Risultati per: Tumore prostata, test della saliva piu’ attendibile del PSA

I progetti in corso all’Humanitas: dai modelli 3D agli organoidi fino all’intelligenza artificiale

To the Editor We read with interest the recent study that compared the fecal immunochemical test (FIT) positivity threshold vs multitarget stool RNA (mt-sRNA) testing for colorectal cancer screening. However, we have concerns regarding the study methodology and the capability of FIT to fully replace the mt-sRNA panel.

In Reply Our study adjusted the FIT cutoff to yield the same overall positivity rate as reported for the mt-sRNA test (17%) to enhance comparability of diagnostic performance of both tests. Below we address each of the 3 points made by Drs Yang and Ma.

Gastric cancer is a leading cause of cancer death globally. Although endoscopy-based screening has led to a decrease in gastric cancer mortality in Eastern Asian countries with populations at high risk, lack of risk stratification and the cost of health care infrastructure and trained personnel limit its use in most of the world. Availability of noninvasive biomarkers for the identification of high-risk individuals could optimize endoscopy-based screening programs for a more general application, including in regions where gastric cancer rates in the general population are low.

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Objectives
This study developed and investigated the possibility of using the walking and turning test (WTT) to indicate fall risk in community-dwelling older adults.

Design
Retrospective diagnostic study.

Setting
The study was carried out in a community setting.

Participants
The study focused on community-dwelling older Thai adults.

Primary and secondary outcome measures
The participants were assessed based on demographics, fear of falls using a ‘yes/no’ question and the Short Falls Efficacy Scale International, as well as fall data in the previous 6 months. The participants then performed the WTT, timed up and go test, five times sit-to-stand test and handgrip strength test (HG) in random order.

Results
There were a total of 86 participants with an average age of 69.95±6.10 years (range from 60 to 88 years), most of whom were female (67.44%). 40 participants (46.51%) reported that they had fallen at least once in the previous 6 months. A comparison of various physical ability tests revealed significant differences between faller and non-faller participants (p

Circulation, Volume 150, Issue Suppl_1, Page A4141670-A4141670, November 12, 2024. Background:Whole blood gene expression is modified in response to signals from various tissues, including the liver. Steatotic (fatty) liver disease (SLD) is a hallmark of cardiometabolic disorder strongly associated with vascular disease (50% of patients undergoing coronary angiography). The main goal of this study was to evaluate the classification performance of peripheral whole blood RNAseq analyzed by artificial intelligence (AI) in identifying or ruling out SLD.Methods:The training set consisted of 118 men 40-70 years and women 50-70 years with no history of cardiovascular disease enrolled in a clinical study for assessing coronary artery calcification via a chest computed tomography scan. SLD was defined as

Circulation, Volume 150, Issue Suppl_1, Page A4143109-A4143109, November 12, 2024. Background:The use of cardiac resynchronization therapy (CRT) devices has significantly increased in usage in recent years. Identifying predictors of mortality in CRT patients remains an area of investigation.Objective:To establish a relationship between timed up-and-go test time (TUGT) and mortality in heart failure patients (HF) with CRT devices.Methods:This retrospective study included 506 patients with heart failure with reduced ejection fraction (HFrEF) who underwent CRT implantation at our institution between 2017-2022. All patients were followed up with a multidisciplinary team, including electrophysiology and HF physicians about 6 months after CRT implantation, where frailty was assessed. We used TUGT as a measure of frailty and divided patients into 2 groups: TUGT: >15 seconds (n=73) and ≤15 seconds (n=433). The primary endpoint was a composite of left ventricular assist device implantation, transplant, or death at 2 years post-CRT. Data was collected retrospectively from electronic medical records.Results:The study population was 65.6% male, with a mean age of 69.1 years, and 79.4% of devices being CRT-D.Response was defined as an improvement in LVEF >5% with reduction in LVESV >10%; anybody not meeting this definition was classified as a non-responder. Responder and non-responder rates among TUGT >15 and TUGT15s have worse outcomes (Figure 1).Conclusion:Frailty testing using TUGT post-CRT implantation is a strong predictor of mortality in HFrEF patients after CRT implantation.

