IPO, mean of first 4 values obtained in the intensive care unit, readings at 2-hour intervals) was correlated directly with PAP/SAP registered in the surgical room just after cardiopulmonary bypass . For the entire cohort, circulating levels of 15 inflammatory markers changed after surgery. Compared with patients with PAP/SAPIPO ≤ 0.40 (n = 22), those above this level (n = 18) had increased pre- and postoperative serum levels of granulocyte colony-stimulating factor (p = 0.040), interleukin-1 receptor antagonist (p = 0.020), interleukin-6 (p = 0.003), and interleukin-21 (p = 0.047) (panel for 36 human cytokines) and increased mean platelet volume (p = 0.018). Using logistic regression analysis, a PAP/SAPIPO > 0.40 and a heightened immediate postoperative serum level of macrophage migration inhibitory factor  were shown to be predictive of significant postoperative cardiopulmonary events , and 3.29 (1.38–7.88)). Thus, the early postoperative behavior of the pulmonary circulation and systemic inflammatory response are closely related and can be used to predict outcomes in this population.There is scarce information about the relationships between postoperative pulmonary hemodynamics, inflammation, and outcomes in pediatric patients with congenital cardiac communications undergoing surgery. We prospectively studied 40 patients aged 11 (8–17) months (median with interquartile range) with a preoperative mean pulmonary arterial pressure of 48 (34–54) mmHg who were considered to be at risk for postoperative pulmonary hypertension. The immediate postoperative pulmonary/systemic mean arterial pressure ratio (PAP/SAP Pulmonary hypertension is an important factor influencing the outcomes following pediatric cardiac surgery. Young patients with unrestrictive congenital cardiac communications have altered pulmonary hemodynamics associated with functional and structural changes in the pulmonary vascular bed. These abnormalities pose a risk for immediate postoperative clinical instability and residual pulmonary hypertension long after the repair of cardiac lesions, particularly in individuals not treated in a timely fashion (early in life). A number of perioperative factors contribute to postoperative systemic and pulmonary vascular tone instability, leading to hemodynamic disturbances. Cardiopulmonary bypass (CPB) with altered flow conditions, tissue ischemia and reperfusion, hypothermia, and the use of blood products or protamine elicit a systemic inflammatory response . SuperimIn more privileged communities, the contemporary incidence of postoperative pulmonary hypertensive crises is probably less than 1% . There hThis study was planned to investigate the relationships between hemodynamics, postoperative clinical events, and inflammatory profiles in a prospective cohort of young pediatric patients undergoing surgery for congenital heart disease who were considered to be at risk for postoperative pulmonary hypertension. This assumption of risk was based on the fact that they represented the population of a tertiary referral center with a high prevalence of Down syndrome and had unrestrictive cardiac communications with elevated pulmonary artery pressure, as suggested by preoperative echocardiographic evaluation. Postoperative hemodynamics was evaluated by continuously registering pulmonary and systemic arterial pressures for 2.5 days. We adopted a more flexible definition of postoperative cardiopulmonary events by including episodes that would not be interpreted as typical pulmonary hypertensive crises. However, we disregarded transient and isolated elevations in pulmonary arterial pressure. Inflammatory profiles were characterized by measuring the circulating levels of several inflammatory markers preoperatively and in the early postoperative period.o. 2.068.696).This single-center study was performed at the Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil. Patients were consecutively enrolled from November 2016 to October 2018 based on the following criteria: age 1 month to 3 years; presence of unrestrictive cardiac communications, i.e., with a diameter of the posttricuspid communication greater than 50% of the aortic annulus diameter on transthoracic echocardiography; absence of pulmonary stenosis; hearts with biventricular physiology; clinical features suggestive of at least moderately elevated pulmonary arterial pressure; absence of extracardiac syndromes other than Down syndrome; and absence of any signs of ongoing or recent inflammatory or infectious diseases. In this study, patients were assigned to cardiac surgery essentially on the basis of noninvasive elevation. Patients with peripheral oxygen saturation lower than 85% and significant right-to-left shunting across the cardiac septal defects, suggesting the presence of advanced pulmonary vasculopathy, were not included. Healthy pediatric subjects with an age as close as possible to the age range of the patients were recruited from the same geographic area and entered the study as controls for the laboratory  tests. This group was also made up of individuals with Down syndrome. Informed consent signed by family members was necessary for inclusion in all instances. The study protocol was approved by the Institutional Scientific and Ethics Committee  + 2 mmHg . The pulIPO), corresponding to the first 6 hours of postoperative care. This parameter was used to characterize hemodynamic groups.Postoperatively, patients were kept under analgesia/sedation according to institutional protocols. In most instances, fentanyl, midazolam, and ketamine were used singly or in combination. Milrinone, epinephrine, and norepinephrine were used as inotropic/vasoactive agents. Inhaled nitric oxide (10–20 ppm) was started in the operating room immediately after CPB termination and was maintained throughout the entire period of mechanical ventilation. Pulmonary and systemic arterial pressures were measured directly in the operating room and by using indwelling catheters in the postoperative care unit. Intraoperatively, pressures were recorded before and after CPB. Postoperatively, readings were taken at 2-hour intervals (12 times a day) for 2.5 days. Pulmonary and systemic arterial pressures were computed, and pressure curves were constructed. The pulmonary/systemic mean arterial pressure ratio (PAP/SAP) was calculated. Immediate postoperative pulmonary hemodynamics was defined as the mean of the first 4 values  with a decline in systemic pressure (≥20%) and oxygen desaturation (<90%) to more severe hypoxemia and hypotension requiring manual ventilation and eventually cardiorespiratory resuscitation. In some instances, pulmonary arterial pressure was not seriously elevated at the onset of clinical instability . Rather, systemic hypotension was the dominant feature requiring changes in the doses of vasoactive-inotropic drugs. In the study, these disturbances are referred to as significant cardiopulmonary events (SCAPEs). Some episodes were prolonged  and/or recurrent. Importantly, transient elevations of pulmonary pressure, even to suprasystemic levels, that were rapidly reversed by manual ventilation were not categorized as SCAPES. Interpretations were made independently by 3 physicians . Patients whose systemic arterial pressure stabilized upon recovery from SCAPEs were started on sildenafil  and kept on it until nitric oxide discontinuation and weaning from mechanical ventilation or for the rest of their hospital stay.α); human CC chemokine I-309 (I-309); intercellular adhesion molecule-1 (ICAM-1); interferon gamma (IFN-γ); interleukins (IL) 1 alpha, 1 beta, 2, 4, 5, 6, 8, 10, 12, 13, 16, 17, 17E, 18, 21, 27, and 32 alpha; interleukin-1 receptor antagonist (IL-1RA); interferon gamma-induced protein-10 (IP-10); interferon-inducible T cell alpha chemoattractant (I-TAC); monocyte chemoattractant protein-1 (MCP-1); macrophage migration inhibitory factor (MIF); macrophage inflammatory protein-1 alpha/beta (MIP-1α/β); regulated on activation, normal T cell expressed and secreted (RANTES); plasminogen activator inhibitor-1 (Serpin E1); stromal cell-derived factor-1 (SDF-1); tumor necrosis factor alpha (TNF-α); and soluble triggering receptor expressed on myeloid cell-1 (sTREM-1). Proteins were analyzed by immunoblotting using a human cytokine array . Samples were processed in duplicate, and proteins were detected semiquantitatively by chemiluminescence. The results are expressed as the average signal of each pair of duplicate spots . For all patients, preoperative and postoperative samples were run in the same assay. Samples from pediatric controls were run in parallel. The control group was within the same age range of patients and included individuals with Down syndrome as well.Hemodynamics and microcirculatory status were monitored via pulmonary and systemic pressure curves, mixed venous oxygen saturation, and serum lactate, particularly on the first 2 to 3 days after surgery. The amount of cardiovascular support required postoperatively was computed using the vasoactive-inotropic score . To inveIn this study, preoperative and postoperative assessments  and laboratory analyses (NYM) were carried out in a blinded fashion.Unless otherwise specified, numeric variables