The Global Transcription Regulator XooClp Governs Type IV Pili System-Mediated Bacterial Virulence by Directly Binding to TFP-Chp Promoters to Coordinate Virulence Associated Functions.

Type IV pili (TFP) play a crucial role in the sensing of the external environment for several bacteria. This surface sensing is essential for the lifestyle transitions of several bacteria and involvement in pathogenesis. However, the precise mechanisms underlying TFP's integration of environmental cues, particularly in regulating the TFP-Chp system and its effects on Xanthomonas physiology, social behavior, and virulence, remain poorly understood. In this study, we focused on investigating Clp, a global transcriptional regulator similar to CRP-like proteins, in Xanthomonas oryzae pv. oryzae, a plant pathogen. Our findings reveal that Clp integrates environmental cues detected through diffusible signaling factor (DSF) quorum sensing into the TFP-Chp regulatory system. It accomplishes this by directly binding to TFP-Chp promoters in conjunction with intracellular levels of cyclic-di-GMP, a ubiquitous bacterial second messenger, thereby controlling TFP expression. Moreover, Clp-mediated regulation is involved in regulating several cellular processes, including the production of virulence-associated functions. Collectively, these processes contribute to host colonization and disease initiation. Our study elucidates the intricate regulatory network encompassing Clp, environmental cues, and the TFP-Chp system, providing insights into the molecular mechanisms that drive bacterial virulence in Xanthomonas spp. These findings offer valuable knowledge regarding Xanthomonas pathogenicity and present new avenues for innovative strategies aimed at combating plant diseases caused by these bacteria. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Empagliflozin and Left Ventricular Remodeling in People Without Diabetes: Primary Results of the EMPA-HEART 2 CardioLink-7 Randomized Clinical Trial.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors have been demonstrated to promote reverse cardiac remodeling in people with diabetes or heart failure. Although it has been theorized that sodium-glucose cotransporter 2 inhibitors might afford similar benefits in people without diabetes or prevalent heart failure, this has not been evaluated. We sought to determine whether sodium-glucose cotransporter 2 inhibition with empagliflozin leads to a decrease in left ventricular (LV) mass in people without type 2 diabetes or significant heart failure. METHODS: Between April 2021 and January 2022, 169 individuals, 40 to 80 years of age, without diabetes but with risk factors for adverse cardiac remodeling were randomly assigned to empagliflozin (10 mg/d; n=85) or placebo (n=84) for 6 months. The primary outcome was the 6-month change in LV mass indexed (LVMi) to baseline body surface area as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and LV end-systolic volumes indexed to baseline body surface area and LV ejection fraction. RESULTS: Among the 169 participants (141 men [83%]; mean age, 59.3±10.5 years), baseline LVMi was 63.2±17.9 g/m2 and 63.8±14.0 g/m2 for the empagliflozin- and placebo-assigned groups, respectively. The difference (95% CI) in LVMi at 6 months in the empagliflozin group versus placebo group adjusted for baseline LVMi was -0.30 g/m2 (-2.1 to 1.5 g/m2; P=0.74). Median baseline (interquartile range) NT-proBNP (N-terminal-pro B-type natriuretic peptide) was 51 pg/mL (20-105 pg/mL) and 55 pg/mL (21-132 pg/mL) for the empagliflozin- and placebo-assigned groups, respectively. The 6-month treatment effect of empagliflozin versus placebo (95% CI) on blood pressure and NT-proBNP (adjusted for baseline values) were -1.3 mm Hg (-5.2 to 2.6 mm Hg; P=0.52), 0.69 mm Hg (-1.9 to 3.3 mm Hg; P=0.60), and -6.1 pg/mL (-37.0 to 24.8 pg/mL; P=0.70) for systolic blood pressure, diastolic blood pressure, and NT-proBNP, respectively. No clinically meaningful between-group differences in LV volumes (diastolic and systolic indexed to baseline body surface area) or ejection fraction were observed. No difference in adverse events was noted between the groups. CONCLUSIONS: Among people with neither diabetes nor significant heart failure but with risk factors for adverse cardiac remodeling, sodium-glucose cotransporter 2 inhibition with empagliflozin did not result in a meaningful reduction in LVMi after 6 months. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04461041.

Predicting Outcomes Following Endovascular Abdominal Aortic Aneurysm Repair Using Machine Learning.

