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No abstract is provided for this article.

Background In patients with 3-vessel coronary artery disease (CAD) and/or left main CAD, individual risk prediction plays a key role in deciding between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Objectives The aim of this study was to assess whether these individualized revascularization decisions can be improved by applying machine learning (ML) algorithms and integrating clinical, biological, and anatomical factors. Methods In the SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) study, ML algorithms (Lasso regression, gradient boosting) were used to develop a prognostic index for 5-year death, which was combined, in the second stage, with assigned treatment (PCI or CABG) and prespecified effect-modifiers: disease type (3-vessel or left main CAD) and anatomical SYNTAX score. The model’s discriminative ability to predict the risk of 5-year death and treatment benefit between PCI and CABG was cross-validated in the SYNTAX trial (n = 1,800) and externally validated in the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome Study in Kyoto) registry (n = 7,362), and then compared with the original SYNTAX score II 2020 (SSII-2020). Results The hybrid gradient boosting model performed best for predicting 5-year all-cause death with C-indexes of 0.78 (95% CI: 0.75-0.81) in cross-validation and 0.77 (95% CI: 0.76-0.79) in external validation. The ML models discriminated 5-year mortality better than the SSII-2020 in the external validation cohort and identified heterogeneity in the treatment benefit of CABG vs PCI. Conclusions An ML-based approach for identifying individuals who benefit from CABG or PCI is feasible and effective. Implementation of this model in health care systems—trained to collect large numbers of parameters—may harmonize decision making globally. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries; NCT00114972)

Background: The impact of the sampling rate (SR) of optical frequency domain imaging (OFDI) on quantitative assessment of in-stent structures (ISS) such as plaque prolapse and thrombus remains unexplored. Methods and Results: OFDI after stenting was performed in ST-segment elevation myocardial infarction (STEMI) patients using a TERUMO OFDI system (Terumo Europe, Leuven, Belgium) with 160frames/s and pullback speed of 20mm/s. A total of 126 stented segments were analyzed. ISS were classified as either attached or non-attached to stent area boundaries. The volume, mean area and largest area of ISS were assessed according to 4 frequencies of SR, corresponding to distances between the analyzed frames of 0.125, 0.25, 0.50 and 1.0mm. ISS volume was calculated by integrating cross-sectional ISS areas multiplied by each sampling distance using the disk summation method. The volume and mean area of ISS became significantly larger, while the largest area became significantly smaller as sampling distance became larger (1.11mm2 for 0.125mm vs. 1.00mm2 for 1.0mm, P for trend=0.036). In addition, variance of difference was positively associated with increasing width of sampling distance. Conclusions: Quantification of ISS is significantly influenced by the applied frequency of SR. This should be taken into account when designing future OFDI studies in which quantitative assessment of ISS is critical for the evaluation of STEMI patients. (Circ J 2012; 76: 2822–2831)

Atherosclerosis is currently appreciated as a disease with a large inflammatory component. The underlying mechanisms, which are uncovered in a rapid pace, are greatly interconnected and as such very complex. Nevertheless, for clinicians it is important have some degree of insight in these immunologic mechanisms in order to interpret the current research advances. The aim of this review is to supply clinicians with this knowledge, avoiding too much detail. All the relevant immunologic basics will be discussed at first, followed by the immunity related theories of atherosclerosis. Finally, current and new immune-modulatory therapies will be discussed.

<i>Background:</i> Sputum induction is increasingly used to study both cellular and biochemical composition of the airways. However, there is a significant rise in the percentage of neutrophils at 8 h after inhalation with hypertonic saline. <i>Objective:</i> The aim of this study was to assess whether markers of inflammation in exhaled air and exhaled air condensate change after sputum induction in normal and asthmatic subjects. <i>Methods:</i> We measured leukotriene B<sub>4</sub> (LTB<sub>4</sub>) and a marker of oxidative stress, 8-isoprostane, (by enzyme immunoassay) in exhaled air condensate and exhaled nitric oxide (NO; by chemiluminescence analyzer) in 15 healthy subjects (8 females, mean age 35 ± 4 years, FEV<sub>1</sub> 97.4% predicted) and in 8 mild asthmatic subjects (5 males, mean age 34 ± 2 years, FEV<sub>1</sub> 70.5% predicted). <i>Results:</i> LTB<sub>4</sub> was significantly higher compared with baseline at 6 h butdid not remain increased at 24 h after sputum induction (134.3 ± 30.15 and 75.4 ± 14.32 vs. 64.6 ± 11.6 pg/ml at baseline; p < 0.02 and p > 0.05, respectively) in healthy subjects. An inverse correlation between LTB<sub>4</sub> and exhaled NO at 6 h after sputum induction was observed in healthy subjects (r = –0.66, p < 0.03). No increase in LTB<sub>4</sub> levels was observed in asthmatic patients. Baseline 8-isoprostane levels were higher in asthmatic patients than in healthy subjects (47.3 ± 37.1 vs. 17.5 ± 8.8 pg/ml; p < 0.01). A trend towards increased levels of 8-isoprostane could be observed at 6 and 24 h after inhalation in healthy subjects (26.2 ± 3.7 and 26.7 ± 3.9 pg/ml; p = 0.09 and p = 0.07, respectively). In healthy subjects, exhaled NO was significantly higher compared with baseline at 6 h and remained increased 24 h after sputum induction (7.96 ± 3.5 vs. 5.61 ± 1.86 ppb; p < 0.01 and p < 0.05, respectively). Exhaled NO levels were increased in asthmatic patients but did not further increase after sputum induction. <i>Conclusions:</i> Sputum induction with hypertonic saline causes an inflammatory response which should be considered when using the technique to monitor airway inflammation.

