To investigate the optimal blood pressure (BP) levels and relative importance of BP and BP variability in the early phase of acute ischemic stroke (AIS) for hypertensive patients with carotid artery stenosis (CAS). A single‐center cohort study included 750 AIS patients with hypertension and tests were performed for CAS. Participants were categorized to Group 1 (SBP < 140 mm Hg and DBP < 90 mm Hg), Group 2: (SBP: 140–159 mm Hg and or DBP: 90–99 mm Hg), and Group 3: (SBP ≥160 mm Hg and/or DBP ≥100 mm Hg) according to the guidelines. The associations of mean BP levels and variability with outcomes  at 6 months were analyzed by Cox proportional hazard models. The associations of BP variability with BP levels and cerebral blood flow (CBF) were analyzed by linear regression and generalized additive models. Both for primary and secondary outcome, more events occurred in Group 1 compared with Group 2, while no significant difference was found in Group 3 with higher BP levels. Lower systolic BP variability showed better prognosis and higher CBF. The associations were more significant in patients with CAS ≥50%. BP variability exhibited a linear negative relationship with BP levels. In the early phase of AIS with hypertension and CAS, maintaining low blood pressure variability may be important to improve outcomes while low BP levels (SBP/DBP < 140/90 mm Hg) were harmful, especially in those patients with CAS ≥ 50%. Ischemic stroke (IS) accounts for about 80% of all strokes.Recent studies have shown that for stroke patients, especially those with stroke and hypertension, BP variability is another important risk for recurrent stroke, cardiovascular disease, renal failure, and mortality.Although there are many studies have suggested reasonable BP level and low BP variability were associated with good outcome, these studies did not focus on AIS patients with hypertension and CAS. It is an interesting question how to weigh BP level and BP variability in AIS patients with hypertension and CAS in the early stage. Unfortunately, no relevant study has been reported. Therefore, this study was aimed to investigate BP variability and proper BP level in early phase of acute ischemic stroke with hypertension and CAS.22.1We carried out a single‐center, prospective cohort study. A total of 968 IS patients with hypertension were registered in the Stroke Registry Database from January 2016 to December 2016. Of cases, 107 cases of carotid stenting and 15 of carotid endarterectomy were excluded. Patient were excluded with any one of the following reasons: severe disturbance of consciousness identified by the level of consciousness on National Institutes of Health Stroke Scale (NIHSS) score > 1; the mRS score 0 before stroke onset (20 patients); severe mental disorders or dementia; serious systemic diseases and life expected < 6 months; previous surgical carotid revascularization; cardiogenic and cryptogenic stroke; severe cerebral infarction . Finally, 750 IS patients with hypertension and CAS were eligible for this study. In addition, in the 750 IS patients with hypertension and CAS, 404 patients with CAS < 50% did not need to undergo carotid revascularization, 283 patients with CAS > 50% but < 70% not undergo carotid revascularization due to the lack of surgical indications, and 63 patients with CAS ≥ 70% refused to undergo carotid revascularization since they were unable to pay for medical expenditure of revascularization surgery or fear of surgery even with severe stenosis. Study flow diagram of patients’ enrollment was shown in Figure 2.22.2.1CTA and ultrasonography were performed on the third day of admission. All CTA and ultrasound examinations were performed by trained cerebrovascular imaging examiners. The CTA scans used the Somatom Definition Flash CT system . Contrast agent tracking was used in selected regions of interest at the aortic arch or carotid arteries to monitor the CT numbers. When the CT number exceeded 100 Hounsfield Units, the scan was automatically triggered with a delay of 4 s. We focused especially upon CAS based on the following causes: (1) extracranial CAS is the most important cause of large‐vessel stroke and is associated with 11.5% of all IS2 × π). The anterior circulation cerebral blood flow (CBF) volume was the sum of flow volumes of ICA both sides.A color Doppler ultrasonography (CDUS) system, vivid E7 , was used for blood flow data acquisition of CBF. The hemodynamic parameters of the bilateral common carotid arteries, extracranial segment of the ICA and V1‐V3 segments of the VA were recorded, including peak systolic flow velocity (PSV), end‐diastolic flow velocity (EDV), and time‐averaged flow velocity (TAV). The intravascular flow volume (ml/min) was calculated by multiplying TAV with the cross‐sectional area (A) of the circular vessel according to the formula: flow volume = TAV × A = TAV × ([d/2]2.2.2The treatments complied with 2013 American Heart Association/American Stroke Association (AHA/ASA) guidelines for the early management of patients with acute IS.2.2.3Blood pressure variability can be defined as the variation in blood pressure during a period of time (standard deviation [SD] or coefficient of variation).2.3Hypertension was defined as a conventional BP of at least 140 mm Hg systolic or 90 mm Hg diastolic, or the use of antihypertensive drugs.All the patients had been taking antihypertensive agent and controlled well before admission. They continued taking drugs as normal after admission to control hypertension. Based on the average BP levels in the 3 days after stroke onset, participants were categorized as controlled BP group (Group 1: SBP < 140 mm Hg and DBP < 90 mm Hg), mild hypertension group (Group 2: SBP :140–159 mm Hg and or DBP: 90–99 mm Hg), and moderate to severe hypertension group (Group 3: SBP ≥160 mm Hg and/or DBP ≥100 mm Hg) according to the Guidelines for Hypertension.2.4All participants were followed up in 6 months by trained neurologists. Primary outcome was recurrent stroke  at 6 months.2.5t test or one‐way ANOVA. Categorical variables were expressed as frequency (percentage) and were compared using χ2 test. Pearson correlation was performed for the association between BP levels and BP variability. To explore nonlinear relations between BP variability and global CBF, generalized additive models (GAMs) were constructed by using R statistical software (version 4.0.2). Kaplan‐Meier (KM) curves were plotted to illustrate event outcomes among groups, and the statistical significance was determined by the log‐rank test. Associations between parameters  and primary and secondary outcomes were analyzed using Cox proportional hazard analysis. Univariate logistic regression was carried out for each risk factor provided on baseline characteristics, p values were more than 0.05 except for SBP and CV of SBP. Multivariable model induced traditional cardiovascular risk factors: age, male, body mass index, smoking, alcohol, diabetes mellitus, coronary artery disease, congestive heart failure, chronic kidney disease, NIHSS according to the relevant literatures,p < 0.05 was considered statistically significant.All statistical analysis was performed with SPSS.V24.0 software packages. Continuous variables were presented as mean (SD) and were compared using the Student 2.6The study was approved by the ethic committee of Lianyungang Hospital. Written informed consent was obtained from each patient or his/her proxy.33.1Of the 750 patients with first‐ever IS and CAS, 404 (53.9%) had mild stenosis, 131 (17.5%) had moderate stenosis, 111 (14.8%) had severe stenosis and 104 (13.9%) had complete occlusion, respectively. Baseline characteristics of 750 patients based on groups of BP levels in the early phase were shown in Table 3.2p < 0.01), all‐cause death and the composite cardiovascular events  at 6 months. However, there were no significant association with patients in higher BP levels group (SBP/DBP ≥160/100 mm Hg) and incidence of primary outcome (p = 0.501) or secondary outcome (p = 0.715). Similar associations were found both in group with CAS < 50% and in group with CAS ≥50%. KM curves .Univariate Cox regression analysis for primary and secondary outcomes are shown in Table 3.3BP variability was also an important risk factor for prognosis. Next, we analyzed the relationship between BP variability and prognosis. Cox regression showed no significant difference between DBP variability and prognosis Table . Figure 3.4p < 0.001). In ischemic stroke patients with CAS ≥50%, a negative linear correlation was observed between SBP variability and CBF compared with ischemic stroke patients with CAS < 50%. The relation between BP variability and global CBF was also shown graphically as GAM plots in Figure p < 0.001).CBF is necessary for conservation of brain function, and hypoperfusion might cause brain infarction, which in turn leads to a poor prognosis. Furthermore, we determined the association of BP variation with CBF. Pearson correlation analysis and curve fitting showed an overall negative correlation between SBP variability and global CBF (3.5p < 0.001)  and DBP (p = 0.021)  led to a poor prognosis, while higher BP levels (> 160/100 mm Hg) did not show better prognosis, and BP levels was negatively correlated with BP variability. On the other hand, low BP variability in the early phase (within 3 days after onset) was associated with adequate cerebral perfusion and then reduced risks of primary and secondary outcomes at 6 months, particularly in those patients with CAS ≥50%. So, maintaining low blood pressure variability may be important to improve outcomes while low BP levels (SBP/DBP < 140/90 mm Hg) were harmful, especially in those patients with CAS ≥ 50%.Hypertension in the acute phase is associated with a poor prognosis but lowering blood pressure might also be harmful. The Scandinavian Candesartan Acute Stroke Trial (SCAST) indicated that blood pressure lowering treatment in acute stroke was associated with an increased risk of stroke progression and poor functional outcomeFurthermore, in the present study, low BP variability in the early phase, measured by CV, was significantly associated with good prognosis. The trend was more obvious in these patients with CAS ≥50%. Our findings are consistent with some previous studies. Bum Joon Kim and coworkers demonstrated that increased BP variability was strongly correlated with the risk of recurrent stroke in patients with hypertension and a history of previous stroke or TIA.Inadequate cerebral perfusion and impaired cerebral autoregulation in the early phase of stoke increased cardiovascular complications, and secondary brain injury. These conditions in turn might cause poor outcome after acute IS. We found lower BP variability was correlated with higher global CBF, and the higher global CBF were more beneficial to prognosis in our study. Patients with lower CV of BP maintained a relatively high global CBF, which was in turn advantageous for prognosis.The relationship between BP variability and prognosis was more significant in patients with CAS ≥50%, while no statistically significant differences in patients with CAS < 50%. In normal condition, cerebral autoregulation maintains blood flow to the brain and regulates cerebral perfusion pressure changes over a wide range. BP level and BP variability are major factors affecting cerebral perfusion. In the IS population with hypertension and mild CAS or none, the collateral circulation would compensate for the influence of blood pressure fluctuations on brain to prevent cerebral hypoperfusion. The circle of Willis is considered to be the primary collateral flow route which can supplement the affected brain tissue area with blood.Therefore, for IS patients with hypertension and CAS ≥50% in the early phase of stroke, a lower blood pressure variability and higher BP levels can compensate for inadequate collateral circulation by maintaining a relatively high cerebral blood flow. The relatively stable and high cerebral perfusion reduces stroke recurrence and improves the prognosis of stroke. Low BP variability and maintaining reasonable BP levels (SBP 140–160 and DBP 90–100 mm Hg) were more beneficial in the present study.This study has limitations. First, we did not include flow volumes of vertebral arteries and only calculated stenosis of carotid arteries, the advantage bias might exist. Second, the sample size of this study was relatively small; however, it was a real clinical practice, in which strict inclusion criteria were used, data were reasonably analyzed, and conclusions was carefully scrutinized.As a result, our study might deliver useful recommendation for BP management in the early phase of IS patients in this group of patients with CAS.5In our study, more events were found in group with the lower BP (SBP < 140 mm Hg and DBP < 90 mm Hg), while there was no obvious association between the highest BP group (SBP ≥160 and/or DBP ≥100 mm Hg) and poor prognosis. Owing to the small number of patients with severe hypertension (SBP≥180 mm Hg and/or DBP ≥110 mm Hg) in our study, this result regarding to extremely high blood pressure levels might not be generalized. It could be concluded that maintaining low BP variability and reasonable BP levels (SBP140 ∼160 and DBP 90 ∼ 100 mm Hg) were important to reduce the risk of recurrent stroke, all‐cause death and the composite cardiovascular events in the early phase of IS with hypertension and CAS.None.Mingli He and Yibo Wang conceived and designed the research, Taotao Wu, Mingyu Wang, Ru Yang, Bo Zhang, Bingchao Xu, Xiaobing He, Guanghui Zhang, Xiaoqin Niu, Zaipo Li, Bei Wang and Bei Xu acquired the data, Bing Cui, Jin'e Wang, Xiao Xiao analyzed and interpreted the data, Bing Cui, Jin'e Wang, Xiao Xiao and Taotao Wu performed statistical analysis, Mingli He and Yibo Wang handled funding and supervision, Bing Cui and Jin'e Wang drafted the manuscript, Rutai Hui made critical revision of the manuscript for important intellectual content.Supporting informationClick here for additional data file.


