying mechanisms and cardioprotective effects of SGLT2i and GLP-1Ra: insights from cardiovascular magnetic resonance.

Originally designed as anti-hyperglycemic drugs, Glucagon-Like Peptide-1 receptor agonists (GLP-1Ra) and Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated protective cardiovascular effects, with significant impact on cardiovascular morbidity and mortality. Despite several mechanisms have been proposed, the exact pathophysiology behind these effects is not yet fully understood. Cardiovascular imaging is key for the evaluation of diabetic patients, with an established role from the identification of early subclinical changes to long-term follow up and prognostic assessment. Among the different imaging modalities, CMR may have a key-role being the gold standard for volumes and function assessment and having the unique ability to provide tissue characterization. Novel techniques are also implementing the possibility to evaluate cardiac metabolism through CMR and thereby further increasing the potential role of the modality in this context. Aim of this paper is to provide a comprehensive review of changes in CMR parameters and novel CMR techniques applied in both pre-clinical and clinical studies evaluating the effects of SGLT2i and GLP-1Ra, and their potential role in better understanding the underlying CV mechanisms of these drugs.

Postpartum Depression and Inflammatory Biomarkers of Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio, and Monocyte-Lymphocyte Ratio: A Prospective Observational Study.

OBJECTIVES: Postpartum depression (PPD) is a severe mental health disorder affecting a significant proportion of mothers, often undiagnosed and untreated, with potential long-term effects. While numerous studies have identified risk factors for PPD, the relationship between inflammatory markers and PPD remains unknown. This study aimed to investigate the potential correlation between indirect inflammatory markers, specifically neutrophil-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR), and the risk of developing PPD, assessed by the Edinburgh Postnatal Depression Scale (EPDS). DESIGN: This was a prospective observational study conducted in a second-level university hospital, from December 2019 to February 2021. PARTICIPANTS: A total of 211 full-term pregnant women were enrolled. Exclusion criteria included specific psychiatric diagnoses, such as severe intellectual disability, schizophrenia, schizoaffective disorder, delusional disorder, bipolar or other unspecified psychotic spectrum disorders. Additionally, pregnancies affected by gestational and pregestational diabetes, chronic hypertension, gestational hypertension, preeclampsia/eclampsia, intrauterine fetal growth restriction, preterm delivery, multiple pregnancies, and fetal abnormalities detected prenatally were excluded. METHODS: Socio-demographic and clinical data were recorded. Blood samples for complete blood count were obtained at hospital admission, focusing on NLR, PLR, and MLR. Analyses were conducted in our laboratory using standard techniques. The postpartum PPD evaluation was conducted 3 days after delivery, with the EPDS Italian version. Statistical analyses included descriptive statistics, group comparisons using t tests or Wilcoxon rank-sum tests for continuous variables, and Pearson χ2 or Fisher's exact tests for categorical variables. Correlation analyses employed Pearson correlation or Spearman's rank correlation tests. Simple logistic regression models, adjusted for various baseline patient characteristics, explored the correlation between inflammatory markers (PLR, NLR, MLR) and postpartum depressive symptoms. Version 4.1.3 of RStudio statistical software was utilized. RESULTS: Overall, 211 pregnant women enrolled were categorized into two groups based on the EPDS scores: <10 (176 patients) and ≥10 (35 patients). The two groups demonstrated homogeneity in different socio-demographic factors. Stepwise regression analysis indicated that PLR, NLR, and MLR were not significantly associated with these variables. The scatterplot of PLR, NLR, and MLR on EPDS was stratified for EPDS groups. The Wilcoxon rank-sum test applied to PLR, NLR, and MLR values and EPDS groups did not reveal a statistical relationship. Additional analyses were conducted using the estimated odds ratios of the logistic regression model on EPDS groups, considering both continuous and binary values of indirect inflammatory markers (PLR, NLR, MLR). The results indicated the absence of a statistical relationship. LIMITATIONS: Our evaluation was restricted to the postpartum period, and data for the first and second trimesters of pregnancy are lacking. CONCLUSIONS: Our findings did not evidence a correlation between indirect inflammatory markers (NLR, PLR, and MPL) and PPD. This novel finding prompts further evaluation of the role of indirect inflammatory markers in PPD, highlighting the need for additional research to clarify the complex relationship between inflammation and psychological health in the postpartum period.

