Hospital outcomes of community-acquired COVID-19 versus influenza: Insights from the Swiss hospital-based surveillance of influenza and COVID-19.

BackgroundSince the onset of the COVID-19 pandemic, the disease has frequently been compared with seasonal influenza, but this comparison is based on little empirical data.AimThis study compares in-hospital outcomes for patients with community-acquired COVID-19 and patients with community-acquired influenza in Switzerland.MethodsThis retrospective multi-centre cohort study includes patients > 18 years admitted for COVID-19 or influenza A/B infection determined by RT-PCR. Primary and secondary outcomes were in-hospital mortality and intensive care unit (ICU) admission for patients with COVID-19 or influenza. We used Cox regression (cause-specific and Fine-Gray subdistribution hazard models) to account for time-dependency and competing events with inverse probability weighting to adjust for confounders.ResultsIn 2020, 2,843 patients with COVID-19 from 14 centres were included. Between 2018 and 2020, 1,381 patients with influenza from seven centres were included; 1,722 (61%) of the patients with COVID-19 and 666 (48%) of the patients with influenza were male (p < 0.001). The patients with COVID-19 were younger (median 67 years; interquartile range (IQR): 54-78) than the patients with influenza (median 74 years; IQR: 61-84) (p < 0.001). A larger percentage of patients with COVID-19 (12.8%) than patients with influenza (4.4%) died in hospital (p < 0.001). The final adjusted subdistribution hazard ratio for mortality was 3.01 (95% CI: 2.22-4.09; p < 0.001) for COVID-19 compared with influenza and 2.44 (95% CI: 2.00-3.00, p < 0.001) for ICU admission.ConclusionCommunity-acquired COVID-19 was associated with worse outcomes compared with community-acquired influenza, as the hazards of ICU admission and in-hospital death were about two-fold to three-fold higher.

Differential immunological signature at the culprit site distinguishes acute coronary syndrome with intact from acute coronary syndrome with ruptured fibrous cap: results from the prospective translational OPTICO-ACS study.

AIMS: Acute coronary syndromes with intact fibrous cap (IFC-ACS), i.e. caused by coronary plaque erosion, account for approximately one-third of ACS. However, the underlying pathophysiological mechanisms as compared with ACS caused by plaque rupture (RFC-ACS) remain largely undefined. The prospective translational OPTICO-ACS study programme investigates for the first time the microenvironment of ACS-causing culprit lesions (CL) with intact fibrous cap by molecular high-resolution intracoronary imaging and simultaneous local immunological phenotyping. METHODS AND RESULTS: The CL of 170 consecutive ACS patients were investigated by optical coherence tomography (OCT) and simultaneous immunophenotyping by flow cytometric analysis as well as by effector molecule concentration measurements across the culprit lesion gradient (ratio local/systemic levels). Within the study cohort, IFC caused 24.6% of ACS while RFC-ACS caused 75.4% as determined and validated by two independent OCT core laboratories. The IFC-CL were characterized by lower lipid content, less calcification, a thicker overlying fibrous cap, and largely localized near a coronary bifurcation as compared with RFC-CL. The microenvironment of IFC-ACS lesions demonstrated selective enrichment in both CD4+ and CD8+ T-lymphocytes (+8.1% and +11.2%, respectively, both P < 0.05) as compared with RFC-ACS lesions. T-cell-associated extracellular circulating microvesicles (MV) were more pronounced in IFC-ACS lesions and a significantly higher amount of CD8+ T-lymphocytes was detectable in thrombi aspirated from IFC-culprit sites. Furthermore, IFC-ACS lesions showed increased levels of the T-cell effector molecules granzyme A (+22.4%), perforin (+58.8%), and granulysin (+75.4%) as compared with RFC plaques (P < 0.005). Endothelial cells subjected to culture in disturbed laminar flow conditions, i.e. to simulate coronary flow near a bifurcation, demonstrated an enhanced adhesion of CD8+T cells. Finally, both CD8+T cells and their cytotoxic effector molecules caused endothelial cell death, a key potential pathophysiological mechanism in IFC-ACS. CONCLUSIONS: The OPTICO-ACS study emphasizes a novel mechanism in the pathogenesis of IFC-ACS, favouring participation of the adaptive immune system, particularly CD4+ and CD8+ T-cells and their effector molecules. The different immune signatures identified in this study advance the understanding of coronary plaque progression and may provide a basis for future development of personalized therapeutic approaches to ACS with IFC. TRIAL REGISTRATION: The study was registered at clinicalTrials.gov (NCT03129503).

