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Background: Acute ischaemic stroke (AIS) after percutaneous coronary intervention (PCI) is a rare, but debilitating, complication. However, contemporary data from real-world unselected patients are scarce., Aims: We aimed to explore the temporal trends, outcomes and variables associated with AIS as well as in-hospital all-cause mortality in a nationwide cohort., Methods: A retrospective analysis of healthcare records from 2006-2021 was implemented. Patients were stratified according to the occurrence of AIS in the setting of PCI. The temporal trends of AIS were analysed. A stepwise regression model was used to identify variables associated with AIS and in-hospital all-cause mortality., Results: A total of 4,910,430 PCIs were included for the current analysis. AIS occurred in 4,098 cases (0.08%). An incremental increase in the incidence of AIS after PCI from 0.03% to 0.14% per year was observed from 2006-2021. The strongest associations with AIS after PCI included carotid artery disease, medical history of stroke, atrial fibrillation, presentation with an ST-segment elevation myocardial infarction (STEMI) or non-STEMI and coronary thrombectomy. For patients with AIS, a higher in-hospital all-cause mortality (18.11% vs 3.29%; p<0.001) was documented. With regard to all-cause mortality, the strongest correlations in the stroke cohort were found for cardiogenic shock, dialysis and clinical presentation with a STEMI., Conclusions: In an unselected nationwide cohort of patients hospitalised for PCI, a gradual increase in AIS incidence was noted. We identified several variables associated with AIS as well as with in-hospital mortality. Hereby, clinicians might identify the patient population at risk for a peri-interventional AIS as well as those at risk for an adverse in-hospital outcome after PCI.

Background: Conventional low-density lipoprotein cholesterol (LDL-C) quantification includes cholesterol attributable to lipoprotein(a) (Lp(a)-C) due to their overlapping densities., Objectives: The purposes of this study were to compare the association between LDL-C and LDL-C corrected for Lp(a)-C (LDL Lp(a)corr ) with incident coronary heart disease (CHD) in the general population and to investigate whether concomitant Lp(a) values influence the association of LDL-C or apolipoprotein B (apoB) with coronary events., Methods: Among 68,748 CHD-free subjects at baseline LDL Lp(a)corr was calculated as "LDL-C-Lp(a)-C," where Lp(a)-C was 30% or 17.3% of total Lp(a) mass. Fine and Gray competing risk-adjusted models were applied for the association between the outcome incident CHD and: 1) LDL-C and LDL Lp(a)corr in the total sample; and 2) LDL-C and apoB after stratification by Lp(a) mass (≥/<90th percentile)., Results: Similar risk estimates for incident CHD were found for LDL-C and LDL-C Lp(a)corr30 or LDL-C Lp(a)corr17.3 (subdistribution HR with 95% CI) were 2.73 (95% CI: 2.34-3.20) vs 2.51 (95% CI: 2.15-2.93) vs 2.64 (95% CI: 2.26-3.10), respectively (top vs bottom fifth; fully adjusted models). Categorization by Lp(a) mass resulted in higher subdistribution HRs for uncorrected LDL-C and incident CHD at Lp(a) ≥90th percentile (4.38 [95% CI: 2.08-9.22]) vs 2.60 [95% CI: 2.21-3.07]) at Lp(a) <90th percentile (top vs bottom fifth; P interaction 0.39). In contrast, apoB risk estimates were lower in subjects with higher Lp(a) mass (2.43 [95% CI: 1.34-4.40]) than in Lp(a) <90th percentile (3.34 [95% CI: 2.78-4.01]) (P interaction 0.49)., Conclusions: Correction of LDL-C for its Lp(a)-C content provided no meaningful information on CHD-risk estimation at the population level. Simple categorization of Lp(a) mass (≥/<90th percentile) influenced the association between LDL-C or apoB with future CHD mostly at higher Lp(a) levels., Competing Interests: Funding Support and Author Disclosures The BiomarCaRE Project is funded by the European Union Seventh Framework Programme Collaborative Project (FP7/2007–2013) under grant agreement no. HEALTHF2-2011–278913. The MORGAM Project has received funding from European Union projects MORGAM (Biomed, BMH4-CT98-3183), GenomEUtwin (Fifth Framework Programme FP5, QLG2-CT-2002-01254), BiomarCaRE (FP7, HEALTH-F2-2011-278913), European Network for Genetic and Genomic Epidemiology (ENGAGE) (FP7, HEALTH-F4-2007-201413), Consortium on Health and Ageing: Network of cohorts in Europe and the United States (CHANCES) (FP7, HEALTH-F3-2010-242244), euCanSHare (Horizon 2020, No. 825903), Digital, Risk-Based Screening for Atrial Fibrillation in the European Community project - European Union (AFFECT-EU) (Horizon 2020, no. 847770), and Medical Research Council, London (G0601463, no. 80983: Biomarkers in the MORGAM Populations). This funding has supported central coordination, workshops, and part of the activities of the MORGAM Data Centre, the MORGAM Laboratories, and the MORGAM Participating Centres; MORGAM Participating Centres are funded by regional and national governments, research councils, charities, and other local sources. Dr Schnabel has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 648131), German Ministry of Research and Education (BMBF 01ZX1408A), and German Center for Cardiovascular Research (DZHK e.V.; grant no. 81Z1710103); and has received personal fees from BMS/Pfizer. Dr Kee has received funding from the National Institute of Health Research United Kingdom. Dr Salomaa was supported by the Finnish Foundation for Cardiovascular Research and the Juho Vainio Foundation; and has received grants from Bayer AG. Dr Zeller was supported by the German Center of Cardiovascular Research (DZHK e.V.; DZHK, 81Z0710102). Dr Blankenberg has received a grant from Abbott Diagnostics during the conduct of the study; has received grants and personal fees from Abbott Diagnostics, Bayer, SIEMENS, and Thermo Fisher; has received grants from Singulex; and has received personal fees from AstraZeneca, AMGEN, Medtronic, Pfizer, Roche, Siemens Diagnostic, and Novartis. Dr Söderberg has been supported by the Swedish Heart-Lung Foundation (20140799, 20120631, and 20100635), the County Council of Västerbotten (ALF, VLL- RV-967561, RV-841381548791), and Umeå University; and has received grants and personal fees from Actelion Ltd. All funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Outside the scope of the present work, Dr Arnold has received consulting fees and grant support from Novartis. Dr Brunner has received grant supports from Daiichi-Sankyo, Novartis, Pfizer, and Sanofi; has received nonfinancial support from Abbott, ASAHI INTECC, and Inari Medical; and has received personal fees from Amgen and Novartis. Dr Bay is supported by a grant from the German Heart Foundation (grant no. S/06/23). Dr Koenig has received consulting fees and lecture fees from AstraZeneca, Novartis, and Amgen; has received consulting fees from Pfizer, The Medicines Company, DalCor Pharmaceuticals, Kowa, Corvidia Therapeutics, Esperion, Genentech, OMEICOS, Novo Nordisk, LIB Therapeutics, TenSixteen Bio, New Amsterdam Pharma, and Daiichi-Sankyo; has received lecture fees from Berlin-Chemie, Bristol Myers Squibb, and Sanofi; and has received grant support and provision of reagents from Singulex, Abbott, Roche Diagnostics, and Dr Beckmann Pharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Percutaneous coronary intervention (PCI) has demonstrated its safety and efficacy in treating left main (LM) coronary artery disease (CAD) in select patients. Polyvascular disease (PolyVD) is associated with adverse events in all-comers with CAD. However, there is little data examining the interplay between PolyVD and LM-PCI, which we sought to investigate in a retrospective single-center study. We included patients who underwent unprotected LM-PCI at a tertiary center from 2012 to 2019. The study population was stratified based on the presence or absence of PolyVD (i.e., medical history of cerebrovascular and/or peripheral artery disease in addition to LM-CAD). The primary outcome was major adverse cardiovascular events (MACE) combining all-cause mortality and spontaneous myocardial infarction within 1 year after index PCI. Overall, 869 patients were included, and 23.8% of the population had PolyVD. Subjects with PolyVD were older and had a greater burden of co-morbidities. After 1-year follow-up, PolyVD patients exhibited significantly higher rates of both MACE (22.8% vs 9.4%, p <0.001) and bleeding events compared with those without PolyVD. MACE was primarily driven by an increase in all-cause mortality (18.3% vs 7.1%, p <0.001). Results persisted after