Postpartum hemorrhage (PPH) is one of the leading causes of maternal mortality. Promptly recovering blood loss is critical for PPH. Intraoperative cell salvage (ICS) is a method to collect and process red blood cells (RBCs) from the blood lost during surgery and transfuse them to the patient’s circulation during or immediately after surgery. Its effectiveness in reducing the demand for allogeneic blood transfusion has been proven, but its effectiveness and safety as a sole treatment for PPH during Cesarean sections are unclear. This is particularly important for patients who cannot or do not want to accept allogeneic blood transfusion.In this prospective randomized controlled study, patients with high risks of PPH were randomized into the ICS group or the control group, receiving ICS or allogeneic RBC transfusion if their hemoglobin level was less than 80 g/L during operation. Data collected include clinical examination, blood cell count, hemoglobin level, coagulation function, and plasma levels of fetal hemoglobin, tissue factor, and alpha-fetoprotein before and after fetal delivery and 0, 2, and 12 h after treatment. Adverse events were recorded.A total of 130 patients were enrolled, aged 33 ± 1 years with a mean gestation period of 37 ± 1 week. The most common cause of Cesarean section was placenta previa, followed by twin pregnancy, scarred uterus, preeclampsia, placental abruption, fetal distress, and placenta accreta spectrum. Bleeding amount was similar between the two groups. The ICS group, compared to controls, had more efficient increases in levels of hemoglobin, RBC, and hematocrit . Coagulation function was maintained in the ICS group but reduced in controls 24 h after transfusion, indicated by significantly reduced fibrinogen level and prolonged prothrombin time (PT), thrombin time (TT), and activated partial thromboplastin time (aPTT) . There was a transient but significant decrease in plasma tissue factor and alpha-fetoprotein levels and an increase in plasma fetal hemoglobin level with ICS treatment in the postpartum period. No adverse event occurred with ICS intervention.ICS is an effective and safe intervention for patients with a high risk of PPH during elective or emergency Cesarean section. It can effectively clear tissue factors and alpha-fetoprotein but not fetal hemoglobin. Obstetric hemorrhage is a leading cause of maternal mortality, accounting for 27.1% of all maternal deaths . This fiIntraoperative cell salvage (ICS) is a technology that collects red blood cells (RBCs) from the blood lost during surgeries and transfuses them back to the patient’s circulation during or immediately after surgery. ICS is a relatively simple technology, which can effectively and significantly reduce the demand for allogeneic blood transfusions and secondary complications . It has We therefore conducted a prospective randomized controlled study in patients undergoing Cesarean section with high risks of PPH to determine whether the routine use of ICS during Cesarean section can effectively and safely improve blood loss using blood cell count, coagulation function, and complications following ICS treatment in comparison with standard allogeneic RBC transfusion. In addition, we sought to assess the impact of ICS on risk factors and fetal components that are involved in maternal hemorrhage, including plasma tissue factor (TF), alpha-fetoprotein (AFP), endothelin-1 (ET-1), and fetal hemoglobin.This is a prospective randomized controlled study. During the period from August 2017 to December 2019, patients undergoing Cesarean section were recruited and randomized at a 1:1 ratio into either the ICS group or the control group receiving allogeneic RBC transfusion. The study was performed in accordance with relevant guidelines/regulations, and the study protocol was approved by the Ethics Committee of Haidian Maternal and Child Health Hospital, Beijing, China. All participants gave written consents. The study design is shown in Inclusion criteria: 1) 21–45 years old; 2) undergo elective or emergency Cesarean section; 3) have high risks of PPH such as placenta previa and placenta accreta spectrum; 4) history of multiple Cesarean section and PPH.Exclusion criteria: 1) preoperative hemoglobin (Hb) <90 g/L; 2) comorbidities including cardiovascular disease, hematological diseases, autoimmune disorders, or acute fatty liver/Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome; 3) Rh-negative; 4) receiving preoperative anticoagulation therapy or allogeneic RBC transfusion within 3 months before the study; 5) participating in other clinical trials during pregnancy; 6) having any diseases that could lead to the inability to cooperate in the study, such as mental illness and language comprehension disorders; 7) refusing to accept allogeneic RBC transfusion.Preeclampsia is defined as new onset of hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90) accompanied by proteinuria. Placenta previa is defined as the placenta partially or completely covering the cervix. Placenta accreta spectrum is defined as when the placenta grows too deeply into the uterine wall and remains attached partially or completely after delivery. PPH is defined as greater than 1,000 ml estimated blood loss during Cesarean delivery.All patients underwent Cesarean sections under general or spinal anesthesia. During the operation, ICS or allogeneic RBCs were given to the patients who had a hemoglobin level <80 g/L to achieve a hemoglobin level ≥80g/L at the end of surgery. The transfusion procedure followed the Annex III of the “Clinical Blood Transfusion Technical Guidelines for Surgery and Trauma Patients” of the Ministry of Health, China. The amount of transfusion was recorded.For patients in the ICS group, an XTRA Autotransfusion System  was installed before the operation Figure 2Before surgery, all patients underwent baseline assessment. Data collected include age, body weight, and medical history of pregnancy and Cesarean section, weeks of gestation, comorbidities, and placental position. Blood was sampled to evaluate blood cell count, hemoglobin and hematocrit levels, blood gas analysis, electrolytes, liver and kidney function, and coagulation tests including the prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT).Intraoperative monitoring included vital signs, bleeding volume, hemoglobin level, transfusion volume of allogeneic RBCs, the volume of recollected and transfused ICS, infusion volume of other blood products, and adverse events. The calculation method of intraoperative blood loss: total bleeding amount = blood wet area of gauze (10 cm * 10 cm = 10 ml) + blood volume in the suction bottle, where the blood volume in the suction bottle = the total amount of liquid in the suction bottle - the total amount of flushing anticoagulant solution.In the ICS group, plasma levels of fetal hemoglobin, TF, AFP, and ET-1 were measured before and after fetal delivery and 0, 2, and 12 h after ICS treatment. In the control group, plasma levels of fetal hemoglobin, TF, AFP, and ET-1 were measured before and after fetal delivery.The newborns were assessed using the Apgar score system, including heart rate, muscle tone, and other signs at 1 and 5 min after birth to determine if any extra medical care or emergency care is required. A score of 8–10 points is normal, 4–7 points indicate mild asphyxia, and 0–3 points indicate severe asphyxia.Postoperative monitoring included vital signs, surgical complications, and infections. The following tests were repeated at 24 h and 3 days after Cesarean section, including hemoglobin level, complete blood cell count, hematocrit level, blood gas analysis, electrolytes, liver and kidney function, and coagulation tests.Biochemistry tests were performed, including chemiluminescence microfluidic immunoassay for AFP, enzyme-linked immunosorbent assay for TF and ET-1, and high-pressure liquid chromatography for fetal hemoglobin.post-hoc tests was used to compare the results of the same test at different time points. In this study, p values <0.05 are considered statistically significant.Statistical analysis was conducted using SPSS version 21.0 . Quantitative variables are presented as mean ± standard deviation (SD) for data with normal distribution or median (range) for data with non-normal distribution. Comparison was conducted using Student t-test or Mann–Whitney U test. Qualitative variables are presented as number (%) and compared with chi-square test. One-way ANOVA followed by Bonferroni During the period from August 2017 to December 2019, 130 patients undergoing Cesarean section were recruited and randomized into either the ICS group (n = 65) or the control group receiving allogeneic RBC transfusion (n = 65) Figure 1In the ICS group, the mean ICS transfusion was 508.92 ± 26.83 ml, and four patients (6.15%) required additional allogeneic RBCs and plasma transfusion due to severe PPH . In the control group, the mean allogeneic RBC transfusion was 689.23 ± 50.97 ml; 23 patients (35.38%) had additional plasma transfusion (p < 0.0001 compared with 6.15% in the ICS group); and six patients had no blood transfusion due to small amount of bleeding (<500 ml). Very few patients had platelet transfusion in both groups .In order to exclude confounding effects of allogeneic RBC transfusion, four patients with additional allogeneic RBC transfusion in the ICS group were excluded. Six patients without blood transfusion in the control group were also excluded. Consequently, blood cell count and biochemistry data were collected from 120 patients (61 in the ICS group and 59 in the control group) for further analysis. As shown in Plasma levels of TF, AFP, fetal hemoglobin, and ET-1 were not significantly different before and immediately after child delivery in both groups . Furthermore, no difference was found in any of these factors between the two groups  Table 4.Within 2 h of ICS, no patient showed worsening bleeding. No adverse events such as amniotic fluid embolism, infection, hypotension, allergy, adverse cardiovascular events, or delayed PPH were reported in the ICS group. In the control group, two patients had rashes following allogeneic RBC transfusion but recovered after intravenous injection of dexamethasone 10 mg. No other adverse events and complications were reported.In this prospective randomized clinical trial, we evaluated the effectiveness and safety of ICS implementation in patients with a high risk of PPH who underwent elective or emergency Cesarean sections. Our results indicated that ICS treatment increased hemoglobin level more effectively and maintained coagulation function compared to allogeneic RBC transfusion. Although ICS treatment led to a transient decrease in plasma TF and AFP levels and an increase in plasma fetal hemoglobin level in the postpartum period, such changes only lasted for less than 24 h. There was no adverse effect such as amniotic fluid embolism, infection, hypotension, or allergy following ICS treatment.PPH is a leading cause of maternal mortality. How to effectively improve blood loss by blood transfusion in PPH patients is therefore critical. Substantial data from previous studies have supported the use of ICS technology in elective and emergency Cesarean sections . HoweverOne of our main findings is that coagulation function was deteriorated with allogeneic RBC transfusion but not with ICS treatment. The underlying mechanisms may be related to the significantly reduced platelet count and plasma fibrinogen level in the controls. A previous study by Yang et al.  demonstrThere are concerns that the slow reinfusion rate of filter may cause the saturation of ICS, thereby inducing bradykinin-mediated hypotension . HoweverAmniotic fluid embolus is a rare but vital condition during child delivery, accounting for high mortality and morbidity rates . It is oIn contrast to TF and AFP, fetal hemoglobin contamination in the blood collected during Cesarean sections is impossible to be cleared by the ICS system. We found that the fetal hemoglobin level was significantly elevated in the filtered RBC suspension and in maternal blood immediately after ICS transfusion, suggesting fetal hemoglobin contamination. Although its level decreased after 2 h, the isoimmunization secondary to the exposure to fetal hemoglobin may lead to erythroblastosis in subsequent pregnancies. In contrast to our findings, Sullivan and Ralph  have repThe present study has some limitations. This is a single-center study. The number of participants recruited in each group is only 65. Nevertheless, all patients recruited had risk factors of PPH. Our findings still provide solid evidence for the implementation of ICS in patients with a high risk of PPH.In conclusion, ICS is an effective and safe intervention for blood loss recovery in patients with a high risk of PPH during elective or emergency Cesarean section. The ICS process can effectively clear TFs and AFP but not fetal hemoglobin. It is necessary to monitor isoimmunization for future pregnancies.