IntroductionChronic kidney disease (CKD) is universally considered a public health burden and the majority of cases are found to be diabetic at the time of diagnosis. Renal biopsy is the prime modality for the complete evaluation of renal injuries but is invasive. Duplex Doppler sonography can help to determine renal resistive index (RRI), which is an excellent marker for demonstrating dynamic or structural changes of intrarenal vessels. In this study, we evaluated the intrarenal hemodynamic abnormalities with RRI in diabetic and non-diabetic kidney disease patients. Also, RRI was correlated with the established parameters of renal dysfunction, i.e., estimated glomerular filtration rate (eGFR) and other biochemical parameters.ResultsThere was a significant correlation of RRI with eGFR and serum creatinine indicating its role as a Doppler parameter, which can be used as complementary to biochemical parameters. A remarkable difference was noted in the RRI values between diabetic and non-diabetic groups in the early stages of CKD, revealing its ability to arrive at etiopathogenesis in the early stages. The renal resistive index increases in a sequential pattern and is an indicator of declining renal function.ConclusionsThe addition of sonographic parameters like renal resistive index could help in the complete evaluation of chronic kidney disease in diabetic and non-diabetic groups. A sequential increase in renal resistive index is a better indicator of the progressive worsening of renal function as opposed to an absolute cut-off value. Chronic kidney disease (CKD) is a worldwide health problem, and its prevalence and incidence are increasing. It is defined as renal injury for more than three months with or without a reduction in glomerular filtration rate (GFR), or a decrease in GFR for more than three months with or without kidney damage . There aDuplex Doppler sonography, which simultaneously measures both real-time and pulsed Doppler sonography, has been in clinical use since ages for sonographic detection of renal vessels . The twoHence, the evaluation of intrarenal hemodynamic abnormalities using Doppler sonography could be an alternative to renal biopsy in detecting intrarenal damage. Also, this study may help identify CKD patients in their early stages and prevent them from going into end-stage renal disease.This article was previously presented as an oral paper at the 75th annual conference of the Tamil Nadu and Pondicherry chapter of the Indian Radiological and Imaging Association (IRIA) on 18th December 2022.This was a cross-sectional comparative study conducted on 114 patients (58 diabetic and 56 non-diabetic patients) over a period of 18 months (1st Dec 2020 to 31st May 2022) at the Department of Radiology, JSS Hospital, Mysuru. Patients were selected according to inclusion criteria, which included all CKD patients (with and without diabetes) who had undergone histopathological examination and were referred to the radiology department for ultrasound evaluation of the abdomen. The subjects excluded from the study were - aged less than 18 years, patients with renal artery stenosis/urinary tract obstruction, renal transplant recipients, and those undergoing renal replacement therapy.After obtaining relevant clinical history and consent from the patients, they were subjected to routine ultrasound examination for renal volume calculation, followed by renal Doppler interrogation of the interlobar arteries using a 1-5 MHz convex probe.Evaluation of the interlobar arteries in bilateral kidneys was done in a supine patient using colour Doppler. The sampling gate of Pulsed Doppler mode was placed at the mid portion of the interlobar arteries (2-4 mm of Doppler sample volume and <60 degrees of angle of insonation) at three poles  in each kidney. As a result, velocities and resistance parameters were obtained. The Renal Resistive Index was calculated as the mean of the six readings from both kidneys.Patients' medical records were examined for various parameters like age, systolic blood pressure, urine albumin excretion, and serum creatinine, and used for the calculation of estimated GFR (eGFR). The patients were stratified into various stages of CKD based on eGFR. The trend of the Renal Resistive Index in varied stages of CKD was evaluated, with a further correlation of the Renal Resistive Index with other parameters such as age, urine albumin excretion, serum creatinine, and systolic blood pressure.Statistical analysisThe lab values of renal function test (RFT) were obtained and eGFR was calculated by the CKD-EPI (CKD Epidemiology Collaboration) formula:GFR (mL/min) = 141 x minα x max-1.209 x 0.993 Age x 1.018 x 1.159(if black)Where, K = 0.7 if female, 0.9 if male; α = -0.329 if female, -0.411 if male; min = the minimum of S Cr/K or 1; max = the maximum of S Cr/K or 1.The renal resistive index was measured by duplex Doppler.Analysis was performed using SPSS version 22  after entering the data into Microsoft Excel . Demographic characteristics and clinical parameters such as age, systolic blood pressure, serum creatinine, and urine albumin were represented using mean, standard deviation, and percentages. The comparison of RRI values between diabetic and non-diabetic kidney disease patients was done using the Independent sample t-test. The comparison of RRI values within diabetic and non-diabetic kidney disease patients across various stages of CKD was done using Analysis of Variance (ANOVA). The