adjusting for confounders. In conclusion, in patients who underwent LM-PCI, the presence of PolyVD is linked to an increased risk of MACE and bleeding after 1 year of follow-up, which highlights the vulnerability of this population., Competing Interests: Declaration of competing interest Dr. Dangas received research grants from institutions and support for attending meetings from Daiichi Sankyo. Dr. Mehran reports institutional research payments from: Abbott, Abiomed, Affluent Medical, Alleviant Medical, Amgen, AM-Pharmacia, Arena, AstraZeneca, AtriCure Inc., Biosensors, Biotronik, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CeloNova, CERC, Chiesi, Concept Medical, Cytosorbents, Daiichi Sankyo, Duke, Element Science, Essential Medical, Faraday, Idorsia Pharmaceuticals, Janssen, MedAlliance, Mediasphere, Medtelligence, Medtronic, MJH Healthcare, Novartis, OrbusNeich, Penumbra, PhaseBio, Philips, Pi-Cardia, PLx Pharma, Population Health Research Institute, Protembis, RecCor Medical Inc., RenalPro, RM Global, Sanofi, Shockwave, Vivasure, Zoll; Personal fees from: Affluent Medical, Cardiovascular Research Foundation (CRF), Cordis, Daiichi Sankyo Brasil, E.R. Squibb & Sons Science/Innovative BioPharma, Europa Group/Boston Scientific, Gaffney Events, Educational Trust, Henry Ford Health Cardiology, Ionis Pharmaceuticals, MedCon International, Novartis, NovoNordisk, PeerView Institute for Medical Education, Terumo Europe N.V., Vectura, VoxMedia, WebMD, IQVIA, Radcliffe, tarsus Cardiology; No Fees from: AMA (Scientific Advisory Board), SCAI (Women in Innovations Committee Member); Faculty CRF; Honorarium: JAMA Cardiology (Associate Editor), ACC (BOT Member, SC Member CTR Program); Equity <1% in: applied Therapeutics, Elixir Medical, Stel, ControlRad (spouse). The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Lipids, including phospholipids and bile acids, exert various signaling effects and are thought to contribute to the development of coronary artery disease (CAD). Here, we aimed to compare lipidomic and bile acid profiles in the blood of patients with and without CAD stratified by sex., Methods: From 2015 to 2022, 3,012 patients who underwent coronary angiography were recruited in the INTERCATH cohort. From the overall cohort, subgroups were defined using patient characteristics such as CAD vs. no CAD, 1st vs. 3rd tertile of LDL-c, and female vs. male sex. Hereafter, a matching algorithm based on age, BMI, hypertension status, diabetes mellitus status, smoking status, the Mediterranean diet score, and the intake of statins, triglycerides, HDL-c and hs-CRP in a 1:1 ratio was implemented. Lipidomic analyses of stored blood samples using the Lipidyzer platform (SCIEX) and bile acid analysis using liquid chromatography with tandem mass spectrometry (LC‒MS/MS) were carried out., Results: A total of 177 matched individuals were analyzed; the median ages were 73.5 years (25th and 75th percentile: 64.1, 78.2) and 71.9 years (65.7, 77.2) for females and males with CAD, respectively, and 67.6 years (58.3, 75.3) and 69.2 years (59.8, 76.8) for females and males without CAD, respectively. Further baseline characteristics, including cardiovascular risk factors, were balanced between the groups. Women with CAD had decreased levels of phosphatidylcholine and diacylglycerol, while no differences in bile acid profiles were detected in comparison to those of female patients without CAD. In contrast, in male patients with CAD, decreased concentrations of the secondary bile acid species glycolithocholic and lithocholic acid, as well as altered levels of specific lipids, were detected compared to those in males without CAD. Notably, male patients with low LDL-c and CAD had significantly greater concentrations of various phospholipid species, particularly plasmalogens, compared to those in high LDL-c subgroup., Conclusions: We present hypothesis-generating data on sex-specific lipidomic patterns and bile acid profiles in CAD patients. The data suggest that altered lipid and bile acid composition might contribute to CAD development and/or progression, helping to understand the different disease trajectories of CAD in women and men., Registration: https://clinicaltrials.gov/ct2/show/NCT04936438 , Unique identifier: NCT04936438., (© 2024. The Author(s).)