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by Ethics Committee of Haidian Maternal and Child Health Hospital. The patients/participants provided their written informed consent to participate in this study.BL and LW contributed to conception and design of the study. BL, MG, XD, SH, XL, and YW involved in data collection. BL performed the statistical analysis and wrote the first draft of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version. LW was the lead of study and funding holder.This study was supported by the Beijing Science and Technology Commission Research Fund . Project number: Z171100001017151.We would like to thank Prof. Hongmei Jia, Prof. Hongqing Jiang, Prof. Fengqiu Li, Prof. Dongru Cao, Dr. Jinxin Hao and Dr. Juan Zuo for their valuable support.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Mild to moderate CKD was an independent predictor of AF recurrences after the blanking period . In conclusion, a multicenter analysis of AF patients treated with cryoablation revealed mild to moderate reductions in renal functions were associated with a higher risk of AF recurrences. Conversely, the procedural success and complication rates were similar in patients with normal, mildly reduced, or mild to moderate reduction in eGFR. The aim of this research was to evaluate if patients with chronic kidney disease (CKD) and mild or mild to moderate depression of renal function have an increased risk of atrial fibrillation (AF) recurrences after cryoballoon (CB) ablation. We performed a retrospective analysis of AF patients undergoing pulmonary vein isolation (PVI) by CB. The cohort was divided according to the KDIGO CKD-EPI classification into a (1) normal, (2) mildly decreased, or (3) mild to moderate reduction in estimated glomerular filtration rate (eGFR). Freedom from AF recurrences was the primary endpoint. A total of 1971 patients were included  in the study. Acute success and complication rates were 99.2% and 3.7%, respectively, with no significant differences among the three groups. After a follow-up of 24 months, AF recurrences were higher in the mildly and mild to moderate CKD groups compared to the normal kidney function group (23.4% vs. 28.3% vs. 33.5%,  Atrial fibrillation (AF) is frequently associated with comorbidities that influence the course of AF, along with time, patient symptoms, thromboembolic risk, and patient outcome ,2,3. AmoThe aim of the present research is to evaluate the follow up of AF patients treated with cryoballoon (CB) ablation for PVI, in order to assess if patients with mild or mild to moderate depression of renal function are associated with an increased risk of AF recurrences at mid to long-term, as compared with patients with normal renal function.Patients with AF who had undergone CB catheter ablation for PVI, and who were participating in the One Shot TO Pulmonary vein isolation (1STOP) project within the One Hospital ClinicalService (OHCS) were considered for the present analysis. The project aims to improve the quality of diagnostic and therapeutic strategies through the use of CB ablations in clinical practice. It consists of a shared environment for the prospective collection, management, analysis, and reporting of data from patients in whom Medtronic devices have been implanted. Patients are prospectively followed by 25 Italian cardiology centers according to clinical practice and guidelines through standard in-hospital visits. An independent scientific committee of physicians prospectively identifies key clinical questions on a yearly basis for analysis and publication. A charter assigns the ownership of data to the centers and governs the conduct and relationship of the scientific committee and Medtronic. The project was approved by each site’s Medical Ethics Committee or medical director, and it conforms to the principles outlined in the Declaration of Helsinki. Each patient provided informed consent for data collection and analysis. 2); (2) mildly decreased kidney function, meaning a mild reduction in eGFR (60–89 mL/min/1.73 m2); (3) mild to moderate CKD, meaning a mild to moderate reduction in eGFR (30–59 mL/min/1.73 m2); (4) severe CKD, meaning a severe reduction in eGFR (15–29 mL/min/1.73 m2). Patients with severe CKD (eGFR 15–29 mL/min/1.73 m2) were excluded from the outcome analysis because they had been clinically judged as a small, non-representative sample of the CB ablation population.The present study is a retrospective analysis of a series of 1971 prospectively enrolled patients. Patients were included if they were treated for AF through PVI with one of four generations of the CB catheter, had a clinical follow-up reported in the OHCS database, had not had any previous PVI or previous AF ablations, and had creatinine data recorded before the ablation. The total patient cohort was divided into the following four groups according to the KDIGO CKD-EPI classification: (1) normal kidney function, meaning a normal or increased eGFR  of a single PV procedure in patients with and without a history of mild to moderate CKD. Ablation is defined as successful in the absence of asymptomatic or symptomatic atrial arrhythmias lasting more than 30 s, as identified by Holter monitoring or AF detected at a 12-lead ECG after the blanking period (3 months since the date of ablation procedure). The occurrence of AF during the first 3 months after the AF ablation was defined as an early recurrence of AF (ERAF) and, as such, was excluded from the main analysis. CKD has been calculated according to the patient’s eGFR class, using the KDIGO CKD-EPI method, and considering the patient’s age and the creatinine value collected at the time of the ablation. The acute success rate of PV has been defined as the ratio between the number of effectively isolated PVs and the number of target PVs.p-values < 0.025. The SAS software, version 9.4,  was used to perform statistical analyses.Baseline characteristics and clinical and procedural data have been summarized for the three considered patient groups according to the KDIGO CKD-EPI classification. Continuous variables were reported as mean and standard deviation (SD) or as median and interquartile range (IQR). Categorical variables were reported as counts and percentages. Patients with normal kidney function were compared with those presenting mildly decreased kidney function and those with mild to moderate CKD using Wilcoxon’s test for continuous variables, and the chi-square test or Fisher’s exact test for extreme proportions in case of categorical variables, as appropriate. Annual rates of AF recurrence were compared by means of a mixed Poisson model. The analyses of time-to-first event were described using Kaplan–Meier curves and compared between the groups with the log-rank test. The follow-up duration (months) was computed from the date of the CB catheter ablation to the date of the last available follow-up or date of the event. To find predictors of AF recurrences, a Cox regression was used for both univariable and multivariable analyses, and the proportional hazard hypothesis was tested. The hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for all potential predictors. The multivariable Cox regression model used stepwise selection with entry = 0.30 and stay = 0.05 criteria, respectively, and AF as the dependent variable. Statistical tests were based on a two-sided significance level of 0.05. The Bonferroni method has been used to adjust for multiple comparisons. According to Bonferroni correction, post-hoc comparisons between patient groups were considered statistically significant for 2), and, as such, were included in the analysis. The patients were then classified according to the following KDIGO CKD-EPI definition: 774 (39.3%) as normal kidney function patients, 1015 (51.5%) as mild decreased kidney function patients, and 182 (9.2%) as mild to moderate CKD patients. The baseline clinical characteristics are shown in p < 0.001), more likely to be female , more frequently had hypertension  and had a higher risk of CHA2DS2-VASC (93.9% vs. 77.6% vs. 54.6%) or any underlying heart disease . Out of the 1976 patients who underwent CB catheter ablation for AF treatment from May 2010 to May 2021, as extracted from the One Hospital ClinicalService 1STOP project, 1971 (99.7%) had non-severe CKD . Despite the fac that no statistically significant differences were found when the total procedure duration has been compared by kidney status (p = 0.142), we have observed slightly increased ablation times for the mild to moderate CKD group when compared with the normal kidney function patients . No differences were found in the risk of acute complications . Index procedure data and acute results are summarized in p = 0.092]. During the follow-up, AF recurrence was reported in 529 patients, 181  in the normal kidney function group, 287  in the mildly decreased kidney function group, and 61  in the mild to moderate CKD group . The Kaplan–Meier 3 year freedom from AF recurrence were 70.2% (66.0–73.9%) vs. 63.6% (59.8–67.2%) vs. 54.7% (44.5–63.7%), respectively,  months with no differences among the three analyzed groups [25 (Q1–Q3: 11–46) months vs. 23 (Q1–Q3: 10–39) months vs. 22 (Q1–Q3: 8–39) months, respectively, in the normal kidney function, mildly decreased kidney function, and mild to moderate CKD group, p = 0.096). Predictors of freedom from AF after the CB catheter ablation are presented in p = 0.010 for mildly decreased vs. normal kidney function, and post-hoc p = 0.008 for mild to moderate CKD vs. normal kidney function, respectively). However, at multivariable analysis  patients. Notably, data from the group with the worst renal function highlighted the highest rate of ERAF  was significantly and independently associated with AF recurrences after the blanking period. Other factors associated with the risk of recurrences were a period from the first episode of AF longer than one year, and AF ablation performed for persistent, i.e., non-paroxysmal, AF.In our multicenter study that included around 2000 patients, a worse renal function was associated with a different clinical profile, as compared with patients with normal renal function, with patients who had a lower eGFR being older, more frequently affected by underlying heart disease, and with a higher CHAOur findings are noteworthy because they are derived from a multi-center collection of data from Italian centers using cryoballoon ablation, a technique widely implemented in daily practice ,17,18,19Balloon cryoablation is now a well-established technique, with some advantage in terms of procedure time and need for re-ablation as compared to radiofrequency ablation ,27,28. OAdvanced CKD and AF share common risk factors with many pathophysiological inter-relationships, with the most powerful influence on AF and clinical outcomes being renal dysfunction and progression in end stage renal disease including dialysis ,34,35. From this perspective, our research is quite reassuring, since it is focused on patients’ mild to moderate reduction of eGFR using cryoballoon technology. The assessment of renal function should be done in accordance with the consensus documents and with formulas for estimating renal function that are more appropriate and validated . DespiteOur results show that the efficacy of cryoablation in preventing AF recurrences is higher when the procedure is performed within one year of the first AF episode. This is in line with current recommendation of not considering AF ablation as a last-resort therapeutic strategy, but rather to propose it before the development of atrial dilatation and atrial cardiomyopathy ,46,47,48The present research has specific limitations that should be acknowledged. This a retrospective analysis of prospectively collected data and, as such, has some limitations linked to its observational nature. A specific limitation is the absence of data regarding the contrast medium used in each procedure. Data presented do not imply causality, but rather describe an association, since we cannot exclude the influence of non-measured confounding forces. However, research endpoints were pre-specified.In a multicenter analysis on AF patients treated with the technique of cryoballoon ablation, even mild to moderate reductions in renal functions are associated with a higher risk of AF recurrences after the blanking period. Conversely, the procedural success rates and acute complications were similar in subgroups with a normal, mildly reduced, or mild to moderate reduction in eGFR.