OBJECTIVE: To develop machine learning (ML) models that predict outcomes following endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). BACKGROUND: EVAR carries non-negligible perioperative risks; however, there are no widely used outcome prediction tools. METHODS: The National Surgical Quality Improvement Program targeted database was used to identify patients who underwent EVAR for infrarenal AAA between 2011 and 2021. Input features included 36 preoperative variables. The primary outcome was 30-day major adverse cardiovascular event (composite of myocardial infarction, stroke, or death). Data were split into training (70%) and test (30%) sets. Using 10-fold cross-validation, 6 ML models were trained using preoperative features. The primary model evaluation metric was area under the receiver operating characteristic curve. Model robustness was evaluated with calibration plot and Brier score. Subgroup analysis was performed to assess model performance based on age, sex, race, ethnicity, and prior AAA repair. RESULTS: Overall, 16,282 patients were included. The primary outcome of 30-day major adverse cardiovascular event occurred in 390 (2.4%) patients. Our best-performing prediction model was XGBoost, achieving an area under the receiver operating characteristic curve (95% CI) of 0.95 (0.94-0.96) compared with logistic regression [0.72 [0.70-0.74)]. The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.06. Model performance remained robust on all subgroup analyses. CONCLUSIONS: Our newer ML models accurately predict 30-day outcomes following EVAR using preoperative data and perform better than logistic regression. Our automated algorithms can guide risk mitigation strategies for patients being considered for EVAR.

Using Machine Learning (XGBoost) to Predict Outcomes After Infrainguinal Bypass for Peripheral Artery Disease.

OBJECTIVE: To develop machine learning (ML) algorithms that predict outcomes after infrainguinal bypass. BACKGROUND: Infrainguinal bypass for peripheral artery disease carries significant surgical risks; however, outcome prediction tools remain limited. METHODS: The Vascular Quality Initiative database was used to identify patients who underwent infrainguinal bypass for peripheral artery disease between 2003 and 2023. We identified 97 potential predictor variables from the index hospitalization [68 preoperative (demographic/clinical), 13 intraoperative (procedural), and 16 postoperative (in-hospital course/complications)]. The primary outcome was 1-year major adverse limb event (composite of surgical revision, thrombectomy/thrombolysis, or major amputation) or death. Our data were split into training (70%) and test (30%) sets. Using 10-fold cross-validation, we trained 6 ML models using preoperative features. The primary model evaluation metric was the area under the receiver operating characteristic curve (AUROC). The top-performing algorithm was further trained using intraoperative and postoperative features. Model robustness was evaluated using calibration plots and Brier scores. RESULTS: Overall, 59,784 patients underwent infrainguinal bypass, and 15,942 (26.7%) developed 1-year major adverse limb event/death. The best preoperative prediction model was XGBoost, achieving an AUROC (95% CI) of 0.94 (0.93-0.95). In comparison, logistic regression had an AUROC (95% CI) of 0.61 (0.59-0.63). Our XGBoost model maintained excellent performance at the intraoperative and postoperative stages, with AUROCs (95% CI's) of 0.94 (0.93-0.95) and 0.96 (0.95-0.97), respectively. Calibration plots showed good agreement between predicted and observed event probabilities with Brier scores of 0.08 (preoperative), 0.07 (intraoperative), and 0.05 (postoperative). CONCLUSIONS: ML models can accurately predict outcomes after infrainguinal bypass, outperforming logistic regression.

Wellness and burnout in cardiac surgery: not black and white.

PURPOSE OF REVIEW: Despite a growing emphasis on burnout in medicine, there remains a paucity of data in cardiac surgery. Herein, we summarize recent data on cardiac surgeon well being and identify factors for consideration in future burnout inquiries and management. RECENT FINDINGS: Overall, 70-90% of cardiothoracic surgeons report job satisfaction in the United States. However, 35-60% still endorse burnout symptoms, and the specialty reports some of the highest rates of depression (35-40%) and suicidal ideation (7%). Such negative experiences are greater among early-stage and female surgeons and may be addressed through targeted, program-specific wellness policies. Canada's single-payer healthcare system might exacerbate surgeon burnout due to lower financial compensation and job autonomy. SUMMARY: Cardiothoracic surgeons appear simultaneously burnt out and professionally fulfilled. They report a high incidence of depression and clock in the most hours, yet the majority would choose this specialty again. These findings reveal a more nuanced state of well being than previously appreciated and speak to ambiguities in how burnout is conceived and measured. A broader examination across surgical and social contexts highlights the hierarchical nature of burnout factors and potential ways forward. Collectively, these insights can inform assessments of burnout in Canadian cardiac surgery that remain absent to date.

