Efficacy of intravascular lithotripsy (IVL) in coronary stenosis with severe calcification: A multicenter systematic review and meta-analysis.

BACKGROUND: With heavily calcified coronary and peripheral artery lesions, lesion preparation is crucial before stent placement to avoid underexpansion, associated with stent thrombosis or restenosis and patency failure in the long-term. Intravascular lithotripsy (IVL) technology disrupts superficial and deep calcium by using localized pulsative sonic pressure waves, making it to a promising tool for patients with severe calcification in coronary bed. AIMS: The aim of the study is to systematically review and summarize available data regarding the safety and efficacy of IVL for lesion preparation in severely calcified coronary arteries before stenting. METHODS: This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies assessing the characteristics and outcomes of patients undergoing IVL before stent implantation. The diameter of the vessel lumen before and after IVL, as well as stent implantation, were analyzed. The occurrence of major adverse cardiovascular events (MACE) was assessed using a random-effects model. RESULTS: This meta-analysis comprised 38 studies including 2977 patients with heavily calcified coronary lesions. The mean age was 72.2 ± 9.1 years, with an overall IVL clinical success of 93% (95% confidence interval [CI]: 91%-95%, I2 = 0%) and procedural success rate of 97% (95% CI: 95%-98%, I2 = 73.7%), while the in-hospital and 30-days incidence of MACE, myocardial infarction (MI), and death were 8% (95% CI: 6%-11%, I2 = 84.5%), 5% (95% CI: 2%-8%, I2 = 85.6%), and 2% (95% CI: 1%-3%, I2 = 69.3%), respectively. There was a significant increase in the vessel diameter (standardized mean difference [SMD]: 2.47, 95% CI: 1.77-3.17, I2 = 96%) and a decrease in diameter stenosis (SMD: -3.44, 95% CI: -4.36 to -2.52, I2 = 97.5%) immediately after IVL application, while it was observed further reduction in diameter stenosis (SMD: -6.57, 95% CI: -7.43 to -5.72, I2 = 95.8%) and increase in the vessel diameter (SMD: 4.37, 95% CI: 3.63-5.12, I2 = 96.7%) and the calculated lumen area (SMD: 3.23, 95% CI: 2.10-4.37, I2 = 98%), after stent implantation. The mean acute luminal gain following IVL and stent implantation was estimated to be 1.27 ± 0.6 and 1.94 ± 1.1 mm, respectively. Periprocedural complications were rare, with just a few cases of perforations, dissection, or no-reflow phenomena recorded. CONCLUSIONS: IVL seems to be a safe and effective strategy for lesion preparation in severely calcified lesions before stent implantation in coronary arteries. Future prospective studies are now warranted to compare IVL to other lesion preparation strategies.

Enhancement of the biological activity of hydroxytyrosol through its oxidation by laccase from Trametes versicolor.

The laccase-catalyzed oxidation of hydroxytyrosol (HT) towards the formation of its bioactive oligomer derivatives was investigated. The biocatalytic oligomerization was catalyzed by laccase from Trametes versicolor in aqueous or various water-miscible organic solvents and deep eutectic solvent (DES)-based media. Mass Spectroscopy and Nuclear Magnetic Resonance were used for the characterization of the products. The solvent system used significantly affects the degree of HT oligomerization. The use of 50 % v/v methanol favored the production of the HT dimer, while other organic solvents as well as DESs led to the formation of hydroxytyrosol trimer and other oligomers. In vitro studies showed that the HT dimer exhibits 3- to 4-fold enhanced antibacterial activity against Gram-positive and Gram-negative bacteria compared to the parent compound. Moreover, the ability of HT dimer to inhibit the activity of soybean lipoxygenase and Candida rugosa lipase was 1.5-fold higher than HT, while molecular docking supported these results. Furthermore, HT dimer showed reduced cytotoxicity against HEK293 cells and exhibited a strong ability to inhibit ROS formation. The enhanced bioactivity of HT dimer indicates that this compound could be considered for use in cosmetics, skin-care products, and nutraceuticals.

