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<div><h4>Merging machine learning and patient preference: a novel tool for risk prediction of percutaneous coronary interventions.</h4><i>Hamilton DE, Albright J, Seth M, Painter I, ... Sukul D, Gurm HS</i><br /><b>Background:</b><br/>and aims</b><br />Predicting personalized risk for adverse events following percutaneous coronary intervention (PCI) remains critical in weighing treatment options, employing risk mitigation strategies, and enhancing shared decision-making. This study aimed to employ machine learning models using pre-procedural variables to accurately predict common post-PCI complications.<br /><b>Methods</b><br />A group of 66 adults underwent a semiquantitative survey assessing a preferred list of outcomes and model display. The machine learning cohort included 107 793 patients undergoing PCI procedures performed at 48 hospitals in Michigan between 1 April 2018 and 31 December 2021 in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) registry separated into training and validation cohorts. External validation was conducted in the Cardiac Care Outcomes Assessment Program database of 56 583 procedures in 33 hospitals in Washington.<br /><b>Results</b><br />Overall rate of in-hospital mortality was 1.85% (n = 1999), acute kidney injury 2.51% (n = 2519), new-onset dialysis 0.44% (n = 462), stroke 0.41% (n = 447), major bleeding 0.89% (n = 942), and transfusion 2.41% (n = 2592). The model demonstrated robust discrimination and calibration for mortality {area under the receiver-operating characteristic curve [AUC]: 0.930 [95% confidence interval (CI) 0.920-0.940]}, acute kidney injury [AUC: 0.893 (95% CI 0.883-0.903)], dialysis [AUC: 0.951 (95% CI 0.939-0.964)], stroke [AUC: 0.751 (95%CI 0.714-0.787)], transfusion [AUC: 0.917 (95% CI 0.907-0.925)], and major bleeding [AUC: 0.887 (95% CI 0.870-0.905)]. Similar discrimination was noted in the external validation population. Survey subjects preferred a comprehensive list of individually reported post-procedure outcomes.<br /><b>Conclusions</b><br />Using common pre-procedural risk factors, the BMC2 machine learning models accurately predict post-PCI outcomes. Utilizing patient feedback, the BMC2 models employ a patient-centred tool to clearly display risks to patients and providers (https://shiny.bmc2.org/pci-prediction/). Enhanced risk prediction prior to PCI could help inform treatment selection and shared decision-making discussions.<br /><br />© 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.<br /><br /><small>Eur Heart J: 21 Feb 2024; 45:601-609</small></div>
Hamilton DE, Albright J, Seth M, Painter I, ... Sukul D, Gurm HS
Eur Heart J: 21 Feb 2024; 45:601-609 | PMID: 38233027
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<div><h4>Clonal haematopoiesis of indeterminate potential and atrial fibrillation: an east Asian cohort study.</h4><i>Ahn HJ, An HY, Ryu G, Lim J, ... Koh Y, Choi EK</i><br /><b>Background:</b><br/>and aims</b><br />Both clonal haematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. This study investigated the potential role of CHIP in the development and progression of AF.<br /><b>Methods</b><br />Deep-targeted sequencing of 24 CHIP mutations (a mean depth of coverage = 1000×) was performed in 1004 patients with AF and 3341 non-AF healthy subjects. Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and AF was evaluated by the comparison of (i) the prevalence of CHIP mutations between AF and non-AF subjects and (ii) clinical characteristics discriminated by CHIP mutations within AF patients. Furthermore, the risk of clinical outcomes-the composite of heart failure, ischaemic stroke, or death-according to the presence of CHIP mutations in AF was investigated from the UK Biobank cohort.<br /><b>Results</b><br />The mean age was 67.6 ± 6.9 vs. 58.5 ± 6.5 years in AF (paroxysmal, 39.0%; persistent, 61.0%) and non-AF cohorts, respectively. CHIP mutations with a variant allele fraction of ≥2.0% were found in 237 (23.6%) AF patients (DNMT3A, 13.5%; TET2, 6.6%; and ASXL1, 1.5%) and were more prevalent than non-AF subjects [356 (10.7%); P < .001] across the age. After multivariable adjustment (age, sex, smoking, body mass index, diabetes, and hypertension), CHIP mutations were 1.4-fold higher in AF [adjusted odds ratio (OR) 1.38; 95% confidence interval 1.10-1.74, P < .01]. The ORs of CHIP mutations were the highest in the long-standing persistent AF (adjusted OR 1.50; 95% confidence interval 1.14-1.99, P = .004) followed by persistent (adjusted OR 1.44) and paroxysmal (adjusted OR 1.33) AF. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (adjusted OR 1.65; 95% confidence interval 1.05-2.60, P = .030). AF patients with CHIP mutations were older and had a higher prevalence of diabetes, a longer AF duration, a higher E/E\', and a more severely enlarged left atrium than those without CHIP mutations (all P < .05). In UK Biobank analysis of 21 286 AF subjects (1297 with CHIP and 19 989 without CHIP), the CHIP mutation in AF is associated with a 1.32-fold higher risk of a composite clinical event (heart failure, ischaemic stroke, or death).<br /><b>Conclusions</b><br />CHIP mutations, primarily DNMT3A or TET2, are more prevalent in patients with AF than non-AF subjects whilst their presence is associated with a more progressive nature of AF and unfavourable clinical outcomes.<br /><br />© 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.<br /><br /><small>Eur Heart J: 07 Mar 2024; 45:778-790</small></div>
Ahn HJ, An HY, Ryu G, Lim J, ... Koh Y, Choi EK
Eur Heart J: 07 Mar 2024; 45:778-790 | PMID: 38231881