Obesity/cardiometabolic phenotype of heart failure with preserved ejection fraction: mechanisms to recent trials.

PURPOSE OF REVIEW: Heart failure with preserved ejection fraction (HFpEF) is a leading and growing cause of morbidity and mortality globally. Of the various phenotypes identified, the obesity (or cardiometabolic) phenotype appears to be most common. The purpose of this review is to provide the clinician with an abridged understanding of recent developments that have elucidated obesity/visceral adiposity as a central mechanism linking inflammation/immune dysregulation to the development of the HFpEF syndrome. Recent clinical trials examining the efficacy of pharmacological treatments that target obesity in HFpEF will also be discussed. RECENT FINDINGS: Recent data indicate that visceral adiposity and insulin resistance in HFpEF serve as key mechanisms driving inflammation and immune dysregulation, which play a critical role in the development of cardiac stiffness, diastolic dysfunction and fibrosis in HFpEF. In obesity, alterations in macrophage polarization, changes in innate and adaptive immune systems and altered myocardial energetics promote metabolic inflammation in HFpEF. Finally, emerging data suggest that inflammatory biomarkers, specifically, IL-6, may provide useful information about HFpEF severity and symptom burden in obesity. SUMMARY: The obesity phenotype of HFpEF is seen in upward of 80% with HFpEF. Obesity is not just a bystander, but plays an essential role in the pathobiology and clinical course of HFpEF. Targeting overweight/obesity in HFpEF with GLP-1 receptor agonists holds promise in these patients.

2023 Update on equity, diversity, and inclusion in Canadian cardiac surgery.

PURPOSE OF REVIEW: Despite efforts to diversify the medical field, cardiac surgery remains amongst the least diverse specialties. Specifically, the percentage of women and racial minorities has remained low in past few decades. This may impact prospective trainee recruitment and surgical care. This paper highlights recent efforts that aim to promote diversity and inclusion of the Canadian cardiac surgical workforce. RECENT FINDINGS: Formal programs have been established to support students at different stages of training. In 2022, the Canadian Society for Cardiac Surgery has released an equity, diversity, and inclusion statement to summarize the current state and the strategic goals to accomplish a more just working environment. At the local level, the University of Toronto Next Surgeon high school pilot program, provided low-income, women, and racial minority students mentorship and experiential exposure to our field. Also, the University of Toronto, scholarships funded summer research with cardiac surgeons for women, as well as Black and Indigenous medical students. SUMMARY: Tangible efforts that target high school, undergraduate, and medical students are underway to promote equity and diversity of cardiac surgeons in Canada. Future studies that evaluate the gaps and identify bottlenecks could better guide interventions at institutions across the country.

Empagliflozin improves circulating vascular regenerative cell content in people without diabetes with risk factors for adverse cardiac remodeling.

Sodium glucose-cotransporter 2 (SGLT2) inhibitors have been reported to reduce cardiovascular events and heart failure in people with and without diabetes. These medications have been shown to counter regenerative cell exhaustion in the context of prevalent diabetes. This study sought to determine if empagliflozin attenuates regenerative cell exhaustion in people without diabetes. Peripheral blood mononuclear cells were collected at the baseline and 6-mo visits from individuals randomized to receive empagliflozin (10 mg/day) or placebo who were participating in the EMPA-HEART 2 CardioLink-7 trial. Precursor cell phenotypes were characterized by flow cytometry for cell-surface markers combined with high aldehyde dehydrogenase activity to identify precursor cell subsets with progenitor (ALDHhi) versus mature effector (ALDHlow) cell attributes. Samples from individuals assigned to empagliflozin (n = 25) and placebo (n = 21) were analyzed. At baseline, overall frequencies of primitive progenitor cells (ALDHhiSSClow), monocyte (ALDHhiSSCmid), and granulocyte (ALDHhiSSChi) precursor cells in both groups were similar. At 6 mo, participants randomized to empagliflozin demonstrated increased ALDHhiSSClowCD133+CD34+ proangiogenic cells (P = 0.048), elevated ALDHhiSSCmidCD163+ regenerative monocyte precursors (P = 0.012), and decreased ALDHhiSSCmidCD86 + CD163- proinflammatory monocyte (P = 0.011) polarization compared with placebo. Empagliflozin promoted the recovery of multiple circulating provascular cell subsets in people without diabetes suggesting that the cardiovascular benefits of SGLT2 inhibitors may be attributed in part to the attenuation of vascular regenerative cell exhaustion that is independent of diabetes status.NEW & NOTEWORTHY Using an aldehyde dehydrogenase (ALDH) activity-based flow cytometry assay, we found that empagliflozin treatment for 6 mo was associated with parallel increases in circulating vascular regenerative ALDHhi-CD34/CD133-coexpressing progenitors and decreased proinflammatory ALDHhi-CD14/CD86-coexpressing monocyte precursors in individuals without diabetes but with cardiovascular risk factors. The rejuvenation of the vascular regenerative cell reservoir may represent a mechanism via which sodium glucose-cotransporter 2 (SGLT2) inhibitors limit maladaptive repair and delay the development and progression of cardiovascular diseases.