are presented as medians with interquartile ranges. Categorical variables are presented as number of cases and percentages, and differences between groups were tested using the Chi-square family of tests. The Wilcoxon test, Friedman's test, and Pearson's coefficient of correlation were used to test for differences and associations within subjects. Inferential statistics were used to analyze postoperative hemodynamics, biological markers, and microcirculatory parameters in hemodynamic groups, as well as potential predictors of outcome. For this purpose, the majority of variables were analyzed after Box-Cox transformation with further testing for the normality of their distributions. The general linear model was used to test for differences between groups at baseline and postoperatively. The general linear model for repeated measures was used to analyze arterial pressure and oxygen saturation curves postoperatively and differences between hemodynamic groups regarding data obtained at baseline and 4 hours and 24 hours after surgery. Logistic regression  was used to identify possible predictors of postoperative cardiopulmonary events. Receiver operating characteristic (ROC) curves were constructed, and sensitivity and specificity levels associated with cutoff values were determined. In all tests, 0.05 was set as the significance level. Statistical analysis was performed using the SPSS statistical software, version 26 .p < 0.001) but not mortality. Other factors associated with prolonged mechanical ventilation (>7 days in 22 patients) were delayed sternal closure, respiratory disturbances, infection, arrhythmias, seizures, and other neurological manifestations. One patient died of septicemia. Another patient died of rapid-onset systemic hypotension followed by bradycardia unresponsive to vasopressin and other life-supporting interventions. There was no need for reoperation in the present cohort.Preoperative and intraoperative data of 40 patients who underwent surgery under CPB are listed in IPO (0.38 (0.32–0.46), range 0.19 to 0.67) was directly correlated with the PAP/SAP registered in the surgical room just after CPB discontinuation . PAP/SAPIPO was even better than post-CPB PAP/SAP at predicting SCAPEs  to categorize postoperative pulmonary hemodynamics and analyze factors that might explain differences in hemodynamic behavior. Compared with patients with PAP/SAPIPO ≤ 0.40 (n = 22), those with PAP/SAPIPO > 0.40 (n = 18) had greater pulmonary arterial pressure for the entire period of hemodynamic monitoring  in comparison with patients with PAP/SAPIPO ≤ 0.40. Besides, in patients with PAP/SAPIPO > 0.40, preoperative oxygen saturation was slightly but significantly lower. Notably, atrioventricular septal defects were present exclusively in subjects with Down syndrome. CPB time was 144 (108–157) minutes and 103 (90–125) minutes in syndromic and nonsyndromic individuals, respectively (p = 0.009). Also, Down syndrome patients had lower preoperative peripheral oxygen saturation compared with nonsyndromic subjects (96% (93%-98%) and 98% (96%-99%), respectively, p = 0.006).While analyzing postoperative hemodynamics, we observed that PAP/SAPg SCAPEs . The cutnitoring . Systemiα, Serpin E1, RANTES, and SDF-1 decreased after surgery. Serum CD40L correlated positively with platelet count before surgery  and 4 hours and 24 hours following CPB . In addition, there was a negative correlation between serum RANTES and vasoactive-inotropic score . Differences between the 2 groups were observed in 5 markers, namely, G-CSF, IL-1RA, IL-6, IL-21, and mean platelet volume, all of them higher in patients with PAP/SAPIPO > 0.40  and IL-16, MIF, and neutrophil-to-lymphocyte ratio measured 4 hours after CPB were associated with a p < 0.05. However, using the forward LR procedure for variable inclusion, only PAP/SAPIPO and MIF remained in the predictive model. The hazard ratio associated with a PAP/SAPIPO > 0.40 was 5.07 ; for post-CPB MIF analyzed as quartiles, it was 3.29 . Variables not significantly correlated with the occurrence of SCAPEs were patient age and presence/absence of Down syndrome; preoperative oxygen saturation, pulmonary/systemic blood flow ratio, and right ventricular systolic function (TAPSE); pre- and post-CPB pulmonary/systemic mean arterial pressure ratio and CPB time; postoperative vasoactive inotropic score, serum lactate, and mixed venous oxygen saturation; and serum levels of inflammatory markers (pre- and postoperative) not shown in By univariate and multivariate logistic regression analyses, variables were tested for their association with SCAPEs. IPO was characterized as a new and potentially useful parameter. We looked at PAP/SAPIPO prior to analyzing the entire pressure curves because during the first 6 hours of postoperative care, patients were still deeply sedated on mechanical ventilation and relatively stabilized in terms of post-CPB physiology. Our findings suggest that the link between Down syndrome and pulmonary hypertension in the setting of congenital heart disease is constituted by features that are present in some but not all syndromic patients  and becomes more evident under certain circumstances . In some patients with Down syndrome, particularly those with atrioventricular septal defect, long perfusion times probably contributed to the upward shift of pulmonary pressure curve after surgery, which was clearly associated with systemic inflammation. Patients with this profile seemed to be at a higher risk of having a difficult postoperative course.In this study, we analyzed the behavior of pulmonary and systemic arterial pressure curves and the occurrence of SCAPEs and investigated how they might be related to systemic inflammation, which we assessed by measuring circulating levels of inflammatory markers pre- and postoperatively. Pulmonary hemodynamic patterns were identified early after surgery and correlated with the levels of 5 inflammatory markers. SCAPEs were related to immediate postoperative hemodynamics and serum level of MIF protein and constituted one of the causes of prolonged mechanical ventilation. The variable PAP/SAPα, Serpin E1, and SDF-1. We were probably unable to detect higher levels for GROα, Serpin E1, and SDF-1 because peak concentrations of these proteins generally occur just after or even during CPB [β and RANTES. The recruitment and activation of neutrophil granulocytes are associated with multiorgan injury [The overall postoperative inflammatory reaction was characterized by changes in the levels of several inflammatory markers, as shown in ring CPB –19. The ring CPB  in additring CPB . In our ring CPB . RANTES ring CPB , as wellring CPB . In pediring CPB . In our ring CPB  and the n injury . In the α or IL-1β (not shown), was not surprising. Because of the spare receptor effect, large quantities (~100-fold) of IL-1RA are required to functionally inhibit the biological effects of negligible amounts of IL-1 [Of the inflammatory markers that were analyzed in the study, IL-6, IL-1RA, G-CSF, IL-21, and mean platelet volume were closely correlated with early postoperative hemodynamic patterns, while higher MIF concentrations 4 hours post-CPB were associated with the occurrence of SCAPEs. In general, IL-6 and IL-1RA are proinflammatory and anti-inflammatory mediators, respectively. G-CSF and IL-21 have effects that characterize them as anti-inflammatory cytokines , 29. In  of IL-1 . Thus, i of IL-1 . There h of IL-1 –37, but IPO > 0.40) may have rendered some patients more susceptible to instabilities triggered by factors known to affect pulmonary vascular tone postoperatively, such as alveolar hypoxia, changes in pH, and right ventricular dysfunction. MIF is a noncanonical ligand of chemokine receptors known to play a central role in innate immunity [SCAPEs occurred in 27.5% of patients. This relatively high prevalence was due to the inclusion of events that would probably not be classified as pulmonary hypertensive crises based on contemporary definitions but contributed to the need for prolonged mechanical ventilation. Of the variables tested for correlation with the occurrence of SCAPEs, immediate postoperative hemodynamics and serum MIF 4 hours post-CPB reached statistical significance in univariate and multivariate analyses. Higher initial levels of pulmonary arterial pressure (i.e., PAP/SAPimmunity  and a nuimmunity . It bindimmunity . Previouimmunity . Of poteimmunity .Based on our findings, we conclude that pulmonary hemodynamic patterns may be identified early after surgery in patients with congenital cardiac communications. A relationship was demonstrated between postoperative systemic inflammatory response and the behavior of the pulmonary circulation. Early postoperative elevation of pulmonary arterial pressure was associated with relevant cardiopulmonary events, which in turn accounted for prolonged mechanical ventilation. Six markers of inflammation present in circulation were directly or indirectly associated with the occurrence of postoperative events. The relationships that we report between hemodynamics, inflammation, and outcome may have implications in terms of treatment planning and prevention of complications in this population.