Background: Individuals suffering from polyvascular atherosclerotic disease (PolyVD) face a higher likelihood of adverse cardiovascular events. Additionally, inflammation, assessed by high-sensitivity C-reactive protein (hsCRP), affects residual risk following percutaneous coronary intervention (PCI). We aimed to explore the interplay between PolyVD and hsCRP in terms of clinical outcomes after PCI., Methods: Patients undergoing PCI for chronic coronary disease at a tertiary center between January 2012 and February 2020 were included for the current analysis. PolyVD was defined by additional history of cerebrovascular and/or peripheral artery disease. HsCRP levels were defined as elevated when the measured baseline concentration was > 3 mg/L. The primary outcome of interest was major adverse cardiovascular events (MACE), a composite of all-cause mortality, spontaneous MI, or target vessel revascularization., Results: Overall, 10,359 participants were included in the current study, with 17.4% affected by PolyVD and 82.6% included in the non-PolyVD subgroup. Patients with PolyVD had higher hsCRP levels than those without. Among the PolyVD group, a larger proportion (33.6%) exhibited elevated hsCRP compared to the non-PolyVD group (24.7%). Patients with both PolyVD and elevated hsCRP levels had significantly higher adverse event rates than all other subgroups at 1-year follow-up. Furthermore, an independent association between elevated hsCRP and MACE was observed within the PolyVD population, while this was not the case for individuals without PolyVD., Conclusion: A residual risk of adverse outcomes after PCI linked to inflammation appears to be present among individuals with PolyVD. This could help define further target populations for anti-inflammatory treatment options., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose of Review: This article focuses on pharmacological agents as well as dietary changes aimed at the reduction of the inflammatory burden measured by circulating C-reactive protein concentrations., Recent Findings: Over the last years, repurposed as well as new anti-inflammatory agents have been investigated in outcome trials in the cardiovascular field. Currently, a specific inhibition of the inflammatory cascade via the interleukin-6 ligand antibody ziltivekimab is being explored in large-scale outcome trials, after the efficacy of this agent with regard to the reduction of inflammatory biomarkers was proven recently. Next to the investigated pharmacological agents, specific dietary patterns possess the ability to improve the inflammatory burden. This enables patients themselves to unlock a potential health benefit ahead of the initiation of a specific medication targeting the inflammatory pathway., Summary: Both pharmacological agents as well as diet provide the opportunity to improve the inflammatory profile and thereby lower C-reactive protein concentrations. Whilst advances in the field of specific anti-inflammatory treatments have been made over the last years, their broad implementation is currently limited. Therefore, optimization of diet (and other lifestyle factors) could provide a cost effective and side-effect free intervention to target low-grade vascular inflammation., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population., Methods: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L)., Results: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024)., Conclusions: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Robotic-assisted percutaneous coronary intervention (rPCI) has proven to be feasible and safe. Comparative analyses of rPCI versus manual PCI (mPCI) are scarce., Aims: We aimed to investigate procedural aspects and outcomes of rPCI using the second-generation CorPath GRX Vascular Robotic System compared with mPCI in patients with chronic coronary syndrome and non-ST-segment elevation myocardial infarction acute coronary syndrome., Methods: From January to April 2021, 70 patients underwent rPCI at the University Heart & Vascular Center Hamburg-Eppendorf and were recruited into the INTERCATH study. By propensity score matching, a control cohort of 210 patients who underwent mPCI from 2015-2021 was identified. Co-primary endpoints were one-year all-cause mortality and major adverse cardiovascular events (MACE) as a composite of cardiovascular death, unplanned target lesion revascularisation, myocardial infarction, and stroke., Results: The median age of the patients (n=280) was 70.7 (25th percentile-75th percentile: 62.0-78.0) years, and 24.6% were female. The Gensini score (28.5 [16.2-48.1] vs 28.0 [15.5-47.0]; p=0.78) was comparable between rPCI versus mPCI. During the PCI procedure, total contrast fluid volume did not differ, whilst longer fluoroscopy times (20.4 min [13.8-27.2] vs 14.4 min [10.4-24.3]; p=0.001) were documented in the rPCI versus mPCI cohort. After 12 months of follow-up, neither all-cause mortality (p=0.22) nor MACE (p=0.25) differed between the groups., Conclusions: rPCI was associated with longer fluoroscopy times compared with mPCI, though without increased use of contrast medium. One-year follow-up revealed no differences in all-cause mortality or MACE, supporting the safety of a robotic-assisted approach.

The inflammatory burden as measured by high-sensitivity C-reactive Protein (hsCRP) is recognized as a cardiovascular risk factor, which can however be affected by lifestyle-related risk factors (LRF). Up-to-date the interplay between hsCRP, LRF and presence and extent of atherosclerotic disease is still largely unknown, which we therefore sought to investigate in a contemporary population-based cohort. We included participants from the cross-sectional population-based Hamburg City Health Study. Affected vascular beds were defined as coronary, peripheral, and cerebrovascular arteries. LRF considered were lack of physical activity, overweight, active smoking and poor adherence to a Mediterranean diet. We computed multivariable analyses with hsCRP as the dependent variable and LRF as covariates according to the number of vascular beds affected. In the 6765 individuals available for analysis, we found a stepwise increase of hsCRP concentration both according to the number of LRF present as well as the number of vascular beds affected. Adjusted regression analyses showed an independent association between increasing numbers of LRF with hsCRP levels across the extent of atherosclerosis. We demonstrate increasing hsCRP concentrations according to both the number of LRF as well as the extent of atherosclerosis, emphasizing the necessity of lifestyle-related risk factor optimization., (© 2023. The Author(s).)