Glucagon-like Peptide-1 Receptor Agonists and Suicidal Ideation: Analysis of Real-Word Data Collected in the European Pharmacovigilance Database.

BACKGROUND: A potential risk of suicide associated with liraglutide or semaglutide treatments has recently emerged. Therefore, we decided to investigate the reporting probability of suicidal events among glucagon-like peptide-1 receptor agonists (GLP-1 RAs). METHODS: A retrospective pharmacovigilance study of the European Pharmacovigilance database was conducted for the period from 1 January 2018 to 10 July 2023. Disproportionality analyses (reporting odds ratio, ROR) were performed to assess the reporting probability of suicidal events among GLP-1 RAs. RESULTS: A total of 230 reports of suicidal events were identified. The most reported GLP-1 RA was liraglutide (38.3%), followed by semaglutide (36.5%) and dulaglutide (16.1%). The most reported events were suicidal ideation (65.3%) and suicide attempt (19.5%). Disproportionality analysis found a higher reporting probability of suicidal events for semaglutide than dulaglutide (ROR, 2.05; 95%CI, 1.40-3.01) and exenatide (ROR, 1.81; 95%CI, 1.08-3.05). In the same way, liraglutide was associated with a higher reporting probability of suicidal events than dulaglutide (ROR, 3.98; 95%CI, 2.73-5.82) and exenatide (ROR, 3.52; 95%CI, 2.10-5.92). On the contrary, a lower reporting probability was found for semaglutide than liraglutide (ROR, 0.51; 95%CI, 0.38-0.69). CONCLUSIONS: Suicidal events were mostly reported with semaglutide and liraglutide, which were also associated with significantly higher reporting probabilities compared to other GLP1 RAs. Although this study provides the reporting frequencies of suicide-related events with GLP-1 RAs, establishing causality requires further investigation, which will probably be addressed by the Pharmacovigilance Risk Assessment Committee of the European Medicine Agency in the future.

(+)-Lipoic acid reduces mitochondrial unfolded protein response and attenuates oxidative stress and aging in an in vitro model of non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a liver disorder characterized by the ac-cumulation of fat in hepatocytes without alcohol consumption. Mitochondrial dysfunction and endoplasmic reticulum (ER) stress play significant roles in NAFLD pathogenesis. The unfolded protein response in mitochondria (UPRmt) is an adaptive mechanism that aims to restore mitochondrial protein homeostasis and mitigate cellular stress. This study aimed to investigate the effects of ( +)-Lipoic acid (ALA) on UPRmt, inflammation, and oxidative stress in an in vitro model of NAFLD using HepG2 cells treated with palmitic acid and oleic acid to induce steatosis. RESULTS: Treatment with palmitic and oleic acids increased UPRmt-related proteins HSP90 and HSP60 (heat shock protein), and decreased CLPP (caseinolytic protease P), indicating ER stress activation. ALA treatment at 1 µM and 5 µM restored UPRmt-related protein levels. PA:OA (palmitic acid:oleic acid)-induced ER stress markers IRE1α (Inositol requiring enzyme-1), CHOP (C/EBP Homologous Protein), BIP (Binding Immunoglobulin Protein), and BAX (Bcl-2-associated X protein) were significantly reduced by ALA treatment. ALA also enhanced ER-mediated protein glycosylation and reduced oxidative stress, as evidenced by decreased GPX1 (Glutathione peroxidase 1), GSTP1 (glutathione S-transferase pi 1), and GSR (glutathione-disulfide reductase) expression and increased GSH (Glutathione) levels, and improved cellular senescence as shown by the markers ß-galactosidase, γH2Ax and Klotho-beta. CONCLUSIONS: In conclusion, ALA ameliorated ER stress, oxidative stress, and inflammation in HepG2 cells treated with palmitic and oleic acids, potentially offering therapeutic benefits for NAFLD providing a possible biochemical mechanism underlying ALA beneficial effects.