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<div><h4>Aspirin-free antiplatelet strategies after percutaneous coronary interventions.</h4><i>Capranzano P, Moliterno D, Capodanno D</i><br /><AbstractText>Dual antiplatelet therapy (DAPT) with aspirin and a platelet P2Y12 receptor inhibitor is the standard antithrombotic treatment after percutaneous coronary interventions (PCI). Several trials have challenged guideline-recommended DAPT after PCI by testing the relative clinical effect of an aspirin-free antiplatelet approach-consisting of P2Y12 inhibitor monotherapy after a short course (mostly 1-3 months) of DAPT-among patients undergoing PCI without a concomitant indication for oral anticoagulation (OAC). Overall, these studies have shown P2Y12 inhibitor monotherapy after short DAPT to be associated with a significant reduction in the risk of bleeding without an increase in thrombotic or ischaemic events compared with continued DAPT. Moreover, the effects of the P2Y12 inhibitor monotherapy without prior DAPT or following a very short course of DAPT after PCI are being investigated in emerging studies, of which one has recently reported unfavourable efficacy results associated with the aspirin-free approach compared with conventional DAPT. Finally, P2Y12 inhibitor alone has been compared with aspirin alone as chronic therapy after DAPT discontinuation, thus challenging the historical role of aspirin as a standard of care for secondary prevention following PCI. A thorough understanding of study designs, populations, treatments, results, and limitations of trials testing P2Y12 inhibitor monotherapy vs. DAPT or vs. aspirin is required to consider adopting this treatment in clinical practice. This review addresses the use of aspirin-free antiplatelet strategies among patients undergoing PCI without a concomitant indication for OAC, providing an overview of clinical evidence, guideline indications, practical implications, ongoing issues, and future perspectives.</AbstractText><br /><br />© 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.<br /><br /><small>Eur Heart J: 21 Feb 2024; 45:572-585</small></div>
Capranzano P, Moliterno D, Capodanno D
Eur Heart J: 21 Feb 2024; 45:572-585 | PMID: 38240716
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<div><h4>Artificial intelligence-derived risk score for mortality in secondary mitral regurgitation treated by transcatheter edge-to-edge repair: the EuroSMR risk score.</h4><i>Hausleiter J, Lachmann M, Stolz L, Bedogni F, ... Rudolph V, EuroSMR Investigators </i><br /><b>Background:</b><br/>and aims</b><br />Risk stratification for mitral valve transcatheter edge-to-edge repair (M-TEER) is paramount in the decision-making process to appropriately select patients with severe secondary mitral regurgitation (SMR). This study sought to develop and validate an artificial intelligence-derived risk score (EuroSMR score) to predict 1-year outcomes (survival or survival + clinical improvement) in patients with SMR undergoing M-TEER.<br /><b>Methods</b><br />An artificial intelligence-derived risk score was developed from the EuroSMR cohort (4172 and 428 patients treated with M-TEER in the derivation and validation cohorts, respectively). The EuroSMR score was validated and compared with established risk models.<br /><b>Results</b><br />The EuroSMR risk score, which is based on 18 clinical, echocardiographic, laboratory, and medication parameters, allowed for an improved discrimination of surviving and non-surviving patients (hazard ratio 4.3, 95% confidence interval 3.7-5.0; P < .001), and outperformed established risk scores in the validation cohort. Prediction for 1-year mortality (area under the curve: 0.789, 95% confidence interval 0.737-0.842) ranged from <5% to >70%, including the identification of an extreme-risk population (2.6% of the entire cohort), which had a very high probability for not surviving beyond 1 year (hazard ratio 6.5, 95% confidence interval 3.0-14; P < .001). The top 5% of patients with the highest EuroSMR risk scores showed event rates of 72.7% for mortality and 83.2% for mortality or lack of clinical improvement at 1-year follow-up.<br /><b>Conclusions</b><br />The EuroSMR risk score may allow for improved prognostication in heart failure patients with severe SMR, who are considered for a M-TEER procedure. The score is expected to facilitate the shared decision-making process with heart team members and patients.<br /><br />© 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.<br /><br /><small>Eur Heart J: 14 Mar 2024; 45:922-936</small></div>
Hausleiter J, Lachmann M, Stolz L, Bedogni F, ... Rudolph V, EuroSMR Investigators
Eur Heart J: 14 Mar 2024; 45:922-936 | PMID: 38243773
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<div><h4>C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease: the BiomarCaRE project.</h4><i>Arnold N, Blaum C, Goßling A, Brunner FJ, ... Koenig W, Waldeyer C</i><br /><b>Background:</b><br/>and aims</b><br />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.<br /><b>Methods</b><br />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).<br /><b>Results</b><br />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).<br /><b>Conclusions</b><br />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.<br /><br />© 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.<br /><br /><small>Eur Heart J: 27 Mar 2024; 45:1043-1054</small></div>
Arnold N, Blaum C, Goßling A, Brunner FJ, ... Koenig W, Waldeyer C
Eur Heart J: 27 Mar 2024; 45:1043-1054 | PMID: 38240386
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<div><h4>The American Heart Association Emergency Cardiovascular Care 2030 Impact Goals and Call to Action to Improve Cardiac Arrest Outcomes: A Scientific Statement From the American Heart Association.</h4><i>Merchant RM, Becker LB, Brooks SC, Chan PS, ... Sasson C, American Heart Association</i><br /><AbstractText>Every 10 years, the American Heart Association (AHA) Emergency Cardiovascular Care Committee establishes goals to improve survival from cardiac arrest. These goals align with broader AHA Impact Goals and support the AHA\'s advocacy efforts and strategic investments in research, education, clinical care, and quality improvement programs. This scientific statement focuses on 2030 AHA emergency cardiovascular care priorities, with a specific focus on bystander cardiopulmonary resuscitation, early defibrillation, and neurologically intact survival. This scientific statement also includes aspirational goals, such as establishing cardiac arrest as a reportable disease and mandating reporting of standardized outcomes from different sources; advancing recognition of and knowledge about cardiac arrest; improving dispatch system response, availability, and access to resuscitation training in multiple settings and at multiple time points; improving availability, access, and affordability of defibrillators; providing a focus on early defibrillation, in-hospital programs, and establishing champions for debriefing and review of cardiac arrest events; and expanding measures to track outcomes beyond survival. The ability to track and report data from these broader aspirational targets will potentially require expansion of existing data sets, development of new data sets, and enhanced integration of technology to collect process and outcome data, as well as partnerships of the AHA with national, state, and local organizations. The COVID-19 (coronavirus disease 2019) pandemic, disparities in COVID-19 outcomes for historically excluded racial and ethnic groups, and the longstanding disparities in cardiac arrest treatment and outcomes for Black and Hispanic or Latino populations also contributed to an explicit focus and target on equity for the AHA Emergency Cardiovascular Care 2030 Impact Goals.</AbstractText><br /><br /><br /><br /><small>Circulation: 20 Mar 2024; 149:e914-e933</small></div>