Left ventricular mass predicts cardiac reverse remodelling in patients treated with empagliflozin.

BACKGROUND: The cardiovascular (CV) benefits of sodium-glucose transport protein 2 inhibitors have been attributed, in part, to cardiac reverse remodelling. The EMPA-HEART CardioLink-6 study reported that sodium-glucose cotransporter-2 inhibition for 6 months with empagliflozin was associated with a significant reduction in left ventricular mass indexed to body surface area (LVMi). In this sub-analysis, we evaluated whether baseline LVMi may influence how empagliflozin affects cardiac reverse remodelling. METHODS: A total of 97 patients with type 2 diabetes and coronary artery disease were randomized to empagliflozin (10 mg/d) or matching placebo for 6 months. The study cohort was divided into those whose baseline LVMi was ≤ 60 g/m2 and those who had a baseline LVMi > 60 g/m2. Subgroup comparisons were conducted using a linear regression model adjusted for baseline values (ANCOVA) that included an interaction term between LVMi subgroup and treatment. RESULTS: Baseline LVMi was 53.3 g/m2 (49.2-57.2) and 69.7 g/m2 (64.2-76.1) for those with baseline ≤ 60 g/m2 (n = 54) and LVMi > 60 g/m2 (n = 43) respectively. The adjusted difference of LVMi regression between those randomized to empagliflozin and placebo were - 0.46 g/m2 (95% CI: -3.44, 2.52, p = 0.76) in the baseline LVMi ≤ 60 g/m2 subgroup and - 7.26 g/m2 (95% CI: -11.40, -3.12, p = 0.0011) in the baseline LVMi > 60 g/m2 subgroup (p-for-interaction = 0.007). No significant associations were found between baseline LVMi and 6-month change in LV end systolic volume-indexed (p-for-interaction = 0.086), LV end diastolic volume-indexed (p-for-interaction = 0.34), or LV ejection fraction (p-for-interaction = 0.15). CONCLUSIONS: Patients with higher LVMi at baseline experienced greater LVM regression with empagliflozin.

Predicting outcomes following open revascularization for aortoiliac occlusive disease using machine learning.

OBJECTIVE: Open surgical treatment options for aortoiliac occlusive disease carry significant perioperative risks; however, outcome prediction tools remain limited. Using machine learning (ML), we developed automated algorithms that predict 30-day outcomes following open aortoiliac revascularization. METHODS: The National Surgical Quality Improvement Program (NSQIP) targeted vascular database was used to identify patients who underwent open aortoiliac revascularization for atherosclerotic disease between 2011 and 2021. Input features included 38 preoperative demographic/clinical variables. The primary outcome was 30-day major adverse limb event (MALE; composite of untreated loss of patency, major reintervention, or major amputation) or death. The 30-day secondary outcomes were individual components of the primary outcome, major adverse cardiovascular event (MACE; composite of myocardial infarction, stroke, or death), individual components of MACE, wound complication, bleeding, other morbidity, non-home discharge, and unplanned readmission. Our data were split into training (70%) and test (30%) sets. Using 10-fold cross-validation, we trained six ML models using preoperative features. The primary model evaluation metric was area under the receiver operating characteristic curve (AUROC). Model robustness was evaluated with calibration plot and Brier score. Variable importance scores were calculated to determine the top 10 predictive features. Performance was assessed on subgroups based on age, sex, race, ethnicity, symptom status, procedure type, and urgency. RESULTS: Overall, 9649 patients were included. The primary outcome of 30-day MALE or death occurred in 1021 patients (10.6%). Our best performing prediction model for 30-day MALE or death was XGBoost, achieving an AUROC of 0.95 (95% confidence interval [CI], 0.94-0.96). In comparison, logistic regression had an AUROC of 0.79 (95% CI, 0.77-0.81). For 30-day secondary outcomes, XGBoost achieved AUROCs between 0.87 and 0.97 (untreated loss of patency [0.95], major reintervention [0.88], major amputation [0.96], death [0.97], MACE [0.95], myocardial infarction [0.88], stroke [0.93], wound complication [0.94], bleeding [0.87], other morbidity [0.96], non-home discharge [0.90], and unplanned readmission [0.91]). The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.05. The strongest predictive feature in our algorithm was chronic limb-threatening ischemia. Model performance remained robust on all subgroup analyses of specific demographic/clinical populations. CONCLUSIONS: Our ML models accurately predict 30-day outcomes following open aortoiliac revascularization using preoperative data, performing better than logistic regression. They have potential for important utility in guiding risk-mitigation strategies for patients being considered for open aortoiliac revascularization to improve outcomes.