Chronic kidney disease became a public health problem increasing healthcare burden. Our aim was to detect the relationship between cardiovascular risk, endothelial dysfunction, inflammation, and kidney function in chronic kidney disease patients and to detect the nontraditional factors affecting the decline in kidney functions.A cross-sectional study including 30 male and female patients with chronic kidney disease stages 3–5. Creatinine clearance and Framingham risk score points were calculated. Carotid intimal medial thickness was measured as well as absolute flow mediated dilatation in brachial artery. Highly sensitive C-reactive protein, parathyroid hormone, kidney function tests, and lipid profile were measured.p 0.0025, 0.0285) respectively. A significant correlation was found between highly sensitive C-reactive protein and Framingham risk score points but not with carotid intimal medial thickness  respectively. An inverse correlation was found between creatinine clearance and highly sensitive C-reactive protein (p 0.0174). Absolute flow mediated dilatation in brachial artery decreases with increasing Framingham risk score points and decreasing creatinine clearance  respectively.Framingham risk score points and carotid intimal medial thickness increased significantly with decreasing creatinine clearance (There is correlation between chronic kidney disease and impaired vascular function, subclinical atherosclerosis, and heightened inflammatory response. Chronic kidney disease patients are at increased risk of cardiovascular events with higher [10-]year cardiovascular risk. Chronic kidney disease (CKD) has shifted from the 36th cause of death in 1990 to the 19th cause in 2013 [There is little information about the pathogenesis of cardiac diseases in CKD, especially in early stages and whether it correlates with the traditional risk factors such as dyslipidemia, diabetes, and hypertension. This is difficult to confirm because atherosclerosis, unless became severe, is often asymptomatic; hence, a direct examination of vessel wall is necessary to detect early atherosclerosis , 5. CaroFramingham risk score (FRS) is the most widely used score to predict the risk of developing CVEs in 10 years. It was first developed in 1988 .There is conflicting data regarding association between inflammation and the progression of CKD. In the Cardiovascular Health Study (CHS), higher levels of C- reactive protein (CRP), white blood cell count, and coagulation factors were associated with increasing creatinine levels . HoweverRecently, it was discovered that measurement of flow-mediated vasodilation (FMD) is considered an index of endothelium-dependent vasodilation, and when measured in the brachial artery using high-resolution ultrasound, it can be used as a method for assessing vascular function . EndotheInformed consent was obtained from all participants at the start of the study.A cross-sectional study was conducted to detect the relationship between cardiovascular risk, kidney function, and inflammation in CKD patients, to detect impairment in vascular function in such patients, and to detect the nontraditional factors affecting the decline in kidney functions such as inflammation, endothelial dysfunction, and CKD-mineral and bone disorder (CKD-MBD).2) of 30 to 59, 15 to 29, and 15 respectively according to the Cockcroft-Gault equation [Thirty male and female patients with CKD stages 3, 4, and 5  were included after accepting to participate in the study. They were admitted to the Nephrology Department at Ain-Shams University hospitals during the period between August and November 2018. Patients were diagnosed to have CKD if they had evidence of abnormalities of kidney structure or function lasting for more than 3 months and were classified into CKD stage 3, 4, and 5, based on estimated glomerular filtration rate (eGFR) level  and the second echogenic line (media–adventitia interface) of the far wall. Three measurements were taken at 0.5, 1, and 2 cm below the carotid bifurcation of the common carotid artery on each side, and their arithmetic averages were calculated. The intimal–medial thickness of both sides (right and left) was also calculated and the average of these two values was calculated. All the CIMT measurements were performed by an experienced radiologist who was blinded to the clinical data.Before measurement, each participant was fasting for at least 6 h and rested for 10–20 min in a quiet, temperature-controlled room. B-mode ultrasound image of the brachial artery in the dominant arm was obtained with the arm supinated and abducted about 80°. The diameter of the brachial artery was measured about 1–3 cm above the ante-cubital fossa in longitudinal plane. A cuff was placed at the forearm, 5–10 cm below the scan area. First brachial artery diameter was measured throughout the cardiac cycle at rest (baseline) according to the published guidelines . It was Blood samples were obtained by venipuncture for measurement of serum creatinine, blood urea nitrogen, calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) levels. Lipid profile required 12 h of fasting. Blood samples were assayed within 24 h. Highly sensitive CRP (Hs CRP) was based on the principle of a solid phase ELISA. Kits were stored at 2–8 °C. All reagents were allowed to reach room temperature (18–22 °C) before use. Patient serum was diluted 100-fold prior to use. Obtained values of Hs CRP were in ng/ml. Patient samples with CRP concentrations greater than 10000 ng/ml were diluted 10-fold after the initial 100-fold dilution . Expected values of Hs CRP were from 68 to 8200 ng/ml.M) and standard deviation (SD) for all quantitative variables. The frequency and percentage for qualitative variables was calculated. Correlation coefficients to find linear relationships between different variables were calculated using r-test or Spearman’s correlation coefficient. Values for p less than 0.05 were considered significant and values less than 0.001 were considered highly significant.Analysis of data was carried out by using the 17th version of SPSS . Data is shown as the mean (p 0.0007), a significant inverse correlation between FRS points and both creatinine clearance and absolute FMD  respectively. FRS points increased significantly with increasing Hs CRP levels (p 0.0043). Regarding lipid profile, there is a highly significant correlation between FRS points and serum triglyceride levels and no significant correlations between FRS points and other laboratory results. Regarding CIMT in Table p 0.0000), a significant correlation between CIMT and serum cholesterol level (p 0.0100), and an inverse correlation between CIMT and creatinine clearance (p 0.0285); otherwise, no other significant correlations were found. Table p 0.0174) and with FRS and CIMT as mentioned before. Absolute FMD decreased with decreasing creatinine clearance (p 0.0269).The mean age of the study population was 58 as shown in Table CKD was found to be a powerful predictor of CVEs. Although the association between decline in kidney function and CVD risk is not fully understood up till now, there are some explanations. The high prevalence of traditional  and non-traditional  cardiovascular (CV) risk factors are the major accused factors in the pathogenesis , 13, 19.2) was associated with an increased 10-year Framingham risk for coronary artery disease. Preston et al. [Both CIMT and FRS points showed inverse correlation with creatinine clearance. The REACTION Study  in Chinan et al.  reportedn et al.  found a A strong inverse correlation was found between FRS points and FMD as a marker of endothelial dysfunction in CKD patients; however, that correlation between FMD and CIMT was insignificant. In the Multi-Ethnic Study of Atherosclerosis, incorporating > 3000 participants, FMD was found to predict future CVEs. In addition, FMD in combination with the FRS helped to classify CV risk better than FMD or the Framingham risk score alone . There aHs CRP correlated with FRS points which agreed with Albert and colleagues  who condImpairment in vascular function was found in CKD patients as predicted by brachial FMD as shown by Kopel et al.  who demoCKD is correlated with impaired vascular function, subclinical atherosclerosis, and heightened inflammatory response. CKD patients are at increased risk of CVEs with higher 10-year CV risk especially in late stages of the disease.The study was conducted on small sample size. Larger samples are needed for better generalization of results and inclusion of patients on hemodialysis. Urinary protein excretion was not performed, which is a well-known risk factor for vascular diseases and atherosclerosis and the study concentrated only on non-traditional risk factors. No longitudinal follow-up for the patients was performed, and we used CG formula to assess kidney functions which measures creatinine clearance (not GFR) which becomes less accurate as the kidney function worsens. We could not exclude age as a confounder in risk factors as it is a part of FRS and of CG formula as well.


ITGAM). The study aimed to assess the relationship between a single nucleotide polymorphism (SNP) -323G > A of the ITGAM and the occurrence of nutritional disorders in patients with CHF. 157 CHF patients underwent clinical and nutritional screening. Body composition was evaluated by bioelectrical impedance analysis (BIA). Patients with cachexia were characterized by significantly lower weight, body mass index (BMI), lower fat mass (FM), albumin, and hemoglobin. Lower values of BIA parameters: capacitance of membrane (Cm), phase angle (PA), and impedance ratio (Z200/Z5) were noted in women. Those patients demonstrated significantly higher values of creatinine, c-reactive protein (CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and pulmonary artery systolic pressure (PASP). A significantly higher risk of cachexia was reported in patients: aged ≥ 74 years (OR 3.55), with renal failure (OR 3.75), New York Heart Association classification (NYHA) III-IV (OR 2.83), with moderate or severe malnutrition according to the score of subjective global assessment (SGA) (OR 19.01) and AA genotype of ITGAM gene (OR 2.03). Determination of the -323G > A SNP in the ITGAM may prove to be a useful marker  in the assessment of the risk of nutritional disorders in patients with CHF.Cardiac cachexia (CC) is an unfavorable metabolic syndrome leading to exacerbation of chronic heart failure (CHF) and a higher risk of death. The main factor contributing to the development of cachexia is the ongoing inflammatory process mediated by genes (e.g. Integrin Subunit Alpha M— The factors associated with the growing number of newly diagnosed cases of CHF are: age (> 70 years) and concomitant diastolic heart