Prevalence of cannabis use disorder and perioperative outcomes in adult colectomy patients: A propensity score-matched analysis.

BACKGROUND: The decriminalization of cannabis across the United States has led to an increased number of patients reporting cannabis use prior to surgery. However, it is unknown whether preoperative cannabis use disorder (CUD) increases the risk of postoperative complications among adult colectomy patients. METHODS: Adult patients undergoing an elective colectomy were retrospectively analyzed from the National Inpatient Sample database (2004-2018). To control for potential confounders, patients with CUD, defined using ICD-9/10 codes, were propensity score matched to patients without CUD in a 1:1 ratio. The association between preoperative CUD and composite morbidity, the primary outcome of interest, was assessed. Subgroup analyses were performed after stratification by age (≥50 years). RESULTS: Among 432,018 adult colectomy patients, 816 (0.19%) reported preoperative CUD. The prevalence of CUD increased nearly three-fold during the study period from 0.8/1000 patients in 2004 to 2.0/1000 patients in 2018 (P-trend<0.001). After propensity score matching, patients with CUD exhibited similar rates of composite morbidity (140 of 816; 17.2%) as those without CUD (151 of 816; 18.5%) (p = 0.477). Patients with CUD also had similar anastomotic leak rates (CUD: 5.64% vs. No CUD: 6.25%; p = 0.601), hospital lengths of stay (CUD: 5 days, IQR 4-7 vs. No CUD: 5 days, IQR 4-7) (p = 0.415), and hospital charges as those without CUD. Similar findings were seen among patients aged ≥50 years in the subgroup analysis. CONCLUSIONS: Though the prevalence of CUD has increased drastically over the past 15 years, preoperative CUD was not associated with an increased risk of composite morbidity among adult patients undergoing an elective colectomy.

Short-Stay Left Colectomy for Colon Cancer: Is It Safe?

BACKGROUND: Advances in surgical practices have decreased hospital length of stay (LOS) after surgery. This study aimed to determine the safety of short-stay (≤24-hour) left colectomy for colon cancer patients in the US. STUDY DESIGN: Adult colon cancer patients who underwent elective left colectomies were identified using the American College of Surgeons NSQIP database (2012 to 2021). Patients were categorized into 4 LOS groups: LOS 1 day or less (≤24-hour short stay), 2 to 4, 5 to 6, and 7 or more. Primary outcomes were 30-day postoperative overall and serious morbidity. Secondary outcomes were 30-day mortality and readmission. Multivariable logistic regression was performed to explore the association between LOS and overall and serious morbidity. RESULTS: A total of 15,745 patients who underwent left colectomies for colon cancer were identified with 294 (1.87%) patients undergoing short stay. Short-stay patients were generally younger and healthier with lower 30-day overall morbidity rates (LOS ≤1 day: 3.74%, 2 to 4: 7.38%, 5 to 6: 16.12%, and ≥7: 37.64%, p < 0.001). Compared with patients with LOS 2 to 4 days, no differences in mortality and readmission rates were observed. On adjusted analysis, there was no statistical difference in the odds of overall (LOS 2 to 4 days: odds ratio 1.90, 95% CI 1.01 to 3.60, p = 0.049) and serious morbidity (LOS 2 to 4 days: odds ratio 0.86, 95% CI 1.42 to 1.76, p = 0.672) between the short-stay and LOS 2 to 4 days groups. CONCLUSIONS: Although currently performed at low rates in the US, short-stay left colectomy is safe for a select group of patients. Attention to patient selection, refinement of clinical pathways, and close follow-up may enable short-stay colectomies to become a more feasible reality.

Direct Oral Anticoagulants use in Patients with Stable Coronary Artery Disease, Acute Coronary Syndrome or Undergoing Percutaneous Coronary Intervention.