Circulation, Volume 150, Issue Suppl_1, Page A4140902-A4140902, November 12, 2024. BACKGROUND:Coronary artery spasm (CAS) is a cause of variant angina and is typically diagnosed by intracoronary provocation test. Investigations regarding association between the burden of coronary artery stenosis and the minimum responsive dose of ergonovine (ERG) required for provocation is limited.METHODS:In this study, 356 patients who underwent the ergonovine (ERG) provocation test and showed CAS between October 2004 and December 2022 were enrolled. Significant CAS was defined as temporary narrowing of ≥70% during the ERG test. Patients were divided into three groups, based on the minimum responsive dose of ERG: E1 group (20ug, n=13), E2 group (40ug, n=53) and E3 group (80ug, n=290).RESULTS:In patients who were documented with positive intracoronary ERG provocation test, 3.7% responded at the lowest dose (20ug), 14.9% responded at the medium dose (40ug) and 81.5% responded only at the highest dose of ERG (80ug). The baseline characteristics of the patients among the 3 groups were similar, demonstrating no significant difference in the prevalence of hypertension, diabetes mellitus, and dyslipidemia. However, patients who responded at E2 dose showed higher proportion of smokers than E3 dose (E2 34.0% vs. E3 25.9%, p=0.043). E1 group demonstrated the highest proportion of severe stenosis (92.3%), followed by E2 group (90.6%) and E3 group (71.4%) (Figure 1). In addition, incidence of focal CAS and multi-vessel CAS were higher among those who responded to lower doses (focal CAS: 23.1% vs. 20.8% vs. 10.0%; multi-vessel CAS: 61.5% vs.50.9% vs. 36.6%).CONCLUSION:In patients with chest pain with positive intracoronary ERG provocation test, higher burden of stenotic lesions was found to be more frequent and more susceptible in patients who responded at lower doses of ERG.

Circulation, Volume 150, Issue Suppl_1, Page A4141692-A4141692, November 12, 2024. Background:Assessment of exercise tolerance is crucial for risk stratification in patients with heart failure (HF), and the six-minute walk test (6MWT) is widely used. While the six-minute walk distance (6MWD) is an established metric, it shows significant variability among elderly patients due to numerous comorbidities and potential confounding factors, making relative risk assessment challenging. Therefore, a new comprehensive indicator for evaluating exercise tolerance in elderly patients with HF is required.Objective:This study aimed to evaluate the novel prognostic value of desaturation during the 6MWT, defined as the average decrease in peripheral oxygen saturation (ΔSpO2-Ex), in predicting rehospitalization in patients with HF.Methods:We retrospectively analyzed the data of 55 patients with acute HF aged ≥ 65 years who were prospectively registered at our hospital. The mean SpO2was calculated from data obtained at rest and during the 6MWT using a wearable pulse oximeter designed to record the SpO2value every second. ΔSpO2-Ex was defined as the difference between the highest SpO2at rest and average SpO2during the 6MWT. Patients were followed-up for 1 year for the composite outcome of rehospitalization due to HF exacerbation and cardiovascular death.Results:The mean age was 80.7 years, with 45 % being female. The mean 6MWD was 237.5 m, and the mean ΔSpO2-Ex was 5.8 %. Patients were categorized based on the cut-off values obtained from the ROC curve for both 6MWD and ΔSpO2-Ex. Kaplan-Meier analysis indicated a significantly higher risk of cardiovascular events when ΔSpO2-Ex exceeded 6.7 % compared to when the 6MWD was less than 220 m (HR 6.66, 95 % CI: 2.96-15.01, p

Circulation, Volume 150, Issue Suppl_1, Page A4146434-A4146434, November 12, 2024. Background:PET/CT stress test may be performed to risk stratify patients including those without known coronary artery disease (CAD) who may be at risk for short-term adverse cardiac events. In patients with low- to moderate (LTM) risk for short-term MACE and without a known history of CAD, a small percentage of these patients will undergo a coronary angiogram within 90-days, of which some will be diagnosed with high-grade stenosis. The purpose of this study is to determine factors associated with this approach and findings.Methods:Patients without a history of known CAD (n=43,271) undergoing a PET/CT from 2018-2023 at Intermountain Health, with scan interpreted clinically as LTM short-term risk for adverse cardiac events, and ischemic burden 70% stenosis in any vessel), an a priori list of clinical data and PET/CT results were examined.Results:Within 90 days of the LTM risk PET/CT, 3,163 (8.2%) had a coronary angiogram. Of these, 806 (25.5% of angiograms and 2.1% of total LTM) had high-grade CAD. The PET/CT ancillary findings were associated with the largest odds of performing an angiogram and the presence of high-grade CAD (Tables). Factors most likely to be associated with performing an angiogram were an ischemic burden of 7.5-10% (adjusted-OR [adj. OR]=11.54), coronary artery calcification (CAC) score of >300 (adj.-OR =1.62), and myocardial blood flow (MBF) of MBF 2.3). Other clinical parameters associated, after adjustment, with an angiogram were age, male sex, hypertension, elevated troponin, and inpatient status. Many of the same factors were found to be associated with the identification of high-grade CAD. However, being an inpatient was associated with increased odds of angiogram but a decrease in odds of high-grade CAD.Conclusions:In patients without a known history of CAD who underwent PET/CT clinically adjudicated as LTM short-term risk and ischemic burden

