Innovations in genomic antimicrobial resistance surveillance.

Whole-genome sequencing of antimicrobial-resistant pathogens is increasingly being used for antimicrobial resistance (AMR) surveillance, particularly in high-income countries. Innovations in genome sequencing and analysis technologies promise to revolutionise AMR surveillance and epidemiology; however, routine adoption of these technologies is challenging, particularly in low-income and middle-income countries. As part of a wider series of workshops and online consultations, a group of experts in AMR pathogen genomics and computational tool development conducted a situational analysis, identifying the following under-used innovations in genomic AMR surveillance: clinical metagenomics, environmental metagenomics, gene or plasmid tracking, and machine learning. The group recommended developing cost-effective use cases for each approach and mapping data outputs to clinical outcomes of interest to justify additional investment in capacity, training, and staff required to implement these technologies. Harmonisation and standardisation of methods, and the creation of equitable data sharing and governance frameworks, will facilitate successful implementation of these innovations.

A systematic review of economic evaluations of whole-genome sequencing for the surveillance of bacterial pathogens.

Whole-genome sequencing (WGS) has unparalleled ability to distinguish between bacteria, with many public health applications. The generation and analysis of WGS data require significant financial investment. We describe a systematic review summarizing economic analyses of genomic surveillance of bacterial pathogens, reviewing the evidence for economic viability. The protocol was registered on PROSPERO (CRD42021289030). Six databases were searched on 8 November 2021 using terms related to 'WGS', 'population surveillance' and 'economic analysis'. Quality was assessed with the Drummond-Jefferson checklist. Following data extraction, a narrative synthesis approach was taken. Six hundred and eighty-one articles were identified, of which 49 proceeded to full-text screening, with 9 selected for inclusion. All had been published since 2019. Heterogeneity was high. Five studies assessed WGS for hospital surveillance and four analysed foodborne pathogens. Four were cost-benefit analyses, one was a cost-utility analysis, one was a cost-effectiveness analysis, one was a combined cost-effectiveness and cost-utility analysis, one combined cost-effectiveness and cost-benefit analyses and one was a partial analysis. All studies supported the use of WGS as a surveillance tool on economic grounds. The available evidence supports the use of WGS for pathogen surveillance but is limited by marked heterogeneity. Further work should include analysis relevant to low- and middle-income countries and should use real-world effectiveness data.

Whole-genome sequencing enhances existing pathogen and antimicrobial-resistance surveillance schemes within a neonatal unit.

In some neonatal units, the screening of isolates for antimicrobial-resistant organisms is a matter of routine, with theoretical benefits including the prevention or early detection of outbreaks. This study sought to use whole-genome sequencing (WGS) retrospectively to characterize the genomic epidemiology of Gram-negative organisms obtained from a screening programme in a 32-bed unit providing intensive, high-dependency and special care at City Hospital, Birmingham, UK, identifying occult transmission events and clinically important antimicrobial-resistance (AMR) genes. WGS was performed for 155 isolates collected from rectal and umbilical screening swabs over a 2 month period from 44 individual neonates. Genomic epidemiological analysis showed possible transmission events involving Escherichia coli, Enterobacter cloacae, Klebsiella oxytoca and Klebsiella pneumoniae not detected by routine screening, with eight putative clusters involving different individuals identified. Within phylogenetic clusters, the relatedness of organisms - as determined by the abundance of SNPs - varied widely, indicating that a variety of transmission routes may be implicated. While clinically important AMR genes were not present in the putative transmission clusters, our observation of suspected interspecies horizontal transfer of blaCTX-M-15 within individuals highlights the potential for their spread between organisms as well as individuals in this environment, with implications for surveillance. Our data show that WGS may reveal occult Gram-negative transmission events, demonstrating the potential of sequencing-based surveillance systems for nosocomial pathogens. Challenges remain in understanding how to utilize WGS surveillance to maximum effect in real-world settings.

A Farm to Fork Risk Assessment for the Use of Wastewater in Agriculture in Accra, Ghana.

