There is a close relationship between blood pressure levels and the risk of cardiovascular events, strokes, and kidney disease. For many years, the gold standard instrument for blood pressure measurement was a mercury sphygmomanometer and a stethoscope, but this century-old technique of Riva-Rocci/Korotkov is being progressively removed from clinical practice. Central blood pressure is considered better than peripheral blood pressure in predicting cardiovascular events, as it assesses wave reflections and viscoelastic properties of the arterial wall which make systolic and pulse pressures vary from central to peripheral arteries, but mean blood pressure is constant in the conduit arteries.The study included 201 patients with primary hypertension (108 patients with chronic kidney disease and 93 patients without kidney disease). All patients underwent blood pressure measurement by OMRON M2 and Mobil-O-Graph devices, kidney function assessment and abdominal ultrasonography.Patients with chronic kidney disease were significantly older , with longer duration of hypertension  in comparison to those without chronic kidney disease. Automated peripheral measurement of systolic blood pressure, diastolic blood pressure and pulse pressure were significantly higher in comparison to central blood pressure. Patients with chronic kidney disease had significantly higher augmentation index  and pulsed wave velocity  in comparison to those without chronic kidney disease. Augmentation index had positive correlation with pulse wave velocity . There was negative correlation between both pulse wave velocity and augmentation index and estimated glomerular filtration rate , and , respectively. Hence, arterial stiffness parameters are good positive test for prediction of chronic kidney disease.There is a strong agreement between non-invasive centrally and automated peripherally measured blood pressure in diagnosis of hypertension. But non-invasive central measurements are preferred over automated measurements for early prediction and detection of renal impairment. Diabetes and hypertension are responsible for up to two-thirds of CKD; less frequent causes include glomerulonephritis, nephrolithiasis, and polycystic kidney disease. [Hypertension (HTN) is well known as a silent killer, there is a close relationship between blood pressure levels and the risk of cardiovascular events, strokes, and kidney disease. The prevalence of chronic kidney disease (CKD) is higher in hypertensive patients than in normotensive subjects . CKD is disease. For long time, the standard instrument for blood pressure (BP) measurement was a mercury sphygmomanometer and a stethoscope, but this old technique is being progressively removed from clinical practice due to the mercury toxicity and the number of faults that may affect this method , 5. SeveSeveral parameters were derived from central BP measurement that helped in prediction of adverse cardiovascular outcomes among hypertensive patients, such as augmentation index and pulse wave velocity (PWV). In the present study, we attempted to assess the difference of blood pressure measurements using central and automated peripheral blood pressure measurement (oscillometric) devices among patients with primary hypertension for early detection of kidney dysfunction and the validity of automated BP measurement device compared with non-invasive central BP measurement device for diagnosis of hypertension. Also, we tried to link between parameters such as augmentation index and pulse wave velocity index and early kidney dysfunction markers.This is a case comparison study design conducted in Assiut University Heart Hospital between May 2018 and September 2019 and included 201 patients with primary hypertension. All patients with primary hypertension (according to the recent ESC guidelines 2018), with age range between 40 and 70 years old, either on anti-hypertensive medications or not were included. Exclusion criteria were patients presenting with secondary hypertension, diabetes mellitus (DM), end stage renal disease (ESRD) on regular dialysis and patients with collagen diseases. We excluded patients younger than 40 years old due to a high propensity of having secondary hypertension. Also, patients older than 70 years old were excluded as well due to the marked effect of vessel wall on the BP value and other parameters such as augmentation index and PWV.2.All patients underwent an initial clinical evaluation, including history taking focusing on age, sex, smoking, anti-hypertensive treatment, duration of HTN and history of previous illness such as DM, collagen disease and CKD  . Body maCentral blood pressure monitoring was done non-invasively using a well calibrated device; Mobil-O-Graph  device with inbuilt ARC solver  utilized the technique of pulse wave analysis where pressure waveforms were recorded from peripheral arteries , 12. TheWe used algorithms to obtain conventional blood pressure readings from brachial systolic and diastolic pressures  . In the Digital measurements of peripheral BP were done by the automatic BP monitor (Oscillometric) named the OMRON M2 basic® device, provided by OMRON Healthcare company, Kyoto, Japan.The patient seated comfortable at the table in a quiet room and relaxed for about 5–10 min before measurement with their arm at heart level rested on a table with the palm facing up. Wrap the cuff around the upper arm, about 2–3 cm above the elbow. This monitor uses inflation by Fuzzy-Logic controlled by electric pump and an automatic rapid pressure release valve for the deflation, its cuff allows BP measurements in arm circumference of 22–42 cm. The device measure BP and pulse rate with a pressure range of 0-299 mmHg and pulse rate range of 40–180 beats/min. The measurement was repeated three times with a two-minute break between them. The mean of them was recorded then the cuff was removed.2) was estimated by Cock croft-Gault method [Five milliliters of venous blood was withdrawn under aseptic condition from patients on presentation for renal function tests including: serum creatinine  and blood urea  . GFR .Kidney damage, as defined by structural abnormalities.The primary end point of the study was the detection of early kidney dysfunction among patients with primary hypertension. Additional secondary hypotheses compared between blood pressure monitored centrally and peripherally among primary hypertensive patients.Informed written consents were obtained from all participants after illustrating all steps of the study. The study was approved by the institutional ethical committee under the IRB number 17,101,738 on 05.04.2018.Data were verified, coded by the researcher, and analyzed using IBM-SPSS 21.0 . Continuous data were expressed in the form of mean ± SD or median (interquartile range) according to their distribution while nominal data were expressed in the form of frequency (percentage). Chi square test was used to compare the difference in distribution of frequencies among different groups. Paired Sample t-test was used to compare the means of BP measurements. Mann-Whitney U test analysis was carried out to compare the medians of dichotomous data that did not follow the normal distribution. Receiver-operating characteristic (ROC) curve was depicted to investigate the diagnostic performance of blood pressure measurements and arterial stiffness parameters for prediction of kidney affection, analyzed as area under the curve (AUC), standard error (SE) and 95% confidence interval (CI). Validity statistics  were calculated. Agreement between various blood pressure measurement modalities was examined using Cohen’s kappa coefficient (κ). A significant p value was considered when it is equal to or less than 0.05.G Power program was used to calculate sample size to detect a significant difference in mean of systolic blood pressure between two groups under the study  among primary hypertensive patients. Hypothesized effect size 0.5, alpha error 0.05, power 0.80, allocation ratio 1:1. At least 80 patients should be included in each group with a total sample size 160 patients.During the study period, 201 patients with primary hypertension were recruited from Assiut University Heart Hospital. According to the presence of CKD, the study population was divided into two groups:Group I: It included 108 with CKD.Group II: It included 93 patients without CKD.Baseline patient characteristics categorized by diagnosis were presented in Table Automatic peripheral measurements of systolic BP, diastolic BP and pulse pressure were significantly higher compared with the central measurements  respectively, Table To test the validity of automatic peripheral BP measurement in comparison to central BP measurements in the diagnosis of HTN, ROC curves were plotted. Figure Our results reported that various BP measurements values didn’t have any significance for prediction of CKD. Hence, all these measurements couldn’t be used for prediction of CKD among patients with HTN.Patients with CKD had significantly higher augmentation index (P < 0.001) and PWV (P = 0.004) in comparison to those without CKD as shown in Table PWV had a negative correlation with e-GFR either among all studied group, non-CKD group and CKD group . While augmentation index showed a negative correlation with e-GFR among only all studied group . This relation was lost among non-CKD and CKD patients, Table Patients with normal ACR had significantly lower PWV (P = 0.002) and augmentation index P = 0.049) in comparison to those with abnormal ACR. Also, patients with normal abdominal ultrasound had significantly lower PWV in comparison to those with echogenic kidney grade I (8.67 ± 5.1 vs. 8.80 ± 1.3) and grade II (8.67 ± 5.1 vs. 8.82 ± 1.6). Augmentation index was significantly lower among patients with normal abdominal ultrasound in comparison to those with echogenic kidney grade I (21.46 ± 12.1 vs. 21.56 ± 8.6) and grade II (21.46 ± 12.1 vs. 21.62 ± 14.5) as shown in Table 9 in compFigure Hypertension is a common problem among older adults, reaching prevalence as high as 70 to 80%. Untreated hypertension is notorious for increasing the risk of mortality and is often described as a silent killer. It may be associated with a risk of atherosclerotic disease among 30% and organ damage among 50% of people within 8–10 years after its onset. End stage renal disease is one of the main complications of HTN particularly among diabetics patients , 18.The current study enrolled 201 hypertensive patients who were classified into 108 