The relationship between ambulatory arterial stiffness index (AASI) and left ventricular diastolic dysfunction (LVDD) in patients with heart failure with preserved ejection fraction (HFpEF) is unknown. We aimed to investigate the association between the AASI and LVDD in HFpEF.We prospective enrolled consecutive patients with HFpEF in Chongqing, China. Twenty-four-hour ambulatory blood pressure monitoring (24 h-ABPM) and echocardiography were performed in each patient. AASI was obtained through individual 24 h-ABPM. The relationship between AASI and LVDD was analyzed.P = 0.001), septal E/e′ , lateral E/e′  and E . After adjusting for conventional risk factors, AASI was still an independent risk factors of mean E/e′ > 10 in patients with HFpEF , and the association between AASI and mean E/e′ > 14 was reduced . AASI had a partial predictive value for mean E/e′ > 10 , while the predictive value for mean E/e′ > 14 was attenuated .A total of 107 patients with HFpEF were included. The mean age was 68.45 ± 14.02 years and 63 (59%) were women. The patients were divided into two groups according to the upper normal border of AASI (0.55). AASI > 0.55 group were more likely to be older, to have higher mean systolic blood pressure and worsen left ventricular diastolic function than AASI group ≤ 0.55. AASI was closely positive related to the diastolic function parameters, including mean E/e′ (r = 0.307, AASI was positive related to E/e′ in HFpEF and might be an independent risk factor for the increase of mean E/e′.The online version contains supplementary material available at 10.1186/s12872-022-02679-6. Ambulatory arterial stiffness index (AASI) is defined as 1 minus the regression slope of diastolic on systolic blood pressure (BP) values obtained from the 24-h ambulatory blood pressure monitoring (ABPM) recordings –5.Heart failure with preserved ejection fraction (HFpEF) is characterized by left ventricular diastolic dysfunction (LVDD) and cardiac remodeling , which has become a major cause of hospitalization for the elders –8. Hyper2). 24-h ABPM and echocardiography were carried out on all patients during hospitalization.From November 2020 to February 2021, we conducted a prospective observational study registry with clinicaltrials.gov identifier NCT05059769. This study initially enrolled 129 patients with HFpEF in the First Affiliated Hospital of Chongqing Medical University and we added 23 patients from March 10 to 24, 2022. Inclusion criteria included age > 18 years and conform to HFpEF diagnostic criteria  , whereasEchocardiography was performed in patients with suspected HFpEF . HFA-PEFF score was calculated by left ventricular diastolic function index and NT-proBNP. Score ≥ 5 was considered to be diagnostic of HFpEF .Twenty-four-hour ABPM was performed using the Mobil-O-Graph NG (Z02505), a non-invasive ambulatory BP monitoring instrument. BP readings were obtained at 15-min intervals during the day and at 30-min intervals during the night. Of the total readings, ≥ 80% was considered valid. Furthermore, for the records valuable, at least 14 measurements during the daytime period or at least 7 measurements during the night or rest period were required ) if they are normally distributed or median (interquartile range: [IQR]) if they are not. XThe study initially enrolled 129 patients with HFpEF and we added 23 patients from March 10 to 24, 2022. Patients who had secondary hypertension (n = 11), severe valvular heart disease (n = 11) and persistent atrial fibrillation (n = 23) were excluded  . In Model II, after adjusting ave-sBP, AASI was independently relevant with mean E/e′ . The results of Model III showed that age  and ave-sBP  were not independently associated with mean E/e′, but AASI was still an independent relevant factor of mean E/e′   (Table We chose mean E/e′ > 10 as the risk threshold for LVDD in Table P = 0.015). Multivariate regression analysis showed that after adjusting for conventional risk factors including female, diabetes, and CAD, AASI was still an independent risk factor   HFpEF with high AASI were more likely to be older, to have higher mean systolic blood pressure and worsen left ventricular diastolic function; (2) AASI was positively correlated with left ventricular diastolic dysfunction parameter (E/e′); (3) AASI might be an independent risk factor for the increase of mean E/e′ in patients with HFpEF.HFpEF is a group of syndromes with left ventricular diastolic dysfunction as the main clinical manifestation, often accompanied by risk factors such as advanced age, hypertension and diabetes , 17, whiIn the present study, we found that HFpEF with high AASI were more likely to be older, to have higher systolic blood pressure. This can be explained by the reason that the elderly and high sBP were major factors contributed to arterial stiffness , 20. TheIn our study, Pearson correlation analysis confirmed that the age and ave-sBP were related to E/e′. However, after adjusting for above mentioned risk factors, an independent correlation between AASI and mean E/e′ was still observed in the multivariate linear regression analysis.Previous studies reported that conventional risk factors such as age, hypertension, diabetes, BMI and so on were closely positive related to cardiac dysfunction –25. E/e′ROC curve analysis indicated that AASI might have a predictive value for mean E/e′ > 10 in patients with HFpEF, while the predictive value for mean E/e′ > 14 was attenuated. AASI is one of the major indicators of arterial stiffness. AASI comes from 24-h ambulatory blood pressure monitoring data and is affected by the dynamic changes of blood pressure. Its measurement is different from the pulse wave pulse speed while it is closely correlated with aortic pulse wave velocity and the central and peripheral systolic augmentation indexes. Our findings supported that arterial stiffness might serve as risk factors for the development of HFpEF , 30. SevThe present study has several limitations that should be considered. First, because this is an observational study, we cannot determine the causality of the results of the study. Second, the sample of this study was small and our findings still need to be further confirmed. Third, because of the small sample, whether AASI was associated with major cardiovascular adverse events in HFpEF could not be determined. Fourth, E/e’ was only one of the indicators chose in our cohort to reflect LVDD, while other indicators should be involved in further study. We found the predicting value of AASI for LVDD was limited, whether it had the predicting value for LVDD needs more research.AASI was positive related to E/e′ in HFpEF and might be an independent risk factor for the increase of mean E/e′.Additional file 1. Table S1. Pearson correlations between clinical characteristics and right ventricular systolic function. Table S2. Logistic regression of AASI > 0.55 predicting mean E/e′ > 14. Figure S1. ROC curve for AASI to predict mean E/e′ > 14.


Syndrome elements are regarded as the smallest unit of syndrome differentiation, which is characterized by indivisibility and random combination. Therefore, it can well fit the goal of syndrome differentiation and unity. t-test and nonparametric test, logistic regression model is used to mine the main syndrome elements, and neural network multilayer perceptron is used to predict the feature model.  Clinical physicochemical indicators are important references for disease diagnosis, but they are often not used too much in the process of TCM syndrome differentiation. In the era of intelligence, communicating TCM syndrome differentiation at the macro level with physiological and pathological processes at the micro level  is an effective tool to realize intelligent medicine. Taking the collected relevant clinical physical and chemical indexes as the research object, on the basis of routine +, TG, LDL, BNP, LVEDd, and EF in blood stasis patients. Taking blood stasis as the dependent variable and the above physical and chemical indexes with statistical significance (P < 0.05) as independent variables. Compared with non-qi depression patients, there were significant differences in atpp, TG, TC, LDL, LVESD, and FS in qi depression patients (P < 0.05). Taking Yin deficiency as dependent variable and the above physical and chemical indexes  with statistical significance (P < 0.05) as independent variables, binary logistic regression analysis was carried out.  Compared with non-blood stasis patients, there were significant differences in HGB, PLT, Pt, PTA, Na The combination pattern of physical and chemical indexes obtained from the neural network model provides a clinical reference basis for identifying the syndrome elements of unstable angina pectoris complicated with anxiety, such as blood stasis, qi depression, Qi deficiency, yin deficiency, phlegm turbidity, and qi stagnation. Chinese medicine has remarkable curative effect in the treatment of patients with heart disease. Traditional Chinese medicine (TCM) has apparent advantages in stabilizing the heart disease, improving heart function, and improving the quality of life. In recent years, inspired by modern medicine, many doctors try to explain the mechanism of syndrome with a single experimental index in order to solve the problem of syndrome inconsistency. Because syndrome is the overall response of multiple system levels , the resSyndrome elements are regarded as the smallest unit of syndrome differentiation, which is characterized by indivisibility and random combination . It is tt-test and nonparametric test, logistic regression model is used to mine the main syndrome elements, neural network multilayer perceptron is used to predict the characteristic model, and the correlation between the main syndrome elements and physical and chemical indexes of unstable angina pectoris complicated with anxiety is analyzed to explore the role and significance of the combination mode of clinical physical and chemical indexes in the diagnosis of syndrome elements.Therefore, based on the syndrome related data collected in the process of clinical epidemiological investigation, this study explored the distribution and combination characteristics of TCM syndrome elements in unstable angina pectoris complicated with anxiety and provides reference for the unity of syndrome differentiation of the disease. Then, taking the collected relevant clinical physical and chemical indexes as the research object, on the basis of routine The cases came from patients hospitalized in the Department of Cardiology of Zhengzhou hospital of traditional Chinese medicine from January 2017 to January 2019. Our study was approved by the institutional review board of the hospital, and written informed consent was obtained from each participant.Diagnostic criteria of unstable angina pectoris: refer to the 2016 guidelines for the diagnosis and treatment of unstable angina pectoris and non-ST segment elevation myocardial infarction. Diagnostic criteria of anxiety state: Under the guidance of psychiatrists, all patients were scored and investigated with HAMA anxiety scale. Specific criteria: ≥29 points are classified as severe anxiety state; ≥21 points, obvious anxiety; ≥14 points, there must be anxiety; ≥7 points, may have anxiety; and <7 points, no anxiety.Referring to the relevant parts in terms of clinical diagnosis and treatment of traditional Chinese medicine syndrome  in 1997 The inclusion criteria are as follows: (1) 18-79 years old; (2) unstable angina pectoris; (3) HAMA anxiety was between 14 and 29 points; (4) normal cognitive function and no reading and writing impairment; and (5) after informed consent, they can voluntarily cooperate and participate in the investigation and research.