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Long-term data on safety and efficacy of instantaneous wave-free ratio (IFR) vs fractional flow reserve (FFR) in guiding percutaneous coronary intervention (PCI) is lacking. This study sought to evaluate the 5-year clinical outcomes of IFR- vs FFR-guided PCI in a real-world setting. We assessed the 5-year outcomes of all patients undergoing IFR or FFR assessment between January 1, 2014, and February 16, 2022, using data from the SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry. Two-to-1 propensity score matching was used to adjust for differences between groups. Additional analyses adjusted for propensity score, PCI center, and baseline differences remaining after matching were conducted. The primary outcome was major adverse cardiac events (MACE) defined as first occurrence of all-cause death, myocardial infarction, or repeat revascularization within 5 years. Among 16,152 (65.6%) of 24,623 FFR and 8,471 (34.4%) of 24,623 IFR patients, IFR led to more frequent deferral of revascularization (5,964 of 8,471 [70.4%] vs 10,615 of 24,623 [65.7%]; P < 0.001). There was no significant difference in Kaplan-Meier event rates in MACE at 5 years between patients who underwent IFR or FFR-guided revascularization (1,993 [31.3% (95% CI: 30.0%-32.6%)] vs 3,961 [31.9% (95% CI: 31.0%-32.8%)]; adjusted HR: 0.96; 95% CI: 0.82-1.12; P = 0.60), including all-cause death, cardiovascular death, cardiac death, coronary death, new myocardial infarction, or revascularization. Subgroup analysis of deferred and treated patients revealed no difference between groups regarding MACE or its individual components. In a large nationwide registry of patients undergoing physiology-based coronary revascularization, there were no significant differences in MACE or all-cause mortality between IFR and FFR-guided revascularization at 5 years. [Display omitted] [ABSTRACT FROM AUTHOR]

Public health systems reported low mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in East Asia, in low-income countries, and for children during the first year of the SARS-CoV-2 pandemic. These reports led commentators to suggest that cross-reactive immunity from prior exposure to other pathogens reduced fatality risk. Resolution of initial infection waves also contributed to speculation that herd immunity prevented further waves prior to vaccination. Serology instead implied that immunity was too limited to achieve herd immunity and that there was little impact from cross-reactive protection. Paediatric deaths exceeded those from influenza, with higher age-specific fatality risk in lower-income nations and similar fatality risk in East Asia compared with demographically similar regions. Neither pre-outbreak exposure to related pathogens nor immunity induced by initial infection waves are necessarily a reliable response to future pathogen outbreaks. Preparedness for future pathogen outbreaks should instead focus on strategies such as voluntary behavioural changes, nonpharmaceutical interventions, and vaccination. [ABSTRACT FROM AUTHOR]

Background. Despite technical advancements, patients with sequential or diffuse coronary lesions undergoing percutaneous coronary intervention (PCI) have an increased risk of cardiovascular events at follow-up. We aimed to analyze the utility of a SyncVision/iFR (S-iFR)-guided PCI strategy versus an angiography-guided strategy in patients with this type of lesions. Methods. Randomized, multicenter, controlled, and open-label trial to compare S-iFR versus angiography-guided PCI in patients with sequential or diffuse angiographic coronary stenosis (ClinicalTrials.gov identifier: NCT04283734). The primary endpoint was the implanted stent length. The main secondary endpoint was targeting vessel failure (TVF) at one year. Results. A total of 100 patients underwent randomization, with 49 patients assigned to the S-iFR group and 51 to the angiography-guided PCI group. There were no differences between groups regarding clinical and anatomical characteristics. The baseline iFR was 0.71 ± 0.16 vs. 0.67 ± 0.19 (p = 0.279) in the S-iFR and angiography group, respectively. The mean lesion length was 42.3 ± 12 mm and 39.8 ± 12 (p = 0.297). The implanted stent length was 32.7 ± 17.2 mm in the S-iFR group and 43.1 ± 14.9 mm in the angiography group (mean difference, −10.4 mm; 95% confidence interval [CI], −16.9 to −4.0; p = 0.002). At one year, target vessel failure (TVF) occurred in four patients: three (6.1%) in the S-iFR group vs. one (1.9%) in the angiography group (p = 0.319). Conclusions. Among patients with sequential or long diffuse coronary lesions, a S-iFR-guided PCI strategy resulted in a reduction of the total stent length compared to an angiography-guided PCI strategy. A nonsignificant increase in TVF was observed in the S-iFR group. [ABSTRACT FROM AUTHOR]

We study the behavior of the failure rate associated with the distribution of a random variable of the form X = Y + U , where Y, U are independent and U has bounded support. First, we obtain monotonicity results and bounds for the failure rate of X in the case where U has a uniform distribution and, in particular we show that, asymptotically, the failure rates of X and Y tend to the same limit. Some of the results are generalized for the case where the distribution of U is not uniform, but has bounded support. Further, we show that if the failure rate of a non negative variable X is constant in some interval (L , ∞) , then X can be written as the sum of two independent random variables, one of which is exponential and the other (which is not necessarily uniform) has support [ 0 , L ] . [ABSTRACT FROM AUTHOR]

Background Coronary pressure indices to assess coronary artery disease are currently underused in patients with aortic stenosis due to many potential physiological effects that might hinder their interpretation. Studies with varying sample sizes have provided us with conflicting results on the effect of transcatheter aortic valve replacement (TAVR) on these indices. The aim of this meta‐analysis was to study immediate and long‐term effects of TAVR on fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs). Methods and Results Lesion‐specific coronary pressure data were extracted from 6 studies, resulting in 147 lesions for immediate change in FFR analysis and 105 for NHPR analysis. To investigate the long‐term changes, 93 lesions for FFR analysis and 68 for NHPR analysis were found. Lesion data were pooled and compared with paired t tests. Immediately after TAVR, FFR decreased significantly (−0.0130±0.0406 SD, P: 0.0002) while NHPR remained stable (0.0003±0.0675, P: 0.9675). Long‐term after TAVR, FFR decreased significantly (−0.0230±0.0747, P: 0.0038) while NHPR increased nonsignificantly (0.0166±0.0699, P: 0.0543). When only borderline NHPR lesions were considered, this increase became significant (0.0249±0.0441, P: 0.0015). Sensitivity analysis confirmed our results in borderline lesions. Conclusions TAVR resulted in small significant, but opposite, changes in FFR and NHPR. Using the standard cut‐offs in patients with severe aortic stenosis, FFR might underestimate the physiological significance of a coronary lesion while NHPRs might overestimate its significance. The described changes only play a clinically relevant role in borderline lesions. Therefore, even in patients with aortic stenosis, an overtly positive or negative physiological assessment can be trusted.