Merchant RM, Becker LB, Brooks SC, Chan PS, ... Sasson C, American Heart Association
Circulation: 20 Mar 2024; 149:e914-e933 | PMID: 38250800
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<div><h4>Effect of Gamification, Financial Incentives, or Both to Increase Physical Activity Among Patients at High Risk of Cardiovascular Events: The BE ACTIVE Randomized Controlled Trial.</h4><i>Fanaroff AC, Patel MS, Chokshi N, Coratti S, ... Small DS, Volpp KGM</i><br /><b>Background</b><br />Physical activity is associated with a lower risk of major adverse cardiovascular events, but few individuals achieve guideline recommended levels of physical activity. Strategies informed by behavioral economics increase physical activity, but their longer-term effectiveness is uncertain. We sought to determine the effect of behaviorally-designed gamification, loss-framed financial incentives, or the combination on physical activity compared with attention control over 12-month intervention and 6-month post-intervention follow-up periods.<br /><b>Methods</b><br />Between May 2019 and January 2024, participants with clinical ASCVD or 10-year risk of myocardial infarction, stroke, or cardiovascular death ≥ 7.5% by the pooled cohort equation were enrolled in a pragmatic randomized clinical trial. Participants received a wearable device to track daily steps, established a baseline, selected a step goal increase, and were randomly assigned to control (n = 151), behaviorally-designed gamification (n = 304), loss-framed financial incentives (n = 302), or gamification + financial incentives (n = 305). The trial\'s primary outcome was change in mean daily steps from baseline through the 12-month intervention period.<br /><b>Results</b><br />A total of 1062 patients (mean [SD] age 67 [8], 61% female, 31% non-white) were enrolled. Compared with controls, participants had significantly greater increases in mean daily steps from baseline during the 12-month intervention in the gamification arm (adjusted difference, 538.0; 95% CI, 186.2-889.9; <i>P</i> = 0.0027), financial incentives arm (adjusted difference, 491.8; 95% CI, 139.6-844.1; <i>P</i> = 0.0062), and gamification + financial incentives arm (adjusted difference, 868.0; 95% CI, 516.3-1219.7; <i>P</i> < 0.0001). During 6-month follow-up, physical activity remained significantly greater in the gamification + financial incentives arm than in the control arm (adjusted difference, 576.2; 95% CI, 198.5-954; <i>P</i> = 0.0028) but was not significantly greater in the gamification (adjusted difference, 459.8; 95% CI, 82.0-837.6; <i>P</i> = 0.0171) or financial incentives (adjusted difference, 327.9; 95% CI, -50.2 to 706; <i>P</i> = 0.09) arms, after adjusting for multiple comparisons.<br /><b>Conclusions</b><br />Behaviorally-designed gamification, loss-framed financial incentives, and the combination of both increased physical activity compared with control over a 12-month intervention period, with the largest effect in gamification + financial incentives. These interventions could be a useful component of strategies to reduce cardiovascular risk in high-risk patients.<br /><br /><br /><br /><small>Circulation: 07 Apr 2024; epub ahead of print</small></div>
Fanaroff AC, Patel MS, Chokshi N, Coratti S, ... Small DS, Volpp KGM
Circulation: 07 Apr 2024; epub ahead of print | PMID: 38583084
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<div><h4>Long-term outcomes of cardioneuroablation with and without extra-cardiac vagal stimulation confirmation in severe cardioinhibitory neurocardiogenic syncope.</h4><i>Pachon-M JC, Pachon-M EI, Pachon CTC, Santillana-P TG, ... Osorio TG, Peixoto LA</i><br /><b>Background</b><br />Cardioneuroablation (CNA) is a novel therapeutic approach for functional bradyarrhythmias, specifically neurocardiogenic syncope or atrial fibrillation, achieved through endocardial radiofrequency catheter ablation of vagal innervation, obviating the need for pacemaker implantation. Originating in the nineties, the first series of CNA procedures was published in 2005. Extra-cardiac vagal stimulation (ECVS) is employed as a direct method for stepwise denervation control during CNA.<br /><b>Objective</b><br />This study aimed to compare the long-term follow-up outcomes of patients with severe cardioinhibitory syncope undergoing CNA with and without denervation confirmation via ECVS.<br /><b>Method</b><br />A cohort of 48 patients, predominantly female (56.3%), suffering from recurrent syncope (5.1 ± 2.5 episodes annually) that remained unresponsive to clinical and pharmacological interventions, underwent CNA, divided into two groups: ECVS and NoECVS, consisting of 34 and 14 cases, respectively. ECVS procedures were conducted with and without atrial pacing.<br /><b>Results</b><br />Demographic characteristics, left atrial size, and ejection fraction displayed no statistically significant differences between the groups. Follow-up duration was comparable, with 29.1 ± 15 months for the ECVS group and 31.9 ± 20 months for the NoECVS group (p = .24). Notably, syncope recurrence was significantly lower in the ECVS group (two cases vs. four cases, Log Rank p = .04). Moreover, the Hazard ratio revealed a fivefold higher risk of syncope recurrence in the NoECVS group.<br /><b>Conclusion</b><br />This study demonstrates that concluding CNA with denervation confirmation via ECVS yields a higher success rate and a substantially reduced risk of syncope recurrence compared to procedures without ECVS confirmation.<br /><br />© 2024 Wiley Periodicals LLC.<br /><br /><small>J Cardiovasc Electrophysiol: 01 Apr 2024; 35:641-650</small></div>