μMol/L), serious electrolyte disorders, blood system and other primary diseases, malignant tumors, pulmonary embolism, diabetes combined with severe complications, hypertension, hyperthyroidism, hypothyroidism, and other serious endocrine diseases or other uncontrollable systemic diseases; and (4) pregnant or lactating women.The exclusion criteria are as follows: (1) severe valvular disease, cardiomyopathy, pericardial disease, congenital heart disease, cardiogenic shock, acute myocarditis, infective endocarditis, and severe arrhythmia with hemodynamic changes; (2) other congenital diseases such as rheumatic aortic stenosis and syphilis; (3) liver dysfunction  and renal insufficiency  patients who were wrongly included, (2) patients whose data were incomplete for various reasons after inclusion and could not be counted; and (3) patients who were unable to complete the study due to mental or physical disorders.All selected patients completed white blood cell (WBC), red blood cell (RBC), hemoglobin concentration (HGB), platelet (PLT), thyroglobulin (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), cardiac troponin (cTnI), myoglobin, CKMB, alt, AST, bun within 1-3 days after admission creatinine (CR), N-terminal pro-B-type natriuretic peptide (NT proBNP), potassium (K+), sodium (Na+), chloride (Cl-), calcium (Ca2+), prothrombin time (PT), prothrombin activity (PTA), partial prothrombin time (APTT), fibrinogen concentration (FIB), D-dimer (D-D), left ventricular end diastolic diameter (LVEDd), left ventricular end systolic diameter (LVESD), left ventricular posterior wall thickness (LVPW), ventricular septal thickness (IVS), left ventricular stroke output (SV), output per minute (CO), left ventricular end diastolic volume (EDV), left ventricular end systolic volume (ESV), ejection fraction (EF), left ventricular short axis shortening rate (FS), left atrial inner diameter (LAD), right ventricular inner diameter (RIV), and other examinations. Fill in the results in the clinical information collection form and attach relevant copies.P < 0.05) entered into logistic in each syndrome element as the covariate and each syndrome element as the dependent variable; a neural network model was established and tested.The dependent variable is a binary variable. Binary logistic regression square analysis is used to assign values to the dependent variable, in which “yes =1” and “no =0.” The method is forward: Wald (forward stepwise method). The test level of the variable entering the model is less than 0.05. Taking the physical and chemical indexes .SPSS21.0 for statistical analysis of data was used. The measurement data of normal distribution is described by (± s), and the counting index is described by frequency and composition ratio. For the hypothesis test of comparison between the two groups, the measurement data of normal distribution adopts From January 2017 to January 2019, 238 eligible cases were collected in the inpatient department of Cardiology of Zhengzhou hospital of traditional Chinese medicine, of which 13 cases were excluded because the score of HAMA anxiety scale was between 7 and 14; 6 cases were excluded due to lack of blood lipid index test results; 11 cases were excluded due to lack of cardiac color Doppler ultrasound results; and 8 cases were excluded due to lack of liver and kidney function test results. There were 137 more women, with a constituent ratio of 68.5%. The average age of the patients was 59.77 ± 10.79, the minimum age was 33 years old, and the maximum age was 79 years old. Most of the patients were between 51 and 70 years old, accounting for 59.0%. The majority of patients were retired, followed by workers and intellectuals. The most common syndrome elements are blood stasis, accounting for 84.5%, followed by qi depression, a total of 137 cases, accounting for 68.5%, followed by qi deficiency and yin deficiency, accounting for 47.0% and 42.5%, respectively, followed by phlegm turbidity and qi stagnation, accounting for 27.0% and 26.0%, with less heat accumulation, Yang deficiency, dampness, and cold coagulation.t-test, compared with nonblood stasis patients, there were significant differences in HGB, PLT, Pt, PTA, Na+, TG, LDL, BNP, LVEDd, and EF in blood stasis patients (P < 0.05), as shown in Due to the small number of cases of heat accumulation, excessive dampness, Yang deficiency, and cold coagulation, it will not be discussed in the correlation analysis. By nonparametric test or +, TG, LDL, BNP, LVEDd, and EF) with statistical significance (P < 0.05) as independent variables, binary logistic regression analysis is carried out. The results are shown in P < 0.05), as shown in Taking blood stasis as the dependent variable and the above physical and chemical indexes , as shown in Compared with non-qi depression patients, there were significant differences in atpp, TG, TC, LDL, LVESD, and FS in qi depression patients (P < 0.05) as independent variables, binary logistic regression analysis was carried out. As shown in P < 0.05), as shown in Taking qi depression as the dependent variable and the above physical and chemical indexes  with statistical significance (P < 0.05), as shown in Compared with non-Qi deficiency patients, the differences of HGB, APTT, K +, BNP, LVEDd, and LAD in Qi deficiency patients were statistically significant (P < 0.05)  as independent variables, binary logistic regression analysis was carried out. As shown in P < 0.05), as shown in Taking Qi deficiency as the dependent variable and the above physical and chemical indexes with statistical significance (P < 0.05), as shown in Compared with non-Yin deficiency, HGB, APTT, CKMB, LVEDd, and LVPW in patients with Yin deficiency were statistically significant (P < 0.05) as independent variables, binary logistic regression analysis was carried out. As shown in P < 0.05), as shown in Taking Yin deficiency as dependent variable and the above physical and chemical indexes  with statistical significance (P < 0.05), as shown in Compared with non-phlegm turbidity, the differences of HGB, PLT, APTT, alt, AST, Cl-, LVEDd, and FS in patients with phlegm turbidity were statistically significant (P < 0.05) as independent variables, binary logistic regression analysis was carried out. As shown in P < 0.05), as shown in Taking phlegm turbidity as dependent variable and the above physical and chemical indexes  with statistical significance (P < 0.05), as shown in Compared with non-qi stagnation, the differences of WBC, HGB, Pt, FIB, HDL, BNP, LVEDd, and LAD in Qi stagnation patients were statistically significant (P < 0.05) were taken as independent variables for binary logistic regression analysis. As shown in The above physical and chemical indexes  with statistical significance (Taking blood stasis as dependent variable and HGB, Pt, PTA, and EF as covariates, build a neural network model and test the model. The results are shown in Taking qi depression as the dependent variable and APTT, TC, and FS as the covariates, the neural network model is established and tested. The results are shown in Taking Qi deficiency as the dependent variable and HGB, LVEDd, and lad as covariates, the neural network model is established and tested. The results are shown in Taking Yin deficiency as dependent variable and APTT, CKMB, LVEDd, and LVPW as covariates, a neural network model is built and tested. The results are shown in Taking phlegm turbidity as dependent variable and alt, APTT, LVEDdm and FS as covariates, build a neural network model and test the model. The results are shown in Taking qi stagnation as the dependent variable and WBC, Pt, BNP, FIB, LVEDd, and lad as the covariates, the neural network mode is established, and the model is tested. The results are shown in Unstable angina pectoris complicated with anxiety has the common characteristics of unstable angina pectoris and anxiety. Literature studies have found that the most common syndrome elements of coronary heart disease complicated with anxiety are qi stagnation, blood stasis, phlegm, and heat accumulation. In this study, blood stasis, qi depression, Qi deficiency, yin deficiency, phlegm turbidity, and qi stagnation are the most common syndrome elements, which is generally consistent with the results of literature research.From the perspective of syndrome combination, the syndrome types of three factor combination and four factor combination appear more in this study, and the syndrome performance tends to be complex. In the combination of syndromes, other syndromes are mainly superimposed on the basis of qi depression and blood stasis, suggesting that qi depression and blood stasis are the key pathogenesis of the disease and the main pathological link. However, blood stasis syndrome accounts for 84.5% of the total cases, indicating that blood stasis is the initiating factor of the occurrence of the disease. As the “syndrome sanctions” says: “the depression within the seven emotions starts with Qi injury, and the blood will follow.”HGB is a protein, whose main function is to transport oxygen. It combines with oxygen in the lungs, then transports it to various tissues and organs of the whole body, and transports the waste away at the same time . After aFS is an index parameter of left ventricular systolic function. It is a sensitive index reflecting myocardial contractility. Its calculation is the ratio of the shortening value of left ventricular diameter at each contraction to the ventricular diameter at each end of diastole. Studies have shown that there is an obvious linear correlation between FS and EF and FS is more accurate and repeatable than EF in evaluating cardiac systolic function . In thisStudies have shown that lad can accurately predict the mortality of patients with coronary heart disease and heart failure . The enlALT is an important raw material for the synthesis of a variety of non-essential amino acids. It is involved in the diagnosis of many diseases. The liver is the most common site of alt, followed by the kidney, heart, and skeletal muscle. ALT includes the following: two isozymes, alts, and ALTM, exist in cytoplasm and mitochondria, respectively, and the activity of the latter is greater than that of the former. The increase of serum ALT generally indicates liver injury, and the damaged hepatocytes are mainly ALTM , while t1, 2 [FIB is a “protagonist” protein synthesized by the liver and playing a role in the coagulation system. It is a class II glycosylated protein synthesized by the liver and free in plasma. Its half-life is 3-6 days, and its molecular metabolic rate is 31-46 mg/kg. It accounts for about 3% of the total plasma protein . When co1, 2 , 17. In To sum up, the combination pattern of physical and chemical indexes obtained from the neural network model provides a clinical reference basis for identifying the syndrome elements of unstable angina pectoris complicated with anxiety, such as blood stasis, qi depression, Qi deficiency, yin deficiency, phlegm turbidity, and qi stagnation.