[Dyspnea : A challenging symptom in the primary care setting]. / Dyspnoe : Eine Herausforderung in der internistisch-hausärztlichen Praxis.

Dyspnea is a very common symptom leading to visits to a general physician (GP). Correct differential diagnosis is the major challenge for the GP. There are no guidelines on dyspnea. This review provides an overview of the main causal diseases for dyspnea, presents methods for history taking and differential diagnosis, and specifies the role of GPs in the primary care setting in the case of dyspnea.

Mineralocorticoid receptor antagonist pre-treatment and early post-treatment to minimize reperfusion injury after ST-elevation myocardial infarction: The MINIMIZE STEMI trial.

BACKGROUND: Mineralocorticoid receptor antagonist (MRA) therapy has been shown to prevent adverse left ventricular (LV) remodeling in ST-segment elevation myocardial infarction (STEMI) patients with heart failure. Whether initiating MRA therapy prior to primary percutaneous coronary intervention (PPCI) accrues additional benefit of reducing myocardial infarct size and preventing adverse LV remodeling is not known. We aimed to investigate whether MRA therapy initiated prior to reperfusion reduces myocardial infarct (MI) size and prevents adverse LV remodeling in STEMI patients. METHODS: STEMI patients presenting within 12 hours and with a proximal coronary artery occlusion with Thrombolysis In Myocardial Infarction flow grade 0 were consented and randomized to either an intravenous bolus of potassium canrenoate, followed by oral spironolactone for 3 months or matching placebo. The primary endpoint was MI size by cardiovascular magnetic resonance at 3 months. RESULTS: Sixty-seven patients completed the study. There was no significant difference in the final MI size at 3 months between the 2 groups (placebo: 17 ± 11%, MRA: 16 ± 10%, P = .574). There was also no difference in acute MI size (26 ± 16% versus 23 ± 14%, P = .425) or myocardial salvage (26 ± 12% versus 24 ± 8%, P = .456). At follow-up, there was a trend towards an improvement in LVEF (placebo: 49 ± 8%, MRA: 54 ± 11%, P = .053), and the MRA group had significantly greater percentage decrease in LVEDV (mean difference: -12.2 (95% CI -20.3 to -4.4)%, P = .003) and LVESV (mean difference: -18.2 (95% CI -30.1 to -6.3)%, P = .003). CONCLUSION: This pilot study showed no benefit of MRA therapy in reducing MI size in STEMI patients when initiated prior to reperfusion, but there was an improvement in LV remodeling at 3 months. Adequately powered studies are warranted to confirm these findings.

Real-time optical coherence tomography coregistration with angiography in percutaneous coronary intervention-impact on physician decision-making: The OPTICO-integration study.

AIMS: Intracoronary optical coherence tomography (OCT) imaging allows for high-resolution characterization of coronary lesions. Difficulties in matching cross-sectional OCT-images with angiographic lesion localization may limit optimal clinical utilization. We sought to prospectively assess the impact of a novel system of real-time OCT coregistration with angiography (ACR) on physician decision-making during percutaneous coronary interventions (PCI). METHODS AND RESULTS: Strategy for PCI (stent - length, - diameter, - strategy, landing zone) and PCI-optimization (stent-malappostion, -underexpansion, edge-dissections, geographical mismatch) was prospectively assessed in 50 patients with 58 coronary lesions after (I) angiography, (II) OCT imaging, and (III) ACR. Preprocedural OCT imaging altered stent-length (58.9%), diameter (33.9%), and PCI-strategy (12.5%) in 40 (71.4%) lesions. The use of ACR resulted in additional changes in PCI strategy in 40.7% of mostly complex lesions in comparison to OCT imaging alone and involved mainly device landing zone (24.1%) and stent length (22.2%). Postprocedural OCT imaging revealed the need for PCI optimization in 52.2% of the lesions, whereas post-procedural ACR had no further impact. CONCLUSIONS: Real-time OCT ACR had significant impact on PCI strategy, favoring mainly complete lesion coverage especially in complex lesions.

Impact of impaired fractional flow reserve after coronary interventions on outcomes: a systematic review and meta-analysis.