failure. As a result of metabolic, anabolic and catabolic disorders associated with CHF, a large number of patients with suspected CHF are diagnosed with left ventricular dysfunction5.Patients with CHF are also often diagnosed with cardiac cachexia (CC). Cachexia is defined as ≥ 5% weight loss over 3–12 months. It is typically accompanied by characteristic symptoms. These symptoms include fatigue, decrease of muscle strength and mass, anorexia, anemia, low albumin level and severe inflammation. The inflammatory process triggers CC pathogenesis and the progression of cachexia. The mortality rate in patients with CC is 20–30% per year. The mechanism of cachexia progression in patients with CHF, in whom the incidence of CC ranges from 8 to 42%, is associated with reduced myocardial perfusion, depletion of high energy stores, cardiomyocyte decline and accumulation of water and lactates in cardiac tissue, accompanied by inflammatory response—ITGAM gene , located on the 16p11.2 chromosome6. Its protein product influences interferon gamma (INF-γ) receptor functioning and inflammatory mediator secretion regulation. In the case of low ITGAM expression on the surface of antigen presenting cells (APCs), there occurs an increase in the production of interleukin (IL), including IL-6 and IL-177. In patients with systemic lupus erythematosus (SLE), studies have demonstrated the effect of rs114367 single nucleotide polymorphism (SNP) on the level of both the ITGAM transcript and monocyte surface protein. The level of mRNA was dependent on the genotype . Over twofold decrease in the level of protein was observed in patients with AA genotype (higher risk patients) compared to GG genotype (lower risk group). These differences in the protein expression may be the result of the allele-specific decrease in transcription repression8. However, as far as we know, no studies have been performed regarding the correlation between the occurrence of nutritional disorders in patients with CHF and the ITGAM gene status. In this study, we have aimed at the assessment of the relationship between ITGAM gene regulatory region (−323G > A) SNPs and the incidence of nutritional disorders in cachectic patients with CHF.The inflammatory process is mediated by genes, including Integrin Subunit Alpha M9. New York Heart Association (NYHA) functional classification was used to assess extent of the disease by qualifying patients to group I–IV according to the disease severity. The inclusion and exclusion criteria for the study participants were defined, as follows: the inclusion criteria—(a) age > 18 years and polish ethnicity; (b) newly diagnosed CHF; (c) signed informed consent to participate in the study; (d) stable patients without rapid changes in body weight and diuretic treatment for a minimum period of 10 days, and the exclusion criteria—(a) extreme renal failure  criteria—glomerular filtration rate (eGFR) below 15 mL/min or dialysis); (b) acute coronary syndrome; (c) presence of metallic implants, pacemakers, implanted cardioverter defibrillator or cardiac resynchronization systems; (d) hyper- or hypothyroidism; (e) recent coronary artery bypass grafting (within last 6 months); (f) an active neoplastic process; (g) amputation in the upper or lower limbs. In terms of smoking, the patients were classified as non-smokers, ex-smokers and current smokers. Non-smokers are those who have never smoked or have smoked fewer than 100 cigarettes in their lifetime. Ex-smokers are people who, at the time of the interview, declared that they did not smoke, but had smoked over 100 cigarettes during their lives. The current smoker is what he was smoking at the time of the interview. The patients were followed up for 60 months (5 years) from January 2015 (baseline) until the January 2020. Baseline characteristic of the study group is presented in Table This study included 157 patients (mean age: 69.5 ± 14 years) with the diagnosis of CHF. Enrolled patients were diagnosed and treated at the Clinic of Cardiology and Internal Medicine, Department of Cardiology, Military Hospital in Lublin, Poland in the period of 2013 and 2014. Patients were enrolled in the study consecutively . Diagnosis of CHF was made on the latest clinical guidelines issued by European Society of Cardiology (ECS), and the applied criteria involve patients’ clinical screening, echocardiographic assessment  followed by laboratory tests 10. The time points were 15 months at which we measured the parameters. Patients enrolled in this study met the above criteria for cachexia.Cachexia was diagnosed according to the criteria of Evans et al., as follows: a weight loss ≥ 5% or more in 12 months or less in the presence of underlying illness, plus three of the following criteria: decreased muscle strength, fatigue, anorexia, low fat-free mass index, abnormal biochemistry (increased inflammatory markers: CRP > 5.0 mg/L), anemia (hemoglobin < 12 g/dL) and low concentration of serum albumin (< 3.2 g/dL)Anthropometric measurements  were taken from all patients and they were also asked to fill in the subjective global assessment (SGA) questionnaire. The bioelectrical impedance analysis (BIA) was used to establish the parameters reflecting the nutritional status and body composition, including: fat mass (FM) and fat-free mass (FFM). The phase angle (PA) (at 50 kHz frequency) and capacitance of membrane (Cm) values were also established using BIA. All study participants had similar conditions of BIA measurements. The measurements were performed in patients lying on the bed in the supine position (patients’ extremities did not come into contact with the torso or each other). The patients rested for at least 5 min before BIA to allow for the equalization of the body fluid level. The body composition parameters were measured using ImpediMed bioimpedance analysis SFB7 BioImp v1.55 device .ITGAM SNP: rs7193943) . The above methods were also described in detail in our previous studies14.Prior to the study, peripheral blood was collected from each study subject in the amount of 5 mL. Before further laboratory analysis , the samples were stored at − 80 °C. The isolation of DNA was conducted using the column method with a dedicated kit according to the manufacturer's recommendations . The concentration and quality of the obtained DNA was spectrophotometrically evaluated using NanoDrop Lite Spectrophotometer . The Real-Time polymerase chain reaction (PCR) technique was used for genotyping reaction on StepOnePlus device  in accordance with the manufacturer’s instructions . Results p < 0.05 were considered statistically significant. Comparisons of the values of independent continuous variables were performed using the Mann–Whitney U test (comparison of 2 groups) or ANOVA Kruskal–Wallis test (comparison of more than 2 groups). All selected continuous variables had distribution different than the normal—it was verified by the D`Agostino-Pearson test). To assess the risk cachexia depending on selected demographic, clinical, and genetic factors the odds ratio test (OR) with 95% Confidence Interval (95% CI)  and logistic regression analysis  was used.All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved of Bioethical Commission in Medical University of Lublin approved the study protocol (no of consent: KE-0254/64/2017).The study group consisted of 157 patients diagnosed with CHF. The study group was dominated by men (58.6%), patients with CHF degree II (29%) and III (25.8%) (according to NYHA). The patient median age was 74 years (range: 27–109 years). Patients were mostly well-nourished (SGA A: 45.5%) or in moderate malnutrition (SGA B: 44.9%). Median BMI was 29.3 (range 18.7–53.2). Most of the patients did not have diabetes (39.7%) or renal failure (37.8%). Patients were mostly current smokers (42.9%). Patients classified as non-smokers were in the minority (35.3%). The remaining patients were ex-smokers (21.8%). Detailed data on demographic-clinical and laboratory variables are presented in Table ITGAM gene, compared to other variants of studied SNP , significantly higher values of weight (94 vs 80 or 81 kg), low-density lipoprotein (LDL) (107.7 vs 83.3 or 71.6 mg/dL) and diastolic blood pressure (90 vs 72.5 or 70 mmHg) were found. In addition, a significantly lower incidence of diabetes mellitus was observed in these patients (7% vs. 64.9% or 28.1%). Detailed data of the comparison of selected variables depending on the occurrence of the ITGAM genotypes were presented in Table In carriers of the GG genotype of the Patients with cachexia were characterized by significantly older age (78.5 vs 68.5 years), obviously lower weight and BMI, as well as lower FM (22.9 vs 26.4 kg), albumin (3 vs 3.7 g/dL) and hemoglobin values (12.5 vs 13.8 g/dL), moreover, lower but only in women values of parameters derived from the BIA: Cm (0.7 vs 1.3 nF), PA (2.8 vs 4.2) and impedance ratio—Z200/Z5 (1.1 vs 1.2). On the other hand, in those patients significantly higher values of creatinine (1.2 vs. 1.1 mg/dL), CRP (14.2 vs. 3.6 mg/dL), NT-proBNP (4255.5 vs. 1806 pg/mL) and pulmonary artery systolic pressure—PASP (45 vs. 35 mmHg) were observed (Table ITGAM gene (OR 2.03) (Table A significantly higher risk of cachexia was reported in elderly patients ≥ 74: OR 3.55), people with renal failure (OR 3.75), with a higher degree of CHF according to NYHA (III-IV: OR 2.83), with moderate or severe malnutrition according to SGA (B or C: OR 19.01) and AA genotype of : OR 3.55CHF is becoming an ever more prevalent public health issue. The incidence of CHF increases with age, so taking into account the problem of the aging society, the prevalence of CHF is likely to grow in the future largely due to such age-related risk factors as hypertension or chronic inflammation. The inflammatory process taking place in CHF patient is responsible for the nutritional disorders that eventually result in chronic cachexia.18. Subsequently, there occurs an increase in the production of the inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), INF-γ, IL-6 and IL-1β. They constitute mediators with confirmed involvement in the mechanisms leading to muscle fiber breakdown in the Ubiquitin–Proteasome Pathway (UPP) through the activation of the muscle ring-finger 1 (MuRF1) and muscle atrophy F box (MAFbx) ligase genes. It has also been confirmed that the inflammatory process is important in the adipose tissue breakdown. The increase in the number of apoptotic fat cells and decrease in the rate of lipogenesis is associated with increased production of TNF-α. It reduces the glucose and free fatty acid (FFA) transport into cells by interacting with IL-1, which is associated with decreased adipose tissue synthesis. The catabolism of both adipose and muscle tissue also takes