Pachon-M JC, Pachon-M EI, Pachon CTC, Santillana-P TG, ... Osorio TG, Peixoto LA
J Cardiovasc Electrophysiol: 01 Apr 2024; 35:641-650 | PMID: 38240356
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<div><h4>Outcomes of Valve-in-Valve Transcatheter Aortic Valve Replacement.</h4><i>Ahmad D, Yousef S, Kliner D, Brown JA, ... Thoma FW, Sultan I</i><br /><AbstractText>Structural valve degeneration is increasingly seen given the higher rates of bioprosthetic heart valve use for surgical and transcatheter aortic valve replacement (TAVR). Valve-in-valve TAVR (VIV-TAVR) is an attractive alternate for patients who are otherwise at high risk for reoperative surgery. We compared patients who underwent VIV-TAVR and native valve TAVR through a retrospective analysis of our institutional transcatheter valve therapy (TVT) database from 2013 to 2022. Patients who underwent either a native valve TAVR or VIV-TAVR were included. VIV-TAVR was defined as TAVR in patients who underwent a previous surgical aortic valve replacement. Kaplan-Meier survival analysis was used to obtain survival estimates. A Cox proportional hazards regression model was used for the multivariable analysis of mortality. A total of 3,532 patients underwent TAVR, of whom 198 (5.6%) underwent VIV-TAVR. Patients in the VIV-TAVR cohort were younger than patients who underwent native valve TAVR (79.5 vs 84 years, p <0.001), with comparable number of women and a higher Society of Thoracic Surgeons risk score (6.28 vs 4.46, p <0.001). The VIV-TAVR cohort had a higher incidence of major vascular complications (2.5% vs 0.8%, p = 0.008) but lower incidence of permanent pacemaker placement (2.5% vs 8.1%, p = 0.004). The incidence of stroke was comparable between the groups (VIV-TAVR 2.5% vs native TAVR 2.4%, p = 0.911). The 30-day readmission rates (VIV-TAVR 7.1% vs native TAVR 9%, p = 0.348), as well as in-hospital (VIV-TAVR 2% vs native TAVR 1.4%, p = 0.46), and overall (VIV-TAVR 26.3% vs native TAVR 30.8%, p = 0.18) mortality at a follow-up of 1.8 years (0.83 to 3.5) were comparable between the groups. The survival estimates were also comparable between the groups (log-rank p = 0.27). On multivariable Cox regression analysis, VIV-TAVR was associated with decreased hazards of death (hazard ratio 0.68 [0.5 to 0.9], p = 0.02). In conclusion, VIV-TAVR is a feasible and safe strategy for high-risk patients with bioprosthetic valve failure. There may be potentially higher short-term morbidity with VIV-TAVR, with no overt impact on survival.</AbstractText><br /><br />Copyright © 2024 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 15 Mar 2024; 215:1-7</small></div>
Ahmad D, Yousef S, Kliner D, Brown JA, ... Thoma FW, Sultan I
Am J Cardiol: 15 Mar 2024; 215:1-7 | PMID: 38232811
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<div><h4>Clinical Impact of In-Stent Calcification in Coronary Arteries: Optical Coherence Tomography Study.</h4><i>Jinnouchi H, Sakakura K, Taniguchi Y, Yamamoto K, ... Seguchi M, Fujita H</i><br /><AbstractText>In-stent restenosis with neoatherosclerosis has been known as the predictor of target lesion revascularization (TLR) after percutaneous coronary intervention. However, the impact of in-stent calcification (ISC) alone on clinical outcomes remains unknown since neoatherosclerosis by optical coherence tomography includes in-stent lipid and calcification. We aimed to assess the effect of ISC on clinical outcomes and clinical differences among different types of ISC. We included 126 lesions that underwent optical coherence tomography-guided percutaneous coronary intervention and divided those into the ISC group (n = 38) and the non-ISC group (n = 88) according to the presence of ISC. The cumulative incidence of clinically driven TLR (CD-TLR) was compared between the ISC and non-ISC groups. The impact of in-stent calcified nodule and nodular calcification on CD-TLR was evaluated using the Cox hazard model. The incidence of CD-TLR was significantly higher in the ISC group than in the non-ISC group (p = 0.004). In the multivariate Cox hazard model, ISC was significantly associated with CD-TLR (hazard ratio [HR] 3.58, 95% confidence interval [CI] 1.33 to 9.65, p = 0.01). In-stent calcified nodule/nodular calcification and in-stent nodular calcification alone were also the factors significantly associated with CD-TLR (HR 3.34, 95%CI 1.15 to 9.65, p = 0.03 and HR 5.21, 95%CI 1.82 to 14.91, p = 0.002, respectively). ISC without in-stent calcified nodule/nodular calcification, which was defined as in-stent smooth calcification, was not associated with CD-TLR. In conclusion, ISC was associated with a higher rate of CD-TLR. The types of calcifications that led to a high rate of CD-TLR were in-stent calcified nodule/nodular calcification and in-stent nodular calcification alone but not in-stent smooth calcification. In-stent calcified nodule and nodular calcification should be paid more attention.</AbstractText><br /><br />Copyright © 2024 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 01 Mar 2024; 214:115-124</small></div>
Jinnouchi H, Sakakura K, Taniguchi Y, Yamamoto K, ... Seguchi M, Fujita H
Am J Cardiol: 01 Mar 2024; 214:115-124 | PMID: 38232806
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<div><h4>Effects of reduced sedentary time on resting, exercise and post-exercise blood pressure in inactive adults with metabolic syndrome - a six-month exploratory RCT.</h4><i>Norha J, Sjöros T, Garthwaite T, Laine S, ... Kalliokoski KK, Heinonen IHA</i><br /><AbstractText>Evidence on the long-term effects of reducing sedentary behaviour (SB) on blood pressure (BP) is scarce. Therefore, we performed a sub-analysis of the BP effects of a six-month intervention that aimed at reducing SB by 1 h/day and replacing it with non-exercise activities. Sixty-four physically inactive and sedentary adults with metabolic syndrome (58% female, 58 [SD 7] years, BP 143/88 [16/9] mmHg, SB 10 [1] h/day) were randomised into intervention (INT, n = 33) and control (CON, n = 31) groups. Resting BP and BP at each stage during and after a graded maximal bicycle ergometer test were measured before and after the intervention. SB, standing, moderate-to-vigorous physical activity (MVPA), and light physical activity (LPA) were measured in six-second intervals at baseline and during the whole six-month intervention using hip-worn accelerometers. The analyses were adjusted for BP medication status. The intervention resulted in a 40 min/day reduction in SB and concomitant 20 min/day increase in MVPA. Resting systolic BP was lower in the CON group before and after the intervention. No group x time interactions were observed in resting BP or BP during exercise at submaximal or maximal intensities, or during recovery. The changes in LPA and MVPA were inversely correlated with the changes in BP during light-to-moderate intensity exercise. An intervention that resulted in a 40 min/day reduction in SB for six months was not sufficient at influencing BP at rest, during or after exercise in adults with metabolic syndrome. However, successfully increasing LPA or MVPA might lower BP during light-to-moderate-intensity activities.