ObjectivesThe first goal of the study is to provide a descriptive overview of the utilization of left ventricular assist device (LVAD) for the treatment of congestive heart failure (CHF) and determine the rates of LVAD use stratified by patients’ demographic and hospitals’ characteristics in the United States. Next, is to measure the hospitalization outcomes of length of stay (LOS) and cost in inpatients managed with LVAD.MethodsWe conducted a cross-sectional study using the nationwide inpatient sample and included 184,115 patients (age ≥65 years) with a primary discharge diagnosis of hypertensive and non-hypertensive CHF and was further classified by inpatients who were managed with LVAD. We compared the distributions of demographic and hospital characteristics in CHF inpatients with versus without LVAD by performing Pearson’s chi-square test for categorical variables, and independent sample t-test for continuous variables.ResultsThe inpatient utilization of LVAD was 0.93%  in CHF patients. The LVAD cohort were younger compared to non-LVAD group . The utilization rate of LVAD was also almost four times higher in males (1.50%) compared to females (0.36%). Although whites (78.5%) accounted for majority of LVAD recipients, the rate of LVAD utilization was highest in blacks (1.04%) and lowest in Hispanics (0.58%) with whites having utilization rate of 0.89%. Medicare was the dominant primary payer to cover the LVAD inpatients (91.1%), though the rate of LVAD utilization is highest in private (2.22%) and lowest in those covered by public insurance (medicaid/medicare). CHF patients in public hospitals (1.79%) were more than twice more likely to receive LVAD than in private hospitals (0.83%) due to higher utilization rate. LVAD utilization rate was approximately 55 times higher in teaching hospitals (1.67%) compared to non-teaching hospitals (0.03%), and 20 times higher in large bed hospitals (1.41%) compared to small bed-size hospitals (0.07%). CHF patients that received LVAD had a significantly longer LOS (34.6 days vs 9.8 days) and higher inpatient treatment costs  compared to non-LVAD group.ConclusionThe inpatient utilization of LVAD was in CHF patients is higher in males, blacks and private health insurance beneficiaries. In terms of hospital characteristics, the utilization of LVAD for CHF management was higher in large bed sized, and public type and teaching hospitals compared to their counterparts. This data will allow us to devise strategies to improve LVAD utilization and increase its outreach for heart failure patients, especially those on the transplant waiting list. Despite its effectiveness, aggressive usage of LVAD is restricted due to cost-effectiveness and lack of technical confidence among medical professional due to complications. American Heart Association (AHA) estimated that there were 6.2 million people with congestive heart failure (CHF) in the United States (US) between 2013 and 2016 .Left ventricular assist device (LVAD) is considered for two groups of patients, one pertains to patients with acute cardiogenic shock and the other includes patient with inotrope-dependent CHF. For the patients with acute cardiogenic shock, mechanical circulatory support (MCS) is indicated if the patient has ventricular function which is unrecoverable without MCS. Ejection fraction <25% and reduced functional capacity are strong indications for the need for LVAD .The concept of MCS developed concomitantly with the field of heart transplantation (HT), as LVADs were originally conceived as temporary bridge-to-transplant (BTT) platforms. Initially, BTT was an effective strategy to rescue patients whose severity of CHF precluded survival on medical therapy alone until a donor organ became available. However, it was recognized early on that utilizing LVAD solely as BTT was inadequate in addressing the growing prevalence of end-stage CHF. With the annual volume of HT in the US stagnating around 3000, implanting LVAD as BTT without addressing this bottleneck only increased the size of the BTT population vying for HT. The proportion of those who received HT as BTT increased from 19.1% in 2000 to 41.0% in 2012 . PatientThere is limited data on the utilization rate of LVAD in the United States, and so we conducted a cross-national study. Our first goal is to provide a descriptive overview of the utilization of LVAD for the treatment of CHF and determine the rates of LVAD use stratified by patients’ demographic and hospitals’ characteristics in the United States. Our second goal is to measure the hospitalization outcomes including length of stay (LOS) and cost in inpatients managed with LVAD.Study sampleWe conducted a cross-sectional study using the nationwide inpatient sample (NIS). The NIS is the inpatient data obtained from 4,411 hospitals across 44 states in the US. The NIS is a de-identified data with the protection of patient’s health information, and so we were not required to take institution review board permission for our study .We included 184,115 elderly patients (age ≥65 years) with a primary discharge diagnosis of hypertensive and non-hypertensive CHF and having major severity of illness as per the variable in the NIS. The sample was further grouped by inpatients who were managed with LVAD as the primary procedure.VariablesDemographic variables included were age, sex, race, primary payer, and region. Hospital variables drawn from the American Hospital Association (AHA) annual survey of hospitals included hospital ownership (public or private), bed size , location , and teaching status (teaching or non-teaching). We included the LOS and total cost during hospitalization for the treatment of CHF as provided in the NIS .Statistical analysisWe compared the distributions of demographic and hospital characteristics in CHF inpatients with versus without LVAD by performing descriptive statistics and Pearson’s chi-square test. Next, we measured the differences in continuous variables i.e., age, LOS and total cost in inpatients with and without LVAD using the independent sample t-test. All analyses were conducted using Statistical Package for the Social Sciences (SPSS) version 26.0  and statistical significance was set at a two-sided P value <0.05.The inpatient utilization of LVAD was 0.93%  in CHF patients. The LVAD cohort were younger compared to non-LVAD group . Males accounted for majority of LVAD recipients (79.4%) and the utilization rate of LVAD was also almost four times higher in males (1.50%) compared to females (0.36%). Although whites (78.5%) accounted for majority of LVAD recipients followed by blacks (13.7%), and hispanic (6.4%), the rate of utilization was highest in blacks (1.04%) and lowest in hispanics (0.58%) with whites having utilization rate of 0.89%.Medicare was the dominant primary payer to cover the LVAD inpatients (91.1%) followed by private (six percent), self-pay (1.5%) and Medicaid 1.3%. But surprisingly, the rate of utilization is highest in private (2.22%) and lowest in Medicaid (0.43%) with medicare and self-pay having utilization rates of 0.83% and 0.88% respectively. Utilization of LVAD varied widely by the US geographic region; the south (40.5%) had the highest LVAD recipients, followed by the midwest (28.7%), the northeast (20.4%) and the west (10.4%). The west region of the US also had the lowest utilization rate of LVAD (0.57%) and rest of other regions have similar utilization rates .Although private hospitals accounted for majority of LVAD recipients 83.1%), CHF patients in public hospitals (1.79%) were more than twice more likely to receive LVAD than in private hospitals (0.83%) due to higher utilization rate. Similarly, larger bed-size (89.1%) and teaching hospitals (98.2%) accounted for most of LVAD recipients and LVAD utilization rate was approximately 55 times higher in teaching hospitals (1.67%) compared to non-teaching hospitals (0.03%). Compared to small bed-size hospitals (0.07%), utilization rate was around five times higher in medium bed-size (0.33%) and 20 times higher in large bed hospitals (1.41%) as shown in Table %, CHF paCHF patients that received LVAD had a significantly longer LOS (34.6 days vs 9.8 days) and higher inpatient treatment costs compared to non-LVAD group. Also, the mean cost for LVAD inpatients was $802,118 which was around nine times higher than that of non-LVAD group  as shown in Table Age is an independent predictor of outcomes for post-LVAD survival, with the older population more likely to have complications as well as increased morbidity and mortality . This isThere are conflicting reports regarding in-hospital mortality and outcomes differences after LVAD implantation based on sex. The eighth annual interagency registry for mechanically assisted circulatory support (INTERMACS) report showed the female sex to be a risk factor for early mortality . HoweverAlthough the percentage of blacks amongst people undergoing LVAD implantation is much less than whites, the rate of LVAD utilization in blacks is more than whites, hispanics, and other races. This observation is similar to findings by previous studies which showed increased LVAD implantation rates among blacks in comparison to other race/ethnicities ,19. The Private ownership of the hospital had higher LVAD implantation by a ratio of more than 4:1 as supported by a previous study . HoweverHistory of coronary artery bypass graft (CABG) or valve surgery, diabetes, ascites, INTERMACS profiles one and two, and low albumin, high blood urea nitrogen (BUN), and high right atrial pressure are associated with high chances of prolonged hospital stay . A studyOur study results should be considered with some limitations. Firstly, the NIS is an administrative database in which variables were identified by the diagnostic coding that is subject to coding inaccuracies and underreporting of comorbidities. NIS lacks detailed patient-level information such as INTERMACS classification, and the pattern of anticoagulation use. This is a cross-sectional study and so a causal relationship cannot be established for factors influencing the utilization of LVAD and associated hospital outcomes. Yet, the NIS offers an incomparable population-based perception of utilization of procedures in a nationally representative inpatient sample. The information is coded independently by individual practitioners and is less likely to have reporting bias.In this new era of technology, MCS devices such as the LVAD will make an immense difference for patients with refractory CHF, and as a durable alternative to a heart transplant. The inpatient utilization of LVAD was in CHF patients is higher in males, blacks and private health insurance beneficiaries. In terms of hospital characteristics, the utilization of LVAD for CHF management was higher in large bed-sized, and public type and teaching hospitals compared to their counterparts. This data will allow us to devise strategies to improve LVAD utilization and increase its outreach for heart failure patients, especially those on the transplant waiting list. Despite its effectiveness, aggressive usage of LVAD is restricted due to cost-effectiveness and lack of technical confidence among medical professionals due to complications. Hence, the indications and usefulness of widespread use of LVAD should be studied with clinical trials enrolling a large number of patients so that more eligible patients can benefit from this therapy and improve their prognosis.