correlation of different categories of age, urine albumin, serum creatinine, systolic blood pressure, and eGFR with RRI was done using ANOVA. The commencement of hemodialysis was compared between the diabetic and non-diabetic groups of patients using ANOVA. Receiver operating characteristic (ROC) analysis was performed to determine a cut-off of RRI value to distinguish stage IV and above stages of CKD from the lower stages.In our study, there was a slight male preponderance, with 62% of them being males and 38% being females. On dividing the patients into four age groups - 18-30 years (group 1), 31-45 years (group 2), 46-60 years (group 3), and above 60 years (group 4) - the majority of them were in the age group of 31-45 years (39%). Diabetic patients ranged from ages 24 to 73 years and non-diabetic patients ranged from 18 to 67 years. The mean age for diabetic patients (51 years) was significantly higher compared to non-diabetic patients (35 years) with a p-value of 0.001.Stratification of patients into various stages of CKD showed that diabetic patients were significantly higher in the advanced stages compared to non-diabetic patients (p=0.007).Subjects with diabetes showed significantly higher RRI values (mean - 0.72) than those without diabetes (mean - 0.65) (p=0.001). However, renal volume did not show any association with the presence/absence of diabetes (p=0.105).The clinical and lab parameters  were divided into various categories and were correlated with RRI. The patients were classified into three groups based on RRI - normal RRI group (RRI <0.65), borderline RRI group (0.65 ≤ RRI < 0.7), and high RRI group (RRI ≥0.7). RRI was seen to be significantly associated with serum creatinine p=0.001) and eGFR (p=0.001), however, it was not associated with patient age, systolic blood pressure, and urine albumin excretion. There was a remarkable negative correlation between RRI and eGFR in CKD patients, signifying that RRI progressively increased from the lower to the higher stages of CKD  Table .In order to improve renal survival, hemodialysis was started in a few of the patients with end-stage renal disease. Among them, the diabetic patients’ proportion was significantly higher compared to non-diabetic (p=0.003). Of the 28 patients who were started on hemodialysis, four belonged to stage IV and 24 to stage V of CKD. Hence, ROC analysis was performed to determine a cut-off of RRI values to distinguish stage IV and above stages of CKD from the lower stages. Using a cut-off of 0.655 for RRI, the area under the ROC curve to distinguish ≥IV stages of CKD from lower stages was 0.645 showing poor discrimination, with a sensitivity and specificity of 95% and 55%, respectively  in ≥IV stages of CKD had a resistive index value of more than 0.655. However, we had 26 patients who were <IV stage of CKD and had a resistive index value of more than 0.655. The rest of the 37 patients of <IV stage of CKD had a resistive index less than 0.655 Figures , 5, 6.Chronic kidney disease is universally considered a public health burden with increasing prevalence and incidence. It involves a range of pathophysiologic processes and is associated with several risk factors such as diabetes, hypertension, obesity, tobacco smoking, and dyslipidemia. Diabetes mellitus is the leading cause of CKD worldwide with diabetic nephropathy being a progressive kidney disease caused by microangiopathy of capillaries in the kidney glomeruli. There are various risk factors associated with Type 2 diabetes mellitus (DM) which include the patient’s age, duration of diabetes, systolic blood pressure, glycosylated haemoglobin (HbA1c), and renal volume. Girach et al performed a study and concluded that the strongest risk factors for DN are glycemic control and duration of diabetes. The modifiable risk factors were hypertension, hyperlipidemia, and smoking, and the unmodifiable risk factors were age at the onset of diabetes and genetic factors . AnothereGFR has been in use for renal function screening since ages, however, it is difficult to assess the pathogenesis of CKD and predict the renal prognosis using only eGFR. Kawai T et al  in theirAdditionally, in our study, RRI was significantly higher in diabetic patients compared to non-diabetics. So diabetes can accelerate vascular damage and RRI can detect this change more sensitively than eGFR. Mean RRI was significantly higher in diabetic patients in stages II and III of CKD, in comparison with those affected by other diseases, with an equivalent GFR. Whereas no significant difference was noted in stages I, IV and V. Greater proportion of patients in stage I of CKD in our study were non-diabetic (13 out of 19), as fewer stage-I diabetic patients were referred for renal biopsy. This may be the reason for no significant difference in stage I patients. Also, the influence of advanced loco-regional alterations  on RRI exceeds systemic factors like pulse pressure and pulse wave velocity with decreasing GFR. Hence, this validates the need for additional incorporation of RRI in the routine protocol to assess the etiopathogenesis of CKD in the early stages. However, renal biopsy will remain the prime modality to assess the complete pathology and alterations of the diseased kidney.Gopalakrishnan SS et al  had showKawai et al  had alsoHowever, our study was consistent with the previous study on the relationship between RRI and systolic blood pressure. No significant correlation was demonstrated, which