Racial and ethnic differences in presentation severity and postoperative outcomes in vascular surgery.

BACKGROUND: We assessed the effect of race and ethnicity on presentation severity and postoperative outcomes in those with abdominal aortic aneurysms (AAAs), carotid artery stenosis (CAS), peripheral arterial disease (PAD), and type B aortic dissection (TBAD). METHODS: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception until December 2020. Two reviewers independently selected randomized controlled trials and observational studies reporting race and/or ethnicity and presentation severity and/or postoperative outcomes for adult patients who had undergone major vascular procedures. They independently extracted the study data and assessed the risk of bias using the Newcastle-Ottawa scale. The meta-analysis used random effects models to derive the odds ratios (ORs) and risk ratios (RRs) and their corresponding 95% confidence intervals (CIs). The primary outcome was presentation severity stratified by the proportion of patients with advanced disease, including ruptured vs nonruptured AAA, symptomatic vs asymptomatic CAS, chronic limb-threatening ischemia vs claudication, and complicated vs uncomplicated TBAD. The secondary outcomes included postoperative all-cause mortality and disease-specific outcomes. RESULTS: A total of 81 studies met the inclusion criteria. Black (OR, 4.18; 95% CI, 1.31-13.26), Hispanic (OR, 2.01; 95% CI, 1.85-2.19), and Indigenous (OR, 1.97; 95% CI, 1.39-2.80) patients were more likely to present with ruptured AAAs than were White patients. Black and Hispanic patients had had higher symptomatic CAS (Black: OR, 1.20; 95% CI, 1.04-1.38; Hispanic: OR, 1.32; 95% CI, 1.20-1.45) and chronic limb-threatening ischemia (Black: OR, 1.67; 95% CI, 1.14-2.43; Hispanic: OR, 1.73; 95% CI 1.13-2.65) presentation rates. No study had evaluated the effect of race or ethnicity on complicated TBAD. All-cause mortality was higher for Black (RR, 1.23; 95% CI, 1.01-1.51), Hispanic (RR, 1.90; 95% CI, 1.57-2.31), and Indigenous (RR, 1.24; 95% CI, 1.12-1.37) patients after AAA repair. Postoperatively, Black (RR, 1.54; 95% CI, 1.19-2.00) and Hispanic (RR, 1.54; 95% CI, 1.31-1.81) patients were associated with stroke/transient ischemic attack after carotid revascularization and lower extremity amputation (RR, 1.90; 95% CI, 1.76-2.06; and RR, 1.69; 95% CI, 1.48-1.94, respectively). CONCLUSIONS: Certain visible minorities were associated with higher morbidity and mortality across various vascular surgery presentations. Further research to understand the underpinnings is required.

Using machine learning to predict outcomes following open abdominal aortic aneurysm repair.