place with IL-6 involvement. It may be of great importance for the assessment of the nutritional status and further prognosis to determine the level of this IL7.The mechanism of the development of nutritional disorders is significantly affected by the development of inflammation19. ITGAM gene is of key importance in the activation, migration and adhesion of leukocytes, its main task being the coding of the αMβ2-integrin chain. B-cell signaling and the function of INF-γ receptors, Toll-like receptors (TLR), B-cell receptors, and Fcγ receptors are regulated with the involvement of CD11b. It is an essential molecule in the pathological mechanism of autoimmune diseases, mostly SLE6. ITGAM may play a role in the production of inflammatory cytokines. It is highly expressed on APCs. If the expression of ITGAM on the surface of APCs is low, the production of IL-6 is intensified and, as a result, there occurs T lymphocyte activation and IL-17 production increase7. A similar correlation is observed in the case of increased production of other pro-inflammatory factors, namely, IL-1β, TNF α and IFN-β20.CC is associated with skeletal myopathy due to genetic changes in a few key regulatory pathwaysITGAM gene status and nutritional disorders in the available literature. The studies that are being available concentrate mainly on ITGAM SNPs’ role in rheumatologic conditions—mainly SLE and lupus nephritis (LN)21. In our recently published paper, it has been demonstrated that the investigated ITGAM SNP (-323G > A) may serve as a useful marker in the assessment of the risk of occurrence of nutritional disorders in head and neck cancer (HNC) patients undergoing radiotherapy (RT)14.We would like to point out that there are no studies directly related to the relationship between ITGAM gene were analyzed: rs1143678 (C > T), rs1143679 (G > A), rs1143683 (C > T) and serum IFN-I level was determined. Each of the analyzed SNPs of the ITGAM gene predisposes to a higher risk of developing SLE. It was shown that the tested SNPs increased the serum IFN-I concentration. In a group of 21 people, the GT haplotype common to both rs1143683  and rs1143679  was confirmed. The GT haplotype was associated with a significantly higher IFN-I concentration in patients diagnosed with SLE . The authors also noted that the disease stage (according to Systemic Lupus Erythematosus Disease Activity Index—SLEDAI) and the presence of ITGAM SNPs were not associated with significant changes in the level of this cytokine. Increased amounts of produced IFN-I indicate a decreased activity of CD11b and an increased inflammatory reaction in patients with the tested SNP variants of the ITGAM gene22. In another study in the blood of 30 patients with CHF (NYHA II-IV), an increase in CD11b integrin was observed on the surface of CD45 + leukocytes (p = 0.03) and in the subpopulation of macrophages, monocytes (p = 0.001) and polymorphonuclear cells (p = 0.002). An influence was demonstrated between the advancement of CHF (NYHA) and CD11b expression on the surface of monocytes, macrophages and polymorphonuclear cells (p = 0.001). The increase in the level of this integrin on the surface of these cells is used as a marker of cellular activity23. In our study a significantly higher risk of cachexia was reported in elderly patients (≥ 74: OR 3.55), people with renal failure (OR 3.75), with a higher degree of CHF according to NYHA (III-IV: OR 2.83), with moderate or severe malnutrition according to SGA (B or C: OR 19.01) and AA genotype of ITGAM gene (OR 2.03). In that aspect AA genotype of ITGAM gene may be a useful marker assessing the risk of nutritional disorders in patients with CHF. However, these results cannot be compared with any others as there are none.In a study conducted on a group of 171 patients with SLE, three SNP variants of the 24.It is known that one of the main causes of left ventricular dysfunction and CHF is acute coronary syndrome (AMI) in the form of ST-elevation myocardial infarction (STEMI). In one of the studies, a significantly increased expression of Bone Marrow Stromal Cell Antigen 1—BST1  and ITGAM  was found already in the acute phase of STEMI in which CHF developed at 6 months of follow-up. It was a factor that differentiated patients with post-STEMI CHF from those without CHF. This makes it possible to use new tools for the early prognosis of patients with post-STEMI CHF and the search for genetic potentiality to the evolution of CHF and LV remodeling after STEMIITGAM gene may significantly impact the expression of the gene and, hence, specific protein production. This may lead to the regulation of the production of pro-inflammatory cytokines such as IL-6. Thus, the chronic inflammatory process occurring due to the increased cytokine production, which is characteristic of patients with CHF, may result in the development of nutritional disorders and lead to irreversible conditions like cachexia. Further studies aimed at finding new markers of inflammation involved in the occurrence of malnutrition leading to CC, as well as explaining their mechanisms of action, may facilitate more efficient diagnosis of nutritional disorders, faster implementation of nutritional treatment and the development of new therapies.The studied SNP’s presence in the regulatory region of the ITGAM SNP (-323G > A) may, after confirmation of its value in further studies, constitute a useful marker in assessing the risk of occurrence of nutritional disorders in CHF patients.Our study has certain limitations, including no assessment of the influence of the diet or of the food intake problems. What is more, we have not investigated the impact of individual genotypes on the expression of the studied gene (and the protein encoded by it). Despite the above limitations, this is, as far as we know, the first study demonstrating that the evaluation of ITGAM (-323G > A) can serve  as a putative promising marker for nutritional disorders screening in CHF patients, because of its correlation with patients’ clinical and nutritional features. Prospective clinical utility of the proposed diagnostic marker requires confirmation in large cohort studies.Until now, there are lack of established criteria or clinical guidelines allowing detection and management of CC in CHF patients. However, assessment of genetic markers, such as


We aimed to develop and validate a nomogram model for predicting CKD after orthotopic liver transplantation (OLT).n = 293) and validation set (n = 106). Multivariable Cox regression analysis was performed in the training set to identify predictors of CKD. According to the Cox regression analysis results, a nomogram model was developed and validated. The renal function of recipients was monitored, and the long-term survival prognosis was assessed.The retrospective data of 399 patients who underwent transplantation and were followed in our centre were collected. They were randomly assigned to the training set (p = 0.018), female sex , preoperative hypertension , preoperative eGFR , uric acid at 3 months , haemoglobin at 3 months , and average concentration of cyclosporine A at 3 months . According to these parameters, a nomogram model for predicting CKD after OLT was constructed and validated. The C-indices were 0.75 and 0.80 in the training and validation sets. The calibration curve of the nomogram showed that the CKD probabilities predicted by the nomogram agreed with the observed probabilities at 1, 3, and 5 years after OLT (p > 0.05). Renal function declined slowly year by year, and there were significant differences between patients divided by these predictors. Kaplan-Meier survival analysis showed that the survival prognosis of recipients decreased significantly with the progression of renal function.The incidence of CKD at 5 years after OLT was 25.6%. Cox regression analysis identified several predictors of post-OLT CKD, including recipient age at surgery (HR 1.036, 95% CI 1.006-1.068; With excellent predictive abilities, the nomogram may be a simple and reliable tool to identify patients at high risk for CKD and poor long-term prognosis after OLT. Chronic kidney disease (CKD) is a common and significant complication after orthotopic liver transplantation (OLT). With the progression of surgical technology, perioperative treatment, and immunosuppressants, the survival rates of patients after OLT have dramatically improved to 90 and 75% at 1 and 5 years after OLT, respectively –4, 15 ~ Studies have shown that the causes of CKD after OLT are complex and may include preoperative  or hypertension, hyperlipidaemia, and hepatitis C) and postoperative  toxicity, prolonged ischaemia, and haemodynamic instability) factors , 10–13. A credible and helpful predictive model to identify which patients are at high risk of developing CKD in clinical practice has not been developed, although it would be a useful tool for designing preventative measures, such as early decreased doses or withdrawal of CNIs and administration of non-nephrotoxic immunosuppressants. In this study, we aimed to develop and validate a reliable nomogram model for predicting CKD after OLT. With this model, we can identify patients at high risk for CKD early and take targeted measures to prevent or slow the development and progression of CKD.2, renal replacement therapy (RRT) before liver transplantation, multiorgan transplantation, follow-up less than 6 months, and age < 18 years. Finally, 399 patients were enrolled in our study. They were randomly allocated to the training set (n = 293) and the validation set (n = 106)  < 60 ml/min/1.73 mThe study was conducted according to the principles of the Declaration of Helsinki and approved by the Medical Ethics Committee of The Affiliated Hospital of Qingdao University .2 for 3 months, regardless of the presence or absence of structural kidney damage [− 1.154 × (age)− 0.203 × 1.212 (if black) × 0.742  [Demographic details, relevant preoperative and postoperative laboratory test results, and concentrations of CNIs were recorded. AKI was defined as an increase in serum creatinine (sCr) of at least 26.5 μmol/l within 48 h or more than 50% within 7 days after transplantation. Peak aspartate aminotransferase (AST) within the first 24 h after transplantation was used as a measure of ischaemia-reperfusion injury (IRI) . New-onsy damage . sCr, eG female) .2; mildly to severely decreased: GFR 30-59 ml/min/1.73 m2, severely decreased: GFR 15-29 ml/min/1.73 m2; and kidney failure: GFR < 15 ml/min/1.73 m2 [According to the Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group, the patients’ renal function was classified as follows : mildly /1.73 m2 .The standard immunosuppressive regimen after OLT consisted of CNIs combined with mycophenolate mofetil (MMF) and