<h3>Importance</h3> Left atrial appendage occlusion (LAAO) has emerged as an alternative to anticoagulation for patients with atrial fibrillation. However, the performance of LAAO among East Asian patients is unknown. <h3>Objective</h3> To document the procedural success rate and configurations, major adverse event rates, and antithrombotic medication regimens during and after LAAO procedures among patients in China. <h3>Design, Setting, and Participants</h3> In this cohort study, consecutive patients from 39 Chinese centers undergoing LAAO were prospectively enrolled between April 1, 2019, and October 31, 2020. Periprocedural and intraprocedural techniques and postprocedural medications were left to the surgeon's discretion. Data were analyzed from July 1 to November 1, 2021. <h3>Exposure</h3> LAAO for patients with atrial fibrillation. <h3>Main Outcomes and Measures</h3> The main outcomes were procedural success and complication rates periprocedure and major adverse event rates of death, stroke, systemic embolism, and bleeding events at 30 days postprocedure; the composite end point of death, stroke, and systemic embolism was also analyzed. Unadjusted and multivariable-adjusted logistic regression analyses were performed to assess the associations of periprocedural techniques (types of anesthesia, intraprocedural imaging modalities, and combined ablation procedure) with 30-day adverse events. <h3>Results</h3> Among 3096 enrolled participants, 1782 participants (57.6%) were men, and the mean (SD) age was 69 (9) years. Participants had a high risk of stroke (mean [SD] cardiovascular risk score, 4.0 [1.8]) and a moderate-to-high risk of bleeding (mean [SD] bleeding risk score, 2.4 [1.2]). A total of 1287 procedures (41.6%) were performed under local anesthesia, while 493 procedures (15.9%) used only fluoroscopy guidance. In 1297 procedures (41.9%), LAAO implantation was combined with radiofrequency ablation or cryoablation for atrial fibrillation. Procedural success was achieved in 3032 patients (97.9%). At 30-day follow-up, the rate of the composite end point of death, stroke, or systemic embolism was 0.52% (95% CI, 0.32%-0.84%), and the rate of any life-threatening or major bleeding was 1.23% (95% CI, 0.90%-1.68%). No significant associations were observed between the procedural success or 30-day adverse events and the types of anesthesia (general or local), intraprocedural imaging (transesophageal echocardiography, fluoroscopy, or intracardiac echocardiography), or whether a combined ablation procedure was performed or not. In centers performing at least 40 procedures per year, compared with those performing fewer than 40 procedures per year, procedural success was significantly higher (adjusted odd ratio [aOR], 1.97; 95% CI, 1.01-3.53;<i>P</i> = .02) and risk of life-threatening or major bleeding was significantly lower (aOR, 0.42; 95% CI, 0.21-0.87;<i>P</i> = .02). <h3>Conclusions and Relevance</h3> These findings suggest that patients with a high risk of stroke and moderate to high risk of bleeding who underwent implantation of a LAAO device in Chinese centers had high rates of procedural success and low rates of short-term ischemic and bleeding events.

The phosphatidylinositol 3-kinase (PI3K) pathway is activated in chronic obstructive pulmonary disease (COPD), but the regulatory mechanisms for this pathway are yet to be elucidated. The aim of this study was to determine the expression and role of phosphatase and tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of the PI3K pathway, in COPD. PTEN protein expression was measured in the peripheral lung of COPD patients compared with smoking and nonsmoking controls. The direct influence of cigarette smoke extract (CSE) on PTEN expression was assessed using primary lung epithelial cells and a cell line (BEAS-2B) in the presence or absence of l-buthionine-sulfoximine (BSO) to deplete intracellular glutathione. The impact of PTEN knockdown by RNA interference on cytokine production was also examined. In peripheral lung, PTEN protein was significantly decreased in patients with COPD compared with the subjects without COPD ( P &lt; 0.001) and positively correlated with the severity of airflow obstruction (forced expiratory volume in 1-s percent predicted; r = 0.50; P = 0.0012). Conversely, phosphorylated Akt, as a marker of PI3K activation, showed a negative correlation with PTEN protein levels ( r = −0.41; P = 0.0042). In both primary bronchial epithelial cells and BEAS-2B cells, CSE decreased PTEN protein, which was reversed by N-acetyl cysteine treatment. PTEN knockdown potentiated Akt phosphorylation and enhanced production of proinflammatory cytokines, such as IL-6, CXCL8, CCL2, and CCL5. In conclusion, oxidative stress reduces PTEN protein levels, which may result in increased PI3K signaling and amplification of inflammation in COPD.