patients with CKD and 93 patients without CKD. We aimed to assess two different methods in BP measurement and test their value in prediction of early renal dysfunction among hypertensive patients.We noticed that patients with CKD had significantly higher mean age and mean duration of HTN in comparison to those without CKD. Also, there was male predominance among CKD group but of no statistical significance. Our results were consistent with Tannor et al. who stated that patients with CKD had significantly higher mean age and longer duration of HTN. Also, they reported that age was considered a predictor for CKD among patients with HTN and male patients had higher risk to progress to CKD in comparison to females . We notiReliability of brachial BP measurement in the physician’s office has its own limitations that make it less reliable than out-of-office BP measurement, using either home BP monitoring or ambulatory BP monitoring (ABPM) techniques . In receBP is traditionally measured at the brachial arteries, so brachial BP measurement is the gold standard method for diagnosis and management of hypertension. However, in many individuals, there are some discrepancies between central and peripheral BP. These discrepancies have long been a common research aspect, and whether central BP is a better clinical surrogate than brachial BP has also been universally debated .Our study revealed that that automatic peripheral BP measurement slightly overestimated SBP and DBP in comparison to central BP measurement with subsequent overestimation of mean BP either among those with CKD or without CKD in consistent with Drawz et al. who found that peripheral measurement of both SBP and mean BP were overestimated due to the consequence of the calibration method .SimilarlTill now, the diagnosis of hypertension, according to office, home, or ambulatory BP measurements, is currently based on recordings from the brachial arteries. Because of the phenomenon of PP amplification, brachial BP and PP are usually higher than the corresponding readings in the central aorta . HoweverOn the other hand, our study demonstrated that diagnostic accuracy of central and automatic peripheral BP measurements had no significant value in the prediction of CKD (P > 0.05). It’s known that central BP may reflect the pulsatile load on the heart and large arteries better than brachial BP and more closely associated with end organ damage . In contRecent technological advances have enabled several non-invasive methods to estimate arterial stiffness. Of these non-invasive measurements; higher PWV and augmentation index as indicators of intra-renal hemodynamics, are known to be associated with worse renal function and further, have a predictive value for renal outcomes among patients with essential HTN .Our study corroborates and extends previous findings that patients with CKD had significantly higher augmentation index (P < 0.001) and PWV (P = 0.004) in comparison to those without CKD. Also, both PWV and augmentation had a negative correlation with eGFR and increased among patients with abnormal ACR. This indicates that PWV and augmentation increases with progression of the renal damage. In concordance with Kusunoki et al. who demonstrated that arterial stiffness indices such as PWV and augmentation index as well renal resistive index (RI) increased with increasing severity of CKD stage among hypertensive patients. They also found that PWV is one of the predictors for advanced renal disease in such patients. This could be explained by excessive pulsatile energy transmission into the susceptible renal microvasculature as an important mechanism of progression of kidney damage and renal resistive index was known to be associated with carotid-femoral PWV and abnormal ACR. So, increased RI was associated with more renal damage .It should be noted that augmentation index at cut-off point 10 had 82% sensitivity (AUC = 0.651) while PWV at cut-off point 7 m/s had 84% sensitivity (AUC = 0.617) for prediction of CKD. Furthermore, combination of augmentation index and PWV improved sensitivity to 94% (AUC = 0.772) for prediction of CKD. Overall, our positive results of the combined augmentation index and PWV agreed with Fouad et al., who revealed that PWV was significantly higher among hypertensive patients compared to normotensive patients which make PWV is a good predictor for end organ damage .It is important to note that, our data indicated that PWV and augmentation index provide complementary information on target organ damage among hypertensive patients, but its predictive role for CKD as organ damage development parameter needs to be assessed in large prospective clinical trials. Also, our data reinforced the concept that automatic peripheral BP measurement may be helpful in diagnosing and monitoring hypertension. But some of the normotensives in the office and some of the controlled hypertensive appeared to show some type of masked hypertension, as well as an increase in central pressure, both of which are associated with the increase in aortic stiffness as measured by PWV and augmentation index.Finally, it has long been recognized that individual discrepancies between central and peripheral BP may be magnified during hemodynamic changes or after pharmacological interventions. The differential responses of central BP vs. brachial BP to various antihypertensive agents are highly variable among individuals in clinical studies .We acknowledge a few limitations for the present study. First, our study is limited by the enrollment of a relatively small sample included from a single center. However, this was overcome using appropriate statistical tests. The results, therefore, are preliminary and need to be confirmed and extended in larger multicenter studies on a larger number of patients to get more valid and reliable diagnostic impact.There is a strong agreement between non-invasive central BP measurements and automated peripheral BP measurements in the diagnosis of HTN. But non-invasive central measurements are preferred over automated measurements for early prediction and detection of renal impairment.


Carbon dioxide (CO2)-derived parameters, namely veno-arterial CO2 difference (ΔCCO2) and the VCO2/VO2 ratio, may represent a potentially valuable addition as sensitive biomarkers to assess tissue perfusion and cellular oxygenation and may represent a valuable addition in shock monitoring. These variables have been mostly studied in the adult population, with a strong association between ΔCCO2 or VCO2/VO2 ratio and mortality. In children, particularly in CICU, few studies looked at these parameters, while they reported promising results on the use of CO2-derived indices for patients’ management after cardiac surgeries. This review focuses on the physiological and pathophysiological determinants of ΔCCO2 and VCO2/VO2 ratio while summarizing the actual state of knowledge on the use of CO2-derived indices as hemodynamical markers in CICU.Shock is a life-threatening condition, and its timely recognition is essential for adequate management. Pediatric patients with congenital heart disease admitted to a cardiac intensive care unit (CICU) after surgical corrections are particularly at risk of low cardiac output syndrome (LCOS) and shock. Blood lactate levels and venous oxygen saturation (ScVO Timely 2) have been used traditionally as markers of tissue perfusion and adequacy of DO2 in case of shock. Nonetheless, ScVO2 and lactate have drawbacks that need to be known in order to correctly interpret their values in the intensive care setting. Moreover, if their role as predictors of unfavorable outcomes is undeniable, resuscitation algorithms based either on lactate or ScVO2 failed to demonstrate clear clinical benefits [Serum lactate level and central venous oxygen saturation ScVO have beebenefits ,5,6,7,8.2 (venous oxygen saturation measured in the pulmonary artery) has become a rarity, especially in pediatric patients, as a pulmonary catheter must be placed, which is a complicated and risky procedure. SvO2 and ScVO2 are closely correlated, provided that the central venous catheter tip is correctly positioned at the junction between the superior venous cava and the right atrium.The measurement of SvO2 use is based on the comparison between the VO2 and the extraction of oxygen by the tissue, using the Fick formula:ScVOThat is2 = Hb × 1.34 × SpaO2 + 0.003 × PaO2 and CvO2 = Hb × 1.34 × ScVO2 + 0.003 × PaO2Knowing that CaOAnd after rearrangement of the equation, the final formula:2. As a result, ScVO2 will decrease proportionally to the reduction of DO2, regardless of the cause that generated the DO2 reduction, thus providing a global picture of the patient’s hemodynamic status. The role of ScVO2 as a marker of both hemodynamic deterioration and clinical response to treatments has been extensively studied in both adult and pediatric ICU patients [2 levels have been associated with progressive hemodynamic deterioration and unfavorable clinical outcomes [A reduction of oxygen delivery (the denominator of the equation) will first lead to an increase in oxygen extraction to maintain the VOpatients . Specifioutcomes ,11.2 should be mentioned, and its interpretation comes with some caveats. In fact, low ScVO2 values indicate a global imbalance between DO2 and VO2 without giving any further information regarding the individual components of these two elements, such as arterial oxygen saturation, hemoglobin, and CO. Moreover, during the early phase of resuscitation, the increase in DO2 may lead to an increase in VO2, which could result in a transitory decrease in ScvO2 levels. In a situation of shock, a mismatch between DO2 and capillary perfusion may lead to a misleadingly normal ScVO2 resulting from oxygen extraction impairment [However, several limitations of ScVOpairment ,12,13.2 could be insufficient to meet cellular metabolism demands. As a consequence, the absence of aerobic mitochondrial metabolism leads to an over-production of lactate from the intracellular excess pyruvate.Serum lactate is a key metabolic parameter that could be related to both hypoperfusion and hypoxia . It is pAs lactate level is a marker of hypoperfusion, serum lactate’s peak level, as well as lactate clearance, are strongly associated with patient outcomes in both adult and pediatric critically ill patients ,6,15,16.2)-derived parameters may represent a potentially valuable addition to serum lactate level and ScVO2 when it comes to the evaluation of tissue perfusion and