There was no association between chemotherapy dose and eGFR. Only two patients showed mild signs of tubulopathy and 11 patients were diagnosed with elevated blood pressure. Conclusion: With adequate supportive measures, such as sufficient hydration according to chemotherapy protocol guidelines, as well as avoidance or close monitoring of additional nephrotoxic medication, impaired kidney function is rare in CNS tumor survivors treated with standard chemotherapy. Nonetheless, long-term follow-up is essential for early detection of mild impairment of kidney function.Purpose: Numerous acute effects of chemotherapeutics on kidney function are well described. However, data on the long-term effects of chemotherapy in the growing population of childhood central nervous system (CNS) tumor survivors is limited. We aimed to evaluate the kidney function of a cohort of long-term CNS tumor survivors treated with different standard chemotherapeutic regimens. Methods: Patients treated for a CNS tumor were prospectively evaluated up to 12 years after completion of their therapy. Examination of kidney function was performed during routine follow-up visits. Blood pressure and blood and urine parameters were analyzed for kidney function evaluation. Glomerular function was assessed by calculating the estimated glomerular filtration rate (eGFR), tubular functions were analyzed by measuring serum electrolytes, bicarbonate and phosphate reabsorption, and proteinuria was assessed by calculating the protein/creatinine ratio and phosphate reabsorption. Results: None of the 65 patients evaluated suffered from clinically relevant kidney impairment (eGFR < 90 mL/min/L, 73 m CNS tumors constitute the most common solid malignancy in the pediatric population with an incidence rate of 2–4/100,000. They are comprised of more than hundred different entities with very divergent biological behavior ,4. GenerThe major chemotherapeutics that impair kidney function are platinum compounds , alkylating agents , and the antifolate agent methotrexate (MTX), which are all included in routine treatment protocols for childhood CNS tumors . NephrotThe aim of this study was to determine the prevalence and severity of chemotherapy-induced nephrotoxicity in the specific group of patients following treatment for a CNS tumor in childhood or adolescence.Patients included in the study were treated for a CNS tumor at the Department of Pediatrics and Adolescent Health, Medical University of Vienna. Between 1999 and 2018, 279 children received chemotherapy for their primary CNS tumor at our institution, and 123 of these patients deceased. Of the 156 children that achieved long-term survival, 19 patients were treated for a recurrent tumor following initial chemotherapy, and 31 patients were lost to follow-up. In total, 65 of potentially 106 eligible patients agreed to participate and were enrolled in the study and prospectively investigated for their kidney function . Data on2/d of prespecified solution). Diuretics were used as defined in their treatment protocol , and blood levels of additional nephrotoxic medication  were closely monitored [Before each initiation of a chemotherapy cycle, all patients were screened for eGFR as a standard procedure. During their chemotherapy, all patients were hydrated sufficiently according to their body surface area (BSA) as recommended in their treatment protocols ) and blood pressure measurement. For each parameter the standard deviation score (SDS) was evaluated. Hypertension was evaluated according to the NCI CTCAE criteria 5.0 ,14. The 2 . Additio2 ), serum 2 ), measurContinuous variables were described by using median and range. Furthermore, standard deviation scores (SDS) were calculated for length, BMI, and blood pressure. For each chemotherapeutic agent, dose ranges . Each test result was considered as significant when the two-sided The study protocol was approved by the Ethics Committee of the Medical University of Vienna (EK 520/2009), and a written informed consent was obtained from all study participants and/or their parents.Among the 65 patients enclosed, 44 children were male (68%) and 21 female , and the overall median age at time of diagnosis was 4.7 years (range 0.0–20.1 years). Chemotherapy started at a median age of 4.8 years (range 0.1–20.1 years). The median patient age at the time of follow-up examination was 12.7 years (range 3.2–25.5 years) and the median time between the end of chemotherapy and follow-up was 3.2 years (range 1.0–12.3 years). Diagnoses were low-grade glioma (n = 15), medulloblastoma (n = 14), high-grade glioma (n = 10), ependymoma (n = 8), CNS germ cell tumor (n = 6), atypical teratoid rhabdoid tumor (n = 4), CNS PNET , pineoblastoma (n = 2), choroid plexus carcinoma (n = 1), epitheloid sarcoma (n = 1), and one diffuse leptomeningeal glioneuronal tumor (n = 1). Localization of tumors is represented in 2, starting at least 12 h before start of chemotherapy, until at least 12 h after the end of chemotherapy.All patients received chemotherapy according to standard treatment protocols  was administered in 58 patients (89%). All patients receiving ifosfamide or cyclophosphamide were treated with the cytoprotective adjuvant mesna. None of the patients suffered from acute kidney injury according to CTCAE 5.0 during the time of treatment as assessed by chart review . In totaAt least one additional nephrotoxic medication, including vancomycin, certomycin, gentamicin and amphotericin, had been applied in 38 patients (58%) during the course of their treatment. Among this group, 14 patients (37%) received nephrotoxic medication concomitant to chemotherapy.2 (range 96.5–253.1 mL/min/1.73 m2). Patients who had received at least two chemotherapeutic agents classified as particularly nephrotoxic had a median eGFR of 150.1 mL/min/1.73 m2 (range 96.5–253.1 mL/min/1.73 m2). By using the original Schwartz formula, none of the patients evaluated had an eGFR below 90 mL/min/1.73 m2. There was no significant association between the cumulative dose of any cytostatic agent and eGFR . These values were reproducible at follow-up (following office visit) in only 11 patients; one patient was lost to follow up, and 11 patients had blood pressure values within the normal range. One patient was diagnosed with a midaortic syndrome, a secondary cause other than cancer treatment . One patient, with a protein/creatinine ratio of 300 mg/g, presented also with increased total protein, glucose, albumin, and alpha-1-microglobulin excretion in the 24-h urine specimen. SDS electrophoresis revealed tubular proteinuria. Another one had an elevated protein/creatinine ratio, albumin/creatinine ratio and a reduction in TmP/GFR. The other four patients presented with normal protein levels in their respective 24-h urine specimens and without further signs of tubulopathy. None of the five remaining patients with a reduction in TmP/GFR had further signs of tubulopathy. One patient was diagnosed with isolated glucosuria. For further details on patient characteristics, see None of the patients suffered from hyponatremia, hypokalemia, hypocalcemia, hypomagnesemia, or low bicarbonate levels at follow-up. None of these patients suffered from hypophosphatemia when using age-adjusted phosphate levels . None ofA decreased kidney function as a consequence of intensive chemotherapy for childhood cancer has been published in several studies ,30,31,322. Serum creatinine, height, age, and sex are readily available parameters, making it a very convenient method for GFR estimation in clinical routine. However, a tendency for overestimation of GFR has been shown in several studies [The GFR is considered the best overall parameter for kidney function; however, variability of methods used to calculate or estimate GFR is broad ,35. In c studies ,37. Alth studies . Loss of2 in all our patients. There was no correlation between the dose of any chemotherapeutic agent or chemotherapy protocol applied and the eGFR , our results may support the theory of a dose-dependent long-term effect of ifosfamide on GFR, despite the lack of a statistically significant difference in eGFR between the dosing groups in our study [Regarding the effect of different chemotherapeutic agents on GFR, ifosfamide is known to cause rather tubulopathy than glomerular dysfunction. However, the reported incidence of reduced GFR ranged from 4% to 50% ,39. Two ectively ,31. Becaur study ,20,34,402 and 500 mg/m2, respectively [2) [2.Cisplatin on its own is also reported to cause long-term reduction in GFR in 29–40% of patients, with median cumulative doses of 528 mg/mectively ,30. Partectively  as well ectively , are in vely [2) . Adequatvely [2) ,44. WithCarboplatin, a second-generation platinum compound, was only rarely described to have a negative effect on GFR, which is in accordance with our study .The acute nephrotoxicity of methotrexate is indisputable , though Despite the use of multiple chemotherapeutic agents for treatment, survivors of CNS tumors in our cohort do not suffer from reduction in GFR. This might be attributed to the comparatively lower dose of each single agent used in protocols for CNS tumor treatment compared to sarcoma protocols.Despite eGFR being an important overall parameter of renal function, chemotherapeutic agents also have important effects on tubular function, which is not reflected by changes of the eGFR. Tubular dysfunction is characterized by electrolyte disturbances, phosphate and magnesium loss and alpha-1-microglobulinuria. The reported prevalence of hypophosphatemia and hypomagnesemia ranges between 0–37%, and 13–71%, respectively ,19. TherIfosfamide does not only induce acute tubular toxicity, but may also result in long-term proximal tubular dysfunction, resulting in Fanconi syndrome and consequently rickets and growth retardation ,48. Subc2 ifosfamide, and the median cumulative dose of cisplatin administered in our study was also lower (300 mg/m2) than in the previously mentioned studies [Of the 65 patients analyzed in our cohort, only two presented with manifest tubulopathy and one with isolated glucosuria. All three had been treated with at least two of the previously characterized especially nephrotoxic drugs and had received additional nephrotoxic medication. None of our patients received more than 50 g/m studies ,29.2 versus 62 g/m2 [A dose dependency of long-term tubular toxicity of ifosfamide was suggested by several authors ,40,43,50 62 g/m2 ).An additional important aspect in the evaluation of renal function is blood pressure regulation. Severe systolic hypertension has been reported in 5–15% of patients after treatment with ifosfamide, cisplatin, or high-dose methotrexate ,19,20,30The contribution of a specific chemotherapeutic agent to the deterioration of any specific renal function parameter is difficult to assess, considering the multi-drug combinations used in most pediatric chemotherapy protocols and the variability of potential effects. The lower doses applied in our cohort of CNS tumor patients when compared to sarcoma patients ,20, and 2 for GFR estimation. Because our laboratory uses the Jaffé method for creatinine measurement, we used the original Schwartz formula [Our study has several limitations. In awareness of the importance of uniform assessment of kidney function, but still considering the difficulty of invasive kidney function measurements in clinical practice, we decided to use the Schwartz formula with the commonest cut-off value of 90 mL/min/1.73 m formula , what miAdditionally, the study population is relatively small, thereby making it impossible to divide the cohort into further subgroups or perform multivariate analyses. This would have been of special interest due to the inhomogeneity in the interval between the end of chemotherapy and kidney function investigation, which might neglect other influencing factors, such as a higher susceptibility for a “second hit” event. Further research should focus on risk stratification and prevention methods, thereby focusing on diagnosis and treatment of hypertension.Taken together, with adequate supportive measures, such as sufficient hydration according to the respective treatment protocol, as well as avoiding or close monitoring of additional nephrotoxic medication , prevalence of long-term nephrotoxicity in CNS tumor is low. To detect mild renal function impairment, long-term follow-up, including basic renal function evaluation  is essential.