could be due to the increased number of patients who were subjected to medical treatment like anti-hypertensives at the time of examination. In the later stages of CKD, atherosclerotic arterial wall stiffening pursues, which reduces the elasticity and diastolic blood pressure with a rise in pulse pressure .In this study, no relationship was established between renal volume and the presence of diabetes. Mancini et al  in theirDialysis and renal transplant are effective means to treat end-stage nephropathy and help to replace the functions of kidneys when they no longer work. Diabetic nephropathy can cause a serious increase in the number of end-stage renal disease patients, requiring hemodialysis in their advanced stages. Chen Q et al  reportedAn attempt was done to derive a cut-off value of RRI to distinguish stage IV and above stages of CKD from the lower stages. The results attained were highly sensitive with poor specificity (RRI cut off = 0.655), noting that it could be used as a screening tool. However, the relationship between RRI and the severity of CKD may not be highly robust, as the area under the ROC curve was <0.7. Hence, such a tool could be used to track renal damage progression, but with poor discrimination between the advanced stages (stage IV and V) from early CKD stages.LimitationsConfounding factors such as age, gender, muscle mass, and BMI were not matched in the study. Most of the patients had already been under medical treatment for hypertension, diabetes, and dyslipidemia at the time of investigation, which would have affected various parameters. Baseline RRI values were not taken for the patients at the initial stages of CKD and a prospective continuous evaluation with serial RRI would have helped more in predicting the outcome.The renal resistive index could be considered a marker of renal function in both diabetic and non-diabetic kidney disease, with an ability to arrive at etiopathogenesis in the early stages. The resistive index correlated well with eGFR and serum creatinine indicating its role as a Doppler parameter, which can be used as complementary to biochemical parameters. With the increasing prevalence of diabetes, diabetic nephropathy remains the prime cause for the commencement of renal replacement therapy. Even though RRI could be used as a screening tool for kidney disease, it does not provide a definite cut-off for efficient discrimination between early and advanced CKD stages. As there is individual diversity with regard to baseline RRI, a sequential increase in RRI is a better sign of disease progression than an absolute value.


Although the assessed intraoperative heart rates (HRs) were also higher , there was no correlation found between the MPG and the HR, or any other parameter of interest, at either time-point. In a further analysis, a moderate to strong correlation was observed in the linear relationship between the CI and the MPG . During the in-hospital follow-up period, no patients died or required an intervention due to LAVV stenosis. Conclusions: The Doppler-based quantification of diastolic transvalvular LAVV mean pressure gradients using intraoperative transesophageal echocardiography seems to be prone to overestimation due to altered hemodynamics immediately after an AVSD repair. Thus, the current hemodynamic state should be taken into consideration during the intraoperative interpretation of these gradients.Background: Left atrioventricular valve (LAVV) stenosis following an atrioventricular septal defect (AVSD) repair is a rare but potentially life-threatening complication. While echocardiographic quantification of diastolic transvalvular pressure gradients is paramount in the evaluation of a newly corrected valve function, it is hypothesized that these measured gradients are overestimated immediately following a cardiopulmonary bypass (CPB) due to the altered hemodynamics when compared to postoperative valve assessments using awake transthoracic echocardiography (TTE) upon recovery after surgery. Methods: Out of the 72 patients screened for inclusion at a tertiary center, 39 patients undergoing an AVSD repair with both intraoperative transesophageal echocardiograms  and an awake TTE  were retrospectively selected. The mean (MPGs) and peak pressure gradients (PPGs) were quantified using a Doppler echocardiography and other measures of interest were recorded , left ventricular ejection fraction, blood pressures and airway pressures). The variables were analyzed using the paired Student’s t-tests and Spearman’s correlation coefficients. Results: The MPGs were significantly higher in the intraoperative measurements when compared to the awake TTE (3.0 ± 1.2 vs. 2.3 ± 1.1 mmHg;  An atrioventricular septal defect (AVSD) is a rare congenital heart anomaly with potentially severe limitations for physical capacity, which is often associated with genetic disorders, other cardiac defects and extracardiac manifestations . As patiThis study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the University of Tuebingen (project number # IRB 773/2019BO2 with an amendment on 29 April 2022). According to German privacy regulations, anonymous retrospective analysis, including the handling of clinically acquired data does not require informed consent from individual patients. For this single-center retrospective cohort study, patients undergoing a surgical AVSD repair, including atrial and ventricular cleft closure between May 2015 and June 2021 