</AbstractText><br /><br />© 2024. The Author(s).<br /><br /><small>J Hum Hypertens: 01 Apr 2024; 38:314-321</small></div>
Norha J, Sjöros T, Garthwaite T, Laine S, ... Kalliokoski KK, Heinonen IHA
J Hum Hypertens: 01 Apr 2024; 38:314-321 | PMID: 38267651
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<div><h4>Use of coronarycomputed tomography for cardiovascular risk assessment in immune-mediated inflammatory diseases.</h4><i>Peverelli M, Maughan RT, Gopalan D, Dweck MR, ... Rudd JHF, Tarkin JM</i><br /><AbstractText>Immune-mediated inflammatory diseases (IMIDs) are recognised risk factors for accelerated atherosclerotic cardiovascular disease (CVD), particularly in younger individuals and women who lack traditional CVD risk factors. Reflective of the critical role that inflammation plays in the formation, progression and rupture of atherosclerotic plaques, research into immune mechanisms of CVD has led to the identification of a range of therapeutic targets that are the subject of ongoing clinical trials. Several key inflammatory pathways implicated in the pathogenesis of atherosclerosis are targeted in people with IMIDs. However, cardiovascular risk continues to be systematically underestimated by conventional risk assessment tools in the IMID population, resulting in considerable excess CVD burden and mortality. Hence, there is a pressing need to improve methods for CVD risk-stratification among patients with IMIDs, to better guide the use of statins and other prognostic interventions. CT coronary angiography (CTCA) is the current first-line investigation for diagnosing and assessing the severity of coronary atherosclerosis in many individuals with suspected angina. Whether CTCA is also useful in the general population for reclassifying asymptomatic individuals and improving long-term prognosis remains unknown. However, in the context of IMIDs, it is conceivable that the information provided by CTCA, including state-of-the-art assessments of coronary plaque, could be an important clinical adjunct in this high-risk patient population. This narrative review discusses the current literature about the use of coronary CT for CVD risk-stratification in three of the most common IMIDs including rheumatoid arthritis, psoriasis and systemic lupus erythematosus.</AbstractText><br /><br />© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 22 Mar 2024; 110:545-551</small></div>
Peverelli M, Maughan RT, Gopalan D, Dweck MR, ... Rudd JHF, Tarkin JM
Heart: 22 Mar 2024; 110:545-551 | PMID: 38238078
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<div><h4>Prediction of preeclampsia from retinal fundus images via deep learning in singleton pregnancies: a prospective cohort study.</h4><i>Zhou T, Gu S, Shao F, Li P, ... Gao P, Hua X</i><br /><b>Introduction</b><br />Early prediction of preeclampsia (PE) is of universal importance in controlling the disease process. Our study aimed to assess the feasibility of using retinal fundus images to predict preeclampsia via deep learning in singleton pregnancies.<br /><b>Methods</b><br />This prospective cohort study was conducted at Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine. Eligible participants included singleton pregnancies who presented for prenatal visits before 14 weeks of gestation from September 1, 2020, to February 1, 2022. Retinal fundus images were obtained using a nonmydriatic digital retinal camera during their initial prenatal visit upon admission before 20 weeks of gestation. In addition, we generated fundus scores, which indicated the predictive value of hypertension, using a hypertension detection model. To evaluate the predictive value of the retinal fundus image-based deep learning algorithm for preeclampsia, we conducted stratified analyses and measured the area under the curve (AUC), sensitivity, and specificity. We then conducted sensitivity analyses for validation.<br /><b>Results</b><br />Our study analyzed a total of 1138 women, 92 pregnancies developed into hypertension disorders of pregnancy (HDP), including 26 cases of gestational hypertension and 66 cases of preeclampsia. The adjusted odds ratio (aOR) of the fundus scores was 2.582 (95% CI, 1.883-3.616; P  < 0.001). Otherwise, in the categories of prepregnancy BMI less than 28.0 and at least 28.0, the aORs were 3.073 (95%CI, 2.265-4.244; P  < 0.001) and 5.866 (95% CI, 3.292-11.531; P  < 0.001). In the categories of maternal age less than 35.0 and at least 35.0, the aORs were 2.845 (95% CI, 1.854-4.463; P  < 0.001) and 2.884 (95% CI, 1.794-4.942; P  < 0.001). The AUC of the fundus score combined with risk factors was 0.883 (sensitivity, 0.722; specificity, 0.934; 95% CI, 0.834-0.932) for predicting preeclampsia.<br /><b>Conclusion</b><br />Our study demonstrates that the use of deep learning algorithm-based retinal fundus images offers promising predictive value for the early detection of preeclampsia.<br /><br />Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.<br /><br /><small>J Hypertens: 01 Apr 2024; 42:701-710</small></div>
Zhou T, Gu S, Shao F, Li P, ... Gao P, Hua X
J Hypertens: 01 Apr 2024; 42:701-710 | PMID: 38230614
