Systematic basic and advanced resuscitation training in medical students and fellows: a proposal from the Working Group on Cardiovascular Urgences and Emergencies of the Italian Society of Cardiology.

Sudden cardiac arrest is a leading cause of death in Europe. High-quality cardiopulmonary resuscitation (CPR) and guidelines compliance of rescuers have been associated with better outcomes after cardiac arrest. However, wide variability in attempting bystander CPR manoeuvres has been reported. Educational programmes for teaching CPR to medical students and fellows are highly advisable in this context. However, there is no homogeneity regarding the CPR education offered by academic institutions. We surveyed 208 Italian medical students and 162 fellows in cardiology regarding the educational offer and needs in CPR. Among the 11 medical schools surveyed, 8 (73%) offer basic (BLS) courses but only 3 (38%) with formal certification of 'BLS provider', while none offers advanced (ACLS/ALS) courses. Among the 30 specialization schools in cardiology surveyed, 10 (33%) offer a BLS course (6 with formal certification of 'BLS provider'), and 8 (27%) offer an ACLS/ALS course (5 with formal certification). Only a minority of students and fellows perceive themselves as highly proficient either in BLS or ACLS/ALS, although most of the fellows were involved at least once in rescuing a cardiac arrest. The present position paper analyses and suggests the strategies that should be adopted by Italian medical and specialization schools to spread the CPR culture and increase the long-standing retention of CPR-related technical and nontechnical skills.

RAS inhibitors and renal and general mortality in patients with heart failure supported by left ventricular assist devices: a registry study.

BACKGROUND: The aim of our study was to analyze the association between renin-angiotensin system inhibitor (RASi) therapy and renal outcomes and mortality in patients with heart failure (HF) supported by left ventricular assist device (LVAD) using a large, nationwide prospective cohort. To date, no studies have comprehensively analyzed the association between RASi and renal outcomes and mortality in patients with HF supported by LVAD. METHODS: We performed a retrospective observational study on LVAD patients in the Interagency Registry for Mechanically Assisted Circulatory Support. The main outcome was a composite of renal event and all-cause mortality. Secondary outcomes were the individual components of the composite outcome. A renal event was defined as a composite of doubling serum creatinine, eGFR decrease ≥ 40%, or need for dialysis. The exposure of interest was RASi therapy, updated during follow-up. Cox regression models adjusted for potential confounders were used to estimate the association between time-updated RASi therapy and the outcomes of interest. RESULTS: The analysis included 6448 patients. During a median follow-up of 12.7 months (IQR 19.8 months), 1632 patients developed the composite outcome. RASi therapy was associated with a lower risk of developing the composite outcome (HR 0.61, 95% CI 0.55, 0.68, P < 0.001). A significant association was confirmed between RASi therapy and renal outcomes (HR 0.74, 95% CI 0.61, 0.89, P = 0.002) and all-cause mortality (HR 0.56, 95% CI 0.50, 0.63, P < 0.001). CONCLUSIONS: Our data suggest a beneficial role of RASi therapy on renal function and all-cause mortality in patients with HF supported by LVAD.

Nephrolithiasis: A Red Flag for Cardiovascular Risk.

Epidemiological evidence shows that nephrolithiasis is associated with cardiovascular (CV) morbidities. The association between nephrolithiasis and CV disease is not surprising because both diseases share conditions that facilitate their development. Metabolic conditions, encompassed in the definition of metabolic syndrome (MS), and habits that promote nephrolithiasis by altering urine composition also promote clinical manifestations of CV disease. By inducing oxidative stress, these conditions cause endothelial dysfunction and increased arterial stiffness, which are both well-known predictors of CV disease. Furthermore, the subtle systemic metabolic acidosis observed in stone formers with CV disease may have a pathogenic role by increasing bone turnover and leading to reduced mineral content and osteoporosis/osteopenia. Heart valves and/or coronary artery and aortic calcifications are frequently associated with reduced mineral density. This is known as the 'calcification paradox' in osteoporosis and has also been observed in subjects with calcium nephrolithiasis. Evidence supports the hypothesis that osteoporosis/osteopenia is an independent risk factor for the development of CV calcifications. In the long term, episodes of renal stones may occur from the onset of metabolic derangements/MS to arterial stiffness/atherosclerosis and CV morbidities. These episodes should be considered a warning sign of an ongoing and silent atherosclerotic process. The evaluation of cardiometabolic risk factors and MS components should be routine in the assessment of renal stone formers. This would allow for treatment and prevention of the development of CV complications, which are much more severe for the patient and for public health.