The optimal management of hypotensive patients during norepinephrine weaning is unclear. The primary study aim was to assess the ability of preload dependence to predict hypotension following norepinephrine weaning. The secondary aims were to describe the effect of norepinephrine weaning on preload dependence, and the cardiovascular effects of fluid expansion in hypotensive patients following norepinephrine weaning.This was a prospective observational monocentric study. We included PiCCO®-monitored patients with norepinephrine-treated septic shock, for whom the physician decided to decrease the norepinephrine dosage during the de-escalation phase. Three consecutive steps were evaluated with hemodynamic measurements: baseline, after norepinephrine decrease, and after 500 mL fluid expansion.p = 0.395)]. After fluid expansion, there was no difference in the prior preload dependence between pressure-responders and non-pressure-responders . The pressure response to norepinephrine decrease was not associated with pressure response after fluid expansion .Forty-five patients were included. Preload dependence assessed by stroke volume changes following passive leg raising was not predictive of pressure response to norepinephrine weaning [AUC of 0.42 (95%CI: 0.25–0.59, Hypotension following norepinephrine decrease was not predicted by preload dependence, and there was no association between arterial hypotension after norepinephrine decrease and fluid response. Fluid therapy and norepinephrine are the main hemodynamic treatments for septic shock , 2. OnceThe objective of the present study was to assess the association between prior preload dependence and the decrease in blood pressure following norepinephrine weaning. The secondary objectives were to describe the effect of norepinephrine weaning on preload dependence and the cardiovascular effects of fluid expansion in hypotensive patients following norepinephrine weaning.Comité de Protection des Personnes Nord-Ouest II CHU–Place V. Pauchet, 80054 AMIENS Cedex 1, 2011-46). All patients or their next of kin provided informed consent to participation. This study was conducted over an 18-month period in the intensive care unit of the department of anesthesia and critical care of the University Hospital of Amiens, France.The study protocol was approved by the local Ethics Committee , indexed global end diastolic volume  and cardiac function index (CFI) were measured using transpulmonary thermodilution, with the injection of three 15-mL cold saline boluses. Systolic, mean and diastolic arterial pressure  were measured from the arterial catheter. Total peripheral resistance (TPR) was calculated as MAP-CVP/CO (mmHg L−1 min−1). Arterial compliance was calculated as SV/arterial pulse pressure (PP) (mL mmHg−1) (V) was approximated by the following formula: Ev = MAP/(GEDV/4-SV)  and femoral arterial catheter thermodilution system connected to a PiCCO® . Cardiac index  . Effecti mmHg−1) , 14. LefDV/4-SV) .−1 min−1. Only a one-step norepinephrine dose reduction was assessed in this study. Fluid expansion consisted of 500 mL of saline solution over a period of 10 min.Patients were evaluated at three consecutive steps. At baseline, the first hemodynamic measurements were performed with passive leg raise (PLR). The second measurements were performed after norepinephrine was decreased. Then, the third measurements were performed after fluid expansion. Thermodilution calibration was performed at each step. Decisions regarding the decrease in norepinephrine dosage and fluid expansion were left to the physician's discretion. Norepinephrine decrease was standardized for all patients at 0.04 μg kgAll patients had mechanical ventilation in volume-controlled mode and were sedated. Ventilator settings  were not modified during the study period.t-test or Mann-Whitney test, as appropriate. Paired data were compared with paired Student's t-test or Wilcoxon signed rank test. A receiver-operating characteristic (ROC) curve was constructed to assess SV changes following PLR, and dynamic arterial elastance to predict pressure response. The threshold for statistical significance was corrected by using Bonferroni adjustment for multiple comparisons and set to p < 0.025. Statistical analysis was performed by using RStudio .In absence of previous data, we performed an observational study with a convenience cohort of 45 patients. The distribution of variables was assessed using histograms, QQ plots, and the Shapiro-Wilk test. Data are expressed as numbers, proportions (in percent), medians [25–75% interquartile range], or as means (± standard deviation), as appropriate. Pressure non-responders and responders were defined by MAP variation (expressed as a percentage) after decreasing the dose of norepinephrine. A positive response was defined as a ≥10% decrease in MAP. Qualitative data were compared with a chi-squared test or Fisher's test, and quantitative data were assessed with a student's Of the 900 patients admitted to our ICU during the study period, forty-five patients were included and analyzed in the study . Their b−1 min−1 for the entire cohort, and, respectively, 0.04  μg kg−1 min−1 for pressure responders, 0.04  μg kg−1 min−1 for pressure non-responders.The median decrease in norepinephrine dosage was 0.04  μg kgp = 1.0). After norepinephrine decrease, seven patients had a significantly decreased SV (by a mean of 2 ± 4%), and they were not associated with prior positive PLR  (p = 0.395) SV during PLR did not predict pressure responders for norepinephrine weaning.A decrease in the norepinephrine dose was associated with decreases in blood pressure , and art= 0.569) . With an−1 IBW crystalloids, with a similar volume between pressure responders (7.6 ± 0.7 mL kg−1 IBW) and non-pressure responders (7.9 ± 0.8 mL kg−1 IBW) (p = 0.174).After norepinephrine decrease, 35 patients underwent fluid expansion . The patp = 1), nor with SV response among these patients (p = 1). Among the 16 SV responders  with fluid expansion, only two patients (13%) were preload dependent at baseline.There was no difference in the prevalence of prior preload dependence  between pressure responders and non-pressure responders . With an AUC of 0.81 , only dynamic arterial elastance predicted pressure response to fluid expansion.The pressure response to norepinephrine decrease was not associated with pressure response after fluid expansion [14 (40%) vs. eight patients (23%), This study demonstrated that prior preload dependence is not associated with arterial hypotension following norepinephrine weaning. Norepinephrine decrease was associated with cardiovascular effects on both cardiac inotropy and arterial load. Fluid expansion in arterial hypotensive patients following norepinephrine weaning did not systematically restore blood pressure despite increasing SV.Few studies have focused on the hemodynamic effects and management of norepinephrine dosage decrease during the weaning process, after the resolution of the acute shock phase , 18. HowThe decrease in blood pressure may be explained by the effects of norepinephrine on cardiac function and arterial load , 19, 20.Blood pressure and blood flow depend preload effects of norepinephrine may depend on norepinephrine dose and acute shock phase. Most studies evaluating the preload effects of norepinephrine were performed in the initial phase of acute circulatory failure , 10. DurIn addition, the effects of norepinephrine on venous return and cardiac preload may be related to high doses and/or dose adjustments of norepinephrine. The mean norepinephrine dose adjustments required to demonstrate such effects was found to be higher in studies on norepinephrine weaning –9, 11. IVasopressor weaning is a dynamic process that requires a careful evaluation of the different components of the cardiovascular system . Physici−1 of IBW). Even though this approach is closer to the daily life practice, a degree of subjectivity cannot be fully eliminated. Nevertheless, our results are in line with a randomized study that evaluated active norepinephrine weaning vs. standard norepinephrine weaning. Furthermore, the design of the study did not allow us to infer causality, and so association are provided in the present manuscript. Finally, it has to be pointed that the patients with septic shock (originating from different origins) are intrinsically complex, as the patients have various comorbidities, and many interventions are possibly performed, e.g. different amounts of fluid administration , albumin supplementation, renal replacement therapy, diuretic therapy. We assessed the EV by using a simplified formula based on the assumption that atria and ventricle volume are equal (V (Firstly, the limitations of our study include its observational, non-randomized, monocentric, open design, and limited sample size. We performed an observational study without power calculation that included patients for whom the physician decided to wean off norepinephrine. Also, the volume of fluid expansion was fixed at 500 mL crystalloids, which is different from some other approaches (5 mL kgre equal . Such siequal (V , 25. NevArterial hypotension following norepinephrine decrease was not associated with preload dependence. Moreover, we found no association between arterial hypotension after norepinephrine decrease and fluid expansion response. Therefore, patients with arterial hypotension following norepinephrine decrease should not be systematically treated with fluid therapy.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Comité de Protection des Personnes Nord-Ouest II CHU - Place V. Pauchet, 80054 AMIENS Cedex 1, 2011-46. The patients/participants provided their written informed consent to participate in this study.SA and P-GG are guarantors of the entire manuscript. OA-A, SA, MN, BB, and P-GG designed the study. OA-A and P-GG collected and analyzed all the data. All the authors helped in the data interpretation and the manuscript draft. All authors read and approved the final manuscript.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.


