In living donor liver transplantation (LDLT), graft-to-recipient weight ratio (GRWR) <0. 8% is an important index for predicted portal hypertension, which may induce the graft small-for-size syndrome (SFSS). Recently, the value of graft-to-spleen volume ratio (GSVR) on predicted portal hypertension had been reported, whether without splenectomy prevent portal hypertension in transplantation remains disputed, we aimed to identify GSVR contributing to portal venous pressure (PVP) and outcomes without simultaneous splenectomy in LDLT.A retrospective study had been designed. Excluded patients with splenectomy, 246 recipients with LDLT between 2016 and 2020 were categorized into a low GSVR group and a normal GSVR group. Preoperative, intraoperative, and postoperative data were collected, then we explored different GSVR values contributing to portal hypertension after reperfusion.P < 0.05). Following the surgical factors, there were significant differences in blood loss and CRBC transfusion (P < 0.05). The low GSVR has demonstrated had a significant relationship with ascites drainage and portal venous flow after LDLT (P < 0.05). Meanwhile, low GSVR heralds worse results which covered platelet count, international normalized ratio (INR), and portal venous velocity. Kaplan–Meier analysis showed that there was a significant difference between the two groups, while the low GSVR group demonstrated worse recipients survival compared with the normal GSVR group (P < 0.05).According to the first quartile of the distributed data, two groups were divided: low GSVR (<1.03 g/mL) and normal GSVR (>1.03 g/mL). For the donors, there were significant differences in donor age, graft type, liver size, GRWR, and GSVR (Without splenectomy, low GSVR was an important predictor of portal hypertension and impaired graft function after LDLT. Liver transplantation is an effective treatment for end-stage liver disease. However, due to the shortage of organs in China, living donor liver transplantation (LDLT) has become the best choice for end-stage liver disease patients. Small-for-size syndrome (SFSS) is a complication that may induce severe outcomes after LDLT . It is wConsidering previous studies , 10, it A single-center retrospective analysis was performed, including all patients who underwent LDLT at the Beijing Friendship Hospital, China, between January 2016 and April 2020. The study was approved by the Beijing Friendship Hospital Research Ethics Committee . A total of 238 patients were enrolled after excluding the following cases: 5 with splenectomy during operation, 25 without whole spleen imaging by preoperative computed tomography, and 80 with incomplete clinical data.Preoperative imaging evaluation of the patients was performed using multislice spiral CT . Compared to the actual liver weight measured during the operation, the evaluation of the influence of the donor's liver volume before the operation is more valuable. The liver and spleen volumes were measured by hand tracing the portal venous phase images in the CT examination with the major vessels were excluded. The area of the organ in each section was multiplied by the slice thickness to calculate the volume. The total volume of the organ was then calculated by adding the individual volumes. The liver and the spleen have similar density as water, so graft weight was defined as the graft volume . The GSVPrimary non-function (PNF) is defined as a clinical disorder that results in liver necrosis or multisystemic dysfunction which usually requires liver retransplantation (during the 90 days) . UnplannAll recipients underwent the same surgical procedure. Portal vein anastomosis was done using 6-0 or 5–0 Prolene sutures in a running fashion with a growth factor. Hepatic artery anastomosis was done using interrupted 8-0 or 7–0 Prolene sutures. Biliary drainage was established by duct-to-duct or by duct-to-Roux-en-Y drainage. The drainage tube was kept unobstructed after the operation and the ascites volume was recorded daily. The immunosuppressive treatment protocols included methylprednisolone and tacrolimus. The first methylprednisolone dose (10 mg/kg) was preferred after the surgery. Dose tapered from 10 to 0.1 mg/kg/day during the postoperative period, using <3 months in duration. Tacrolimus (0.01–0.05 mg/kg/day) was the first choice for immunosuppressive therapy at the third-day post-LDLT and the mycophenolate mofetil (10−30 mg/kg/day) were initiated on postoperative day 3. The methylprednisolone trough level of tacrolimus was adjusted to 8–10 ng/ml , 14.Focusing on the prognosis of liver transplantation, we intendedto describe a cut-off value of GSVR; patients were separated into two groups .U-test for continuous variables and the Chi-square test for categorical variables as appropriate. The PNF was analyzed using the univariate analysis, and variables significant at a p < 0.20 in the univariate analysis were used in the multivariate logistic regression model  was used for all statistical analyses.Continuous data are expressed as medians with ranges or interquartile ranges (IQRs) as appropriate. Categorical data are presented as numbers and percentages. Comparisons were expressed by the Mann–Whitney on model . Graft sn = 59) or normal GSVR  . The 1st and 3rd quartiles were 1.03 and 3.37 g/ml. The cut-off value according to the IQR is based on 246 measured values. According to the research of previous scholars, low GSVR lead to bad endings; then the 1st quartile as the threshold, recipients were assigned to two groups: low GSVR  .P < 0.05). The median age and spleen size were significantly larger in the normal GSVR group than in the low GSVR group. For the donors, there were significant differences in donor age, graft type, liver size, GRWR, and GSVR (P < 0.05). Regarding the surgical factors, there were significant differences in blood loss and CRBC transfusion (P < 0.05). Thus, there were no differences in postoperative outcomes.All recipients (children and adults) are described in p = 0.001). This suggested that GSVR might be a useful predictor of portal hyperperfusion syndrome in LDLT, while for the recipients, low GSVR presumes to extend the drainage tube time. Portal flow velocity was measured after arterial reconstruction by Doppler the first day after LDLT, all the recipients had been attached PVF. The GSVR showed a positive correlation with the PVF after LDLT. There was a statistically significant relationship noted between GSVR and PVF  was calculated. As shown in p = 0.025) independently affected early graft survival after liver transplantation.Risk factors for PNF were assessed among the two groups. The graft-to-recipient weight ratio (GRWR) was analyzed with Cox proportional hazards models . Multivap = 0.006)  .Liver transplantation is an effective treatment for end-stage liver disease. However, due to the shortage of organs in China, LDLT has become the prior choice for patients with end-stage liver disease. This study included a variety of diseases, including biliary atresia and liver failure, represented by cirrhosis, and metabolic diseases, represented by non-cirrhosis. Hypersplenism function and volume increase are common complications in patients with liver cirrhosis. At the same time, the blood flow of the spleen contributes 52% of the blood flow of the portal vein of the liver . TherefoFirst, we focused on the clinical recovery after LDLT. We defined the GSVR as 1.03, the patients were divided into 2 groups (GSVR > 1.03 and GSVR <1.03), and the observation of total protein, bilirubin, ascites, INR, and PLT have been recorded. These indicators represent the recovery of liver function and the possibility of small liver syndrome. Yao  deemed lStudies have revealed that high PVP after reperfusion is a key factor in the occurrence of SFSS. As we know, three factors reflect PVP: the size of the graft, outflow from the hepatic vein, and portal hemodynamic status. Since PVP was not tested during and after the operation, in this study we focused on the volume of ascites, the average catheterization time, and PVF of the patients after the operation. Vasavada  believedThis study did not detect intraoperative portal pressure, as the replacement, Doppler has been used to check the postoperative liver portal vein blood flow and flow rate, which is an indirect reflection of the portal vein pressure, but this examination reduced the accuracy of the portal vein pressure, and brought difficulty in the judgment of postoperative ascites volume and SFSS. In this study, we excluded patients who underwent splenectomy due to hypersplenism. As our study showed, it took a long time for the platelets to return to normal and longer drainage tube days in the low GSVR group. During the operation, we faced the challenge of deciding whether to perform splenectomy or splenic artery modulation during the operation. Umeda  reportedP < 0.05), and GSVR <1.03 g/ml is not a key factor of PNF. Previous results .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.


