Risultati per: Sviluppo di un test meno invasivo per la malattia infiammatoria intestinale

Objectives
Point-of-care tests (POCTs) for infection offer accurate rapid diagnostics but do not consistently improve antibiotic stewardship (ASP) of suspected ventilator-associated pneumonia. We aimed to measure the effect of a negative PCR-POCT result on intensive care unit (ICU) clinicians’ antibiotic decisions and the additional effects of patient trajectory and cognitive-behavioural factors (clinician intuition, dis/interest in POCT, risk averseness).

Design
Observational cohort simulation study.

Setting
ICU.

Participants
70 ICU consultants/trainees working in UK-based teaching hospitals.

Methods
Clinicians saw four case vignettes describing patients who had completed a course of antibiotics for respiratory infection. Vignettes comprised clinical and biological data (ie, white cell count, C reactive protein), varied to create four trajectories: clinico-biological improvement (the ‘improvement’ case), clinico-biological worsening (‘worsening’), clinical improvement/biological worsening (‘discordant clin better’), clinical worsening/biological improvement (‘discordant clin worse’). Based on this, clinicians made an initial antibiotics decision (stop/continue) and rated confidence (6-point Likert scale). A PCR-based POCT was then offered, which clinicians could accept or decline. All clinicians (including those who declined) were shown the result, which was negative. Clinicians updated their antibiotics decision and confidence.

Measures
Antibiotics decisions and confidence were compared pre-POCT versus post-POCT, per vignette.

Results
A negative POCT result increased the proportion of stop decisions (54% pre-POCT vs 70% post-POCT, 2(1)=25.82, p

This article presents results from a prospective pivotal study in which individuals completed a multitarget stool RNA test prior to undergoing a colonoscopy to determine the sensitivity for detecting colorectal cancer and advanced ademonas.

Annals of Internal Medicine, Ahead of Print.

Annals of Internal Medicine, Ahead of Print.

Circulation, Volume 148, Issue Suppl_1, Page A16196-A16196, November 6, 2023. Introduction:The ratio of early transmitral flow velocity (E) to early diastolic mitral annular velocity (e’) is a surrogate for left ventricular (LV) filling pressure. Post-stress E/e’ has been shown to predict exercise capacity, but few studies have investigated this correlation with baseline E/e’. Our aim was to evaluate the relationship between baseline E/e’ and exercise capacity during stress test.Methods:All patients undergoing exercise stress testing at University of Virginia from 1/2015 through 9/2015 with the required echo data were included in this study. E/e’ was categorized into quartiles. ANOVA was used to evaluate the relationship between quartiles of E/e’ and exercise duration or METS. Multivariate linear regression was used to adjust for the variables: age, sex, ejection fraction, systolic blood pressure, heart rate, and regional wall motion abnormalities.Results:Baseline characteristics of the 312 participants based on E/e’ quartiles are shown in Table 1; those with higher E/e’, on average, had higher baseline SBP, were older, and had a higher percentage of females. There was a significant difference in exercise duration and METS between E/e’ quartiles (Table 2A) [p < 0.001]. There was an inverse correlation between E/e’ and exercise capacity; the significance was more pronounced with increasing E/e’ (Table 2A) and was present even after adjusting for multiple covariates (Table 2B).Conclusions:Baseline E/e’ correlates with exercise capacity (both duration of exercise and total METS achieved). This suggests that elevated LV filling pressures at rest can predict exercise capacity and may be targeted in future studies to improve exercise tolerance.

Circulation, Volume 148, Issue Suppl_1, Page A13988-A13988, November 6, 2023. Introduction:High-sensitivity cardiac troponin I (hs-cTnI) assays provide comparable diagnostic information that allow for better detection of myocardial injury. However, hs-cTnI release after cardiac stress testing and its potential utility for identifying inducible myocardial ischemia and risk-stratification are unclear.Aim:This pilot study examined integrating hs-cTnI biomarker testing into cardiac imaging stress testing to improve detection of inducible ischemia and aid in risk-stratification in patients with chest pain being evaluated for acute coronary syndrome (ACS).Methods:We prospectively enrolled 200 consecutive adult patients referred by the Emergency Room for cardiac stress testing for evaluation of possible ACS. A venous blood sample was collected between 0.5 and 2 hours post stress testing; cTnI concentrations were measured in-house by high sensitivity methods. Changes from pre-stress test hs-cTnI concentrations were calculated and association with outcome was explored using a logistic regression model.Results:Patient median age was 62 years, IQR 54-70; 49% were women. ACS known risk factors included hypertension 81.5%, cigarette smoking 49.5% and diabetes 33.5%. Median BMI was 31.63 kg/m2, IQR 27.24-35.84. Pre-stress test hs-cTnI median levels were 6 ng/L, IQR 5-9, for women (URL