Gastroschisis is a congenital abdominal wall defect that presents an increasing occurrence at great cost for the health system. The aim of the study is to detect the main factors of an unfavorable evolution in the case of gastroschisis and to find the best predictors of death. Methods: we conducted a retrospective cohort study of neonates with gastroschisis treated in a tertiary pediatric center during the last 30 years; 159 patients were eligible for the study. Logistic regression was used to determine the risk of death, estimated based on independent variables previously validated by the chi-square test. Results: if the birth weight is below normal, then we find an increased risk (4.908 times) of evolution to death. Similarly, the risk of death is 7.782 times higher in the case of developing abdominal compartment syndrome, about 3 times in the case of sepsis and 7.883 times in the case of bronchopneumonia. All four independent variables contributed 47.6% to the risk of death. Conclusion: although in the past 30 years in our country we have seen transformational improvements in outcome of gastroschisis, survival rates increasing from 26% to 52%, some factors may still be ameliorated for a better outcome. Gastroschisis is a relatively benign malformation, but is associated with substantial perinatal morbidity and there is still no consensus about the best mode and time of delivery, about the algorithm for its treatment, and about the main risk factors for morbidities . AlthougAppearance, Pulse, Grimace, Activity, and Respiration), gender, birth weight (BW), associated abnormalities, time to surgery, presence of compromised bowel , mode of delivery, APGAR score (fication ), type oWe initially performed a descriptive statistical process, separately over the three decades. Then we investigated whether there is any link or reciprocal influence between the aforementioned statistical variables  and the risk of death of patients with gastroschisis. First, the chi-square test and the contingency tables (cross tabulation) were used in the analysis, the studied variables being of nominal type . Subsequp-values were two-sided with values less than 0.05 considered statistically significant. SPSS statistical software (version 25) was used for this investigation.All A measure of goodness-of-fit often used to evaluate the fit of a logistic regression model is based on the simultaneous measure of sensitivity (true positive) and specificity (true negative) for all possible cutoff points. First, we calculate sensitivity and specificity pairs for each possible cutoff point and plot sensitivity on the y axis by (1-specificity) on the x axis using the ROC (Receiver Operating Characteristic) curve. The area under the ROC curve ranges from 0.5 and 1.0 with larger values indicative of better fit.One hundred and sixty-seven newborns with gastroschisis were admitted in our hospital during the 30 years and 159 were eligible for the study; we noticed a slight ascending trend of the appearance of the malformation during the last three decades, respectively 41/59/59 newborns (we have included 2020 in the last decade). Over the three decades analyzed, the rate of antenatal diagnosis and cesarean births increased significantly and the age at the time of surgery improved, as can be seen in Reciprocal influence between statistical variables and death was statistically proved for only four independent variables: BW, ACS, sepsis and bronchopneumonia. It can be seen from the graphical representations  that theAccording to omnibus tests of model coefficients, all of the variables entered in the equation for our model have a significant effect .In order to estimate the coefficient of determination as a model summary, we used Nagelkerke’s R-square which shows us that all four independent variables contribute 47.6% to the risk of death.Goodness-of-fit statistics are very useful to determine whether the model adequately describes the data. The Hosmer–Lemeshow statistic indicates a poor fit if the significance value is less than 0.05. In our regression equation, we observed that the model adequately fits the data .The classification table  comparesiβ are marked with B and EXP (B) represents odds ratio for each factorial variable, which is In the final table, Variables in the equation , we can Therefore, we shall have the logistic regression equation:If the BW is below normal then we have an increased risk (4908 times) of evolution to death. Similarly, as seen from the logistic regression equation, the risk of death is 7782 times higher in the case of developing ACS, about three times in the case of sepsis, and 7883 times in the case of bronchopneumonia. All 4 independent variables contribute 47.6% to the risk of death.In our analysis by logistic regression method, we save the composed probabilistic value of the 4 variables (predicted probability PRE_1) from the proposed model  and then we will use this value as a test in the graph of the ROC curve together with the dependent variable (state variable) death.p-value is 0.000 meaning that the diagnostic accuracy of our previously presented logistic regression model is very good for predicting the contribution of the four independent variables to the risk of death  of the antenatal diagnosis rate led in our country to the significant increase of the number of births by cesarean section and implicitly to the decrease of GA, as observed in Elective preterm delivery by cesarean section appears favorable with respect to intestinal injury, feeding and sepsis . AlthougThere has been a lot of controversy about GA at delivery. Some studies suggest that elective earlier delivery anticipation may reduce intestinal damage and enhance neonatal outcome ; this coCurrently, the most important determinant of gastroschisis outcomes in high resource settings is whether the condition is associated with intestinal complications, such as atresia, necrosis, perforation, or volvulus. Although some report that complex cases occur in up to one third of pregnancies affected by gastroschisis ,15, the The technique for surgical closure depends on the degree of intestinal inflammation or other intestinal abnormalities, the size of the defect, and the general conditions of the newborn. The classical approach is to perform primary closure in the first hours of life, with the newborn under general anesthesia, in an operating room; this was done in 73% of our cases. Silo placement and delayed closure is indicated in cases with viscero-abdominal disproportion due to the risk of compartment syndrome. ACS is directly correlated with an unfavorable evolution, increasing the risk of death 7.78 times in our study and we must avoid this complication in the future through stricter intra and postoperative monitoring of abdominal pressure. 19 of our patients (12%) developed ACS, a complication that could have been avoided by adopting the Schuster method instead of primary closure for patients with viscero-abdominal disproportion. High intra-abdominal pressure can lead to vascular compromise and bowel ischemia resulting in complications. The risk of ACS has been reported to be significantly more common among patients undergoing direct closure of congenital abdominal wall defect . A recenp did not reach the threshold of statistical significance (p = 0.083 between the second and third decade), the constant decrease in age at the time of surgery was certainly another positive factor in significantly increasing the survival rate in our group. The constant and significant increase of the antenatal diagnosis rate also contributed to this positive aspect.Although the value of As in other studies ,19, sepsAccording to the ROC curve, the diagnostic accuracy of our presented logistic regression model was very good for predicting the contribution of the four independent variables to the risk of death. All four independent variables contributed 47.6% to the risk of death in our study.There are limitations intrinsic to this study as the review was retrospectively performed and it is a single-center study. This study included cases from 30 years, which means many medical knowledge and therapeutic concepts might have been different in more recent decades. In a retrospective review, this issue will lead to bias.Strengths of the study: the results of this study are drawn from the largest population-based study in our country, our hospital serving the entire northeastern region of Romania, which in mid-2020 accounted for 18% of Romania’s population, numbering approximately 4 million people. However, we cannot generalize the results obtained in our region to the entire country.In the past 30 years in our country we have seen transformational improvements in outcomes of gastroschisis due to advances in neonatal intensive care and enhanced integration between the disciplines of maternal fetal medicine, neonatology and pediatric surgery. However, some factors such as sepsis, bronchopneumonia, abdominal compartment syndrome and low birth weight may still be ameliorated for better outcomes in these patients.


Background: Hyperuricemia is very common in patients with chronic kidney disease (CKD); the role of hyperuricemia in the occurrence and progression of kidney disease remains an interesting and unresolved issue for nephrologists, and whether urate-lowering therapy (ULT) is warranted in CKD patients is still in controversy. To summarize and compare the clinical outcomes and adverse events (AEs) of three common ULT drugs, we performed a systematic review and network meta-analysis of randomized clinical trials (RCTs).Method: PubMed, MEDLINE, Clinical Trials.gov, EMBASE, and the Cochrane Central Register of Controlled Trials electronic databases were searched. The network meta-analysis was performed using the “gemtc 0.8-7” and its dependent packages in R software. The primary outcome was the change of renal function and uric acid; creatinine, proteinuria, blood pressure, and adverse events were assessed as the secondary outcomes.Results: 16 RCTs involving 1,943 patients were included in the final network analysis. Febuxostat, allopurinol, and benzbromarone were not found to exert superior effects over placebo upon renoprotective effect. With respect to lowering urate, the three drugs showed to be statistically superior to placebo, while febuxostat could better lower urate than allopurinol . It is also indicated that febuxostat was superior to placebo at controlling blood pressure, while no differences were observed when allopurinol and benzbromarone were compared to placebo. These results are stable in subgroup analysis.Conclusion: There is insufficient evidence to support the renoprotective effects of the three urate-lowering agents in CKD patients with hyperuricemia; febuxostat shows a tendency to be superior to allopurinol on lowering the decline of eGFR and increment of proteinturia, but the difference does not reach a statistical significance. Regarding its urate-lowering effect, febuxostat appears to be a satisfactory alternative to allopurinol and benzbromarone, and can control blood pressure better. Chronic kidney disease (CKD) is a public health problem that causes substantial morbidity and mortality because of its potential to progress to end-stage renal disease and promote high risk of cardiovascular events . ProgresHyperuricemia is very common in CKD patients because of reduced urinary excretion of uric acid . HyperurXanthine oxidase inhibitors are considered the primary class of ULT for patients with CKD. Although there are concerns over use of allopurinol , it is still recommended as first-line therapy . HoweverTo summarize and compare the clinical outcomes and adverse events (AEs) associated with these three common drugs, we performed a systematic review and network meta-analysis of relevant randomized clinical trials (RCTs).Trials.gov, EMBASE, and Cochrane Central Register of Controlled Trials electronic databases were comprehensively searched up to June 1, 2020. Search terms are shown in This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement extension for network meta-analysis  and PRISAll non-RCTs were excluded and language was restricted to English. Selected RCTs were those that 1) included CKD patients aged 18 years or older with hyperuricemia and who were being treated with the specified interventions ; and 2) reported changes in renal function through measurement of the estimated glomerular filtration rate (eGFR), creatinine, or proteinuria. Considering that the definition of hyperuricemia has not reached a consensus at the current stage , it was Primary outcomes were changes in eGFR, uric acid, creatinine, proteinuria, and blood pressure, while AEs were assessed as secondary outcomes.Data were collected in duplicate (XL and DHL), and primary authors were contacted when additional clarification was required. Concrete data points included study information  and features of study subjects . Two authors (XL and DUL) reciprocally evaluated the extracted data, while another author (YXQ) resolved all disagreements when a consensus was not reached. Two authors (XL and DUL) independently evaluated the quality of each pair of comparison using the Cochrane risk-of-bias tool .https://www.r-project.org). A multiple treatment comparison was conducted using a Bayesian network framework with a Monte Carlo Markov chain (MCMC) model  model . We simuC) model  to calcup < 0.05 was considered statistically different. Heterogeneity was examined using the Q-test and I statistic (p < 0.1 or I2 > 50%). Otherwise, the fixed-effects model was applied. All pairwise meta-analyses were conducted in R with the “meta 4.15-1” package.For pairwise meta-analysis, MDs and ORs were calculated with 95% confidence intervals. tatistic . A randoA total of 1,233 titles were identified during the initial search, 1,202 of which were excluded upon screening of titles and abstracts. Following a full-text review of 31 studies, 16 RCTs involving 1,943 patients were included in the final network analysis  Yu et a. Details2 and hyperuricemia  provided data on ULT. Network meta-analysis demonstrated that febuxostat, allopurinol, and benzbromarone were statistically superior to placebo at lowering urate, while febuxostat was associated with superior improvement in uric acid levels compared with allopurinol  , I = 3% uricemia  . Data on patients with over 6 months of follow-up were available in nine studies with 1,150 patients. The difference between febuxostat and allopurinol was not statistically significant in these patients ; I ≤10% Indicators of CKD progression, including the change in eGFR, proteinuria, and serum creatinine, were analyzed. Regarding eGFR, 14 trials with 1,594 patients were available for assessment . Febuxos2 = 7%, Reginato et al., 2012, respectively). Notably, febuxostat was associated with better control of systolic blood pressure than allopurinol in patients with eGFR < 60 ml/min/1.73 m2 and hyperuricemia   . No diffo −0.69) .AEs including deterioration of kidney function , liver dysfunction (seven studies with 939 patients), cardiovascular events , gastrointestinal symptoms , and hypersensitivity  were analyzed. There are no differences found in these AEs among the four interventions ; febuxos2. Furthermore, a subgroup analysis was performed based on follow-up time (≤6 or >6 months). As described above, sensitivity and the subgroup analysis did not affect our findings to an appreciable degree, highlighting the robustness of our study. The risk of bias for each study is shown in Sensitivity analysis was performed by excluding studies that included patients without hyperuricemia and studies with eGFR ≥ 60 ml/min/1.73 mIt is well established that reduced kidney function is accompanied by increased serum urate levels resulting from decreased kidney clearance . HoweverThis is the first systematic review and network meta-analysis to investigate differences in effectiveness of three commonly used drugs at promoting renal protection and urate reduction in patients with CKD and hyperuricemia. We found that febuxostat can lower serum uric acid and control blood pressure better than allopurinol and benzbromarone. However, the three agents were found to not exert renoprotective effects, including improvement in eGFR, creatinine, or proteinuria. Similar observations were made in subgroup analyses stratified by the CKD stage and follow-up time.Our findings are consistent with select RCTs in which ULT was shown to have no obvious effects on renal function . A recenWe also found that febuxostat was superior at lowering uric acid and controlling blood pressure. Inadequate dosing of allopurinol may explain its poor effectiveness, as the dose of allopurinol in most included studies was less than 300 mg/d  because Compared with previous meta-analyses , the preThis study also had limitations. First, the methodological quality of trials was suboptimal, as allocation concealment was unclear in most studies because of unexhaustive description of methods, and double-blinding was rated as a high risk in one-third of the trials analyzed. Second, evaluation of renal function focused on eGFR , creatinine (seven studies with 620 patients), and proteinuria (five studies with 290 patients), while evaluation of progression to end-stage renal disease was insufficient (no data). Finally, while our findings have a reference value, they should not be applied to patients with only CKD or hyperuricemia, as the patients included in our study suffered from both hyperuricemia and CKD.There is insufficient evidence to support the renoprotective effects of the three urate-lowering agents in CKD patients with hyperuricemia. Regarding its urate-lowering effect, febuxostat appears to be a satisfactory alternative to allopurinol and benzbromarone. It is more effective at lowering serum uric acid and controlling blood pressure in hyperuricemic patients with CKD. Interestingly, febuxostat shows a tendency to be superior to allopurinol on lowering the decline of eGFR and increment of proteinturia, although the difference does not reach a statistical significance; large, double-blind RCTs that study differences in the renoprotective effects of different urate-lowering agents are necessary.