A prospective study was conducted from June 2012 to January 2016 to asses how DO2i influences the pathogenesis of CSA-AKI, as well as its most favorable cut-off value. DO2 levels were recorded at the beginning, middle, and end of the CPB. The association between DO2i and CSA-AKI was investigated using multivariable logistic regression analysis. The optimal cut-off of DO2i as a predictor of CSA-AKI was determined using Classification and Regression Tree (CART) analysis. A total of 782 consecutive patients were enrolled. Of these, 231 (29.5%) patients developed AKI. Optimal DO2i thresholds of 303 mL/min/m2 during the CPB and 295 mL/min/m2 at the end of the intervention were identified, which increased the odds of CSA-AKI almost two-fold (Odds Ratio (OR), 1.90; 95% CI, 1.12–3.24) during the surgery and maintained that risk  until the end. Low DO2i during cardiopulmonary bypass is a risk factor for CSA-AKI that cannot be ruled out. Continuous renal oxygen supply monitoring for adult patients could be a promising method for predicting AKI during CPB.One of the strongest risk factors for death in individuals undergoing cardiac surgery is Cardiac Surgery Associated-Acute Kidney Injury (CSA-AKI). Although the minimum kidney oxygen delivery index (DO Cardiac Surgery-Associated Acute Kidney Injury (CSA-AKI) is a severe complication and one of the strongest risk factors for mortality in patients after cardiac surgery, with an incidence varying from 8.9% to 42.5% according to the intricacy or complexity of the operation ,2. In it2i) [2 diminished CSA-AKI in patients who had undergone moderately hypothermic CPB [Non-modifiable predisposing variables for CSA-AKI include age, preoperative kidney insufficiency, female gender, low ejection fraction, diabetes, and emergency surgery. Modifiable factors include hemodilution, red blood cell transfusion, redo surgery, mean arterial pressure, postoperative hypotension, low cardiac output, cardiopulmonary bypass (CPB) period, and low oxygen delivery (DO2i) ,6. Low o2i) . Recentlrmic CPB .2). Renal vascular resistance increases from 15 to 23 percent during CPB as a result of the neuroendocrine response to CP. This includes increases in norepinephrine, vasopressin, and angiotensin II, causing blood flow to redistribute away from the kidneys [2) of 10 to 20 mmHg, but the renal cortex has a pO2 around 50 mmHg [2 and is more vulnerable to harm, as commonly assessed through kidney tubular damage biomarkers. As a result, it is not unexpected that the kidneys could be one of the first organs to be damaged by a global decrease in DO2.Despite all of this, not much is known about the effects of CPB on renal blood flow (RBF), the primary regulator of kidney oxygen supply DO. Renal v kidneys ,10. The  kidneys . This is 50 mmHg ,13. Thus2i throughout CPB has been determined as an independent risk factor for dialysis [2i have been identified to be 272 and 260 mL/min/m2, respectively. Nonetheless, none of these values are based on the novel CART analysis, which is a useful tool for classifying subjects into various risk categories and can partially overcome the risk of misclassification from the traditional Receiver Operating Characteristic (ROC) curve-based criteria to find the best cut-off value [The minimum DOdialysis  and the dialysis . The criff value .2i, leading to a kidney oxygen delivery/consumption imbalance. This study aims to determine the effects of DO2i on the appearance of AKI, in addition to determining the threshold value related to it.We hypothesize that normothermic CPB causes a diminished DOThis investigation (identification number PI 19-1382) was authorized by both the Clinical Research Ethic Committee, which is a group of fifteen individuals, and the local Institutional Research Review Board.2i on CSA-AKI using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria  [2i threshold value related to CSA-AKI. We used the SCr levels recorded during the hospital entrance exam, as well as the peak SCr levels reached during the postoperative period of seven days.We designed a prospective observational study to evaluate the effect of DOvention) . FurtherThis study took place in the Clinical University Hospital of Valladolid, a tertiary-level medical hospital with 800 beds, from June 2012 to January 2016. Approximately 450 open-heart interventions under CPB in adult patients are performed annually by the Cardiac Surgery Department, using two theaters on a daily basis. An intensive care unit (ICU) with 10 beds is dedicated exclusively for patients who have undergone cardiac surgery.A total of 782 consecutive patients due to undergo elective heart surgery with cardiopulmonary bypass (CPB) were included in this study. Previous renal failure, off-pump surgery, urgent/emergency surgery, and patients with a kidney transplant were exclusion criteria .2, So2, preoperative hemoglobin, and preoperative SCr.Population information included age, sex, body mass index (BMI), diabetes mellitus, hypertension, peripheral vascular disease, left ventricle ejection fraction (LVEF), logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE), kidney depth, baseline bSo2); oxygen delivery index (Do2i); and lactate at the beginning, during, and completion of CPB. Perioperative variables collected included type of intervention; CPB duration; cross-clamp time; hematocrit (Hct); partial pressure of oxygen ), where hemoglobin, O2 saturation and pO2 were determined using blood gas analysis during CPB. Utilizing the same equation, the estimated DO2i for each patient was determined using the mean real time CI during CPB; the hemoglobin value; and the pO2 during the start, middle, and culmination of CPB.Oxygen content = (hemoglobin (g/dL) × 1.34 × oxygen saturation (%)) +  were used. The mean arterial pressure was kept between 60 and 80 mmHg. Protamine was used to reverse the heparin effect at a 1.5:1 ratio after CPB completion and cannulae removal.According to a normal distribution, categorical data are represented as percentages, and continuous variables are reported as mean standard deviations (SDs) or medians (interquartile ranges (IQR)) as applicable. The Shapiro–Wilk and Kolmogorov–Smirnov tests were used to determine normality.2, and for continuous data the Student’s t-test or the Mann–Whitney U test were utilized according to the normality criteria.For categorical data, the relationship between CSA-AKI and other variables was identified using χp value < 0.1, variables were included in the multivariable logistic regression model.Data were used in a univariate logistic regression analysis to obtain 95% confidence intervals (CIs) for estimates. A stepwise approach was used to develop a multivariable logistic regression model. If the 2, the optimal cut-off value for a higher risk for CSA-AKI was obtained using the Classification and Regression Tree (CART) Analysis, which is especially appropriate to the generation of clinical decision making. The capacity of this cut-off value to predict CSA-AKI development was further estimated using multivariate logistic regression analysis. The Hosmer–Lemeshow test was used to determine model calibration.Regarding DOp values <0.05. IBM SPSS Statistics for Windows version 24.0 was used to analyze the data . The R software was used to perform the CART analysis .The odds ratio (OR) was calculated using a 95% confidence interval. Statistical significance was defined as 2i values throughout the procedure in comparison to those who do not develop CSA-AKI (p < 0.001). A total of 231 (29.5%) patients developed CSA-AKI. In total, 48.7% of the individuals (n = 381) were female, and the median age was 70 . Regarding the underlying conditions, the rates of hypertension, smoking, and EuroSCORE II were significantly higher in patients with CSA-AKI. They underwent longer CPB and cross-clamp periods, presented higher lactate levels, needed more red blood cell transfusions, and showed lower DO2i < 303 mL/min/m2 during the CBP and <295 mL/min/m2 by the end of the intervention as the optimal cut-off values where there is already a risk for developing CSA-AKI , CPB , and aortic cross-clamp  as risk factors for CSA-AKI. Continuous DO CSA-AKI .2i and CSA-AKI. DO2i < 303 mL/min/m2 during the surgery  and DO2i < 295 mL/min/m2  at the end of the intervention were significantly related to CSA-AKI. Other independent risk factors for CSA-AKI were age  and CPB  (p < 0.021) (to 1.02) . Mixing < 0.021)  was obta2i were significantly associated with CSA-AKI. Second, a decline in DO2i greater than 303 mL/min/m2 was correlated to postoperative CSA-AKI, as depicted in There were two major findings in this study. First, age, CBP time, lactate levels, and DOThe incidence of CSA-AKI varies from 7% to 40%, depending on its numerous classifications and definitions . In this2i were significantly associated with CSA-AKI. These data are supported by reported data, which show CSA-AKI etiopathogenesis to be highly complex [Multivariable logistic regression analysis identified that age, CPB time, lactate level, and DO complex . Firstly complex . Secondl complex .2 supply [2i of 272 mL/min/m2 as a risk for acute kidney failure needing dialysis and postoperative peak SCr levels in 1048 patients who underwent coronary revascularization under CPB [2i level < 262 mL/min/m2 is independently related to AKI. Most recently, in 2017, Magruder et al. [2i > 300 mL/min/m2 during CPB lowered the occurrence of CSA-AKI. Likewise, Ranucci et al. determined, in the GIFT trial with 326 patients, that a DO2i < 280 mL/min/m2 increases the appearance of CSA-AKI [2i above 303 mL/min/m2 is related to a decreased likelihood of developing CSA-AKI. The risk of CSA-AKI rises by 2% when the minimum DO2i is lower than this threshold value.Kidney function is particularly dependent on O2 supply . In 2005nder CPB  showed tr et al.  found th2 [2 [2i, as a strategy to lower the occurrence of AKI after heart surgery. The exterior kidney medulla is already on the verge of hypoxia under normal circumstances. This kidney oxygen delivery/consumption mismatch, which is already present before CPB, is even more exacerbated during intervention. Lannemyr et al. [2 at a constant Vo2, an impaired arterial oxygen content due to hemodilution, and a re-distribution of blood flow away from the kidneys, despite an increase in systemic perfusion flow rate during CPB. This persistent state causes later ischemia-reperfusion kidney injury, leading to a lower kidney oxygenation and proximal tubular damage. Hence, predictors for AKI after heart surgery may not be precisely evaluated without taking into account the duration of low DO2 as a continuous variable.Typically, to achieve full-body perfusion, CPB perfusion flows of 2.0 to 2.4 L/min/m2  or 2.5 t2 [2  at a mea2 and renal failure after surgery [2 under the cutoff value of 300 mL/min/m2 is preferable compared with established or fixed nadir DO2 parameters in predicting CSA-AKI. In addition, preventing hemodilution and excessive transfusion and improving CPB pump flow are of paramount importance to maintaining a DO2 over 300 mL/min per m2 [2 cut-off value and showed that an AUC lower than the DO2 of 300 mL/min/m2 and the cumulative time beneath that threshold value were more useful parameters for predicting CSA-AKI compared with nadir DO2. They found that when the aggregated time under 300 mL/min/m2 DO2 exceeded 15 min, the incidence of CSA-AKI increased considerably. This measurement included both momentary and continuous drops in DO2. However, while research on renal hypoxia has found that repeated transitory renal ischemia  does not significantly harm the kidneys, continuous ischemia for 20 min caused moderate kidney tubular injury due to ischemia reperfusion lesion [2 < 272 mL/min/m2 was independently related to CSA-AKI.Previous studies have shown the association between nadir DO surgery . However surgery  found thn per m2 . Recentln per m2  assessedn lesion . Rasmussn lesion  showed t2 is variable and every patient has unique oxygen requirements, recommending the use of a personalized O2 supply target. Relying solely on one critical DO2 value for every individual is not reasonable. Without a patient’s VO2, nadir DO2 cannot be determined, which is dependent on the patient’s unique features and can be influenced by factors such as temperature and anesthesia technique, resulting in varying VO2 levels (ranging from 38 to 76 mL/min/m2) and, hence, unique DO2 demands for each patient. Thus, a perfusion goal focused solely on a generic fixed level for DO2 right over a universal critical value cannot always guarantee adequate DO2 for every patient. Furthermore, adjusting DO2 to the patient BSA allows for differences in physique, but does not consider distinctions in variables such as gender and age. As a result, oxygen demands during CPB are influenced by a variety of parameters, including the anesthetic method used and temperature regulation. Hence, VO2 should indeed be considered when addressing DO2.Recently, Hendrix et al.  suggeste2 cannot be maintained via aerobic energy generation at a crucial DO2 level, anaerobic metabolism is initiated to provide energy to the cells [Because VOhe cells .2 nadir is approximately 300 mL/min/m2. In this study, we identified that under anesthesia and normothermia, when the Do2 is lower than 303 mL/min/m2 kidney function begins to deteriorate.In a conscious human under normothermic conditions, the crucial Do2, raising the odds of CSA-AKI [Several investigations have evaluated the association between mean arterial pressure during CPB and the development of AKI after heart surgery. Nevertheless, there are still conflicting data. While Ranucci et al. showed that hypotension during CPB may lead to a low DO CSA-AKI , Azau et CSA-AKI . Similar CSA-AKI  and Sirv CSA-AKI ,35.2 may also be induced by the dilution of hemoglobin due to the prime solution used for the CPB circuit, usually a cell-free crystalloid solution [2, oxidative stress activation, and the intensification of inflammatory responses [Patients with AKI had considerably lower levels of hemoglobin during CPB, which is understandable considering hemoglobin’s role in oxygen supply. A reduced DOsolution . The extsolution . Furthersolution . This issolution ,38. As aesponses ,40.2) and the regional assessment of kidney oxygenation using near-infrared spectroscopy [2i monitoring and the patient-specific prediction of individual DO2i thresholds.Physiological indications could be employed to provide continuous bedside monitoring of the hemodynamics and functional processes involved in the development of CSA-AKI, rather than the current practice of sampling blood gas. Such kidney function measurements may permit the continuous real-time assessment of renal function just as the ventilation and hemodynamic are monitored, providing a functional approach for the application of kidney-protective strategies. Such monitoring could comprise kidney venous oximetry , which can record the DOld level . Thus, t2i during cardiopulmonary bypass. Low DO2i during cardiopulmonary bypass is a risk factor for CSA-AKI that cannot be ruled out. Continuous kidney oxygen supply monitoring may be a useful technique for preventing renal failure in adult patients undergoing cardiopulmonary bypass.The present data suggest that the appearance of renal failure after heart surgery is linked to DO