were identified within the digital clinical database system. Only patients with both intraoperative TEEs and pre-discharge TTEs, allowing for the quantification of the below mentioned echocardiographic measures, were included in the final analysis.General anesthesia with endotracheal intubation and positive pressure ventilation were applied either as total intravenous anesthesia (using a combination of midazolam and fentanyl) or balanced anesthesia (with sevoflurane and sufentanil). All infants received advanced hemodynamic monitoring with arterial cannulation and central venous pressure monitoring. Surgical repair of the AVSD using the double patch technique and cleft closure was routinely performed via sternotomy with the use of CPB and aortic cross clamping. Prior to the completion of the surgery, an appropriate minimum LAVV orifice area was routinely evaluated using a Boulito probe standardized to the patients’ body surface area (BSA), and the water probe method was used to exclude any significant LAVV regurgitation.Intraoperative TEE was performed after separation from the CPB and the establishment of a steady hemodynamic state by specially trained cardiac anesthesiologists and congenital cardiologists using commercially available probes . Postoperative echocardiography was performed around the day of discharge by congenital cardiologists using commercially available probes . All echocardiographic studies were stored in the institutional digital database system  and the offline measurements were performed within the software’s interface.At least two tracings of the diastolic pulsed-wave or continuous-wave Doppler spectra over the LAVV in the apical/mid-esophageal four-chamber view yielded the following: mean pressure gradient (MPG), peak pressure gradient (PPG) and velocity-time integral (VTI). At the time of the measurements, the heart rate (HR) was recorded. With the help of the color-coded Doppler recordings in the same view, the diameter of the LAVV orifice was measured. A non-invasive surrogate of the cardiac output (CO) was calculated according to the following formula: CO [L/min) = (LAVV diameter [mm]/2)² × 3.141 × VTI [mm] × HR/1,000,000. The cardiac index (CI) was calculated as follows: CI [L/min/m²] = CO [L/min]/BSA [m²]. The left ventricular volumes and ejection fractions (LVEF) were quantified using the uniplane or biplane Simpson’s method.0.5. The exact surgical intervention, CPB times and intraoperative hemodynamics were extracted from the clinical database, including the mean arterial pressure (MAP), central venous pressure (CVP) and airway pressures, at the time of the intraoperative TEE. The Vasoactive-Inotropic Score (VIS) was calculated as previously described  = (height [cm] × weight [kg]/3600)escribed .The follow-up data included the postoperative length of stay in the intensive care unit and the hospital, the duration of the postoperative mechanical ventilation and any adverse events within the primary hospital stay. Long-term follow-up data was recorded if the patients were admitted to our center within the study period.p-values of < 0.05 were regarded as significant for most analyses. For extensive multiple testing (Spearman’s correlation matrices), the significance level α was corrected according to the Bonferroni method. In the figures, significant p-values are highlighted as * p < 0.05, ** p < 0.01 and *** p < 0.001. Prism  and MedCalc  were used for statistical calculations and data presentation.Normally distributed continuous variables are presented as the mean ± standard deviation, while nonnormally distributed continuous variables are presented as the median (interquartile range). The categorical variables are reported as absolute numbers and percentages. Comparisons of the parameters between the two echocardiographic time-points were performed using the paired Student’s t-tests for normally distributed continuous variables, Wilcoxon matched-pairs signed rank tests for nonnormally distributed continuous variables and Chi-square tests to compare the proportions. Spearman’s correlation coefficient (r) was used to assess the degree of linear relationship between two non-normally distributed variables and Pearson’s r was used if both samples were normally distributed. The degree of correlation was defined as follows: “none” for r from 0 to ±0.2, “weak” for r from ±0.2 to ±0.4, “moderate” for r from ±0.4 to ±0.6, “strong” for r from ±0.6 to ±0.8 and “very strong” for r from ±0.8 to ±1. Within the study period, 72 patients underwent an AVSD repair at our center. Among this group of patients, 29 (40%) patients did not receive Doppler measurements over the LAVV prior to discharge and four (6%) patients’ image quality was insufficient in either of the performed echocardiograms, resulting in the inclusion of 39 patients in the final analysis. Baseline demographic and clinical characteristics are displayed in p < 0.01; p < 0.001; p < 0.001) between the non-invasively determined CI and the LAVV MPG immediately after weaning from the CPB , while the remaining patients were analyzed with the continuous-wave Doppler. The Doppler measurements were compared concomitantly .  