Background: Stroke after a cardiovascular procedure (CVP) is a devastating complication adversely affecting outcome. Mechanical thrombectomy (MT) has not been investigated systematically in this population., Objective: To carry out a retrospective study in patients undergoing MT for early stroke after CVP, aiming to further characterize this cohort of patients, and to evaluate the efficacy, safety, procedural characteristics, and outcome of MT., Methods: A single-center stroke registry of patients who received MT was analyzed. Baseline and procedural parameters, mortality, functional outcome, recanalization rates, and complications were evaluated. Propensity score matching was carried out, identifying a control cohort with non-periprocedural large vessel occlusion (LVO)., Results: Overall 913 patients were included (mean age 73.0 (±13.0) years, 52.5% female, median National Institutes of Health Stroke Scale score 15 (10-19)). Eleven patients with a LVO after a recent (<30 days postoperatively) CVP were identified (n=3 transcatheter aortic valve and n=1 surgical aortic valve replacements (SAVR), n=3 coronary bypass grafting (CABG) surgeries, n=2 SAVR+CABG, and n=2 aortic surgeries). After matching, 8 patients in the CVP group were compared with 16 patients in the matched cohort. Comparable rates of reperfusion were achieved. Time from symptom onset to groin puncture (171.5 min (136.3, 178.3) vs 284.0 min (215.0, 490.5); p=0.039), as well as recanalization (195.0 min (146.0, 201.0) vs 419.0 min (274.0, 613.0); p=0.028) was faster in the CVP group. However, this was not reflected by an improved outcome (modified Rankin Scale score after 90 days: 5.5 (3.3, 6.0) vs 5.0 (4.0, 6.0), mortality after 90 days 50.0% vs 37.5%). Complications did not differ between the groups., Conclusions: Use of MT for LVO stroke in patients after a recent CVP is a safe and efficient treatment in comparison with patients with a non-periprocedural LVO undergoing MT., Competing Interests: Competing interests: GT reports receiving consulting fees from Acandis, grant support and lecture fees from Bayer; lecture fees from Boehringer Ingelheim, BristolMyersSquibb/Pfizer, and Daiichi Sankyo; and consulting fees and lecture fees from Portola and Stryker. JF research support from the German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions-/Förderbank (IFB), Medtronic, Microvention, Philips, Stryker; consultancy appointments; Acandis, Bayer, Boehringer Ingelheim, Cerenovus, Covidien, Evasc Neurovascular, MD Clinicals, Medtronic, Medina, Microvention, Penumbra, Route92, Stryker, Transverse Medical; stock holdings for Tegus; and serves on the editorial board of JNIS., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: We aimed to evaluate the feasibility and safety of implementing a sameday discharge (SD ) protocol for robot-assisted radical prostatectomy (RARP) and pelvic lymph node dissection., Methods: We performed a prospective cohort study including all consecutive eligible patients undergoing RARP in 2021 following initiation of SDD RARP protocol in April. Baseline characteristics were compared using t-tests, Mann-Whitney U tests, and odds ratios (OR ) calculated using multiple logistic regression to assess for predictors of SD success., Results: A total of 117 patients underwent RARP in 2021 following initiation of the SDD protocol. Fifty-seven patients were initiated on the SD pathway and 60 patients underwent surgery as an inpatient (IP-RARP). Of those on the SD pathway (SD-RARP), 33 (58%) were successfully discharged the same day of surgery, while 24 (42%) failed SD . Baseline demographics were well-balanced between cohorts. Case order, increased patient age, and distance travelled to the hospital were factors associated with selection of patients for the IP-RARP protocol. In total, 12 SD and 12 IP patients presented to the emergency department (p=1.0), and none within 24 hours of discharge. There were no hospital admissions in the SD cohort, with four readmissions in the IP cohort (p=0.1). Multiple logistic regression revealed that case order (first case) was the only predictive factor for SD success (OR 4.08, 95% confidence interval 1.59-11.62, p=0.005)., Conclusions: Implementation of an SD pathway following RARP is feasible, with no increase in rates of complications, unscheduled visits, or readmissions.