hypoxia, as underlined by the recent recommendation on hemodynamic monitoring adult experts when lack of data prevented pediatric experts from giving such recommendations [2-derived parameters measurement at the bedside makes them an attractive tool to guide resuscitation in the clinical setting.Given the aforementioned limitations in the interpretations of conventional tissue oxygenation markers, supplementary tools to assess the hemodynamic status of critically ill patients are needed ,27. Carbndations ,29. The 2-derived parameters and their physiological underpinnings, as well as their potential clinical applications in CICU.The purpose of this review is to describe currently available CO2 is produced by cellular metabolism (VCO2) under both aerobic and anaerobic conditions. Under aerobic metabolism, CO2 is produced by the mitochondrial metabolism as a by-product of substrate oxidation. In the case of anaerobic metabolism, CO2 is also produced by bicarbonate buffering of H+ derived from lactic acid production and ATP hydrolysis. Carbon dioxide diffuses from the intracellular to the extracellular compartment. Once in the blood, CO2 transportation occurs in three forms: dissolved, as bicarbonate after the reaction of CO2 with H2O in red blood cells, and finally, as carbamino compounds within circulating proteins, particularly hemoglobin. The dissolved fraction of CO2 is in equilibrium with the partial pressure of CO2 (PCO2) according to Henry’s law of gas solubility, depending on the gas solubility, the atmospheric pressure, and P CO2 itself. The majority of CO2 is transported in the blood as bicarbonate. As CO2 diffuses nearly freely in red blood cells, it reacts with H2O to form carbonic acid (H2CO3). In turn, H2CO3 will dissociate to form both bicarbonate (HCO3−) and H+. Eventually, H+ will be buffered by hemoglobin, and HCO3− exits the red blood cell. A small proportion of CO2 is transported as carbamino compounds that are linked to proteins, particularly to hemoglobin.CO2, bicarbonate, and protein bounded CO2 varies between the arterial and venous compartments. In arterial blood, bicarbonate accounts for 90% of total CO2 content, while 5% is dissolved and 5% is bound to proteins. In venous blood, only 70% of the total CO2 content corresponds to bicarbonate, while 10% is dissolved, and a carbamino compound contributes 20%. The total content of CO2 (CCO2) in the blood under physiological conditions equals the dissolved CO2 + the bicarbonate (HCO3) + the CO2 linked to hemoglobin (R-NH2-CO2).The proportion of diluted CO2 (CCO2) is dependent on several variables and can be precisely calculated. According to the Douglas formula [2 could be determined using the content of CO2 in the plasma, the blood pH, and temperature:The content of CO formula , the CCO2 in the plasma are used:For the final calculation, the hemoglobin level, the saturation in oxygenation, and the total amount of CO2 gives the opportunity to appreciate the complexity of factors that are impacting the transport and content of CO2. However, despite its accuracy, this formula is extremely difficult to use at the bedside due to its computational complexity. Importantly, CO2 partial pressure (PCO2) is easier to obtain at the bedside, and a relationship exists between both CCO2 and PCO2 [2 = k × CCO2, where k is a constant. This relationship follows a curvilinear curve with a near-linear relationship only in physiological PCO2 [2 in place of CCO2 in multiple clinical studies and expert opinion reports [2 as the PCO2 will mostly divert significantly from the PCO2. The curvilinear relationship is directly impacted by the complex interaction of numerous variables such as the blood pH and temperature, the dissolved CO2, the CO2 bound to hemoglobin, and the CO2 as bicarbonate, as it is suggested by the multiple variables incorporated in the complete calculation of CCO2. The relationship between both CCO2 and pCO2 could be shifted by four factors: PO2, plasma pH and temperature, as well as hemoglobin levels. Those factors impact the k constant, with k increasing in case of a rise in PO2, acidosis, temperature, and hemoglobin level. Of special importance is the impact of oxygen on the content of CO2 through the Haldane effect. The Haldane effect describes the ability of hemoglobin to carry, at any PCO2, increased amounts of CO2 in the deoxygenated state compared to the oxygenated state [2, the CO2-carrying capacity increases so that the blood may remove the excess CO2. On the contrary, as blood enters the pulmonary circulation and binds O2, the CO2-carrying capacity decreases, thus facilitating CO2 removal from the lungs. In light of all the factors impacting the relationship between CCO2 and PCO2, we would argue for preferentially using CCO2 or, in case the PCO2 is used, it seems crucial that the clinicians understand the limitations of such approximation [The complete formula for the calculation of CCOand PCO2 ,32. Thiscal PCO2 ,32,33. T reports ,35,36,37ed state . Consequximation ,39,40.2 is slightly higher in the venous compartment as a result of aerobic production of CO2 in tissues and alveolar elimination, thus creating a CO2 gradient between the venous and the arterial compartments. This difference will also be present under anaerobic circumstances due to the non-aerobic production of CO2. The increase in CO2 on the venous side will create an obligatory difference between the arterial and the venous blood, which could be estimated using the Fick equation.Circulating CO2 (VCO2) could be described as follows:2 is the difference in CCO2 between the venous and arterial compartments (CvCO2-CaCO2).In accordance with the Fick principle, the production of CO2 and CCO2 show a near-linear relationship at physiological ranges. Consequently, PCO2 values may be regarded as surrogate measures for CCO2 at the bedside.As mentioned above, PCO2 with CCO2:A modified Fick equation can be obtained by substituting PCO2  diameter and the aortic velocity time integral . Nonethe2 and ΔCCO2 only depend on CO under stable VO2 conditions makes its use in the ICU setting a reliable way to estimate the adequacy of CO with respect to tissue metabolic demand [2 and CO has been studied in previous reports. A progressive decrease in ΔPCO2 in parallel to an increase in CO in patients receiving escalating doses of dobutamine has been described [2 remains stable under hypoxic conditions, and low DO2 provides a normal and stable CO [2 does not change in the case of cellular hypoxia [2 in tissues caused by the absence of sufficient blood flow but not hypoxia was responsible for the increase in ΔPCO2 in patients after cardiac arrest [2 and elevated ΔPCO2) from cellular hypoxia in the presence of normal CO  [2, ΔPCO2 might play an important role as a further easy-to-use bedside tool to monitor CO regardless of the presence of hypoxemia.The fact that ΔPCOc demand . The relescribed ,53. Moretable CO . It is i hypoxia ,56,57. Ic arrest . Clinicil ΔPCO2) ,59. Thus2 can be helpful in assessing global hemodynamics with some caveats, it is not suitable for the evaluation of microcirculatory imbalances. Indeed, ScVO2 may exert normal values in case of microcirculation derangements because of a lower oxygen extraction [2 regardless of CO [If ScVOtraction ,12,13. Iss of CO .2 under anaerobic circumstances. The excess CO2 will then diffuse across well-perfused capillaries, and the ΔCCO2 will increase. The association between abnormal ΔPCO2 with altered microcirculatory blood flow has been demonstrated in septic shock patients [2 should be regarded as a potential tool for the evaluation of microcirculatory perfusion abnormalities, even in the absence of low CO. Under such circumstances, the increase in CO might improve tissue perfusion [Hypo-perfused areas will accumulate COpatients ,62,63,64erfusion ,65,66,672 and ΔPCO2 are associated with patient mortality [2 and ΔPCO2 with CO, along with the detection of microcirculation anomalies, could be the main reasons for such findings. Higher ΔPCO2 levels are also associated with both post-operative complications after cardiac surgery and mortality in general ICU patients [2 might indicate microcirculatory derangements and predict patient mortality in adult patients on ECMO [2 and increased mortality in shocked ICU patients [2 plays no role as a marker of tissular hypoxia but rather as a marker of adequacy between CO2 production and CO. In fact, high-flow shocks should result in a decrease rather than an increase in ΔPCO2.In adult patients with septic shock, both ΔCCOortality ,65,66,68patients ,70,71,72 on ECMO . A recenpatients . Importa2, and ΔPCO2 as a marker of insufficient CO have been proposed [2 with a cut-off value of 6 mmHg (0.8 kPa). Higher values will mostly indicate that CO is not able to meet global metabolic demands. In case of shock, a high ΔPCO2 could prompt clinicians to increase CO (fluid bolus and/or inotropes). In the absence of shock, a high ΔPCO2 might indicate a state of high oxygen demand and CO2 production. A normal ΔPCO2 might also indicate that CO is correct, while other determinants of oxygen delivery  should possibly be improved in the presence of anaerobic metabolism (increased lactate and/or VCO2/VO2 ratio). Many of the available algorithms propose the use of both ScVO2 and ΔPCO2 to help clinicians to identify anemia, hypoxemia, or low CO as possible causes of tissue hypoxia. To our knowledge, though, none of those algorithms have been clinically validated.Several treatment algorithms based on the combined use of serum lactate, ScVOproposed ,31,32. M2 and CO measures [Studies in the pediatric population are scarce and showed promising but conflicting results. A recent pediatric study in children with septic shock failed to detect a clear association between higher ΔPCOmeasures .2 have been conducted in the CICU setting. A study from Furqan et al. suggests a possible association between higher ΔPCO2 and low ScVO2 after pediatric cardiac surgeries [2 was sometimes accompanied by increased ΔPCO2. Unfortunately, the association of normal ScVO2 and low ΔPCO2 with clinical outcomes was not explored.Most of the studies on ΔPCOurgeries . In this2 and unfavorable outcomes in the immediate post-operative period in children after cardiac surgery has been recently studied , might explain these conflicting results. Although encouraging, current literature on the relation between CO2-derived parameters and clinical outcomes in ICU is not yet conclusive. As ΔPCO2 is directly linked to the CO, a more immediate and precise outcome, such as the duration of inotrope/vasopressor support or the need for mechanical circulatory support, may be more suited.We found three studies looking at the possible association between increased ΔPCO studied  [35,77,7ic score . On the 2) and CO2 production (VCO2) are directly proportional to CO. Under aerobic steady-state conditions, the ratio between VO2 and VCO2 (VCO2/VO2 ratio) varies between 0.7 and 1, depending on the main metabolic substrate used for oxidative metabolism [2 should not exceed O2 availability; therefore, the ratio should not exceed one. However, under anaerobic conditions, during circulatory shock, both VO2 and VCO2 are globally reduced. However, due to buffering of cations (H+) by bicarbonate, a small production of CO2 remains [2 production” would result in a relative rise of VCO2 in comparison to VO2. As a result, under anaerobic metabolism and dysoxia, the VCO2/VO2 ratio will be higher than one [Oxygen consumption .