Background: To assess whether hydrostatic pressure gradients caused by coronary height differences in supine versus prone positioning during invasive physiological stenosis assessment affect resting and hyperaemic pressure-based indices or coronary flow. Methods: Twenty-three coronary stenoses were assessed in twenty-one patients with stable coronary artery disease. All patients had a stenosis of at least 50% visually defined on previous coronary angiography. Pd/Pa, iFR, FFR, and coronary flow velocity (APV) measured using a Doppler were recorded across the same stenosis, with the patient in the prone position, followed by repeat measurements in the standard supine position. Results: When comparing prone to supine measurements in the same stenosis, in the LAD, there was a significant change in mean Pd/Pa of 0.08 ± 0.04 (p = 0.0006), in the iFR of 0.06 ± 0.07 (p = 0.02), and in the FFR of 0.09 ± 0.07 (p = 0.003). In the Cx, there was a change in mean Pd/Pa of 0.05 ± 0.04 (p = 0.009), iFR of 0.07 ± 0.04 (p = 0.01), and FFR of 0.05 ± 0.03 (p = 0.006). In the RCA, there was a change in Pd/Pa of 0.05 ± 0.04 (p = 0.032), iFR of 0.04 ± 0.05 (p = 0.19), and FFR of 0.04+−0.03 (p = 0.004). Resting and hyperaemic coronary flow did not change significantly (resting delta APV = 1.6 cm/s, p = 0.31; hyperaemic delta APV = 0.9 cm/s, p = 0.85). Finally, 36% of iFR measurements and 26% of FFR measurements were re-classified across an ischaemic threshold when prone and supine measurements were compared across the same stenosis. Conclusions: Pd/Pa, iFR, and FFR were affected by hydrostatic pressure variations caused by coronary height differences in prone versus supine positioning. Coronary flow did not change signifying a purely pressure-based phenomenon. [ABSTRACT FROM AUTHOR]

In this article we discuss how an investment firm established outside the EU may provide services (to clients) in the EU. We explore how such third country firms may enter the European market and discuss the current state of the third country regimes as provided (partly) under EU law, their use—or notable lack thereof—and the challenges involved in the supervision of third country firms. We note that the recent updates to the third country equivalence regime for the provision of services to professional clients render the use of this regime even more difficult. In respect of the (optional) third country regime for the provision of services to retail clients, we observe that this regime is much akin to a full license requirement, albeit with notable difficulties when it comes to supervision and enforcement. Altogether, we come to the unfortunate conclusion that the EU third country regime for investment firms established in third countries can barely be called successful. [ABSTRACT FROM AUTHOR]

Abstract Coronary angiography has a limited ability to predict the functional significance of intermediate coronary lesions. Hence, physiological assessment of coronary lesions, via fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR), has been introduced to determine their functional significance. An accumulating body of evidence has consolidated the role of physiology-guided revascularization, particularly among patients with stable ischemic heart disease. The use of FFR or iFR to guide decision-making in patients with stable ischemic heart disease and intermediate coronary lesions received a class I recommendation from major societal guidelines. Nevertheless, the role of coronary physiology testing is less clear among certain patients’ groups, including patients with serial coronary lesions, acute coronary syndromes, aortic stenosis, heart failure, as well as post-percutaneous coronary interventions. In this review, we aimed to discuss the utility and clinical evidence of coronary physiology (mainly FFR and iFR), with emphasis on those specific patient groups.

Coronary angiography has a limited ability to predict the functional significance of intermediate coronary lesions. Hence, physiological assessment of coronary lesions, via fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR), has been introduced to determine their functional significance. An accumulating body of evidence has consolidated the role of physiology-guided revascularization, particularly among patients with stable ischemic heart disease. The use of FFR or iFR to guide decision-making in patients with stable ischemic heart disease and intermediate coronary lesions received a class I recommendation from major societal guidelines. Nevertheless, the role of coronary physiology testing is less clear among certain patients' groups, including patients with serial coronary lesions, acute coronary syndromes, aortic stenosis, heart failure, as well as post-percutaneous coronary interventions. In this review, we aimed to discuss the utility and clinical evidence of coronary physiology (mainly FFR and iFR), with emphasis on those specific patient groups. [ABSTRACT FROM AUTHOR]

Background: Stable coronary artery disease (CAD) presents with intermediate lesions that complicate treatment decisions. Visual assessment of coronary angiography may not accurately reflect the hemodynamic significance of these lesions. Instantaneous Wave- Free Ratio (IFR) is a new physiological index providing objective information on lesion functional significance. This study aimed to detect magnitude and direction of reclassification of intermediate lesions treatment after hemodynamic assessment by IFR in patients with stable CAD. Methods: This prospective observational study was carried out on 50 patients with stable coronary artery disease admitted to a single center. Patient received coronary angiography for a consultant's visual evaluation in order to identify the first treatment protocol. Hemodynamic assessment using IFR was performed for intermediate lesions to reclassify the treatment strategy. Results: The mean age of the patients was 64.2 ± 12.11 years, with 76% males and 24% females. The majority of patients had hypertension (74%), followed by diabetes mellitus (46%), hyperlipidemia (64%), smoking history (62%), and chronic kidney disease (22%). Based on the IFR assessment, 80% of patients were reclassified to receive medical treatment, while 20% underwent PCI. Conclusion: Our study results show that IFR is a reliable and accurate tool for guiding revascularization decisions in CAD patients. The majority of patients in our study, 80%, were safely reclassified to medical treatment based on IFR results. In the remaining 20% of patients, IFR results showed significant lesions that required PCI. [ABSTRACT FROM AUTHOR]