Nutrition disturbances occur at all stages of chronic kidney disease and progress with the decrease of the kidney filtration rate. Kidney transplantation (KTx) as the best form of kidney replacement therapy poses various nutritional challenges. Prior to transplantation, recipients often present with mild to advanced nutrition disturbances. A functioning allograft not only relieves uremia, acidosis, and electrolyte disturbances, but also resumes other kidney functions such as erythropoietin production and vitamin D3 metabolism. KTx recipients represent a whole spectrum of undernutrition and obesity. Since following transplantation, patients are relieved of most dietary restrictions and appetite disturbances; they resume old nutrition habits that result in weight gain. The immunosuppressive regimen often predisposes them to dyslipidemia, glucose intolerance, and hypertension. Moreover, most recipients present with chronic kidney graft disease at long-term follow-ups, usually in stages G2–G3T. Therefore, the nutritional status of KTx patients requires careful monitoring. Appropriate dietary and lifestyle habits prevent nutrition disturbances and may improve kidney graft function. Despite many nutritional guidelines and recommendations targeted at chronic kidney disease, there are few targeted at KTx recipients. We aimed to provide a brief review of nutrition disturbances and known nutritional recommendations for kidney transplant recipients based on the current literature and dietary trends. Chronic kidney disease (CKD) affects over 10% of the worldwide population and is one of the leading causes of mortality . The besSeveral subtypes of nutrition disturbances have been described in the CKD population. Despite many obese individuals in this population, undernutrition is more common in the forms of protein–energy wasting (PEW), malnutrition-inflammation-atherosclerosis syndrome (MIA syndrome), and dynapenia and uremic wasting ; naturalThe progression of CKD and the associated toxemia exacerbate malnutrition. Diminished appetite is a common complaint of CKD patients, who often suffer from taste disturbances, delayed gastric emptying, and constipation. Uremia and anemia increase the incidences of gastropathy, Helicobacter pylori infection, and uremic gastritis . Bowel e2 is considered a modifiable exclusion criterion for KTx in most transplantation centers [KTx as the best form of kidney replacement therapy poses different nutritional challenges. A functioning allograft not only relieves uremia, acidosis, and electrolyte disturbances, but also resumes other kidney functions such as erythropoietin production and vitamin D3 metabolism. Studies suggest that kidney transplantation is protective against endotoxemia-induced chronic inflammation associated with bacterial translocation . However centers . 2 for obese individuals and 1.9 ± 2.4 kg/m2 for those with a normal BMI [KTx recipients represent a whole spectrum of undernutrition and obesity. While a higher BMI is rarely related to adverse outcomes in HD patients , it appermal BMI . Weight rmal BMI . Althougrmal BMI . A meta-rmal BMI . The immunosuppressive regimen alone has a disadvantageous effect on the nutritional status. Calcineurin inhibitors (CNIs: tacrolimus (TAC) and cyclosporine A) and m-TOR inhibitors (everolimus and sirolimus) included in the standard immunosuppressive regimen have an unfavorable metabolic profile. They all lead to dyslipidemia, hypertension, and hyperkalemia. CNIs (mainly TAC) and m-TOR inhibitors, as well as glucocorticosteroids (GCSs), may cause PTDM. Additionally, they may be a cause of fluid retention . CyclospAdverse effects of GCSs also include a loss of skeletal muscle mass, increased appetite, and visceral obesity . Those cDrug–food interactions are crucial in the KTx population to maintain the desired blood trough levels of immunosuppressive medications and to avoid rejection or drug toxicity. CNIs are metabolized via the cytochrome P450 and the CYP3A4 and CYP3A5 enzymes. Restricted products include grapefruit and grapefruit juice, pomelo, and spices such as turmeric and ginger ,26. HerbIn the early post-transplant period, symptoms such as nausea, vomiting, diarrhea, and abdominal pain are highly prevalent as medication doses are typically higher to meet target blood trough levels. Over 60% of KTx recipients suffer from dyslipidemia, with hyperlipidemia being the most common presentation. The immunosuppressive regimen is the main risk factor of the development of lipid disturbances in this population ,30,31. W2; an age > 40 years; a family history of DM; and Hispanic, African American, or Asian ethnicity. Several conditions, such as cystic fibrosis, polycystic kidney disease, hepatitis C, and CMV virus infection, also increase the odds of PTDM [PTDM is a frequent complication of KTx, affecting about 10–40% of kidney recipients . Risk fa of PTDM ,43. Post of PTDM . CNIs ma of PTDM . While T of PTDM . Wissing of PTDM . However of PTDM . CNIs al of PTDM . Likewis of PTDM . In fact of PTDM . There h of PTDM . There are no nutritional guidelines specifically targeted at patients with PTDM; thus, they must follow the same basic recommendations for all diabetic and CKD patients: limited monosaccharide consumption, a low salt intake, increased fiber consumption, and moderate physical activity performed for 150 min/week . There aKTx recipients are prone to vitamin D deficiency from insufficient consumption, avoiding sunlight, and finally impaired kidney metabolism . Due to Vitamin D levels depend on body mass and composition ; in the Vitamin K, mainly K2, is believed to play a protective role for both CV and skeletal systems ,63. MostDespite the important role of vitamin K2 in many physiological processes, there are no separate dietary requirements for its intake . The exiVitamin B12 and folic acid ought to be supplemented when subjects show clinical signs of deficiency. However, hyperhomocysteinemia associated with CKD is not in itself a recommended indication for folate and/or B12 supplementation . Again, KTx patients are prone to hyperuricemia, which is an important risk factor of CV complications. It has been established that uric acid levels rise alongside decreasing eGFR—from both transplanted and native kidneys—which is the main risk factor of hyperuricemia aside from CsA treatment . Uric acThe high intake of fructose by patients with kidney failure, including KTx patients, leads to increased serum levels of uric acid and TG . KTx recSeveral studies prospectively analyzed the macronutrient pre- and post-transplantation intake with inconclusive results ranging from no significant changes within the first 6 months  to an inKTx recipients have no fixed set of dietary guidelines safe for those related to food–drug interactions. Most restrictions and recommendations result from individual comorbid conditions , metabolic disorders, and of course graft function and the presence of proteinuria.The daily protein intake varies based on the time after KTx, graft function, and proteinuria.In the first 4 to 6 weeks after transplantation, tissue recovery combined with stress, increased catabolism, and high doses of GCSs lead to protein hypercatabolism. An adequate protein supply is necessary for quick recovery, wound healing, and lesser susceptibility to infections. Therefore, the early post-KTx period revolves around recovery. The target daily protein intake ranges from 1.2 to 2 g/kg of the ideal body weight ,76. As wDue to low tubular reabsorption and disproportionately high parathormone levels, hypophosphatemia is common in the first few weeks following KTx . In the Gastrointestinal distress, dyspepsia, and diarrhea are often observed in the early weeks after transplantation. These often result from immunosuppressive medications, mainly mycophenolate mofetil and TAC. Thus, from our clinical practice, products including or based on milk, as well as rich in fiber, should be excluded to avoid the further exacerbation of gastrointestinal distress. Instead, an easily digestible diet is preferred. In addition, as hyperglycemia is often observed, monosaccharide intake is restricted.Recipients’ physical fitness in the early post-KTx phase is limited by their low activity level from the dialysis period, early post-operation stage and frequently suboptimal allograft function, anemia, fluid overload, and mineral disturbances ,82. As sDietary recommendations for recipients in the long term after KTx depend largely on kidney graft function, maintenance therapy, including immunosuppressive drugs, and pre-existing and new comorbidities, as well as PTDM, HA, CV diseases, lipid disturbances, or hyperuricemia. Patients with good and stable graft function ought to follow the same basic recommendations as the general population. Likewise, they can partake in the same physical activity recommended for their age and non-renal comorbidity burden ,85.A prospective study showed that the physical activity of KTx recipients increased up to 30% and reached a plateau after the first 12 months of follow-up . The KDODuring the maintenance period, the recommended daily energy intake for KTx patients should be 25–35 kcal/kg/day . The 202Due to a high prevalence and risk of dyslipidemia, KTx recipients are recommended to follow a low-fat, low-cholesterol diet. Between 30 and 35% of calories consumed daily should come from fats with less than 8–10% coming from polyunsaturated and trans fatty acids, while some sources suggest that monounsaturated fatty acids may account for up to 20% of daily calories . AdditioAs hypertension arteriosum is highly prevalent in the KTx population, over 90% of recipients require anti-hypertensive medication ; HA neceWhile recommendations individually refer to macro- and micronutrients, patients consume their meals as a whole, and thus, while specific guidelines prove useful for clinicians, individual patients require a more realistic, comprehensible approach, such as whole dietary patterns.The Dietary Approaches to Stop Hypertension (DASH) has been investigated as a potentially beneficial intervention in KTx due to its proven effect on high blood pressure. The key principles include a low sodium intake and the moderate consumption of lean protein and fish with the avoidance of red and processed meats, combined with a high intake of fruits, vegetables, whole grains, low-fat dairy, and fiber. This pattern facilitates low fat consumption, with a preference of monounsaturated fats over saturated and trans fats. In a large cohort study of over 600 KTx recipients, the DASH eating pattern was associated with a lower risk of decreased graft function and all-cause mortality . In the Likewise, the Mediterranean diet has a proven beneficial effect on kidney graft function . It focuBoth of these eating patterns appear beneficial against insulin resistance, inflammation, oxidative stress, and dyslipidemia . InteresIn recent years, the interest in vegetarian and vegan diets has increased worldwide. The potential superiority of plant-based sources of protein has spiked an ongoing debate in the nephrology community . Plant-bDue to the high incidence of mineral and bone disorders in this population, recipients must monitor their calcium intake; the recommended daily dose is 800–1000 mg, unless hypercalcemia occurs , with a The key to preventing malnutrition is screening; bi-annual assessments are recommended to find patients at risk of developing both PEW and obesity . In KTx Preventing nutrition disturbances is crucial in the KTx population in order to minimize the risk of CV events, metabolic complications, and to maintain good graft function. A comprehensive set of guidelines dedicated to kidney transplant recipients ought to be developed to aid physicians and clinical dietitians in providing the patients with the best care possible.