Interaction between VA-ECMO and the right ventricle.

BACKGROUND: The response of the right ventricle (RV) to the hemodynamic effects of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is currently unpredictable. We hypothesized that the presence of uni- or bi-ventricular failure before implantation and the cannulation strategy may influence this interaction. We sought to assess the RV performance during VA-ECMO support and identify RV-related predictors of successful weaning. METHODS: Changes in RV size and function during VA-ECMO support by echocardiography were retrospectively analyzed in 87 consecutive adult patients between February 2008 and June 2017. Predictors of successful weaning due to myocardial recovery were evaluated by multivariable logistic regression. RESULTS: RV echocardiographic parameters did not vary significantly during VA-ECMO support and neither after stratification by the type of cannulation or the presence of isolated or biventricular failure. Successful weaning was conditioned by the absence of RV dysfunction before implantation (OR, 14.7; 95% CI, 13.3-140.3; p = 0.025) or in the last day of support (OR, 9.5; 95% CI, 1.6-54; p = 0.011) and was favored by a total or partial recovery of RV function during the assistance (OR, 6.2; 95%CI, 1.7-22.4; p = 0.005). RV improvement was more often observed in patients with acute RV failure and longer support, while VA-ECMO configuration, additional mechanical support, or pharmacological therapy had no effect. CONCLUSIONS: Preservation or improvement of RV function during VA-ECMO is essential for successful weaning. RV echocardiographic performance does not change significantly during VA-ECMO support and is not influenced by cannulation type or the presence of uni- or bi-ventricular failure before implantation.

Volume of contrast to creatinine clearance ratio predicts early mortality and AKI after TAVI.

The volume of contrast to creatinine clearance ratio (CV/CrCl) is a useful indicator of the risk of acute kidney injury (AKI) in patients undergoing percutaneous interventional procedures. Association between CV/CrCl and adverse outcome after transcatheter aortic valve implantation (TAVI) was suggested but it is not well established. A large retrospective multicenter cohort of 1381 patients treated with TAVI was analyzed to assess the association between CV/CrCl and the risk of AKI and mortality at 90 days and 1 year after TAVI. Patients receiving renal replacement therapy at the time of TAVI were excluded. CV/CrCl ≥ 2.2 was associated with the risk of AKI and 90 days mortality after TAVI after adjustment for age, sex, diabetes, baseline left ventricular function, baseline chronic kidney disease (CKD), previous myocardial infarction and peripheral vascular disease (hazard ratio [HR]: 1.16, 95% confidence interval [CI]: 1.09-1.22, p < 0.0001). Importantly, CV/CrCl was associated with the adverse outcome independently from the presence of baseline CKD (p for interaction = 0.22). CV/CrCl was independently associated with the individual components of the composite primary outcome including AKI (odds ratio: 1.18, 95% CI: 1.08-1.28, p < 0.0001) and 90 days mortality (HR: 1.90, 95% CI: 1.01-3.60, p = 0.047) after TAVI. AKI (HR: 1.94, 95% CI: 1.21-3.11, p = 0.006) but not CV/CrCl was associated with the risk of 1-year mortality after TAVI. CV/CrCl is associated with excess renal damage and early mortality after TAVI. Procedural strategies to minimize the CV/CrCl during TAVI may improve early clinical outcomes in patients undergoing TAVI.

Impact of physiologically diffuse versus focal pattern of coronary disease on quantitative flow reserve diagnostic accuracy.