The investigation for the optimal anticoagulation strategy for patients with stable coronary artery disease, acute coronary syndromes, and undergoing percutaneous coronary intervention constitutes a great challenge for physicians and is a field of extensive research. Although aspirin is commonly recommended as a protective measure for all patients with coronary artery disease and dual antiplatelet therapy for those undergoing procedures, such as percutaneous coronary intervention or coronary artery bypass graft surgery, the risk of recurrent cardiovascular events remains significant. In this context, the shortcomings associated with the use of vitamin K antagonists have led to the assessment of direct oral anticoagulants as promising alternatives. This review will explore and provide a comprehensive analysis of the existing data regarding the use of direct oral anticoagulants in patients with stable coronary artery disease or acute coronary syndrome, as well as their effectiveness in those undergoing percutaneous coronary intervention or coronary artery bypass graft surgery.

Factors associated with not undergoing surgery for locally advanced rectal cancers: An NCDB propensity-matched analysis.

BACKGROUND: The traditional treatment paradigm for patients with locally advanced rectal cancers has been neoadjuvant chemoradiation followed by curative intent surgery and adjuvant chemotherapy. This study aimed to assess surgery trends for locally advanced rectal cancers, factors associated with forgoing surgery, and overall survival outcomes. METHODS: Adults with locally advanced rectal cancers were retrospectively analyzed using the National Cancer Database (2004-2019). Propensity score matching was performed. Factors associated with not undergoing surgery were identified using multivariable logistic regression. Kaplan-Meier and log-rank tests were used for 5-year overall survival analysis, stratified by stage and treatment type. RESULTS: A total of 72,653 patients were identified, with 64,396 (88.64%) patients undergoing neoadjuvant + surgery ± adjuvant therapy, 579 (0.80%) chemotherapy only, 916 (1.26%) radiation only, and 6,762 (9.31%) chemoradiation only. The proportion of patients who underwent surgery declined over the study period (95.61% in 2006 to 92.29% in 2019, P trend < .001), whereas the proportion of patients who refused surgery increased (1.45%-4.48%, P trend < .001). Factors associated with not undergoing surgery for locally advanced rectal cancers included older age, Black race (odds ratio 1.47, 95% CI 1.35-1.60, P < .001), higher Charlson-Deyo score (score ≥3: 1.79, 1.58-2.04, P < .001), stage II cancer (1.22, 1.17-1.28, P < .001), lower median household income, and non-private insurance. Neoadjuvant + surgery ± adjuvant therapy was associated with the best 5-year overall survival, regardless of stage, in unmatched and matched cohorts. CONCLUSION: Despite surgery remaining an integral component in the management of locally advanced rectal cancers, there is a concerning decline in guideline-concordant surgical care for rectal cancer in the United States, with evidence of persistent socioeconomic disparities. Providers should seek to understand patient perspectives/barriers and guide them toward surgery if appropriate candidates. Continued standardization, implementation, and evaluation of rectal cancer care through national accreditation programs are necessary to ensure that all patients receive optimal treatment.

Impact of preoperative chemotherapy on perioperative morbidity in combined resection of colon cancer and liver metastases.

BACKGROUND: Preoperative chemotherapy, or neoadjuvant therapy (NAC) can be used to improve resectability but can also have hepatotoxic effects on the future liver remnant. The purpose of this study was to investigate the impact of NAC on 30-day morbidity among patients undergoing a resection of primary colon cancer and synchronous liver metastases (sLM). METHODS: This was a retrospective study using the National Surgical Quality Improvement Program database (2012-2020). The association between NAC and 30-day overall morbidity, the primary outcome, was assessed. Subgroup analyses for low and high-risk procedures were performed. RESULTS: Among 968 patients who underwent the combined resection, 571 (58.99%) received NAC. There was a lower rate of 30-day overall morbidity among patients who received NAC (34.50% vs. 41.56%, p = 0.026) and no difference in rates of postoperative liver failure, bile leak, need for invasive intervention for hepatic procedure, and anastomotic leak. On adjusted analyses, patients who received NAC had decreased odds of overall morbidity (OR 0.73, 95% CI 0.55-0.97, p = 0.031) compared to patients who did not receive NAC. On subgroup analyses, patients who received NAC prior to a low risk combined resection had lower rates of overall morbidity on both adjusted and unadjusted analyses. Among those undergoing high-risk combined resections, there was no difference in overall morbidity. DISCUSSION AND CONCLUSION: Patients who are deemed to be candidates for preoperative chemotherapy can proceed with planned neoadjuvant chemotherapy prior to combined resection of primary colon cancer and sLM as preoperative neoadjuvant chemotherapy does not appear to be associated with increased postoperative morbidity.