Background: The difficulty in identifying SARS‐CoV‐2 infections has not only been the major obstacle to control the COVID‐19 pandemic but also to quantify changes in the proportion of infections resulting in hospitalization, intensive care unit (ICU) admission, or death. Methods: We developed a model of SARS‐CoV‐2 transmission and vaccination informed by official estimates of the time‐varying reproduction number to estimate infections that occurred in Italy between February 2020 and 2022. Model outcomes were compared with the Italian National surveillance data to estimate changes in the SARS‐CoV‐2 infection ascertainment ratio (IAR), infection hospitalization ratio (IHR), infection ICU ratio (IIR), and infection fatality ratio (IFR) in five different sub‐periods associated with the dominance of the ancestral lineages and Alpha, Delta, and Omicron BA.1 variants. Results: We estimate that, over the first 2 years of pandemic, the IAR ranged between 15% and 40% (range of 95%CI: 11%–61%), with a peak value in the second half of 2020. The IHR, IIR, and IFR consistently decreased throughout the pandemic with 22–44‐fold reductions between the initial phase and the Omicron period. At the end of the study period, we estimate an IHR of 0.24% (95%CI: 0.17–0.36), IIR of 0.015% (95%CI: 0.011–0.023), and IFR of 0.05% (95%CI: 0.04–0.08). Conclusions: Since 2021, changes in the dominant SARS‐CoV‐2 variant, vaccination rollout, and the shift of infection to younger ages have reduced SARS‐CoV‐2 infection ascertainment. The same factors, combined with the improvement of patient management and care, contributed to a massive reduction in the severity and fatality of COVID‐19. [ABSTRACT FROM AUTHOR]

Using fuzzy sets for reasoning is what we mean when we talk about fuzzy logic. Contradictory natures are prevalent phenomena in the medical field. Guidelines are used by anesthesiologists when taking care of patients. After gauging the patient’s vitals, he may make adjustments to the flow of medication and fluids, or even the ventilator settings. Knowledge about the real world is typically sketchy, inaccurate, and inconsistent. Due to the inherent representation of subjective human conceptions used in much medical decision making, fuzzy logic seems well-suited for use in anaesthesia. We have developed a fuzzy expert system using fuzzy methodology for the aim of fluid management during general anaesthesia. The desired intravenous fluid rate (IFR) is the defuzzified value that is output by the fuzzy expert system. Fuzzy inputs serve as antecedent parts of rules for a fuzzy expert system, and some examples of such inputs are mean arterial pressure (HUO), hourly urine output (HUO), and central venous pressure (CVP). It would only cost a little sum to have a human operator sometimes enter MAP, HUO, and CVP values into a personal computer for this purpose. The study’s overarching goal was to devise a method for approximating IFR by making use of a linguistic description of MAP and HUO. Fuzzy sets, including decreasing, constant, and growing MAP and HUO rates of change, would assist to illustrate the trend in a patient’s fluid state. To regulate fluid levels more precisely would be possible. Expert guidance in addition to the calculated use of fuzzy methods are essential for achievement of the desired outcome. Patients must be in generally good health before this mode may be used on them, and they must be undergoing minimally invasive surgery. Moderate to severe blood loss after surgery need more complex modalities involving more factors. [ABSTRACT FROM AUTHOR]

RESUMEN Introducción y objetivos: La seguridad de la revascularización fisiológica en pacientes diabéticos ha sido poco investigada. El objetivo fue determinar la seguridad de diferir la revascularización basándose en la reserva fraccional de flujo (FFR) o en el índice instantáneo libre de ondas (iFR) en pacientes con diabetes mellitus. Métodos: Análisis retrospectivo, unicéntrico, de pacientes con estenosis coronarias intermedias en quienes se había diferido la revascularización en función de unos valores de FFR > 0,80 o de iFR > 0,89. Se analizó la incidencia a largo plazo de eventos cardiovasculares adversos mayores, una combinación de muerte por cualquier causa, infarto miocárdico y revascularización del vaso diana (RVD) en pacientes con y sin diabetes. También se evaluó la incidencia de RVD según el tipo de índice fisiológico utilizado para diferir la revascularización. Resultados: Se evaluaron 164 pacientes diabéticos (214 vasos) y 280 pacientes no diabéticos (379 vasos), con una mediana de seguimiento de 43 meses. No se observaron diferencias significativas en los eventos cardiovasculares adversos mayores entre pacientes con y sin diabetes mellitus (20,1 frente a 13,2%; p = 0,245). La mortalidad por cualquier causa y de causa cardiaca no fue estadísticamente diferente entre ambos grupos en el análisis ajustado (p > 0,05). Se observó una tendencia a una mayor incidencia de infarto de miocardio en los pacientes con diabetes mellitus (6,7 frente a 2,9%; p = 0,063), pero el infarto relacionado con el vaso diana fue similar en ambos grupos (p = 0,906). En general, la RVD fue similar en diabéticos y no diabéticos (4,7 frente a 4,2%; p = 0,787); sin embargo, cuando se analizó según el índice fisiológico, los diabéticos tuvieron una mayor tasa numérica de RVD cuando se utilizó la FFR en la toma de decisiones en comparación con el iFR (6,4 frente a 0,0%; p = 0,064). Conclusiones: Diferir la revascularización de estenosis intermedias en pacientes con diabetes mellitus según la FFR o el iFR es seguro en términos de RVD e infarto relacionado con el vaso diana, con una tasa de eventos en el seguimiento a largo plazo similar a la observada en pacientes sin diabetes mellitus.