The traditional causes of Chronic Kidney Damage (CKD) are Diabetes and Hypertension. However, recent studies reported the possible relations between metal exposure and CKD. This study aims to explore the status of metals in CKD patients compared to their healthy counterparts at Narayanganj, Bangladesh, through a cross-sectional study. In this study, 50 volunteers were involved; 30 CKD patients and 20 healthy controls. Five metals were measured from serum [Copper (Cu) and Zinc (Zn)] and urine  using Atomic Absorption Spectrometry. Compared to the controls the CKD patients exhibited significantly higher levels of Pb, Cd and Cr levels in their urine samples. This signifies a potential association between heavy metal exposure and CKD. The serum levels of Cu were much higher than expected for CKD patients than controls, and the Zn values were in accordance with established literature. However, the level of Zn in blood was significantly lower in the CKD group compared to the control. This data suggests that the Cu imbalance in the serum of the CKD subjects might have been related to a myriad of reasons, the most plausible of which being exposed to large concentrations of the nephrotoxic metals such as Pb, Cd and Cr in this study. Our study has shed a much needed light on the correlation between CKD and exposure to heavy metals and imbalance of essential metals in blood serum, in a rural locality of Bangladesh. CKD; Copper; Zinc; Urine; Cadmium; Chromium; Lead. Alterations in Zinc and Copper metabolism have been frequently observed in patients with chronic kidney disease (CKD) and those with diabetes. These elements have essential roles in the biological systems, as components of proteins, enzymes, and antioxidants. Anorexia, low taste sensibility, hypogeusia glucose intolerance, healing difficulties, and anemia are conventional features of both CKD and diabetes associated with copper and zinc abnormalities. Scarce information exists on the effects of the association between CKD and diabetes in the metabolism of Zn and Cu .−1 and 260–302 μg g−1 respectively, in TSP. For DAP it was 21.43–371.4 μg g−1 for Pb and 1210–1390 μg g−1 for Cr. For MoP the content was 148.6–188.6 μg g−1 for Pb and 296–310 μg g−1 for Cr. For all the cases maximum allowable limit was 100 μg g−1 for Pb, 500 μg g−1 for Cr, and 10 μg g−1 for Cadmium (Cd)  . Anotherium (Cd) .Farmers, in general, belong to the low-income groups and are not well aware of their health risks from heavy metals or concerns for heavy metal or pesticide accumulation in the soil. Their chief objective is to maximize crop yield and, consequently, make a profit . A WorldHeavy metals hamper homeostatic metabolic processes by binding to proteins or cation or sulfate/bicarbonate transporters or replacing metals in enzymes or by inducing reactive oxygen species (ROS). Moreover, it is to be noted that these heavy metals are ultimately transported to the kidney for excretion. It happens so that the heavy metals concentrations in the blood are not altered as significantly as in urine. Hence for the study of chronic renal failure due to low-level environmental exposure of heavy metals, it might be a matter of interest to study heavy metals  concentrations in the urine of CKD patients, and also by studying the levels of essential metals  in the blood serum to get an intriguingclue about the kidney functions. Therefore, this research aimed to investigate the concentrations of Cd, Pb, Cr in urine and Cu and Zn in the blood serum samples of CKD affected people as well as healthy people. Besides, to examine the possible association between environmental heavy metal exposures and CKD for the first time in Bangladesh.22.1A Cross-sectional study on a rural area, namely Sonargaon, Narayanganj, Dhaka, was performed because this area is abundant with industrial and agricultural activities, and geographical means of heavy metal contamination. Narayanganj is flanked by the rivers Shitalaksya and the Buriganga . Rivers The sampling population selected were adults who were full-time or part-time involved in agricultural activities. A voter list of the 47 villages of Sonargaon was collected, and certain people were requested to appear at the Research sites as volunteers for this study. The selected people were invited to the research center and briefed about the cause of the invitation and were assigned IDs. Researchers along with physicians filled up datasheets, which recorded the healthy and CKD, affected people of the selected area age, profession, habits, occupation, education, monthly income, food habits, etc. The healthy and CKD affected people of the selected area were told to come early in the morning on a different day when their blood and urine were collected. The biological samples (Blood and Urine) of 50 representative people from 16 of the 47 villages were collected in metal-free containers. The controls and CKD affected people of the selected area have been divided into two groups, namely 'exposed' and 'controls'. Structural or functional abnormalities of the kidneys for more than three months as manifested by kidney damage, with or without decreased GFR. In this study, the patients of CKD were confirmed by examining parameters like eGFR, serum creatinine, and ACR over 3 months. Only the confirmed cases of CKD, who did not have High Blood Pressure or Diabetes but had abnormal levels of eGFR and ACR were considered for our study. The controls are the people who have not been diagnosed with CKD see .Figure 1This study was approved by the ethics committee of the collaborating hospital and the Institutional Review Board (IRB), Atomic Energy Centre, Bangladesh Atomic Energy Commission, Dhaka, and written informed consent was obtained from all of the volunteers, including patients and healthy controls.2.21 was used for the preparation of all solutions. Nitric acid (HNO3)  was obtained from Sigma Aldrich . Single element standard reference metal solution of Pb, Cd, Cr, Cu, Zn  from Agilent Technologies  was procured. Quality control standard was prepared from multielement standard solution .In our study, all chemical reagents were of analytical grade or supra pure quality . High purity deionized water  with the resistivity of 18.2MΩ cm−The microcentrifuge tubes  and pipette tips were unused. They were directly soaked in 5% nitric acid for 24 h, followed by washing in deionized water for another 24 h, and then dried and kept in cleaned capped plastic containers.2.3The urine was transported from the sample collection site in sterilized containers in iceboxes and was finally preserved at -80 °C. Blood was collected in metal-free polypropylene tubes and stored in an icebox. Later it was subjected to centrifugation at 3000 rpm for 15 min at room temperature. Thus, serum was obtained, and the serum was preserved at -80 °C in metal-free polypropylene tubes.After receiving the serum and urine samples in the Analytical Chemistry Laboratory, dilution of samples was rendered to 10 mL using ultrapure deionized water if required. Analytical calibration standards, internal quality control, and spiked samples with a matrix from known standards were prepared from the standard 1000 ppm stock solution purchased from Spectropure, USA. A calibration curve for each metal of 0.1–10 μg/L was constructed. The Pb, Cr, and Cd in urine and Cu, Zn in serum were determined by Atomic Absorption Spectrophotometer (Varian AA240 FS) equipped with hollow cathode lamps. The wavelength and lamp current of Pb, Cd, Cr, Cu, Zn are 217.0 nm and 10mA, 228.8 nm and 4mA, 357.9 nm and 7mA, 324.8 nm and 4mA, 213.9 nm and 3mA, respectively. The type of flame was Air/Acetylene, the flow rate of Air and Acetylene was 13.50 L/min and 2.90 L/min, respectively. Moreover, the purity of Acetylene gas was 99.99% pure used for the flame. Replicate samples/standards, quality control standard, spike recovery, and method blanks were used to monitor the performance of the instrument and the quality of the data. The recoveries of spiked samples were from 88 to 99%.2.4For statistical analysis SPSS Statistics 22.0  was used, including analysis of variance, correlation analysis, and principal component analysis. Origin 2019  was used for distribution tests and charting. The Monto Carlo simulation was performed using Crystal Ball Software .2.5The probabilistic risk assessment of heavy metals was performed using a simulation of Monte Carlo. Weak correlation or independence between the input variables was assumed in this simulation. Input variables  were modeled as specific probability distribution functions . To ensu33.1The concentrations of metals in the urine samples of CKD patients and control subjects with their descriptive statistics are presented in 3.2In the blood samples of CKD patients and their healthy counterparts, two metals were studied, i.e., Cu and Zn. The descriptive statistics of the data are given in . The mea3.3Pearsons' correlation was performed to find a possible association among different variables . A signi3.4th percentile risk value of metals studied in the control and CKD group showed the pattern as follows: Cu > Pb > Cr > Cd , and only 20 samples have Lead concentration levels (10–90 μg/L), which are comparatively lower. According to Yaman et al. , the norThe mean urinary Cadmium for case and control was 20.67 μg/L and 17.51 μg/L, respectively. The CKD patients had higher levels of Cadmium in their urine in contrast to controls. This agrees with the reported trend  but to aThe mean urinary Chromium, for exposure and control, are 85.35 μg/L and 18.00 μg/L. Though the urinary excretion of Cadmium and Chromium are lower in the 16 villages, they are well above the recommended range for almost all of the villages. The urinary excretion of all three metals is highest for Panam Gabtoli and Haria Baidyer Para, while the lowest values can be attributed to Bhabanipur, Khamargaon, Dighi Chandpur, and Dakarband.The above paragraphs depict that the urinary excretion of Lead, Cadmium, and Chromium are higher for the cases than the controls. One of our principle research parameters is that the CKD patients who did not have hypertension or diabetes were specifically chosen. It proves a positive correlation between chronic exposure to nephrotoxic heavy metals and CKD. Also, this exposure might have caused an imbalance of Copper concentration in their blood serum, which have affected their kidneys and might affect other internal organs in the long term. These findings also support the out of the probalilistic health risk assessment of this study . The hig5In comparison with other lethal ailments, CKD is comparatively obscure in Bangladesh. This collaborative study being the first of its kind in Bangladesh, has established a positive correlation between CKD and chronic exposure to heavy metals. Which is essentially supported by the fact that the residents with the highest values of Pb, Cd, Cr in their urine suffered from CKD and an imbalance of Cu concentrations in their blood serum. Although in our study, a positive correlation was established, further research into the correlation between nephrotoxic metals and CKD is necessary to comprehend CKDu and its treatment.Tasrina Rabia Choudhury: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.Sk. Zubaer Zaman: Analyzed and interpreted the data; Wrote the paper.Tanzina Iveen Chowdhury & Md. Anwarul Islam: Conceived and designed the experiments.Bilkis Ara Begum: Contributed reagents, materials, analysis tools.Md. Mostafizur Rahman: Analyzed and interpreted the data.10.13039/100007225Ministry of Science and Technology, Government of the People’s Republic of Bangladesh .This work was supported by Data included in article/supplementary material/referenced in article.The authors declare no conflict of interest.No additional information is available for this paper.