the CPB A, while The data collected on the postoperative course of the studied patients is summarized in The presented study investigated the relationship between the diastolic LAVV transvalvular pressure gradients, quantified using Doppler measurements, in intraoperative TEE studies after weaning from a CPB and postoperative TTE studies. As hypothesized, LAVV MPGs were significantly overestimated intraoperatively when compared to the awake postoperative examinations prior to discharge. The MPGs showed a linear correlation to a non-invasive surrogate of the CI, suggesting a dependency on the current hemodynamic condition after a CPB. Interestingly, this relationship was not observed in the awake TTE studies and most hemodynamic measures did not further differ between the two time-points. While the patients’ HRs differed significantly between the two examinations, no correlation between the LAVV transvalvular pressure gradients and the HRs were observed.Depending on the various types of AVSDs, the LAVV often requires reconstruction during AVSD surgery . LAVV reThe choice of the acoustic window for an echocardiographic examination of the LAVV is mostly determined by the diagnostic time-point, the clinical environment and patient-specific factors, e.g., inaccessibility of the surgical site or insufficient transthoracic ultrasound quality. Whereas TTE is routinely used in awake patients outside the operating room, the TEE is performed intraoperatively or in sedated patients in the pediatric intensive care unit. The purpose of intraoperative TEE is mainly the detection of acute complications, the evaluation of the surgical result and the identification of additional surgical revision needed , while aWhile conducting an acute evaluation of the surgical result after weaning from a CPB using an intraoperative TEE, there is a fine line between confirming a successful AVSD repair and suggesting an immediate need for an additional surgical correction. While residual shunts are routinely quantified by color and pulsed-waved Doppler measurements, the reconstructed LAVV should be evaluated morphologically and functionally in multiple views . To ensuThe translation of our results to the general population is limited by the retrospective study design and the small number of included patients. Furthermore, patients with dramatically increased postoperative LAVV pressure gradients are underrepresented in our cohort. Due to the long study period, improvements in perioperative management and surgical techniques are possible and might lead to skewed observations. Owing to the retrospective data acquisition, many important measures were not systematically available–e.g., invasively quantified transvalvular gradients, invasively determined cardiac output or head-to-head comparisons of TTE- and TEE-derived parameters–which hinders the interpretation of the obtained results. The comparability of LV volumes and LVEF between TEE and TEE might be limited in pediatric patients. The surrogates of the CO and the CI used in this analysis are only simplified surrogates of the invasively determined parameters derived from gold-standard right-heart catheterization. Using only the LAVV orifice diameters acquired from a single plane might result in inadequate representation of the complex anatomy of the LAVV orifice area and lead to distinct variations between patients. While three-dimensional echocardiography is superior for the calculation of valve orifices, three-dimensional echocardiography data were not available in our retrospectively recruited cohort. Furthermore, three-dimensional transesophageal probes do not exist for neonates and infants. Lastly, long-term follow-up data was sparse.Stenosis of the LAVV following the surgical repair of AVSD is a rare complication. In the presented investigation, the diastolic Doppler-quantified MPGs over the LAVV in an intraoperative TEE immediately after weaning from a CPB were significantly overestimated when compared to the gold-standard awake TTE prior to a hospital discharge. The LAVV MPGs showed a linear correlation to non-invasive surrogate measures of the CI. According to these findings, the current hemodynamic state should be taken into account during the interpretation of the LAAV gradients.


Background: It is well-accepted that antihypertensive therapy is the cornerstone of treatment for abdominal aortic aneurysm (AAA) patients with hypertension. Direct-acting vasodilators were used in the treatment of hypertension by directly relaxing vascular smooth muscle but may have destructive effects on the aortic wall by activating the renin–angiotensin system axis. Their roles in AAA disease remain to be elucidated. In this study, we used hydralazine and minoxidil, two classical direct-acting vasodilators, to investigate their influence and potential mechanisms on AAA disease.Methods and results: In this study, we investigated the plasma renin level and plasma renin activity in AAA patients. Simultaneously, age and gender ratio-matched patients diagnosed with peripheral artery disease and varicose veins were selected as the control group using a ratio of 1:1:1. Our regression analysis suggested both the plasma renin level and plasma renin activity are positively associated with AAA development. In view of the well-established relationship between direct-acting vasodilators and increased plasma renin concentration, we established a porcine pancreatic elastase-infused AAA mouse model, followed by oral administration of hydralazine (250 mg/L) and minoxidil (120 mg/L) to investigate effects of direct-acting vasodilators on AAA disease. Our results suggested both hydralazine and minoxidil promoted the progression of AAA with increased aortic degeneration. Mechanistically, the vasodilators