ABSTRACT Introduction and objectives: The safety of physiology-based revascularization in patients with diabetes mellitus has been scarcely investigated. Our objective was to determine the safety of deferring revascularization based on the fractional flow reserve (FFR) or the instantaneous wave-free ratio (iFR) in diabetic patients. Methods: Single-center, retrospective analysis of patients with intermediate coronary stenoses in whom revascularization was deferred based on FFR > 0.80 or iFR > 0.89 values. The long-term rate of major adverse cardiovascular events, a composite of all-cause mortality, myocardial infarction, and target vessel revascularization (TVR), was assessed in diabetic and non-diabetic patients at the follow-up. The rate of TVR based on the type of physiological index used to defer the lesion was also evaluated. Results: We evaluated 164 diabetic (214 vessels) and 280 non-diabetic patients (379 vessels). No significant differences in the rate of major adverse cardiovascular events was seen between diabetic and non-diabetic patients (20.1% vs 13.2%; P = .245) at a median follow-up of 43 months. All-cause mortality and cardiac death were not statistically different between both groups in the adjusted analysis (P > .05). A trend towards a higher rate of myocardial infarction was seen in diabetic patients (6.7% vs 2.9%; P = .063). However, the rate of target vessel myocardial infarction was similar in both groups (P = .874). Overall, TVR was similar in diabetics and non-diabetics (4.7% vs 4.2%; P = .814); however, when analyzed based on the physiological index, numerically, diabetics had a higher rate of TVR when the FFR was used in the decision-making process compared to when the iFR was used (6.4% vs 0.0%; P = .064). Conclusions: Deferring the revascularization of intermediate stenoses in patients with DM based on the FFR or the iFR is safe regarding the risk of TVR or target vessel myocardial infarction, with a rate of events at the long-term follow-up similar to that seen in non-diabetic patients.

Atherosclerosis is a widespread disease affecting coronary arteries. Diffuse atherosclerotic disease affects the whole vessel, posing difficulties in determining lesion significance by angiography. Research has confirmed that revascularization guided by invasive coronary physiology indices improves patients' prognosis and quality of life. Serial lesions can be a diagnostic challenge because the measurement of functional stenosis significance using invasive physiology is influenced by a complex interplay of factors. The use of fractional flow reserve (FFR) pullback provides a trans-stenotic pressure gradient (ΔP) for each of the lesions. The strategy of treating the lesion with greater ΔP first and then reevaluating another lesion has been advocated. Similarly, non-hyperemic indices can be used to assess the contribution of each stenosis and predict the effect of lesion treatment on physiology indices. Pullback pressure gradient (PPG) integrates physiological variables of coronary pressure along the epicardial vessel and characteristics of discrete and diffuse coronary stenoses into a quantitative index that can be used to guide revascularization. We proposed an algorithm that integrates FFR pullbacks and calculates PPG to determine individual lesion importance and to guide intervention. Computer modeling of the coronaries and the use of non-invasive FFR measurement together with mathematical algorithms for fluid dynamics can make predictions of lesion significance in serial stenoses easier and provide practical solutions for treatment. All these strategies need to be validated before widespread clinical use.

Keywords: Coronary heart disease; iFR; FFR; Non-hyperaemic pressure ratio; Mortality; Revascularization EN Coronary heart disease iFR FFR Non-hyperaemic pressure ratio Mortality Revascularization 4388 4390 3 11/02/23 20231101 NES 231101 Background The DEFINE-FLAIR[1] and iFR-SWEDEHEART[2] clinical trials compared non-hyperaemic (resting) instantaneous wave-free ratio (iFR™)-guided management vs. hyperaemic fractional flow reserve (FFR)-guided management of patients being considered for coronary revascularization. Coronary heart disease, iFR, Non-hyperaemic pressure ratio, FFR, Mortality, Revascularization. [Extracted from the article]

Background and Objectives: The revascularization strategy for percutaneous coronary intervention (PCI) in patients with multivessel (MV) acute coronary syndrome (ACS) remains controversial. Certain gaps in the evidence are related to the optimal timing of non-culprit lesion revascularization and the utility of instantaneous wave-free ratio (iFR) in the management of MV ACS intervention. The major benefits of iFR utilization in MV ACS patients in one-stage complete revascularization are: (1) the possibility to virtually plan the PCI, both the location and the extension of the necessary stenting to achieve the prespecified final hemodynamic result; (2) the opportunity to validate the final hemodynamic result of the PCI, both in culprit artery and all non-culprit arteries and (3) the value of obliviating the uncomfortable, costly, time consuming and sometimes deleterious effects from Adenosine, as there is no requirement for administration. Thus, iFR use fosters the achievement of physiologically appropriate complete revascularization in MV ACS patients during acute hospitalization. Materials and Methods: This pilot study was aimed to test the feasibility of a randomized trial research protocol as well as to assess patient safety signals of co-registration iFR-guided one-stage complete revascularization compared with that of standard staged angiography-guided PCI in de novo patients with MV ACS. This was a single-center, prospective, randomized, open-label clinical trial consecutively screening patients with ACS for MV disease. The intervention strategy of interest was iFR-guided physiologically complete one-stage revascularization, in which the virtual PCI planning of non-culprit lesions and the intervention itself were performed in one stage directly following treatment of the culprit lesion and other critical stenosis of more than ninety percent. Seventeen patients were recruited and completed the 3-month follow-up. Results: Index PCI duration was significantly longer while the volume of contrast media delivered in index PCI was significantly greater in the iFR-guided group than in the angiography-guided group (119.4 ± 40.7 vs. 47 ± 15.5 min, p = 0.004; and 360 ± 97.9 vs. 192.5 ± 52.8 mL, p = 0.003). There were no significant differences in PCI-related major adverse cardiovascular events (MACE) between the groups during acute hospitalization and at 3-months follow-up. One-stage iFR-guided PCI requires fewer PCI attempts until complete revascularization than does angiography-guided staged PCI. Conclusions: Complete revascularization with the routine use of the virtual planning tool in one-stage iFR-guided PCI is a feasible practical strategy in an everyday Cath lab environment following the protocol designed for the study. No statistically significant safety signals were documented in the number of PCI related MACE during the 3-month follow-up. [ABSTRACT FROM AUTHOR]