It accounts for 8% and 25% in the hospitalized and general population, respectively. The present study was conducted to determine the prevalence and correlates of diastolic dysfunction in hypertensive patients living in Saudi Arabia.a multicentric, cross-sectional study was conducted from February 2019 to February 2020 at King Khalid Hospital and Prince Sultan Center for Health Services, Prince Sattam Bin Abdulaziz University hospital in Al Kharj, and Al Kharj Military Industries Corporation hospital, KSA. All patients with hypertension who underwent an echocardiography were included in the study. Logistic regression analysis was performed to determine factors associated with left ventricular diastolic dysfunction (LVDD).the study included a total of 104 participants, where 51.9% were females and the mean age of the patients was 48.01±12.81 years. Most patients had an abnormal echocardiography finding . The most common abnormalities were left ventricular (LV) hypertrophy , and diastolic dysfunction, . The study revealed that age  and dyslipidemia  have significant association with LVDD in the patients with hypertension.in conclusion, diastolic dysfunction is prevalent among older hypertensive patients and those with dyslipidaemia. Age and dyslipidaemia were non-modifiable and modifiable factors associated with LVDD in hypertensive patients, respectively. Heart failure (HF) is a global pandemic and serious health concern affecting 64.34 million people all over the world, posing significant morbidity, mortality, and expenditure . ApproxiDiastolic HF causes lesser annual deaths as compared to that of systolic HF . HoweverStudy design and setting: this was a multicentric, cross-sectional study conducted from February 2019 to February 2020 at the cardiology units of three hospitals in the Kingdom of Saudi Arabia (KSA)including King Khalid Hospital and Prince Sultan Center for Health Services, Prince Sattam Bin Abdulaziz University hospital in Al Kharj, KSA, and Al Kharj Military Industries Corporation hospital. These units have adequate human resources and are fully equipped to diagnose and manage the full spectrum of cardiovascular diseases according to international standards.Study population: all patients with previously diagnosed primary hypertension who underwent an echocardiography at the study sites during the study period were evaluated for inclusion into the study. Hypertensive patients showing signs and symptoms of heart failure, or chest x ray findings of structural heart disease or cardiomegaly were indicated to undergo echocardiography at the 3 hospitals. We included males and females of all ages and nationalities. Patients with newly diagnosed hypertension, those with secondary hypertension, those who refused to consent to participate in the study, and those with any data missing from their electronic medical records were excluded. The calculated minimum required sample size was 97 patients. This sample size was calculated using an open Epi sample size calculator, taking the prevalence of LV diastolic dysfunction to be 50.3% among hypertensive patients who underwent echocardiography [iography  at margiData collection: patient medical information pertaining to their age, gender, nationality, history of present illness, including hypertensive symptoms  and/or complications , co-morbidities , smoking history, blood pressure readings, body mass index (BMI), biochemical tests for dyslipidaemia, and echocardiography findings were collected through a survey of their electronic medical records. The outcome of interest was the presence of echocardiography findings suggestive of LVDD. After at least 5 min of rest, blood pressure (BP) was measured in a sitting position from non-dominant arm placed at the level of the heart, using adults´ cuffs (32-42 cm) adapted to an automated sphygmomanometer. Hypertension was diagnosed based on blood pressure recordings measured according to the 2017 American College of Cardiology (ACC) and American Heart Association (AHA) clinical practice guidelines [idelines . Hyperteidelines . Normal idelines . Those pidelines .Statistical analysis: data was entered and analysed using the Statistical Package for Social Services version 22. Descriptive statistics were obtained for study variables. Mean and standard deviation were computed for quantitative variables i.e., age and BMI. Frequency and percentages were used to summarise qualitative variables. The association of study variables with LVDD was assessed by constructing a binary logistic regression model. Variables with a p value of less than 0.20 in the univariable analysis were included in the multivariable model. Two-tailed p-values <0.05 were considered statistically significant.Ethical considerations: the study was approved by the Medical Ethics Committee of the Prince Sattam Bin Abdulaziz University  and was conducted according to its guidelines. A written informed consent was obtained from all study participants  before enrolment into the study. All patient information obtained from electronic health records was completely anonymized.General characteristics: after exclusion of 25 participants, the study included a total of 104 participants. The study population included mostly non-Saudi nationals, around 60%, where 51.9% were females and the mean age of the patients was 48.01±12.81 years. Most, nearly 80%, were obese or suffered from mild hypertension (HTN). thirty-seven point five percent (37.5%) of participants suffered from ischemic heart disease, 29.8% from dyslipidaemia, while 26% of them had diabetes mellitus . The most common abnormalities were left ventricular (LV) hypertrophy (44.2%), and LVDD, (35.6%) ( (35.6%) .Factors associated with diastolic dysfunction: in the initial univariable analysis age, gender, obesity, severity of hypertension, diabetes mellitus, ischaemia heart disease, dyslipidaemia, and left ventricular hypertrophy reached a statistical significance of p < 0.2. In the multivariable analysis only 2 of the included variables reached statistical significance (ificance . ParticiThis cross-sectional study was conducted to determine the prevalence and correlates of diastolic dysfunction in hypertensive patients living in Saudi Arabia. The study revealed that age and dyslipidemia have significant association with LVDD in the patients with hypertension. The prevalence of LVDD among hypertensive patients increases with advancing age and more likely to occur in those with dyslipidemia as compared to those without it. It has been observed that LVDD is one of the first noticeable manifestations among the patients with hypertension which can be detected on echocardiography as left ventricular filling abnormality even when it is clinically unnoticeable . A retroet al. [et al. [Several correlates of LVDD among hypertensive patients have been reported. A large study has reported that factors associated with LVDD include advanced age, duration of hypertension, tobacco use, high systolic blood pressure, uncontrolled high blood pressure, and slow heart rate .Similarlet al.  retrospe [et al.  conducteThe strength of the study is that it is the first study, to the best of our knowledge, to perform echocardiographic evaluations for LVDD among hypertensive patients attending tertiary care centers in KSA. It revealed significant associations between age and dyslipidemia with LVDD. This may provoke further studies and certain strategies to adopt to prevent LVDD. The limitation includes small size of the study as large population suffers from hypertension. Further, given that only we only included patients who underwent echocardiographic study for hypertension evaluation, inclusion of patients with more severe hypertensive disease as opposed to those whose hypertension did not warrant echocardiographic evaluation is an inherent sampling bias in this study. This along with a high margin of error of 10% precludes the extrapolation of our research findings to the general Saudi population . FurtherLeft ventricular diastolic dysfunction is frequent among hypertensive patients where main risk factors are old age and dyslipidaemia. Elderly participants and those with dyslipidemia were more likely to be diagnosed with LVDD. Therefore, preventive measures and lifestyle modifications would help improve dyslipidaemia among hypertensive patients, reducing the risk of LVDD.The prevalence of left ventricular diastolic dysfunction has been reported to be up to 82.86% of patients with hypertension;Determinants of diastolic dysfunction include myocardial relaxation, myocardial stiffness, chamber geometry, wall thickness, preload and afterload, passive properties of ventricular wall and heart rate.It is the first study to perform echocardiographic evaluations for LVDD among hypertensive patients attending tertiary care centers in KSA.The prevalence of left ventricular diastolic dysfunction as 44.2%;Age and dyslipidemia have significant association with left ventricular diastolic dysfunction among the patients with hypertension in Saudi Arabia.