aggravated aortic inflammation by increased leukocyte infiltration and inflammatory cytokine secretion.Conclusion and relevance: The plasma renin level and plasma renin activity are positively associated with AAA development. Direct vasodilators aggravated experimental AAA progression, which raised cautionary concerns about their applications in AAA disease. Abdominal aortic aneurysm (AAA) is the dilation of the abdominal aorta 1.5 times its original size, generally more than 3 cm, with structural disruptions of the aortic vasculature . The incArterial hypertension is an important population-attributable risk factor for AAA, which is linked to an increased risk of cardiovascular events and adverse prognosis, following AAA . PreviouDirect-acting vasodilators are a heterogeneous group of drugs, which can directly dilate peripheral arterioles and lower blood pressure, and are generally used in systemic hypertension, especially in patients with refractory hypertension, stage III hypertension, or renal dysfunction . DespiteIn the study, we investigated the relationship between the plasma renin level (PRL) and plasma renin activity (PRA) with AAA in patients using a case–control design, which suggested PRL and PRA are positively associated with AAA development. Given that direct vasodilators may increase the PRL and PRA, we explored the effect of direct vasodilators on AAA disease using hydralazine and minoxidil. Our results suggested direct vasodilators aggravated experimental AAA progression, raising cautionary concerns about their applications on arterial disease and AAA disease.Patients diagnosed with AAA were selected for pre-onset PRL and PRA determination according to the disease diagnosis code of the 10th edition of the International Classification of Diseases (ICD) as the case group. AAA is defined as 50% dilation of the abdominal aorta, generally more than 3 cm of normal . At the Given the possibility of increased plasma renin levels in arterial disease , we inclWe obtained patient data from the hospital electronic medical database. The following general, clinical, and laboratory data were collected: general data , anthropometric data , biochemical measurements , comorbidities , and medication history .After approval of Xiangya Hospital Institutes’ Review Board and Ethics Committee of the Xiangya Hospital, Central South University, blood collection was carried out at dawn of the second day of patients’ admission to ensure the measurements of recumbent position PRL and PRA are comparable. Then, the blood samples were transported to and evaluated at the clinical laboratory of Xiangya Hospital immediately.ad libitum access to food and water. Calculation of the sample size was determined by power analysis, as previously reported , hydralazine group (n = 9), and minoxidil group (n = 13), and we declared no excluding animals. Hydralazine (250 mg/L) and minoxidil (120 mg/L) were administered via drinking water and were replaced every other day. The dosage, time points, and route of administration were chosen based on the prior literature  for determining the internal diameter or using a digital camera for the external diameter. Measurements of the aortic extra-diameter were performed before and after perfusion on day 0, and before euthanasia on day 14. Measurements of the aortic intro-diameter were performed on days 0 and 14 by investigators blinded to the group assignment.AAA was monitored via serial transabdominal high-frequency ultrasound , CD68+ macrophages , CD31+ mural vessels , and MMP9 . The same concentration of rabbit control IgG  serves as the negative control.Mice were euthanized 14 days after PPE infusion. Aortae were harvested, fixed in 4% paraformaldehyde, embedded in paraffin, and horizontally cut into sections. For histological analyses, hematoxylin–eosin (H&E) staining, Masson, elastic Van Gieson (EVG) staining, and a two-step standard immunoperoxidase procedure for immunohistochemistry were conducted to identify CD3GTGCTATGTTGCTCTAGACTTCG and reverse primer: ATGCCACAGGATTCCATACC; NOS2, forward primer: GTTCTCAGCCCAACAATACAAGA and reverse primer: GTGGACGGGTCGATGTCAC; CCL2, forward primer: TAAAAACCTGGATCGGAACCAAA and reverse primer: GCATTAGCTTCACATTTACGGGT; IFN-γ, forward primer: CAGCAACAGCAAGGCGAAAAAGG and reverse primer: TTTCCGCTTCCTGAGGCTGGAT; IL-1β, forward primer: GAAATGCCACCTTTTGACAGTG and reverse primer: TGGATGCTCTCATCAGGACAG.Mice were euthanized 14 days after PPE infusion. The total RNA of aortae was extracted using the TRIzol reagent , according to the manufacturer’s instruction. A measure of 500 nanograms of total RNA was used for reverse transcription using a PrimeScript RT Reagent Kit (TaKaRa). Quantitative RT-PCR on a real-time PCR system (Applied Biosystems) was performed using SYBR Premix Ex Taq qRT-PCR assays (TaKaRa). The Ct value of mRNA was normalized to GAPDH, and the fold change was calculated using the ΔΔCt method. The primer sequences for genes are listed as follows: ACTB, forward primer: +, and serum Na+ among the three groups, and the independent sample t-test was used between two groups. If the data did not meet the normal distribution, the quantile-quantile graph was used to check its distribution. If the data were located near the diagonal, there was an approximate normal distribution between the groups . Non-parametric tests  were provided to compare the difference among ranked data and continuous variables that do not satisfy normal distribution