Background Several non-hyperemic pressure-derived Indexes (NHPI) have been introduced for the assessment of coronary stenosis, showing a good correlation with fractional flow reserve (FFR). Notably, either the assessment of NHPI during adenosine administration (NHPI ADO) or the Hybrid Approach (NHPI HA), combining NHPI with FFR, have been showed to increase the accuracy of such indexes. It remains unclear whether diagnostic performance might be affected by the extent of the subtended myocardial mass. Methods. We enrolled consecutive patients with an intermediate coronary stenosis assessed with NHPI and FFR. NHPI were also measured during adenosine (ADO) administration (NHPI ADO). The amount of jeopardized myocardium was assessed using the Duke Jeopardy Score (DJS). With FFR as reference, we assessed the accuracy of NHPI, NHPI ADO and NHPI HA according to the extent of the subtended myocardium. Results. One-hundred-seventy stenoses from 151 patients were grouped according to the DJS as follows: A) Small Extent (SE, n = 82); B) Moderate Extent (ME, n = 53); C) Large Extent (LE, n = 35). As compared with FFR, NHPI showed a significantly different accuracy, as assessed by the Youden's index, according to the extent of the jeopardized myocardium (SE: 0.39 ± 0.05, ME: 0.68 ± 0.06, LE: 0.28 ± 0.06, p < 0.001). Conversely, both the NHPI ADO (SE: 0.76 ± 0.02, ME: 0.88 ± 0.02, LE: 0.82 ± 0.02, p = 0.72) and NHPI HA (SE: 0.82 ± 0.07, ME: 0.84 ± 0.02, LE: 0.88 ± 0.02, p = 0.70) allowed for a better diagnostic accuracy regardless of the amount of myocardium subtended. Conclusions. Diagnostic performance of NHPI might be affected by the extent of myocardial territory subtended by the coronary stenosis. A hybrid approach might be useful to overcome this limitation. • Diagnostic accuracy of NHPI is significantly affected by the extent of myocardium subtended by the coronary stenosis. • A misclassification of intermediated stenoses might occur and the hybrid approach might be useful for a better assessment. • Future studies should consider this limitation promoting the Hybrid Approach for the assessment of coronary artery stenoses. [ABSTRACT FROM AUTHOR]

Despite the now routine integration of invasive physiologic systems into coronary catheter laboratories worldwide, it remains critical that all operators maintain a sound understanding of the fundamental physiologic basis for coronary pressure assessment. More specifically, performing operators should be well informed regarding the basis for hyperemic (ie, fractional flow reserve) and nonhyperemic (ie, instantaneous wave-free ratio and other nonhyperemic pressure ratio) coronary pressure assessment. In this article, we provide readers a comprehensive history charting the inception, development, and validation of hyperemic and nonhyperemic coronary pressure assessment. [ABSTRACT FROM AUTHOR]

Percutaneous coronary intervention is increasingly guided by coronary physiology and optimized using intravascular imaging. Pressure-based measurements determine the significance of a stenosis using hyperemic or nonhyperemic pressure ratios (eg, the instantaneous wave-free ratio). Intravascular ultrasound and optical coherence tomography provide cross-sectional and longitudinal detail regarding plaque composition and vessel characteristics. These facilitate lesion preparation and optimization of stent sizing and positioning. This review explores the evidence-base and practical aspects of coregistering pressure gradient assessment and intravascular imaging with angiography. We then discuss gaps in the evidence and what is needed to help integrate these techniques into clinical practice. [ABSTRACT FROM AUTHOR]

Modern coronary intervention requires integration of angiographic, physiologic, and intravascular imaging. This article describes the use and techniques needed to understand coronary physiology pullback data and how use it to make revascularization decisions. The article describes instantaneous wave-free ratio, fractional flow reserve, and the data that support their use and how they differ when used in tandem disease. Common practical mistakes and errors are discussed together with a brief review of the limited published research data. [ABSTRACT FROM AUTHOR]

RESUMEN Introducción y objetivos: Los pacientes con estenosis en el tronco coronario izquierdo (TCI) han sido excluidos de los ensayos que apoyan la no inferioridad del cociente de presiones en el índice diastólico instantáneo sin ondas (iFR) respecto a la reserva fraccional de flujo (RFF) en la toma de decisiones sobre revascularización coronaria. El presente estudio propone valorar de manera prospectiva la concordancia entre los dos índices en lesiones del TCI y validar el valor de corte del iFR de 0,89 para su uso clínico. Métodos: Registro multicéntrico nacional, prospectivo, observacional, con la inclusión de 300 pacientes consecutivos con lesiones intermedias (estenosis angiográfica 25-60%) en el TCI. Se realizará un estudio con guía de presión y determinación de RFF e iFR. En caso de resultado concordante negativo (RFF > 0,80 / iFR > 0,89), no se realizará tratamiento; en caso de resultado concordante positivo (RFF ≤ 0,80 / iFR ≤ 0,89), se realizará revascularización; en caso de resultado discordante (RFF > 0,80 / iFR ≤ 0,89 o RFF ≤ 0,80 / iFR > 0,89), se realizará estudio con ecocardiografía intravascular y se considerará diferir la revascularización si el área luminal mínima es > 6 mm2. El criterio de valoración clínico primario será la incidencia del combinado de muerte cardiovascular, infarto no mortal relacionado con la lesión del TCI o necesidad de revascularización de la lesión del TCI a los 12 meses. Conclusiones: La demostración de la seguridad clínica en la toma de decisiones del iFR en pacientes con lesiones intermedias en el TCI tendría un impacto clínico importante y justificaría su uso sistemático para la decisión del tratamiento en estos pacientes de potencial alto riesgo. Registrado en ClinicalTrials.gov (identificador: NCT03767621).