OBJECTIVE: Prediction of outcomes following open abdominal aortic aneurysm (AAA) repair remains challenging with a lack of widely used tools to guide perioperative management. We developed machine learning (ML) algorithms that predict outcomes following open AAA repair. METHODS: The Vascular Quality Initiative (VQI) database was used to identify patients who underwent elective open AAA repair between 2003 and 2023. Input features included 52 preoperative demographic/clinical variables. All available preoperative variables from VQI were used to maximize predictive performance. The primary outcome was in-hospital major adverse cardiovascular event (MACE; composite of myocardial infarction, stroke, or death). Secondary outcomes were individual components of the primary outcome, other in-hospital complications, and 1-year mortality and any reintervention. We split our data into training (70%) and test (30%) sets. Using 10-fold cross-validation, six ML models were trained using preoperative features (Extreme Gradient Boosting [XGBoost], random forest, Naïve Bayes classifier, support vector machine, artificial neural network, and logistic regression). The primary model evaluation metric was area under the receiver operating characteristic curve (AUROC). Model robustness was evaluated with calibration plot and Brier score. The top 10 predictive features in our final model were determined based on variable importance scores. Performance was assessed on subgroups based on age, sex, race, ethnicity, rurality, median area deprivation index, proximal clamp site, prior aortic surgery, and concomitant procedures. RESULTS: Overall, 12,027 patients were included. The primary outcome of in-hospital MACE occurred in 630 patients (5.2%). Compared with patients without a primary outcome, those who developed in-hospital MACE were older with more comorbidities, demonstrated poorer functional status, had more complex aneurysms, and were more likely to require concomitant procedures. Our best performing prediction model for in-hospital MACE was XGBoost, achieving an AUROC of 0.93 (95% confidence interval, 0.92-0.94). Comparatively, logistic regression had an AUROC of 0.71 (95% confidence interval, 0.70-0.73). For secondary outcomes, XGBoost achieved AUROCs between 0.84 and 0.94. The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.05. These findings highlight the excellent predictive performance of the XGBoost model. The top three predictive features in our algorithm for in-hospital MACE following open AAA repair were: (1) coronary artery disease; (2) American Society of Anesthesiologists classification; and (3) proximal clamp site. Model performance remained robust on all subgroup analyses. CONCLUSIONS: Open AAA repair outcomes can be accurately predicted using preoperative data with our ML models, which perform better than logistic regression. Our automated algorithms can help guide risk-mitigation strategies for patients being considered for open AAA repair to improve outcomes.

Machine learning to predict outcomes following endovascular abdominal aortic aneurysm repair.

BACKGROUND: Endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) carries important perioperative risks; however, there are no widely used outcome prediction tools. The aim of this study was to apply machine learning (ML) to develop automated algorithms that predict 1-year mortality following EVAR. METHODS: The Vascular Quality Initiative database was used to identify patients who underwent elective EVAR for infrarenal AAA between 2003 and 2023. Input features included 47 preoperative demographic/clinical variables. The primary outcome was 1-year all-cause mortality. Data were split into training (70 per cent) and test (30 per cent) sets. Using 10-fold cross-validation, 6 ML models were trained using preoperative features with logistic regression as the baseline comparator. The primary model evaluation metric was area under the receiver operating characteristic curve (AUROC). Model robustness was evaluated with calibration plot and Brier score. RESULTS: Some 63 655 patients were included. One-year mortality occurred in 3122 (4.9 per cent) patients. The best performing prediction model for 1-year mortality was XGBoost, achieving an AUROC (95 per cent c.i.) of 0.96 (0.95-0.97). Comparatively, logistic regression had an AUROC (95 per cent c.i.) of 0.69 (0.68-0.71). The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.04. The top 3 predictive features in the algorithm were 1) unfit for open AAA repair, 2) functional status, and 3) preoperative dialysis. CONCLUSIONS: In this data set, machine learning was able to predict 1-year mortality following EVAR using preoperative data and outperformed standard logistic regression models.

Anticoagulation for rheumatic mitral stenosis, INVICTUS in perspective.

PURPOSE OF REVIEW: Rheumatic mitral stenosis (MS) while declining in high- and middle-income countries, continues to be a major cause of death and disability in low-income countries. Although the nonvitamin-K antagonist oral anticoagulants (NOACs) have essentially supplanted vitamin K antagonists (VKA) in patients with nonvalvular atrial fibrillation (AF), their efficacy for stroke prevention in patients with rheumatic MS and AF has not been widely studied until recently. The purpose of this review is to provide a succinct synopsis of the current anticoagulation recommendations for patients with native and prosthetic heart valve disease, with a specific focus on patients with rheumatic MS. RECENT FINDINGS: The INVICTUS trial was the first large randomized evaluation of a NOAC vs. VKA in approximately 4600 patients with moderate to severe rheumatic MS and AF. The primary outcome of stroke, systemic embolization, myocardial infarction, vascular and all-cause death, VKA treated patients exhibited lower event rates (including mortality) compared to rivaroxaban. We discuss and contextualize these findings as they relate to the broader use of anticoagulants in patients with valvular heart disease, with and without concomitant AF. SUMMARY: VKA remains the standard of care for patients with moderate to severe rheumatic MS who have concomitant AF. Rates of stroke in anticoagulated patients with rheumatic MS and AF are lower than what is traditionally held, while nonstroke related deaths remain the most common mechanism of mortality.