IgA nephropathy (IgAN) remains one of the most common forms of glomerulonephritis, especially in developed countries with a low prevalence of infectious diseases. Despite supportive measures that slow the rate of progression of chronic kidney disease (CKD) in IgAN, many patients still progress to end-stage kidney disease. Proteinuria has been shown to be an adverse prognostic factor in IgAN. Data support the use of proteinuria reduction as a reasonably likely surrogate endpoint for a treatment’s effect on progression to end-stage renal disease (ESRD) in IgAN. Currently employed immunosuppressive strategies lack conclusive efficacy data, while there is evidence for treatment-induced toxicity. The current standard of care for the management of IgAN is intensive goal-directed supportive care. Recently the role of sodium-glucose cotransporter 2 (SGLT2) inhibitors in decreasing proteinuria and progression of CKD is widely being recognized. In this case report, we present a 44-year-old male with proteinuria and biopsy-proven IgAN who remained in remission after six months of steroids using the Pozzi protocol. He developed proteinuria five years after remission. At this point, canagliflozin was added to his angiotensin-receptor blocker (ARB) therapy resulting in a significant reduction in his proteinuria. Our case report may intrigue researchers to look into the role of canagliflozin in decreasing albuminuria in non-diabetic kidney disease, thus slowing the progression to ESRD. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been used to substantially reduce CKD progression and decrease albuminuria. Dapagliflozin has been shown to be effective in both diabetic and non-diabetic CKD. The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease Trial (DAPA-CKD) included 4,304 participants with glomerular filtration rate 25 to 75 mL per minute per 1.73 m2 and urine albumin:creatinine  ratio 200-5,000 mg/g. This study demonstrated that in patients with CKD with or without diabetes mellitus, the risk of decline of at least 50% in estimated glomerular filtration rate (eGFR), ESRD, death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo [2 and urinary alb:cr ratio >300-5,000 mg/g) who were already receiving an angiotensin-converting enzyme inhibitor (ACEi) or ARB [Canagliflozin also safely reduces kidney and cardiovascular events in people with type 2 diabetes and severely increased albuminuria . In the ) or ARB . In thesA 44-year-old Hispanic man presented in 2014 with a history of hypertension and had a urine protein (pr): creatinine (cr) ratio of 1.34 with 5-10 red blood cells per high power field on urine microscopy. His BUN was 14 and serum creatinine 0.7 mg/dL. Serological workup was negative. Kidney biopsy revealed IgAN with mesangial proliferative and sclerosing changes with mild to moderate activity and mild chronicity. By the updated 2017 Oxford classification of IgAN, he had M1, E0, S1, T0, C2 where M is Mesangial hypercellularity, E is endocapillary proliferation, S is segmental sclerosis, T is tubular atrophy and interstitial fibrosis and C is crescents. In addition, he had mild arteriolosclerosis.After a four-month trial of an ARB, losartan, titrated to the highest dose, he still had urine pr:cr ratio of 1.16. He then received the Pozzi protocol consisting of six months of corticosteroids with three-day boluses of intravenous solumedrol on months 1, 3, and 5 and prednisone 0.5 mg per kg body weight on alternate days throughout the six month period. He went into remission with a decrease of urine pr:cr ratio to 0.19 within four months by March 2015.He remained in remission on losartan 100 mg while tested with semiannual urine pr:cr ratios through October 2019. In March 2020, he acquired a COVID-19 infection but was not hospitalized. At an outside laboratory, his urine alb:cr ratio increased to 555 mg/g in August 2020. As noted in Table IgAN is one of the most common forms of glomerulonephritis, which despite the use of renin-angiotensin-aldosterone-system blockers and immunosuppressants, often progresses to kidney failure . There iIn the CREDENCE trial, the median baseline urine alb:cr ratio was 927 mg/g. In addition, the relative kidney benefits were consistent over the entire range of albuminuria levels studied. Canagliflozin reduced efficacy outcomes for all urine albumin to creatinine ratio levels with no evidence that relative benefits varied between levels . The subClinicalTrials.gov Identifier: NCT03594110) has recruited a large population of CKD patients and is likely to provide further information on the effectiveness and safety of SGLT2 inhibitors in patients with IgAN.Although this decrease in albuminuria and proteinuria with canagliflozin in IgAN is a new finding, the conclusions drawn from this case report can only be considered as interesting. This is an evaluation based on a single patient and we have only one data point after starting canagliflozin. In addition, the ARB dose was also increased prior to measuring the effect of canagliflozin on urine protein and urine albumin. We believe the ARB would have played a minor role here since the ARB offered a minimal decrease in proteinuria after four months of use at the time of his initial IgAN diagnosis. Proteinuria is a surrogate endpoint and not the clinically more meaningful important endpoint of reducing the risk of kidney failure used in the DAPA-CKD and CREDENCE studies. However, in IgAN, there is a strong relationship between the level and duration of proteinuria and loss of kidney function . There iIt is possible that COVID-19 may have played a role in the relapse of IgAN in this patient leading to proteinuria. Huang et al. report increased proteinuria and gross hematuria as a consequence of exacerbation of a patient's biopsy-proven IgAN concurrent with a COVID-19 infection . AbramsoDapagliflozin has demonstrated decreased albuminuria and renal protection in patients with IgA nephropathy. Canagliflozin has demonstrated similar results in patients with CKD and type 2 diabetes with severely increased albuminuria. In our case presented, a patient with known IgA nephropathy and a recent increase in albuminuria and proteinuria had a 69% decline in albuminuria after the addition of canagliflozin to his ARB. This highlights the potential of canagliflozin acting to offer renal protection in IgA nephropathy if borne out by the further study. The association of COVID-19 and this patient’s increased albuminuria in the context of current case reports call attention to the consideration of the possible role of canagliflozin ameliorating COVID-19-induced glomerulonephritis.