Global dissemination of minimally invasive living donor hepatectomy: What are the barriers?

Minimally invasive donor hepatectomy (MIDH) is a relatively novel procedure that can potentially increase donor safety and contribute to faster rehabilitation of donors. After an initial period in which donor safety was not effectively validated, MIDH currently seems to provide improved results, provided that it is conducted by experienced surgeons. Appropriate selection criteria are crucial to achieve better outcomes in terms of complications, blood loss, operative time, and hospital stay. Beyond a pure laparoscopic technique, various approaches have been recommended such as hand-assisted, laparoscopic-assisted, and robotic donation. The latter has shown equal outcomes compared to open and laparoscopic approaches. A steep learning curve seems to exist in MIDH, mainly due to the fragility of the liver parenchyma and the experience needed for adequate control of bleeding. This review investigated the challenges and the opportunities of MIDH and the barriers to its global dissemination. Surgeons need expertise in liver transplantation, hepatobiliary surgery, and minimally invasive techniques to perform MIDH. Barriers can be categorized into surgeon-related, institutional-related, and accessibility. More robust data and the creation of international registries are needed for further evaluation of the technique and the acceptance from more centers worldwide.

Cardiac arrest and cardiopulmonary resuscitation in "hostile" environments: Using automated compression devices to minimize the rescuers' danger.

Mechanical automated compression devices are being used in cardiopulmonary resuscitation instead of manual, "hands-on", rescuer-delivered chest compressions. The -theoretical- advantages include high-quality non-stop compressions, thus freeing the rescuer performing the compressions and additionally the ability of the rescuer to stand reasonably away from a potentially "hazardous" victim, or from hazardous and/or difficult resuscitation conditions. Such circumstances involve cardiopulmonary resuscitation (CPR) in the Cardiac Catheterization Laboratory, especially directly under the fluoroscopy panel, where radiation is well known to cause detrimental effects to the rescuer, and CPR during/after land or air transportation of cardiac arrest victims. Lastly, CPR in a coronavirus disease 2019 patient/ward, where the danger of contamination and further serious illness of the health provider is very existent. The scope of this review is to review and present literature and current guidelines regarding the use of mechanical compressions in these "hostile" and dangerous settings, while comparing them to manual compressions.

Colorectal Surgery Outcomes in the United States During the COVID-19 Pandemic.

INTRODUCTION: The purpose of this study was to assess colorectal surgery outcomes, discharge destination, and readmission in the United States during the COVID-19 pandemic. METHODS: Adult colorectal surgery patients in the American College of Surgeons National Surgical Quality Improvement Program database (2019-2020) and its colectomy and proctectomy procedure-targeted files were included. The prepandemic time period was defined from April 1, 2019 to December 31, 2019. The pandemic time period was defined from April 1, 2020 to December 31, 2020 in quarterly intervals (Q2 April-June; Q3 July-September; Q4 October-December). Factors associated with morbidity and in-hospital mortality were assessed using multivariable logistic regression. RESULTS: Among 62,393 patients, 34,810 patients (55.8%) underwent colorectal surgery prepandemic and 27,583 (44.2%) during the pandemic. Patients who had surgery during the pandemic had higher American Society of Anesthesiologists class and presented more frequently with dependent functional status. The proportion of emergent surgeries increased (12.7% prepandemic versus 15.2% pandemic, P < 0.001), with less laparoscopic cases (54.0% versus 51.0%, P < 0.001). Higher rates of morbidity with a greater proportion of discharges to home and lesser proportion of discharges to skilled care facilities were observed with no considerable differences in length of stay or worsening readmission rates. Multivariable analysis demonstrated increased odds of overall and serious morbidity and in-hospital mortality, during Q3 and/or Q4 of the 2020 pandemic. CONCLUSIONS: Differences in hospital presentation, inpatient care, and discharge disposition of colorectal surgery patients were observed during the COVID-19 pandemic. Pandemic responses should emphasize balancing resource allocation, educating patients and providers on timely medical workup and management, and optimizing discharge coordination pathways.