BACKGROUND: FFR is routinely used to guide percutaneous coronary interventions (PCI). Visual assessment of the angiographic result after PCI has limited efficacy. Even when the angiographic result seems satisfactory FFR after a PCI might be useful for identifying patients with a suboptimal interventional result and higher risk for poor clinical outcome who might benefit from additional procedures. The aim of this meta-analysis was to investigate available data of studies that examined clinical outcomes of patients with impaired vs. satisfactory fractional flow reserve (FFR) after percutaneous coronary interventions (PCI). METHODS: This meta-analysis was carried out according to the Cochrane Handbook for Systematic Reviews. The Mantel-Haenszel method using the fixed-effect meta-analysis model was used for combining the results. Studies were identified by searching the literature through mid-January, 2016, using the following search terms: fractional flow reserve, coronary circulation, after, percutaneous coronary intervention, balloon angioplasty, stent implantation, and stenting. Primary endpoint was the rate of major adverse cardiac events (MACE). Secondary endpoints included rates of death, myocardial infarction (MI), repeated revascularisation. RESULTS: Eight relevant studies were found including a total of 1337 patients. Of those, 492 (36.8 %) had an impaired FFR after PCI, and 853 (63.2 %) had a satisfactory FFR after PCI. Odds ratios indicated that a low FFR following PCI was associated with an impaired outcome: major adverse cardiac events (MACE, OR: 4.95, 95 % confidence interval [CI]: 3.39-7.22, p <0.001); death (OR: 3.23, 95 % CI: 1.19-8.76, p = 0.022); myocardial infarction (OR: 13.83, 95 % CI: 4.75-40.24, p <0.0001) and repeated revascularisation (OR: 4.42, 95 % CI: 2.73-7.15, p <0.0001). CONCLUSIONS: Compared to a satisfactory FFR, a persistently low FFR following PCI is associated with a worse clinical outcome. Prospective studies are needed to identify underlying causes, determine an optimal threshold for post-PCI FFR, and clarify whether simple additional procedures can influence the post-PCI FFR and clinical outcome.

Local versus general anesthesia for transcatheter aortic valve implantation (TAVR)--systematic review and meta-analysis.

BACKGROUND: The hypothesis of this study was that local anesthesia with monitored anesthesia care (MAC) is not harmful in comparison to general anesthesia (GA) for patients undergoing Transcatheter Aortic Valve Implantation (TAVR).TAVR is a rapidly spreading treatment option for severe aortic valve stenosis. Traditionally, in most centers, this procedure is done under GA, but more recently procedures with MAC have been reported. METHODS: This is a systematic review and meta-analysis comparing MAC versus GA in patients undergoing transfemoral TAVR. Trials were identified through a literature search covering publications from 1 January 2005 through 31 January 2013. The main outcomes of interest of this literature meta-analysis were 30-day overall mortality, cardiac-/procedure-related mortality, stroke, myocardial infarction, sepsis, acute kidney injury, procedure time and duration of hospital stay. A random effects model was used to calculate the pooled relative risks (RR) with 95% confidence intervals. RESULTS: Seven observational studies and a total of 1,542 patients were included in this analysis. None of the studies were randomized. Compared to GA, MAC was associated with a shorter hospital stay (-3.0 days (-5.0 to -1.0); P = 0.004) and a shorter procedure time (MD -36.3 minutes (-58.0 to -15.0 minutes); P <0.001). Overall 30-day mortality was not significantly different between MAC and GA (RR 0.77 (0.38 to 1.56); P = 0.460), also cardiac- and procedure-related mortality was similar between both groups (RR 0.90 (0.34 to 2.39); P = 0.830). CONCLUSION: These data did not show a significant difference in short-term outcomes for MAC or GA in TAVR. MAC may be associated with reduced procedural time and shorter hospital stay. Now randomized trials are needed for further evaluation of MAC in the setting of TAVR.

The impact of modern noninvasive cardiac imaging on coronary intervention rates.

OBJECTIVES: It remains still unclear whether the use of modern noninvasive diagnostic modalities for evaluation of coronary artery disease (computed tomography coronary angiography (CTCA), nuclear myocardial perfusion imaging (MPI)) were able to change the "diagnostic yield" of invasive coronary angiography (ICA). METHODS: The total number of ICA in the years 2000-2009 was related to the number of percutaneous interventions (PCIs) and we assessed whether there was a significant trend over time using time series analyses. We compared these data with the number of patients undergoing CTCA and nuclear MPI in the same time period. RESULTS: During the 10-year observational period, 23,397 ICA were performed. The proportion of purely diagnostic ICA (without PCI) remained stable over the whole study period (tau = -0.111, P = 0.721). A CTCA program was initiated in 2005 and 1,407 examinations were performed until 2009. Similarly, the number of nuclear MPI increased from 2,284 in the years 2000-2004 to 5,260 in the years 2005-2009 (P = 0.009). CONCLUSION: Despite increasing availability, noninvasive testing modalities did not significantly alter the rate of purely diagnostic ICA, and still are underused as gatekeeper to ICA. Further effort is needed to optimize the use of noninvasive imaging modalities in the work-up process for coronary artery disease.