Objectives: Although the PARAGON-HF trial failed to reach its primary endpoint, subgroups of patients with heart failure with preserved ejection fraction (HFpEF) still appear to benefit from Sacubitril/Valsartan therapy. As HFpEF patients with pulmonary hypertension display a specifically high mortality and morbidity, we evaluated the effect of Sacubitril/Valsartan in this subgroup of HFpEF patients.Methods: In this retrospective case-series of 18 patients with HFpEF and pulmonary hypertension, right heart catheterisation (RHC) for determination of invasive pulmonary pressure were performed at baseline  and 99 (71–156) days after transition from angiotensin-converting enzyme inhibitors and angiotensin receptor blockers to Sacubitril/Valsartan . Results are given as median and interquartile range.Results: After conversion to Sacubitril/Valsartan, RHC showed significantly reduced pulmonary artery pressure (PAP) and mean pulmonary capillary wedge pressure (PCWP) compared to pre-Sacubitril/Valsartan . Median Sacubitril/Valsartan dosage was 24/26 mg BID (24/26 BID−49/51 mg BID). Clinically, New York Heart Association functional class improved in 12 of the 18 patients (p < 0.01) after conversion to Sacubitril/Valsartan. Echocardiographic parameters of left ventricular function and cardiovascular co-medication did not differ markedly between pre- and post-Sacubitril/Valsartan.Conclusion: Sacubitril/Valsartan therapy is associated with an improvement of pulmonary hypertension in HFpEF patients. Heart failure with preserved ejection fraction (HFpEF) is by now the most common form of heart failure and its incidence still continues to grow worldwide, but an approved guideline therapy is still not available . Only reIn rat models of pulmonary hypertension, Sacubitril/Valsartan has been shown to reduce pulmonary pressures and histological vascular remodeling , 5 and oWe therefore sought to investigate whether Sacubitril/Valsartan would impact pulmonary hypertension in this subgroup of otherwise heterogeneous HFpEF patients diagnosed according to the HFA-PEFF algorithm .This is a retrospective case-series of 18 patients with HFpEF and dyspnoea as the leading symptom for hospital admission (January 2018 to August 2020) in whom Sacubitril/Valsartan was initiated at the discretion of the treating physician. Determination of invasive pulmonary pressure was performed by right heart catheterisation (RHC) at baseline in the absence of Sacubitril/Valsartan . Following this, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were converted to Sacubitril/Valsartan at 24/26 mg BID and was titrated to the highest clinically and hemodynamically tolerated dose. Effects of Sacubitril/Valsartan on pulmonary pressures were documented 99 (71–156) days later during a planned second hospital admission with follow-up RHC .All RHC were performed in the catheterisation laboratory with a Philips Allura Xper FD10 cardiovascular X-ray system including Xper Flex Cardio Physiomonitoring System for recording of end-expiratory pulmonary artery pressure (PAP), mean pulmonary capillary wedge pressure (PCWP), right atrial (RA) pressure and calculation of pulmonary vascular resistance (PVR), cardiac output (CO), cardiac index (CI), and systemic vascular resistance (SVR). CO was calculated according to Fick's principle. Pre- and post-Sacubitril/Valsartan RHC were performed by the same cardiologist each and transfemoral venous access using a 7F Swan-Ganz catheter was the preferred approach. HFpEF was diagnosed according to the recommendations from the Heart Failure Association of the European Society of Cardiology .p-value of < 0.05 was considered statistically significant.Statistical analysis was performed using GraphPad Prism 7.0 . Continuous data are presented as median and interquartile range; frequencies and percentages are used to describe discrete variables. Continuous data were analyzed using the Wilcoxon matched-pairs signed rank test and categorical variables using the two-tailed Fisher's exact-test. A 5] (p < 0.01). Invasive determination further revealed a markedly reduced RA pressure at follow-up  presumably as a consequence of decreased PAP. Other invasive parameters such as PVR, CO, CI, and SVR did not differ significantly between pre- and post-Sacubitril/Valsartan, respectively . Furthermore, echocardiographic parameters of left ventricular function and cardiovascular co-medication did not differ significantly between pre- and post-Sacubitril/Valsartan (Clinical patient characteristics are summarized in 5] . After c5] . Median alsartan .To the best of our knowledge, this is the first human study to demonstrate that Sacubitril/Valsartan therapy is associated with improvement of pulmonary hypertension in HFpEF patients by lowering pulmonary artery pressures. Interestingly, although patients only received the lowest approved dosage of Sacubitril/Valsartan when hemodynamic control measurements were performed, patients experienced a significant improvement not only concerning the hemodynamic readout but also concerning NYHA classification. Invasive hemodynamic data are scarce as to Sacubitril/Valsartan therapy because invasive phenotyping of patients was never included in randomized controlled trials. Cacciatore et al. recently reported a similar impact of Sacubitril/Valsartan on pulmonary hypertension in end stage HFrEF patients that were listed for heart transplantation . Thus, SIt should, however, be acknowledged, that this is a small single-center retrospective observational study and thus only generates a working hypothesis.Our data insinuate that Sacubitril/Valsartan might prove to be a novel therapeutic approach in HFpEF patients to treat pulmonary hypertension. Larger trials employing invasive phenotyping of pulmonary hemodynamics are thus eagerly awaited to solve an ever growing problem imposing a heavy burden of mortality and morbidity.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The study protocol was approved by an institutional review and safety board at the Heart and Vascular Center Bad Bevensen. Written informed consent was not required for this study, in accordance with the local legislation and institutional requirements.Data acquisition, analysis, and interpretation was done by JB, HS, and MJ. CB and BR drafted the manuscript. JB, HS, and MJ revised the article for important intellectual content. All authors gave final approval of the version to be published, involved in the conception of the present study, and fully accountable for the content of the 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.


There is no generally accepted comprehensive risk prediction model cooperating risk factors associated with heart failure and pulmonary hemodynamics for patients with pulmonary hypertension due to left heart disease (PH-LHD). We aimed to explore outcome correlates and evaluate incremental prognostic value of pulmonary hemodynamics for risk prediction in PH-LHD.Consecutive patients with chronic heart failure undergoing right heart catheterization were prospectively enrolled. The primary endpoint was all-cause mortality. Individual variable selection was performed by machine learning methods. Cox proportional hazards models were conducted to identify the association between variables and mortality. Incremental value of hemodynamics was evaluated based on the Seattle heart failure model (SHFM) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) scores.2) were the hemodynamic predictors most strongly associated with mortality , with consistent significance after adjusted for SHFM  or MAGGIC  scores. The inclusion of DPG and SvO2 improved risk prediction compared with using SHFM  or MAGGIC  scores alone.A total of 276 PH-LHD patients were enrolled, with a median follow-up time of 34.7 months. By L1-penalized regression model and random forest approach, diastolic pressure gradient (DPG) and mixed venous oxygen saturation (SvOIn PH-LHD, pulmonary hemodynamics can provide incremental prognostic value for risk prediction.Clinical trial registration: NCT02164526 at https://clinicaltrials.gov. Pulmonary hypertension due to left heart disease (PH-LHD), typically characterized by a passive increase in pulmonary artery wedge pressure (PAWP) in response to a backward transmission of elevated left-sided filling pressures, is the most frequent cause of pulmonary hypertension (PH) , 2. PH-LHowever, to the date, the most commonly applied comprehensive risk prediction strategies for PH, including the REVEAL risk score (RRS), the risk assessment proposed by the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines and its abbreviated versions, have been derived from pulmonary arterial hypertension (PAH), while its application to PH-LHD has yet to be validated , 11–14. Accordingly, the objectives of our study were: (1) to evaluate prognostic value of the established risk prediction strategies for PAH and HF in a cohort of PH-LHD and identify other outcome correlates; (2) to explore incremental prognostic value of pulmonary hemodynamics for risk prediction in PH-LHD.. Written informed consent was obtained from all enrolled patients. This study complied with the Declaration of Helsinki. The study protocol was approved by the ethics committee of Fuwai hospital .In this national multicenter prospective registry study, patients with symptomatic chronic heart failure undergoing first right heart catheterization (RHC) during hospitalization were consecutively enrolled from January 2013 to August 2016 in 11 participating medical centers throughout China. The study has been registered on ClinicalTrials.gov (Identifier: NCT02164526). Patients in the current study were included if: (1) their age were between 18 and 80; (2) they were diagnosed with chronic heart failure with NYHA II-IV; (3) the etiology of their heart failure was ischemic heart disease, hypertension or idiopathic cardiomyopathy; (4) they underwent RHC and had hemodynamically defined post-capillary PH. Patients were excluded if they: (1) had pulmonary hypertension of other types; (2) had organic valvular heart disease; (3) had right ventricular outflow tract obstruction; (4) had pericardial disease, including pericarditis, a thickened or calcified pericardium; (5) had chronic pulmonary diseases such as interstitial fibrosis, chronic obstructive pulmonary disease or primary parenchymal lung disease; (6) had hypertrophic obstructive cardiomyopathy; and (7) previous acute myocardial infarction and/or received revascularization in the previous six monthsElectrocardiogram (ECG), chest X ray, transthoracic echocardiography, pulmonary function test, high-resolution computed tomography of the chest, ventilation/perfusion scintigraphy lung scan (if necessary) and pulmonary angiography (if necessary) were performed to evaluate the severity of heart failure, exclude pulmonary hypertension due to other causes and conditions in the exclusion criteria, such as lung diseases or chronic thromboembolism pulmonary hypertension.The indications of RHC were based upon referring physicians, mostly for the diagnosis of suspected pulmonary hypertension with an elevated systolic pulmonary arterial systolic pressure (PASP) at echocardiography, for decreased exercise capacity despite initial standard therapies, or for assessment and monitoring of hemodynamics. Catheterizations were also performed for transplantation eligibility assessments, or prior to percutaneous interventions or surgical procedures. Catheterizations were performed in stable, non-acute clinical conditions; in other words, patients with acute decompensated HF were excluded, with only stable chronic HF patients enrolled.For patients who met the inclusion and exclusion criteria, the following data were collected: (1) demographics, medical history, clinical symptoms and vital signs; (2) results of laboratory tests, echocardiography and catheterizations; and (3) drug treatments .RHC was centralized using a standard protocol across all the participating centers. During the procedure, patients were positioned supine with legs flat. A 7F Swan-Ganz catheter  was inserted from a femoral or jugular approach, with zeroing calibration in the mid-axillary line to atmospheric pressure. Correct positioning of the catheter was verified by chest fluoroscopy. Hemodynamics, including right atrial pressure (RAP), diastolic pulmonary arterial pressure (dPAP), systolic