The need to minimise consumer risk, especially for food that can be consumed uncooked, is a continuing public health concern, particularly in places where safe sanitation and hygienic practices are absent. The use of wastewater in agriculture has been associated with disease risks, though its relative significance in disease transmission remains unclear. This study aimed at identifying key risk factors for produce contamination at different entry points of the food chain. Over 500 produce and ready-to-eat salad samples were collected from fields, markets, and kitchens during the dry and wet seasons in Accra, Ghana, and over 300 soil and irrigation water samples were collected. All samples were analysed for E. coli, human adenovirus and norovirus using standard microbiological procedures, and real time RT-PCR. Finally, critical exposures associated with microbial quality of produce were assessed through observations and interviews. The study found that over 80% of produce samples were contaminated with E. coli, with median concentrations ranging from 0.64 to 3.84 Log E. coli/g produce. Prepared salad from street food vendors was found to be the most contaminated (4.23 Log E. coli/g), and that consumption of salad exceeded acceptable health limits. Key risk factors identified for produce contamination were irrigation water and soil at the farm level. Storage duration and temperature of produce had a significant influence on the quality of produce sold at markets, while observations revealed that the washed water used to rinse produce before sale was dirty. The source of produce and operating with a hygiene permit were found to influence salad microbial quality at kitchens. This study argues for a need to manage produce risk factors at all domains along the food chain, though it would be more effective to prioritise at markets and kitchens due to cost, ease of implementation and public health significance.

Detection of aortic wall instability with the new dissectometer: Correlation with histological findings.

OBJECTIVES: Although risk stratification for aortic dissection or rupture based on aortic diameter is quite suboptimal, alternative methods for the assessment of the aortic wall stability are rare. We assessed the mechanical properties of the aortic wall by a new custom-made device mimicking transversal aortic wall shear stress during open heart surgery in comparison with histological examination. MATERIAL AND METHODS: One-hundred and five aortic walls were tested by the 'dissectometer' (seven different measured and two calculated values) as well as histological examination was performed. RESULTS: Histological examination classified the aortic wall as normal in 54 (51.4%) patients and pathologic in 51 (48.6%) patients. Six out of nine parameters assessed by the dissectometer showed a significant correlation to histological findings. Using ROC-analysis, the most reliable parameter (P9) showed a sensitivity of 93.3% and a specificity of 80.4% with an area under the curve of 0.89 when using a cut-off value of 3.4. In the logistic regression analysis, P9 was an independent predictor for aortic wall instability (OR 28.983, 95% CI 11.507-72.993, p < 0.0001). CONCLUSION: The dissectometer is suitable for discriminating between stable and unstable aortic walls with a good correlation to histological examination holding promise for direct and quick intraoperative identification of aortic walls at risk for dissection.

Comparison of ascending aortic cohesion between patients with bicuspid aortic valve stenosis and regurgitation.

OBJECTIVES: A bicuspid aortic valve (BAV) is commonly associated with aortic wall abnormalities, including dilatation of the ascending aorta and increased potential for aortic dissection. We compared the mechanical properties of the aortic wall of BAV patients with aortic valve stenosis (AS) and regurgitation (AR) using a dissectometer, a device mimicking transverse aortic wall shear stress. METHODS: Between March 2010 and February 2013, 85 consecutive patients with bicuspid aortic valve undergoing open aortic valve replacement at our institution were prospectively enrolled, presenting either with stenosis (Group 1, n = 58) or regurgitation (Group 2, n = 27). Aortic wall cohesion measured by the dissectometer (Parameters P7, P8 and P9), aortic diameters measured by transoesophageal echocardiography (TOE) and thickness of the wall were compared. One patient presenting with the Marfan syndrome was excluded from the study. RESULTS: Patients with aortic regurgitation were significantly younger (48.2 ± 15.8 vs 64.7 ± 10.7, P < 0.001), and had a significantly thicker aortic wall (2.30 ± 0.49 mm vs 2.06 ± 0.35 mm, P = 0.029). Transoesophageal echocardiography diameters (annulus, aortic sinuses and sinotubular junction) were significantly larger in the AR group (27.3 ± 3.6 vs 25.5 ± 2.4, P = 0.008; 41.1 ± 7.7 vs 36.7 ± 8.0, P = 0.011; 37.6 ± 9.7 vs 33.8 ± 9.1, P = 0.049). The ascending aortic diameter did not differ (43.2 ± 10.6 vs 40.3 ± 9.1, P = 0.292). Patients with AR had significantly worse aortic cohesion, as measured by shear stress testing (P7: 97.2 ± 45.0 vs 145.5 ± 84.9, P = 0.015; P8: 2.00 ± 0.65 vs 3.82 ± 1.56, P < 0.001; P9: 2.96 ± 0.82 vs 4.98 ± 1.80, P < 0.001) compared with those with AS. CONCLUSIONS: We observed significantly worse aortic wall cohesion, a thicker aortic wall and a larger aortic root in patients presenting with bicuspid AR compared with patients with AS. These results suggest that bicuspid AR represents a different disease process with possible involvement of the ascending aorta, as demonstrated by dissectometer examination.