Circulation, Volume 150, Issue Suppl_1, Page A4145321-A4145321, November 12, 2024. Introduction:Pulmonary dysfunction is a risk factor for increased mortality in patients with acute coronary syndromes (ACS). The purpose of this study was to investigate the association between thrombogenicity and pulmonary function test abnormalities in patients with ACS.Methods:We included ACS patients who underwent successful percutaneous coronary intervention (PCI). Pulmonary function was assessed by spirometry based on the forced expiratory volume in one second (FEV1%pred) after PCI. Thrombogenicity was evaluated with the thromboelastography and conventional hemostatic measures.Results:Among 323 patients, 90 patients (28.8%) had pulmonary dysfunction (moderate or severe spirometric abnormality, FEV1%pred

Circulation, Volume 150, Issue Suppl_1, Page A4143506-A4143506, November 12, 2024. Background:Anatomic burden of coronary artery disease (CAD) has been considered a consistent prognostic marker. Inflammation also increases the cardiovascular risk and plays a significant role in the evolution of atherosclerosis. The progression of CAD impacts the responses to exercise, reducing functional capacity. Despite this knowledge, the specific interplay between inflammation and atherosclerotic burden in influencing submaximal exercise capacity, particularly oxygen uptake (VO2) kinetics, remains underexplored in CAD. This study aims to investigate how these factors correlate with VO2on-kinetics in the Six-minute Walk Test (6MWT) in patients with CAD.METHODS:Patients with obstructive CAD, confirmed by coronary angiography, underwent a 6MWT using a mobile telemetric cardiopulmonary monitoring to assess functional capacity and the VO2on-kinetics through the mean response time corrected by work (wMRT). Inflammatory markers were analyzed by dosage of high-sensitivity C-reactive protein, interferon-gama, tumor necrosis factor alpha and interleukins (IL), IL-6, IL-8 and IL-10. Coronary atherosclerotic burden was evaluated by the Grading Scale for Anatomic Burden of Disease from COURAGE Trial. Correlation analyses were performed according to the symmetric distribution of data, using Pearson’s (r) or Spearman’s rank correlation coefficients(rs).RESULTS:A total of thirty-four patients aged between 60.3±8.0 years were enrolled, presenting body mass index of 26.0±3.7kg/cm2, left ventricular ejection fraction of 0.50±0.14, walking distance of 443±66m, VO2at steady-state (VO2SS) of 896±240ml/min and wMRT of 1.64×10-3± 1.00×10-3min2/ml. Although correlated with distance and VO2SS(r=-0.472;p=0.002 and r=-0.434;p=0.015, respectively), atherosclerotic burden was not associated with wMRT (p=0.17). High-sensitivity C-reactive protein and IL-8 were negatively associated with both distance and VO2SS(rs=-0.428;p=0.001/ rs=-0.543;p=0.001 and rs=-0.438;p=0.014/ rs=-0.407;p=0.019) and positively correlated with wMRT (rs=0.412;p=0.022/ rs=0.505;p=0.003).CONCLUSION:In contrast to anatomic burden, inflammatory markers were associated with both walking intensity and VO2kinetics. Therefore, inflammation may be more crucial to exercise response mechanisms than coronary stenosis, suggesting a paradigm shift in our understanding of clinical repercussions of obstructive CAD. Actions able to attenuate the inflammatory profile may improve exercise capacity and prognosis.