Clinical impact of cerebral protection during transcatheter aortic valve implantation.

BACKGROUND: Embolization of debris can complicate transcatheter aortic valve implantation (TAVI) causing stroke. Cerebral embolism protection (CEP) devices can divert or trap debris. PURPOSE: To evaluate the efficacy of CEP during TAVI vs the standard procedure. DATA SOURCES: PubMed, SCOPUS and DOAJ 1/01/2014-04/12/2023. STUDY SELECTION: Randomized and observational studies comparing CEP versus standard TAVI, according to PRISMA. PRIMARY OUTCOME: stroke. SECONDARY OUTCOMES: death, bleeding, vascular access complications, acute kidney injury and infarct area. DATA EXTRACTION: Two investigators independently assessed study quality and extracted data. DATA SYNTHESIS: Twenty-six articles were included (540.247 patients). The primary endpoint was significantly lower (RR = 0.800 95%CI:0.682-0.940; p = 0.007) with CEP. Similarly, death rates were significantly lower with CEP (RR = 0.610 95%CI:0.482-0.771; p < 0.001). No difference was found for bleeding (RR = 1.053 95%CI:0.793-1.398; p = 0.721), vascular complications (RR = 0.937 95%CI:0.820-1.070; p = 0.334) or AKI (RR = 0.982 95%CI:0.754-1.279; p = 0.891). CONCLUSIONS: Use of CEP during TAVI is associated with improved outcomes. Future studies will identify patients who benefit most from CEP.

Commissural alignment during TAVR reduces the risk of overlap to coronary ostia.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) showed safety and efficacy in patients with severe aortic stenosis. Commissural alignment (CA) during TAVR has the potential to reduce the impact of the prostheses on accessibility of coronary arteries, as misalignment of the neocommissures could cause partial overlap with coronary ostia. Therefore, the aim of this study was to investigate the impact of CA on coronary overlap rates. METHODS: We examined the techniques of CA and their impact on coronary access. Eligible studies were searched for on Pubmed, SCOPUS and DOAJ and selected using PRISMA guidelines. The primary endpoint was the incidence of a severe coronary overlap or failed coronary re-access. Results of the analysis are expressed as Risk Ratio (RR) with 95% CI. RESULTS: Four studies were included in this analysis. In these, 681 patients underwent TAVR with CA and 210 underwent TAVR without CA. We examined Evolut valves and Acurate Neo valves. The primary endpoint occurred in 138 patients undergoing TAVR with CA and in 154 patients without CA (RR = 0.279; 95% CI 0.201-0.386; p < 0.001). Neither prosthesis-related, nor patient-related factors had a significant interaction with the measured effect. CONCLUSIONS: Commissural alignment was associated with significantly lower rates of commissure-to-coronary ostia overlap and failure of coronary access. Consequently, a modified insertion technique could reduce coronary overlap and coronary occlusion, particularly in supra-annular valves. Therefore, controlled orientation of prostheses by CA during TAVR could favour coronary access, especially in younger patients that could require coronary re-access after TAVR.

Clinical impact of coronary revascularization over medical treatment in chronic coronary syndromes: A systematic review and meta-analysis.