Substrate Specificity of the Highly Thermostable Esterase EstDZ3.

Esterases are among the most studied enzymes, and their applications expand into several branches of industrial biotechnology. Yet, despite the fact that information on their substrate specificity is crucial for selecting or designing the best fitted biocatalyst for the desired application, it cannot be predicted from their amino acid sequence. In this work, we studied the substrate scope of the newly discovered hydrolytic extremozyme, EstDZ3, against a library of esters with variable carbon chain lengths in an effort to understand the crucial amino acids for the substrate selectivity of this enzyme. EstDZ3 appears to be active against a wide range of esters with high selectivity towards medium- to long-carbon chain vinyl esters. In-silico studies of its 3D structure revealed that the selectivity might arise from the mainly hydrophobic nature of the active site's environment.

Sex Differences in Clinical Outcomes of Patients with Stable Coronary Artery Disease after Percutaneous Coronary Intervention.

Potential sex-related differences in the periprocedural and long-term postprocedural outcomes of coronary angioplasty in patients with stable coronary artery disease have been studied thoroughly over the last few decades, to determine whether female sex should be regarded as an independent risk factor that affects clinical outcomes. Based on a significant number of observational studies and meta-analyses, sex has not yet emerged as an independent risk factor for either mortality or major cardiac and cerebrovascular events, despite the fact that in the early 1980s, for several reasons, female sex was associated with unfavourable outcomes. Therefore, it remains debatable whether the female sex should be considered as an independent risk factor for periprocedural and long-term bleeding events. The pharmacological and technological advancements that support current coronary angioplasty procedures, as well as the non-delayed treatment of coronary artery disease in females, have certainly lessened the outcome differences between the two sexes. However, females show fluctuations in blood coagulability through their lifetime and a higher prevalence of bleeding episodes associated with the antithrombotic treatment following transcatheter coronary reperfusion interventions. In conclusion, the clinical results of percutaneous coronary intervention in patients with stable coronary artery disease, during the periprocedural and long-term postprocedural periods, appear to show no significant differences between the two sexes, except for bleeding rates, which seem to be higher in females, a difference that mandates further systematic research.

Cross-Priming Dendritic Cells Exacerbate Immunopathology After Ischemic Tissue Damage in the Heart.