pulmonary arterial pressure (sPAP), mean pulmonary arterial pressure (mPAP) and PAWP, were obtained during spontaneous breathing. All pressures were recorded after at least 6 stable cardiac cycles during several respiratory cycles. PAWP was measured at end-diastole. Cardiac output (CO) was measured by the thermodilution method . The DPG was assessed as the difference between dPAP and PAWP. TPG was calculated by subtracting PAWP from mPAP. PVR was obtained by the equation: PVR = (mPAP-PAWP)/CO. PAC was calculated as stroke volume divided by the difference between sPAP and dPAP.Symptomatic chronic heart failure was diagnosed based on the presence of HF signs, symptoms and other indications as recommended in the 2012 HF guidelines, which differentiates HFpEF from HFrEF by echocardiographically estimated LVEF, with a cut-off value of 50% . Post-caAs for PH risk prediction strategies, the algorithm incorporated 9 evaluable elements used to calculate RRS: NYHA functional class II, renal insufficiency, males whose age > 60 years, systolic blood pressure (SBP), heart rate (HR), N-terminal pro-brain natriuretic peptide (NT-proBNP), RAP and PVR , 18. Dat2) were available but 6MWD was not available in the current cohort, we counted the number of the following low-risk criteria: (1) NYHA functional class II, (2) RAP < 8 mmHg, (3) cardiac index ≥ 2.5 L·min−1·m−2, (4) NT-proBNP < 300 ng/L and (5) SvO2 > 65%.The French registry invasive risk stratification method classifies patients according to the presence of the ESC/ERS low-risk criteria . As NT-pAs regards the risk prediction scores for heart failure, SHFM and MAGGIC risk scores were calculated in the current study as previous reported , 16. As The primary endpoint of this study was all-cause mortality. Overall survival was measured from the date of RHC to the date of death from any cause. Follow-up was performed by telephone calls, outpatient visits or inpatient admissions every 6 months ± 2 weeks. In each follow-up, it was confirmed whether patients died or received transplantations and whether they had received any surgical or intervention treatments or had any instances of cardiac hospitalization. Patients were followed until death or until the end of the study (July 2017).Continuous variables are presented as the mean ± standard deviations, or median (interquartile range [IQR]). For normally distributed variables, the differences between groups were compared by the Student’s t test, while for non-normally distributed variables, the analyses were carried out by the Mann–Whitney test. Categorical variables are shown as frequencies and percentages, and chi-square tests were used to compare the differences between two subgroups. The performance of two established risk prediction strategies for PAH  and two risk scores for HF  were evaluated by Harrell’s C-index in the current cohort.To identify variables associated with mortality, L1-penalized regression model (LASSO) with tenfold cross-validation and the random forest approach were applied. Based on previous literature and clinical relevance, the following variables were assessed: demographics , clinical assessments , comorbidities , clinically assessed biomarkers , echocardiographic and hemodynamic parameters, as well as treatment strategies. As the variables selected by both methods were included either in the SHFM or in the MAGGIC risk scores, and also due to the reason that the sample size as well as the number of events of the study cohort were relatively small, the analyses regarding hemodynamics thereafter were based on the two HF risk scores.P value was < 0.05. All analyses were performed with R statistical package .Cox proportional hazards analyses were performed to compute hazard ratios (HRs) with 95% confidence intervals (CIs). The proportional hazards assumption was examined by inspection of Schoenfeld residuals. In bivariate Cox analyses, which included hemodynamic variables and SHFM or MAGGIC scores, multiple testing was adjusted by Bonferroni correction. Only hemodynamic variables, which were selected by both the LASSO and random forest approach, and remained consistently significant after adjusted by SHFM or MAGGIC scores in the bivariate Cox analyses, were considered to be included in the HF scores to evaluate their incremental prognostic value. Model performance was evaluated for discrimination and calibration. Discrimination power was assessed by Harrell’s C-index and compared by net reclassification improvement (NRI) and integrated discriminatory index (IDI), while likelihood ratio test and Akaike information criteria (AIC) were used to assess calibration properties. Internal validation was estimated with bootstrapping. Differences were considered statistically significant when the two-sided A total of 607 patients who underwent RHC were recruited in the registry. Of those, 276 post-capillary PH patients who met the inclusion and exclusion criteria were enrolled in the current study Fig. . The meaDuring a median follow-up time of 34.7 months (IQR 17.77 to 39.63), 53 patients died. The 3- year survival estimate of the study cohort was 79.3% (95% CI: 74.3–84.8%). In addition, 4 patients underwent pacemaker implantation, while no cardiac resynchronization therapy, implantable cardioverter defibrillator implantation, radiofrequency ablation, or any other interventions/operations were carried out.P = 0.001), had worse NYHA class (P = 0.004) and higher NT-proBNP , more frequently had CKD , with worse hemodynamics, as indicated by higher mPAP , DPG , RVSP , RVEDP  and lower SvO2 .As shown in Table The median of the SHFM score was 2 (range from 0 to 3), and the mean of the MAGGIC score was 18 ± 6 points. Both strategies showed significant prognostic value in the univariate Cox models, and could discriminate survivors from non-survivors, indicated by a C-index of 0.593 (95% CI: 0.519–0.667) and 0.62 (0.540–0.700), respectively , while the majority of the patients met two or one low risk criteria included in the French method, which accounted for 34.8% and 31.9% of the analyzed cohort, respectively. The two PH risk prediction strategies demonstrated C-statistic of 0.634 0.552–0.716) and 0.587 (0.505–0.669), respectively  and SvO2  remained to be significant predictors for all-cause mortality. When adjusted by MAGGIC score, dPAP , DPG , CI  and SvO2  were independent predictors for mortality. Thus, DPG and SvO2 were selected to be included in the SHFM or MAGGIC scores thereafter to identify their incremental prognostic value.As shown in Table 2 to the SHFM or the MAGGIC score respectively ; IDI: 0.092 (0.035–0.171); LR test: P < 0.001] or MAGGIC  scores.We established two multivariate Cox models by adding DPG and SvOely Fig. A, B. TabP < 0.001; for MAGGIC: NRI: 0.162 (0.016–0.510), IDI: 0.066 (0.028–0.155), LR test: P < 0.001] , which could somehow be explained by the reason that compared to the French method, the REVEAL score involved additional risk factors related to demographics and comorbid conditions [Neither the PH risk assessment strategies nor the HF risk scores demonstrated satisfactory performance for discriminating survivors from non-survivors in the current PH-LHD cohort. As regards the two modalities for PH, both methods ignore risk factors associated with HF nature to some extent, such as the medications for HF treatment, variables reflecting the function of left-sided heart, and even the etiologies of HF like ischemic heart disease. Notably, among the REVEAL score and the French method, the former tool showed a better discrimination power  with pure increasing pressure in post-capillary components, and combined post- and pre-capillary PH (Cpc-PH) with potential pulmonary vascular remodeling , 2. The sumption . A decrege in HF , 21. Furge in HF . Althougical use , 22.In addition to systolic or diastolic dysfunction of left ventricle, other types of left heart disease can also cause pulmonary hypertension with potential different characteristics and mechanism from heart failure. Unlike heart failure induced by coronary artery disease, cardiomyopathy or arterial hypertension, where the changes in pulmonary circulation are caused mainly by systolic or diastolic dysfunction of left ventricle, other types of left heart disease, such as valvular heart disease, often affect pulmonary hemodynamics by their inherent mechanical dysfunction. Thus, in those scenarios, though they can also cause heart failure and pulmonary hypertension, the changes in pulmonary hemodynamics can be attributed to two aspects: heart failure and mechanical changes. In the current study, as we tried to identify the characteristics of pulmonary hypertension induced by heart failure, we excluded those with comorbidities that could have potential effects on pulmonary hemodynamics due to other mechanical reasons in addition to systolic or diastolic dysfunction of left ventricle..The majority of patients enrolled in the current study have less advanced heart failure, indicated by relatively better NYHA FC, LVEF or mPAP. Actually, instead of patients with severe HF hospitalized in Cardiac Care Unit (CCU) or Heart Failure Care Unit (HFCU), patients enrolled in the current study admitted to hospital mainly due to requirements for standard follow-ups of heart failure, with/without decreased exercise capacity, or for further examinations of the underlying etiologies of heart failure, such as coronary artery disease. Usually, due to the invasive nature of RHC, patients with coronary heart disease, for whom the coronary angiography is required in their follow-ups, are more willing to receive RHC, while in other etiologies, a great percentage of patients are more likely to decline to receive this invasive examination despite the need for assessment of hemodynamics. It should be noted that patients with coronary heart disease in out cohort underwent RHC in combination with coronary angiography and left heart catheterization. Therefore, this could explain the high percentage of patients with coronary artery disease enrolled in the study. In addition, it should be noted that, in our country, most invasive examinations, such as coronary angiography, left and right heart catheterizations, are required to be conducted during hospitalization, though most patients are in a stable condition. Thus, the majority of patients underwent RHCs during their follow-up hospitalizations for chronic heart failureOur study has several limitations. First, there could be an inherent patient selection bias in our study due to the relatively small sample size. The limited sample size could be attributed to our inclusion criteria, as we only enrolled patients undergoing RHC, which was not common in clinical practice among patients with left heart disease. It should be noted that although we found incremental prognostic value of hemodynamic variables in risk prediction, it not necessarily requires all HF patients to receive RHC in daily practice. Instead, it implies that among patients who undergo RHC due to suspected PH or other indications, an incorporation of hemodynamics and traditional risk prediction strategies for HF could better help stratification. Inherent patient selection bias could also attribute to the less advanced HF patients enrolled in the study, as mentioned above. Another main limitation is the small number of events, which could affect the number of variables entering the Cox regression analyses. Accordingly, to avoid overfitting, we applied machine learning algorithms to select the risk factors most strongly associated with mortality, and on the other hand, the SHFM and MAGGIC scores, which integrated HF-related risk factors, were utilized as composite variables to enter Cox analyses. In addition, except the MAGGIC score, the other three risk prediction models explored in the current study all have some variables not available, which could potentially affect the model performance. Notably, the lack of data on diuretics dose is one of the potential limitations of the current study. The SHFM score included dose of diuretics as one of the prognostic variables; however, in a study reported by Bilchick et al., where diuretic use was also not available, the authors created a slightly revised version of the SHFM score with comparable statistical power . NeverthIn PH-LHD, pulmonary hemodynamics can provide incremental prognostic value for risk prediction.