ΔPCO2/VO2 ratio can identify anaerobic metabolism, and it has shown to be closely correlated with lactate levels, the usual dysoxia marker [2/VO2 ratio might represent a possible alternative to lactate levels in specific situations that are frequently encountered in the ICU setting, such as hyperglycemia or catecholamine-induced hyperlactatemia.The VCOa marker ,39. More2/VO2 ratio has been less studied than ΔCO2. The princeps study by Mekontso-Dessap et al., carried out nearly 20 years ago, showed the role of the VCO2/VO2 ratio as a mortality marker in adult septic shock [2/VO2 ratio was strongly associated with a worse outcome. Other reports described the link between the VCO2/VO2 ratio and patients’ outcome both in septic shock and after cardiac surgery. Interestingly, both Ospina-Tascon et al. and He et al. showed an association between the VCO2/VO2 ratio and outcome in shocked patients with normal ScVO2 [2 levels are within normal ranges, possibly signaling low O2 extraction and/or capillary perfusion disturbances [The VCOic shock . More reic shock . Interesal ScVO2 ,82. Thesurbances ,83. This2/VO2 ratio has also been described as a possible tool for the prediction of fluid responsiveness. In patients with a hypotensive episode, only those with an elevated VCO2/VO2 ratio showed a rapid increase in VO2 after the fluid challenge [The VCOhallenge ,84.2, several algorithms propose the use VCO2/VO2 ratio in the initial patient assessment as a sign of tissue dysoxia. As for lactates, an elevated VCO2/VO2 ratio > one indicates anaerobic metabolism and should prompt a complete hemodynamic assessment of the patient and the possible implementation of rapid therapeutic measures to restore aerobic metabolism. On the other hand, a VCO2/VO2 ratio < one could also point to hyperglycemia or adrenergic stimulation as possible alternative causes of elevated lactate levels. Several cut-off values have been proposed to predict unfavorable outcomes, varying from 1.2 to 1.6 [2, none of those algorithms has been validated in the clinical setting.As with the ΔCO2 to 1.6 ,37,85. U2/VO2 ratio in the pediatric population. Xu et al. studied the impact of elevated increased VCO2/VO2 ratio on acute kidney injury after pediatric cardiac surgery [2/VO2 ratio might represent a sign of anaerobic metabolism at the kidney level and indicate a possible kidney injury in CICU patients [2/VO2 ratio may possibly help detect patients at risk of end-organ lesions in the context of anaerobic metabolism.To the best of our knowledge, only one study looked at the VCO surgery . As bloopatients . Despite2 in CICU and PICU. Currently, reference values are derived from adult patients with septic shock. However, those values may differ significantly in children, especially in the cardiac population after a cardio-pulmonary bypass, where alterations of microcirculation may increase the ΔPCO2 value without macrohemodynamic disturbances. Our experience confirms current pediatric literature describing large ΔPCO2 regardless of clinical outcomes. Multicenter prospective cohort studies are also needed to better define the relationship between ΔPCO2.and cardiac output in the case of LCOS. The description and validation of the impact of CO2-derived parameters in patient management, both adult and pediatric patients, are highly needed. Whether the introduction of CO2-derived parameters into clinical algorithms may improve patients’ outcomes is unknown.Future studies are warranted to establish reference values of ΔPCO2-derived parameters such as ΔPCO2 and VCO2/VO2 ratio represent valuable markers of hemodynamic derangements from macrocirculation to microcirculation. Moreover, unlike traditional markers of cardiac output, they seem to be reliable in specific situations commonly encountered in the post-cardiac surgery setting, such as hyperglycemia and catecholamine use. Their integration with classical markers of hypoperfusion into treatment algorithms holds the promise of adding substantial information that might help refine the management of patients suffering from shock in the adult and in the pediatric population alike. Further studies are needed to clearly define the role of those attractive tools in guiding resuscitation in the clinical setting.Despite the many limitations and the lack of robust data, CO


Postoperative sore throat (POST) is a common postoperative complication after endotracheal tube removal. There are still no effective preventive methods for POST. The aim of this trial is to confirm whether maintaining intraoperative cuff pressure below the tracheal capillary perfusion pressure could effectively reduce the incidence of POST among patients undergoing gynecological laparoscopic surgery.This study is a single-center, randomized, parallel-controlled, superiority trial with a 1:1 allocation ratio. Sixty patients whose age is between 18 and 65 years and scheduled for gynecological laparoscopic surgery will be randomized to the cuff pressure measurement and adjustment (CPMA) group and the only cuff pressure measurement without adjustment group (control group). The primary endpoint is the incidence of sore throat at rest within 24 h after extubation. The secondary endpoints include the incidence of cough, the incidence of hoarseness, the incidence of postoperative nausea and vomiting (PONV), POST, and pain intensity within 24 h after extubation. Blocked randomization will be conducted with a computer-generated central randomization online service. The blind method will be applied to subjects, data collectors, outcome evaluators, and statisticians. Outcome assessments will be performed at 0 h and 24 h post-extubation.This randomized controlled study hypothesizes that cuff pressure is the primary influencing factor of POST. By continuous monitoring of endotracheal tube cuff pressure and maintaining it within the range of 18–22 mmHg compared with only continuous measurement without adjustment, it aims to prove that continuous measurement and adjustment of endotracheal tube cuff pressure could be effective in reducing the incidence of POST in gynecological laparoscopic surgery patients. The result of this study could be used as a reference for future multicenter studies to confirm the effect of cuff pressure on POST and provides a scientific theoretical basis for preventing POST to further support comfort medicine.Chinese Clinical Trial Registry ChiCTR2200064792. Registered on 18 October 2022. This protocol  was approved by the Ethics Committee of Beijing Chaoyang Hospital. As one of the problems frequently complained about by patients, postoperative sore throat (POST) is a common postoperative complication after extubation with an incidence of 14–62% . POST re2O (18–22 mmHg) after inflation, lower than the capillary perfusion pressure of the tracheal mucosa [2O [Some studies suggest that high cuff pressure of the endotracheal tube may be a vital contributing factor , 6. The l mucosa , 8. At pl mucosa . Most recosa [2O . Moreovecosa [2O –13 as a Cuff pressure measurement by the manometer can reduce the incidence of POST in patients scheduled for gynecological laparoscopic surgery . HoweverThe aim of this study is to confirm whether continuous measurement of endotracheal tube cuff pressure and maintaining it at the normal value (18–22 mmHg) compared with only continuous measurement without adjustment could effectively reduce the incidence of POST in patients undergoing gynecological laparoscopic surgery.This is a single-center, parallel-group, randomized controlled, superiority trial with a 1:1 allocation ratio. The time schedule of the protocol  classes I–II must voluntarily sign a written informed consent before the intervention.Patients scheduled for elective gynecological laparoscopic surgery under general anesthesia will be recruited. Participants with ages between 18 and 65 years, body mass index (BMI) of 18–30 kg/mPatients will not be eligible with one of the following criteria: preoperative cough, sore throat, or upper respiratory tract infection; preoperative nasogastric tube insertion; smoking history; history of nausea and vomiting; history of oropharynx and larynx surgery; or other conditions that will interfere with the benefits of patients in the trial identified by researchers.No preoperative medication will be used in all patients. After entering the operating room, patients will be routinely monitored for non-invasive arterial blood pressure, electrocardiogram, pulse oxygen saturation, end-tidal carbon dioxide, and then inhale oxygen through a mask. After peripheral venous catheterization, midazolam (0.02–0.05 mg/kg), sufentanil (0.2–0.5 μg/kg), propofol (2–3 mg/kg), and rocuronium (0.6–0.8 mg/kg) will be injected intravenously during induction of general anesthesia. The anesthesiologists with at least two years of experience will select polyvinyl chloride endotracheal tubes of 7.0 mm internal diameter for video laryngoscope-guided intubation. In the cuff pressure measurement and adjustment (CPMA) group, the anesthesiologist will connect the pressure transducer to the spring-loaded one-way valve of the pilot balloon through a three-way connector and then inflate or deflate the tube cuff with a syringe connected to a tee-junction to maintain 18–22 mmHg cuff pressure intraoperatively. In the control group, the tube cuff pressure will be adjusted by anesthesiologists’ experience with pilot balloon finger palpation before the operation and will not be adjusted during the operation but will be monitored blindly on the portable monitor which screen will be