ABSTRACT Introduction and objectives: Patients with left main coronary artery (LMCA) stenosis have been excluded from the trials that support the non-inferiority of the instantaneous wave-free ratio (iFR) compared to the fractional flow reserve (FFR) in the decision-making process of coronary revascularization. This study proposes to prospectively assess the concordance between the two indices in LMCA lesions and to validate the iFR cut-off value of 0.89 for clinical use. Methods: National, prospective, and observational multicenter registry of 300 consecutive patients with intermediate lesions in the LMCA (angiographic stenosis, 25% to 60%. A pressure gudiewire study and determination of the RFF and the iFR will be performed: in the event of a negative concordant result (FFR > 0.80/iFR > 0.89), no treatment will be performed; in case of a positive concordant result (FFR ≤ 0.80/iFR ≤ 0.89), revascularization will be performed; In the event of a discordant result (FFR> 0.80/iFR ≤ 0.89 or FFR ≤ 0.80/iFR> 0.89), an intravascular echocardiography will be performed and revascularization will be delayed if the minimum lumen area is > 6 mm2. The primary clinical endpoint will be a composite of cardiovascular death, LMCA lesion-related non-fatal infarction or need for revascularization of the LMCA lesion at 12 months. Conclusions: Confirm that an iFR-guided decision-making process in patients with intermediate LMCA stenosis is clinically safe and would have a significant clinical impact. Also, justify its systematic use when prescribing treatment in these potentially high-risk patients. Registered at ClinicalTrials.gov ( Identifier: NCT03767621).

We obtain new bounds for the renewal function, as well as for the expected number of renewals over an interval (t , t + h ] . Improved bounds are given when the interarrival distribution belongs to certain aging classes. Our results are compared with existing ones in the literature, both theoretically and with the aid of numerical resuts. [ABSTRACT FROM AUTHOR]

Combinations of multiple inorganic fillers have emerged as viable synergistic agents for boosting the flame retardancy of intumescent flame retardant (IFR) polymer materials. However, few studies on the effect of multiple inorganic fillers on the flame retardant behavior of rigid polyurethane (RPU) foam have been carried out. In this paper, a flame retardant combination of aluminum hydroxide (ATH) and traditional flame retardants ammonium polyphosphate (APP), pentaerythritol (PER), melamine cyanurate (MC), calcium carbonate (CC), and expandable graphite (EG) was incorporated into RPU foam to investigate the synergistic effects of the combination of multiple IFR materials on the thermal stability and fire resistance of RPU foam. Scanning electron microscopy (SEM) and thermogravimetric analysis (TGA) revealed that 8 parts per hundred polyols by weight (php) filler concentrations were compatible with RPU foam and yielded an increased amount of char residue compared to the rest of the RPU samples. The flame retardancy of multiple fillers on intumescent flame retardant RPU foam was also investigated using cone calorimeter (CCTs) and limiting oxygen index (LOI) tests, which showed that RPU/IFR1 (APP/PER/MC/EG/CC/ATH) had the best flame retardant performance, with a low peak heat release rate (PHRR) of 82.12 kW/m2, total heat release rate (THR) of 15.15 MJ/m2, and high LOI value of 36%. Furthermore, char residue analysis revealed that the use of multiple fillers contributed to the generation of more intact and homogeneous char after combustion, which led to reduced decomposition of the RPU foam and hindered heat transfer between the gas and condensed phases. [ABSTRACT FROM AUTHOR]

After initially having low levels of SARS-CoV-2 infections for much of the year, Bulgaria experienced a major epidemic surge at the end of 2020, which caused the highest recorded excess mortality in Europe, among the highest in the word (Excess Mortality Rate, or EMR ∼0.25%). Two more major waves followed in 2021, followed by another one in early 2022. In this study, we analyze the temporal and spatial patterns of excess mortality at the national and local levels and across different demographic groups in Bulgaria and compare those to the European levels. Bulgaria has continued to exhibit the previous pattern of extremely high excess mortality, as measured both by crude mortality metrics (an EMR of ∼1.05%, up to the end of March 2022) and by standardized ones—Potential Years of Life Lost (PYLL) and Aged-Standardized Years of life lost Rate (ASYR). Unlike Western Europe, the bulk of excess mortality in Bulgaria, as well as in several other countries in Eastern Europe, occurred in the second year of the pandemic, likely related to the differences in the levels of vaccination coverage between these regions. We also observe even more extreme levels of excess mortality at the regional level and in some subpopulations (e.g., total EMR values for males ≥ 2% and EMR values for males aged 40–64 ≥ 1% in certain areas). We discuss these observations in light of the estimates of infection fatality rate (IFR) and eventual population fatality rate (PFR) made early in the course of the pandemic. [ABSTRACT FROM AUTHOR]