Background The association between high-sensitivity troponin T (hsTnT) and high-sensitivity troponin I (hsTnI) and outcome when adjusted for confounders including the angiographical severity of coronary artery disease (CAD) remains largely unknown. We therefore aimed to explore whether hsTnT and hsTnI blood levels increase with CAD severity and add independent predictive information for future major adverse cardiovascular events and all-cause mortality in stable patients. Methods and Results Patients from the INTERCATH cohort with available coronary angiography and hsTnT and hsTnI concentrations were included. Troponin concentrations were quantified via hsTnT (Roche Elecsys) and hsTnI (Abbott ARCHITECT STAT). To investigate the association of hsTnT and hsTnI with outcome, a multivariable analysis adjusting for classical cardiovascular risk factors, low-density lipoprotein cholesterol, estimated glomerular filtration rate, hs-CRP (high-sensitivity C-reactive protein), NT-proBNP (N-terminal pro-brain natriuretic peptide), and Gensini score was carried out. Of 1829 patients, 27.9% were women, and the mean age was 68.6±10.9 years. Troponin blood concentrations were higher in patients with diagnosed CAD compared with those without. Using a linear regression model current smoking, arterial hypertension, estimated glomerular filtration rate, hs-CRP, NT-proBNP, and CAD severity as graded by the Gensini and SYNTAX scores were associated with high-sensitivity troponin levels. Patients were followed for 4.4 years (25th and 75th percentiles: 4.3, 4.4). After multivariable adjustment, all-cause mortality was predicted by hsTnT (hazard ratio [HR], 1.7 [95% CI, 1.5-2.2], P <0.001) as well as hsTnI (HR, 1.5 [95% CI, 1.2-1.8], P <0.001). However, only hsTnI (HR, 1.2 [95% CI, 1.0-1.4], P =0.032) remained as an independent predictor of major adverse cardiovascular events after adjusting for most possible confounders, including CAD severity (hsTnT: HR, 1.0 [95% CI, 0.9-1.2], P =0.95). Conclusions After adjusting for classical cardiovascular risk factors, low-density lipoprotein cholesterol, estimated glomerular filtration rate, hs-CRP, NT-proBNP, and CAD severity, hsTnT and hsTnI were independently associated with all-cause mortality, but only hsTnI was associated with major adverse cardiovascular events in stable patients undergoing coronary angiography. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT04936438.

Introduction: Same-day discharge (SDD) following robot-assisted radical prostatectomy (RARP) is emerging as the standard of care. We conducted a systematic review and meta-analysis to evaluate the differences in perioperative characteristics, complication/readmissions rates and satisfaction/cost data between inpatient (IP) RARP and SDD RARP., Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was prospectively registered with PROSPERO (CRD42021258848). A comprehensive search of PubMed®, Embase®, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and conference abstract publications was performed. A leave-one-out sensitivity analysis was performed to control for heterogeneity and risk of bias., Results: A total of 14 studies were included with a pooled population of 3,795 patients, including 2,348 (61.9%) IP RARPs and 1,447 (38.1%) SDD RARPs. SDD pathways varied, though many commonalities were present in patient selection, perioperative recommendations and postoperative management. When compared to IP RARP, SDD RARP had no differences in ≥grade 3 Clavien-Dindo complications (RR: 0.4, 95% CI 0.2, 1.1, p=0.07), 90-day readmission rates (RR: 0.6, 95% CI 0.3, 1.1, p=0.10) or unscheduled emergency department visits (RR: 1.0, 95% CI 0.3, 3.1, p=0.97). Cost savings per patient ranged between $367 and $2,109, and overall satisfaction was high at 87.5%-100%., Conclusions: SDD following RARP is both feasible and safe, while potentially offering health care cost savings with high patient satisfaction rates. Data from this study will inform the uptake and development of future SDD pathways in contemporary urological care such that it may be offered to a broader patient population.

Previously, the simultaneous presence of endocarditis (IE) has been reported in 3-30% of spondylodiscitis cases. The specific implications on therapy and outcome of a simultaneous presence of both diseases are not yet fully evaluated. Therefore, the aim of this study was to investigate the influence of a simultaneously present endocarditis on the course of therapy and outcome of spondylodiscitis. A prospective database analysis of 328 patients diagnosed with spontaneous spondylodiscitis (S) using statistical analysis with propensity score matching was conducted. Thirty-six patients (11.0%) were diagnosed with concurrent endocarditis (SIE) by means of transoesophageal echocardiography. In our cohort, the average age was 65.82 ± 4.12 years and 64.9% of patients were male. The incidence of prior cardiac or renal disease was significantly higher in the SIE group (coronary heart disease SIE n = 13/36 vs. S n = 57/292, p < 0.05 and chronic heart failure n = 11/36 vs. S n = 41/292, p < 0.05, chronic renal failure SIE n = 14/36 vs. S n = 55/292, p < 0.05). Complex interdisciplinary coordination and diagnostics lead to a significant delay in surgical intervention (S = 4.5 ± 4.5 days vs. SIE = 8.9 ± 9.5 days, p < 0.05). Mortality did not show statistically significant differences: S (13.4%) and SIE (19.1%). Time to diagnosis and treatment is a key to efficient treatment and patient safety. In order to counteract delayed therapy, we developed a novel therapy algorithm based on the analysis of treatment processes of the SIE group. We propose a clear therapy pathway to avoid frequently observed pitfalls and delays in diagnosis to improve patient care and outcome., (© 2021. The Author(s).)