fully covered. The number of tracheal intubation attempts, cricoid compression, and cough during intubation will be recorded. After successful endotracheal intubation, volume-controlled ventilation will be performed with a tidal volume of 6–8 ml/kg, a respiratory rate of 12–18 breaths per minute, an inspiratory-to-expiratory ratio of 1:2, an inspired oxygen fraction of 80%, and a flow rate of 1–2 L/min to adjust end-expiratory carbon dioxide partial pressure to 35–45 mmHg. Total intravenous anesthesia will be maintained with propofol (4–6 mg/kg/h) and remifentanil (0.1–0.25 μg/kg/min). Additional rocuronium 10–20 mg and sufentanil 5–10 μg will be administered as needed during the operation. After the establishment of carbon dioxide pneumoperitoneum, the patients in both groups will be placed in the Trendelenburg position required for gynecological laparoscopic surgery. The pneumoperitoneum pressure will be kept at 14 mmHg. Hemodynamic changes will be monitored and recorded every 5 min during the operation. Operation time and endotracheal tube indwelling time will also be recorded. After the surgery, gentle suction of oropharyngeal secretions will be performed in both groups . The administration of intravenous muscle relaxant antagonist (neostigmine 40 μg/kg) will be determined based on the assessment of muscle strength recovery. Once the patient is fully awake, the tidal volume has been restored to normal, and sufficient oxygen saturation can be maintained, air will be withdrawn from the cuff, and the endotracheal tube will be removed. In addition, the number of coughs before extubation will be recorded. Both groups of subjects will receive postoperative pain control via an analgesic pump with sufentanil at a rate of 2 μg/h and a total dose of 100 μg. Sore throat at rest and its severity, cough, hoarseness, nausea and vomiting, and pain score will be recorded immediately after extubation (0 h after extubation) and within 24 h after extubation. The investigators will record conditions in which enrolled subjects are deemed unfit to proceed with the study due to the following reasons: occurrence of adverse events, including severe adverse events, and other circumstances identified by the researchers as unsuitable for further experimentation. To enhance participants’ adherence with the intervention measures, researchers will employ clear and comprehensible language to communicate with patients, conduct timely follow-ups, and engage in interactive discussions. The researchers will also record timely during the intervention and follow-up process to monitor the compliance of the subjects.The primary outcome is the incidence of sore throat at rest within 24 h after extubation. The total number of patients with sore throat at rest between two assessment time points (0 h and 24 h post-extubation) will be recorded.The secondary outcomes include the following: (1) the incidence of cough within 24 h after extubation; (2) the incidence of hoarseness within 24 h after extubation; (3) the incidence of PONV within 24 h after extubation; (4) the intensity of POST within 24 h after extubation graded on a 0–3 scale: 0 = no sore throat, 1 = mild sore throat (less pain than a cold), 2 = moderate sore throat (like a cold), and 3 = severe sore throat (more severe than a cold) –19; and α) of 0.025. In a randomized controlled study of gynecologic laparoscopic surgery [2O group (using the manometer) and 68.3% (41/60) in the control group . Based on this study of a similar surgery, we estimate the incidence of sore throat at rest within 24 h post-extubation is 32% in the CPMA group and 68% in the control group. Then, 54 participants should be needed according to the conditions mentioned above. Eventually, a total of 60 patients (30 in each group) will be recruited so as to allow for a 10% dropout rate. The sample size was calculated using tests for two proportions in the PASS software .The sample size estimation is based on the incidence of sore throat while resting within 24 h post-extubation. This superiority trial with a 1:1 allocation ratio will achieve 80% power (1 − β) and a one-sided significance level . After the data monitoring staff verifies the accuracy and completeness of the source document, the data entry personnel will establish the database with the EpiData software . For any subjects who drop out of or deviate from the trial for any reason, the reasons will be recorded as thoroughly as possible. Prompt and appropriate measures will be taken to address or treat their withdrawal, ensuring completion of follow-up and reporting of all observed outcomes. After logical range checks for data values, the database with independent double data entry will be locked and backed up.P < 0.05 for all statistical tests. The continuous variables will be expressed as a mean with standard deviation  or a median with interquartile range (skewed distribution). Student’s t test will be used to compare normally distributed continuous variables, and the Mann–Whitney U test will be used to compare non-normally distributed continuous variables. The categorical variables such as the incidence of sore throat, cough, hoarseness, and PONV within 24 h after extubation will be described as counts and percentages. Differences between the groups of these categorical variables will be compared with χ2 analysis or Fisher’s exact test. The missing data will be handled by multiple imputation.All data will be analyzed by the SPSS software . Both the intention-to-treat analysis and the per-protocol analysis will be performed for the primary outcome. Subgroup analyses will be performed based on the values of the incidence of cough, hoarseness, and PONV; the intensity of POST; and NRS for pain intensity within 24 h after extubation. A two-sided significance level will be set at Due to the short duration of this study and the minimal known safety risks, no formal data monitoring committee will be established. However, a trained auditor will monitor the progress of the study every month. The auditor must ensure that the clinical facilities at the research center will meet the requirements of the study and that the investigators will follow the protocol and accurately record the results of the study. For each inspection, the auditor will check the eCRF, the original documents, and the storage conditions of drugs and devices. The auditor will also ensure that each participant has signed informed consent.All adverse events, including serious adverse events, observed in the clinical trial will be recorded on the eCRF. The duration of the adverse event, its severity, its relationship with the study device, and its appropriate treatment will be recorded. The patients will be followed up until remission or recovery from adverse events.For modifications that do not affect the rights of the participants and the evaluation of trial results, exemption applications can be made by the principal investigator and submitted to the Ethics Committee of Beijing Chaoyang Hospital for record keeping. All other modifications to the trial protocol will require approval from the Beijing Chaoyang Hospital Ethics Committee.The researchers will introduce themselves and explain the purpose, procedures, and potential risks and benefits of the trial to the potential participants. The researchers will obtain participants’ written consent by providing consent forms. These forms will outline the key points of the trial and will be signed by the participants.Strict confidentiality measures will be implemented throughout the trial. Personal information collected from potential and enrolled participants will be treated as sensitive and confidential. It will be stored securely, with access limited to authorized personnel only.The final trial dataset will typically have restricted access and will be available to authorized individuals. The principal investigator and members of the study team directly involved in the trial will have access to the final trial dataset. These individuals will be responsible for analyzing and interpreting the data for research purposes.The results will be disseminated in a peer-reviewed journal and at academic conferences.Authorship eligibility guidelines will be established to ensure transparency and fairness in assigning authorship for clinical trial reports. The authors should have made substantial contributions to the design, conduct, interpretation, and reporting of the clinical trial. Merely providing general support or administrative assistance will not be typically considered sufficient for authorship. Before publicly providing the full protocol, participant-level dataset, and statistical code, we will ensure that the data is appropriately processed and de-identified to protect the privacy and data security of the participants.POST may be disappearing within 48 h in most cases, but it is not conducive to the postoperative comfort of patients. If it is not taken seriously, patients who have retained the endotracheal tube for a long time (such as patients in intensive care units) may have more serious complications than POST, such as tracheomalacia, laryngotracheal stenosis, and tracheoesophageal fistula. This is a parallel-group, randomized controlled, superiority trial with a robust methodology to confirm whether maintaining intraoperative endotracheal tube cuff pressure below the tracheal capillary perfusion pressure could effectively reduce the incidence of POST in patients undergoing gynecological laparoscopic surgery. The method of using a pressure transducer to measure cuff pressure continuously is more convenient and accurate than a cuff pressure manometer. This trial’s methodological strengths include Internet central randomization, computer-generated assignment, allocation concealment, blinded assessment, and appropriate estimation of sample size. Considering this is a single-center study, the conclusion might not be generalizable. The result of this study could be used as a reference for future multicenter studies to confirm the effect of cuff pressure on POST and provides a scientific theoretical basis for preventing POST to further support comfort medicine.This protocol  was approved by the Ethics Committee of Beijing Chaoyang Hospital and registered at the Chinese Clinical Trial Registry on 18 October 2022 (registration number ChiCTR2200064792). The recruitment started on 21 November 2022. When the manuscript is submitted, the enrollment is still in progress. The recruitment will be completed approximately in May 2023.