corticosteroids. Most patients were treated with a triple-drug regimen of tacrolimus (FK506) or cyclosporine A (CsA), MMF, and corticosteroids. Methylprednisolone was given on the day of transplantation, followed by tapering, and then converted to methylprednisolone for oral administration, which was gradually reduced. When renal function was impaired, the introduction of CNIs was delayed. Some patients were switched to mammalian target of rapamycin (mTOR) inhibitor therapy when plasma FK506 failed to reach target levels or if CKD developed. The dose of immunosuppressant was adjusted according to blood concentration.U test was performed to compare parametric variables. Categorical variables were expressed as quantities and percentages, and comparisons were made using the chi-square test or Fisher’s exact test. A Cox proportional hazards model was implemented in the training set to identify predictors of the development of CKD after liver transplantation. Factors with p < 0.05 in the univariable Cox analysis and several factors with clinical significance in previous studies were enrolled in the multivariable Cox analysis. The final Cox regression model was chosen by using forward stepwise regression with the Akaike information criterion (AIC) as the stopping rule. The AIC value for the final model was minimized with the fewest number of variables [p-values of < 0.05 were considered statistically significant.R version 4.0.3 , STATA 15.0 , and SPSS 25.0 were used to analyse the data. The median and interquartile range (IQR) were used to describe continuous variables, and the Mann–Whitney ariables . For furA total of 399 patients were enrolled in our study with a median follow-up of 31.5 months (IQR 18.3-51.6 months), of whom 293 patients were allocated to the training set and 106 patients were allocated to the validation set. The median age at transplantation of all patients was 52 years (IQR 45-59 years), and the majority of recipients were males (82.9%). The main indications for OLT at our centre were hepatitis B virus (HBV)-associated hepatocellular carcinoma (49.1%), followed by HBV-associated cirrhosis (27.5%). During the first week after liver transplantation, 71.1% of the recipients developed AKI, and 36.8% developed severe AKI (stage 2-3).2. At 1 year, 13.0% of recipients had eGFR < 60 ml/min/1.73 m2, and 0.8% had eGFR < 30 ml/min/1.73 m2. The incidences of CKD at 1, 3, and 5 years after OLT were 11.0, 20.3, and 25.6%, respectively. During the entire follow-up period, 28.6% of the recipients had renal function decreaesd, and the majority (55.1%) had eGFR mildly decreased. The mildly to severely decreased eGFR, severely decreased eGFR and end-stage renal disease (ESRD) (eGFR < 15 ml/min/1.73 m2 or long-term RRT) were observed in 26.8, 1.5, and 0.5% of the recipients, respectively. Only one recipient received a kidney transplant 19 months after OLT at our centre.During the first week after OLT, 44.4% of recipients experienced a significant decrease in eGFR of more than 50%, including 8.3% of patients who had an eGFR of less than 30 ml/min/1.73 mp > 0.05). Except for several factors with p < 0.05, including sCr, eGFR before OLT, serum albumin (ALB), and platelet-to-lymphocyte ratio (PLR) at 3 months after OLT, there were no significant differences between the training set and validation set regarding the demographic details, relevant preoperative and postoperative laboratory test results, and concentrations of CNIs (p > 0.05) , female sex , preoperative hypertension , preoperative eGFR , uric acid (UA) at 3 months , haemoglobin (Hb) at 3 months , and average concentration of CsA at 3 months after OLT  .The incidences of CKD were 26.6 and 27.3% in the training set and validation set, respectively . Points were assigned to the seven identified predictors based on their regression coefficients. For an individual patient, the points of each factor can be summed to calculate the estimated probabilities of CKD at 1, 3, and 5 years after OLT. Then, the nomogram was validated in the training set and validation set. The C-indices were 0.75 (95% CI 0.72-0.78) and 0.80 (95% CI 0.75-0.85) in the training set and validation set, respectively. The calibration curve of the nomogram showed that the CKD probabilities predicted by the nomogram agreed with the observed probabilities at 1, 3, and 5 years after OLT (p > 0.05) . Kaplan-Meier survival analysis with the log-rank test showed that survival was significantly different among these three groups  at 24 h after OLT as the most important risk factor. However, uNGAL-24 h is not routinely examined in other centres. Moreover, this prediction model has not been validated in terms of its calibration abilities . RecentlCompared with these models, our model has the following advantages. First, it is the first nomogram model constructed based on OLT recipients for predicting CKD. Second, the predictors included in our model were readily available at surgery or routinely tested in follow-up, which is conducive to the popularization of the model. Third, our model had excellent discrimination and calibration abilities in the training set and validation set. It is a simple and reliable tool to distinguish recipients at high risk for CKD after OLT at 1, 3, and 5 years. In addition, this model can be used earlier at 3 months after OLT, assisting clinicians in adjusting immunosuppressive drugs in advance.This study had several limitations. First, this study had a retrospective single-centre design, and the sample size was small, so the model should be evaluated prospectively in other large multi-centre studies to demonstrate its applicability. Second, the use of MDRD to assess renal function may lack accuracy in candidates awaiting liver transplantation, possibly because of reduced muscle mass and/or hyperbilirubinemia. It would overestimate renal function in patients with poor function (GFR < 40 mL/min) and underestimate renal function in patients with reasonable renal function (GFR > 40 mL/min) . HoweverIn conclusion, the renal function of most recipients decreased and recovered rapidly in the first week after OLT and then decreased slowly year by year. Patients with severe CKD had a poor survival prognosis. We constructed a nomogram model for predicting post-OLT CKD for the first time. With excellent discrimination and calibration, this nomogram model can accurately predict patients at high risk for CKD after OLT. Therefore, we can take measures to prevent or slow the development and progression of CKD in advance, such as reducing UA levels, improving Hb levels, and withdrawing or minimizing the use of CNIs in follow-up.


Atrial fibrillation is an arrhythmia that results from abnormal depolarization of the atrium. Atrial fibrillation occurs in 5–40% of patients with cardiovascular bypass surgery, usually occurs on 2 to 4 days postoperatively. The aim of this study was Effect of variability of central venous pressure values to prevent atrial fibrillation after coronary bypass grafting.The present clinical trial study was performed on 150 patients undergoing cardiac surgery referred to Ayatollah Rohani Hospital of Babol. Patients were divided into 3 groups, with normal range pressure (8 to 12 mmHg), low pressure (less than 8), high pressure (greater than 12) based on central venous pressure measurements. Patients were evaluated every 4 hours to 72 hours for central venous pressure, AF incidence and urine output. Finally, the data are analyzed by spss statistical software.In this study 79 (52.7%) patients were male and 71 (47.3%) were female. In examining changes in central venous pressure, the time effect also significantly increased central venous pressure. The results of independent t-test showed that the mean of central venous pressure changes in subjects with at day 16, second day at 16, 20, 24, third day at 4, 8, 12, 16, 20 and 24 hours Atrial fibrillation. Significantly more than those without atrialfibrillation (P<0.05).In the study, central venous pressure changes the effect of time significantly increases the central venous pressure. Individuals with atrial fibrillation also had significantly greater central venous pressure changes than those without atrial fibrillation. Coronary artery bypass graft (CABG) surgery depends on the severity of the symptoms, coronary anatomy, and left ventricular function. Candidate patients have problematic or debilitating symptoms that, with medical treatment, are not completely controlled, or they cannot tolerate medical treatment and want to live a more active life, or stenosis in several branches of the coronary artery. They have severe. Atrial fibrillation is the most common postoperative arrhythmia that results from abnormal depolarization of the atrium, leading to a lack of atrial contraction -3. This Atrial fibrillation has been reported between 12-7% in patients undergoing non-cardiac surgery . The tim Atrial fibrillation in the postoperative period of CABG, due to the increased risk of congestive heart failure and embolic events, especially stroke, in the long run leads to worsening of patients' hemodynamic conditions. Strokes are so serious complications that are seen in 2% of surgical patients. In addition, atrial fibrillation is associated with increased hospital mortality and worsening long-term prognosis . One of An important indicator of right ventricular filling pressure is the right ventricular filling pressure, ie the amount of blood pumped with each heartbeat . It is aCVP monitoring is more accurate than measuring blood pressure, because changes in circulating volume are reflected in the CVP as soon as the blood volume decreases, and the CVP changes rapidly. The first stage of shock is followed by blood loss, while the blood volume decreases, the compensatory mechanisms act and the blood pressure remains normal, and only the CVP shows this decrease, while blood pressure is normal. CVP increases when there is an increase in the volume of the circulatory system or heart failure, and CVP decreases as result bleeding or fluid shifts inside the body compartments or volume loss (such as shock or as diabetes insipidus) , 12. TheIn sporadic studies in Iran, 25 to 45% of the relative deaths were due to cardiovascular disease . CoronarCoronary artery bypass graft surgery is one of the most valuable treatments that, if performed in a timely manner, can play a key role in reducing mortality and complications from these diseases. In this operation, which may be open or closed heart surgery, a bypass is created between the blocked arteries to supply blood to the heart muscle. Approximately 598,000 coronary artery bypass graft surgeries are performed annually in the United States alone, and although much progress has been made in drug therapy