'Paradoxical' low-flow, low-gradient severe aortic valve stenosis: an entity with limited improvement following transcatheter aortic valve implantation.

BACKGROUND AND AIM OF THE STUDY: The aim of this single-center observational study was to determine the outcome of patients with 'paradoxical' low-flow, low-gradient aortic valve stenosis (PLF-LG-AS) after transcatheter aortic valve implantation (TAVI). METHODS: Based on pre-procedural echocardiographic data, a total of 150 patients with severe aortic valve stenosis (AS) (indexed aortic valve area (AVA) ≤ 0.6 cm2/m2) who underwent TAVI at the authors' institution were allocated retrospectively to three groups: Group 1: PLF-LG-AS (ejection fraction (EF) ≥ 50%, indexed stroke volume (SV) ≤ 35 ml/m2, mean AV gradient < 40 mmHg; n = 30); Group 2: Classical low-flow, low-gradient AS (CLF-LG-AS: EF < 50%, SV ≤ 35 ml/m2, mean AV gradient < 40 mmHg; n = 21); and Group 3: High-gradient AS (HG-AS: EF < or ≥ 50%, mean AV gradient ≥ 40 mmHg; n = 99). RESULTS: PLF-LG-AS was associated with an increased relative wall thickness (RWT) and a higher post-procedural systolic blood pressure (sBP) and pulse pressure (PP) (RWT 60.6 ± 15.3%, sBP 144 ± 14 mmHg, PP 79 ± 15 mmHg) compared to patients with HG-AS or CLF-LG-AS: (RWT 52 ± 13% and 40 ± 9%, p < 0.001; sBP 138 ± 15 mmHg and 125 ± 25 mmHg, p = 0.006; PP 68 ± 16 mmHg and 60 ± 21 mmHg, p = 0.01). These patients experienced less improvement in a 6-min walk test (improvement for PLF-LG-AS 14 ± 84 m, for CLF-LG-AS 86 ± 83 m, for HG-AS 87 ± 66 m; intergroup p < 0.007). PLF-LG-AS and CLF-LG-AS were also associated with significantly increased one-year overall mortality (PLF-LG-AS 31%, CLF-LG-AS 19%, HG-AS 6%; p = 0.001) and cardiovascular mortality (PLF-LG-AS 20%, CLF-LG-AS 19%, HG-AS 3%; p = 0.002). CONCLUSION: Patients with PLF-LG-AS may represent a subgroup with a worse clinical outcome after TAVI.

Post-procedural arterial hypertension: implications for clinical outcome after transcatheter aortic valve implantation.

BACKGROUND AND AIM OF THE STUDY: Persistent arterial hypertension (HT) has been associated with increased morbidity and mortality after surgical aortic valve replacement (AVR). The impact of increased blood pressure (BP) after transcatheter aortic valve implantation (TAVI) has not yet been fully elucidated. METHODS: The mean systolic and diastolic BP after TAVI were calculated from the last 10 non-invasive recordings performed before discharge in 176 patients. The primary end-point was symptomatic improvement after 6-12 months according to BP control at the time of discharge. RESULTS: In patients with controlled BP (<140/90 mmHg), the symptomatic response after TAVI was significantly better compared to patients with uncontrolled BP (> or =140/90 mmHg), as reflected by NYHA functional class (+1.4 +/- 0.8 versus +0.8 +/- 1.0, p = 0.002) and six-minute walk test (6-MWT) distance improvement (+100 +/- 71 m versus +30 +/- 64 m, p < 0.001) at 6-12 months' follow up. A 10 mmHg decrease in systolic BP was associated with an 18 m increase in 6-MWT distance (p = 0.001). In addition, reverse left ventricular (LV) remodeling was significantly impaired in uncontrolled BP individuals, as reflected by regression of LV mass (-15 +/- 61 g versus -37 +/- 54 g, p = 0.041) and relative wall thickness (-0.02 +/- 0.09 versus -0.07 +/- 0.1, p = 0.01). Cumulative all-cause and cardiovascular mortality were significantly lower in patients with controlled BP compared to those with uncontrolled BP (6.5% versus 16%, p = 0.04; cardiovascular 3.7% versus 11.6%, p = 0.035). CONCLUSION: Uncontrolled HT after TAVI may contribute to diminished symptomatic improvement.