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<div><h4>Carotid Intima-Media Thickness and Improved Stroke Risk Assessment in Hypertensive Black Adults.</h4><i>Abe TA, Olanipekun T, Yan F, Effoe V, ... Benjamin EJ, Echols M</i><br /><b>Background</b><br />We aim to determine the added value of carotid intima-media thickness (cIMT) in stroke risk assessment for hypertensive Black adults.<br /><b>Methods</b><br />We examined 1,647 participants with hypertension without a history of cardiovascular (CV) disease, from the Jackson Heart Study. Cox regression analysis estimated hazard ratios (HRs) for incident stroke per standard deviation increase in cIMT and quartiles while adjusting for baseline variables. We then evaluated the predictive capacity of cIMT when added to the pool cohort equations (PCEs).<br /><b>Results</b><br />The mean age at baseline was 57 ± 10 years. Each standard deviation increase in cIMT (0.17 mm) was associated with approximately 30% higher risk of stroke (HR 1.27, 95% confidence interval: 1.08-1.49). Notably, cIMT proved valuable in identifying residual stroke risk among participants with well-controlled blood pressure, showing up to a 56% increase in the odds of stroke for each 0.17 mm increase in cIMT among those with systolic blood pressure <120 mm Hg. Additionally, the addition of cIMT to the PCE resulted in the reclassification of 58% of low to borderline risk participants with stroke to a higher-risk category and 28% without stroke to a lower-risk category, leading to a significant net reclassification improvement of 0.22 (0.10-0.30).<br /><b>Conclusions</b><br />In this community-based cohort of middle-aged Black adults with hypertension and no history of CV disease at baseline, cIMT is significantly associated with incident stroke and enhances stroke risk stratification.<br /><br />© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Am J Hypertens: 15 Mar 2024; 37:290-297</small></div>
Abe TA, Olanipekun T, Yan F, Effoe V, ... Benjamin EJ, Echols M
Am J Hypertens: 15 Mar 2024; 37:290-297 | PMID: 38236147
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Abstract
<div><h4>Exosomes From IgE-Stimulated Mast Cells Aggravate Asthma-Mediated Atherosclerosis Through circRNA CDR1as-Mediated Endothelial Cell Dysfunction in Mice.</h4><i>Yang H, Chen J, Liu S, Xue Y, ... Wang J, Zhao H</i><br /><b>Background</b><br />IgE has been known for mediating endothelial cell dysfunction and mast cell (MC) activation to fuel asthma-aggravated high-fat diet-induced atherosclerosis. However, it remains unclear for the mechanism of asthma-mediated atherosclerosis, especially the potential involvement of IgE in the exacerbation of asthma-mediated atherosclerosis with a standard laboratory diet, and the cross talk between endothelial cells and MCs.<br /><b>Methods</b><br />Asthma-mediated atherosclerosis mice models under a standard laboratory diet and FcεR1 knock-out mice were used to determine the role of IgE-FcεR1 signaling in asthma-mediated atherosclerosis, which was assessed by Oil Red O staining and immunohistochemistry. Various in vitro assays including nanoparticle tracking analysis and transmission electron microscopy were used to evaluate exosome characteristics. Immunofluorescence and fluorescent in situ hybridization approaches were used to evaluate the effect and mechanism of MC-secreted exosomes encapsulated circular RNA CDR1as (cerebellar degeneration-related 1 antisense) on endothelial cells in vivo and in vitro. Finally, cohort studies examined the plasma CDR1as levels in patients with atherosclerosis with or without allergies.<br /><b>Results</b><br />Asthma mice with a standard laboratory diet showed increased atherosclerotic lesions and inflammatory infiltration depending on IgE-FcεR1 signal. FcεR1 knockout mice and blockage of IgE-FcεR1 signaling with IgE monoclonal antibody, omalizumab, all significantly alleviated asthma-mediated atherosclerosis and vascular inflammatory remodeling. Anti-inflammation with dexamethasone and stabilization of MC with cromolyn partially alleviated atherosclerotic lesions and mitigated the inflammatory infiltration in arteries. Mechanistically, IgE stimulation upregulates MC CDR1as expression in exosomes and upregulates the endothelial cell adhesive factors VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) via the CDR1as-FUS (fused in sarcoma)-phos-p65 axis. Knockdown of CDR1as in vivo significantly decreased the endothelial adhesion function and mitigated asthma-mediated atherosclerosis. Furthermore, a cohort study indicated higher plasma CDR1as levels in patients with atherosclerosis with allergies than in patients with atherosclerosis and healthy controls.<br /><b>Conclusions</b><br />Exosomes from IgE-stimulated MCs aggravated atherosclerosis through circular RNA CDR1as-mediated endothelial dysfunction, providing a novel insight into asthma-mediated atherosclerosis and potential diagnostic and therapeutic targets.<br /><br /><br /><br /><small>Arterioscler Thromb Vasc Biol: 01 Mar 2024; 44:e99-e115</small></div>
Yang H, Chen J, Liu S, Xue Y, ... Wang J, Zhao H
Arterioscler Thromb Vasc Biol: 01 Mar 2024; 44:e99-e115 | PMID: 38235556
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<div><h4>Clot or Not? Reviewing the Reciprocal Regulation Between Lipids and Blood Clotting.</h4><i>Zhang Z, Rodriguez M, Zheng Z</i><br /><AbstractText>Both hyperlipidemia and thrombosis contribute to the risks of atherosclerotic cardiovascular diseases, which are the leading cause of death and reduced quality of life in survivors worldwide. The accumulation of lipid-rich plaques on arterial walls eventually leads to the rupture or erosion of vulnerable lesions, triggering excessive blood clotting and leading to adverse thrombotic events. Lipoproteins are highly dynamic particles that circulate in blood, carry insoluble lipids, and are associated with proteins, many of which are involved in blood clotting. A growing body of evidence suggests a reciprocal regulatory relationship between blood clotting and lipid metabolism. In this review article, we summarize the observations that lipoproteins and lipids impact the hemostatic system, and the clotting-related proteins influence lipid metabolism. We also highlight the gaps that need to be filled in this area of research.</AbstractText><br /><br /><br /><br /><small>Arterioscler Thromb Vasc Biol: 01 Mar 2024; 44:533-544</small></div>
Zhang Z, Rodriguez M, Zheng Z
Arterioscler Thromb Vasc Biol: 01 Mar 2024; 44:533-544 | PMID: 38235555