or homogeneity of variance . We used the χ2 analysis (χ2 test) to compare categorical variables, frequencies, and proportions . Multivariate logistic regression analysis was used to evaluate the relationship between the PRL, PRA and AAA among the three groups, and binary logistic regression analysis was used for two groups. The multivariate linear regression analysis was used to test the collinearity between variables. Odds ratio and 95% CI were reported. A two-tailed p-value of 0.05 is considered significant. SPSS 26.0 version was used for data management and analysis.Continuous variables are expressed as mean values ± standard deviation, unless otherwise stated. For the duration of hypertension, triglyceride, alanine aminotransferase, aspartate aminotransferase, serum creatinine, serum uric acid, PRL, and PRA, the medians in the 25th and 75th percentile ranges are provided because they do not satisfy the normal distribution. One- or Two-way ANOVA was used to compare the normal distribution of continuous variables including age, body mass index, systolic blood pressure, diastolic blood pressure, pulse rate, AAA diameter (for both humans and mice), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, serum Kp = 0.014) showed statistically significant differences between AAA and other two groups when compared in a pairwise manner (p = 0.031), the coronary heart disease composition ratio , and systolic blood pressure  were observed when comparing the PAD group with the VV group  versus 9.29 (8.42∼20.16) versus 6.17 (4.21∼9.24), AAA versus PAD versus VV pg/ml, and p < 0.001] than the PAD and VV groups. Similarly, compared to the non-AAA group, the AAA group also showed a higher PRL  and higher PRA  , and p = 0.041] compared with PAD  was performed between the PRL and PRA, with the piece of evidence that the Spearman correlation coefficient of the PRL and PRA is 0.883 . Therefowith PAD . Similar with VV . Similar with VV . Surpris with VV .p = 0.007] for the PRL and 1.070  for PRA, and adjusted OR of 1.100  for PRL and 1.075  for PRA in model 1 and 1.102  for PRL and 1.088  for PRA in model 2, respectively , and ectively .γ = 0.529; p < 0.001) and PRA   and PRA .As PAD and AAA shared similar etiology and pathological mechanisms, the elevated risk of AAA was reported in PAD patients . Thus, a= 0.021) . HoweverHydralazine and minoxidil, the most commonly prescribed direct-acting vasodilators in hypertension , were sep < 0.001 for systolic blood pressure 82.45 ± 22.17 versus 103.06 ± 10.45 mmHg and p = 0.007 for diastolic blood pressure) on day 7, this significant difference disappeared on day 14  .Monitoring external diameters using a digital camera, our results suggested AAA diameters in the three groups were comparable after PPE infusion but increased more rapidly in hydrazine and minoxidil groups than those in the vehicle group  . These iNext, histological analyses demonstrated that both hydrazine and minoxidil promoted inflammatory cell infiltration and deposited collagen fibers compared to the vehicle group in H&E and Masson staining . Further+ T cells, CD68+ macrophages, and MMP9  channel-opening agent in the vascular smooth muscle cells, minoxidil allows potassium efflux and reduces calcium influx, which ultimately relaxes vascular smooth muscle cells, dilates the aortic lumen, and lowers blood pressure  in Ang II-infused mice, although the differences were not significant (Despite the lack of evidence that hypertension is linked to AAA progression and remains a potential risk factor for the development and prognosis of AAA . Thus, ipressure . In our nificant . In addinificant . Other dnificant . Consistnificant . Howevernificant . These cnificant . Therefo+ channels in vascular smooth muscle cells in the aorta. This phenomenon was also observed in another ATP-dependent K+ channel opener, levcromakalim, which attenuated vascular relaxation in NO-donors after 2 weeks of administration in rats (It is worth mentioning that as a direct vasodilator, minoxidil has a direct antihypertensive effect when initially administered. However, long-term administration can weaken this hypotensive effect, which is attributed to the desensitization of K in rats . Now, mi in rats . Adverse in rats . AlthougThe risk factors for AAA are mainly old age, male gender, hypertension, and hyperlipidemia, which are consistent with the risk factors for PAD . A prospNonetheless, this study has several limitations. First, a small sample size was a major drawback of the present study. A more comprehensive analysis is needed to determine the relationship between renin and AAA disease. Second, direct-acting vasodilators are a heterogeneous group of drugs. Although hydralazine and minoxidil are the most commonly prescribed direct vasodilators, they may not be representative of all vasodilators in the study. More retrospective studies are needed to assess their safety in vascular disease. Therefore, future studies with larger samples and longitudinal measurements of people taking vasodilators are warranted to overcome the limitations to our study and establish cause-and-effect relationships.PRL and PRA are positively associated with AAA development. Hydralazine and minoxidil promote the progression of AAA in a mouse model, which might be associated with increased PRL and PRA. Direct-acting vasodilators should be used with caution in patients with AAA, as well as in those at high risk for AAA disease and other artery diseases.