Nonsteroidal mineralocorticoid receptor antagonists (MRAs) present a promising therapeutic option in cardiorenal diseases, mitigating the limitations of steroidal MRAs. Finerenone, a third-generation nonsteroidal MRA, has demonstrated beneficial effects in heart failure (HF) and chronic kidney disease (CKD). Clinical trials, including FIDELIO-DKD and FIGARO-DKD, revealed finerenone’s efficacy in improving kidney and cardiovascular (CV) outcomes. Patients with CKD and type 2 diabetes (T2DM) on finerenone experienced reduced rates of cardiovascular events, including hospitalization for HF. However, these trials excluded symptomatic HF patients, focusing on asymptomatic or early-stage HF. The ongoing FINEARTS-HF trial evaluates finerenone in HF with preserved ejection fraction (HFpEF). Additionally, studies exploring finerenone and sodium-glucose cotransporter 2 (SGLT2) inhibitors’ (Empagliflozin) combination effects in CKD and T2DM (CONFIDENCE) and the selective MR modulator AZD9977 with another SGLT2 inhibitor (dapagliflozin) in HF and CKD (MIRACLE) aim to expand treatment options. While SGLT-2 inhibitors were shown to reduce hyperkalemia risk in FIDELIO-DKD and potentially lower new-onset HF incidence in FIGARO-DKD, further research is essential. So far, the evidence for the beneficial effect of finerenone in the spectrum of cardiorenal diseases is based only on the results of studies conducted in patients with T2DM, and clinical trials of finerenone in patients with nondiabetic kidney disease are ongoing. Nonsteroidal MRAs hold significant potential as pivotal treatment targets across the cardiorenal disease spectrum. This review will focus on the effects of finerenone on cardiorenal disease. Steroidal mineralocorticoid receptor (MR) antagonists (MRAs), namely spironolactone and eplerenone, elicit antihypertensive effects and ameliorate the progression of chronic kidney disease (CKD). Nevertheless, their clinical application is limited by their side effects, including hyperkalemia, gynecomastia, impotence, and amenorrhea . TherefoSpironolactone was the first MRA to undergo investigation for use in HF ,3. Epler2 of body surface area [Aldosterone predominantly exerts its effects in the distal tubule of the nephron, promoting the enhanced reabsorption of water and sodium, which in turn leads to extracellular fluid expansion. Notably, extensive research has compellingly demonstrated that beyond its regulatory role in body fluid and electrolyte balance, aldosterone and its interaction with the MRs profoundly impacts diverse cellular functions, culminating in inflammation and tissue fibrosis. Furthermore, it is noteworthy that aldosterone production may also occur locally in peripheral tissues . Evidencace area . MR overace area .Many classes of drugs are used in medical therapy for HF such as diuretics, beta blockers, RAAS blockade, SGLT2 inhibitor, nitrates and MRAs, many of which are also used for the prevention of CKD progression. Diabetes is the most common cause of CKD in the USA. Despite guideline-directed therapy, the risk of renal failure is high in diabetics. The renoprotective effect of RAAS blockers is well known, but 40% of patients experience “aldosterone escape” where serum aldosterone rises to pretreatment levels after many weeks of RAAS blockade . SGLT2 i2) over 30 days [In 2021, finerenone received FDA approval for use in patients with CKD associated with T2DM. Early indications of finerenone’s beneficial impact on cardiac function in HF were observed in the phase II Mineralocorticoid Receptor Antagonist Tolerability Study (ARTS) trial , a safet 30 days . Notably 30 days . Overall 30 days .The ARTS-HF trial was a randomized double-blind study that compared the effects of finerenone (at doses up to 20 mg/day) and eplerenone (at doses ranging from 25 mg/day to 50 mg/day) in patients diagnosed with both T2DM and CKD, who were experiencing worsening HFrEF within 7 days of hospitalization. Patients treated with finerenone demonstrated good tolerability, and a comparable percentage of patients on eplerenone experienced a reduction of 30% or more in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels. The safety profile of finerenone was similar to that of eplerenone .A meta-analysis of the ARTS, ARTS- HF, and ARTS- HF Japan trials by Pei et al.  showed t2 with diabetic retinopathy or a UACR of 300–5000 mg/g and an eGFR of 25–75 mL/min/1.73 m2 [The successful outcomes observed in the ARTS series paved the way for two groundbreaking phase III trials: “Finerenone in reducing kidney failure and disease progression in diabetic kidney disease” (FIDELIO-DKD) and “Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease” (FIGARO-DKD). In the FIDELIO-DKD trial, patients were randomized in a double-blind manner to receive finerenone at daily doses of 10 or 20 mg or a placebo. The study enrolled patients with either a UACR of 30–300 mg/g and an eGFR of 25–60 mL/min/1.73 m/1.73 m2 .p = 0.03) compared to those on placebo [The FIDELIO-DKD trial was pivotal in obtaining FDA approval for finerenone and provided essential insights into the appropriate patient population for its use and the expected benefit-to-risk ratio. The study demonstrated that finerenone improved kidney outcomes in patients with predominantly stage 3 or 4 CKD and severely elevated albuminuria, combined with T2DM, a population at high risk for kidney-related complications . Additio placebo , mainly In the FIGARO-DKD trial, despite excluding patients with symptomatic HF and reduced ejection fraction, hospitalization for HF emerged as a significant driver of the primary outcome . ConsideIn both trials, the occurrence of the composite kidney outcome (reduction in the eGFR of at least 57% from baseline (more sensitive compared to an eGFR decrease of ≥40%) was lower in the finerenone group . PatientA prespecified pooled analysis, known as FIDELITY, was conducted on data from both phase 3 trials  that demonstrated that finerenone treatment had beneficial effects on both CV and kidney outcomes, showing improvements across the various stages of CKD severity ,37.Steroidal MRAs have been proven to be advantageous in CKD by effectively mitigating endothelial dysfunction and oxidative stress, thereby leading to a reduction in the degree of albuminuria .Finerenone exhibited a comparable impact on nephropathy, resulting in a reduction in albuminuria and an improvement in eGFR. These beneficial effects were attributed to increased nitric oxide concentrations and reduced oxidative stress ,40.A recent study conducted on ZSF1 rats, an established preclinical model of HFpEF in male hypertensive and diabetic rats, revealed that finerenone treatment (at a dose of 10 mg/kg/day for 12 weeks) resulted in reduced kidney hypertrophy and cardiac fibrosis, while also improving cardiac diastolic function and perfusion . FinerenCV and kidney disease outcomes associated with finerenone have already been extensively studied in patients with T2DM and CKD. The ongoing FIND-CKD study  is a phaThere exists compelling evidence supporting the use of steroidal MRAs in HFrEF, leading to reduced morbidity and mortality in affected patients. Nonetheless, this notable efficacy is accompanied by an increased risk of hyperkalemia, necessitating meticulous monitoring. In contrast, the evidence for MRA use in HFpEF is currently less conclusive.2), 40 mg finerenone (for those with eGFR > 60 mL/min/1.73 m2), or a placebo. The study aims to evaluate the impact of finerenone on CV death and HF events [The ongoing FINEARTS-HF study NCT04435626) is designed to assess the efficacy and safety of finerenone in patients with HF and left ventricular ejection fraction greater or equal to 40% (HFpEF with or without T2DM). Participants will be randomly assigned to receive either 20 mg finerenone  is evaluating the efficacy, safety, and tolerability of the selective MR modulator AZD9977 along with the SGLT-2 inhibitor dapagliflozin in patients with HF (LVEF < 60%) and CKD. Participants with HF and CKD (eGFR ≥ 20 to ≤60 mL/min/1.73 m2) will be treated with different doses of AZD9977 in combination with dapagliflozin (10 mg) or dapagliflozin (10 mg) alone [The ongoing phase 2 MIRACLE study  is a parallel-group treatment, phase II, double-blind, and three-arms study designed to investigate the combination effect of finerenone and empagliflozin in participants with CKD and T2DM using a UACR endpoint. The study will compare the effect of the combination of finerenone and empagliflozin with either drug administered alone on the relative changes from baseline in UACR at 180 days [The CONFIDENCE trial  have been shown to reduce albuminuria to normal levels if added to the regimen in patients already receiving therapy with RAAS inhibition drugs .In conclusion, nonsteroidal mineralocorticoid receptor antagonists (MRAs) represent a promising advancement in the management of cardiorenal diseases. Finerenone, the first FDA-approved nonsteroidal MRA, has shown efficacy in HF and CKD, with significant improvements in kidney and CV outcomes. Ongoing trials, such as FINEARTS-HF, MIRACLE, and CONFIDENCE, explore further treatment possibilities. SGLT-2 inhibitors may potentially complement the benefits of finerenone, warranting future investigations. These groundbreaking agents hold potential as critical therapeutic options in the cardiorenal disease spectrum, addressing the limitations of steroidal MRAs and improving patient outcomes in this complex and challenging patient population.