Our study suggested that the ABI was higher in patients with LVH than in those without . The prevalence of LVH in patients with the lowest (0.9 < ABI≤1.03), second (1.04≤ABI≤1.11), the third (1.12≤ABI≤1.20), and the highest quartile (1.21≤ABI < 1.40) of ABI was 37.2%, 38.2%, 45.5%, 45.7%, respectively. Logistic regression analysis suggested that the highest and third quartile of ABI were significantly associated with increased LVH risk . The association of ABI at second quartile with LVH was nonsignificant. Similar results were observed in less than 60 years and without coronary heart disease or diabetes group. Our observations in Chinese patients with hypertension indicated high ABI may be an important risk factor for LVH in hypertension patients among Han Chinese, even in the normal range.Left ventricular hypertrophy (LVH) is the most common target organs damage in the hypertension patients. Abnormal low (≤0.9) or high (≥1.40) ankle brachial index (ABI) are associated with an increased risk of cardiovascular events. However, the relationships between a high ABI in the normal range (0.9–1.4) and LVH in Han Chinese hypertension are not entirely elucidated. This study included 3953 hypertension patients aged 40–75 years among Han Chinese. Hypertension was defined as systolic blood pressure≥140 mm Hg, diastolic blood pressure≥90 mm Hg, or history of antihypertensive drug use. Left ventricular mass (LVM) was measured by transthoracic echocardiography. LVH was diagnosed by using the criteria of LVM ≥49.2 g/m Ultimately, 3953 patients (1363 men and 2590 women) with integrated clinical and echocardiography data were remained in the present study.This was a community‐based cross‐sectional study, and participants were recruited from the Xinyang County, in the middle region in China from 2004 to 2005. We used a multistage cluster sample method to select a representative sample of rural community residents aged 40–75 years. A total of 13,444 patients (5270 men and 8174 women) incorporated into the survey, which were from 63 district of Xinyang's seven residential communities and yielding a response rate of 84.9%. Among them, 5421 hypertensive patients were identified and thoroughly examined. Hypertension was defined as diastolic blood pressure (DBP) of ≥90 mm Hg, SBP of ≥140 mm Hg, physician diagnosis or current medication for hypertension (as defined by WHO 1999). Of 5421 hypertensive patients, 4805 patients had measured LVM through echocardiography, and 4460 patients underwent optimal voluntarily ABI measurements. The patients with ABI ≤ 0.9  and standard 12‐cm cuff in each arm with the patients resting for at least 5 min. The Doppler Stethoscope was placed at the humeral artery fluctuation, quickly inflate the cuff to 20–30 mm Hg above the palpated SBP, and then deflated at the rate of 2–6 mm Hg/s. The first sound heard is the systolic pressure of the brachial artery. The cuff was then placed over the posterior tibial artery to measure ankle SBP of each leg.The ABI was defined as the ankle SBP/ brachial SBP ratio. In present study, the ABI of each leg was calculated as the SBP in the posterior tibial artery divided by the higher of the two arms SBPs. The reason for using higher arm SBP was the strong association between PAD and subclavian artery stenosis. Patients‐specific ABIs were defined as the higher of their two legs ABI because of the lower value of ABI may represent arterial stenosis. Patients were divided into four groups according to ABI quartile: quartile 1 (0.9 < ABI≤1.03), quartile 2 (1.04≤ABI≤1.11), quartile 3 (1.12≤ABI≤1.20), and quartile 4 (1.20≤ABI < 1.40).2.3Transthoracic echocardiography was performed according to standard protocols, under the supervision of two ultrasound physicians with at least 2 years of experience, and performed by two technicians trained in echocardiography at the Institute of Cardiology, Chinese Academy of Medical Sciences. HP 5500  or HDI 3000  was used to carry on M‐mode, two‐dimensional (2D) and color doppler records from the parasternal long axis and short axis windows, and 2D and color Doppler evaluations from the apical window to yield 2‐, 3‐, and 4 chamber images. The transducer frequency was 2.5–3.5 MHz. Patients who were unable to reach the local study center were screened using the Optigo echocardiographic recorders .As recommended by the American Society of Echocardiography, the echocardiographic measurements were made after the correct orientation of the two‐dimensional and Doppler imaging planes was confirmed using standard procedures, with the patients respiring quietly in the left decubitus position. The echocardiographic indicators were measured at the end of systolic and end diastolic periods of up to three cardiac cycles, including left atrium diameter, diastolic left ventricular inner diameter (LVIDD), diastolic left ventricular posterior wall thickness (PWTd), diastolic interventricular septal thickness (IVSd), E wave deceleration time, transmitted E wave velocity, and transmitted A wave velocity.2.43—LVIDD2.7 (LVMIh2.7). Relative wall thickness (RWT) was calculated using Devereux method, that is, 2×PWTd / LVIDD. LVH was diagnosed by using the criteria of LVMI more than 49.2 g/m2.7 for men and 46.7 g/m2.7 for women. Body surface area (BSA) was calculated by using the Stevenson formula: BSA (m2) = 0.0061 × height (cm) + 0.0128 × weight (kg) ‐ 0.1529. Body mass index (BMI) was calculated as the ratio of the weight in kg divided by the square of the height in m.LVM was calculated by using the equation: 0.8×1.04 ((IVSd + LVIDD + PWTd)2.5p value < .05.Data management and statistical analysis was performed using SPSS 22.0 for Windows . Data are reported as the mean ± standard deviation for continuous variables and as percentages for categorical variables. Continuous variable independent sample t‐test and classified variable chi‐square test were used for the differences between LVH group and non‐LVH group. All participants were stratified by quartiles of ABI, baseline differences in clinical variables and echocardiography data between groups using analysis of variance (ANOVA) for continuous variables, and chi‐squared test for categorical variables. The logistic regression analysis was used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). We used the binary logistic regression model, and multivariate analysis to evaluate the relationship between ABI categories and LVH. Sequential models were developed. Model 1 was adjusted for sex and age. Model 2 included all model 1 variables plus the BMI, SBP, DBP, serum glucose, triglyceride, cholesterol, high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), blood urea nitrogen (BUN), history of stroke, CAD, and diabetes mellitus (DM). The differences were considered significant if a 2‐tailed 33.1In the whole group of 3953 hypertension patients, there were 1646 patients with LVH. The prevalence of LVH was 41.64%. The clinical characteristics of the study population by LVH are described in Table 3.2Baseline characteristics of the patients according to the ABI categorical are presented in Table 3.3p value was 6093 (p>.05), suggesting that the relationship between ABI and LVH was linear  is a risk factor of LVH as a continuous variable by using Logistic regression model adjusted for age, sex, SBP, DBP, BMI, serum glucose, triglyceride, cholesterol, HDL‐C, LDL‐C, BUN, the history of stroke, CAD and DM, even though it is within the normal range. Then we divided patients into four groups according to ABI quartile: quartile 1 (0.90 < ABI≤1.03), quartile 2 (1.04≤ABI≤1.11), quartile 3 (1.12≤ABI≤1.20), and quartile 4 (1.21≤ABI < 1.40). Table p < .001) and in the model 1 after adjusted sex and age . The relationship remained significantly after further adjustment for SBP, DBP, BMI, height, weight, serum glucose, triglyceride, cholesterol, HDL‐C, LDL‐C, BUN, the history of stroke, CAD and DM in the model 2 . Similar results were observed in patients with third quartile of ABI, which had significantly increased LVH risk in unadjusted model , model 1 , and model 2  compared with those with the lowest quartile of ABI. However, their OR values were lower than patients with the highest quartile of ABI. The association of ABI at second quartile with LVH was nonsignificant, before or after adjustment for several covariates.We draw a restricted cubic spline (RCS) of ABI and LVH to clarify the linear relationship between them with R, the results showed that the non‐linear test result r Figure . Then weWe further conducted a stratification analysis of the correlation between LVH and ABI category, and the results are shown in Table Because ABI associated with arteriosclerotic disease, the relationships between ABI and LVH were examined separately (CAD group and non‐CAD group). For non‐CAD group, the association with LVH was significant in third and highest quartile of ABI groups, both in unadjusted model and multivariate‐adjusted model. However, in CAD group, OR for LVH was not significant for patients with a higher ABI in all models. We also performed a subgroup analysis for diabetes and the results were similar to those for CAD, that is, in the non‐diabetic group, the association between the third and highest of ABI and LVH was significant. However, in the diabetes group, there was no significant association between LVH and patients with higher ABI in all models.4In this study, we observed a strong cross‐sectional association of normal high ABI and increased LVH risk in Chinese hypertensive patients that have a high risk for developing cardiovascular diseases. We found a graded relationship between higher ABI in normal range and increased LVH morbidity which was determined by echocardiography, and this correlation was not affected when adjusted for sex, age, and traditional CVD risk factors. Our results indicated that the higher ABI within the normal range could not only be used as a predictor of asymptomatic organ damage caused by hypertension, but also provided better discrimination for patients with high risk who had traditional risk factors because it could further identify the patients at very high risk of LVH in hypertension groups.LVH is one of the most common hypertension‐mediated organ damages and is an independent predictor of cardiovascular morbidity and mortality.The ABI increases with arterial stiffness and age.In the stratified analysis, we found that the significant association between normal high ABI and LVH was observed in male, female, less than 60 years, non‐diabetic group and without CAD group, but this correlation was rendered no longer statistically significant in people with at least 60 years, diabetic group, and CAD group. Previous studies have considered that ABI is an important index to predict cardiovascular events such as acute myocardial infarction, heart failure with decreased ejection fraction, and total mortality.Our results show that in the group under 60 years old, there is a significant correlation between high ABI and LVH in the normal range, and the average age of different groups of ABI groups is increasing. However, in the group over 60 years old, there was no significant difference in the average age of ABI among different groups, and the association with LVH was not significant before and after adjustment for several covariates. Previous studies have shown that aging induces degradation and breakdown of elastic fibersThe incidence of cardiovascular events and mortality in patients with LVH are significantly higher than those in the normal population. Hypertension is the most common risk factor and complication of LVH. Currently, there are 245 million people with hypertension in China, so early identification of the high‐risk groups of LVH among hypertension patients and early intervention are of vital importance. Our study observed that a high ABI within the normal range can further identify the extremely high‐risk group of LVH in the hypertension group, providing a new critical point for the prediction of ABI in hypertension‐induced organ damage. In addition, our study examined a large population of patients with hypertension in the Chinses rural area, which minimizes selection bias. We estimated the LVM by echocardiographic, which is more sensitive and specific than ECG.There are still several limitations of the study should be considered. First, our study only included the hypertensive population of the Han nationality in rural China, which could not represent the urban population. Second, the proportion of men to women included in the study is uneven, with far fewer men than women, which may be due to a large number of male rural residents leaving home to work in cities. Third, this is a cross‐sectional study, so that we can only observe the correlation between ABI and LVH, but not know the causal relationship between the two. Prospective studies are needed to confirm our conclusions. Finally, we speculate that the correlation between normal high ABI and LVH is due to arterial stiffness or increased wave reflex caused by MAC, but we do not have lower limb X‐ray data and wave reflection index to confirm this conjecture. Therefore, the cut‐off points of ABI we used may only be used as reference index for MAC screening in patients with hypertension.In conclusions, this study shows that there is a significant association between normal higher ABI (1.12–1.39) and LVH in hypertensive people, but this result is more consistent in relatively young patients (≤60 years) and patients without CAD. There was no significant correlation between ABI and LVH in elderly patients with hypertension or hypertension complicated with CAD. Based on the above results, we believe that high ABI within the normal range may be a marker of arterial stiffness in hypertensive patients and is significantly associated with asymptomatic LVH. Therefore, the determination of ABI should be included in the routine examination of patients with hypertension, so as to help identify the very high‐risk population of LVH in patients with hypertension.All the authors declared that they have no conflict of interest.Jin Sun contributed to data interpretation, critical review of the manuscript, drafting the manuscript and revising the comment of reviewers. Shuxia Wang contributed significantly to data collection, the conception of the study and revising the comment of reviewers. Man Li and Yongkang Su contributed to manuscript preparation, analysis tools and assist with data analysis. Shouyuan Ma and Yan Zhang contributed to manuscript revisions. Anhang Zhang, Shuang Cai, Bokai Cheng and Qiligeer Bao helped with data analysis. Ping Zhu contributed to the conception of the study and helped perform the analysis with constructive discussions.Supporting InformationClick here for additional data file.