In the whole CKD population, we found a positive correlation of RNSL concentration and both MACE occurrence  and all-cause death . There was a significant increase in MACE occurrence probability in patients with elevated renalase levels (>25 μg/mL). Conclusions: Elevated renalase levels can be used as a risk factor of MACE in patients with CKD, but its long-term utility needs further research. High renalase levels are a risk factor of death among CKD patients. In HD patients, all deaths were observed among patients with >30 μg/mL; this level could be used as a “red flag” marker in future studies.Background: Renalase is an enzyme and a cytokine involved in cell survival. Since its discovery, associations between it and both cardiovascular and kidney disease have been noted. Recognizing this, we conducted a study in which we followed patients with chronic kidney disease. Material and methods: The study involved 90 CKD patients with varying stages of the disease and 30 healthy controls. Renalase was measured with an ELISA kit, and patients were followed-up after a median of 18 months. During the follow-up, we asked about the occurrence of MACE, all-cause mortality and the need for dialysis initiation. Results: In CKD subgroups, RNSL correlated with all-cause death only in the HD group (Rs = 0.49,  RNLS gene is expressed in many other cells and tissues, including the nervous system, endocrinal and digestive tract organs, lungs or heart in humans and some other mammals [2+-ATPase-4b (PMCA4b) [Renalase (RNLS) is a small flavoprotein produced mainly by the kidney. However, the latest investigations show that RNLS might be an “organolase”, as the  mammals . RNLS shDespite reported discrepancies in observed serum renalase levels in humans, most analyses indicate that serum RNLS levels significantly increase in people with chronic kidney disease (CKD). As in the case of many other markers, this relationship would demonstrate the usefulness of the RNLS concentration assessment in the diagnosis and prognosis of kidney diseases and accompanying disorders. Seeing that CVD is the most significant contributor to mortality of CKD patients, we sought to answer whether RNLS could be a predictive factor for CVD in CKD.One hundred twenty people (aged 40–79) were enrolled into the study. We divided 90 CKD patients into subgroups, each consisting of 30 participants: CKD stage III (CKD III), CKD stage IV (CKD IV), CKD stage 5D who were hemodialyzed (HD) and 30 adults (15 women and 15 men) with no signs of chronic kidney disease (control). Both groups were signed up for the study during treatment at a Nephrology Ward and its Admissions Department, Outpatient Clinic and Dialysis Centre.g, room temperature). The obtained material was then transferred to separate tubes and frozen at −80 °C until renalase levels were measured. eGFR, HDL, LDL and TG levels were assessed in an analytical laboratory as soon as possible after sample collection.To obtain blood serum, blood was drawn into test tubes  and left for 30 min at room temperature. The tubes were then centrifuged , where Scr is serum creatinine (mg/dL), κ is 0.7 for females and 0.9 for males, α is −0.329 for females and −0.411 for males, min indicates the minimum of Scr/κ or 1 and max indicates the maximum of Scr/κ or 1) [Cardiovascular risk (CV) was calculated using the ASCVD (atherosclerotic cardiovascular risk) algorithm, which includes: age, sex, race, systolic and diastolic blood pressure, total cholesterol and HDL/LDL fractions, diabetes, smoking and hypertension . ParticiFollow-up was administered by means of a questionnaire during an outpatient clinic visit, dialysis treatment or a telephone call. Mean follow-up time was 17.3 months. Two patients were lost to follow-up—one patient in control and one in the CKD IV group. In the follow-up, we asked about the first major adverse cardiovascular event (MACE). We defined MACE as an occurrence of either ischemic stroke, acute coronary syndrome, hospitalization due to heart failure or death attributed to a cardiac event. We also looked for all-cause mortality and a need to start renal replacement therapy (RRT).Obtained data were evaluated using Statistica 13.0 software . Since almost all parameters had distributions different than normal, non-parametric tests were used. Differences between two groups (control and CKD) were evaluated using the Mann–Whitney U test. Differences between analyzed parameters in subgroups  were assessed using Kruskal–Wallis ANOVA with post-hoc Dunn’s test. Correlations were evaluated using Spearman’s Rank Correlation Coefficient. The analysis of the occurrence of MACE and overall survival was performed using the Kaplan–Meier method. The significance level was set at α = 0.05.The study population’s demographic and descriptive data are shown in When analyzing the control group and CKD-based subgroups, renalase levels were significantly higher in HD than in any other group and the CKD IV group compared to the CKD III group. There was no significant difference in renalase levels between the control group and CKD III and IV groups.Renalase levels in subgroups are shown graphically below in p < 0.05). There was also a borderline correlation with systolic  and diastolic  blood pressure.In the control group, renalase correlated negatively with body weight  and body weight .In the CKD III group, renalase did not correlate with any of the analyzed parameters, but in the stage IV CKD group, it correlated again with eGFR  and positively with residual diuresis .In the HD group, renalase correlated negatively with eGFR .Comparing adults with no kidney disease and the whole CKD group, there was no significant difference in renalase levels, but this difference was at the borderline significance level (p < 0.001), as shown in In the whole CKD group, we found a strong negative correlation between renalase levels and eGFR , eGFR  and body weight .When analyzing data from all participants together (control and CKD patients), renalase correlates with diastolic blood pressure , but no other significant correlation was found.In CKD subgroups, RNLS correlated with all-cause death occurrence in the HD group  and a negative correlation with time to first MACE occurrence . The correlation of RNLS and MACE occurrence was stronger than that of the algorithm derived, calculated risk . All-cause death also correlated positively with renalase concertation .When analyzing the whole CKD patient population, we found a positive correlation of RNLS concentration and MACE occurrence , time to MACE  and all-cause death . This conclusion takes into account that a small number of endpoints were observed in the control group.Data pooled from all participants (both with and without CKD) concerning endpoints have shown a correlation between RNLS and MACE occurrence  and 9 with lower renalase levels (<25 µg/mL). A Mantel–Cox test There was no difference in the occurrence of death between subgroups divided basing on the 25 µg/mL threshold.p = 0.09), as presented in When a higher threshold was assumed, and patients with CKD were divided into groups with levels of RNLS higher or lower than 30 µg/mL, not only did the higher probability of MACE remain significant, but a higher probability of all-cause death was also observed , other cardiac events become more and more prevalent as kidney function declines. Non-atherosclerotic CVD, arrhythmias, sudden cardiac deaths, arterial calcifications, valve calcifications and haemorrhagic strokes may be caused by uraemia, CKD-MBD, LVH or be dialysis-related events . A growiStandard risk factors and assessment tools underperform in CKD patients, as their predictive risk is much lower than observed CVD events . MoreoveRenalase has been linked to CKD and CVD in numerous studies. In a seminal paper describing renalase discovery, Xu et al. postulated a link to the cardiovascular system ; unfortuAdditionally, since 2014, renalase’s other function has been observed—that of a cytokine. It was found that a part of renalase protein – RP 220  are a risk factor of MACE in patients with chronic kidney disease, but its long-term utility needs further research.High renalase levels (>30 µg/mL) can be a risk factor of death among CKD patients.In HD patients, all deaths were observed among patients with a renalase serum concentration greater than 30 μg/mL. Further research could show a possible “threshold” level, prompting an evaluation of patients to either intensify treatment or start discussing palliative measures.