Myocardial reperfusion injury: looking beyond primary PCI.

Coronary heart disease (CHD) is the leading cause of death and disability in Europe. For patients presenting with an acute ST-segment elevation myocardial infarction (STEMI), timely myocardial reperfusion using either thrombolytic therapy or primary percutaneous coronary intervention (PPCI) is the most effective therapy for limiting myocardial infarct (MI) size, preserving left-ventricular systolic function and reducing the onset of heart failure. Despite this, the morbidity and mortality of STEMI patients remain significant, and novel therapeutic interventions are required to improve clinical outcomes in this patient group. Paradoxically, the process of myocardial reperfusion can itself induce cardiomyocyte death-a phenomenon which has been termed 'myocardial reperfusion injury' (RI), the irreversible consequences of which include microvascular obstruction and myocardial infarction. Unfortunately, there is currently no effective therapy for preventing myocardial RI in STEMI patients making it an important residual target for cardioprotection. Previous attempts to translate cardioprotective therapies (antioxidants, calcium-channel blockers, and anti-inflammatory agents) for reducing RI into the clinic, have been unsuccessful. An improved understanding of the pathophysiological mechanisms underlying RI has resulted in the identification of several promising mechanical (ischaemic post-conditioning, remote ischaemic pre-conditioning, therapeutic hypothermia, and hyperoxaemia), and pharmacological (atrial natriuretic peptide, cyclosporin-A, and exenatide) therapeutic strategies, for preventing myocardial RI, many of which have shown promise in initial proof-of-principle clinical studies. In this article, we review the pathophysiology underlying myocardial RI, and highlight the potential therapeutic interventions which may be used in the future to prevent RI and improve clinical outcomes in patients with CHD.

Haemodynamically irrelevant pericardial effusion is associated with increased mortality in patients with chronic heart failure.

AIMS: Pericardial effusion (PE) is a common finding in cardiac patients with chronic heart failure. The prognostic relevance of a small, haemodynamically non-compromising PE in such patients, however, remains to be determined. METHODS AND RESULTS: All patients referred to our heart failure clinic and having a baseline echocardiography and follow-up clinical visits were included. Patients with a haemodynamically relevant PE, acute myo-/pericarditis, systemic sclerosis, rheumatoid arthritis, heart transplantation, heart surgery within the last 6 months or malignancies within the last 3 years were excluded. Patients with or without a haemodynamically irrelevant PE were compared regarding all-cause mortality as the primary and cardiovascular death or need for heart transplantation as secondary outcomes. A total of 897 patients (824 patients in the control vs. 73 patients in the PE group) were included. In the PE group, left ventricular ejection fraction (LVEF) was lower [31%, interquartile range (IQR): 18.0-45.0] than in controls (34%, IQR: 25.0-47.0; P = 0.04), while the end-systolic diameters of the left ventricle and the left atrium were larger (P = 0.01 and P = 0.001, respectively). Similarly, in patients with PE, the right ventricle (RV) systolic function was lower (P < 0.005 for both the fractional area change and the tricuspid annulus movement), the dimensions of RV and right atrium (RA) were larger (P < 0.05 for RV and P < 0.01 for RA), and the degree of tricuspid regurgitation was higher (P < 0.0001). Furthermore, in the PE group, the heart rate was higher (P < 0.001) and the leukocyte count as well as CRP values were increased (P = 0.004 and P < 0.0001, respectively); beta-blocker use was less frequent (P = 0.04), while spironolactone use was more frequent (P = 0.03). The overall survival was reduced in the PE group compared with controls (P = 0.02). Patients with PE were more likely to suffer cardiovascular death (1-year estimated event-free survival: 86 ± 5 vs. 95 ± 1%; P = 0.01) and to require heart transplantation (1-year estimated event-free survival: 88 ± 4 vs. 95 ± 1%; P = 0.009). A multivariate Cox proportional hazard model revealed the following independent predictors of mortality: (a) PE (P = 0.04, hazard ratio (HR): 1.95, 95% confidence interval (CI): 1.0-3.7), (b) age (P = 0.04, HR: 1.02, 95% CI: 1.0-1.04) and (c) LVEF <35% (P = 0.03, HR: 1.7, 95% CI: 1.1-2.8). CONCLUSION: In chronic heart failure, even minor PEs are associated with an increased risk of all-cause mortality, cardiac death, and need for transplantation.