Carotid FTc can predict fluid responsiveness better than PPV during low VT ventilation. However, further studies using automated continuous monitoring system are needed before its clinical use.Predicting fluid responsiveness in patients under mechanical ventilation with low tidal volume (VT) is challenging. This study evaluated the ability of carotid corrected flow time (FTc) assessed by ultrasound for predicting the fluid responsiveness during low VT ventilation. Patients under postoperative mechanical ventilation and clinically diagnosed with hypovolemia were enrolled. Carotid FTc and pulse pressure variation (PPV) were measured at VT of 6 and 10 mL/kg predicted body weight (PBW). FTc was calculated using both Bazett’s (FTcB) and Wodey’s (FTcW) formulas. Fluid responsiveness was defined as a ≥15% increase in the stroke volume index assessed by FloTrac/Vigileo monitor after administration of 8 mL/kg of balanced crystalloid. Among 36 patients, 16 (44.4%) were fluid responders. The areas under the receiver operating characteristic curves (AUROCs) for the FTcB at VT of 6 and 10 mL/kg PBW were 0.897  and 0.895 (95% CI: 0.748–0.972), respectively. The AUROCs for the FTcW at VT of 6 and 10 mL/kg PBW were 0.875 (95% CI: 0.722–0.961) and 0.891 (95% CI: 0.744–0.970), respectively. However, PPV at VT of 6 mL/kg PBW  showed significantly lower accuracy than that of PPV at VT of 10 mL/kg PBW (AUROC: 0.867, 95% CI: 0.712–0.957;  The precise assessment of preload responsiveness to guide fluid administration is extremely important for improving the outcomes of critically ill patients. Insufficient intravascular volume can result in decreased cardiac output, leading to tissue hypoxia . On the Pulse pressure variation (PPV) is one of the more widely used predictors of fluid responsiveness in patients under positive pressure ventilation ,5. PPV iRecently, corrected flow time (FTc) measured in the carotid artery has been reported as a reliable predictor of fluid responsiveness during spontaneous breathing ,12. AddiThis study aimed to evaluate whether carotid FTc measured by Doppler ultrasound could be a reliable predictor of fluid responsiveness in mechanically ventilated patients with low VT in critical care settings. We also compared the predictability of carotid FTc and PPV measured during low VT ventilation with each of the parameters measured when increasing the VT to 10 mL/kg PBW.The study protocol was approved by the Institutional Review Board of the Yonsei University Health System, Seoul, South Korea  and registered in ClinicalTrials.gov . After receiving written informed consent, we enrolled 37 patients from October 2019 to September 2020.2; common carotid artery stenosis, of >50% which was previously diagnosed  or newly detected during the study period; cardiac rhythm other than sinus rhythm observed during the study period; moderate to severe valvular heart disease detected by preoperative echocardiography; left ventricular ejection fraction of <50%; right ventricular failure; moderate to severe chronic obstructive pulmonary disease; pulmonary mean arterial pressure of >25 mmHg; suspected or diagnosed increased intracranial pressure; pregnancy; patients who were unable to read the consent form ; and need for vasopressor infusion to maintain normal blood pressure before being transferred to the ICU. Furthermore, we excluded patients whom the ultrasound probe could not reach the carotid artery because of an overlapping position of the surgical wound and exam site.This prospective single-center study was performed in the surgical intensive care unit (ICU) of a university hospital. The inclusion criteria were as follows: patients aged >19 years who were planned to be transferred to the ICU for mechanical ventilation after surgery, clinically diagnosed with hypovolemia, and planned to be resuscitated with fluid administration by the attending physicians. Hypovolemic status was diagnosed based on at least one of the clinical signs presented in 2O; and respiratory rate, 15−18 times per minute. All patients were placed in the 30° semirecumbent position.After surgery, 0.05 mg/kg of midazolam and 0.6 mg/kg of rocuronium were administered to maintain the sedation status until transferred to the ICU. Upon arrival to the ICU, the IntelliVue MX700 monitor  was used to monitor the hemodynamic variables, including PPV, using the previously described algorithms . A radia6), PPV at a VT of 6 mL/kg PBW (PPV6), driving pressure (plateau pressure − PEEP) and compliance of the respiratory system were recorded. After recording this data set, the VT setting was increased from 6 to 10 mL/kg PBW. The same data set, including carotid FTc (FTc10) and PPV at a VT of 10 mL/kg PBW (PPV10), was measured five minutes after increasing the VT. Then, we reset the VT to 10 mL/kg PBW and administered 8 mL/kg ideal body weight of balanced crystalloid solution  over 10 min. Five minutes after the completion of fluid administration, the above-mentioned parameters were recorded again. No vasoactive medication was administered during the assessment period, and all measurements were obtained when the blood pressure and heart rate did not fluctuate. Fluid responsiveness was defined as a ≥15% increase in SVI after fluid administration.The study design is illustrated in The FTc was assessed using an ultrasound device  as previously described by Blehar and colleagues . A 6.0−1A previous study reported that the area under the receiver operating characteristic curve (AUROC) of FTc measured in the descending aorta to predict fluid responsiveness was 0.82 . We assup < 0.05.The continuous variables were analysed by using the independent t-test or Mann–Whitney U test, according to the results of the Shapiro-Wilk test for normality. The categorical variables were analysed by the chi-square test or Fisher’s exact test. The binary data are presented as numbers (%), while the continuous data are presented as the means and standard deviations if normally distributed, or as medians and interquartile ranges if otherwise. The AUROC was calculated to measure the ability of the indices to predict fluid responsiveness. A comparison of the AUROCs was performed using the non-parametric technique proposed by DeLong and colleagues . The optOf the 52 patients assessed for eligibility, 37 were enrolled. One patient was dropped out because of unreliable hemodynamic values owing to the malfunctioning of the arterial line monitoring during the study. Thus, 36 patients were included in the final analysis . No signp < 0.0001, rho = 0.656, 95% CI: 0.417–0.810; p < 0.0001, respectively) (Changes in hemodynamic and respiratory variables at each point of the study are shown in ctively) .6B and FTc10B were 0.897  and 0.895 , respectively  and 0.891 , respectively. The optimal cut-off values of the FTc6W and FTc10W were 325.8 ms and 335.8 ms, respectively. There were no significant differences in the AUROCs both between the FTc6B and FTc10B and between the FTc6W and FTc10W. The AUROCs for the PPV6 and PPV10 were 0.714  and 0.867 , respectively. However, the predictive accuracy for fluid responsiveness of PPV6 was significantly lower than that of PPV10 (p = 0.034).The AUROCs for the FTcectively . The optThe inter-observer reproducibility for estimating FTcB and FTcW was excellent with an ICC of 0.98 (95% CI: 0.96–0.98) and a CV of 1.2% and an ICC of 0.98 (95% CI: 0.97–0.99) and a CV of 1.1%, respectively. Using Bland-Altman analysis for testing inter-observer agreement in estimating FTcB and FTcW, the mean biases were −0.42 ms (with 95% limits of agreement [LOA] between −11.80 and 12.65 ms) and −0.44 ms (with 95% LOA between −10.11 and 10.99 ms), respectively .This study demonstrated that carotid FTc measured by Doppler ultrasound is a valid and reliable predictor for determining fluid responsiveness in patients receiving positive pressure mechanical ventilation in either a low VT or an increased VT setting. In contrast, PPV showed a limited accuracy in the presence of low VT than that of in the presence of increased VT.After reported by the ARDS network, a low VT ventilation strategy is known to be the basic principle to reduce ventilator-induced lung injury ,10. TherThe rationale of FTc is based on the usefulness of the Doppler waveform in the descending thoracic aorta about guiding fluid management ,26. FTc Our study estimated the predictability of fluid responsiveness by using the absolute value of FTc. However, there are some limitations of using the FTc value, as it can be affected not only by preload but also by cardiac contractility or afterload variability. We excluded patients who had a history of heart failure. Additionally, we excluded patients receiving vasopressor infusion, and the PEEP level was fixed during measurement. These conditions might minimise the effects other than preload to FTc; thus, FTc showed high predictability in our study. There are some reports on the predictability of changes in carotid FTc for fluid responsiveness ,27. Due 6 and FTc10. However, a recent study showed that the respiratory cycle could induce a variation in FTc [Our study has some limitations. First, we assumed that the variations in intrathoracic pressure during respiration did not significantly affect the carotid FTc. In addition, there were little differences between FTcn in FTc . This con in FTc . It is an in FTc . Howevern in FTc . Therefon in FTc ,32,33. Tn in FTc . A compun in FTc . We may In conclusion, the carotid artery FTc measured by Doppler ultrasound was found to be a useful predictor for evaluating fluid responsiveness in mechanically ventilated patients using low VT. Unlike PPV, which showed low predictability during low VT, carotid FTc showed high predictability during both low and high VT mechanical ventilation. The wide grey zone, which can limit the clinical use of FTc, should be overcome in larger clinical trials.