Background: The advantages of mechanical assistance during ventricular tachycardia (VT) ablation have not been clinically demonstrated. We propose and discuss a technique, set up by us, that makes use of minimally invasive extra-corporeal circulation (MiECC) type III associated with a venous reservoir system, which allows complete cardiac flow support and blood oxygenation as well as hemodynamic stability during long-lasting procedures. Methods: We present a retrospective case series of ten patients with valvular heart disease and unresponsive Ventricular Tachycardia (VT) who underwent VT ablation with MiECC support. The mean age of the patients was 72 ± 8 years and the left ventricular ejection fraction was 36 ± 12%. All patients underwent a clinical evaluation to identify the cause of VT unresponsiveness . Results: A total of 140 min, the following parameters were evaluated and recorded for 140 min. Central venous pressure (CVP) was used to evaluate excess volume. During the first 5 min, the mean was 15 mmHg, with a pump flow of 1.5 L/min and a mean systemic arterial pressure of 100 mmHg while setting up the circulation support. Following drainage in a volumetric bag of 1 L of blood, CVP was reduced to a value of 5 mmHg with a flow rate of 5 L/min and a mean systemic arterial pressure of 65 mmHg. In the case of small and low-weight patients our “1 L protocol” can be modified. Conclusions: In this preliminary retrospective case series, the MiECC type III system may represent the ideal support system during VT ablation, and further studies are needed to support this preliminary report. Catheter ablation is an elective therapeutic strategy for the treatment of ventricular tachycardia (VT) in structural heart diseases with and without comorbidities . ClinicaHistorically, passive intra-aortic balloon counter pulsation has been the most frequently used hemodynamic support has been the passive intra-aortic balloon counter pulsation . HoweverMore recently, extracorporeal membrane oxygenation (ECMO) has emerged as a valid alternative support method in clinical practice . In contThis pilot study aimed to report our experience with endocardial catheter ablation of VT supported by a ventricular assistance system with the possibility of simultaneously oxygenating the blood and managing the blood volume. We describe a special use of MiECC type III, which preserves the main principles of the minimally invasive extra-corporeal technology, such as a closed extra-corporeal circulation circuit, biologically inert blood contact surfaces, and reduced priming volume while maintaining the equilibrium and the ability to manage excessive volume in a closed extra-corporeal circuit .We present a case series of ten patients with valvular heart disease and unresponsive VT who underwent VT ablation with MiECC support. The mean age of the patients was 72 ± 8 years and the left ventricular ejection fraction was 36 ± 12% . The patient characteristics are shown in More specifically, we modified the classical ECMO circuit by adding a volumetric bag for blood volume management  and 2. CThe internal research board of our institution, Anthea Hospital, approved this study (Prot. 01/2020), and all patients provided their consent for the procedure and the use of data.In our practice, a double team experienced in ablation and MiECC performed these procedures . The “keIn the first 3 min, volume overload causes flow reduction and left ventricular afterload excess. Since afterload excess might overload the left ventricle (given the presence of aortic regurgitation), to reduce wall tension, excess fluid was actively drained from the outlet of the oxygenator in the volumetric bag .Central venous pressure (CVP) was used to evaluate excess volume. For example, during the first 5 min, the mean was 15 mmHg, with a pump flow of 1.5 L/min and a mean systemic arterial pressure of 100 mmHg while setting up the circulation support. Following drainage in a volumetric bag of 1 L of blood, CVP was reduced to a value of 5 mmHg with a flow rate of 5 L/min and a mean systemic arterial pressure of 65 mmHg. In the case of small and low-weight patients our “1 L protocol” can be modified.The volume was subsequently distributed gradually in the venous line near the centrifugal pump during the procedure using the antihypertensive drug Ebrantil  that allowed immediate volume redistribution without excessive hypotension [Volume management in MiECC type III, in VT ablation procedures with and without the presence of heart valve disease, with mean Left ventricular ejection fraction (%) 36 ± 12 allowed in the procedures a better drainage from a central venous pressure (CVP) of 15 ± 4 to a CVP of 4 ± 3, an improvement in relation to flow rate of the pump from 1.5 ± 0.6 L/min to 5 ± 0.7 L/min, in relation to mean arterial pressure (MAP) from 100 ± 18 to 65 ± 13 mmHg, with an mean hemoglobin value of 9.78 ± 1.19 g/dL Continuous data are expressed as mean ± standard deviation or median with interquartile range, and categorical data as percentages. Cumulative survival was evaluated using the Kaplan–Meier method.Based on our experience, the insertion of a soft-shell venous reservoir in the MiECC type III system improved volume management in patients with large surfaces and volumes, reduced afterload , and impThe circuits that we used in this context for MiECC are usually employed for conventional extracorporeal circulation with a polypropylene oxygenator (maximum duration of 6 h). This avoids the use of devices  specifically designed for ECMO and for prolonged use . VT ablation is a short-term procedure, and conventional materials can be used with subsequent economic advantages. In patients with a high bleeding risk, it may be convenient to use “prolonged” ECMO circuits, which require a lower activated clotting time (ACT) to ensure less bleeding risk. However, in the case of ACT >400 s (and/or <400 s), concomitantly with inguinal preparation for contralateral groin cannulation, we deemed it necessary to place the introducers for the subsequent mapping and ablation catheters before heparin administration to facilitate puncture and reduce the risk of hematoma.Another advantage of our modified MiECC system is the presence of a heat exchanger that heats the patient’s blood as the ECMO system. This system, which maintains the patient’s temperature despite the prolonged procedure not only facilitates hemodynamic and coagulation stability but also allows direct patient extubation soon after the end of the procedure, so that the patient does not need to stay in an intensive care unit.We agree with Virk et al.  that thead hoc organization is required for the proposed strategy .It is also worth noting that, in contrast to Impella, an systematic organization, in addition to a more invasive procedure than the Impella device.In summary, the MiECC III system has the advantages of allowing patient oxygenation and facilitating volume management compared with ECMO. However, the MiECC III system requires expertise and To the best of our knowledge, our experience is the first study to describe the successful application of the MiECC type III system during VT ablation.In conclusion, in this preliminary retrospective case series, given the aforementioned aspects, we believe that the MiECC type III system may represent an ideal support system during VT ablation. At present, our experience is still limited and should be regarded as a “how to do it” description and a “pilot.” Well-designed randomized trials are needed to support the use of these systems during VT ablation, and we suggest the adoption of only MiECC support to demonstrate a clinical advantage in patients receiving hemodynamic support compared to those without support.