Circulation, Volume 148, Issue Suppl_1, Page A12748-A12748, November 6, 2023. Background:The 6-minute walk test (6MWT) is an established test to assess functional exercise performance and the 6-minute walk distance (6MWD) is strongly correlated with the functional capacity and the prognosis in patients with heart failure (HF). However, the clinical implication of sequential changes in percutaneous oxygen saturation (SpO2) during 6MWT has not been investigated in HF patients.Purpose:To prospectively clarify the association between sequential changes in SpO2 during 6MWT and prognosis in patients with HF.Methods:Fifty patients admitted with acute heart failure were enrolled. The 6MWT was performed at the time before discharge, after hemodynamic stability was confirmed. The average of SpO2 was calculated from data obtained at rest and during 6MWT by employing the wearable pulse-oximeter which is designed to record the SpO2 value every second. Alternations in SpO2 (ΔSpO2) were obtained by subtracting the average during 6MWT from that at rest. Patients were followed up to 9 months for the composite outcome of heart failure-hospitalization and death.Results:The mean age of participants was 78.8 years, and 23 (46%) were female. The mean EF was 46.1% and the number of patients with EF ≦40 was 22. The 6MWD was 250 ± 112m and the ΔSpO2 was 2.88 ± 4.3%. All cases were classified by walk distance and ΔSpO2; long- ( >220m) vs. short-distance group (≦220m) and low- (

Circulation, Volume 148, Issue Suppl_1, Page A11520-A11520, November 6, 2023. Background:Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Autonomic neuromodulation, including injection of botulinum toxin into epicardial fat pads, may suppress and/or attenuate atrial fibrillation. The respiratory safety of a potential preventative treatment for AF is critical.Aim:To assess efficacy and pulmonary safety of botulinum toxin type A (BoNT/A; AGN-151607) 125U and 250U vs placebo for prevention of POAF after coronary artery bypass graft and/or valve surgery.Methods:NeurOtoxin for the PreVention of post-operative Atrial fibrillation (NOVA; NCT03779841) was a phase 2, international, multicenter, randomized, placebo-controlled trial. The primary endpoint was proportion of patients with continuous AF ≥30 seconds within the first 30 days. Respiratory function was assessed via pulmonary function tests (PFTs) performed at baseline and day 30 after treatment. Adverse events (AEs), serious adverse events (SAEs), and time to extubation were recorded.Results:A total of 323 patients were randomized: BoNT/A 125U (n=106), 250U (n=109), placebo (n=108). The primary endpoint occurred in 46.1% of the placebo group, 36.5% of the 125U group (relative risk [RR] vs placebo, 0.80 [95% CI: 0.58, 1.10];P=0.16), and 47.2% of the 250U group (RR vs placebo, 1.04 [95% CI: 0.79, 1.37];P=0.78). Baseline, day 30, and change from baseline PFT results were similar for active treatment vs placebo (Table). Median time to extubation was 9.7, 9.6, and 9.6 h in the placebo, 125U, and 250U groups, respectively. Respiratory AEs were reported in 42.9%, 38.1%, and 50.5% of patients, and respiratory SAEs in 11.4%, 6.7%, and 5.5% of patients in the placebo, 125U, and 250U groups, respectively.Conclusion:In this analysis of respiratory function, there appeared to be no detrimental effect of AGN-151607 compared with placebo, as evidenced by similar outcomes in PFT parameters and respiratory AE/SAE incidences among treatment arms.

Circulation, Volume 148, Issue Suppl_1, Page A11613-A11613, November 6, 2023. Background:Adverse hemodynamic responses on exercise stress testing have prognostic impact, but the cumulative effect of multiple abnormalities is not known. These markers include chronotropic incompetence, reduced metabolic equivalents achieved, abnormal hemodynamic gain index, impaired heart rate recovery, and abnormal blood pressure response.Research Questions:In a contemporary population undergoing exercise stress testing, what is the cumulative prevalence and prognostic impact of the number of abnormal stress hemodynamic markers (asHD)?Aims:We measured the prevalence of increasing values of asHD and the associated burden of all-cause mortality and non-fatal myocardial infarction (death/NFMI).Methods:We performed a retrospective, single-center analysis of patients referred for exercise stress myocardial perfusion imaging from 2015-2017. Multivariable Cox proportional hazards modeling was used to explore the relationship between cumulative burden of asHD markers and death/NFMI.Data:The study population included 1,595 patients (mean age 62.1, 36.9% female) with mean follow-up 4.8 years stratified by number of asHD markers (0, 1, 2, or 3+). 60.2% of patients tested had at least one asHD marker. The cumulative burden was 1 asHD in 32%, 2 asHD in 19%, and 3+ asHD in 9.3%. Patients with any asHD were at greater risk for death/NFMI compared to patients with 0 asHD (HR 1.98 [95% CI, 1.39 – 2.83], p