Purpose: The lowered LDL-C treatment goal of the 2019 European Society of Cardiology dyslipidemia guidelines results in a significant increase in the projected need for cost-intensive proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Addition of bempedoic acid (BA) to established oral lipid-lowering medication (LLM) has the potential to enable affordable LDL-C goal attainment, particularly in patients with statin intolerance (SI). The goal of this study was to quantify the target populations for BA and PCSK9 inhibitors as well as the related treatment costs to achieve the LDL-C goal of <55 mg/dL and a ≥50% reduction assuming the addition of BA to LLM., Methods: This study included 1922 patients with coronary artery disease (CAD) from the contemporary observational cohort study INTERCATH. A Monte Carlo simulation incorporating an algorithm adding sequentially a statin, ezetimibe, optionally BA, and a PCSK9 inhibitor was applied to achieve the LDL-C treatment goal, with consideration of both partial and total SI. Two scenarios were simulated for both a moderate (2% full and 10% partial) and a high (12% full) rate of SI: (1) without BA; and (2) with BA., Findings: Patients' mean age was 69.3 years, and the median baseline LDL-C level was 86.0 mg/dL. The need for a PCSK9 inhibitor would be 41.4% for a moderate rate of SI and 46.1% for a high rate of SI. Addition of BA would: (1) reduce the need for a PCSK9 inhibitor to 25.3% and 29.4%, thus lowering the annual overall treatment cost incurred through PCSK9 inhibitor ± BA per 1 million patients with CAD by 13.3% and 10.5%; (2) lower the cost per prevented event in the entire cohort (-5.0% and -6.3%), although at the price of fewer prevented events (-8.7% and -4.5%); and (3) reduce the cost per prevented event (-6.8% for both rates of SI) while preventing more events (7.6% and 6.9%) in the subpopulation of patients with full SI., Implications: Use of BA is projected to reduce the need for PCSK9 inhibitors as well as the treatment cost for add-on LLM. The subpopulation of patients with full SI might profit particularly., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The recently updated European Society of Cardiology (ESC) dyslipidaemia guidelines recommend a lower low-density lipoprotein cholesterol (LDL-C) goal of <55 mg/dL for patients with atherosclerotic cardiovascular disease (ASCVD), with a concomitant Class IA upgrade for proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) for patients not reaching their LDL-C goal under conventional lipid-lowering therapy., Aims: We aim to quantify the need for PCSK9i and the related costs to achieve the revised LDL-C goal in ASCVD patients compared to former ESC recommendations, in particular the risk-based 2017 ESC consensus update., Methods and Results: We included patients with ASCVD from an observational cohort study ongoing since 2015. A Monte Carlo simulation incorporating a treatment algorithm adding sequentially a statin, ezetimibe, and a PCSK9i was applied with consideration of partial and total statin intolerance. The need for PCSK9i was calculated for three different ESC recommendations (2019 guidelines, 2016 guidelines, 2017 consensus update). Preventable events and treatment costs due to PCSK9i were calculated for a range of annual event rates from 2% to 8% and annual treatment costs of ca. 6050 €. We included 1780 patients (mean age 69.5 years). Median LDL-C at baseline was 85.0 mg/dL, with 61% of patients taking lipid-lowering medication. The need for PCSK9i was simulated to be 42.0% (ESC 2019), 31.9% (ESC 2016), and 5.0% (ESC 2017). The LDL-C goals were achieved in 97.9%, 99.1%, and 60.9% of patients, respectively. Annual treatment cost for PCSK9i per 1 000 000 ASCVD patients would be 2.54 billion € (ESC 2019) compared to 0.30 billion € (ESC 2017). Costs per prevented event due to PCSK9i initiation differed widely, e.g. 887 000 € for an event rate of 3% and a treatment goal of <55 mg/dL compared to 205 000 € for an event rate of 7% and risk-based use of PCSK9i., Conclusion: The revised LDL-C treatment goals increase the projected need for PCSK9i with a substantial increase in associated treatment cost. An allocation strategy based on residual LDL-C and clinical or angiographic risk factors leads to a more tailored target population for PCSK9i with a reasonable benefit/cost ratio., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Necrotizing enterocolitis (NEC) is an often-fatal neonatal disease involving intestinal hyperinflammation leading to necrosis. Despite ongoing research, (1) conflicting results and (2) comorbidities of NEC patients make early NEC detection challenging and may complicate therapy development. Most research suggests that NEC pathogenesis is multifactorial, involving a combination of (1) gut prematurity; (2) abnormal