Statins and the risk of cancer after heart transplantation.

BACKGROUND: Although newer immunosuppressive agents, such as mTOR (mammalian target of rapamycin) inhibitors, have lowered the occurrence of malignancies after transplantation, cancer is still a leading cause of death late after heart transplantation. Statins may have an impact on clinical outcomes beyond their lipid-lowering effects. The aim of the present study was to delineate whether statin therapy has an impact on cancer risk and total mortality after heart transplantation. METHODS AND RESULTS: A total of 255 patients who underwent heart transplantation at the University Hospital Zurich between 1985 and 2007 and survived the first year were included in the present study. The primary outcome measure was the occurrence of any malignancy; the secondary end point was overall survival. During follow-up, a malignancy was diagnosed in 108 patients (42%). The cumulative incidence of tumors 8 years after transplantation was reduced in patients receiving a statin (34% versus 13%; 95% confidence interval, 0.25-0.43 versus 0.07-0.18; P<0.003). Statin use was associated with improved cancer-free and overall survival (both P<0.0001). A Cox regression model that analyzed the time to tumor formation with or without statin therapy, adjusted for age, male sex, type of cardiomyopathy, and immunosuppressive therapy (including switch to mTOR inhibitors or tacrolimus), demonstrated a superior survival in the statin group. Statins reduced the hazard of occurrence of any malignancy by 67% (hazard ratio, 0.33; 95% confidence interval, 0.21-0.51; P<0.0001). CONCLUSIONS: Although it is not possible to adjust for all potential confounders because of the very long follow-up period, this registry suggests that statin use is associated with improved cancer-free and overall survival after cardiac transplantation. These data will need to be confirmed in a prospective trial.

Drug eluting balloons for de novo coronary lesions - a systematic review and meta-analysis.

BACKGROUND: The role of drug-eluting balloons (DEB) is unclear. Increasing evidence has shown a benefit for the treatment of in-stent restenosis. Its effect on de novo coronary lesions is more controversial. Several smaller randomized trials found conflicting results. METHODS: This is a systematic review and meta-analysis of randomized controlled trials (RCT) evaluating the effect of local Paclitaxel delivery/drug eluting balloons (DEB) (+/- bare metal stent) compared to current standard therapy (stenting) to treat de novo coronary lesions. Data sources for RCT were identified through a literature search from 2005 through 28 December 2012. The main endpoints of interest were target lesion revascularization (TLR), major adverse cardiac events (MACE), binary in-segment restenosis, stent thrombosis (ST), myocardial infarction (MI), late lumen loss (LLL) and mortality. A random effects model was used to calculate the pooled relative risks (RR) with 95% confidence intervals. RESULTS: Eight studies (11 subgroups) and a total of 1,706 patients were included in this analysis. Follow-up duration ranged from 6 to 12 months. Overall, DEB showed similar results to the comparator treatment. The relative risk (RR) for MACE was 0.95 (0.64 to 1.39); P = 0.776, for mortality it was 0.79 (0.30 to 2.11), P = 0.644, for stent thrombosis it was 1.45 (0.42 to 5.01), P = 0.560, for MI it was 1.26 (0.49 to 3.21), P = 0.629, for TLR it was 1.09 (0.71 to 1.68); P = 0.700 and for binary in-stent restenosis it was 0.96 (0.48 to 1.93), P = 0.918. Compared to bare metal stents (BMS), DEB showed a lower LLL (- 0.26 mm (-0.51 to 0.01)) and a trend towards a lower MACE risk (RR 0.66 (0.43 to 1.02)). CONCLUSION: Overall, drug-eluting balloons (+/- bare metal stent) are not superior to current standard therapies (BMS or drug eluting stent (DES)) in treating de novo coronary lesions. However, the performance of DEB seems to lie in between DES and BMS with a trend towards superiority over BMS alone. Therefore, DEB may be considered in patients with contraindications for DES. The heterogeneity between the included studies is a limitation of this meta-analysis; different drug-eluting balloons have been used.

Donor-specific anti-HLA antibodies detected by Luminex: predictive for short-term but not long-term survival after heart transplantation.