Comparison between different risk scoring algorithms on isolated conventional or transcatheter aortic valve replacement.

BACKGROUND: There are a number of scoring systems for risk evaluation in cardiac surgery, the most important of which are the European System for Cardiac Operative Risk Evaluation (EuroSCORE), The Society of Thoracic Surgeons (STS) score, the ACEF score (acronym for age, preoperative creatinine, and ejection fraction), and more recently, the new EuroSCORE-II. The aim of our study was to analyze and compare the predictive value of these scores in patients undergoing aortic valve replacement (AVR) or transcatheter aortic valve replacement (TAVR). METHODS: A total of 1,512 consecutive patients undergoing either conventional AVR (n = 1,066) or TAVR (transfemoral, n = 291; transapical, n = 155) were enrolled. Logistic and additive EuroSCORE of all patients were 13.3% ± 13.2% and 7.8% ± 3.3%, on average. The mean STS score, ACEF score, and EuroSCORE-II were 5.7% ± 5.0%, 1.5% ± 0.7%, and 4.2% ± 4.9%, respectively. RESULTS: Overall mortality at 30 days was 6.3%. The area under the curve (AUC) was 73.8 for the logistic EuroSCORE and 73.5 for the additive EuroSCORE. The STS score gave an AUC of 70.8. The AUCs for the ACEF and EuroSCORE-II were 63.8 and 71.2, respectively. In the transfemoral TAVR group, AUCs were 59.8 and 59.3 for the logistic and additive EuroSCORE, respectively, 63.2 for the STS score, and 55.9 and 55.4 for the ACEF and EuroSCORE-II, respectively. In the transapical TAVR group, AUCs were 88.0 and 82.8 for the logistic and additive EuroSCORE, respectively, 79.0 for the STS score, and 61.7 and 83.7 for the ACEF and EuroSCORE-II, respectively. CONCLUSIONS: Overall, 30-day mortality was best predicted by the STS score. Discrimination threshold predicting mortality was equal between all other risk calculators. Surprisingly, the new EuroSCORE-II was not superior to other models in risk prediction for AVR and TAVR patients.

The new St Jude Trifecta versus Carpentier-Edwards Perimount Magna and Magna Ease aortic bioprosthesis: is there a hemodynamic superiority?

OBJECTIVES: The Trifecta valve (St Jude Medical, St Paul, Minn) is a new bioprosthetic heart valve designed for supra-annular aortic valve replacement. We compared the hemodynamic performance of the Trifecta against the Perimount-Magna and Magna-Ease valve prostheses (Edwards Lifesciences, Irvine, Calif) in a nonrandomized, observational, single-center study. METHODS: A total of 346 consecutive patients with aortic valve disease underwent aortic valve replacement between January 2003 and November 2011, with implantation of the Trifecta (group 1, n = 121), the Perimount-Magna (group 2, n = 126), or the Magna Ease bioprosthesis (group 3, n = 99). Clinical and hemodynamic data were prospectively recorded and compared. Hemodynamic performance was evaluated by transthoracic echocardiography, including mean pressure gradient (MPG) and aortic valve area (AVA) at baseline, discharge, and 6-month follow-up. A multivariate model of covariance analysis was constructed to further compare the primary study end points of MPG and AVA at 6-month follow-up. RESULTS: For all valve sizes, unadjusted MPGs did not differ (P = .08), but AVAs differed (P < .001) between groups at 6-month follow-up. After final adjustment by a multivariate model of covariance analysis, neither the MPGs (P = .16) nor the AVAs (P = .92) at 6 months postoperatively were influenced by the type of prosthesis used. CONCLUSIONS: The present observational study is the first to compare the new Trifecta valve with well-established supra-annular aortic valve bioprostheses from a hemodynamic perspective. Although mean pressure gradients and aortic valve areas seem to be advantageous at 6-month follow-up with the new Trifecta valve, after multivariate covariance analysis, no influence of prosthesis type on mean pressure gradient or aortic valve area could be demonstrated.

Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial.

BACKGROUND: Remote ischaemic preconditioning has been associated with reduced risk of myocardial injury after coronary artery bypass graft (CABG) surgery. We investigated the safety and efficacy of this procedure. METHODS: Eligible patients were those scheduled to undergo elective isolated first-time CABG surgery under cold crystalloid cardioplegia and cardiopulmonary bypass at the West-German Heart Centre, Essen, Germany, between April, 2008, and October, 2012. Patients were prospectively randomised to receive remote ischaemic preconditioning (three cycles of 5 min ischaemia and 5 min reperfusion in the left upper arm after induction of anaesthesia) or no ischaemic preconditioning (control). The primary endpoint was myocardial injury, as reflected by the geometric mean area under the curve (AUC) for perioperative concentrations of cardiac troponin I (cTnI) in serum in the first 72 h after CABG. Mortality was the main safety endpoint. Analysis was done in intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT01406678. FINDINGS: 329 patients were enrolled. Baseline characteristics and perioperative data did not differ between groups. cTnI AUC was 266 ng/mL over 72 h (95% CI 237-298) in the remote ischaemic preconditioning group and 321 ng/mL (287-360) in the control group. In the intention-to-treat population, the ratio of remote ischaemic preconditioning to control for cTnI AUC was 0·83 (95% CI 0·70-0·97, p=0·022). cTnI release remained lower in the per-protocol analysis (0·79, 0·66-0·94, p=0·001). All-cause mortality was assessed over 1·54 (SD 1·22) years and was lower with remote ischaemic preconditioning than without (ratio 0·27, 95% CI 0·08-0·98, p=0·046). INTERPRETATION: Remote ischaemic preconditioning provided perioperative myocardial protection and improved the prognosis of patients undergoing elective CABG surgery. FUNDING: German Research Foundation.

Adjustment of aortic annulus size during David re-implantation (how to do it).

Stability of the aortic annulus is a key factor in achieving long-term durability of the aortic valve re-implantation. We propose a new method of sub-annular fixation of the root prosthesis, enabling post-procedural transesophageal echocardiography (TEE)-guided adjustment of the aortic annulus dimensions.

Is there any difference in aortic wall quality between patients with aortic stenosis and those with regurgitation?

OBJECTIVES: The interaction between aortic valve (AV) and aortic wall pathology is currently unclear. No intraoperative examination or investigation is able to predict postoperative dissection or aneurysm formation in patients operated on for primary AV pathology. The aim of the present study was therefore to evaluate the mechanical and histological properties of the aortic wall in patients operated on for aortic stenosis (AS) or regurgitation (AR). METHODS: The aortic walls of 229 patients (age 67.5 ± 11.0 years) operated on for AS (n = 135, Group 1) or AR (n = 94, Group 2) were subjected to mechanical stress testing and postoperative histological examination. Ascending aortic diameter was ≥50 mm in 46/229 patients and 40-49 mm in 52/229 patients. RESULTS: AR was associated with an increased tendency to aortic media disruption (P < 0.001) and with media degeneration (P < 0.001) compared with AS patients. The incidence of aortic aneurysm (≥50 mm) was increased in AR patients (35 in AR and 11 in AS, P < 0.01). The aortic wall cohesion was better in patients with an aortic diameter of <40 mm compared with those with moderate dilatation of 40-49 mm (P = 0.009) or an aortic aneurysm (P = 0.002). CONCLUSIONS: Our study proves that patients presenting for AV replacement with AR have a poorer quality of the ascending aorta despite a superior thickness compared with patients with AS. In addition, patients with a slightly dilated aorta (40-49 mm) have a poorer cohesion of the aortic wall than those with normal aortic dimensions.

Coronary ostium topography: an implication for transcatheter aortic valve implantation?