BACKGROUND: Ischemic heart disease is a leading cause of heart failure and despite advanced therapeutic options, morbidity and mortality rates remain high. Although acute inflammation in response to myocardial cell death has been extensively studied, subsequent adaptive immune activity and anti-heart autoimmunity may also contribute to the development of heart failure. After ischemic injury to the myocardium, dendritic cells (DC) respond to cardiomyocyte necrosis, present cardiac antigen to T cells, and potentially initiate a persistent autoimmune response against the heart. Cross-priming DC have the ability to activate both CD4+ helper and CD8+ cytotoxic T cells in response to necrotic cells and may thus be crucial players in exacerbating autoimmunity targeting the heart. This study investigates a role for cross-priming DC in post-myocardial infarction immunopathology through presentation of self-antigen from necrotic cardiac cells to cytotoxic CD8+ T cells. METHODS: We induced type 2 myocardial infarction-like ischemic injury in the heart by treatment with a single high dose of the ß-adrenergic agonist isoproterenol. We characterized the DC population in the heart and mediastinal lymph nodes and analyzed long-term cardiac immunopathology and functional decline in wild type and Clec9a-depleted mice lacking DC cross-priming function. RESULTS: A diverse DC population, including cross-priming DC, is present in the heart and activated after ischemic injury. Clec9a-/- mice deficient in DC cross-priming are protected from persistent immune-mediated myocardial damage and decline of cardiac function, likely because of dampened activation of cytotoxic CD8+ T cells. CONCLUSION: Activation of cytotoxic CD8+ T cells by cross-priming DC contributes to exacerbation of postischemic inflammatory damage of the myocardium and corresponding decline in cardiac function. Importantly, this provides novel therapeutic targets to prevent postischemic immunopathology and heart failure.

Correction to: The mystery of "missing" visits in an emergency cardiology department, in the era of COVID-19.; a time-series analysis in a tertiary Greek General Hospital.

The original version of this article unfortunately contained a mistake.

The mystery of "missing" visits in an emergency cardiology department, in the era of COVID-19.; a time-series analysis in a tertiary Greek General Hospital.

BACKGROUND: In the era of the current COVID-19 health crisis, the aim of the present study was to explore population behavior as regards the visits in the Εmergency Cardiology department (ECD) of a tertiary General Hospital that does not hospitalize SARS-CoV-2 infected patients METHODS AND RESULTS: Daily number of visits at the EDC and admissions to Cardiology Wards and Intensive Care Unit of a tertiary General Hospital, in Athens, Greece, were retrieved from hospital's database (January 1st-April 30th 2018, 2019 and 2020). A highly significant reduction in the visits at ECD of the hospital during March and April 2020 was observed as compared with January and February of the same year (p for linear trend < ·001); in particular the number of visits was 41.1% lower in March 2020 and 32.7% lower in April 2020, as compared to January 2020. As the number of confirmed COVID-19 cases throughout the country increased (i.e., from February 26th to April 2nd) the number of visits at ECD decreased (p = 0.01), whereas, the opposite was observed in the period afterwards (p = 0.01).The number of acute Myocardial infarctions (MI) cases in March 2020 was the lowest compared to the entire three year period (p < 0·001); however, the number of acute MI cases in April 2020 was doubled as compared to March 2020, but still was lower than the preceding years (p < 0·001). CONCLUSIONS: It is hard to explain the mystery of the "missing" emergency hospital visits. However, if this decline in cardiovascular disease related hospital visits is "true", it is something that needs to be rigorously studied, to learn how to keep these rates down.

Characterization of acute TLR-7 agonist-induced hemorrhagic myocarditis in mice by multiparametric quantitative cardiac magnetic resonance imaging.

Hemorrhagic myocarditis is a potentially fatal complication of excessive levels of systemic inflammation. It has been reported in viral infection, but is also possible in systemic autoimmunity. Epicutaneous treatment of mice with the Toll-like receptor 7 (TLR-7) agonist Resiquimod induces auto-antibodies and systemic tissue damage, including in the heart, and is used as an inducible mouse model of systemic lupus erythematosus (SLE). Here, we show that overactivation of the TLR-7 pathway of viral recognition by Resiquimod treatment of CFN mice induces severe thrombocytopenia and internal bleeding, which manifests most prominently as hemorrhagic myocarditis. We optimized a cardiac magnetic resonance (CMR) tissue mapping approach for the in vivo detection of diffuse infiltration, fibrosis and hemorrhages using a combination of T1, T2 and T2* relaxation times, and compared results with ex vivo histopathology of cardiac sections corresponding to CMR tissue maps. This allowed detailed correlation between in vivo CMR parameters and ex vivo histopathology, and confirmed the need to include T2* measurements to detect tissue iron for accurate interpretation of pathology associated with CMR parameter changes. In summary, we provide detailed histological and in vivo imaging-based characterization of acute hemorrhagic myocarditis as an acute cardiac complication in the mouse model of Resiquimod-induced SLE, and a refined CMR protocol to allow non-invasive longitudinal in vivo studies of heart involvement in acute inflammation. We propose that adding T2* mapping to CMR protocols for myocarditis diagnosis improves diagnostic sensitivity and interpretation of disease mechanisms.This article has an associated First Person interview with the first author of the paper.