This paper describes the findings of a study of the soil plugging progressive formation process during pipe pile penetration using a transparent soil model test. The objective of this study is to visually investigate the factors affecting the plugging effect such as the pile diameter, penetration speed, relative density, and wall thickness. To measure the plugging development, an image measurement system was utilized. It found that pile diameter, relative density, and wall thickness were more sensitively influencing factors and that changing penetration speed had a minor influence on the degree of soil plug. The visualization analysis results show that the formation of plugging is not continuous, but intermittent and progressive. The soil plug was an alternate process from formation to destruction repeatedly. In addition, it revealed that the mobilization of internal frictional resistance depends on the height of the formed plugging and that the degree of soil plug only affects the magnitude of unit internal friction resistance. The underlying dynamic evolutionary mechanism of plugging formation was further discussed. In addition, a linear empirical formula between the incremental filling ratio and plug length ratio value was proposed. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Use of invasive physiological assessment in patients with coronary artery disease varies widely and is perceived to be low. We aimed to examine adoption rates as well as patterns and determinants of use in an unselected population undergoing invasive coronary angiography over a long time frame. Methods: We retrospectively determined the per-procedure prevalence of physiological assessment in 40 821 coronary cases performed between 2007 and 2018 in two large-volume centers. Adoption was examined according to procedure type and patient- and operator-related variables. Its association with relevant scientific landmarks, such as the release of clinical trial results and practice guidelines, was also assessed. Results: Overall adoption was low, ranging from 0.6% in patients undergoing invasive coronary angiography due to underlying valve disease, to 6% in the setting of stable coronary artery disease (CAD); it was 3.1% in patients sustaining an acute coronary syndrome. Of scientific landmarks, FAME 1, the long-term results of FAME 2 and the 2014 European myocardial revascularization guidelines were associated with changes in practice. Publication of instantaneous wave-free ratio (iFR) trials had no influence on adoption rates, except for a higher proportion of iFR use. In 42.9% of stable CAD patients undergoing percutaneous coronary intervention there was no objective non-invasive evidence of ischemia, nor was physiological assessment performed. Younger operator age (4.5% vs. 4.0% vs. 0.9% for ages 55 years, respectively; p 55 anos, respetivamente; p < 0,001) e a hora de realização do procedimento (2,9% entre as 6-8PM versus 4,4% durante o restante dia) relacionaram-se inversamente com a utilização de fisiologia durante os procedimentos. Conclusões: Esta análise confirma a baixa de utilização da avaliação funcional invasiva na prática clínica. A disponibilidade de evidência sobre o uso de índices não hiperémicos não aumentou a adoção. São necessárias estratégias dirigidas que potenciem a implantação das recomendações, de forma que o manejo dos doentes com doença coronária e os benefícios clínicos da estratificação invasiva possam ser aprimorados.

Background:A number of estimates of the infection fatality ratio (IFR) of SARS-CoV-2 in different countries have been published. In Brazil, the fragile political situation, together with socioeconomic and ethnic diversity, could result in substantially different IFR estimates.Methods:We infer the IFR in Brazil in 2020 by combining three datasets. We compute the prevalence via the population-based seroprevalence survey, EPICOVID19-BR. For the fatalities we obtain the absolute number using the public Painel Coronavírus dataset and the age-relative number using the public SIVEP-Gripe dataset. The time delay between the development of antibodies and subsequent fatality is estimated via the SIVEP-Gripe dataset. We obtain the IFR for each survey stage and 27 federal states. We include the effect of fading IgG antibody levels by marginalizing over the test detectability time window.Results:We infer a country-wide average IFR (maximum posterior and 95% CI) of 1.03% (0.88–1.22%) and age-specific IFRs of 0.032% (0.023–0.041%) [< 30 years], 0.22% (0.18–0.27%) [30–49 years], 1.2% (1.0–1.5%) [50–69 years], and 3.0% (2.4–3.9%) [≥ 70 years]. We find that the fatality ratio in the country increased significantly at the end of June 2020, likely due to the increased strain on the health system.Conclusions: Our IFR estimate is based on data and does not rely on extrapolating models. This estimate sets a baseline value with which future medications and treatment protocols may be confronted.

The present study aimed to investigate some microbial infections and immunological parameters associated with Covid-19 patients admitted to the intensive care unit (ICU) of Al-Amal Specialized Hospital in AL-Najaf Governorate during February and March 2021. The study included 50 patients who were assigned to two groups: 20 patients aged =70 years and 30 patients aged =70 years. The method of microbial culture was adopted to isolate bacteria and yeasts by collecting sputum specimens and oral swabs from patients and cultivating them on diagnostic media and then confirming the diagnosis by Vitek. Moreover, serum samples were collected from patients' blood to diagnose fungal infections. Thereafter, some immunological criteria were assessed, including Covid-19 diagnosis by measuring Immunoglobulin M (IgM) and IgG, as well as examining the concentration of cytokines (Interleukin 6 (IL-6) and IF) using the enzyme-linked immunosorbent assay (ELISA) method. The results demonstrated that bacterial species Streptococcus pneumonia (n=5; 25%), Haemophilus Influenzae (n=7; 35%), and Moraxella catarrhalis (n=3; 15%) were isolated from the first group of patients (=70 years). The recorded data pointed out that Streptococcus pneumonia (n=10; 33.3%), Streptococcus pyogenes (n=5; 16.6%), Streptococcus viridans (n=1; 3.3%), Haemophilus Influenzae (n=6; 20%), Mycobacterium tuberculosis (n=2; 6.6%), and Pseudomonas aeruginosa (n=2; 6.6%) were the isolated and identified microorganisms in the second age group (= 70 years). The results revealed that the isolated yeast from the first age group was Candida albicans (n=5; 25%) and Candida glabrata (n=3; 10%), while in the second age group, 1 (3.3%) Candida albicans was isolated. The results of this study proved that 30% and 10% of patients in the first and second age groups had invasive pulmonary aspergillosis co-infection by detecting Galactomannan (GM) in the blood serum (1.05±0.59, 1.25±0.38), respectively. The results indicated that IgM and IgG levels in the serum of patients in the first age group were 11.42±6.82 and 0.47±6.82, respectively. Moreover, the levels of IgM and IgG in the second age group were 14.84±9.21 and 0.12±0.11, respectively. Furthermore, IF and IL6 levels were 98.37±65.70, and 146.12±46.35 in the first group, while IF and IL6 were obtained at 110.69±47.60 and 133.28±116.94 in the second group, respectively. Elderly patients with severe COVID-19 are more frequently admitted to ICUs since the proportion of severe cases and comorbidities caused by a weakened immune system is higher among this age group. Secondary bacterial infections can also occur, especially Gram-negative bacteria which are among the most significant public health problems worldwide. Moroever, aspergillosis may infect patients hospitalized with COVID-19 and lead to death. [ABSTRACT FROM AUTHOR]