OBJECTIVES: Shorter distances from coronary ostia to the calcified aortic valve may result in occlusion with potential infarction during transcatheter aortic valve implantation. We hypothesized that preoperative CT-scan measurements might predict coronary occlusion. METHODS: Distances from the coronary ostia to the calcified aortic valve were measured during open heart aortic valve replacement in 60 consecutive patients. Distances were compared to preoperative CT-scan measurements evaluating distance of the coronary ostia as well (n = 15). RESULTS: The distances of the lower lip of the left and the right coronary artery ostia measured from the aortic annulus were 14.7 ± 3.9 mm and 13.4 ± 4.0 mm, respectively. The left, right and noncoronary cusp heights were 13.9 ± 2.5 mm, 12.8 ± 3.0 mm and 13.3 ± 3.1 mm, respectively. Coronary ostia topography indicated variations from the middle to the noncoronary commissure in 40% for the left and 63% for the right coronary ostium. CT-scan based measurements resulted in a distance of 12.8 ± 3.5 mm for the left and 13.9 ± 4.0 mm for the right coronary ostium, compared to 14.2 ± 4.2 mm and 13.5 ± 4.3 mm measured intraoperatively. A mild correlation between both measurements could be observed (r = 0.374, P = 0.188, left and r = 0.46, P = 0.09, n = 15). CONCLUSIONS: CT-scan-based measurements differed from the intraoperative measurements, however preoperative CT-scan evaluation may be a useful tool to identify patients with short distance of coronaries.

Remote ischemic preconditioning: the surgeon's perspective.

Since cardiac surgery began, surgeons have aimed to find methods of minimizing myocardial injury resulting from ischemia and reperfusion. The concept of somehow conditioning the heart in order to attenuate ischemia and reperfusion-related injury has evolved in cardiovascular research over decades, from ischemic preconditioning and postconditioning to, more recently, remote ischemic preconditioning (and postconditioning). Although many strategies have proven to be beneficial in the experimental arena, a few have been successfully translated into clinical practice. Remote ischemic preconditioning, with the use of brief episodes of ischemia and reperfusion of vascular territories remote from the heart, has been shown convincingly to decrease myocardial injury. To date, the translation of this powerful innate mechanism of myocardial and/or multiorgan protection from the animal lab to the operating theatre, using transient occlusion of blood flow to the upper limb with a blood-pressure cuff before cardiac surgery, has shown promising results, with several proof-of-principle and first randomized controlled clinical trials reporting benefits for patients undergoing cardiac surgery. If the efficacy of remote ischemic preconditioning can be conclusively proven, the clinical applications in cardiac surgery could be almost infinite, providing multiorgan protection in various surgical scenarios.

Management of high-risk patients with aortic stenosis and coronary artery disease.

BACKGROUND: Aortic valve replacement with coronary artery bypass graft surgery is currently the standard therapy for patients with aortic stenosis and concomitant coronary artery disease. We sought to determine whether transcatheter aortic valve implantation combined with percutaneous coronary intervention might be an equivalent strategy. METHODS: A total of 243 high-risk patients (Society of Thoracic Surgeons [STS] score >10% and/or European System for Cardiac Operative Risk Evaluation [EuroSCORE] >15%) presenting with aortic stenosis with concomitant coronary artery disease were studied. Patients were treated either by surgical aortic valve replacement combined with coronary artery bypass graft (group 1, n = 184) or by percutaneous coronary intervention within 12 months before transapical or transfemoral transcatheter aortic valve implantation (group 2, n = 59). A propensity score adjusted regression analysis was used to compare 30-day mortality as the primary study endpoint between the groups. RESULTS: Group 1 mean age (75 ± 6 years), EuroSCORE (18.1% ± 13.8%), and STS score (13.1% ± 8.7%) were significantly different from group 2 (mean age 80 ± 6 years, EuroSCORE 27.5% ± 16.3%, and STS score 16.7% ± 10.5%; p < 0.001). Thirty-day mortality was 12.5% in group 1 compared with 11.9% in group 2 (odds ratio 0.94, 95% confidence interval: 0.38 to 2.32, p = 0.89). Univariate analysis revealed left ventricular ejection fraction, pulmonary hypertension, renal insufficiency, STS score, EuroSCORE, and previous cardiac surgery as predictors for 30-day mortality (p < 0.05). Risk-adjusted multivariate regression analysis showed only left ventricular ejection fraction to be strongly associated with 30-day mortality and confirmed no significant difference between the groups (p = 0.44). To further control for study bias, a 10-layer propensity score model based on the univariate analysis again indicated equivalence regarding the primary endpoint (p = 0.33). CONCLUSIONS: The present study demonstrates that transcatheter aortic valve implantation in combination with prior percutaneous coronary intervention within 12 months produces similar results in a propensity score matched high-risk patient population.