Functional capacity (FC) is known to affect morbidity and mortality in kidney transplantation. Despite this important role, little is known about the variables influencing post-transplant FC. Our study aims at identifying these crucial associations.Our study included 16,684 renal transplant recipients (RTR). Patients had transplant between 1 September 2018 and 1 September 2019. Mild functional impairment was defined as those with a KPSS score > or = 80; moderate functional impairment was defined as those with a KPSS score between 50 and 70 and severe functional impairment was defined as those with a KPSS score < or =40. The outcome measured was FC at follow-up one-year post-transplant. Abnormal FC at follow-up was defined as those with KPSS score less than 80%. Normal FC at follow-up was defined as those with KPSS score equal or above 80%. Multivariate logistic regression was used to assess with the relationship between patient characteristics and abnormal functional status post-transplant.n = 8388), those who had moderate impairment at time of transplant  and those who had severe impairment at time of transplant . Abnormal FC at one-year post transplant was present in 7.69%, 28.89%, 49.49% of patients in group A, B and C, respectively. Glucocorticoid withdrawal was associated with lower risk of developing abnormal FC post-transplant , while recipient diabetes was associated with higher risk of abnormal FC  in adjusted model.Three groups were identified; those with none-to-mild functional impairment at time of transplant (Group A; Kidney transplantation is associated with substantial improvement in all stages of FC in KTRs.Glucocorticoid withdrawal and diabetes mellitus are potentially modifiable factors of FC and merit further considerations during pre-transplant workup and post-transplant immunosuppressive therapeutic planning.Kidney transplantation is associated with substantial improvement in all stages of FC in KTRs. Glucocorticoid withdrawal and diabetes mellitus are potentially modifiable factors of FC and merit further considerations during pre-transplant workup and post-transplant immunosuppressive therapeutic planning. Frailty is defined as a state of decreased physiologic reserve and diminished ability to recover from physiologic stressors . FunctioKidney transplantation (KT) is the best treatment option with superior survival for patients with end-stage kidney disease (ESKD). However, data are limited regarding potential influencing factors on FC and its outcome in kidney transplant recipients (KTR) . ChronicStudies demonstrate that frailty is associated with a two-fold increased risk of delayed graft function, 1–2-fold increased risk of protracted initial hospital stay and 1–6-fold increased risk of hospital readmission within one month post-transplant . AdditioUsing data from the United States Organ Procurement and Transplantation Network (OPTN) from 1 September 2018 till 1 September 2019, we retrospectively reviewed all renal transplant patients who had FC assessments at the time of transplant and one-year post-transplant. Data including age, gender, ethnicity, functional status, diabetes (diagnosed before the date of transplantation), body mass index, cold ischaemia time, number of previous transplants, panel reactive antibodies, donor type, donor age, HLA-mismatches, number of acute rejection episodes, induction therapies, maintenance immunotherapy on discharge were collected. The outcome measured was FC one-year post-transplant and was classified according to KPSS score. Exclusion criteria were: patients less than 18 years old, organ transplantations other than the kidneys, multiple organ transplantations, patients who were discharged on non-tacrolimus-based immunotherapy, patients with missing FC assessment at time of transplant or one-year post-transplant and patients who had FC assessments by methods other than KPSS. The study was exempted from institutional approval as it was performed with publicly available, de-identified data.Appendix Table 1 in the Supplementary data. None-to-mild functional impairment was defined as those with a KPSS score ≥80. Moderate functional impairment was defined as those with a KPSS score between 50 and 70. Severe functional impairment was defined as those with a KPSS score KPSS score ≤40. The outcome measured was FC at follow-up one-year post-transplant. The main hypothesis of our research was that among renal transplant patients, the majority will have normal functional status (which we defined as a KPSS score ≥ 80). Contrarily, abnormal FC at follow-up was defined as those with KPSS score less than 80. In this paper, nomenclature to describe kidney-associated variables is used in keeping with last KDIGO consensus statement [KPSS measures the patient’s ability to perform ordinary tasks on a scale of 0 to 100. FC measurement definitions are outlined in p value less than or equal to.05 in the univariate logistic regression analysis were included in the multivariate model. Backward stepwise approach was used to get the best fit for the multivariate logistic regression model. In order to perform the backward stepwise approach, variables with p value more than .2 were removed from the model. Scaled Schoenfeld residuals were used to assess for proportionality assumption for each variable and for the whole model. Variables assessed in the univariate analysis were: recipient age, recipient sex, recipient ethnicity, diabetes, time on maintenance dialysis pre-transplant, recipient body mass index (BMI), donor type (extended criteria donor or not), corticosteroid withdrawal post-transplant and post-operative serum creatinine at the time of discharge. These variables were chosen based on clinical judgement. Hosmer–Lemeshow goodness-of-fit analysis was performed to assess calibration of the models. Sensitivity of the model was assessed using area under the curve (AUC) analysis. Linktest was used to assess the specification error. A p value less than or equal to .05 was the cut-off point for identifying poor fit or specification error for the model. To perform a sensitivity analysis, we performed a subgroup analysis among elderly population. As elderly patients aged 65 years or above are more prone to have abnormal functional performance, we performed a subgroup analysis using the same multivariate logistic regression analysis (with the same variables) on this subgroup of patients.After removing duplicates from the STARFILES, the files were merged using 1:m mode. Categorical variables were described in numbers and percentages. Continuous variables were described as means and standard deviation. Chi-square analysis was used for comparison between categorical variables, while Kruskal–Wallis test was used for comparison between continuous variables. T independent test was used to compare means of KPSS score at the time of transplant and at one-year post-transplant. Multivariate logistic regression analysis was used to assess the relationship between patient characteristics and abnormal functional status post-transplant. Variables that had a n = 8388), those who had moderate impairment at the time of transplant  and those who had severe impairment at the time of transplant . Baseline characteristics of the identified groups are shown in A total of 16,684 patients were included in our study. Details of selecting patients from the cohort are shown in p value < .001. Out of 16,684 patients included in our study, 13,516 patients had normal FC at one-year post transplant (81.01%), while only 3168 patients had abnormal FC through the same time period (18.99%). Abnormal FC at one-year post transplant was present in 7.69%, 28.89%, 49.49% of patients in group A, B and C, respectively. Details of changes in functional status at transplant and at follow-up are shown in There was significant improvement in KPSS score at one-year post transplant  in comparison to KPSS score at the time of transplant  with p = .27) as well as no evidence of specification error (p = .54) . Glucocorticoid withdrawal protocol  and Asian ethnicity  were associated with lower risk of developing abnormal FC. Extended criteria donors, time on dialysis (months), black ethnicity, recipient age and recipient diabetes were associated with increased risk of abnormal functional status at follow-up .Multivariate logistic regression analysis to assess variables associated with abnormal FC is shown in p value = .02, 95% confidence intervals: 0.64 to 0.97). Diabetes mellitus was associated with higher risk of having abnormal FC post-transplant . AUC for this model was 0.58. There was no evidence of poor fit with p value = .29 as well as no evidence of specification error with p value = .66.To perform a sensitivity analysis, we did the same multivariate logistic regression analysis among patients older than or equal to 65 years old. Results are shown in n = 16,684) demonstrates that KT led to significant improvements in all stages of FC regardless of pre-transplant FC. Moreover, at one-year follow up and after performing sensitivity analysis, withdrawal of glucocorticoids was associated with significant improvements in FC, while baseline diabetes was associated with worsening FC. To our knowledge, this is the first study to show an effect of diabetes mellitus and glucocorticoid withdrawal on FC in KTRs maintained on tacrolimus therapy.Our retrospective study with a large number of patients from the OPTN database (n = 443) showed improvement in both initially frail and non-frail recipients with more marked improvements noted in frail KTRs [Reese et al.  utilizedail KTRs . Our resail KTRs ,14. Receail KTRs ,16. The A major finding of our study is the positive association between glucocorticoid withdrawal and improved FC. Corticosteroid maintenance versus withdrawal protocols in KTRs remain subject of substantial controversy among transplant experts, with sifting trade-offs between risks and benefits of immunosuppressive therapy across the spectrum of baseline health . Some faSeveral studies have proved adverse outcomes of diabetes and its impact on functional status of the patients. However, studies assessing the impact of diabetes on functional status post renal transplant are scarce. In our study, diabetes mellitus is one of the risk factors for abnormal FC post-transplant.The mechanisms by which KT can improve post-transplant FC have not yet been defined. It was suggested that renal transplantation can play a role in improving heart failure and low ejection fraction . We hypoWe want to acknowledge the limitations of our findings that include the retrospective study design, missing data about other comorbidities for renal transplant patients and the utilization of only one FC measurement tool (KPSS). Notwithstanding these, we present novel findings that may potentially have impact on the current management and selection strategies for RT: limiting corticosteroid use post-RT and adequate control of diabetes might contribute to improved post-transplant FC. Their contributions to this important clinical outcome in the MMF/FK era post-KT merit further study.Click here for additional data file.