Background: Instantaneous wave-free ratio (iFR) can reliably assess the physiological significance of coronary artery disease (CAD). Previous studies have demonstrated its interchangeability with other non-hyperaemic pressure ratios (NHPR), but there is no data exploring whether this association is maintained in patients with severe aortic stenosis (AS).Methods: Forty-two patients (67 lesions) with severe AS were recruited and underwent invasive pressure-wire assessment. Data were extracted to calculate iFR, resting Pd/Pa, diastolic pressure ratios (DPR and dPR), and Diastolic Hyperaemia-Free Ratio (DFR). iFR was then compared with other NHPR to determine agreement and accuracy.Results: Mean aortic gradient and dimensionless index were 44.3 ± 11.6 mmHg and 0.23 ± 0.04, respectively. Of the 67 vessels, 57% were LAD, 15% LCx, 13% RCA and 12% other. There was strong positive correlation between iFR and all other NHPR, including Pd/Pa (r = 0.91, p < 0.001), DPR (r = 0.99, p < 0.001), dPR (r = 0.97, p < 0.001) and DFR (r = 0.98, p < 0.001). While Bald-Altman analysis demonstrated that Pd/Pa and DFR were numerically different from iFR, ROC analyses demonstrated iFR ≤0.89 was accurately identified by all NHPRs; Pd/Pa (AUC = 0.965, 95% CI [0.928-0.994]), DPR (AUC = 1.000, 95% CI [1.000-1.000]), dPR (AUC = 0.974, 95% CI [0.937-1.000]), DFR (AUC = 0.989, 95% CI [0.968-1.000]).Conclusion: In patients with severe AS, all the included NHPR in this analysis accurately predicted iFR < 0.89. These data should reassure clinicians that use of alternative NHPR to iFR is reasonable when assessing the physiological significance of CAD in patients with severe AS. [ABSTRACT FROM AUTHOR]

In this study, the influence of the addition of intumescent flame retardants (IFRs) on the non‐isothermal crystallization of high‐density polyethylene (HDPE) was studied. The investigations were carried out for polyethylene compositions containing two different IFRs, ammonium polyphosphate (APP) and a mixture of copper phosphate and melamine phosphate (CUMP). Both IFRs have been incorporated with a constant amount of 20 wt%. Non‐isothermal kinetic parameters were calculated from differential scanning calorimetry (DSC) analysis using the Jeziorny and Mo methods. The research demonstrates the appropriateness of using the latter approach to evaluate the HDPE‐based crystallization process changes. The results of the obtained kinetic parameters describing HDPE crystallization were related to the activation energy assessed by the Friedman method, microscopic analysis performed using polarized light microscopy, and wide‐angle X‐ray scattering (WAXS). Despite the increase in the activation energy (EX) of the flame retarded polyethylene series, the degree of crystallinity was comparable to that of unmodified HDPE due to a limited dependence effect of EX on relative crystallinity. Investigations made using polarized light microscopy showed an increase in the density of spherulite impingement for HDPE/IFRs. Moreover, despite introducing crystalline organic compounds, polyethylene did not reveal any polymorphic changes according to WAXS. [ABSTRACT FROM AUTHOR]

Aims: Assess the correlation between diameter stenosis, lesion length, location, diffuse coronary disease and with fractional flow reserve (FFR). Methods/Results: We performed quantitative coronary analysis analysis on 384 lesions with stable coronary artery disease undergoing FFR assessment. Vessels were 59.1% left anterior descending artery (LAD), 16.1% left circumflex artery and 14.8% right coronary artery. Median diameter stenosis was 58% ± 2.5 and median lesion length was 10 mm ± 7.36. 21% of vessels were diffusely diseased. Lesions were 33.6% proximal, 44% mid-vessel and 12% distal. Median FFR was 0.85. Diameter stenosis correlated with lower FFR (p < 0.005, odds ratio [OR]: 2.4 [95% CI: 0.99-5.63]). There was no association between lesion length, location, number of proximal side branches and FFR. Vessels with diffuse disease had a nonsignificant trend for lower FFR (0.84 vs 0.85, p = 0.375, OR: 1.26 [95% CI: 0.76-2.09]). LAD lesions had significantly lower FFR compared with non-LAD (p < 0.001, OR: 2.55 [95% CI: 1.61-4.04]); including left circumflex artery and right coronary artery lesions (p = 0.001, OR: 3.4 [95% CI: 1.7-6.9]) and p = 0.02, OR: 2.55 [95% CI: 1.17-4.34]). Conclusion: FFR is not related to lesion length, location or number of proximal branches. [ABSTRACT FROM AUTHOR]

Whether physiology-guided complete revascularization of nonculprit lesions is superior to culprit lesion-only percutaneous coronary intervention (PCI) in patients with myocardial infarction (MI) and multivessel disease remains debated. Online databases were searched for randomized controlled trials comparing physiology-guided complete revascularization and culprit lesion-only PCI in patients with MI. The outcomes of interest were all-cause death, cardiovascular (CV) death, repeat revascularization, MI, stent thrombosis, and contrast-associated nephropathy/acute kidney injury. Pooled odds ratios, along with 95% confidence intervals (CI) were calculated. A total of 4,849 patients (n = 2,288 physiology-guided complete revascularization, n = 2,561 culprit lesion-only PCI) were included. The mean age was 66 years and 76% were men. At a mean follow-up of 2.5 years, physiology-guided complete revascularization was associated with significant reductions in CV death (odds ratio 0.72, 95% CI 0.54 to 0.97, p = 0.03) and repeat revascularizations (0.50, 95% CI 0.38 to 0.66, p <0.00001) compared with culprit lesion-only PCI. There were no differences between the 2 approaches in all-cause death (0.91, 95% CI 0.69 to 1.19, p = 0.50), MI (0.85, 95% CI 0.59 to 1.21, p = 0.36), stent thrombosis (1.24, 95% CI 0.58 to 2.69, p = 0.58), and contrast-associated nephropathy/acute kidney injury (1.07, 95% CI 0.88 to 1.31, p = 0.50). In conclusion, among patients with MI and multivessel disease, physiology-guided complete revascularization was associated with significant reductions in CV death and revascularizations compared with culprit lesion-only PCI., Competing Interests: Declaration of competing interest J. Dawn Abbott - research (Boston Scientific, Shockwave, Med Alliance), consulting (Medtronic, Recor, Abbott, Penumbra). Aakash Garg - speaker for edwards Lifesciences. All other authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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