M age = 48.28; 76.7% women; 85.0% White) with MS were referred for neuropsychological assessment at a large, Midwestern academic medical center. Patients were placed into “credible” (n = 100) or “noncredible” (n = 33) groups based on a standalone PVT criterion. Classification statistics for four CVLT-II and BVMT-R PVTs of interest in isolation were poor (AUCs = 0.58–0.62). Several arithmetic and logistic regression-derived multivariate formulas were calculated, all of which similarly demonstrated poor discriminability (AUCs = 0.61–0.64). Although embedded PVTs may arguably maximize efficiency and minimize test burden in pwMS, common ones in the CVLT-II and BVMT-R may not be psychometrically appropriate, sufficiently sensitive, nor substitutable for standalone PVTs in this population. Clinical neuropsychologists who evaluate such patients are encouraged to include standalone PVTs in their assessment batteries to ensure that clinical care conclusions drawn from neuropsychological data are valid.Within the neuropsychological assessment, clinicians are responsible for ensuring the validity of obtained cognitive data. As such, increased attention is being paid to performance validity in patients with multiple sclerosis (pwMS). Experts have proposed batteries of neuropsychological tests for use in this population, though none contain recommendations for standalone performance validity tests (PVTs). The California Verbal Learning Test, Second Edition (CVLT-II) and Brief Visuospatial Memory Test, Revised (BVMT-R)—both of which are included in the aforementioned recommended neuropsychological batteries—include previously validated embedded PVTs , with no prior work exploring their utility in pwMS. The purpose of the present study was to determine the potential clinical utility of embedded PVTs to detect the signal of non-credibility as operationally defined by below criterion standalone PVT performance. One hundred thirty-three (133) patients ( Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating condition that can present with diverse patterns of physical, cognitive, and psychiatric symptoms ,2,3,4. IClinical neuropsychologists are tasked with identifying bona fide neuropsychological dysfunction while ensuring that extraneous factors –which may negatively influence results and clinical conclusions—are considered. Notably, noncredible presentations of cognitive impairment can seriously reduce overall neuropsychological performance above and beyond disease- or injury-related variables ,13. SeveImportantly, clinical neuropsychologists must determine the validity of cognitive data—typically via standalone and/or embedded performance validity tests (PVTs)—to ensure clinical decisions and aspects of continued medical care for pwMS are pursued ethically and responsibly ,25. As aIn contrast to standalone PVTs, which require their own administration time and materials and tend to have improved psychometric properties, embedded PVTs offer their own balance of benefits and detriments . On one Unfortunately, these embedded PVTs remain infrequently examined in the context of MS despite their potential for clinical value. To the authors’ knowledge, only Domen and colleagues  have expAs such, the present study examined the clinical utility of embedded PVT variables in CVLT-II and BVMT-R—recommended by many experts for routine use in pwMS—in identifying noncredible performance, operationally defined as below criterion performance on a well-validated, standalone, memory-based PVT, in a sample of pwMS. We evaluated select variables both in isolation and in combination  to determine their possible utility.Patients with MS (pwMS) were identified by retrospective analysis of an archival clinical dataset of individuals referred for clinical neuropsychological assessment within a large, Midwestern, academic medical center. All patients underwent neuropsychological assessment between 2017 and 2021. Inclusion criteria were: (1) complete data for all variables of interest; (2) estimated premorbid intellectual ability, as measured by a word reading test, ≥70; and (3) most recent or only neuropsychological evaluation.M age = 48.28, SD = 12.55; M Education = 13.96 years, SD = 2.49). Most patients were women (76.7%) and identified as White/Caucasian (85.0%). Most patients were diagnosed with a relapsing-remitting subtype (75.2%), with relatively fewer primary (15.0%) and secondary (9.8%) progressive subtypes. Patients (n = 118 with data for this variable) had an average disease duration (since reported symptom onset) of 13.34 years (SD = 10.53).The sample included 133 patients   was usedThe Victoria Symptom Validity Test (VSVT)  is a widForced Choice Recognition (C-FCR) and Recognition Hits (C-RH) from the CVLT-II  and RecoApproval from the first and third authors’ institution’s IRB was obtained prior to data analysis. All patients were referred for neuropsychological assessment as part of medical care and were evaluated by a board-certified clinical neuropsychologist or clinical psychologist trained under Houston Conference Guidelines. All measures were administered by either a board-certified or trained psychometrist, clinical psychology doctoral student, or postdoctoral neuropsychology fellow proficient in test administration and scoring. Patients with VSVT Total Accuracy scores ≥41 were categorized as “credible” and those with VSVT Total Accuracy scores ≤40 were categorized as “noncredible” [χ2 or Mann-Whitney U tests. Embedded PVTs in isolation and arithmetically and logistic regression-derived formulas were evaluated. Five arithmetic formulas were computed to determine if combining variables resulted in improved classification. These combinations of variables were:C-FCR + C-HR + B-HR + B-RD;C-FCR + B-RH;C-FCR + B-RD;C-RH + B-RH; andC-RH + B-RD.All analyses were conducted with SPSS 26.0. Demographic variables were compared between credible and noncredible groups using Five logistic regressions (LRs) were performed with the combinations of variables described in the formulas above entered as predictors as one set  with credible/noncredible group membership as the binary outcome variableχ2, Mann-Whitney U, and AUC analyses due to the abundance of repeated analyses to minimize the likelihood of Type 1 error. AUC values ≥0.70 suggest at least acceptable discriminability, and values below 0.70 indicate poor classification ability and are generally considered unacceptable [Mann-Whitney U tests, areas under the receiver operating characteristic curve (AUCs), sensitivity, and specificity were calculated for PVTs in isolation using credible vs. noncredible group membership as the criterion variable. AUCs were additionally computed for each arithmetically- and logistic regression-derived formula. A conservative adjusted criterion α of 0.013  was used for ceptable .M WRAT-4 Reading Standard Score = 96.79, SD = 10.79). Regarding the VSVT, 100 (75.2%) patients were classified as having “credible” neuropsychological test performance and 33 (24.8%) were classified as having “noncredible” neuropsychological test performance [On average, the premorbid intellectual ability was in the average range (formance .ps ≥ 0.08). The credible and noncredible groups differed in terms of gender and years of education (ps ≤ 0.01). However, the magnitude  of the gender difference was negligible-to-weak (Cramer’s V = 0.23) [Demographic characteristics for both groups are displayed in  = 0.23) , consist = 0.23) , and was = 0.23) ,47.ps > 0.017), with notably small effect sizes (ds ranged from 0.22–0.37). AUCs for each of the four embedded PVT variables ranged from 0.58 (C-FCR) to 0.62 (B-RD), all of which were not statistically significant (ps ranged from 0.034 to 0.195) and unacceptable . Sensitivities for these variables at previously validated cutoff scores ranged from 0.12 (B-RD ≤ 3) to 0.33 . Specificity values generally hovered around 0.90, with the exception of C-FCR ≤ 15, which yielded lower specificity of 0.80. Classification accuracy ranged from 0.68 (C-FCR ≤ 15) to 0.77 (C-RH ≤ 10 and B-RH ≤ 4). Various cutoff scores and their sensitivity, specificity, and total accuracy values are displayed in Mann-Whitney U tests revealed that each of the four embedded PVT variables  were not significantly different between groups  and unacceptable. Additionally, five logistic regressions (LRs) were performed with the combinations of variables described in the five formulas above entered as predictors as one set  with credible/noncredible group membership as the binary outcome variable. Exponentiated equations were derived from LR results, with similarly unacceptable AUC variables for each (0.61–0.64) such that were all nonsignificant compared to the conservative critical α (ps > 0.02). Due to these poor results and lack of potential clinical utility, cutoff scores and sensitivity/specificity values were not identified for these novel exponentiated equation variables as they appeared psychometrically inadequate.As stated above, five arithmetic formulas were computed to determine if combining embedded PVT variables resulted in improved classification. AUCs for these variables ranged from 0.61 to 0.63 and were all nonsignificant compared to the conservative critical α  variables in the CVLT-II and BVMT-R, commonly used in various clinical neuropsychological samples, in patients with MS. These variables were considered in isolation and in combination with both arithmetical and logistic regression-derived methods. Given the base rates of noncredible performance reported in patients with MS  and the First and foremost, current findings extended prior work and indicated that general discriminability for several embedded CVLT-II and BVMT-R PVTs were unacceptably low, with none of the AUC values exceeding 0.70  nsensitivities were notably lacking, such that they likely do not have sufficient ability to detect the “signal” of noncredible performance during the neuropsychological assessment of pwMS. The embedded PVTs herein appeared to fall short of the “Larrabee limit” [Relatedly, current findings, at least in part, further replicate recent work on embedded PVTs in MS. Domen and colleagues  reportede limit”   to use will be made on the basis of the best available evidence and clinical judgment according to each patient’s presenting problems and neuropsychologist’s expertise. As an aside, the authors believe that the VSVT may be appropriate given its routine use in previous MS literature ,21 and rThe present study is not without limitations. First, noncredible performance was defined by the below criterion scores on a single, standalone PVT. Although the PVT chosen is widely used clinically and is psychometrically robust at detecting the “signal” of non-credibility without being negatively affected by bona fide weaknesses in aspects of processing speed, working memory, and attention , this meIn all, the present paper is the first to explore the possible clinical utility of four embedded PVTs in the CVLT-II and BVMT-R specifically within a sample of pwMS. Current findings revealed fairly poor classification statistics for these variables and highlight the need for a psychometrically sound assessment of performance validity in this population. The authors encourage clinicians who work with pwMS in a neuropsychological context to not rely solely on the available embedded metrics explored herein, but rather to routinely utilize standalone PVT(s) to maximize the interpretive quality of their cognitive data. Furthermore, the authors recommend that researchers explore the utility of various types of PVTs in pwMS.