Research on long-term renal outcomes in patients with acute kidney injury (AKI) and trauma, especially those with traumatic brain injury (TBI), has been limited.In this study, we enrolled patients with stage 3 AKI as per the Kidney Disease Improving Global Outcomes guidelines, who initiated renal replacement therapy (RRT). These patients were divided into 2 groups depending on the presence of TBI. Comparing the baseline characteristics and management strategies of each group, we analyzed whether TBI affects the progression of kidney disease.Between January 1, 2014 and June 30, 2020, 51 patients who initiated RRT due to AKI after trauma were enrolled in this study. TBI was identified in 20 patients, and the clinical conditions were not related to TBI in the remaining 31. The study endpoint was set to determine whether the patients of each group needed RRT persistently at discharge and at the time of recent outpatient clinic. Six (30.0%) out of 20 patients with TBI and 2 (6.5%) out of 31 patients without TBI required conventional hemodialysis, as per the most recent data. No significant within-group differences were found in terms of the baseline characteristics and management strategies. In the logistic regression analysis, TBI was independently associated with disease progression to end-stage renal disease.TBI is a risk factor for end-stage renal disease in patients with trauma and stage 3 AKI who initiate RRT. Patients with trauma are highly exposed to conditions aggravating kidney injury, such as shock, ischemia, reperfusion, nephrotoxic agents, abdominal compartment syndrome, and direct kidney injury. Emergency laparotomy, interventions, or systemic infections throughout resuscitation trigger these initial AKI risk factors, which leads to impaired renal dysfunction.Acute kidney injury (AKI) is one of the most common complications seen in critically ill patients. Several studies have reported that the incidence of AKI in patients with trauma varies from 1% to 50%. As such, many studies have been conducted on AKI in patients with severe trauma; however, few studies have focused on long-term outcomes, especially, disease progression to end-stage renal disease (ESRD).AKI is associated with prolonged intensive care unit stay and a significantly higher risk of mortality, which increases public health expenses. However, this association between TBI and renal disease progression to chronic kidney disease (CKD) or ESRD is not well-known.Recent studies proposed that the traumatic brain injury (TBI) is associated with impaired renal function.In this study, we classified patients with trauma of stage 3 AKI, as per the Kidney Disease Improving Global Outcomes (KDIGO) guidelines, who initiated renal replacement therapy (RRT) into 2 groups depending on the presence of TBI. Comparing the baseline characteristics and management strategies of each groups, we analyzed whether TBI affects the disease progression.22.1This retrospective observational study was based on data obtained from the registry of a single level 1 trauma center. The study protocol was approved by the Institutional Review Board of Ulsan University Hospital (2020-10-027), which waived the need for informed consent.2.2Between January 1, 2014 and June 30, 2020, 123 patients underwent RRT due to AKI after trauma, which corresponds to stage 3 AKI according to KDIGO guideline  in the univariate analysis were analyzed by logistic regression for their association with the disease progression. A P-value of <.05 was considered statistically significant. All statistical analyses were performed using SPSS version 21.0 .The categorical variables were represented as frequencies and percentages, and the continuous variables were reported as medians and ranges. The categorical variables were compared using the chi-squared test or Fisher exact test (when the chi-squared test was not available). The continuous variables were compared using the Student 33.1Of the 123 patients, 72 were excluded based on the study criteria, and consequently, 51 were enrolled. The median age was 55 years and 76.5% of the patients were male. The median injury severity score (ISS) was 25 and the median Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score was 26. Of the total study participants, 39.2% had TBI, 33.3% had hypertension, and 7.8% had diabetes. Forty-six patients required emergency surgeries on multiple sites, and 8 out of 51 patients underwent RRT at discharge as the disease progressed. The median number of follow-up was 489 days. The baseline characteristics of the patients are shown in Table 3.2P < .05).We divided the patients into 2 groups according to the presence of TBI, and the groups were compared for their demographic and clinical characteristics Table . There w3.3t test or Mann–Whitney test for continuous variables separately in advance. Significant variables (P < .25) in the univariable analysis were analyzed by logistic regression for their association with persistent RRT. Factors known to affect kidney functions and thought to be clinically relevant were also included in the analysis. Table We conducted the chi-squared test or Fisher exact test for categorical variables, and Student es P < .2 in the u4 In order to find the cause of the significant difference in the results, we further investigated the treatment strategies of the patient groups, but none of the variables showed a significant difference, including fluid and nephrotoxic drug usage, which was observed only in a single patient of the persistent RRT group.Based on previous studies that investigated the relationship between TBI and renal function, we compared and analyzed the enrolled patients according to whether they had TBI. We found that patients with TBI required persistent RRT at discharge and at the latest outpatient clinic points, which was significantly more than in those without TBI. In this study, 8 patients with trauma required RRT, and the sole risk factor of persistent RRT due to disease progression was TBI. All other variables appeared to have no significant difference among patients with or without TBI. Moreover, the 2 groups showed no difference in the APACHE II and ISS scores, implying that the injuries were of the same magnitude. Inflammatory cascades after brain injury converged with complement activation and inflammatory cytokine release. These proinflammatory mediators pass the damaged blood brain barrier into systemic circulation, causing organ injury. Civilett et al carried out an in vitro study with human tubular epithelial cells to clarify the association between severe TBI and acute tubular injury. This study showed that the inflammatory process associated with TBI correlates with renal function. TBI triggers a complex cascade of cellular events, leading to systemic inflammation and damage of kidney and other organs. Civilett et al also mentioned that this hypothesis might be supported by the increased neutrophil gelatinase-associated lipocalin level, which was significantly elevated, even if biomarkers currently used for the diagnosis of AKI appeared to be within the normal range. Although it cannot be considered statistically meaningful due to the small number of subjects, the correlation between inflammatory markers and kidney disease progression also can be glimpsed in the Table Although the mechanism of AKI in patients with TBI have not been fully elucidated, it can be considered from 2 main perspectives, trauma and brain injury. First, patients with trauma are highly exposed to conditions aggravating kidney injury, such as hypovolemic shock, frequent use of nephrotoxic agents for diagnosis, and direct kidney injury. Routinely administered medications such as NSAIDS also deteriorate kidney function. Second, brain injury leads to excessive secretion of antidiuretic hormone, causing hyponatremia and fluid imbalance. In addition, stimulated sympathetic nervous activity with increased level of plasma catecholamine, results in hypertension with decreased kidney perfusion. However, the circumstances under which the disease progresses into ESRD has not been precisely evaluated. Nonetheless, a recent study provided clues to estimate the conditions of disease progression.AKI to CKD transition is mainly caused by maladaptive repair of kidney injury. This process includes many pathophysiological processes, for example, cell death or acute tubular necrosis, renal fibrosis, which are characterized by the accumulation of extra cellular matrix, capillary rarefaction by endothelial to mesenchymal transition, tubular epithelial cell senescence, and consequent inflammatory processes. performed a retrospective observational analysis of long-term renal outcomes of patients with TBI and found that patients with TBI developed significantly more CKD than those without; however, there was no difference in the progression to ESRD. The study covered nationwide population of patients with TBI regardless of kidney function, whereas we focused on patients with stage 3 AKI who initiated RRT at the critical phase of management. The estimated reason for the difference in the result comes from the kidney function of enrolled patients at the starting point of analysis. In future studies, significant conclusions about long-term kidney function might be drawn through the analysis in accordance with the presence or absence of TBI in each AKI stage as per KDIGO guideline. These results would be highly versatile in terms of their clinical implications and may enable to anticipate the graft function of the brain-dead kidney donors.Wu et alA considerable limitation of this study is the heterogeneity in the management; patients with TBI were managed mainly by neurosurgeons and those without TBI were managed by general surgeons. Therefore, consistent treatments were not applied to the study patients. In addition, this study was a retrospective analysis conducted using registry data from a single trauma center and consisted of a relatively small number of patients in each group. Thus, selection and information biases might have affected the results. Moreover, the diagnosis of AKI and initiation of RRT were based on patients’ clinical status judged by diverse physicians. It was also a limitation of this study that long-term follow-up of the patients was not performed.5TBI is a risk factor for ESRD in patients with trauma who develop stage 3 AKI, as per the KDIGO guideline. TBI patients might benefit by prudent monitoring of kidney function and early detection of disease. Through early initiation of multidisciplinary management, especially with nephrology, it is possible to reduce the possibility of disease progression by restricting clinical conditions that can cause nephrotoxicity while maintaining volume status.Conceptualization: Kyunghak Choi, Kyu-Hyouck Kyoung, Jihoon T Kim.Data curation: Min Soo Kim, Min Ae Keum, Seongho Choi, Sungjeep Kim.Formal analysis: Kyunghak Choi.Methodology: Kyu-Hyouck Kyoung.Project administration: Minsu Noh.Resources: Kyunghak Choi, Min Soo Kim, Min Ae Keum, Seongho Choi, Kyu-Hyouck Kyoung, Jihoon T Kim, Sungjeep Kim, Minsu Noh.Writing – original draft: Kyunghak Choi.Writing – review & editing: Jihoon T Kim, Minsu Noh.