Sickle cell disease is the most common inherited blood disorder in humans and constitutes a major public health burden. It is a multisystemic condition with long-term renal complications. Early detection of sickle cell nephropathy and initiation of appropriate interventions are associated with improved survival and quality of life. This study aimed to compare the cystatin C-derived estimated glomerular filtration rate (GFR) of the study groups and also, to correlate the clinical features of chronic kidney disease (CKD) with decreased GFR in children with sickle cell anaemia (SCA).This hospital-based cross-sectional analytic study recruited 86 SCA subjects in steady-state and 86 age and sex-matched healthy HbAA controls aged 1–14 years who attended the Paediatric Haematology and Outpatient clinics of Federal Medical Centre Bida over six months. Data were collected using a semi-structured questionnaire, and participants’ length/height, weight, and blood pressure were measured using standard procedures. Blood samples were drawn for serum cystatin C assay via the sandwich enzyme-linked immunosorbent assay (ELISA) technique. Filler’s equation was used to calculate the glomerular filtration rate.2 vs. 106 ± 24mL/min/1.73m2 for the SCA and control groups, respectively (p = 0.017). The prevalence of supernormal GFR (i.e. GFR > 140mL/min/1.73m2) and decreased GFR (i.e. GFR < 90mL/min/1.73m2) was 19.8% and 22.1%, respectively, in children with SCA. There was no significant association between the age at diagnosis of SCA, blood transfusions, blood pressure, packed cell volume and presence of peripheral oedema with decreased GFR in the study subjects.There was a significant difference in the mean cystatin C-derived GFR between the two groups, i.e. 116 ± 30mL/min/1.73mSupernormal GFR is common in children with SCA and there is no significant association between clinical features of CKD with decreased GFR. Regular evaluation of renal function is, however, recommended in children with SCA for early detection and treatment of renal complications in order to halt the progression to end-stage kidney disease (ESKD). Sickle cell disease (SCD) is the most common inherited blood disorder in humans and was originally restricted to people occupying malaria-endemic regions of the world , 2. Due Sickle cell disease is prevalent in the tropics with the largest burden in sub-Saharan African countries of Nigeria and the Democratic Republic of Congo . More thSickle cell anaemia is a multisystemic illness with manifestations of acute illness and progressive organ damage due to vascular obstruction from sickled red cells. The kidney is affected in several ways  and is a common cause of morbidity and mortality. The absence of a comprehensive paediatric renal registry in most sub-Saharan African countries suggests that the true burden of kidney disease is largely unknown. Nevertheless, it is said to account for 16–18% of mortality among patients with SCD . FurtherSickle cell nephropathy manifests during early childhood. As such, there has been a rising interest in its prevention, detection and treatment. The lack of neonatal screening programmes in most African settings has caused significant delays in SCA diagnoses. Serum cystatin C is a highly sensitive renal biomarker that is influenced less by demographic variables such as age, sex and muscle mass , 9. UnliThis was a hospital-based, cross-sectional analytic study.0 North, longitude 6.020 East and 151 m above sea level. The study participants were recruited over six months, i.e. from October 2019 to March 2020, and blood samples were analysed for serum cystatin C assay at the chemical pathology laboratory of the institution.This study took place in the Paediatric Haematology and Outpatient clinics of the Federal Medical Centre Bida, North-Central Nigeria. Bida, an ancient town of the Nupe kingdom, is situated at latitude 9.08The study participants consisted of children with SCA and their age and sex-matched HbAA control age range of 1–14 years via a one-to-one pairing system. Children with SCA were selected based on the documented result of haemoglobin electrophoresis from the Paediatric Haematology Clinic. The controls were children on follow-up visits at the paediatric medical/surgical outpatient clinics discharged from the hospital for ailments such as malaria, pneumonia, asthma, cerebral palsy and minor surgical procedures. Patients who had previously been diagnosed with kidney disease, cardiac disease, HIV/AIDS, or those on systemic steroids were excluded from participation. The participants were selected by purposive sampling and enrolled consecutively in the study until each group’s desired sample size was achieved.The study sample size of 172 participants comprised 86 children with SCA in steady-state  and 86 healthy age- and sex-matched HbAA controls. This was achieved using a standard formula for comparing two independent group means and setting the study power at 90%. Data on eGFR in children with SCA from a published study were used in the calculation to derive our sample size .Relevant sociodemographic and clinical data were collected using a semi-structured questionnaire. The participants’ length/height, weight, and blood pressure were measured using standard procedures. Whereas the participants’ blood pressure was interpreted according to the updated American Academy of Pediatrics Clinical Practice Guidelines for Screening and Management of High Blood Pressure in Children and Adolescents , the bodBlood was drawn from a venepuncture site using an aseptic technique. The haemoglobin phenotype of the participants was ascertained using cellulose acetate paper electrophoresis at a pH of 8.6. Two millilitres of blood were emptied into a plain bottle, left to clot at room temperature, and then centrifuged at 1000 rpm for 15 min. The resultant serum was transferred into a separate plain bottle and stored at -80 °C for the cystatin C assay.2 was calculated using a cystatin C-based equation by Filler and Lapage as its diagnostic performance was validated in children aged 1–18 years and is represented thus [2 was used to define decreased GFR in SCA subjects because the standard definition of CKD (i.e. GFR < 60mL/min/1.73m2) may represent a greater decline from “normal” kidney function in SCA patients when compared to the general population.Quantitative analysis of cystatin C was carried out via the sandwich enzyme-linked immunosorbent assay (ELISA) principle. Two 96-well kits manufactured by Elabscience® Biotechnology Inc., Texas, one each for the two groups of participants, were used in this study. The ensuing product of the sandwich was read spectrophotometrically at 450 nm using a TC-96 micro-well reader . The estimated glomerular filtration rate (eGFR) in mL/minute/1.73mted thus : Log, we calculated the uncertainty coefficient and correlation ratio between variables as well as built models to predict decreased eGFR from clinical and demographic data. A p value of ≤ 0.05 was considered statistically significant.The data obtained were verified and statistical analysis was carried out using the Statistical Package for Social Sciences version 28.0 software . Categorical variables are presented in tables. Upon ascertainment of data normality, the means of continuous variables were compared using an The sociodemographic distribution, medical history and physical examination findings of the study participants are depicted in Table The mean serum cystatin C levels for the SCA and control groups were 0.872 ± 0.3  and 0.922 ± 0.2 , respectively. The mean eGFR of the participants based on age categories is shown in Table 2, approximately one-fifth of them had values greater than 140mL/min/1.73m2 as shown in Table While 22.1% of children with SCA had eGFR levels below 90mL/min/1.73m2. Additionally, a child on hydroxyurea had a low eGFR  and other demographic and clinical variables tested. This is shown in the first column of Fig. There was no significant association (uncertainty coefficient) between eGRF  at 78%, area under the curve (AUC) at 50%, recall at 100% and harmonic mean (F1) at 87.5%. The QDA confusion matrix is shown in Fig. 2 in children with SCA, was comparable among the study participants but was more common among children in the control group. Furthermore, factors such as the steady-state PCV, blood pressure and the occurrence of peripheral oedema in children with SCA are not associated with decreased GFR.The glomerular filtration rate (GFR) is a dependable indicator of renal function, as it is widely regarded as the best overall index both in health and disease . This stet al [Our finding of a significant difference in eGFR among the study groups in this study is comparable to previous studies using different renal biomarkers , 18. Thiet al . Generalet al , 26.2 and 60mL/min/1.73m2 respectively. Using a similar cutoff value, this value of 22.1% in SCA children is similar to that reported by Ajite et al. in Nigeria [2 but with evidence of kidney damage  given a large prevalence of stage I CKD. Although derived for use in children with CKD, the Schwartz method of GFR estimation is known to overestimate GFR [The prevalence of “decreased GFR” in this study was 22.1% and 1.2% for the SCA and HbAA groups, using a cutoff of 90mL/min/1.73m Nigeria . McPhers Nigeria . Similar Nigeria . In contmate GFR . The biamate GFR .Clinical manifestations of CKD include hypertension, worsening anaemia and peripheral oedema. The measured systolic and diastolic blood pressures in this current study were significantly lower in children with SCA relative to the controls. This is similar to most previous work on the subject, with only a few documenting hypertension among their participants , 32. TheOur study found elevated blood pressure in 5.8% of the SCA group which was in discordance with the 16.7% reported by Bodas et al. . Given tAnaemia is a well-known occurrence in people with SCA. Despite the majority of our participants having mild-to-moderate anaemia, this neither predicts nor correlates with a “decreased GFR”. In the same vein, peripheral oedema does not predict a decreased GFR among our participants. The occurrence of peripheral oedema in SCA is a function of the degree of glomerular damage, and its emergence appears to be similar to the development of hypertension indicating that proteinuria causing oedema is a feature of progressive renal damage .Our study recruited SCA children as young as 1 year of age as only a few studies have involved this category of patients. This allowed us to investigate their eGFR characteristics relative to those of grown-up children. We also recruited a one-to-one age-appropriately paired control group to counter possible selection bias that could have untoward effects on the conclusion of the study.In addition to the cost and scarce availability of cystatin C test kits in the country, our participants would have been better followed up at 3 months after enrollment for adequate and appropriate diagnosis of CKD. This study did not consider urine examination in addition to the serum cystatin C assay and could constitute another limitation. This would, however, serve as a template for further studies.Hyperfiltration manifesting as supernormal GFR is common among children with SCA. Likewise, the prevalence of decreased GFR is high. Clinical features such as age at diagnosis, frequency of crises, haematuria, blood pressure, and peripheral oedema were marginally associated with decrease GFR in children with SCA. It is, however, pertinent that the presence of any of these features should raise suspicion for further renal evaluation for early diagnosis of renal insufficiency.