Factor XI inhibitors: what should clinicians know.

PURPOSE OF REVIEW: Factor XI (FXI) inhibitors were developed to address unmet needs and limitations of current anticoagulants and are currently being studied in several indications. In this paper, we review the rationale for the development of these agents and summarize what clinicians should know about drugs that target FXI. RECENT FINDINGS: Patients with FXI deficiency may have a lower risk of venous thromboembolism and cardiovascular events and have a variable but generally mild bleeding diathesis. FXI has been proposed as a target for anticoagulants due to the potential for reduction in thrombosis with a lower risk of bleeding than current anticoagulant agents. Several classes of drugs that target FXI are under development, of which three classes (small molecule inhibitors, antisense oligonucleotides and monoclonal antibodies) have been studied in Phase II trials. At least three large Phase III trial programs are planned or are underway, and will study the efficacy and safety of FXI inhibitors in tens of thousands of patients across a variety of indications including atrial fibrillation, stroke and cancer-associated venous thromboembolism. SUMMARY: FXI inhibitors were developed with the hope of attenuating thrombosis with reduced bleeding/impairment of haemostasis. These agents have shown promise in preliminary trials with a low rate of bleeding. Ongoing Phase III investigations will inform the utility of these agents in clinical practice.

Is there a role for biomarkers in asymptomatic severe chronic primary mitral regurgitation?

PURPOSE OF REVIEW: Chronic primary mitral regurgitation (MR) is a common heart valve disease with a rising prevalence with the aging populations worldwide. The timing of surgical intervention in patients who have severe MR but remain asymptomatic is often debated. Herein we synthesize the latest American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology/ European Association for Cardio-Thoracic Surgery (ESC/EACTS) heart valve guidelines in such patients and illustrate how circulating and/or imaging biomarkers can be used to help refine decision making algorithms. RECENT FINDINGS: The approach to decision making and strength of guideline recommendations in patients with asymptomatic stage C1 (left ventricular ejection fraction [LVEF] > 60% and left ventricular end systolic dimension [LVESD] < 40 mm) and stage C2 disease (LVEF ≤ 60% and/or LVESD ≥ 40 mm) are reviewed. While surgical intervention is clearly indicated in patients with stage C2 disease, a multifaceted approach that integrates repairability, expertise, sub-clinical evidence of left ventricular (LV) dysfunction, and patient preferences is required to identify the optimal approach to surveillance vs. surgery. The role of imaging (3D echocardiography, contrast echocardiography, left ventricular global longitudinal strain, and cardiovascular magnetic resonance imaging [CMR]) and circulating (natriuretic peptides) biomarkers in decision making is also reviewed. SUMMARY: The decision making around timing of intervention in chronic primary MR requires a personalized approach that is based on accurate assessments of severity of MR, LV dimensions, LV function, valve morphology/repairability, surgeon and center expertise, and patient wishes. Biomarkers hold promise in refining decision making.

Bicuspid aortic valve associated aortopathy: 2022 guideline update.

PURPOSE OF REVIEW: Bicuspid aortic valve (BAV) disease is observed in 1-2% of the general population. In addition to valve-related complications (such as aortic stenosis and aortic regurgitation), individuals with BAV often develop dilatation of the proximal aorta (aortic root and ascending aorta), a condition termed BAV aortopathy. The development of BAV aortopathy can occur independent of valvular alterations and can lead to aneurysm formation, aortic dissection or aortic rupture. This review aims to update the clinician with an approach to BAV aortopathy decision making in keeping with the 2022 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline recommendations. RECENT FINDINGS: The ACC/AHA 2022 guidelines provide a contemporary and comprehensive approach to the diagnosis and treatment of aortic pathologies. We review the thresholds for replacement of the aortic root and/or ascending aorta along with the strength and level of evidence recommendations. We also review the various Class 2A and 2B recommendations for earlier intervention, which emphasize the importance of experienced surgeons, and multidisciplinary aortic teams (MATs). SUMMARY: BAV aortopathy is a common and heterogenous clinical problem. The decision making around timing of intervention requires a personalized approach that is based on the aortic dimensions, valve function, rate of growth, family history, patient factors, and surgical experience within MATs.