Circulating fibrinogen-to-albumin ratio (FAR) has been proposed as a novel inflammatory biomarker and a cardiovascular disease risk predictor. However, its prognostic value in patients with acute decompensated heart failure (ADHF) and different glycemic metabolic states remains ambiguous.A total of 1031 hospitalized patients with ADHF from January 2018 to May 2021 were included in the study. The primary endpoints were the major adverse cardiac and cerebral events (MACCEs). Patients were categorized into high-level FAR (FAR-H) and low-level FAR (FAR-L) groups based on the optimal cut-off value of FAR obtained from restricted cubic spline function analysis. The Kaplan–Meier plots and three multivariate-adjusted Cox proportional hazard models were used to determine the association between FAR and the risk of developing MACCEs in patients with ADHF at different glycemic metabolic states.MACCEs occurred in 483 (46.8%) patients during a median follow-up time of 520 days. The optimal FAR cut-off value was 0.079. Upon analyzing the Kaplan–Meier plots, the incidence of MACCEs was significantly different between the FAR groups in all patients and patients with diabetes mellitus (p < 0.05). After adjusting for the confounding factors, the hazard ratio (HR) for MACCEs in the FAR-H group was 1.29 compared with the FAR-L group in all patients . Additionally, high FAR was associated with MACCEs in three multivariate Cox models  in DM patients. But no significant differences were found between the FAR groups for prediabetes mellitus (Pre-DM) and normal glucose regulation (NGR) using the three Cox models .Elevated FAR was independently associated with poor prognosis in patients with ADHF and DM and thus could be used as a risk stratification tool and a potential therapeutic target in the future. Although systemic inflammation has been considered a common pathophysiological characteristic of acute and chronic heart failure (HF) , 2, the Fibrinogen is a glycoprotein complex synthesized in the liver that takes part in the processes of inflammation and thrombosis , 10. PreAs common comorbidity of heart failure, DM creates a chronic low-grade inflammatory environment, leading to further impairment of cardiac structure and function , 23. PatThe single-center retrospective analysis of 1502 consecutive patients with ADHF admitted to Nanjing Drum Tower Hospital from January 2018 to May 2021 was carried out. The ADHF was defined using the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure . The excTrained physicians retrieved patient demographics, clinical history, anthropometric data, laboratory test results, echocardiographic data, and information on medication during hospitalization from the electronic medical records.2. Based on the recommendations from the American Diabetes Association [FAR was defined as the proportion of the plasma fibrinogen (g/L) to the plasma albumin level (g/L). Body mass index (BMI) was denoted as weight (kg)/(height [m])ociation , DM was The peripheral venous blood samples were initially collected after overnight fasting (> 8 h) and the different variables were determined in the laboratory. Fibrinogen, albumin (ALB), C-reactive protein (CRP), B-type natriuretic peptide (BNP), hemoglobin, hematocrit, uric acid (UA), creatinine, white blood cell count (WBC), FPG, HbA1c, total cholesterol, triglycerides, LDL-C, HDL-C, serum sodium, serum potassium, alanine aminotransferase (ALT), and aspartate transaminase (AST) were measured.The primary endpoint was MACCEs, such as all-cause death, cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and chronic HF worsening.Patients were followed up by telephone and/or during clinic visits every six months.Continuous variables were expressed as mean ± standard deviation (SD) or median [interquartile range (IQR)]. Categorical variables were expressed as numbers (percentages).A restricted cubic spline regression analysis was performed to determine the optimal cut-off value of the FAR. Patients were categorized into two groups based on their FAR values [FAR-L (< 0.079) and FAR-H (≥ 0.079)]. Continuous variables were compared using analysis of variance (ANOVA) or the Kruskal–Wallis test. Categorical variables were compared using the χ2 test.The cumulative event-free survival rate was calculated using the Kaplan–Meier plots and the log-rank test. Multivariate Cox proportional hazards models were applied to determine the associations of FAR with the incidence rates of MACCEs. Schoenfeld residuals were visually interpreted to validate the assumptions of proportional hazards before these analyses. The baseline variables with a p-value of < 0.1 or clinically significant were included in the Cox proportional hazards models. Multicollinearity was tested in the multivariate models with a threshold of variance inflation factor of < 5. Finally, three multivariate regression models remained: Model 1 with the adjustment for age, sex, BMI, SBP, DBP, and heart rate; Model 2 with the adjustment for variables included in Model 1 plus BNP, creatinine, WBC, sodium, UA, ALT, and left ventricular ejection fraction (LVEF); Model 3 with the adjustment for variables included in Model 2 plus history of hypertension, valvular heart disease, atrial fibrillation, and use of aldosterone antagonist, β-Blockers, ACEI/ARB/ARNI, or SGLT2i. Moreover, the prognostic value of FAR for MACCEs at different glucose metabolic states was also assessed by the models. Hazard ratios (HRs) were calculated and the results were reported as HRs and 95% confidence intervals (CIs). The low FAR was used as a reference in the three models. The correlation between FAR and cardiometabolic-related factors was analyzed using Spearman’s rank correlation. The subgroup analyses including age, sex, BMI, and glucose metabolism state were shown as the forest plot. All data were analyzed using R version 4.1.0, GraphPad Prism version 8.0.1, and SPSS for windows version 26. A P-value of < 0.05 was considered statistically significant.The clinical characteristics of the participants relevant to the occurrence of MACCEs are listed in Table Based on the restricted cubic spline analysis Fig. , the optThe FAR was significantly associated with the incidence of MACCEs in all participants, as shown in Fig. Specific to different glucose metabolism states, the Kaplan–Meier curves Fig. B–D showeThe Spearman’s rank correlation analysis outcomes are reported in Table On post-hoc subgroup analysis, the FAR-H was associated with a high incidence of MACCEs, which was consistent across subgroups, age, sex, and BMI Fig.. There wIn this retrospective study, the relationship between FAR, a simple proportion, and the risk of MACCEs in patients with ADHF was explored in a clinical setting. Upon analysis, the FAR was positively correlated with the indicators of glucose metabolism, such as HbA1C and FPG. Moreover, high FAR was significantly associated with the increased risk of MACCEs in patients with ADHF and DM. However, we did not find a significant correlation in patients with ADHF at pre-DM state.FAR, as a proportion of fibrinogen and albumin, has been elucidated in several diseases. Numerous studies demonstrated that preoperative FAR was associated with the adverse prognosis after surgery in many cancers, such as hepatocellular carcinoma, cholangiocarcinoma, and glioblastoma –31. AddiFibrinogen, an inflammatory marker , was incWang et al. showed that a higher level of FAR with the DM state was associated with the worse 5-year outcome in patients with CAD undergoing PCI . The rolThe underlying mechanism between FAR and ADHF needs to be elucidated. Acute phase reactants (APR) are inflammatory markers, which are produced in the liver in response to interleukin-6 (IL-6) . APR canPrevious research demonstrated that fibrinogen up-regulated the expression of proinflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) . In the This study also had several limitations. First, due to the retrospective design, the FAR was not dynamically measured in patients over the follow-up period. Second, as this was a single-center study with limited sample size, data bias could not be avoided despite correcting multiple confounding factors. Third, prospective cohort studies are required to validate these findings.This study demonstrated that FAR was independently associated with the adverse prognosis in patients with ADHF at DM state, but this association was not observed in patients at pre-DM and NGR states.