In heart transplantation, the clinical significance of pretransplant donor-specific antibodies (DSA) detected by solid phase assay (SPA), which is more sensitive than the conventional complement-dependent cytotoxicity (CDC) assays, is unclear. The aim was to evaluate SPA performed on pretransplant sera for survival after heart transplantation. Pretransplant sera of 272 heart transplant recipients were screened for anti-HLA antibodies using CDC and SPA. For determination of pretransplant DSA, a single-antigen bead assay was performed. The presence of anti-HLA antibodies was correlated with survival. Secondary outcome parameters were acute cellular rejection, graft coronary vasculopathy and ejection fraction. In Kaplan-Meier analysis, SPA-screening did not predict survival (P = 0.494), this in contrast to CDC screening (P = 0.002). However, the presence of pretransplant DSA against HLA class I was associated with decreased short-term survival compared to non-DSA (P = 0.038). ROC curve analysis showed a sensitivity of 76% and specificity of 73% at a cutoff of 2000 MFI. In contrast, the presence of anti-HLA antibodies had no influence on long-term survival, rejection incidence, and graft function. Thus, detection of DSA class I in pretransplant serum is a strong predictor of short-term, but not long-term survival and may help in the early management of heart transplant patients.

Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study.

AIMS: Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive. METHODS AND RESULTS: Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P < 0.0001), while no change was observed with placebo (5.4 ± 2.4 to 4.7 ± 2.0; P = 0.051). This difference between study groups was significant [estimated treatment effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F(2t)-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo. CONCLUSION: This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress.

Safe and secure vehicle routing: a survey on minimization of risk exposure.

Safe and secure vehicle routing problems refer to the transportation of dangerous (e.g., flammable liquids) or valuable goods (e.g., cash), the surveillance of streets (e.g., police patrols) or other areas (e.g., those within a factory or building), and the response to sudden incidents (e.g., robberies or street disruptions). It thus covers a multitude of models and methods with each having its own objective and constraints, such as unpredictability or risk. We review and classify literature in this field and thereby identify a starting point for researchers in this evolving and practically relevant field. Our study reveals that there are 82 articles that cover aspects related to safe and secure routing, a majority of which were published in the last five years. We classify the articles into five main categories: (i) transportation of hazardous materials, (ii) patrol routing, (iii) cash-in-transit, (iv) dissimilar routing problems, and (v) modeling of multi-graphs. Categories (i)-(iv) elaborate on the problem studied, while (v) provides a general concept based on road network characteristics most commonly found in safe and secure routing problems. Relevant methods and instances, along with their similarities and dissimilarities, have also been discussed in the paper. Furthermore, specific problem characteristics and future research directions are identified.

Hospital Outcomes of Community-Acquired SARS-CoV-2 Omicron Variant Infection Compared With Influenza Infection in Switzerland.

Importance: With the ongoing COVID-19 pandemic, it is crucial to assess the current burden of disease of community-acquired SARS-CoV-2 Omicron variant in hospitalized patients to tailor appropriate public health policies. Comparisons with better-known seasonal influenza infections may facilitate such decisions. Objective: To compare the in-hospital outcomes of patients hospitalized with the SARS-CoV-2 Omicron variant with patients with influenza. Design, Setting, and Participants: This cohort study was based on a national COVID-19 and influenza registry. Hospitalized patients aged 18 years and older with community-acquired SARS-CoV-2 Omicron variant infection who were admitted between January 15 and March 15, 2022 (when B.1.1.529 Omicron predominance was >95%), and hospitalized patients with influenza A or B infection from January 1, 2018, to March 15, 2022, where included. Patients without a study outcome by August 30, 2022, were censored. The study was conducted at 15 hospitals in Switzerland. Exposures: Community-acquired SARS-CoV-2 Omicron variant vs community-acquired seasonal influenza A or B. Main Outcomes and Measures: Primary and secondary outcomes were defined as in-hospital mortality and admission to the intensive care unit (ICU) for patients with the SARS-CoV-2 Omicron variant or influenza. Cox regression (cause-specific and Fine-Gray subdistribution hazard models) was used to account for time-dependency and competing events, with inverse probability weighting to adjust for confounders with right-censoring at day 30. Results: Of 5212 patients included from 15 hospitals, 3066 (58.8%) had SARS-CoV-2 Omicron variant infection in 14 centers and 2146 patients (41.2%) had influenza A or B in 14 centers. Of patients with the SARS-CoV-2 Omicron variant, 1485 (48.4%) were female, while 1113 patients with influenza (51.9%) were female (P = .02). Patients with the SARS-CoV-2 Omicron variant were younger (median [IQR] age, 71 [53-82] years) than those with influenza (median [IQR] age, 74 [59-83] years; P < .001). Overall, 214 patients with the SARS-CoV-2 Omicron variant (7.0%) died during hospitalization vs 95 patients with influenza (4.4%; P < .001). The final adjusted subdistribution hazard ratio (sdHR) for in-hospital death for SARS-CoV-2 Omicron variant vs influenza was 1.54 (95% CI, 1.18-2.01; P = .002). Overall, 250 patients with the SARS-CoV-2 Omicron variant (8.6%) vs 169 patients with influenza (8.3%) were admitted to the ICU (P = .79). After adjustment, the SARS-CoV-2 Omicron variant was not significantly associated with increased ICU admission vs influenza (sdHR, 1.08; 95% CI, 0.88-1.32; P = .50). Conclusions and Relevance: The data from this prospective, multicenter cohort study suggest a significantly increased risk of in-hospital mortality for patients with the SARS-CoV-2 Omicron variant vs those with influenza, while ICU admission rates were similar.