bacterial colonization; and (3) ischemia-reperfusion (I/R) injury. As neutrophil extracellular traps (NETs) partially mediate I/R injury and drive inflammation in NEC, we hypothesized that NETs contribute to NEC development; particularly in cardiac patients. Methods: A retrospective analysis of baseline characteristics, clinical signs, laboratory parameters, and imaging was conducted for surgically verified NEC cases over 10 years. Patients were stratified into two groups: (1) prior medically or surgically treated cardiac disease (cardiac NEC) and (2) no cardiac comorbidities (inflammatory NEC). Additionally, histology was reassessed for neutrophil activation and NETs formation. Results: A total of 110 patients (cNEC 43/110 vs. iNEC 67/110) were included in the study, with cNEC neonates being significantly older than iNEC neonates ( p = 0.005). While no significant differences were found regarding clinical signs and imaging, laboratory parameters revealed that cNEC patients have significantly increased leucocyte ( p = 0.024) and neutrophil ( p < 0.001) counts. Both groups also differed in pH value ( p = 0.011). Regarding histology: a non-significant increase in staining of myeloperoxidase within the cNEC group could be found in comparison to iNEC samples. Neutrophil elastase ( p = 0.012) and citrullinated histone H3 stained ( p = 0.041) slides showed a significant markup for neonates diagnosed with cNEC in comparison to neonates with iNEC. Conclusion: The study shows that many standardized methods for diagnosing NEC are rather unspecific. However, differing leucocyte and neutrophil concentrations for iNEC and cNEC may indicate a different pathogenesis and may aid in diagnosis. As we propose that iNEC is grounded rather in sepsis and neutropenia, while cNEC primarily involves I/R injuries, which involves neutrophilia and NETs formation, it is plausible that I/R injury due to interventions for cardiac comorbidities results in pronounced neutrophil activation followed by a hyperinflammation reaction and NEC. However, prospective studies are necessary to validate these findings and to determine the accuracy of the potential diagnostic parameters., (Copyright © 2021 Klinke, Wiskemann, Bay, Schäfer, Pagerols Raluy, Reinshagen, Vincent and Boettcher.)

The occurrence of renal cell carcinoma (RCC) and urothelial carcinoma (UC) synchronously in the same kidney is exceedingly rare. All reported cases have been managed with either nephroureterectomy or nephrectomy. We report on a patient who required renal-sparing management of his double malignancy, including open partial nephrectomy of his pT1a RCC and endoscopic laser ablation of his low-grade Ta renal pelvis UC. After 4 years, the patient is in good health and disease-free under strict surveillance. It, therefore, would appear justified to combine partial nephrectomy for RCC and endoscopic management of UC in the same kidney of an appropriately selected patient.

Background: Choline is an important constituent of acetylcholine. Choline is needed for acetylcholine in the nonneuronal acetylcholine system that includes epithelial cells of the lung and intestine, endothelial cells, and immune cells. Plasma free choline concentrations are low in children with cystic fibrosis (CF), but the implications for acetylcholine are unknown., Objective: We determined the relation between plasma free choline and related metabolites and leukocyte acetylcholine in children with CF and in a control group of healthy children without CF., Design: This was a cross-sectional study in 34 children with CF who were pancreatic insufficient and taking pancreatic enzyme-replacement therapy and in 16 healthy children. Plasma free choline, betaine, dimethylglycine, methionine, homocysteine, and leukocyte acetylcholine concentrations were quantified by using isotope-dilution HPLC-tandem mass spectrometry., Results: Mean (±SE) plasma free choline was 9.30 ± 0.37 and 6.54 ± 0.38 μmol/L (P < 0.05) and leukocyte acetylcholine was 1.21 ± 0.016 and 0.077 ± 0.011 pmol leukocyte acetylcholine/10(6) cells (P < 0.05) in control children and children with CF, respectively. Leukocyte acetylcholine was positively correlated with plasma free choline concentration in children with CF (r = 0.412, P < 0.05) but not in control children. Plasma betaine, dimethylglycine, and methionine concentrations were also lower in children with CF than in control children (P < 0.05)., Conclusions: A low free choline and methyl status in children with CF is associated with reduced acetylcholine in leukocytes. Whether these changes are explained by a mutation in the CF transmembrane conductance regulator or disturbances in choline metabolism and the implications for immune cell dysfunction in CF are unknown. This trial was registered at clinicaltrials.gov as NCT01150136.