BACKGROUND: Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) disagree in about 20% of intermediate coronary lesions. As the physiological pattern of coronary artery disease has a significant influence on FFR-iFR discordance, we sought to assess it may impact on the diagnostic accuracy of quantitative flow reserve (QFR). METHODS: One hundred and ninety-four patients with 224 intermediate coronary lesions were investigated with iFR, FFR, and QFR. The physiological pattern of disease was assessed with iFR Scout pullback and QFR virtual pullback in all the cases. RESULTS: A predominantly physiologically focal pattern was observed in 81 (36.2%) lesions, whereas a predominantly physiologically diffuse was observed in 143 (63.8%) cases. QFR demonstrated a significant correlation (r = 0.581, p < 0.001) and a substantial agreement with iFR, both in diffuse (AUC = 0.798) and in focal (AUC = 0.812) pattern of disease. Discordance between QFR and iFR was observed in 51 (22.8%) lesions, consisting of iFR+/QFR- (64.7%) and iFR-/QFR+ (35.3%). Notably, the physiological pattern of disease was the only variable significantly associated with iFR/QFR discordance. QFR virtual pullback demonstrated an excellent agreement (83.9%) with iFR Scout pullback in classifying the physiological pattern of disease. CONCLUSIONS: QFR has a good diagnostic accuracy in assessing myocardial ischemia independently of the pattern of coronary disease. However, the physiological pattern of disease has an influence on the QFR/iFR discordance, which occurs in ~20% of the cases. The QFR virtual pullback correctly defined the physiological pattern of disease in the majority of the cases using the iFR pullback as reference.

Impact of early glomerular filtration rate decline in response to antihypertensive treatment on risk of end-stage kidney disease and cardiovascular outcomes: a systematic review and meta-analysis.

Blood pressure control, which can induce a slight decrease in the glomerular filtration rate (GFR), plays a nephron- and cardioprotective role. However, the more important early decline in GFR associated with antihypertensive therapy and strict blood pressure targets is still of concern. Since few data are available from trials and observational studies, and the phenomenon is relatively rare, we performed a meta-analysis of available studies. We conclude that major reductions in the glomerular filtration rate occurring soon after starting angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and/or under intensive blood pressure control predict end-stage kidney disease.

Heart, kidney and left ventricular assist device: a complex trio.

BACKGROUND: Heart failure (HF) is a complex syndrome affecting the whole body, kidneys included. The left ventricular assist device (LVAD) is a valid option for patients with very severe HF. Focusing on renal function, LVAD implantation could theoretically reverse the detrimental effects of HF syndrome on kidneys. However, implanting an LVAD is a high-risk surgical procedure, and LVAD patients have higher risk of bleeding, device thrombosis, strokes, renal impairment, multi-organ failure and infections. Furthermore, an LVAD has its own particular effects on the renal system. METHODS: In this review, we provide a comprehensive overview of the complex interaction between LVAD and the kidneys from the pathophysiological and clinical perspectives. An analysis of the different effects of pulsatile-flow and continuous-flow LVAD is provided. RESULTS: Despite their limitations, creatinine-based estimated glomerular filtration rate (eGFR) formulas help to stratify patients by their post-LVAD placement prognosis. Poor basal renal function, the onset of acute kidney injury or the need for renal replacement therapy after LVAD implantation negatively influences a patient's prognosis. LVAD can also prompt an improvement in renal function, however, with some counterintuitive effects on a patient's prognosis. CONCLUSION: It is still hard to say whether different trends in eGFR depend on different renal conditions before LVAD placement, on a patient's better overall status or on a particular patient management strategy before and/or after the device's implantation. Steps should be taken to solve this question because finding the best candidates for LVAD implantation is of paramount importance to ensure the best outcomes.

Refractory vasospastic angina in a patient with fibromuscular dysplasia: A case report.

A 49-year-old woman affected by fibromuscular dysplasia (FMD) of the carotid artery with recurrent coronary vasospasm, refractory to medical therapy was admitted for anginal pain. Coronary involvement related to FMD is uncommon and its diagnosis "in vivo" still represents a challenge. Although a clear association between FMD and spontaneous coronary artery dissections is described, the presentation as severe coronary vasospasm is rare and it is associated with unfavorable outcome, especially when treated by means of percutaneous coronary intervention. The use of intravascular ultrasound played a key role in choosing the appropriate strategy for the management of the patient. .

Association of hemodynamic factors and progressive aortic dilatation following type A aortic dissection surgical repair.