Implementation of the ESC STEMI guidelines in female and elderly patients over a 20-year period in a large German registry.

AIMS: We investigated the implementation of new guidelines in ST-segment elevation myocardial infarction (STEMI) patients in a large real-world patient population in the metropolitan area of Berlin (Germany) over a 20-year period. METHODS: From January 2000 to December 2019, a total of 25 792 patients were admitted with STEMI to one of the 34 member hospitals of the Berlin-Brandenburg Myocardial Infarction Registry (B2HIR) and were stratified for sex and age < 75 and ≥ 75 years. RESULTS: The median age of women was 72 years (IQR 61-81) compared to 61 years in men (IQR 51-71). PCI treatment as a standard of care was implemented in men earlier than in women across all age groups. It took two years from the 2017 class IA ESC STEMI guideline recommendation to prefer the radial access route rather than femoral until > 60% of patients were treated accordingly. In 2019, less than 60% of elderly women were treated via a radial access. While the majority of patients < 75 years already received ticagrelor or prasugrel as antiplatelet agent in the year of the class IA ESC STEMI guideline recommendation in 2012, men ≥ 75 years lagged two years and women ≥ 75 three years behind. Amongst the elderly, in-hospital mortality was 22.6% (737) for women and 17.3% (523) for men (p < 0.001). In patients < 75 years fatal outcome was less likely with 7.2% (305) in women and 5.8% (833) in men (p < 0.001). After adjustment for confounding variables, female sex was an independent predictor of in-hospital mortality in patients ≥ 75 years (OR 1.37, 95% CI 1.12-1.68, p = 0.002), but not in patients < 75 years (p = 0.076). CONCLUSION: In-hospital mortality differs considerably by age and sex and remains highest in elderly patients and in particular in elderly females. In these patient groups, guideline recommended therapies were implemented with a significant delay.

Smoking trends and health equity in Switzerland between 1992 and 2017: dependence of smoking prevalence on educational level and social determinants.

Background: Switzerland ranks among the top three healthcare systems in the world with regards to healthcare access, suggesting a high degree of health equity. However, Switzerland has few preventive strategies against smoking abuse. The aim of this study is to clarify whether educational level and citizenship status have an influence on the prevalence of smoking in Switzerland and whether there is health inequity related to a lack of preventive strategies. Methods: We based our analysis on publicly available health data published in the Swiss government's Swiss health survey (1992-2017). We compared the prevalence of smoking across the years and correlated these data with levels of educational attainment, citizenship status and age. Results: A continuous significant decline in smokers is observed in the highest education group (TERT). Over time, prevalence was reduced from 29% in 1992 to 23% in 2017 (p < 0.001). The intermediate-level educational group (SEK 2) showed smaller but also significant decline on a 0.05 sigificance level over the same period, from 31% to 29% (p = 0.003). The lowest educational group showed a nonsignificant decline from 28% to 27% (p = 0.6). The population who holds Swiss citizenship showed a decrease in smoking from 28% to 26% within the time frame (p < 0.001). People without Swiss citizenship had a much higher prevalence of smokers, at 38% in 1992 and declining to 32% in 2017 (p < 0.001). All cohorts from age 15 to age 64 have a far higher prevalence of smokers than cohorts at an older age, with the highest prevalence in the 25-34 age group. Conclusion: In Switzerland, individuals with lower levels of education and non-Swiss populations are more susceptible to health risk of smoking. This is despite the existence of a high-quality healthcare system that has nevertheless failed to negated health inequities.