Office, central blood pressure and PWV were measured on first (0 week), second (4–8 weeks) and third visit (10–12). Difference in BP (in each arm and between arms) was calculated along all visits.Pulse wave velocity (PWV) and central blood pressure (CBP) have been intoduced into managment of hypertensive patients. PWV is positively correlated with arterial wall stiffness while central aortic pressure becomes better predictor of cardiovascular outcome than peripheral pressure. Reduction in CBP provides protective properties against subclinical organ damage. This work aims to investigate the effect of a new combination therapy of Amlodipine/Nebivolol (A/N) on central BP, peripheral BP and PWV. The results of using this combination will be compared to the well-established fixed-dose combination of Amlodipine/Valsartan (A/V). The study conducted between October 2018 and August 2020. One hundred and two hypertensive patients were assigned for Amlodipine 10 mg/Valsartan 160 mg combination therapy  affords a significant reduction in CBP, PBP and PWV with minor and tolerable side effects. It has provided comparable results to Amlodipine/Valsartan (A/V) combination therapy. Central aortic pressure (CBP) becomes a better predictor of cardiovascular outcome than peripheral pressure, particularly in individuals with prominent pulse pressure (PP) amplification , 2. ReduThis is a prospective open-label randomized study which aims to investigate the effect of Amlodipine 10 mg/Nebivolol 5 mg (A/N) combination therapy in comparison with Amlodipine 10 mg/Valsartan 160 mg (A/V) on central hemodynamics parameters. The study was conducted in a hypertension clinic in hospital between October 2018 and August 2020. All moderate to severe adult hypertensive patients were included. Patients with contraindication to Amlodipine, Valsartan and Nebivolol or pregnant, lactating women or females of childbearing potential not practicing contraception were excluded. The included hypertensive patients were either newly diagnosed or previously received antihypertensive medications and still with uncontrolled hypertension , left ventricular (LV) dimensions, septal and posterior wall thickness and valvular affection were obtained. Diastolic dysfunction was also assessed. Albumin-to-creatinine ratio was used as a marker for nephropathy assessment. LVH was detected by ECG and echocardiography.A/V combination is a single-pill combination was administrated on fixed daily dose, day or night, while A/N combination is a two-pill combination were administrated separately on fixed times. Amlodipine 10 mg is administrated at day time while Nebivolol 5 mg is administrated at night.Diagnosis, patient’s inclusion and follow-up visits depended on office blood pressure readings. Three office blood pressure measurements were obtained by properly calibrated mercury sphygmomanometer at each visit by the same operator. A standard operating procedure for measuring BP was followed –11. For P values of less than 0.05 were considered significant.Data were analyzed using the software, Statistical Package for Social Science . Frequency distribution, as a percentage and descriptive statistics in the form of mean and standard deviation, was calculated. Chi-square, t-test and correlations were done in order to compare the two groups in relation to age, gender, BMI, HTN, DM, dyslipidemia, AF and smoking; We tested data normality before conducting the analysis, and the data were normally distributedBaseline patients’ characteristics were comparable between both groups. No statistical significant difference was found between A/V and A/N regarding age, gender, BMI and CV history Table .P = 0.006.Echocardiographic baseline data in both groups showed no statistically significant difference Table . EjectioP values are illustrated in Table P = 0.355, P = 0.808, P = 0.786 and P = 0.505. Al/Cr ratio and fundus examination also did not show significant difference in both groups , left ventricular hypertrophy (LVH), retinopathy, stroke and nephropathy. ps Table .P = 0.443, P = 0.236, P = 0.039 and P = 0.730, Table Office blood pressure (OBP) and CBP had no statistically significant difference between both groups. Mean OBP value was 158.3 ± 15.0/99.9 ± 8.4 in A/V vs. 154.7 ± 12.3/97.7 ± 6.1 in A/N (Table i.Office Blood Pressure (OBP)ii.Central Blood Pressure (CBP)OBP difference between all visits showed no statistically significant difference between both groups; P sys = 0.168 and P dys = 0.936, Tables CBP difference between all visits did not reveal statistically significant difference between A/V and A/N group; P sys = 0.331and P dys = 0.318. For each group, reduction in CBP in every visit was statistically significant compared to the previous one Fig. , Table 4P value of HR 3–HR 1 = 0.017. No statistical difference was found regarding PP between both groups; P = 0.155 ,  and   and (AIX 3–AIX 1) was statistically significant; P = 0.003 and P = 0.000   combination itself or to compare it with the well-established combination of Amlodipine/Valsartan (A/V). BP reduction in hypertensive patients is associated with a lower rate of cardiovascular events. Combina0) Table . Central0) Table , 3. CBP Target OBP (< 140/90) was not obtained in four patients in A/N group versus five patients in A/V group . Ambulatory blood pressure (AMBP) was done for those patients to exclude white coat hypertension (WCH); this revealed two patients with white coat hypertension in A/N versus one patient in A/V group. Patients with WCH in the A/N group had uncontrolled AMBP during night times only. This result could be attributed to the morning administration of Amlodipine instead of night administration. Flack et al.  had discP = 0.382 and P = 0.722). Diabetes, dyslipidemia, BMI and smoking status are comparable in both groups. Patients on A/N combination had significant reduction in PWV; this was revealed through the three follow-up visits (P = 0.000) with no final statistical difference in comparison with those on A/V (P = 0.379).PWV values are affected by aging process , 25, impP = 0.803).Using AIx as a co-marker for AS , 31) in P = 0.017), but not between both groups (P = 0.155). Baseline HR was not statistically different between both groups; A/V HR = 80.8 ± 14.5 and A/N HR = 74.9 ± 14.2 (P = 0.039).Reduction in HR was significant only within A/N patients (P = 0.730). PP values were decreased significantly within A/N over the three follow-up visits, but not in A/V group (P = 0.002) vs. (P = 0.234)  affords a significant reduction in CBP, PBP and PWV with minor and tolerable side effects. It has provided comparable results to the well-known Amlodipine/Valsartan (A/V) combination therapy.


Intraoperative hypotension (IOH) is common during major surgery and is associated with a poor postoperative outcome. Hypotension Prediction Index (HPI) is an algorithm derived from machine learning that uses the arterial waveform to predict IOH. The aim of this study was to assess the diagnostic ability of HPI working with non-invasive ClearSight system in predicting impending hypotension in patients undergoing major gynaecologic oncologic surgery (GOS). In this retrospective analysis hemodynamic data were downloaded from an Edwards Lifesciences HemoSphere platform and analysed. Receiver operating characteristic curves were constructed to evaluate the performance of HPI working on the ClearSight pressure waveform in predicting hypotensive events, defined as mean arterial pressure < 65 mmHg for > 1 min. Sensitivity, specificity, positive predictive value and negative predictive value were computed at a cutpoint . Thirty-one patients undergoing GOS were included in the analysis, 28 of which had complete data set. The HPI predicted hypotensive events with a sensitivity of 0.85 [95% confidence interval (CI) 0.73–0.94] and specificity of 0.85 (95% CI 0.74–0.95) 15 min before the event [area under the curve (AUC) 0.95 (95% CI 0.89–0.99)]; with a sensitivity of 0.82 (95% CI 0.71–0.92) and specificity of 0.83 (95% CI 0.71–0.93) 10 min before the event [AUC 0.9 (95% CI 0.83–0.97)]; and with a sensitivity of 0.86 (95% CI 0.78–0.93) and specificity 0.86 (95% CI 0.77–0.94) 5 min before the event [AUC 0.93 (95% CI 0.89–0.97)]. HPI provides accurate and continuous prediction of impending IOH before its occurrence in patients undergoing GOS in general anesthesia.The online version contains supplementary material available at 10.1007/s10877-021-00763-4. Intraoperative hypotension (IOH) represents a common event during general anaesthesia, with a reported incidence, varying with the chosen threshold, from 5 to 99% . IntraopGynaecological oncological surgery (GOS) for cancer mass reduction is carried out through laparoscopy or laparotomy and is often associated with unstable hemodynamics and significant blood loss , 8. HypoMachine learning, a discipline within computer science used to analyse large data sets and to develop predictive models, has evident applications in health care –13. SeveThe Hypotension Prediction Index—HPI  is an algorithm based on the complex analysis of features in high fidelity arterial pressure recordings developed to detect the interconnection signatures in the arterial pressure waveform when hypotension is impending . The algThe aim of this study was to assess the diagnostic ability of the HPI algorithm derived from non-invasive ClearSight system in predicting impending hypotension in patients scheduled for elective major GOS.This is a retrospective analysis of data collected during a limited period of time in which new hemodynamic monitoring sensors (ClearSight) were evaluated. The study was approved by the Internal Ethic Committee . Written informed consent to treatment of data was obtained from the patients. This manuscript adheres to the applicable STROBE guidelines.Data were gathered from patients who had perioperative monitoring with the HemoSphere platform with ClearSight non-invasive hemodynamic monitoring and with the HPI software enabled at IRCCS Policlinico Agostino Gemelli Foundation of Rome, Italy. Data were collected from 1 December 2019 to 31 January 2020.All patients scheduled for GOS who had intact complete data sets available for analysis were enrolled in the study. Exclusion criteria were: < 18 years of age, an American Society of Anesthesiologists score (ASA) > 3, significant cardiac arrhythmias or aortic regurgitation, permanent atrial fibrillation, coagulation disorders, emergency surgery, preoperative infection and patient’s refusal to treatment of personal data.Standard monitoring  included a 5-lead electrocardiogram, pulse oximetry, non-invasive blood pressure (NIBP) and eventual invasive blood pressure (IBP). In addition to standard monitoring, all patients had a non-invasive hemodynamic monitoring with ClearSight .After arriving at the operating theatre, NIBP measurement using an automated digital sphygmomanometer on the right arm was started and the ClearSight system was attached to a finger of the left arm of the patients Fig. , panel AThe attending anesthesiologist was blinded to the advanced hemodynamic parameters from the ClearSight system , except for the continuous arterial pressure value read from the finger cuff (CS-BP), which was reported on the main monitor. NIBP measurement using the automated digital sphygmomanometer was performed at 5-min intervals.A large bore i.v. catheter was inserted in a forearm vein, and Cefazoline 2 gr, Dexamethasone 4 mg and Omeprazole 40 mg were administered. General anesthesia was induced with sufentanil 0.2 mcg/kg , propofol 2 mg/kg , and rocuronium 0.6 mg/kg . During surgery, patients were positioned in Trendelenburg position with both arms spread out on arm-positioning devices. Anesthesia was maintained with Sevoflurane to maintain a Bispectral Index value between 40 and 50. Additional boluses of sufentanil and rocuronium were administered when needed.For therapy purposes we defined hypotension as an absolute value of CS-BP MAP < 65 mmHg. Incidence and duration of hypotensive episodes and interventions were registered. Bradycardia was defined as a heart rate (HR) < 60 bpm. Clinicians were free to manage haemodynamic state of the patients using any type of intravenous fluids, vasopressors, and inotropes, according with their personal judgement and institutional clinical practice.All data were downloaded from the HemoSphere monitor, including HPI, CS-MAP, CS systolic arterial pressure, CS diastolic arterial pressure. All downloaded data consisted of 20-s interval averaged data points. Data were transferred to a computer for analysis via an USB drive. Every file was appointed with an automated generated code by the machine and was identifiable by an ID number contained within it.The HPI algorithm estimates the probability of occurrence in the near future of a hypotensive event taking the arterial pressure waveform as the input to compute an index value that ranges between 0 and 100. In this study, instead of invasive arterial waveform data, we used the non-invasive arterial pressure waveform of ClearSight. The alarm threshold for HPI is fixed at 85, and it was silenced, as all the other ClearSight variables.In the HemoSphere monitor, poor quality arterial waveforms were automatically detected by the arterial waveform processing algorithms and excluded from the computation of the 20-s averages.A data analysis and statistical plan was designed after the data were accessed. An a priori sample size