A new self-expandable transcatheter aortic valve for transapical implantation: feasibility in acute and chronic animal experiments.

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) is currently expanding worldwide, however all available prostheses share some fundamental design drawbacks. We investigated the feasibility, safety and hemodynamic performance of the innovative transapical Acurate TA™ self-expandable device, which has the unique advantage of offering anatomically correct self-alignment within the aortic root. DESIGN: Transapical TAVI was performed in six acute swine and six chronic sheep procedures, with follow-up of 7, 14, 21, 28, 60 and 90 days. TAVI was performed under TEE and angiographic guidance without rapid pacing. RESULTS: A partial sternotomy approach was used to access the LV-apex. All valve implantations were performed as planned and all animals survived the implantation procedure. After deployment, no migration, embolization or coronary obstruction was observed during the observation period. Intraoperative TEE examination identified no signs of intravalvular leakage or valve dysfunction. Transvalvular mean pressure gradients were 5.4 ± 2.2 mmHg decreasing during follow-up (1.6 ± 0.8 mmHg, 1.8 ± 0.8 mmHg, 1.3 ± 0.2, 1.8 ± 0.7 mmHg, 1.6 ± 0.8 mmHg), with a slight increase atday 90 (4.0 ± 2.4 mmHg, P < 0.05). Macroscopic examination at necropsy showed correct anatomical positioning of the valve stent without any signs of structural valve deterioration. CONCLUSIONS: These first results of the innovative self-expandable transapical ACURATE TA™ device explore the feasibility and safety of anatomically correct off-pump implantation with optimal hemodynamic results.

Prognostic significance of cardiac troponin I on admission for surgical treatment of acute pulmonary embolism: a single-centre experience over more than 10 years.

OBJECTIVES: Cardiac troponin I (cTnI) is a highly sensitive, specific marker for myocardial cell injury. We sought to determine whether cTnI on admission may help to identify patients with increased risk of open surgical embolectomy with acute pulmonary embolism (PE). METHODS: Forty-six consecutive patients with confirmed acute PE were enrolled in this prospective study. PE was confirmed by pulmonary angiography, computed tomography (CT) scan or echocardiography. Severity of PE was assessed by clinical data, and cTnI was measured within 12 h after admission. RESULTS: cTnI was elevated in 28 patients with acute PE. Preoperative right ventricular dysfunction [odds ratio (OR): 15.2; 95% confidence interval (CI): 2.02-144.8; P < 0.002], prolonged hypotension with cardiogenic shock (OR: 14.9; 95% CI: 2.2-131.1; P < 0.002) and preoperative need for resuscitation (OR: 6.0; 95% CI: 0.6-143.8; P = 0.12) were more prevalent in patients with elevated cTnI serum concentrations. cTnI-positive patients were also more likely to require inotropic support (OR: 10.0; 95% CI: 1.8-65.1; P < 0.005) and mechanical ventilation (OR: 13.5; 95% CI: 2.2-95.6; P < 0.005). Moreover, an elevated cTnI level on admission significantly correlated with both primary endpoints, in-hospital mortality (OR: 9.0; 95% CI: 1.0-215.2; P = 0.03) and major adverse clinical events (OR: 8.3; 95% CI: 1.5-62.5; P = 0.006). After multivariable risk adjustment, a positive cTnI value remained an independent predictor of in-hospital mortality (OR: 13.6; 95% CI: 3.22-145.8; P = 0.014) and major adverse clinical events (OR: 15.7; 95% CI: 4.15-133.7; P = 0.031). CONCLUSIONS: cTnI on admission may improve risk assessment of patients undergoing open surgical embolectomy due to acute PE.