Baveno VI criteria, based on liver stiffness (LS) measured by transient elastography and platelet counts (PLT), have been proposed to avoid unnecessary endoscopy screening for high-risk varices (HRVs). However, the cut-off value of LS measured by 2D-SWE and PLT to predict HRVs in compensated hepatitis B-related cirrhotic patients remains unknown.  To prospectively analyze the cut-off of the combination of LS measured by 2D-SWE and PLT in predicting HRVs and the influence of antiviral therapies in its efficacy.  Serum parameters, LS, and endoscopy results were obtained from 160 compensated hepatitis B-related cirrhotic patients. The accuracy of the combined algorithm was assessed in the whole cohort and subgroups with or without consecutive antiviral therapies in the past 6 months. 9/L can be excluded from HRVs . Conversely, a LS value of ≥14.5 kPa and a PLT value of ≤110 × 109/L indicated HRVs, with accurate rates of 82.35%, and 10.63% of patients can avoid additional endoscopy screening. Moreover, antiviral therapy had no significant effect on the accuracy and rates saved from further endoscopy screening, when comparing patients with or without antiviral therapies .  In the whole cohort, the optimal cut-off value of LS for HRVs was 14.5 kPa. Patients with a LS value < 14.5 kPa with a PLT value > 110 × 109/L) can predict HRVs accurately in compensated hepatitis B-related cirrhotic patients without significant interference of antiviral therapy histories. The combination of LS (14.5 kPa) measured by 2D-SWE and PLT (110 × 10 Hepatic cirrhosis and portal hypertension are the common consequences of chronic hepatitis B infection. Patients with clinically significant portal hypertension are at risk of developing esophageal varices (EVs), and varix bleeding is one of the major causes of death in patients with hepatitis B-related cirrhosis . Due to Several noninvasive indexes have been tested to predict HRVs in cirrhotic patients, such as Doppler ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and elastography techniques. CT and MRI allow direct visualization of esophageal varices after intravenous contrast administration, whereas the cost of both methods is higher compared to other noninvasive methods. Various indexes measured by Doppler ultrasonography have been proposed as noninvasive predictors for EVs. However, all these parameters fail to accurately predict the presence of large varices and display a lower accuracy than that of liver elastography . TransieSerum indexes are another kind of noninvasive markers for the prediction of HRVs. Platelet counts (PLT) have been attracted more attention among these indexes, since thrombocytopenia is mostly associated with portal hypertension in cirrhotic patients. Another advantage of PLT lies in its easy availability in the clinical practice without an increase in expense for cirrhotic patients . MoreoveIn this prospective study, we recruited 160 compensated hepatitis B-related cirrhotic patients who were ready to undergo 2D-SWE and endoscopic examinations. We aimed to investigate the cut-off and diagnostic efficacy of the combination of the LS measured by 2D-SWE and PLT to predict HRVs.Patients with compensated hepatitis B-related cirrhosis at Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, were recruited in this prospective study from May 2017 to June 2018. The inclusion criteria were (1) presence of hepatitis B surface antigen for at least six months and (2) cirrhosis detected by liver histology or unequivocal clinical and imaging data. The exclusion criteria were (1) coinfection with hepatitis C virus or other chronic liver diseases; (2) history of liver surgery and liver transplantation; (3) portal or hepatic vein thrombosis detected by imaging techniques; (4) previous treatments with transjugular intrahepatic portosystemic shunts, EVs banding ligations, or nonselective beta-blockers; (5) moderate-to-severe ascites; (6) hepatic encephalopathy; (7) the history or presence of variceal hemorrhage; (8) AST and/or ALT elevation > 5 × the upper limit of normal; (9) right heart failure; and (10) obstructive jaundice. Informed consent was obtained from all participants in this study. All procedures followed the 1964 Declaration of Helsinki and were approved by the Ethics Committee of Shandong Provincial Hospital. This study has been registered in the Chinese Clinical Trial Registry (1900020560).Two experienced technicians (both of them have conducted more than 500 examinations), blinded to the upper gastrointestinal endoscopy results, performed 2D-SWE  with a convex broadband SC6-1 probe. After an overnight fast, 2D-SWE measurements were performed within 1 week after admission. Readings were taken in three different regions of interest (ROI) in the right lobe of the liver. The measurement of LS should be performed at least 10 mm below the liver capsule. The final LS value was calculated as the mean of the recorded acquisitions. Each acquisition was considered successful if the following three conditions are met , standard deviation (SD) of the LS value was ≤1.75 kilopascals (kPa), and big vessels and biliary tracts were not included in ROI). Measurements not fulfilling these requirements were considered failed, and such patients were excluded from the study.EVs were detected by one expert endoscopist (having conducted more than 200 examinations per year) to avoid the influence of interobserver variability. Endoscopies were performed within 1 week after admission. EVs were staged according to the previously published criteria as follows: grade I: varices were flattened by insufflation; grade II: varices nonconfluent and protruding in the lumen despite insufflation; grade III: confluent varices were not flattened by insufflation . The preThe demographic data and blood samples of patients were obtained at the time of hospital admission and were performed at the same admission as endoscopic and hepatic elastography evaluation. Blood samples were collected after a 12 h, overnight fast to detect alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total bilirubin (TBIL), albumin (ALB), prothrombin time (PT), international normalized ratio (INR), platelet count (PLT), serum creatinine, and hepatitis B DNA load. Liver function was assessed by the Child-Pugh classification and model for end-stage liver disease (MELD) score , 17. Thet-test, or Kruskal-Wallis test. Missing data were interpolated using the Expectation-Maximization method [Statistical analyses were performed with STATA 14.0  and MedCalc 11.2 . The Shapiro-Wilk test was used for testing the distribution of numerical variables. Continuous variables were presented as mean ± SD or median (interquartile range) and categorical variables as numbers and percentages. Intergroup differences were assessed for significance using the Chi-squared test, Mann–Whitney test, Student's n method . Resultsp < 0.1) were included in the multiple regression models. Relationships between these parameters were characterized using Spearman correlation coefficients. The performance of noninvasive tests was assessed in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio, false-positive rate (FPR), false-negative rate (FNR), and area under the receiver operating characteristic curves (AUC). A comparison between AUCs was made by the Hanley and McNeil method [p value of < 0.05 denoted statistical significance.To avoid the omission of meaningful factors, variables significant in univariate analysis , history of liver surgery (n = 2), portal or hepatic vein thrombosis detected by imaging techniques (n = 5), and previous treatments with EVs banding ligations (n = 1). Eight patients failed 2D-SWE examinations, resulting in 160 patients in the final analysis (p < 0.001). According to multivariate analysis, BMI was the only factor associated with unsuccessful LS measurements . In patients with successful measurements, the IQR/median was 0.051 ± 0.032 (range: 0.003-0.177), thus, all patients fulfilled the reliable criteria recommended by EFSUMB guidelines [In this prospective study, 178 patients were initially recruited. Ten patients were excluded for the following reasons: coinfection with hepatitis C virus . Clinical characteristics of the included patients are summarized in The prevalence of EVs was 26.88% (43/160), and HRVs were present in 26 (16.25%) patients. In addition, patients with antiviral therapy histories accounted for 36.88% (59/160) of the total cases, and the prevalence of HRVs in patients with antiviral histories was 20.34% (12/59), which was not significantly different from patients without antiviral histories (p < 0.001)  .  Table p = 0.426), but slightly overestimated the probability of HRVs (p = 0.116).Moreover, the calibration of 2D-SWE was good by the Hosmer-Lemeshow test ( of HRVs . Similarp = 0.157).To improve the accuracy of 2D-SWE, multivariable analysis for significant indicators in 9/L) from the expanded Baveno VI criteria was verified [9/L) were less likely to be diagnosed with HRVs (NPV = 99.07%). One hundred and eight out of the 160 patients (67.50%) fulfilled the criteria and, consequently, avoided endoscopy screening. By combining LS (≥14.5 kPa) and PLT (≤110 × 109/L) to assess HRVs, patients can only be diagnosed with 82.35% certainty, and 17 (10.63%) patients can avoid endoscopy screening. Overall, 125 patients (78.13%) could avoid endoscopic examinations, and the accuracy was 96.80% (121/125), which was better than that of LS alone   .p = 0.016). Moreover, all patients who were underestimated using a cut-off of 14.5 kPa had antiviral therapy histories. Thus, patients with antiviral therapy histories had a higher FNR compared with those without antiviral histories , but the rates of discordance and FPRs were not statistically significant . Furthermore, the logistic regression analysis showed that AST values were associated with underestimated results by 2D-SWE in patients with HRVs . Overall, the above results indicated that the history of antiviral therapy was an important confounding factor that may underestimate HRVs by attenuating hepatic cirrhosis and inflammation.A subgroup analysis was conducted to investigate the impact of antiviral therapy histories on the performance of LS measured by 2D-SWE in the prediction of HRVs. The AUC was higher in patients without antiviral history than those who received the treatment , and only one patient was misclassified by the combined algorithm. Moreover, significantly lower discordance rates  and FPRs  were observed for the combined algorithm in patients without antiviral therapy histories.On the other hand, the combined algorithm exhibited a significantly lower FNR than LS alone in patients with antiviral therapy histories   .This study assessed the accuracy of combining the LS value, as measured by 2D-SWE, and the PLT value for predicting HRVs in patients with hepatitis B-related cirrhosis. Our findings demonstrated that in comparison with the LS value alone, this combined algorithm could further improve the accuracy of predicting HRVs. Nearly all patients without HRVs could be excluded and may be used as a first-line screening method to identify high-risk patients. Besides, the combination of LS with PLT displayed excellent accuracy even in patients with histories of antiviral treatment.One of the major concerns for using 2D-SWE in cirrhotic patients is its feasibility and applicability. In this study, failed measurements only accounted for 4.76% (8/168). This desired result could be attributed to the technique's improvement by integrating 2D-SWE into traditional ultrasound machines, thereby ensuring the homogeneity of the elastic image , obesityAnother concern about predicting HRVs using 2D-SWE in compensated hepatitis B-related cirrhotic patients is its diagnostic efficacy. In the present study, LS showed higher NPVs than PPVs, which could probably be due to the lower prevalence of EVs. In this cohort, the prevalence of EVs and HRVs was 26.88% and 16.25%, respectively, and the differences in etiology may explain this lower prevalence . This as9 cells/L can avoid the need for screening endoscopy [9/L) improved the ability to exclude patients with HRVs and reduced the need for endoscopy by 68%. Only one patient was misclassified, whose clinical characteristics were LS = 12.5 kPa, PLT = 225 × 109/L, BMI = 29.38 kg/m2, implying the influence of obesity on LS measurement or instability around the cut-off values. In patients fulfilling LS ≥ 14.5 kPa and PLT ≤ 110 × 109/L, HRVs can be identified with more than 80% certainty, which was better than LS alone. More methods that may further improve the accuracy of the prediction of HRVs are needed in the future.In order to further improve the diagnostic accuracy for ruling out HRVs, the expanded Baveno VI guidelines proposed that patients with compensated advanced chronic liver disease with an LS value by TE of <25 kPa and a platelet count >110 × 10ndoscopy . HoweverFactors affecting the accuracy of noninvasively diagnostic technique for HRVs are also issues of concern to clinical work , 27. Morμmol/L), we cannot further analyze the impact of these confounders. Future studies should expound their influence in the results. Additionally, the application of spleen stiffness (SS) has been attracted more and more attention [Our study has certain limitations. The size of the population is slightly smaller than those in previous studies. Moreover, except for excluding HRVs, we also want to find a method to rule in patients with a high risk of HRVs. Though higher ALT and TBIL levels may increase FPRs, however, it does not affect the most important characteristic of this algorithm, i.e., the safety profile. Since the level of ALT/AST of 90% (144/160) included patients were ≤2 × upper limit of normal, and 77.5% (124/160) of them were within the normal level of TBIL (<23.9 ttention , althougttention , 34. Howttention  and may ttention . More ev9/L should be consent to perform endoscopic screening, and primary prophylaxis is required for patients with medium or large varices. The other patients in the “grey zone” need to consider combining other noninvasive tests or undergo endoscopy screening directly (Figure Last but not least, the practical implications of our findings can be concluded as follows. The most compelling evidence is that the LS value measured with 2D-SWE would safely avoid the need for additional endoscopy screening in patients with hepatitis B-related cirrhosis who are most likely to be free from HRVs. We recommend that the combination of LS with PLT is used for patients with antiviral history in predicting HRVs. Moreover, patients who meet the criteria LS ≥ 14.5 kPa and PLT ≤ 110 × 10y Figure .