Circulation, Volume 148, Issue Suppl_1, Page A16973-A16973, November 6, 2023. Introduction:Despite several off-the-shelf ultrasound systems being used for large vessel access, reliable and safe vascular access remains a problem. This is especially true during combat casualty care where skilled operators may not be available. We tested a novel small-footprint platform for efficacy and timeliness of large vessel access at normovolemic and hypovolemic statesHypothesis:A custom-designed device with optimized ergonomics and workflow will yield high success rates and low training needs for large vessel accessMethods:Vu-Path has a pen-size 10 mm ultrasound transducer with a proprietary needle guide and a lightweight engine deployed with a tablet or laptop. The display has an overlay showing the needle insertion path. Once the vessel is visible within the overlay, insertion of the needle using the needle guide directs insertion to the vessel. We used 3 models to simulate femoral vessel access: 1) a commercially available phantom (CAE Blue Phantom); 2) a custom in-vitro tissue phantom mimicking swine normovolemic and hypovolemic femoral vascular states; 3) an ex-vivo model of a euthanized swine lower-body section with canulated femoral vessels looped with a peristaltic pump to simulate normovolemic and hypovolemic states.Results:Vu-Path tested in these 3 models resulted in 87% successful insertions across all models and conditions; 100% success on the commercial model versus 83% in the custom tissue phantoms. In every model, 2 metrics were evaluated as summarized in Figure: total time to align vessel in the needle track window, and total time after aligning to confirmed insertion. Mean attempts needed to gain system expertise was 6.Conclusions:Vu-Path had high success rates for vessel visualization and needle access guidance in 3 models simulating normovolemic and hypovolemic conditions. Training requirements were minimal. These data suggest Vu-Path is capable of potentially improving safety and reliability of large vessel access.

Circulation, Volume 148, Issue Suppl_1, Page A13902-A13902, November 6, 2023. Background:Nonalcoholic steatohepatitis (NASH) is associated with increased cardiovascular outcomes. Assessment of the impact of NASH therapy on cardiovascular risk is an important element of NASH drug development but is challenging particularly in early phase trials. Aptamer-based proteomic profiles (Somalogic®) in serum have been used to develop and validate a risk score as a surrogate for cardiovascular (CV) risk.Hypothesis:Improvement in NASH histology will result in improved proteomic cardiovascular risk scores.Methods:A post-hoc analysis of proteomic profiles of serum samples, using the Somalogic® platform, from the Pioglitazone vs. Vitamin E vs. Placebo for Treatment of Nonalcoholic Fatty Liver Disease (PIVENS) trial was conducted. PIVENS was a 96-week trial of nondiabetic participants with (NASH). We applied the proteomic CV risk scores to samples from baseline, on therapy and end of treatment visits (n=7) visits and received liver histology results at baseline and 96 weeks on N = 209 (84.6%) study participants. Generalized linear and mixed models were used to assess the association between CV risk score, treatment arm and change in liver biopsy results.Results:Baseline scores were similar across groups (mean 0.19, SD 0.14). There was no association between treatment arms and changes in scores during therapy and end of treatment. However, improvement in histological markers of activity (lobular inflammation and NAFLD activity score) and fibrosis were associated with improved cv risk scores (Figure) (p< 0.05 for all).Conclusions:Improvement in hepatic inflammation, NAFLD activity score and fibrosis were associated with improved proteomic CV risk scores regardless of treatment provided. Additional prospective validation of these findings is warranted. Proteomic profiling can potentially be used to track changes in cardiovascular risk profile changes in response to therapy in the short term NASH treatment trials.