Patients with congestive heart failure (CHF) are vulnerable to contrast-induced kidney injury (CI-AKI), but few prediction models are currently available. Therefore, we aimed to establish a simple nomogram for CI-AKI risk assessment for patients with CHF undergoing coronary angiography.  A total of 1876 consecutive patients with CHF  were enrolled and randomly (2:1) assigned to a development cohort and a validation cohort. The endpoint was CI-AKI defined as serum creatinine elevation of ≥0.3 mg/dL or 50% from baseline within the first 48–72 hours following the procedure. Predictors for the simple nomogram were selected by multivariable logistic regression with a stepwise approach. The discriminative power was assessed using the area under the receiver operating characteristic (ROC) curve and was compared with the classic Mehran score in the validation cohort. Calibration was assessed using the Hosmer–Lemeshow test and 1000 bootstrap samples. n = 109) in the development cohort, and 9.92% (n = 61) in the validation cohort (P=0.367). The simple nomogram including four predictors  demonstrated a similar predictive power as the Mehran score , as well as a well-fitted calibration curve.  The incidence of CI-AKI was 9.06% (170) in the total sample, 8.64% ( The present simple nomogram including four predictors is a simple and reliable tool to identify CHF patients at risk of CI-AKI, whereas further external validations are needed. Contrast-induced kidney injury (CI-AKI) is a common complication following coronary angiography (CAG) or percutaneous coronary intervention (PCI), and the occurrence of CI-AKI has been demonstrated to be related to poor outcomes –3. PubliThe current study population was based on a prospective observation cohort  which enrolled consecutive patients undergoing CAG/PCI in Guangdong Provincial People's Hospital between January 2010 and October 2012. In this study, patients with CHF (defined as New York Heart Association (NYHA) functional class II-IV or Killip class II-IV) undergoing CAG/PCI were enrolled. [The procedures were conducted by interventional cardiologists following published guidelines, institutional policy, and clinical routine.  Patients2) = 186 ∗ (SCr ^  − 1.154) ∗ (Age ^  − 0.203) ∗ 0.742 . The unit of SCr in this formula is mg/dl. CKD was defined as eGFR <60 mL/min/1.73 m2. Patients were further divided into 5 CKD stages according to the guidelines . [The endpoint of this study was CI-AKI defined as a SCr elevation of ≥0.3 mg/dL or 50% from baseline within the first 48 to 72 hours following contrast exposure.  Baseline.73 m2).  And theyt-test and are expressed as the mean ± SD or were compared through the Wilcoxon rank-sum test and are expressed as the median ± interquartile. Categorical variables were compared using the χ2 test or Fisher's exact test and are expressed as percentages. Kaplan–Meier curve and multivariable Cox proportional hazard regression adjusted for known risk factors in the context of long-term prognosis were performed to explore the association between CI-AKI and long-term mortality. [All the patients involved were randomly assigned to a development cohort and a validation cohort in a 2:1 ratio. Continuous variables were compared with an unpaired, 2-tailed rtality. , 18.P < 0.1) covariates until all the remaining variables were statistically significant. Then, we manually investigated the contribution of the remaining variables to determine the final predictors. Collinearity between variables was also evaluated. A nomogram was then formulated based on the results and by using the rms package of R. To form the nomogram, each regression coefficient in the multivariate logistic regression was proportionally converted into a 0- to 100-point scale. The variable with the highest β coefficient  was assigned 100 points. The points are added across each variable to calculate the total points, which are finally converted to predicted probabilities. The performance of the nomogram was assessed using the area under the receiver operating characteristic (ROC) curve and concordance C-statistic for discriminative ability. For validation, a bootstrap method (1000 times) was performed in both the development and validation cohorts to evaluate the stability of the C-statistic. Calibration was assessed using the Hosmer–Lemeshow test and the 1000 bootstrap samples to decrease the overfit bias [P < 0.05 was considered statistically significant. All analyses were conducted with R software  and SPSS (version 26.0).To build the nomogram, candidate variables that were imbalanced between groups in the development cohort or that are clinically important, such as risk factors included in the traditional Mehran score, were included in the univariable logistic analysis. Variables with >15% missing values were not considered candidates, i.e., low-density lipoprotein-C and HbA1c. Significant variables from the univariable logistic analysis were then included in the multivariable logistic analysis. A backward stepwise approach was performed to screen the variables by successively removal of nonsignificant  during the procedure.The details and missing data of the included patients are listed in Supplementary n = 170) in the total sample, 8.64% (109 patients) in the development cohort, and 9.92% (61 patients) in the validation cohort (P=0.367). The distribution of the SCr value within the time frame (24–72 hours after the procedure) is shown in Supplementary The incidence of CI-AKI was 9.06% .The results of univariate logistic analysis are detailed in A simple nomogram based on the selected predictors was formed . The nomP=0.061, In the validation cohort, the simple nomogram demonstrated a C-statistic of 0.80 (95% CI 0.75–0.86), which was similar to that of the Mehran score  among patients with CHF P=0.061,  and a boThe discriminative ability and calibration were also tested among patients with different stages of CHF and stages of CKD, respectively. No significant difference in discriminative ability was identified, except for the comparison between “Heart function II” and “Heart function IV.” Hosmer–Lemeshow statistic suggested a good fit in all stages of CHF and stages of CKD , 50 ≤ scores < 100 (risk = 4.71%), 100 ≤ scores < 150 (risk = 13.90%), 150 ≤ scores < 200 (risk = 39.09%), and scores ≥ 200 (risk = 65.78%). The rates of CI-AKI in the validation cohort were close to those in the development cohort inside each of the 5 score categories (Supplementary P < 0.001) and the validation cohort .The optimal cut-off value of the total nomogram scores to identify patients at risk was determined to be 100. The sensitivity and specificity used to differentiate the presence from the absence of CI-AKI were 69.7% and 75.6% in the development cohort and 70.0% and 74.5% in the validation cohort, respectively. The total nomogram scores of 100 to identify patients at risk also demonstrated a good discriminative power in both the development cohort  was constructed. In particular, the simple nomogram demonstrated a similar discriminative power as the classic Mehran score in the validation cohort, as well as good stability and calibration.To define CHF patients in this study, two classification methods (NYHA and Killip) were used interchangeably. Previous studies had already taken this method to identify CHF patients , 22. In In this study of the CHF population, the overall incidence of CI-AKI was 9.06%. The previously reported incidence of CI-AKI has not been consistent among different studies. Among the patients with a low-risk of ordinary coronary artery disease, the CI-AKI incidence was as low as 2-3%, while in the high-risk population, the CI-AKI incidence could be as high as 19% or 50% , 24, theThe present simple nomogram was constructed based on age, AMI, IABP, and CKD, which are common risk factors associated with CI-AKI, as reported by numerous previous studies , 26, 27.The nomogram developed in this study is a simple but efficient prediction model that includes only four predictors. We noticed that some important risk factors reported by previous results were not included in the current simple nomogram, such as contrast volume and diabetes . The nonThe Mehran score is one of the most classic CI-AKI risk estimating system, which was developed based on 8,357 patients undergoing PCI . CompariWe also noticed that several researches have provided nomograms to predict acute kidney injury (AKI) lately. However, these nomograms were developed for different patients specifically –39. By aOverall, in this study, we established a novel CI-AKI risk prediction nomogram specified for the CHF population. In this simple nomogram, patients with more than 100 total points are identified as at-risk patients, accounting for nearly 30% of the entire CHF cohort. The threshold of 100 points (approximately 10% risk) was also similar to the risk threshold of previous models , 29.Our study had some limitations. First, this study was an analysis of single-centre data and the nomogram we established is not a general one for CI-AKI risk evaluation in any radiological study, but specifically for coronary study/intervention. However, no relevant study had so far elucidated the specified risk factors of CI-AKI in CHF patients. Our study provided a new tool for CI-AKI risk assessment among CHF patients, prompting more attention and further studies on risk assessment of patients with comorbidities undergoing coronary catheterization. Second, the present nomogram was not externally validated, although there was a calibration with 1000 bootstrap samples to decrease the overfit bias. Third, our nomogram did not demonstrate better discriminative power than the Mehran score. However, our model has less variables, which makes it easier for clinical implement. Fourth, some other potential risk factors, especially procedural context , were not included due to the insufficient data. Finally, some patients were discharged within 72 hours after the CAG/PCI, so creatinine levels were not measured on day 3 in these patients, which might lead to the underestimation of the incidence of CI-AKI.The presented nomogram with four predictors  is a simple and reliable tool for CI-AKI risk stratification among CHF patients, which enables physicians to identify patients at risk and implement precise prevention strategies in time. However, further external validations are needed before clinical generalization.