OBJECTIVE: To provide a quantitative comparison between myocardial revascularization (REVASC) and optimal medical treatment (OMT) alone in patients with chronic coronary syndrome (CCS). METHODS: Pertinent studies were searched for in PubMed/Medline until 12/03/2023. Randomized controlled trials that compare REVASC to OMT reporting clinical outcomes were selected according to PRISMA guidelines. The primary outcome was cardiovascular death. Two investigators independently assessed the study quality and extracted data. RESULTS: Twenty-eight randomized controlled studies (RCTs) including 20692 patients were included in this meta-analysis. The rate of cardiovascular mortality was significantly lower among patients treated with myocardial revascularization [risk ratio (RR) 0.79, 95% CI 0.69-0.90]. Age (p = 0.03), multivessel disease (p < 0.001), and follow-up duration (p = 0.001) were significant moderators of CV mortality. Subgroup analyses showed a larger benefit in patients treated with drug-eluting stents and those without chronic total occlusion. Among secondary outcomes, myocardial infarction was less frequent in the REVASC group (RR = 0.74; p < 0.001), while no significant difference was found for all-cause mortality (p = 0.09) nor stroke (p = 0.26). CONCLUSIONS: The present analysis showed lower rates of CV mortality and myocardial infarction in CCS patients treated with myocardial revascularization compared to OMT. This benefit was larger with increasing follow-up duration. Personalized treatment based on patient characteristics and lesion complexity may optimize clinical outcomes in patients with CCS.

Perspective use of bio-adhesive liquid crystals as ophthalmic drug delivery systems.

The success of many drugs in ophthalmic treatments is hindered by their physico-chemical properties and the limited precorneal retention time. Here, lyotropic liquid crystals are proposed as a new ophthalmic drug delivery system. Acyclovir was chosen as model drug for its solubility and its controlled release from cubic phase was achieved. We demonstrated the effortless application of lamellar phase on corneal surface and its ability to convert itself in cubic phase in situ. While the complex viscosity of lamellar phase was affected by temperature (5.1 ± 1.4 kPa·s at 25 °C and 0.12 ± 0.001 Pa·s at 35 °C, respectively), the cubic phase shown no changes in viscosity values and shear thinning behaviour at both temperatures and even in presence of the drug The degradation kinetic of drug-loaded cubic phase was slightly slower than the empty formulation, recording 27.92 ± 1.43% and 33.30 ± 3.11% of weight loss after 8 h. Ex vivo studies conducted on porcine eyeballs and isolated cornea confirmed the instantaneous transition to cubic phase, its ability to resist to gravity force, and forced dripping of simulated tear fluid. Histopathological investigation showed how treated cornea did not report changes in epithelial and stroma structures. In summary, lyotropic liquid crystals could represent an advantageous ophthalmic drug delivery system.

Clinical and Procedural Outcomes of IVUS-Guided vs. Angiography-Guided CTO-PCI: A Systematic Review and Meta-Analysis.

Chronic total occlusions (CTO) in coronary angiographies present a significant challenge nowadays. Intravascular ultrasound (IVUS) is a valuable tool during CTO-PCI, aiding in planning and achieving procedural success. However, the impact of IVUS on clinical and procedural outcomes in CTO-PCI remains uncertain. This meta-analysis aimed to compare IVUS-guided and angiography-guided approaches in CTO-PCI. The study included five studies and 2320 patients with stable coronary artery disease (CAD) and CTO. The primary outcome of major adverse cardiac events (MACE) did not significantly differ between the groups (p = 0.40). Stent thrombosis was the only secondary clinical outcome that showed a significant difference, favoring the IVUS-guided approach (p = 0.01). Procedural outcomes revealed that IVUS-guided procedures had longer stents, larger diameters, and longer procedure and fluoroscopy times (p = 0.007, p < 0.001, p = 0.03, p = 0.002, respectively). Stent number and contrast volume did not significantly differ between the approaches (p = 0.88 and p = 0.33, respectively). In summary, routine IVUS use did not significantly improve clinical outcomes, except for reducing stent thrombosis. Decisions in CTO-PCI should be individualized based on patient characteristics and supported by a multi-parametric approach.