and catheterization procedures, surgical interventions are still the bases for the treatment of these diseases .A 2017 study by Costa MACD et al. in Brazil found that keeping the central venous pressure lower  in the first 72 hours after surgery was relatively less risky. It is from POST CABG AF and can even prevent arrhythmias . In a stThis study was performed on patients who referred to Rouhani Hospital for open heart surgery between 2018 and 2019, after obtaining permission from the ethics committee of Babol University of Medical Sciences with the ethics code: IR.MUBABOL.HRI.REC.1398.009. The sample size was assumed to be 40% in AF and with 95% confidence level and 8% accuracy, with the following formula, the sample size was calculated as 145 patients, which we collected a total of 150 patients.Inclusion criteria for patients who are candidates for open heart surgery and exclusion criteria’s, were patients with large atrium (either right or left), presence of moderate to high heart failure at the same time (mean ejection fraction less than 35%), the presence of AF before Operation, previous renal, hepatic, pulmonary disease, moderate to upper heart valve disorders, and peripheral vascular disease were considered. Then patients whom underwent CABG surgery and were transferred to the intensive care unit Based on central venous pressure measurements, patients were divided into two groups: the group with increased or decreased central venous pressure during hospitalization. With treatment, we normalized the central venous pressure in both groups, so that in the low-pressure group, giving fluids and, if necessary, vasopressor, and in the high-pressure group, limiting fluids and giving IV Furosemide. Then we examined the patients every 4 hours to 72 hours (3 days and nights), in terms of central venous pressure digitally with Saadat computer device and also continuous cardiac monitoring with 12-lead electrocardiogram device in terms of AF incidence and urine output control. The data and obtained from the two groups were analyzed by SPSS statistical software and when comparing the data, if the data distribution is normal, t-test and Chi-square, and if the data distribution is not normal, from Non-parametric tests were used. P value less than 0.05 was considered significant. Normal (8 to 12 mm Hg), low pressure group (less than 8), high pressure group (more than 12).In this study, 150 patients with cardiovascular bypass surgery were studied, of which 79 (52.7%) were male and 71 (47.3%) were female. 16 patients (10.7%) had atrial fibrillation and 134 patients (89.3%) did not develop this complication. The minimum age of patients was 41 years and the maximum age was 85 years and the mean age of patients was 65.30 years with a standard deviation of 8.76 years Table (1-4).In men, 5 patients (6.3%) and in women, 11 patients (15.5%) developed atrial fibrillation, which did not show a statistically significant difference (P=0.07). In the study of mean age between people with atrial fibrillation and those who did not, it was found that people with atrial fibrillation had a mean age of 65.50 7 7.27 and those who did not have atrial fibrillation had a mean age of 65.16 94 8.94 This difference was not statistically significant (P=0.56) -4.In estimating the mean time of atrial fibrillation in patients using Kaplan Meyer method, the mean time was equal to 77.0 hours with a standard deviation of 5.72 hours which can be seen in In the study of changes in central venous pressure, the results of analysis of variance with repeated data showed that the effect of time significantly increases the central venous pressure . Also, patients with atrial fibrillation had significantly more changes in central venous pressure than those without atrial fibrillation . Finally, the interaction between time and atrial fibrillation was also reported to be significant .The results of independent t-test showed that at the time of the first day at 16:00, the second day at 16, 20, 24, the third day at 4, 8, 12, 16, 20 and 24 the average changes in central venous pressure in people with Atrial fibrillation is significantly higher than people who did not have atrial fibrillation (P<0.05) .In a study conducted by Costa MACD et al. In 2017 in Brazil entitled "Comparison of the effect of two strategies of central venous pressure control on the incidence of POST CABG AF" on 140 patients in two groups of 70, one with central venous pressure 15 and Another was performed with a central venous pressure of 20, concluding that keeping the central venous pressure lower  in the first 72 hours after surgery was relatively less risky than POST CABG AF, and even Can prevent arrhythmia, which in our study also showed that people with atrial fibrillation had significantly more changes in central venous pressure than people without atrial fibrillation. The study also showed that the average age of people was between 60-63 years , which lead to abnormal resistance and conduction and atrial fibrillation is possible.A 2012 study by Wen-Hwa et al. In China entitled "Left Atrial Dilatation, a Criteria for POST CABG AF and Hospital Mortality after Cardiovascular Reconstruction Surgery" was performed on 197 patients without known valvular problems. They compared two groups of people with POST CABG AF and those without POST CABG AF who underwent heart surgery and concluded that left atrial dilatation was an independent factor in the development of POST CABG AF and nosocomial mortality   and the highest frequency in patients with lower than normal central venous pressure was related to the time 12 hours after admission to the ward. (6.26%) Also, the highest frequency of normal central venous pressure is related to the time 4 hours after the patient enters the ward . While tAlavi et al. Conducted a study in 2016 with the aim of comparing the index of pulse pressure fluctuations and central venous pressure in assessing fluid volume and its optimal optimization in patients after heart surgery. Their results showed that the rate of changes in central venous pressure after from receiving the volume of fluids has reached a considerable level. However, this increase was not in line with the increase in cardiac index and other cardiac function indices, and it can be concluded that any increase in central venous pressure is associated with an increase in these indices, which was not the case, and it can be concluded that any increase Significantly  in central venous pressure cannot be clinically effective in improving the prognosis of patients . But in our study, the results showed that people who had atrial fibrillation had significantly more changes in central venous pressure than people who did not have atrial fibrillation. Evaluating fluids and determining intravascular volume clinically in critically ill patients undergoing major surgery such as heart surgery is a major challenge. The purpose of assessing intravascular volume status in patients with hemodynamic instability is primarily to determine whether they benefit from fluid administration. Among the limitations of this study, blinding was not performed in the CVP evaluation of this study. Thus, physicians' responses to CVP values may lead to underestimating the relationship between CVP and outcome.In conclusion CABG is associated with postoperative complications and risks, although its advantages far outweigh its disadvantages, so it is important to know enough about these complications and related factors to get the best results to increase patient survival. Found. The results of the Current study showed that in the study of changes in central venous pressure, the effect of time significantly increases the central venous pressure, so that on the third day the mean changes in central venous pressure in people with atrial fibrillation are significantly higher than those who They did not develop atrial fibrillation. Also, people with atrial fibrillation had significantly more changes in central venous pressure than people who did not.


Background: Transplant glomerulopathy (TG) is one of the main causes of post-transplant proteinuria (PU). The features and possible risk factors for proteinuria in TG patients are uncertain.Methods: We investigated all patients who had biopsy-proven TG from 2000 to 2018 in our center. The clinical and histological data were compared between two groups with or without PU (cut-off = 0.3 g/day). Spearman correlation analysis was used to evaluate the relationship between PU and pathological changes. The risk factors for PU in TG patients were determined by multivariable logistic regression analysis.Results: One hundred and twenty-five (75.76%) of all enrolled 165 TG patients had proteinuria ≥0.3 g/day at the time of biopsy. TG patients' PU level was significantly correlated with Banff lesion score cg , and mm . Systolic blood pressure ≥140 mmHg , diastolic blood pressure ≥90 mmHg , peak PRA ≥5% , positive C4d staining , tacrolimus-based regimen , and calcium channel blocker usage  were independent risk factors for PU.Conclusions: Proteinuria is common in TG patients. systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, peak PRA ≥5%, positive C4d staining, tacrolimus-based regimen, and calcium channel blocker usage are associated with proteinuria in TG patients. Transplant glomerulopathy (TG) is characterized by glomerular basement membrane (GBM) double contours  as a result of chronic endothelial cell injury by various mechanisms –3. The iProteinuria is common after kidney transplantation and is also one of the most cardinal features of TG . MoreoveThere is limited research specifically on proteinuria in patients with TG, and most of the existing studies focus on proteinuria as one of the prognostic risk factors for TG , 13, 14.Thus, this study was designed to investigate the incidence, potential risk factors for proteinuria after the diagnosis of TG in kidney transplant recipients. Additionally, the clinicopathologic features of TG patients with proteinuria were assessed.A retrospective cross-sectional study was performed on kidney transplant recipients at Charité-Universitätsmedizin Berlin  from 1st January 2000 to 31st December 2018. All study activities were following the Declaration of Helsinki 2000 and the Declaration of Istanbul 2018. All patients' information was obtained from the transplant database system (TBase) which is specially designed for kidney transplant patients under local regulation and European Union General Data Protection Regulation . The guide novo glomerulopathy, thrombotic microangiopathy (TMA), and hepatitis C virus-associated membranoproliferative glomerulonephritis (MPGN). Patients with mammalian target of rapamycin (mTOR) inhibitors-induced proteinuria were