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<div><h4>High-Serum Brain-Derived Neurotrophic Factor Levels Are Associated With Decreased Risk of Poststroke Cognitive Impairment.</h4><i>Chang X, You J, Yang P, He Y, ... Zhang Y, Zhu Z</i><br /><b>Background</b><br />BDNF (brain-derived neurotrophic factor) is widely implicated in the pathophysiological process of stroke, but the effect of BDNF on poststroke cognitive impairment (PSCI) remains unclear. We aimed to investigate the association between baseline serum BDNF and the risk of PSCI at 3 months in a multicenter study based on a preplanned ancillary study of the CATIS trial (China Antihypertensive Trial in Acute Ischemic Stroke).<br /><b>Methods</b><br />We examined serum BDNF levels at baseline and used the Mini-Mental State Examination and Montreal Cognitive Assessment to evaluate cognitive function at 3-month follow-up after ischemic stroke. PSCI was defined as Mini-Mental State Examination score <27 or Montreal Cognitive Assessment score <25. Logistic regression analyses were performed to evaluate the association between serum BDNF and the risk of 3-month PSCI.<br /><b>Results</b><br />In this ancillary study, a total of 660 patients with ischemic stroke with hypertension were included, and 593 patients (mean age, 59.90±10.44 years; 410 males and 183 females) were finally included in this analysis. According to mini-mental state examination score, after adjustment for age, sex, education, baseline National Institutes of Health Stroke Scale score, <i>APOE ɛ4</i> carriers, and other potential confounders, the odds ratio of PSCI for the highest tertile of BDNF was 0.60 ([95% CI, 0.39-0.94]; <i>P</i>=0.024) compared with the lowest tertile. Multiple-adjusted spline regression model showed a linear association of serum BDNF levels with PSCI at 3 months (<i>P</i> value for linearity=0.010). Adding serum BDNF to conventional prognostic factors slightly improved the risk reclassification of PSCI (net reclassification improvement: 27.46%, <i>P</i>=0.001; integrated discrimination index: 1.02%, <i>P</i>=0.015). Similar significant findings were observed when PSCI was defined by the Montreal Cognitive Assessment score.<br /><b>Conclusions</b><br />Elevated serum BDNF levels were associated with a decreased risk of PSCI at 3 months, suggesting that serum BDNF might be a potential predictive biomarker for PSCI among patients with ischemic stroke with hypertension.<br /><br /><br /><br /><small>Stroke: 01 Mar 2024; 55:643-650</small></div>
Chang X, You J, Yang P, He Y, ... Zhang Y, Zhu Z
Stroke: 01 Mar 2024; 55:643-650 | PMID: 38235585
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<div><h4>Altered whole blood thrombin generation and hyperresponsive platelets in patients with pancreatic cancer.</h4><i>Willems RAL, Konings J, Huskens D, Middelveld H, ... de Laat B, Roest M</i><br /><b>Background</b><br />Thromboembolic disease is a major complication in patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often have altered blood cell counts, which are associated with venous thromboembolism (VTE) development. The high thrombotic risk in patients with PDAC may be partially caused by procoagulant blood cells.<br /><b>Objectives</b><br />The aim of this study was to compare blood cell-dependent coagulation between patients with PDAC (n = 18) and healthy controls matched for age and sex (n = 18).<br /><b>Methods</b><br />Thrombin generation (TG) was measured in whole blood (WB) and plasma. The capacity of platelets to release granules (PGRCs) was measured in WB. We explored the occurrence of thromboembolic events in patients with PDAC during a 6-month follow-up.<br /><b>Results</b><br />Patients showed an increased endogenous thrombin potential in WB compared with controls. This difference was not observed in plasma, indicating a procoagulant effect of blood cells. Both in WB and plasma, the lag time was prolonged in patients compared with controls. Patients had hyperresponsive platelets, with a shorter time to peak granule release. Of the 18 patients with PDAC, 4 developed a venous thromboembolism (22%) and 1 developed an arterial thrombosis (6%). A shorter lag time in WB, but not in plasma, and an increased PGRC were associated with thromboembolic events.<br /><b>Conclusion</b><br />Patients with PDAC have an increased and delayed WB TG coagulation profile compared with controls. A shorter lag time in WB TG and increased PGRC are associated with the incidence of thromboembolic events. Platelets appear to be key players in thrombosis development. Measuring hemostasis in WB could improve thrombosis risk estimation in patients with PDAC.<br /><br />Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Thromb Haemost: 01 Apr 2024; 22:1132-1144</small></div>
Willems RAL, Konings J, Huskens D, Middelveld H, ... de Laat B, Roest M
J Thromb Haemost: 01 Apr 2024; 22:1132-1144 | PMID: 38237861
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<div><h4>Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19 B cell tumors: a phase 1/2 trial.</h4><i>Marin D, Li Y, Basar R, Rafei H, ... Shpall EJ, Rezvani K</i><br /><AbstractText>There is a pressing need for allogeneic chimeric antigen receptor (CAR)-immune cell therapies that are safe, effective and affordable. We conducted a phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 chimeric antigen receptor and interleukin-15 (CAR19/IL-15) in 37 patients with CD19<sup>+</sup> B cell malignancies. The primary objectives were safety and efficacy, defined as day 30 overall response (OR). Secondary objectives included day 100 response, progression-free survival, overall survival and CAR19/IL-15 NK cell persistence. No notable toxicities such as cytokine release syndrome, neurotoxicity or graft-versus-host disease were observed. The day 30 and day 100 OR rates were 48.6% for both. The 1-year overall survival and progression-free survival were 68% and 32%, respectively. Patients who achieved OR had higher levels and longer persistence of CAR-NK cells. Receiving CAR-NK cells from a cord blood unit (CBU) with nucleated red blood cells ≤ 8 × 10<sup>7</sup> and a collection-to-cryopreservation time ≤ 24 h was the most significant predictor for superior outcome. NK cells from these optimal CBUs were highly functional and enriched in effector-related genes. In contrast, NK cells from suboptimal CBUs had upregulation of inflammation, hypoxia and cellular stress programs. Finally, using multiple mouse models, we confirmed the superior antitumor activity of CAR/IL-15 NK cells from optimal CBUs in vivo. These findings uncover new features of CAR-NK cell biology and underscore the importance of donor selection for allogeneic cell therapies. ClinicalTrials.gov identifier: NCT03056339 .</AbstractText><br /><br />© 2024. The Author(s).<br /><br /><small>Nat Med: 01 Mar 2024; 30:772-784</small></div>