Type A aortic dissection (TAAD) involves the ascending aorta or the arch. Acute TAAD usually requires urgent replacement of the ascending aorta. However, a subset of these patients develops aortic rupture due to further dilatation of the residual dissected aorta. There is currently no reliable means to predict the risk of dilatation following TAAD repair. In this study, we performed a comprehensive morphological and hemodynamic analysis for patients with and without progressive aortic dilatation following surgical replacement of the ascending aorta. Patient-specific models of repaired TAAD were reconstructed from post-surgery computed tomography images for detailed computational fluid dynamic analysis. Geometric and hemodynamic parameters were evaluated and compared between patients with stable aortic diameters (N = 9) and those with aortic dilatation (N = 8). Our results showed that the number of re-entry tears and true/false lumen pressure difference were significantly different between the two groups. Patients with progressive aortic dilatation had higher luminal pressure difference (6.7 [4.6, 10.9] vs. 0.9 [0.5, 2.3] mmHg; P = 0.001) and fewer re-entry tears (1.5 [1, 2.8] vs. 5 [3.3, 7.5]; P = 0.02) compared to patients with stable aortic diameters, suggesting that these factors may serve as potential predictors of aneurysmal dilatation following surgical repair of TAAD.

Association of individual aortic leaflet calcification on paravalvular regurgitation and conduction abnormalities with self-expanding trans-catheter aortic valve insertion.

BACKGROUND: Complication rates of paravalvular aortic regurgitation (PVR) and permanent pacemaker insertion remain high in patients undergoing trans-catheter aortic valve insertion for severe aortic stenosis. The spatial distribution of calcium between individual aortic valve leaflets, and its potential role in these complications is gaining interest. We aimed to assess the accuracy of individual aortic valve leaflet calcium quantification, and to determine its effect on the frequency of these complications. METHODS: This was a retrospective study of 251 patients who underwent trans-catheter aortic valve insertion using the Evolut RTM valve. The off-line Terarecon software platform was used for Agatston scoring the short axis views. RESULTS: There was a correlation between the sum of the individual leaflet and the total aortic valve calcium score. There was a univariate association between an increase [per 100 Agatston unit (AU)] in both right coronary leaflet (RCL) and left coronary leaflet (LCL) calcium with the risk of PVR. There was an association between an increase in LCL calcium score (per 100 AU) and need for post-implantation balloon aortic valvuloplasty (BAV). There was no association between individual leaflet calcification on the risk of permanent pacemaker insertion. CONCLUSIONS: This study supports the idea that a quantifiable and reproducible method of individual valve leaflet calcification score may serve as an independent risk factor for paravalvular regurgitation, beyond visual assessment of asymmetry. However, the same may not be true of spatial calcium distribution and permanent pacemaker implantation (PPI).

Insights on safety and efficacy of renal artery denervation for uncontrolled-resistant hypertension in a high risk population with chronic kidney disease: first Italian real-world experience.

AIMS: To evaluate the safety and efficacy of catheter-based radiofrequency renal sympathetic denervation (RSD) in a daily practice population of patients with uncontrolled resistant hypertension, on top of medical therapy. METHODS: Consecutive unselected patients with uncontrolled resistant hypertension undergoing RSD were enrolled. Office and ambulatory blood pressure (BP) measurements were collected at baseline and 3, 6 and 12 months after RSD. Efficacy was assessed even in patients with an estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m2. Patients were defined as responders if systolic BP decreased by at least 5 mmHg at ambulatory BP or by 10 mmHg at office BP at their last follow-up visit. RESULTS: Forty patients with multiple comorbidities underwent RSD from 2012 to 2019. Baseline office and ambulatory BP was 159.0/84.9 ± 26.2/14.9 mmHg and 155.2/86.5 ± 20.9/14.0 mmHg, respectively. At 12-month follow up a significant reduction in office and ambulatory systolic BP, respectively by - 19.7 ± 27.1 mmHg and by - 13.9 ± 23.6 mmHg, was observed. BP reduction at 12-month follow-up among patients with eGFR < 45 mL/min was similar to that obtained in patients with higher eGFR. Twenty-nine patients (74.4%) were responders. Combined hypertension, higher ambulatory systolic BP and lower E/E' at baseline emerged as predictors of successful RSD at univariate analysis. No major complications were observed and renal function (was stable up to 12 months), even in patients with the lowest eGFR values at baseline. CONCLUSION: RSD is safe and feasible in patients with uncontrolled resistant hypertension on top of medical therapy, even in a high-risk CKD population with multiple comorbidities, with a significant reduction in systolic BP and a trend towards a reduction in diastolic BP lasting up to 12 months.