Circulation, Volume 150, Issue Suppl_1, Page A4117646-A4117646, November 12, 2024. Introduction:The HeartMate 3 (HM3) LVAD, was shown to have a higher survival free of hemocompatibility related adverse events (HRAE) compared to its predecessors (HM2, HVAD). Superior HM3 outcomes are attributed to wide blood flow pathways coupled with frictionless movement and intrinsic pulsatility, reducing shear stress and blood stasis. It is unknown if improved hemocompatibility can withstand pump restart after prolonged shutdown. We herein report a case of HM3 pump stoppage without subsequent HRAE.Case Presentation:A 41-year-old male underwent HVAD implant in 2019 for advanced non-ischemic cardiomyopathy. This was exchanged to HM3 for recurrent neurological events despite therapeutic anticoagulation. Ten months after exchange, he awakened one morning to find his LVAD had been off for an unknown period but had not heard any device alarms (85dB if on battery power, 165dB if on wall power). Since he felt well he changed to battery power resulting in immediate pump restart. Log file analysis showed pump stoppage 2 am – 10 am, without preceding low flow alarms or power elevations.Management and Outcomes:In the ER INR was 1.5 (2.8 one week prior) and systemic heparin was started. Evaluation included: 1) CT brain without acute infarcts 2) echocardiogram without intracardiac thrombus 3) CT Angiography with patency of the inflow cannula and outflow graft 4) stable serial LDH measurements. The controller was exchanged, and analysis noted normal function. 1-year later the patient is maintained on warfarin and aspirin 325mg without further HRAE. Given the patient’s neurologic history and pump stoppage event, we did not invoke ARIES trial guidance and thus continued aspirin.Conclusion:Pump stoppage occurs when there is complete battery depletion, disconnection of both power leads, or the percutaneous lead from system controller. Our case is unique in that the duration of pump shutdown was 8 hours and INR subtherapeutic, without HRAE in the background of neurologic events on HVAD support. It has been previously reported that complete outflow graft thrombosis can occur shortly after LVAD decommissioning. The HM3 User Manual recommends restarting the pump immediately if off for a few minutes and using clinical judgment for longer durations due to increased risk for thromboembolic events. Our case adds to the paucity of existing data on improved hemocompatibility of the HM3 during rare circumstances of the ultimate test in hemocompatibility: complete pump shut down.

Circulation, Volume 150, Issue Suppl_1, Page A4146883-A4146883, November 12, 2024. Introduction:Peripheral arterial disease (PAD) is caused by a lack of blood flow to the musculature relative to its metabolism which results in pain. PAD impacts up to 20% of patients around the world. PAD involves macrovascular and microvascular dysfunction. Near-infrared spectroscopy (NIRS) measures muscle oxygenation levels and assesses microvascular function. The standard of care for diagnosing PAD is the ankle-brachial index (ABI), which assesses macrovascular disease, and the 6-minute walk test (6MWT), which measures gait speed and claudication. NIRS has the potential to monitor progression of PAD.Hypothesis:NIRS measurement of muscle oxygenation, during a standard test of vascular occlusion and post-occlusive hyperemia, the vascular occlusion test (VOT), is predictive of PAD severity as determined by ABI and 6MWT.Methods:We studied 24 patients diagnosed with PAD. The mean age of the patients was 71.3 years, including 54% (n=13) males and 46% (n=11) females. The VOT consisted of rest, occlusion, and reperfusion phases each lasting 5 min (15 min total). Muscle oxygen saturation levels were recorded at 2 hertz. For every patient, 6 features were extracted from the VOT data using computational methods. The VOT features from 15 patients were used to train function-fitting neural network models to predict ABI and 6MWT Continuous Distance. The models were then used to predict ABI and 6MWT Continuous Distance from the VOT features of 9 test patients not used in the training,Results:For patients in the test set, the ABI and 6MWT Continuous Distance predicted by the models differed from the actual measurements by 14%±13% and 15%±17%, respectively (Figure 1). For patients in the training set, the ABI and 6MWT Continuous Distance predicted by the models differed from the actual measurements by 0±0% and 12%±11%, respectively (Figure 1).Conclusion:The VOT has the potential to predict the ABI and 6MWT Continuous Distance of patients diagnosed with PAD, suggesting that the VOT can be automated and used to monitor the severity of PAD. With more data from both healthy patients and PAD patients, and improvement of the model, we anticipate that the VOT will complement ABI and 6MWT in the diagnosis and monitoring of PAD.