calculation was not performed.Normally distributed continuous data are presented as mean (SD), non-normally distributed data as median (25th–75th percentile). Categorical data are presented as n (%). Normality of data distribution was assessed with the Shapiro–Wilk test and visually with histograms; the equality of variance was verified with the variance ratio test. P values < 0.05 were considered statistically significant.Hypotensive events (defined as a MAP < 65 mmHg for > 1 min) were analysed in terms of number, absolute duration, area under the threshold of 65 mmHg, and time-weighted average under the threshold, calculated as area under the threshold/duration of monitoring, similar to as described by Maheshwari et al. . The numReceiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the HPI algorithm working on the ClearSight blood pressure waveform. Sensitivity was reported on the y-axis and 1-specificity on the x-axis. The area under the curve (AUC) estimating the ability of HPI to discriminate between hypotensive versus non hypotensive events at 5, 10 and 15 min before the actual event occurred was computed. Sensitivity, specificity, positive predictive value, and negative predictive value were computed at a cutpoint, identified as the value that minimizes the difference between sensitivity and specificity .A true positive was considered any hypotensive event (MAP < 65 mmHg for at least 1 min) with HPI value greater than or equal to a chosen threshold (the cutpoint) at 5, 10, or 15 min. A true negative was any non-event data point (MAP > 65 mmHg) with HPI value less than the chosen threshold. Sensitivity is the ratio of true positives to all events. Specificity is the ratio of true negatives to all non-events. Positive predictive value was calculated as the number of true positive events divided by all positive ones. Negative predictive value was the number of true negative events divided by all negative ones.ROC analysis was also used to evaluate the performance of the change of CS-MAP (ΔMAP) to predict hypotension 5, 10 and 15 min before its occurrence.In the ROC analysis, the repeated measures from the same patient were compensated using the bootstrapping method: 28 patients were randomly chosen from the total 28 patients with replacement. This process was repeated 2000 times from which the standard error was calculated. The bootstrap CI was calculated as a 95% asymptotic confidence interval.Data analysis was performed using STATA MP 15.1 (Stata Corp) for Windows, Microsoft Excel, Matlab , and Acumen Analytics software .Fifty-six patients undergoing major GOS from 1 December 2019 to 31 January 2020 were screened during study recruitment. Twenty-five cases were not included because they did not meet the inclusion criteria. Thirty-one patients with a mean age of 50 (± 10.44) years were included in the analysis. In 3 cases data were incomplete for technical problems with HPI monitoring and were excluded from ROC analysis. The data collected from remaining 28 women were complete ; at the cutpoint of 41.6, sensitivity was 0.82 (95% CI 0.71–0.92), specificity was 0.83 (95% CI 0.71–0.93) with a positive predictive value of 0.79 (95% CI 0.56–0.93) and a negative predictive value of 0.85 (95% CI 0.73–0.94). The positive data points analysed were 41, the negative data points 49.The AUC for prediction of hypotension 5 min before the event was 0.93 (95% CI 0.89–0.97); at the cutpoint of 44.1, sensitivity was 0.86 (95% CI 0.78–0.93), specificity was 0.86 (95% CI 0.77–0.94) with a positive predictive value of 0.88 (95% CI 0.77–0.96) and a negative predictive value of 0.82 (95% CI 0.70–0.91). The positive data points analysed were 64, the negative data points 49.Results of ROC analysis are showed in Table This study demonstrates that the HPI algorithm working with non-invasive arterial pressure waveforms monitoring (ClearSight) can predict hypotension with high accuracy in patients undergoing major GOS up to 15 min before the event.Blood pressure is one of the main determinants of organ perfusion. Profound IOH is common in patients undergoing surgery and is associated with hypoperfusion and organ failure. To date, treatment of hypotension is “reactive”, and the physician acts only after low blood pressure values have already occurred.Recent studies have suggested that the prodromal stage of hemodynamic instability is characterized by complex changes in different physiologic variables, reflecting altered compensatory mechanisms, and resulting in unique dynamic signatures in arterial waveforms heralding the occurrence of the vast majority of hypotensive events –17. PredApproximately two thirds of our patients underwent laparoscopic surgery with Trendelemburg position up to 30°, which is well known to increase MAP, while one third of the patient underwent a laparotomic intervention with minimal to none Trendelemburg position. The hypotensive load of our patients measured as median TWA-MAP < 65 mmHg  is similar to that of other cohorts  . ExpecteThere is growing evidence regarding the performance of the HPI applied to invasive arterial waveforms in large cohort of patients , 22. MorThe non-invasive ClearSight system uses an implementation of vascular unloading technique or volume clamp method Fig. , panel BIn the present study ROC analysis also showed that the performance of ΔMAP in predicting hypotension at 5, 10, and 15 min was low compared with HPI, in agreement with the findings of Hatib and Davies on invasive arterial waveforms , 17.Our results enable prediction, and potentially also prevention of hypotension in a much larger patient population exposed to the risk of IOH but in which arterial cannulation is seldom used. Moreover, arterial cannulation imposes the risk of several complications , and is therefore currently restricted to selected surgical cases . Given tIn our opinion there are also translational aspects in this study to be considered, that rely above all on the fact that engineering advances and machine learning models applied to medical research as in the case of HPI, could facilitate the physicians to treat IOH always more as a potentially modifiable risk factor for major postoperative complications whose association although well established, still needs further characterization in terms of clinical outcomes , 29. FurThis study has several limitations. The first is the small sample size, with heterogeneous characteristics of kind of GOS. The minimum amount recommended for external validation of a multivariable model such as HPI is 100 (in this case hypotensive) events, and we analysed 135 events . The widThe second limitation is due to lacking information on detailed doses of vasopressors and fluids that were administered to treat hypotensive events, so we are unable to determine the correlation between the HPI value and the interventions performed. Unfortunately, this is inherent in the retrospective nature of this data analysis: vasopressors and fluids were administered in response to hypotensive events, and we are unable to determine the correlation between the HPI value and the interventions performed to treat hypotension. This may have limited the duration of some hypotensive events, because only those lasting more than 1 min have been considered. As stated by Davies et al., this would lead to an increased false positive rate for the prediction index and could reduce the predictive ability of HPI . Only prIn conclusion, the HPI working with non-invasive ClearSight finger cuff provides real time and accurate prediction of impending arterial hypotension in patients undergoing GOS.Supplementary file1 (DOCX 18 kb)Below is the link to the electronic supplementary material.


To understand the characteristics and clinical presentation of patients with Congestive Heart Failure (CHF) visiting the emergency department (ED), and to examine the factors associated with clinical outcomes and medical resource utilization amongst the studied population.We analyzed the 2014–2016 ED visit data collected by the National Hospital Ambulatory Medical Care Survey Emergency Department Subfile. We described patients’ characteristics and clinical outcomes after ED visits with CHF vs. without CHF. Logistic regression models were used to estimate the association between these characteristics and CHF.ED visits with CHF visits represented 3.9% of annual ED visits . ED patients with CHF were mostly non-Hispanic White (69.9%). Compared with other ED patients, those with CHF were older, including 71.2% that were were older than 60. ED patients with CHF were more likely to be admitted to the hospital  and intensive care unit (ICU) .This study describes the demographic, socioeconic, and clinical characteristics of patients who present to the ED with CHF through analysis of a comprehensive national survey. These patients require a higher level of emergency care due to their higher chance of admittance to the hospital and ICU.The online version contains supplementary material available at 10.1186/s12873-021-00564-7. Congestive heart failure (CHF) is a national public health problem in the United States with significant prevalence and mortality , 2. An eWhile CHF is a complex clinical syndrome with a variety of etiologies and clinical presentations, many patients with CHF present with reduced left ventricular function and have the related symptoms of dyspnea with peripheral and pulmonary edema . The absVisiting the Emergency Department (ED) can often be unavoidable for most patients with CHF. The ED is an important venue for care of patients with CHF , 13. It We performed a secondary data analysis on the National Hospital Ambulatory Medical Care Survey Emergency Department Subfile (NHAMCS-ED) to estimate the national characteristics of patients with congestive heart failure who utilize the ED, explore the association between congestive heart failure and related clinical presentations, and to follow health outcomes of patients with in the ED setting.N = 42,832, Weighted N = 278,699,057) [The study design and statistical analysis is similar to our previous study on ED visits by patients with depression . We perf699,057) , a natio699,057) . The sur699,057) , 22. GenThe primary study outcome is patient congestive heart failure status identified using the variable “congestive heart failure status,” which was checked from the patients’ electronic health records or claims data. NHAMCS defined congestive heart failure status as including “the inability of the heart to supply sufficient blood flow to meet the needs of the body. Does not include asystole or cardiac arrest.”Secondary outcomes of the study included the Emergency Severity Index (ESI) ; hospital/intensive care unit (ICU) admission; blood test; medical imaging ; clinical procedures ; whether the patient left before triage or treatment; length of stay; and whether the patient died in the ED/hospital.The study covariates that are examined include demographic characteristics ; socioeconomic status indicators, including residence  and insurance ; day and mode of arrival; triage vital signs ; and reason for the ED visit.Population characteristics between congestive heart failure and non-congestive heart failure groups were described and compared. The proportion of medical imaging use among different racial/ethnic groups and covariates between groups were compared using chi-square tests. We used unweighted logistic regression to test the association between the outcome (ED patients with congestive heart failure) and the covariates. We imputed the missing with the median of each covariate when modelling the multivariable logistic regression. α = 0.05 was set as the statistical significance threshold. We used SAS (version 9.4) for analyses.p < 0.001). The proportion of the male patients is 43.0% .A total of 278,699,057 adult ED visits in the US were reported in the data, corresponding to approximately 92,899,685 annual ED visits from 2014 to 2016 (Table p < 0.01). A greater proportion of ED patients with CHF belonged to the 50–59, 60–74, and > =75 age groups when compared to their non-CHF counterparts . ED patients with CHF comprised a higher proportion of non-Hispanic Whites relative to those without CHF .The proportion of ED visits by patients with CHF varied by US census region: Northeast, 14.5%; Midwest, 30.0%; South, 41.3%; and West, 14.2%  for CHF. Future studies may examine more data related to CHF characteristics, comorbidities, treatment history, and other finer-grained clinical data, which allows for better understanding of the associated factors related to CHF ED care. Thirdly, the data on the acute and chronic CHF is unknown in the survey, which should be collected in the future studies.This study describes the demographic, socioeconomic, and clinical characteristics of patients who present to the ED with CHF through analysis of a comprehensive national survey. The study describes the characteristics of CHF patients who visit the ED on a national scale. We found that there are gender, age, and racial/ethnic differences between ED patients with and without CHF. These patients require a higher level of emergency care due to their higher chance of admittance to the hospital and ICU.Additional file 1: Supplement Table 1. Association between ED visiting with Congestive heart failure and patient visiting characteristics, NHAMCS 2014–2016. Note: the adjusted OR was from a logistic regression including all variables in the table.