Circulation, Volume 148, Issue Suppl_1, Page A15645-A15645, November 6, 2023. Coronary heart disease (CHD) costs the United States healthcare system at least $216 Billion in treatment cost and $147 billion in lost productivity annually. Therefore, there is an urgent need for cost-effective solutions to reduce both the human and economic burden of CHD. Because the initial CHD diagnostic approach has a large impact on subsequent costs and healthcare outcomes, risk bearing entities are keen to determine the optimal algorithmic approach for guiding the use of CHD diagnostic tools. In order to better understand the economic and clinical impact of a newly developed Precision Epigenetic test for assessing CHD status, PrecisionCHD, we conducted a budget impact analysis comparing the use of PrecisionCHD to the use of conventional exercise ECG and coronary computed tomographic angiography (CCTA) (in a 75:25 ratio) as the initial diagnostic assessment of CHD using nationally published cost estimates, generally accepted side effects, sensitivity and specificity metrics for each test, with all positive tests resulting in the initiation of moderate to high dose statin therapy as per treatment guidelines. Our analysis showed that for an insurance plan with 1 million covered individuals, a $20 co-pay for office visits and 10% co-insurance, the use of PrecisionCHD over exercise ECG and CCTA would result in $92 million in annual cost savings with a significant portion of those savings being secondary to the inferior performance of exercise ECG. Increasing the number of CCTA test performed increases the number of CHD cases detected, but also results in greater costs including costs secondary to contrast dye induced kidney damage. We conclude that the use of PrecisionCHD for CHD detection can improve healthcare outcomes and decrease CHD related costs. Given current trends in the developments in epigenetics-based approaches, it is likely that this advantage will increase further.

Circulation, Volume 148, Issue Suppl_1, Page A11812-A11812, November 6, 2023. Background:Cardiopulmonary exercise test (CPET )is currently used to quantify functional limitation and to evaluate the indications for surgery among patients with hypertrophic cardiomyopathy (HCM). Patients with HCM often have atrial fibrillation (AF) and their relationship is not clear.Objective:To investigate the function limitation among HCM patients who meet indications for septal myectomy and the association between it and AF. Method: We reviewed 565 consecutive patients who underwent myectomy from February 2019 to October 2021, of which 212 did CPET and 24h Holter before surgery.Results:In this cohort (median age: 50.55(37.6-58) years; male: 126(59.4%); left ventricular outflow tract gradient (LVOTG)≥ 50 mmHg: 190(89.6%)), there was a severely impaired function (Peak Oxygen consumption (Peak VO2): 16.44 ± 4.02 ml/min/kg, adjusted Peak VO2%: 58.27%). Comparing different groups divided by Peak VO2, the lowest group was characterized by older age (58 vs 50 vs 43.9 years, p < 0.001), more female patients (57.7% vs 38% vs 25.7%, p < 0.001), higher NT-proBNP level (1299 pg/ml vs 1049 pg/ml vs 742.5 pg/ml, p = 0.004), and larger left atrial diameter (46.8mm vs 43.77 mm vs 42.71 mm, p < 0.001). The incidence of AF also significantly increased (30.98% vs 14.08% vs 7.14%, p < 0.001). Among various indicators of CPET, Peak VO2 showed the strongest correlation with AF (point-biserial correlation coefficient: -0.347, p < 0.001; 0.2279, p = 0.011; -0.2502, p < 0.001; for Peak VO2, ventilatory efficiency, and anaerobic threshold, respectively). Additionally, the incidence of AF decreased with increasing severity of obstruction (60% vs 33.3% vs 16.2% vs 7.1% among non-obstructive, 30≥maximum LVOTG < 50 mmHg, 50≥LVOTG < 100 mmHg, >100 mmHg patients, respectively, p = 0.001). In multivariate regression analysis adjusting for age, sex, BMI, and left atrial diameter, Peak VO2 and LVOTG remained independently associated with the development of AF (OR 0.854, 95% CI 0.743-0.973, p = 0.021 and OR 0.969, 95% CI 0.949-0.987, p = 0.002, respectively).Conclusions:CPET indicator, particularly PeakVO2, was independently associated with the occurrence of AF in eligible surgical patients with HCM. We also found that the higher extent of obstruction, the lower the incidence of AF.