Symptomatic intracranial hemorrhage (sICH) after intravenous thrombolysis is closely related to the poor outcome of stroke.To determine the serum biomarkers associated with sICH based on the INTRECIS study.Enrolled patients with sICH and without any ICH were matched by propensity score matching with the ratio of 1:1. Preset 49 biomarkers were measured by protein microarray analysis. Gene Ontology and Pathway Enrichment Analysis and protein-protein interaction network (PPI) were analyzed in the identified biomarkers.Of the consecutive 358 patients, eight patients occurred with sICH, which was assigned as an sICH group, while eight matched patients without any ICH were assigned as a Non-sICH group. A total of nine biomarkers were found significantly different between groups, among which the levels of interferon (IFN)-γ and interleukin (IL)-4 were higher, while the levels of C-reactive protein (CRP), glial cell line-derived neurotrophic factor (GDNF), insulin-like growth factor-binding protein (IGFBP)-6, lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, matrix metalloprotein (MMP)-2, plasminogen activator inhibitor (PAI)-1, and platelet-derived growth factor (PDGF)-AA were lower in the sICH group compared with those in the Non-sICH group.Our finding indicated that baseline serum CRP, GDNF, IFN-γ, IGFBP-6, IL-4, LYVE-1, MMP-2, PAI-1, and PDGF-AA levels were associated with post-thrombolytic sICH in stroke. Intravenous thrombolysis, with recombinant tissue plasminogen activator (rtPA), is an effective treatment for acute ischemic stroke within 4.5 h of symptom onset . SymptomPrevious studies have investigated clinical, radiological, and laboratory risk factors of hemorrhagic transformation in ischemic stroke –8. ContrIn INtravenous Thrombolysis REgistry for Chinese Ischemic Stroke within 4.5 h of onset (INTRECIS) , five ceClinicalTrials.gov NCT 02854592). The INTRECIS is a nationwide, multi-center, prospective, and registry study of consecutive adult patients who were eligible for treatment with intravenous thrombolysis within 4.5 h of the onset of symptoms. Details of the study design and results of the primary outcomes have been reported recently  to evaluate the presence of intracranial hemorrhage. According to European Cooperative Acute Stroke Study (ECASS)—II definition, sICH was defined as an increase of ≥4 on the NIHSS scores caused by intracranial hemorrhage within 36 h .The study was centrally approved by the Institution Human Research Ethics Committees of General Hospital of Northern Theater Command.About 4 ml of peripheral venous blood samples were collected from each patient just prior to intravenous thrombolysis. The blood samples were centrifuged at 1,000 × g for 10 min at 4°C, and then transferred into a 1.8-milliliter cryotube and stored at −80°C until measurement.p < 0.05, and fold change > 1.20 or <0.83. Functional enrichment analysis and protein-protein interactions (PPI) network were performed to explore the possible mechanism between identified biomarkers.According to the instructions of the manufacturer, pre-customized protein microarray analysis (Raybiotech Inc.) was used to simultaneously detect and quantify the 49 biomarkers in the collected blood samples, which were preset based on published data. Identified biomarkers were defined as those variations with t-tests were used to analyze the normally distributed continuous variables. Categorical variables were described as numbers and proportions. Categorical variables included gender, current smoking, alcohol consumption, medical history, previous use of antiplatelet, and TOAST classification. The Pearson χ2 tests were used to analyze the categorical variables.Descriptive statistics was performed to compare variables between two groups. Continuous variables with normal distribution were described as means and standard deviation. Continuous variables include age, systolic blood pressure, diastolic blood pressure, blood glucose, symptom onset to thrombolysis time, NIHSS score, and detected serum concentration of biomarkers. The p is obtained from the moderated t-statistic with a false discovery rate of adjustment for multiple testing. In all analyses, differences were considered statistically significant with a p < 0.05. The free statistical language R (version 3.10.3) was used for the outcomes and graph in the propensity score matching and microarray analysis.The value of As shown in , 358 patp < 0.05). Patients with sICH showed higher pretreatment serum levels of interferon (IFN)-γ and interleukin (IL)-4, and lower pretreatment serum levels of C-reactive protein (CRP), glial cell line-derived neurotrophic factor (GDNF), insulin-like growth factor-binding protein (IGFBP)-6, lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, matrix metalloprotein (MMP)-2, plasminogen activator inhibitor (PAI)-1, and platelet-derived growth factor (PDGF)-AA than the matched patients in Non-sICH  enrichment analysis was used to gain a deeper insight into the main functions of the identified biomarkers. The GO analysis consisted of biological process, molecular function, and cellular component analysis. The biological process analysis showed that GDNF, IFN-γ, and PAI-1 were mostly included in the regulation of epithelial cell differentiation . The molBased on the information of the Search Tool for the Retrieval of Interacting Genes (STRING) database, the PPI network constructed by the above nine identified biomarkers was obtained . The resIn the present study, we found that baseline serum levels of 9 biomarkers were differently expressed in thrombolytic patients with sICH compared with Non-sICH group: higher IFN-γ and IL-4, and lower CRP, GDNF, IGFBP-6, LYVE-1, MMP-2, PAI-1, and PDGF-AA. Of those biomarkers, IGFBP-6, LYVE-1, and PDGF-AA were firstly found associated with sICH.Up to date, several mechanisms and potential biomarkers for sICH were previously investigated , 10. In For the first time, we found that lower PDGF-AA, IGFBP-6, and LYVE-1 were associated with sICH. The previous studies suggested that lower PDGF-AA may be associated with lower endothelial remodeling degree and higher vascular permeability . The IGFAdditionally, we did not detect a significant difference in other preset biomarkers, such as MMP-9, which has been reported to be associated with post-thrombolytic hemorrhagic transformation , 24. A pBased on functional enrichment analysis, epithelial cell differentiation, growth factor activity, platelet alpha granule lumen, and JAK/STAT signaling pathway were significantly enriched items. As the initial phase of blood-brain barrier disruption, brain microvascular endothelial cell injury, induced by stroke, played a key role in hemorrhagic transformation . Growth in vivo experiments. Finally, although the effect of identified biomarkers was independent of other preset biomarkers, the different levels as a result of an acute-phase reaction or previous systemic diseases cannot be ruled out.The strength of this study was to explore the key biomarkers associated with post-thrombolytic sICH through comprehensively screening the preset biomarkers in a prospective cohort and find several new biomarkers, which have never been reported previously. However, we acknowledge that our study has several limitations. First, it is a small-sample study with only eight stroke patients with post-thrombolytic sICH and blood samples. Thus, the results should be further confirmed by a large cohort study with different subtype hemorrhagic transformations, such as asymptomatic and symptomatic intracranial hemorrhage. Second, these identified biomarkers were not confirmed by other methods, such as western blot analysis, enzyme-linked immunosorbent assay, or other Our finding indicated that baseline serum levels of CRP, GDNF, IFN-γ, IGFBP-6, IL-4, LYVE-1, MMP-2, PAI-1, and PDGF-AA were associated with post-thrombolytic sICH in acute ischemic stroke. The role and predictive value of these identified biomarkers warrant further investigation.https://doi.org/10.5281/zenodo.5801880.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: The studies involving human participants were reviewed and approved by Institution Human Research Ethics Committees of General Hospital of Northern Theater Command. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.H-SC designed and reviewed. W-HM supervised the manuscript writing. YC conducted the analyses and drafted the manuscript. YZ, S-YC, B-YS, and L-HW contributed to the implementation of blood sample collection. All authors contributed to the article and approved the submitted version.The study was funded by grants from National Key R&D Program of China (2017YFC1308203), the Project on Research and Application of Effective Intervention Techniques for Chinese Stroke Guidelines from the National Health, and Family Planning Commission in China (GN-2016R0008).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.