Pros and Cons of Different Types of Mechanical Circulatory Support Device in Case of Postinfarction Ventricular Septal Defect.

Postinfarction ventricular septal defect (VSD) is an uncommon but almost lethal complication. The optimal timing for VSD repair is matter of debate, and mechanical circulatory support (MCS) devices allow to hemodynamically support the patient and postpone the VSD closure until myocardial tissue is less friable and the patient's condition is less compromised. However, data are lacking to guide the choice of the best types of MCS in case of VSD. We present a case of a large postinfarction VSD and the use of central venoarterial extracorporeal membrane oxygenation support to stabilize the patient until the VSD surgical repair. This case offers the opportunity to revise the indications and characteristics of different MCS, highlighting pros and cons of each one.

Early Small Creatinine Shift Predicts Contrast-Induced Acute Kidney Injury and Persistent Renal Damage after Percutaneous Coronary Procedures.

PURPOSE: Little is known on the impact of contrast-induced acute kidney injury (CI-AKI) on mid- and long-term renal function after percutaneous coronary procedure. The aim of the study was to investigate the incidence of persistent renal damage (PRD) after CI-AKI in a cohort of patients undergoing coronary angiography and/or intervention. Moreover, we sought to assess the predictive value of small creatinine change at 12-24 h (SCrΔ%12-24 h) from contrast exposure in predicting CI-AKI and PRD. METHODS: Complete clinical and biochemical data of 731 patients were retrospectively analyzed at sequential time intervals at baseline, 12-24 h and 48-72 h from the procedure. Data at 30 ±â€¯10 days and 12-24 months were available in 59% and 49% of the cases respectively. Logistic regression was used to assess variables associated with CI-AKI and PRD. ROC analysis was used to test the diagnostic accuracy of SCrΔ%12-24 h in predicting CI-AKI and PRD. RESULTS: CI-AKI occurred in 130/731 patients (17.8%). At 30 ±â€¯10 days PRD occurred in 54.8% patients who developed CI-AKI. A SCrΔ%12-24 h >5% demonstrated independent predictive value (OR = 1.05, CI = 1.04-1.06, p < 0.001) and fair accuracy (AUC = 0.80, CI = 0.77-0.84) for CI-AKI. CONCLUSION: CI-AKI was associated with PRD in >50% of the cases in this single centre cohort. A small and early SCrΔ%12-24 h demonstrated high predictive value for CI-AKI and may be used as a useful tool to unmask a group of patients at risk for PRD after percutaneous coronary procedures.

Preventive left main and right coronary artery stenting to avoid coronary ostia occlusion in high-risk stentless valve-in-valve transcatheter aortic valve implantation.

Transcatheter aortic valve implantation is becoming an attractive and promising alternative to redo surgery for aortic bioprosthetic valves degeneration, especially in high-risk patients. However, valve-in-valve transcatheter aortic valve implantation itself carries some procedural risks and potential challenges that interventionists must be aware of. An accurate preprocedural planning is fundamental for the prevention of potentially fatal complications. This case describes a novel strategy of simultaneous right and left coronary artery stenting preventing bilateral coronary obstruction in a patient with a stentless surgical aortic valve and extremely low origin of the 2 coronary arteries.

Functional Assessment of Coronary Artery Disease in Patients Undergoing Transcatheter Aortic Valve Implantation: Influence of Pressure Overload on the Evaluation of Lesions Severity.