Circulation, Volume 148, Issue Suppl_1, Page A15449-A15449, November 6, 2023. Background:The six-minute walking test (6MWT) is a commonly used test for assessing the functional capacity of patients with pulmonary hypertension (PH), providing functional and prognostic information. Functional capacity depends on RV-PA coupling, the matching of right ventricular contractility to afterload. However, the dynamics of RV-PA coupling during the 6MWT have never been studied.Methods:We used a wireless hemodynamic monitoring system (CorLog, emka-medical, Germany) to continuously measure right ventricular pressure in 10 patients with PH (8 = group I, 1 = III, 1 = IV) during a 6MWT. We calculated right ventricular ejection fraction (RVEF) and Ees/Ea based on the pressure signal as shown in the figure (panel a). Dyspnea was evaluated using the Borg scale.Results:By analyzing the hemodynamic response during the 6MWT, we identified two patterns: 1) Improved/preserved coupling: Five patients exhibited an initial improvement in Ees/Ea and maintained coupling at least at the baseline level throughout the test, without requiring pauses. 2) Uncoupling associated with pauses: Five patients experienced a slight increase in Ees/Ea at the beginning, followed by a progressive loss of coupling and ejection fraction, necessitating pauses. During pauses, Ees/Ea values restored, enabling patients to resume walking. Patients of the second phenotype reported higher levels of dyspnea. The highest reported Borg score was 8 ± 0.9 vs. 4.6 ± 1.2 in the first group. Also, the covered distance was shorter in the second group (159 ± 64m vs. 288 ± 88m, p=0.03). Both groups showed differences in Ees/Ea (0.47 [0.46 – 0.57] vs. 0.34 [0.30 – 0.43], P=0.05) and RVEF (34 ± 4.1% vs. 28.5 ± 2.6%, P=0.03) at baseline, with Group One exhibiting superior values.Conclusion:This is the first investigation into the significance of RV-PA coupling in real-life exercise limitation and dyspnea during the 6MWT. Pauses observed during the 6MWT can serve as indicators of exercise-induced uncoupling.

Circulation, Volume 148, Issue Suppl_1, Page A16552-A16552, November 6, 2023. BACKGROUND:Coronary artery spasm (CAS) is a major cause of variant angina in patients with chest pain without significant coronary stenosis. However, whether there are differences in the incidence of CAS according to the severity of underlying coronary artery fixed stenosis is limited.Methods:A total of 608 patients without significant coronary artery disease (CAD) who underwent the ergonovine (ERG) provocation test between January 2018 and December 2021 were enrolled. Significant CAS was defined as having≥70% of temporary narrowing by ERG test. Patients were divided into three groups, based on the presence of coronary artery stenosis: None group (n=456), mild group (30-49%,n=114) and moderate group (50-69%,n=38).Results:In patients with chest pain without significant coronary artery stenosis, mild stenosis was 18.8%, and moderate stenosis was 6.3% in the population. The baseline characteristics of the patients were worse in the mild and moderate group than in the None group, including age, hypertension, diabetes, and smoking habit. In the ERG test, CAS occurred in 44.4% (270/608) of the overall population. The incidence of CAS of the mild (55.3%) and moderate (52.6%) groups were higher than the None group (41.0%). Also, in the case of CAS occurrence, focal CAS (Length

Circulation, Volume 148, Issue Suppl_1, Page A12194-A12194, November 6, 2023. Introduction:We previously reported that a computational modeling-guided antiarrhythmic drug (AAD) test was feasible for assessing diverse AADs in patients with atrial fibrillation (AF). In this study, we took the virtual AAD test (V-AAD) in patients who took AADs after AF catheter ablation (AFCA).Hypothesis:Patients using an effective drug in the VAAD test will have fewer AF recurrences than patients using an ineffective drug.Methods:This single-center retrospective study included 246 patients (72.8% male, 60.7±10.2 years of age, 38.6% paroxysmal AF) prescribed AADs within 3 months after AFCA. Using realistic computational modeling, we evaluated the effects of five AADs (amiodarone, sotalol, dronedarone, flecainide, and propafenone; 2 doses for each drug). Clinical AADs (C-AAD) were chosen at the discretion of the physicians blinded to the V-AAD test. We defined the effective V-AAD as the V-AAD that terminated AF or converted AF to atrial tachycardia (AT) and the best V-AAD as the V-AAD that ended virtual AF the fastest. We compared AF recurrence rates after the AAD prescription depending on the results of the V-AAD test.Results:The ineffective and best V-AAD were administered in 64 (26.0 %) and 70 patients (28.5%). The recurrence rate within a year after using the ineffective, effective, and best V-AAD were 46.9%, 35.7%, and 25.7%, respectively (log-rank p=0.013). The recurrence rate within a year in patients with at least one V-AAD terminating AF and those without was 33.9% and 50.0%, respectively (log-rank p=0.034). The use of best V-AAD (OR 0.43, 95% CI [0.18-0.96]; p=0.042, vs. ineffective V-AAD) is an independent predictor of AF recurrence within a year of using AAD after AFCA.Conclusions:The digital twins-guided V-AAD test was feasible for evaluating the efficacy of multiple AADs in patients with AF who had a high chance of recurrence after AFCA. We need a prospective randomization study to assess the prediction power of the V-AAD test.