Marin D, Li Y, Basar R, Rafei H, ... Shpall EJ, Rezvani K
Nat Med: 01 Mar 2024; 30:772-784 | PMID: 38238616
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<div><h4>Cell-type-specific CAG repeat expansions and toxicity of mutant Huntingtin in human striatum and cerebellum.</h4><i>Mätlik K, Baffuto M, Kus L, Deshmukh AL, ... Pearson CE, Heintz N</i><br /><AbstractText>Brain region-specific degeneration and somatic expansions of the mutant Huntingtin (mHTT) CAG tract are key features of Huntington\'s disease (HD). However, the relationships among CAG expansions, death of specific cell types and molecular events associated with these processes are not established. Here, we used fluorescence-activated nuclear sorting (FANS) and deep molecular profiling to gain insight into the properties of cell types of the human striatum and cerebellum in HD and control donors. CAG expansions arise at mHTT in striatal medium spiny neurons (MSNs), cholinergic interneurons and cerebellar Purkinje neurons, and at mutant ATXN3 in MSNs from SCA3 donors. CAG expansions in MSNs are associated with higher levels of MSH2 and MSH3 (forming MutSβ), which can inhibit nucleolytic excision of CAG slip-outs by FAN1. Our data support a model in which CAG expansions are necessary but may not be sufficient for cell death and identify transcriptional changes associated with somatic CAG expansions and striatal toxicity.</AbstractText><br /><br />© 2024. The Author(s).<br /><br /><small>Nat Genet: 01 Mar 2024; 56:383-394</small></div>
Mätlik K, Baffuto M, Kus L, Deshmukh AL, ... Pearson CE, Heintz N
Nat Genet: 01 Mar 2024; 56:383-394 | PMID: 38291334
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<div><h4>The role of N-terminal phosphorylation of DGK-θ.</h4><i>Barbernitz MX, Devine LR, Cole RN, Raben DM</i><br /><AbstractText>Diacylglycerol kinases (DGKs) are lipid kinases that mediate the phosphorylation of diacylglycerol (DAG) leading to the production of phosphatidic acid (PtdOH). To examine the role of phosphorylation on DGK-θ, we first identified the phosphorylated sites on endogenous DGK-θ from mouse brain and found four sites: S15, S17, which we refer to phosphomotif-1 sites, and S22 and S26 which we refer to as phosphomotif-2 sites. This study focused on the role of these phosphorylated sites on enzyme activity, membrane binding, thermal stability, and cellular half-life of DGK-θ. After generating a construct devoid of all non-catalytic phosphorylation sites (4A), we also generated other constructs to mimic phosphorylation of these residues by mutating them to glutamate (E). Our data demonstrate that an increase in membrane affinity requires the phosphorylation of all four endogenous sites as the phosphomimetic 4E but not other phosphomimietics. Furthermore, 4E also shows an increase in basal activity as well as an increase in the Syt1-induced activity compared to 4A. It is noteworthy that these phosphorylations had no effect on the thermal stability or cellular half-life of this enzyme. Interestingly, when only one phosphorylation domain (phosphomotif-1 or phosphomotif-2) contained phosphomimetics (S15E/S17E or S22E/S26E), the basal activity was also increased but membrane binding affinity was not increased. Furthermore, when only one residue in each domain mimicked an endogenous phosphorylated serine (S15E/S22E or S17E/S26E), the Syt1-induced activity as well as membrane binding affinity decreased relative to 4A. These results indicate that these endogenous phosphorylation sites contribute differentially to membrane binding and enzymatic activity.</AbstractText><br /><br />Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Lipid Res: 01 Mar 2024; 65:100506</small></div>
Barbernitz MX, Devine LR, Cole RN, Raben DM
J Lipid Res: 01 Mar 2024; 65:100506 | PMID: 38272356
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<div><h4>Prospective prenatal cell-free DNA screening for genetic conditions of heterogenous etiologies.</h4><i>Zhang J, Wu Y, Chen S, Luo Q, ... Xu C, Huang H</i><br /><AbstractText>Prenatal cell-free DNA (cfDNA) screening uses extracellular fetal DNA circulating in the peripheral blood of pregnant women to detect prevalent fetal chromosomal anomalies. However, numerous severe conditions with underlying single-gene defects are not included in current prenatal cfDNA screening. In this prospective, multicenter and observational study, pregnant women at elevated risk for fetal genetic conditions were enrolled for a cfDNA screening test based on coordinative allele-aware target enrichment sequencing. This test encompasses the following three of the most frequent pathogenic genetic variations: aneuploidies, microdeletions and monogenic variants. The cfDNA screening results were compared to invasive prenatal or postnatal diagnostic test results for 1,090 qualified participants. The comprehensive cfDNA screening detected a genetic alteration in 135 pregnancies with 98.5% sensitivity and 99.3% specificity relative to standard diagnostics. Of 876 fetuses with suspected structural anomalies on ultrasound examination, comprehensive cfDNA screening identified 55 (56.1%) aneuploidies, 6 (6.1%) microdeletions and 37 (37.8%) single-gene pathogenic variants. The inclusion of targeted monogenic conditions alongside chromosomal aberrations led to a 60.7% increase (from 61 to 98) in the detection rate. Overall, these data provide preliminary evidence that a comprehensive cfDNA screening test can accurately identify fetal pathogenic variants at both the chromosome and single-gene levels in high-risk pregnancies through a noninvasive approach, which has the potential to improve prenatal evaluation of fetal risks for severe genetic conditions arising from heterogenous molecular etiologies. ClinicalTrials.gov registration: ChiCTR2100045739 .</AbstractText><br /><br />© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.<br /><br /><small>Nat Med: 01 Mar 2024; 30:470-479</small></div>
Zhang J, Wu Y, Chen S, Luo Q, ... Xu C, Huang H
Nat Med: 01 Mar 2024; 30:470-479 | PMID: 38253798
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This program is still in alpha version.