also excluded.All adult kidney transplant recipients with a biopsy-proven diagnosis of TG defined by the Banff consensus guideline were eligible for this study. Biopsies with secondary glomerular pathology that can cause glomerular basement membrane double contours were excluded, such as recurrent/n = 17) without a 24-h urine test, spot urinary protein concentrations (mg/L) were converted to 24-h urine test unit (g/24 h) assuming 2L urinary output per day . For recipients with multiple biopsies, only the first identified TG diagnosis was considered for enrollment in the study.vasa recta (C4d), interstitial fibrosis (ci), tubular atrophy (ct), vascular fibrous intimal thickening (cv), glomerular basement membrane double contours (cg), arteriolar hyalinosis (ah), and mesangial matrix expansion (mm).Formalin-fixed paraffin-embedded sections were cut at 3 μm and stained with HE, Masson's trichrome, periodic acid-Schiff, silver methenamine staining for light microscopy. C4d was detected on formalin-fixed tissue stained with polyclonal anti-C4d antibody . Two pathologists (K.W. and B.R.) examined the biopsies independently, blinded to clinical data. All biopsy features were evaluated and scored semiquantitatively according to the Banff 2018 classification. These scores included grade of interstitial inflammation (i), tubulitis (t), intimal arteritis (v), glomerulitis (g), peritubular capillaritis (ptc), endothelial cells C4d staining extent of peritubular capillary and medullary All kidney transplantation was performed based on negative complement-dependent cytotoxicity crossmatch using T- and B-lymphocytes. Panel reactive antibody (PRA) was detected by the solid-phase assay. PRA was calculated as the percentage of positive reaction against a panel of HLA-antigens in donor blood.All patients' serum samples were obtained at allograft dysfunction or once a year after transplantation since 2006 as previously described . Samplest-tests. Continuous variables from different distribution were described using medians (ranges) and were compared within two groups using the non-parametric Mann-Whitney U-test. Categorical variables were summarized by numbers (percentages) and were compared between two groups with Chi-squared test (or Fisher exact test if appropriate). The relationships between the level of proteinuria and Banff lesion scores were determined by Spearman correlation analysis. All tests were two-tailed.The normality of data was tested using the Kolmogorov-Smirnov test. Normally distributed data were expressed as mean ± standard deviations and were compared between two groups using Student's P < 0.1) in the univariable analysis that were considered clinically relevant were fitted into a multivariable logistic regression model according to a forward selection, likelihood ratio test with an elimination threshold of 0.1. The Hosmer Lemeshow test was performed to test the goodness of fit for logistic regression models. The multicollinearity of covariables was tested by examining tolerance and the variance inflation factor. No collinearity was detected in our dataset after continuous variables were dichotomized. Internal validation was performed using 2,000 bootstrap samples to reduce overfit bias. The discriminative performance of models was evaluated using the area under the curve (AUC) of the receiver operator characteristic (ROC) analysis. An AUC value of 0.7–0.8 denotes a clinically useful test and a value of 0.8–0.9 is considered as an excellent predictive value. The performance of both the initial model and adjusted model was assessed in terms of discrimination and calibration .The logistic regression model was developed and reported in accordance with recommendations for the assessment and reporting of multivariable logistic regression in transplantation literature . The indP < 0.05 was considered to indicate statistically significant difference.Statistical analyses were performed using IBM SPSS Statistics 26.0 , SPSS Modeler 12.0 , and GraphPad Prism 8.0  software. de novo glomerulonephritis (n = 32), TMA (n = 31), hepatitis C-virus associated MPGN (n = 2) were excluded. After further excluding the patients with mTOR inhibitors-induced proteinuria , a total of 165 patients were enrolled in this study  were found in 346 biopsies  from 251 kidney transplant recipients. Biopsy cases with recurrent/is study .The baseline demographics and clinical characteristics of the 165 patients with TG after kidney transplantation are presented in Fifty patients (30.3%) had experienced delayed graft function. Several baseline characteristics varied significantly between two groups categorized according to proteinuria (0.3 g/24 h) were therefore appropriately considered as confounders in multivariable analysis.P < 0.05) (The first biopsy-proven TG was diagnosed at a median of 72 months (from 2 to 224 months) from transplantation to biopsy when the average age of kidney transplant recipients was 50.47 ± 14.82. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) of TG patients were 140.01 ± 21.01 mmHg and 83.74 ± 15.38 mmHg, respectively, at the time of biopsy. Among the enrolled patients, 126 patients  showed antibody-mediated rejection (ABMR) (including 79 cases of chronic active ABMR and 47 cases of chronic ABMR), and 39 patients  were classified as isolated transplant glomerulopathy (iTG). The maintenance immunosuppressant regimens consisted mostly of tacrolimus  and mycophenolate mofetil . The majority of patients  were treated with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) followed by calcium channel blocker (CCB) . TG patients with proteinuria had significantly higher SBP, DBP, and percentage of tacrolimus and CCB usage ( < 0.05) .n = 43) had a cg score of 1; 31.52% (n = 52) had a cg score of 2; 42.42% (n = 70) had a cg score of 3. More than half of TG patients had chronicity scores  and i score as well as mm score. As features of microvascular inflammation (MVI), Banff lesion score g and ptc of TG patients were relatively low. The patients with positive staining for peritubular capillary C4d accounted for 20% (33/165).The distribution of histological changes in all TG patients is shown in When stratified by proteinuria, the Banff scores showed no statistically significant differences between patients with or without proteinuria (defined as ≥0.3 g/24 h) other than cg and mm scores . cg scorP < 0.001). As forms of MVI, Banff lesion score g and ptc correlated with each other significantly . Interstitial fibrosis/tubular atrophy scores ci and ct were highly correlated   .P = 0.003) and mm , whereas the interstitial fibrosis/tubular atrophy scores, C4d scores , and cv  were unrelated  were analyzed by multivariable logistic regression, peak PRA ≥5%, SBP ≥ 140 mmHg, DBP ≥90 mmHg, tacrolimus-based regimen, use of CCB, positive C4d staining were independently associated with the development of proteinuria in TG patients ) + (1.478×use of CCB = yes)-1.56  and excellent discrimination . The internal validation using bootstrap with 2,000 repetitions showed a similar AUC of 0.80 (95% CI 0.72–0.87)  + (1.576×DBP ≥90 mmHg) + (1.867×peak PRA ≥5%) + (1.515×C4d = positive) + (1.252×tacrolimus-based regimees)-1.56 . This mo72–0.87) . This mo72–0.87) .In this study, we investigated the clinical and histological features of TG patients and further identified the risk factors of proteinuria in TG patients based on almost two decades of consecutive patients' data. Based on the model developed using multivariable logistic regression, we found SBP ≥140 mmHg, DBP ≥90 mmHg, peak PRA ≥5%, positive C4d staining, tacrolimus-based regimen, and CCB usage were independent risk factors for proteinuria. After internal validation, this model still afforded high discrimination  and good calibration (slope of 1.007 and intercept of −0.004).n = 10) had undergone at least 9 months of dialysis treatment in our study, proteinuria was not considered to originate from the native kidneys  in our study was 75.76%. Due to the relatively low threshold for defining proteinuria, the incidence of proteinuria was relatively high compared to a previous study, in which proteinuria was present in 40% out of 55 TG patients with cut-off defined as 0.5 g/day . It is plausible that the use of ACEI/ARB, to a certain extent, represents the potential existence of proteinuria or cardiovascular diseases which may also associate with proteinuria.Similar to other kidney transplant patients, the application of CCB therapy increased the risk of proteinuria in TG patients. This may be due to the vasodilatory effect of dihydropyridine CCB that increases intraglomerular pressure and thus leads to proteinuria , 32. YetContrary to the results of previous studies, C4d deposition in PTC was identified as a risk factor for proteinuria in TG patients in our study , 25. PerUp to 91.43% of TG patients with peak PRA ≥5% had proteinuria, previous reports also noted the association of PRA with proteinuria , 34. IntThe impact of immunosuppressants on proteinuria requires specific analysis. Unlike CNIs and mycophenolate compounds, mTOR inhibitors including sirolimus and everolimus are clearly related to proteinuria , 35. ThuThe present study has several limitations. First, although our study involves one of the largest biopsy-proven TG patients to date, the sample size is still relatively small. Second, due to the lack of external validation strength of our model is unknown for another independent patient population, despite bootstrap is considered the most reliable technique to validate internally for the logistic regression model . Third, Another disadvantage is the fact that no electron microscopy data were available. Regardless of anything else, this must be mentioned that all the data were acquired either at the of transplantation or at the time of biopsy it would be hard to infer the association between “risk factors” and proteinuria. Therefore, further studies should be performed to determine the causation.Taken together, our findings demonstrate that hypertension, peak PRA ≥5%, positive C4d staining, tacrolimus-based regimen, and CCB usage were significantly associated with proteinuria in TG patients. Our multivariable logistic regression model showed good predictive accuracy and optimal calibration, it may assist clinicians in deciding whether a further adjustment should be taken after further prospective study confirmation.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.QZ, KB, BR, and KW participated in research design. QZ, KB, FH, MD, MN, MM, WD, BR, and KW participated in the writing of the paper. QZ, KB, DS, FK, BR, and KW participated in the performance of the study. QZ, KB, and KW participated in data analysis. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.