Background: Administration of terlipressin can reverse hypotension in potential organ donors with norepinephrine-resistance. The aim of this study was to determine the effects of terlipressin on the hemodynamics, liver function, and renal function of hypotensive brain-dead patients who were potential organ donors.Methods: A retrospective study was conducted by using the ICU database of one hospital. 18 patients in a total of 294 brain-dead cases were enrolled and administered terlipressin intravenously. All physiological parameters of recruited patients were obtained at baseline, 24 and 72 h after administration, and immediately before organ procurement.Results: Terlipressin induced significant increases in mean arterial pressure (MAP) from 69.56 ± 10.68 mm Hg (baseline) to 101.82 ± 19.27 mm Hg (immediately before organ procurement) and systolic blood pressure (SBP) from 89.78 ± 8.53 mm Hg (baseline) to 133.42 ± 26.11 mm Hg (immediately before organ procurement) in all patients. The increases in MAP were accompanied by significant decreases in heart rate (HR) from 113.56 ± 28.43 bpm (baseline) to 83.89 ± 11.70 bpm (immediately before organ procurement), which resulted in the decrease of norepinephrine dose over time from 0.8 ± 0.2 μg/kg/min (baseline) to 0.09 ± 0.02 μg/kg/min (immediately before organ procurement). There were no changes in central venous pressure, liver function including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin. Renal function, assessed by serum creatinine (SCr), urine output (UOP), creatinine clearance rate (CCr), and estimated glomerular filtration rate (eGFR), improved significantly.Conclusion: Our analysis of brain-dead patients with hypotension indicates that administration of terlipressin can significantly increases MAP, SBP, UOP, CCr, and eGFR, while decreases HR and Scr. Terlipressin appears to help maintain hemodynamic stability, reduce vasoactive support, and improve renal function. Organ transplantation is considered as the optimal treatment for many patients with end-stage organ disease . HoweverThere are many significant systemic changes during brain death, and hemodynamic instability is among the most notable. During the pathogenesis of brain death, after the hypertensive phase of the “catecholamine storm” , arteriavia V1 receptors, couples to phospholipase C, and increases intracellular Ca2+ concentration  mediates vasoconstriction ntration . After bntration . Terliprntration . A smallntration .However, data on the efficacy of terlipressin infusion in brain-dead patients are limited, and the physiological function of liver and kidney is unknown. In this study, we evaluate the effects of terlipressin on hemodynamics, liver function, and renal function in potential hypotensive organ donors with brain death.ClinicalTrials.gov (NCT03477461).This study is a retrospective analysis by using the ICU database of the East Division of the First Affiliated Hospital, Sun Yat-sen University, which is a tertiary teaching hospital. We analyzed the records of brain-dead patients admitted between January 2015 and January 2018. The research protocol was compliant with the ethics committee norms of our institution, and due to its retrospective design, the committee abandoned the need for informed consent. The trial was registered with 18 patients in a total of 294 brain-dead cases were enrolled, all of whom were potential organ donors—had been confirmed clinical brain death, but not yet by TCD, SLSEP, and EEG. In each case, the diagnosis of brain death was confirmed according to international standards . RecruitAfter confirmation of clinical brain death, when urine output <0.5 ml/kg/h following adequate fluid resuscitation and high-dose norepinephrine (>0.5 μg/kg/min), continuous infusion of low-dose terlipressin (0.02–0.06 μg/kg/min) were added according to the urine output. If there was no significant increase in urine output, the dose of the infusion of terlipressin should be increased . After sTerlipressin was administered intravenously into all enrolled patients. All physiological parameters of recruited patients were obtained at baseline, 24 and 72 h after administration, and immediately before organ procurement.Each patient had a systemic arterial catheter  and a central venous catheter. Hemodynamic parameters, including heart rate (HR), mean arterial pressure (MAP), systolic blood pressure (SBP), and central venous pressure (CVP), were collected over time. The use of different vasopressor agents, such as norepinephrine and terlipressin, was recorded.2. The estimated glomerular filtration rate (eGFR) was then calculated using the Modification of Diet in Renal Disease (MDRD) formula . The creatinine in 4 h urine samples (UCr) and in serum (SCr) were measured by an autoanalyzer using the Jaffe method. Measurements of UCr and SCr (mg/dl) and ultrafiltration (UF) rate  were then used to calculate the creatinine clearance rate  by using the formula: CCr = (UCr × V)/(SCr). The CCr was corrected for body surface area by dividing the calculated body surface area 1.73 m formula . The folAll results are presented as means ± standard deviations (SDs). To evaluate the significance of changes over time in the systemic hemodynamic indexes, biochemical indexes, liver function indexes, and renal function indexes, an analysis of variance on repeated measures was performed for all quantitative variables, considering “time” as the “within” factor at the four measurements .p values are two tailed, and a p value below 0.05 was considered statistically significant. Statistical analyses were performed using SPSS ver. 22.0 .All p < 0.001), osmotic pressure decreased from 349.7 ± 36.0 to 325.6 ± 26.9 mOsm/L (p < 0.001), and brain natriuretic peptide decreased from 9122.9 ± 1512.5 to 5279.5 ± 1895.3 pg/ml (p < 0.001), while lactate and troponin I remained unchanged.p < 0.001), SBP , and a significant decrease in HR  in these brain-dead patients. The CVP declined slightly but not significantly. After administration of terlipressin, the dose of norepinephrine was decreased from 0.8 ± 0.2 μg/kg/min (baseline) to 0.09 ± 0.02 μg/kg/min (immediately before organ procurement), and the dose of terlipressin was decreased from 0.05 ± 0.01 μg/kg/min (baseline) to 0.02 ± 0.01 μg/kg/min (immediately before organ procurement) (urement) .There were no significant changes in AST, ALT, or bilirubin following administration of terlipressin . Urine oThe major result of this retrospective study of hypotensive brain-dead patients who were potential organ donors is that terlipressin infusion significantly increases MAP, SBP, UOP, CCr, and eGFR, while decrease HR, SCr and the dose of norepinephrine. During the treatment, the dose of terlipressin could be decreased gradably from 0.05 ± 0.01 to 0.02 ± 0.01 μg/kg/min, the dose of norepinephrine was decreased from 0.8 ± 0.2 μg/kg/min (baseline) to 0.09 ± 0.02 μg/kg/min (immediately before organ procurement). Thus, terlipressin appears to improve hemodynamic stability, reduce vasoactive support, and improve renal function. As we know, it is the largest scale study of terlipressin on brain-dead donor.The pathogenesis of brain death is characterized by failure of the autonomic nervous system and defects of several vasoconstrictor systems. Catecholamine deficiency and a transient “autonomic storm” lead to hypotension and diminished end organ perfusion . The goa1 receptor than vasopressin which plays a vasoconstrictive role . There are three major findings of our study. First, terlipressin infusion increases the MAP and SBP, and the increased MAP is accompanied by a significant decrease of HR. This effect remains until the organ procurement. Moreover, the dose of norepinephrine declines steadily and significantly over time. This is important because high-dose norepinephrine (>0.05 μg/kg/min) is associated with increased cardiac graft dysfunction. The extent and duration of catecholamine vasopressor therapy may contribute to the pathogenesis of adverse cardiac events, and should be avoided if possible . Second,Several previous studies examine the efficacy of terlipressin as a pressor agent in solid organ donors with hypotension . In partThere are several limitations of this study. First, because of the retrospective design, there is no suitable control group. Moreover, most of the potential donors are from traffic accidents, relative young age (mean age 38.1 ± 1.7 years), and only two causes of brain death , may not be representative enough. Thus, we cannot be certain that all the observed effects are due to terlipressin. It is possible that the conditions of all 18 patients would have improved spontaneously over time, although we believe this is unlikely. Second, we only examined 18 patients from a single institution, so the results are not necessarily applicable to other patient populations. Confirmation by a study with a much larger and diverse sample is necessary. Third, we focus on the effects of terlipressin in potential organ donors, and do not evaluate graft survival in recipients. Future studies should be extended to organ recipients, and include evaluation of graft function, incidence of primary nonfunctional or delayed recovery of graft function, and survival rates.The major results of this retrospective clinical study are terlipressin infusion could stabilize hemodynamic stability, reduce vasoactive support, and improve renal function in hypotensive brain-dead patients who are potential organ donors. In the future, a further properly powered, randomized, controlled trial is needed to confirm these results.