BACKGROUND: Aortic valve stenosis may influence fractional flow reserve (FFR) of concomitant coronary artery disease by causing hypertrophy and reducing the vasodilatory reserve of the coronary circulation. We sought to investigate whether FFR values might change after valve replacement. METHODS AND RESULTS: The functional relevance of 133 coronary lesions was assessed by FFR in 54 patients with severe aortic valve stenosis before and after transcatheter aortic valve implantation (TAVI) during the same procedure. A linear mixed model was used to verify the interaction of TAVI effect with the FFR values. No significant overall change in FFR values was found before and after the aortic valve stenosis removal (0.89±0.10 versus 0.89±0.13; P=0.73). A different trend in FFR groups (positive if ≤0.8; negative if >0.8) was found after TAVI (P for interaction <0.001). Positive FFR values worsened after TAVI (0.71±0.11 versus 0.66±0.14). Conversely, negative FFR values improved after TAVI (0.92±0.06 versus 0.93±0.07). Similarly, FFR values in coronary arteries with lesions presenting percent diameter stenosis >50 worsened after TAVI (0.84±0.12 versus 0.82±0.16; P=0.02), whereas FFR values in arteries with mild lesions (percent diameter stenosis <50) tended toward improvement after TAVI (0.90±0.07 versus 0.91±0.09; P=0.69). Functional FFR variations after TAVI changed the indication to treat the coronary stenosis in 8 of 133 (6%) lesions. CONCLUSIONS: Coronary hemodynamics are influenced by aortic valve stenosis removal. Nevertheless, FFR variations after TAVI are minor and crossed the diagnostic cutoff of 0.8 in a small number of patients after valve replacement. Borderline coronary lesions might become functionally significant after valve replacement, although FFR-guided interventions were infrequent even in patients with angiographically significant lesions.

Clinical outcomes of transcatheter aortic valve implantation: from learning curve to proficiency.

OBJECTIVE: The use of transcatheter aortic valve implantation (TAVI) is growing rapidly in countries with a predominantly elderly population, posing a huge challenge to healthcare systems worldwide. The increment of human and economic resource consumption imposes a careful monitoring of clinical outcomes and cost-benefit balance, and this article is aimed at analysing clinical outcomes related to the TAVI learning curve. METHODS: Outcomes of 177 consecutive transfemoral TAVI procedures performed in 5 years by a single team were analysed by the Cumulative Sum of failures method (CUSUM) according to the clinical events comprised in the Valve Academic Research Consortium (VARC-2) safety end point and the VARC-2 definition of device success. Margins for events acceptance were extrapolated from landmark trials that tested both balloon or self-expandable percutaneous valves. RESULTS: 30-day and 1-year survival rates were 97.2% and 89.9%, respectively. Achievement of the primary end point (number of cases needed to provide the acceptable margin of the composite end point of any death, stroke, myocardial infarction, life-threatening bleeding, major vascular complications, stage 2-3 acute kidney injury and valve-related dysfunction requiring a repeat procedure) required the performance of 54 cases, while the learning curve to achieve 'device success' identified 32 cases to reach the expected proficiency. In this experience, the baseline clinical risk as assessed by the Society of Thoracic Surgeons (STS) score determined the long-term survival rather than the adverse events related to the learning curve. CONCLUSIONS: A relatively large number of cases are required to achieve clinical outcomes comparable to those reported in high-volume centres and controlled trials. According to our national workload standards, this represents more than 2 years of continuous activity.

Long-Term (3 Years) Prognosis of Contrast-Induced Acute Kidney Injury After Coronary Angiography.

Contrast-induced acute kidney injury (CI-AKI) after coronary angiography or interventions is relatively frequent and portends adverse outcomes. The lack of a "universally accepted" definition, however, limits the integration and comparison of available data. We aimed to detect the CI-AKI definition that best correlates with the occurrence of clinical events at long-term in a 3-year follow-up study of patients at intermediate-to-high risk for CI-AKI. Furthermore, we sought to describe the incidence and long-term evolution of persistent renal damage (PRD) after CI-AKI and clarify the role of early (<12 hours) increments of serum creatinine (SCr) in CI-AKI prediction. Among a total of 216 patients enrolled at our center and followed for a median of 37 months, CI-AKI was diagnosed in 18.1% of cases (SCr increment ≥25% of baseline), 7.4% (SCr increment ≥0.5 mg/dl), and in 17.1% (SCr increment ≥0.3 mg/dl), according to 3 different definitions. The third definition was the only one significantly associated with the occurrence of events at 3 years (Cox regression, p = 0.04). PRD at 30 days, as detected by the same cutoff, significantly and independently identified patients at risk of worst outcomes at 3 years (p = 0.04 at multivariate Cox regression). Furthermore, a slight 5% to 10% increment of SCr compared with baseline, occurring as early as 12 hours postprocedure, was confirmed as a strong predictor of inhospital CI-AKI occurrence. In conclusion, an absolute increase in SCr ≥0.3 mg/dl seems to be most clinically informative cutoff for CI-AKI and PRD detection.