An increase in the red blood cells transfused per hour after surgery increased the risk of developing pulmonary edema. This increase can be considered as a risk factor for pulmonary edema.In patients with intraoperative massive bleeding, the effects of fluid and blood volume on postoperative pulmonary edema are uncertain. Patients with intraoperative massive bleeding who had undergone a non-cardiac surgery in five hospitals were enrolled in this study. We evaluated the association of postoperative pulmonary edema risk and intra- and post-operatively administered fluid and blood volumes in patients with intraoperative massive bleeding. In total, 2090 patients were included in the postoperative pulmonary edema analysis, and 300 patients developed pulmonary edema within 72 h of the surgery. The postoperative pulmonary edema with hypoxemia analysis included 1660 patients, and the condition occurred in 161 patients. An increase in the amount of red blood cells transfused per hour after surgery increased the risk of pulmonary edema (hazard ratio: 1.03; 95% confidence interval: 1.01–1.05;  Massive bleeding during surgery can be fatal in the operating room and increases postoperative mortality . Large vIntraoperative fluid therapy is complex and generally aims to meet maintenance requirements and to address existing fluid deficits and blood loss due to surgical wounds. Accurate evaluation of intraoperative blood loss volume  and safeIn this study, we aimed to accurately determine the intra- and post-operative fluid and transfusion volumes. We also investigated the effects of intra- and post-operative transfusion volumes on the development of postoperative pulmonary edema in patients with massive intraoperative bleeding using a time-varying hazards analysis.This retrospective cohort study was approved by the Clinical Research Ethics Committee of Chuncheon Sacred Heart Hospital, Hallym University. The study was conducted in accordance with the relevant guidelines and regulations of the committee. We enrolled at-risk individuals, such as brain trauma patients. The need for informed consent was waived because of the retrospective study design. The data were obtained from the clinical data warehouses of five hospitals at Hallym University Medical Center between 1 January 2010 and 31 December 2019. A clinical data warehouse is a database of medical records, prescriptions, and test results, which can be used to identify patients based on prescriptions, examinations, and diagnostic data. The timing and results of investigations, drugs administered, transfusion status, and other information can be extracted in an unstructured text format. The requested data are provided in a de-identified form, but the data for a specific person can be extracted using a key.Age < 18 years;Patients undergoing cardiac surgery;Patients who underwent a previous surgery within 7 days of the current surgery; 2/FiO2 ≤ 300).Patients with preoperative pulmonary edema or hypoxemia  data could not be obtained, patients who did not receive oxygen therapy postoperatively due to an absence of respiratory symptoms and those who did not have evidence of pulmonary edema on a chest X-ray were considered non-hypoxemic.2/FiO2 ≤ 300. The results with the shortest interval between the chest X-ray and ABG analysis were used. Patients who had no pulmonary edema on the chest X-ray and who did not receive oxygen postoperatively were considered to be free of pulmonary edema. As pulmonary edema can occur up to 3 days postoperatively, it was evaluated until 72 h after surgery.The primary outcome was the presence of pulmonary edema on a postoperative chest X-ray. Chest X-rays, evaluated by a radiologist, were used for consistency. The secondary outcome was postoperative pulmonary edema with hypoxemia. Hypoxemia was defined as PaOThe major variables evaluated in this study were divided into intra- and post-operative variables. Intraoperative variables included the total and hourly amounts of fluid, red blood cells (RBCs), and fresh frozen plasma (FFP) administered during surgery.Postoperative variables included the total and hourly amounts of fluid, RBCs, and FFP administered after surgery. All of the major postoperative variables were time-varying variables. The amounts of fluid and blood administered after surgery were measured based on the ABG analysis or chest X-ray times. For the analysis of pulmonary edema with hypoxemia, in which both an ABG and chest X-ray were performed, the ABG analysis time was used for the analysis, unless there were no respiratory symptoms and only the chest X-ray test was performed, in which case the chest X-ray time was used. The administered fluid and blood volumes are expressed as percentages of the patient’s average blood volume. Each patient had 1–3 time-varying variables and observation periods, depending upon the number of measurements (which varied according to the test frequency). The first observation period was between the end of anesthesia and the first test; the second was between the first and second tests; and the third was between the second and third tests.Other covariates were adjusted to prevent residual confounding and biases. Demographic variables included old age (≥70 years), male sex, and obesity (body mass index ≥ 30). Preoperative variables included emergency, an American Society of Anesthesiologists physical status >2, smoking, brain trauma, multiple fractures, hyponatremia (<135 mmol/L), hypoalbuminemia (<3.5 g/dL), and glomerular filtration rate (GFR). Intraoperative variables included general anesthesia, anesthesia time, type of surgery , massive transfusion (packed RBCs ˃ 4 pints/h) , urine op-values were two-sided, and a p-value < 0.05 was considered to indicate statistical significance. SPSS software  was used for all statistical analyses except for time-varying Cox regression analysis, which was performed using Anaconda  and Lifelines package .Continuous variables are expressed as medians and interquartile ranges due to skewness. Categorical variables are expressed as frequencies and percentages. Continuous data were analyzed using the Mann–Whitney test to compare patients with and without postoperative pulmonary edema. Categorical data were analyzed using the chi-square test. Cox’s time-varying hazards model was used to obtain the hazard ratios of the major variables with respect to the occurrence of postoperative pulmonary edema within 72 h after surgery. Time-varying covariance occurs when a covariate changes over time during the period in which it is tracked. These variables can be analyzed with a time-varying Cox regression model to estimate their effect on event occurrence time . A subgr2 or FiO2 data, and the remaining 1630 patients were included. There were 161 patients with postoperative pulmonary edema with hypoxemia  and the postoperative RBCs per hour  showed significant associations with postoperative pulmonary edema. The postoperatively administered total fluid  and the postoperative RBCs per hour  also showed significant associations with postoperative pulmonary edema with hypoxemia. The intraoperative FFP per hour was significantly associated with postoperative pulmonary edema , but the other major variables were not (The unadjusted and adjusted hazard ratios (aHRs) of major and kidney-related variables  for 72-h postoperative pulmonary edema both with and without hypoxemia are shown in were not .The cut-off values of blood and fluid for the development of pulmonary edema with and without hypoxemia are summarized in The aHRs of major and kidney-related variables for 72-h postoperative pulmonary edema with and without hypoxemia are shown in Through time-varying Cox regression, it was shown that the total amount of fluid administered after surgery and the amount of RBCs administered per hour were associated with an increased postoperative risk for pulmonary edema, both with and without hypoxemia. However, the association with the amount of RBCs had low statistical significance for emergency surgeries. The hazard ratio of the total amount of fluid administered postoperatively for pulmonary edema was too small to be clinically significant.Our findings showed that in patients with massive intraoperative bleeding, the amount of RBCs administered per hour postoperatively was significantly associated with the risk of postoperative pulmonary edema. Exacerbations of pre-existing anemia, intraoperative bleeding, and repeated laboratory blood tests were common causes of postoperative anemia ,18,19. MThe principle of fluid balance is that the amount of fluid administered should be equal to the amount of fluid lost . HoweverIn this study, intraoperatively administered fluids and blood were not related to the risk of postoperative pulmonary edema with or without hypoxemia. Perioperative fluid and blood transfusions can cause hypothermia ,36,37, wIn this study, increased hourly FFP administration during surgery increased the risk of postoperative pulmonary edema. While FFP is used in cases of clotting factor deficiencies to prevent hemorrhage, it puts patients at risk for transfusion-related acute lung injury  and can Kidney function is also closely related to the development of pulmonary edema ,61,62. WIn this study, it was observed that postoperative pulmonary edema may occur in a significant proportion of patients with massive intraoperative bleeding. This may occur in patients with or without serious cardiovascular disease, in which fluid overload in the postoperative period may be a significant factor. Alternatively, negative pressure pulmonary edema may develop, which may be a different and important clinical entity in the period immediately after extubation and may progress rapidly. Negative pressure pulmonary edema may result from acute upper airway obstruction following the creation of acute negative intrathoracic pressure. Although negative pressure pulmonary edema can be a life-threatening complication during surgery without timely diagnosis and treatment, it is recognized as having a good prognosis if recognized immediately and if treated appropriately . In furtIn this study, time-varying Cox regression was used to obtain hazard ratios. Time-varying covariance is commonly seen in clinical studies when a given covariate changes over time during the follow-up period ,71. In cAlthough this study included a large number of patients with massive intraoperative bleeding, it is difficult to perform a randomized controlled trial of massive bleeding patients. This study used a retrospective design, which is subject to bias. Pulmonary edema is either cardiogenic or non-cardiogenic, but we could not stratify the patients based on the type of pulmonary edema. Although the different types of pulmonary edema have different causes, it is difficult to distinguish them because of their similar clinical features. In addition, the causes can be complex in critically ill patients , and botThis study demonstrated that the incidence of postoperative pulmonary edema is higher in patients with massive intraoperative bleeding and in those receiving large RBC transfusions postoperatively. These findings are in agreement with previous studies. In patients with massive intraoperative bleeding, close monitoring and rapid correction of the causes of postoperative anemia and bleeding may be more important. Further prospective population-based studies are needed to explain the mechanisms underlying the association between postoperative RBC transfusion and the risk of developing postoperative pulmonary edema in patients with massive intraoperative bleeding.