Racial and ethnic differences in aortic stenosis: the tip of the iceberg.

PURPOSE OF REVIEW: There is a lack of data on the epidemiology and management of severe aortic stenosis (AS) in diverse populations. We summarize the contemporary literature on the racial and ethnic differences in AS prevalence, treatment and outcomes and discuss possible explanations for these disparities to inform future research and improve the delivery of care to under-represented patient groups. RECENT FINDINGS: African American (AA) patients have significantly less prevalence of severe AS than White patients whereas paradoxically having higher traditional risk factors for severe AS. Non-White patients have less referral for aortic valve replacement (AVR) after adjusting for clinical and echocardiographic parameters. Surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) are both underutilized in non-White patients. Differences in race and ethnicity have not shown to result in worse in-hospital and long-term survival outcomes after either SAVR or TAVR. SUMMARY: Much research is warranted to explore the epidemiology, true prevalence and treatment outcomes of severe AS in diverse populations. Greater inclusion of non-White ethnic groups in the primary analysis of prospective trials is needed. Lastly, further research is warranted to explore the complex causes of racial and ethnic disparities in utilization of surgical and transcatheter interventions.

Sword Bean (Canavalia gladiata): a new host of Bean common mosaic virus.

BACKGROUND: Sword bean (Canavalia gladiata) is an underutilized legume that has the potential to become an important food source owing to its wide range of nutritional and medicinal properties. In May 2023, symptoms induced by a possible virus infection such as mosaic, mottling and vein banding were observed on the leaves of about 20% of the Sword bean plants growing at the experimental research farm of the Indian Agricultural Research Institute in Pune, Maharashtra, India. METHODS AND RESULTS: Symptomatic and asymptomatic samples were screened by ELISA for the presence of Potyvirus, Cucumber mosaic virus and Tobacco mosaic virus. All symptomatic samples tested positive for Potyvirus in ELISA as well as in RT-PCR assay using the universal potyvirus primer pair (CPUP /P9502) which amplify c. 700 bp of the partial coat protein region and 3'UTR. Asymptomatic samples tested negative for all tested viruses in both serological and molecular assays. BLASTn sequence analysis of the amplicons revealed that the sequence shares more than 98% identity with an Indian isolate of Bean common mosaic virus (BCMV). Sequence analysis enabled the identification of the Potyvirus as BCMV. Furthermore, the present Sword bean isolate clustered with other BCMV isolates in the phylogenetic analysis. CONCLUSION: In the present study, BCMV was found to be naturally infecting Sword bean for the first time in the world. This is of epidemiological importance, as BCMV is known to cause significant yield losses in legumes and could severely hamper Sword bean production.

Effect of empagliflozin on cardiac remodelling in South Asian and non-South Asian individuals: insights from the EMPA-HEART CardioLink-6 randomised clinical trial.

BACKGROUND: This exploratory sub-analysis of the EMPA-HEART CardioLink-6 trial examined whether the previously reported benefit of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin on left ventricular (LV) mass (LVM) regression differs between individuals of South Asian and non-South Asian ethnicity. METHODS: EMPA-HEART CardioLink-6 was a double-blind, placebo-controlled clinical trial that randomised 97 individuals with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) to either empagliflozin 10 mg daily or placebo for 6 months. LV parameters and function were assessed using cardiac magnetic resonance imaging. The 6-month changes in LVM and LV volumes, all indexed to baseline body surface area, for South Asian participants were compared to those for non-South Asian individuals. RESULTS: Compared to the non-South Asian group, the South Asian sub-cohort comprised more males, was younger and had a lower median body mass index. The adjusted difference for LVMi change over 6 months was -4.3 g/m2 (95% confidence interval [CI], -7.5, -1.0; P = 0.042) for the South Asian group and -2.3 g/m2 (95% CI, -6.4, 1.9; P = 0.28) for the non-South Asian group (Pinteraction = 0.45). There was no between-group difference for the adjusted differences in baseline body surface area-indexed LV volumes and LV ejection fraction. CONCLUSIONS: There was no meaningful difference in empagliflozin-associated LVM regression between South Asian and non-South Asian individuals living with T2DM and CAD in the EMPA-HEART CardioLink-6 trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02998970 (First posted on 21/12/ 2016).