Impact of Valve Over-Sizing After Transcatheter Aortic Valve Implantation With a Self-Expanding Valve: A Multislice Computed Tomography Study.

BACKGROUND: In transcatheter aortic valve implantation (TAVI), prosthesis over-sizing prevents paravalvular leak (PVL). Strategies of over-sizing for self-expanding bioprostheses are not well established at present. METHODS: Patients with aortic valve stenosis scheduled for TAVI underwent preprocedural multislice computed tomography. Based on the degree of over-sizing, a ROC curve was drawn to define the optimal value of valve sizing for reducing PVL after TAVI. RESULTS: A total of 152 consecutive patients were included in the study (mean age, 79.95 ± 7.71 years; log EuroScore: 23.87 ± 8.93%). Based on the ROC curve, sizing of 14% was the optimal that would lead to less moderate/severe PVL (P<.01). Group 1 was defined as sizing <14% (n = 49 patients) and group 2 was defined as sizing ≥14% (n = 103 patients). During a follow-up period of 36 ± 14 months, a total of 9 patients died from group 1 vs 4 patients from group 2 (P<.01). Two of the patients who died had moderate/severe PVL and 11 had no/mild PVL (P=.27). From the population, a total of 49 patients (32%) were found to be in the "borderline" zone. Patients who received the smaller valve had lower mean left ventricular outflow tract diameter (P=.048), higher rate of calcium load (mild: 10 [32%] vs 13 [72%]; moderate: 16 [52%] vs 3 [17%]; severe: 5 [16%] vs 2 [11%]; P=.02) and lower mean of sinus of Valsalva diameter (P=.046) compared with patients who received the bigger valve. CONCLUSIONS: In patients undergoing TAVI, over-sizing the prosthesis at least 14% reduces PVL. In borderline cases, taking into consideration additional anatomical parameters may result in low rates of PVL.

Immunomodulatory interventions in myocardial infarction and heart failure: a systematic review of clinical trials and meta-analysis of IL-1 inhibition.

Following a myocardial infarction (MI), the immune system helps to repair ischaemic damage and restore tissue integrity, but excessive inflammation has been implicated in adverse cardiac remodelling and development towards heart failure (HF). Pre-clinical studies suggest that timely resolution of inflammation may help prevent HF development and progression. Therapeutic attempts to prevent excessive post-MI inflammation in patients have included pharmacological interventions ranging from broad immunosuppression to immunomodulatory approaches targeting specific cell types or factors with the aim to maintain beneficial aspects of the early post-MI immune response. These include the blockade of early initiators of inflammation including reactive oxygen species and complement, inhibition of mast cell degranulation and leucocyte infiltration, blockade of inflammatory cytokines, and inhibition of adaptive B and T-lymphocytes. Herein, we provide a systematic review on post-MI immunomodulation trials and a meta-analysis of studies targeting the inflammatory cytokine Interleukin-1. Despite an enormous effort into a significant number of clinical trials on a variety of targets, a striking heterogeneity in study population, timing and type of treatment, and highly variable endpoints limits the possibility for meaningful meta-analyses. To conclude, we highlight critical considerations for future studies including (i) the therapeutic window of opportunity, (ii) immunological effects of routine post-MI medication, (iii) stratification of the highly diverse post-MI patient population, (iv) the potential benefits of combining immunomodulatory with regenerative therapies, and at last (v) the potential side effects of immunotherapies.