Lung protective ventilation with low tidal volume (TV) and increased positive end-expiratory pressure (PEEP) can have unfavorable effects on the cardiovascular system. We aimed to investigate whether lung protective ventilation has adverse impact on hemodynamic, renal and hormonal variables.2O (LTV-h.PEEP) or ventilation with a TV of 10 ml/IBW and PEEP of 4 cm H2O (HTV-l.PEEP). Before, during and after surgery, hemodynamic variables were measured, and blood and urine samples were collected. Blood samples were analyzed for plasma concentrations of electrolytes and vasoactive hormones. Urine samples were analyzed for excretions of electrolytes and markers of nephrotoxicity.In this randomized, single-blinded, placebo-controlled study, 24 patients scheduled for robot-assisted radical prostatectomy were included. Patients were equally randomized to receive either ventilation with a TV of 6 ml/IBW and PEEP of 10 cm Hp = 0.033), albumin excretion (p = 0.012) and excretion of epithelial sodium channel (p = 0.045) in the LTV-h.PEEP ventilation group compared to the HTV-l.PEEP ventilation group. In the combined cohort, we found a significant decrease in creatinine clearance  and a significant increase in plasma concentrations of renin, angiotensin II, and aldosterone.Comparable variables were found among the two groups, except for significantly higher postoperative levels of plasma brain natriuretic peptide (Lung protective ventilation was associated with minor adverse hemodynamic and renal effects postoperatively. All patients showed a substantial but transient reduction in renal function accompanied by activation of the renin-angiotensin-aldosterone system.NCT02551341. Registered 13 September 2015.ClinicalTrials, The online version contains supplementary material available at 10.1186/s12871-021-01401-x. Radical prostatectomy is the golden standard for surgical treatment of localized prostate cancer . CompareMoreover, RARP requires pneumoperitoneum and Trendelenburg position in order to access the prostate gland during surgery. The increased intra-abdominal pressure (IAP) associated with pneumoperitoneum results in several hemodynamic alterations, including reduced cardiac output and increased vascular resistance due to compression of the abdominal vasculature and compensatory release of stress hormones . This in2 and lung function postoperatively for patients undergoing RARP, which has been reported previously [The primary purpose of this randomized study was to evaluate the effect of LTV-h.PEEP ventilation versus HTV-l.PEEP ventilation on PaOeviously . Seconda2, estimated glomerular filtration rate < 15 ml/min, history of lung disease requiring treatment, severe heart disease classified as New York Heart Association III or above, acute myocardial infarction within the previous year or neuromuscular disease. Withdrawal criteria were complications during surgery i.e. severe bleeding exceeding 1000 ml, saturation below 95% despite increasing fraction of inspired oxygen (FiO2) to 0.6, plateau pressure persistently above 30 cm H2O, prolonged postoperative procedure due to infection or reoperation, open-surgery conversion or withdrawal of patient consent.From September 2015 to January 2017, we recruited 24 patients at the Department of Urology, Regional hospital of West Jutland, Holstebro, Denmark. Included patients were men aged > 18 years and scheduled for RARP. Exclusion criteria were body mass index > 35 kg/m2O or B) HTV-l.PEEP ventilation: TV of 10 ml/IBW and PEEP of 4 cm H2O. The primary outcomes were PaO2 2 h postoperatively after breathing spontaneously at atmospheric air and postoperative change in lung function, which has been described elsewhere [The study was conducted as a randomized, single-blinded, placebo-controlled study on patients undergoing RARP . Randomilsewhere . In thisBefore surgery all patients received paracetamol 1000 mg, fentanyl 4 microg/kg and a prophylactic dose of cefuroxime 1500 mg and ondansetron 4 mg. Patients were preoxygenated with 100% oxygen for 3 min, after which the anesthesia containing propofol 1–2 mg/kg, remifentanil 2–3 microg/kg and rocuronium 0.5 mg/kg was induced. Anesthesia used for maintenance was propfol 2.2–3.2 microgram/ml, remifentanil 14–20 nanogram/ml and rocuronium 0.2 mg/kg/h. Fluid infusion of Ringer-Acetat 2 ml/kg/hour was maintained during surgery. Any bleeding was replaced with 1–1.5 ml Ringer-Acetat per ml bleeding.2O and a FiO2 of 0.4. When the patients were considered hemodynamic stable, pneumoperitoneum was induced and the ventilation procedure switched according to allocation. In both groups the respiratory rate was regulated to obtain normoventilation . All patients were placed in 30 ° Trendelenburg during the entire operation. IAP was controlled at 12 mmHg during surgery and increased to 20 mmHg at the end of surgery for vesicourethral anastomosis suturing. By the end of surgery, FiO2 was increased to 0.6 and the patient was extubated. After extubation the patient received an oxygen supply of 4 l/min and was transferred to the recovery room. Patients received a suppository of morphine 10 mg, atropinsulfattrituration 5 mg and paraverine 40 mg, and if necessary morphine 5 mg orally or intravenously. Additional anesthetic and surgical procedures have been described previously [During induction of anesthesia all patients were ventilated with a TV of 10 ml/IBW, a PEEP of 4 cm Heviously .Non-invasive blood pressure and HR were measured preoperatively in the outpatient clinic (Measure 1) and postoperatively at day 1 (Measure 4), day 2 (Measure 5), and day 7 (Measure 6) using standard blood pressure measurement equipment. After induction of anesthesia, blood pressure and HR were measured from an arterial line (Infinity Deltra from Dräger) after 1 h in Trendelenburg (Measure 2) and at the end of operation (Measure 3).Blood samples were taken after 30 min’ rest preoperatively at the day of surgery (Blood 1), after 1 h in Trendelenburg perioperatively (Blood 2), at the end of operation (Blood 3), and postoperatively at day 1 (Blood 4), day 2 (Blood 5), and day 7 (Blood 6). P-Na, p-K, p-crea, p-alb, and p-BNP were measured by routine methods at the Department of Clinical Biochemistry. P-renin and p-aldo were measured using immunoradiometric assays, whereas p-angII and p-AVP were measured using radioimmunoassay (RIA) at the University Clinic in Nephrology and Hypertension as previously described . All bloA 24-h urine sample was collected the day before surgery (Urine 1). At the onset of operation, a urinary catheter was inserted to collect urine during surgery (Urine 2), postoperatively until 8.00 am the next morning (Urine 3), and subsequently 24-h to 8.00 am the day after (Urine 4). U-Na, u-K, u-crea and u-alb were measured by routine procedures at the Department of Clinical Biochemistry. U-AQP2 and u-ENaC were determined by RIA and u-NGAL by ELISA at the University Clinic in Nephrology and Hypertension as previously described , 11. AllP values were estimated as two-sided values with a statistical significance level less than 0.05. Data were analyzed according to allocation by intention-to-treat. Single comparisons between groups (LTV-h.PEEP versus HTV-l.PEEP) were analyzed by the unpaired t test and the Mann-Whitney U test for parametric and non-parametric data, respectively. Multiple comparisons between groups were compared for LTV-h.PEEP group versus HTV-l.PEEP group by a general linear model or a generalized linear model for parametric and non-parametric data, respectively. Comparisons between single means or medians from baseline were analyzed by the paired t test for parametric data and the Wilcoxon signed rank test for non-parametric data. Comparisons between several means or medians within groups were analyzed by the ANOVA test or the Friedmann test, respectively. Spearman correlation was used to run univariate correlation analyses for difference in CrCl from baseline to surgery (∆ CrCl). Sample size was determined by power calculation, which has been described previously [Normally distributed data are reported as means with standard deviations (SD); non-normally distributed data are reported as medians with 25–75% quartiles; frequency data are reported as numbers with percentage. eviously . StatistA total of 24 patients were included; none of the patients meet the prior exclusion criteria. Patients were equally randomized with 12 patients in each group. Comparable baseline characteristics were found among the HTV-l.PEEP and LTV-h.PEEP groups  were excluded from the analyses (supplementary). Overall, dBP and HR tended to be lower in the LTV-h.PEEP group compared to the HTV-l.PEEP group, though not statistically significant Table .Table 2Through all measurements in both groups combined, sBP and dBP were significantly lower with a marked decrease during surgery compared to baseline levels. HR decreased during anesthesia, but in reverse increased at day 2 postoperatively. In correlation analyses, increased baseline dBP and decreased baseline pulse pressure were associated with a decline in ∆ CrCl Table  and 2.TCr) at day 7 postoperatively were seen in the LTV-h.PEEP group compared to the HTV-l.PEEP group  and u-ENaC  (Table Cr) increased significantly during surgery but quickly normalized at day 1 postoperatively. Also, u-ENaCCr increased significantly during surgery and at day 1 and 2 postoperatively, whereas the creatinine adjusted u-AQP2 (u-AQP2Cr) showed no considerable change across measurements.In both groups combined, CrCl decreased significantly from 112.0 ml/min at baseline to 45.1 ml/min during surgery, while the patients had increased IAP in Trendelenburg position . In a cohort of patients without acute lung injury they found no beneficial effects of ventilation with low tidal volume (6 mL/kg) compared to high tidal volume (10 mL/kg) . In contCr and UACR increased, indicating renal tubular and glomerular injury, respectively. Also, the minor increase in p-BNP suggested some wall stress of the cardiac myocytes, probably due to the altered ITP despite of the anesthesia-induced decrease in sBP and dBP. In total, these findings suggest considerable hemodynamic, renal, and hormonal alterations associated with the RARP procedure. The mechanisms resulting in these effects are likely multifactorial. The hemodynamic, renal and hormonal outcomes of RARP may be affected by several factors, including the level of IAP, degree of Trendelenburg position, baseline volume status, insufflated CO2, oxidative stress, and other hormonal factors i.e. endothelin and NO [For both cohorts combined, a significant decrease in CrCl associated with a substantial activation of RAAS was seen in relation to RARP. Furthermore, u-NGALn and NO , 16, 17.Few other studies investigated renal and hormonal outcomes for patients undergoing radical prostatectomy. Similar to our study, Kancir et al. found a perioperative decrease in CrCl and an increase in u-alb that remained elevated at day 14 postoperatively for patients undergoing ORP. Also, Kancir et al. reported activation of RAAS, but not as substantial as our findings, which may be explained by the procedure being ORP and not RARP as in our study. In contrast to our study, they reported elevated u-NGAL at discharge but not during surgery . HoweverInterestingly, higher baseline dBP was associated with an aggravated decrease in ∆ CrCl compared to men with lower dBP at baseline. Also, lower baseline pulse pressure was associated with an aggravated decrease in ∆ CrCl, which likely reflects an isolated elevation of the baseline dBP. These findings suggest that the decrease in renal function observed during surgery, at least partly could be explained by hemodynamic mechanisms such as the presence of diastolic hypertension. In contrast to our findings, Jin et al. found similar baseline dBP in patients developing AKI and patients who did not develop AKI after cardiac surgery. Also, they reported nadir values of postoperative diastolic perfusion pressure  to be associated with the development of AKI .A major strength in this study is a systematic blood and urine sample collection before, during and after surgery, which improves the evidence of chronological measures for an entire RARP procedure. Though we drew blood samples 1 week after surgery, urine samples were only collected until day 2 postoperatively and thus no long-term effects were examined.Like other previous studies, we chose a pragmatic approach by using fixed levels of PEEP . AnotherAnother limitation of this study is the small sample size, which may have been inadequate to reveal differences between the two types of ventilation or properly estimate hemodynamic, renal and hormonal variables. Also, our cohort consisted of 24 relatively young and healthy men, who physiologically may compensate sufficiently to the effects of RARP due to better hemodynamic tolerance and renal adjustment. In a cohort of elderly men with more comorbidity the effects of RARP or ventilation strategy may be more prolonged and clinically significant. Also, our findings may only apply to patients with BMI < 35, since obese patients with BMI > 35 in Trendelenburg are more likely to develop pulmonary and extra-pulmonary complications such as renal impairment . We did Our study indicated minor adverse renal and hemodynamic effects of LTV-h.PEEP ventilation compared to HTV-l.PEEP ventilation for patients undergoing RARP. Ventilation strategy did not seem to have hormonal consequences. However, in the combined cohort we found a profound, but transient decrease in CrCl accompanied by RAAS activation when IAP was elevated to 12 mmHg and patients were positioned in 30-degree Trendelenburg.Additional file 1 Table S2. Hemodynamic outcomes – day 7 postoperatively.