Deep vein thrombosis (DVT) has been considered as a frequent and serious consequence of intertrochanteric femoral fractures in the elderly. Several negative repercussions of DVT can be considerably mitigated by its timely recognition and treatment. The current work was aimed at exploring the factors independently predicting DVT among cases suffering from intertrochanteric femoral fractures and validate their predictive usefulness in diagnosing DVT.Between April 2017 and July 2022, clinical information from 209 cases showing preoperative DVT for femoral intertrochanteric fractures were retrospectively evaluated. In patients with femoral intertrochanteric fractures, logistic regression analysis with a backward stepwise method was adopted for detecting independent predictors for the diagnosis of preoperative DVT. Using multivariate logistic regression, a nomogram prediction model was developed and verified with the testing group.P = 0.042), neutrophil/lymphocyte ratio (NLR) , and systemic immune-inflammation index (SII)  were independent predictors for DVT before surgery among cases developing intertrochanteric femoral fracture. AUC values were 0.862 and 0.767 for training and testing groups, separately, while their mean errors in the calibration curve were 0.027 and 0.038 separately. Decision curve analysis (DCA) curve revealed a high value of clinical application for both groups.According to multivariate logistic regression model, body mass index (BMI) (OR 0.79, 95% CI 0.63–0.99, Upon admission, BMI, NLR, and SII are independent predictors of DVT before surgery among cases developing intertrochanteric femoral fractures. Additionally, the nomogram based on the BMI, NLR, and SII can assist clinicians in determining if preventive and symptomatic therapies are required to improve DVT prognosis and reduce its associated mortality.The online version contains supplementary material available at 10.1186/s13018-023-03966-4. Intertrochanteric femoral fracture is a type of hip fracture that accounts for 63% of all hip fractures. It is the most commonly seen fracture in the elderly, accounting for 10–15% of all fractures in the elderly population . DVT is Because of its non-invasive nature and good reproducibility, ultrasound Doppler is most commonly used for diagnosing lower limb DVT . Color DApart from those three major factors in the pathophysiology of thrombus formation, namely, stasis or blood flow changes, blood hypercoagulation, and vascular wall injury, inflammatory molecules, and immune cells are now considered to be major contributors to thrombosis. Budnik and Brill detailed immune factors’ effects on DVT pathogenesis in their review . CollingTherefore, the present study aimed to find independent risk factors for thrombosis in intertrochanteric femoral fractures by integrating the risk factors of thrombosis and novel immune inflammatory indices. On this basis, a prediction model was built to assess the DVT event among cases suffering from intertrochanteric femoral fractures simply and effectively.This study is a retrospective one, with the research questions and assessments being predetermined and not determined by the patient’s priorities, experience, and preferences. Ethics Committee of First People's Hospital of Huizhou reviewed this work and determined that it would not harm the patient or present any potential risk factors. Therefore, no patient involvement or informed consent was required. Moreover, the findings of the study will be reported to the participants and used in clinical trials to observe any potential clinical benefits. The interventions of this study are examinations which are already available to the patient during their hospitalization and do not require any additional cost to the patient.In this retrospective study, patients whose intertrochanteric femoral fractures were diagnosed in the orthopedic department of Huizhou First Hospital during April 2017–July 2022 were included. Patients conforming to criteria below were included: (1) cases hospitalized within 5 days (120 h) of disease inception with a definitive radiographic fracture diagnosis, and (2) those aged over > 60 years . Cases conforming to criteria below were eliminated: (1) patients having insufficient information including medical records and preoperative vascular color doppler ultrasonography results ; (2) those aged under 60 years ; (3) patients with the following conditions: multiple fractures diagnosed at this admission, pathological fracture diagnosed at this admission, previous and recent anticoagulant use, inflammatory diseases, unclear diagnosis of infection at admission, and anti-infective drug use . Ultimately, a sum of 209 patients was incorporated into our research.The current work was performed following the Helsinki Declaration and was approved by Huizhou First Hospital's ethical committee . Based on the retrospective character of the investigation, no written informed consent was required. With the aim of protecting patients’ privacy, the identifying information of those who took part in this study was rendered anonymous.9/L and (130–175) × 109/L for women and men, respectively, for RBC count, (4.3–5.8) × 109/L, for WBC count, (2–7) × 109/L, for NC count, (2–7) × 109/L, for LYM count, (0.8–3.5) × 109/L, for MNC count, (0.1–0.6) × 109/L, for PLT count, (100–300) × 109/L, for FIB, (1.8–3.5) g/L, for TT, (14–21) s, for PT–INR, (0.85–1.20), for APTT, (22.5–34.0) s, for D-dimer, (0–0.5) mg/L, and PT, (9.8–13.2) s. Values outside the above-mentioned normal ranges were considered to be abnormal. The correlation inflammatory-immune index was evaluated by collecting PLT, NC, LYM, and MNC data during routine blood investigations performed at the emergency department or right after admission. The formulae used were:This work gathered basic clinical information from each case, containing their age, sex, fracture site, time of injury to the hospital , diastolic blood pressure (DBP), systolic blood pressure (SBP), temperature (the first measurement on admission), breaths per minute , pulse (the first measurement on admission), and a medical history of hypertension, diabetes, smoking, and alcoholism. We determined hypertension with the past hypertension history and SBP/DBP of 140/90 mmHg on admission, whereas diabetic with having the past diabetes history, random blood glucose of 11.1 mmol/L on admission and fasting blood glucose (FBG) of 7 mmol/L. Patients' routine blood, hemostatic function, and other serological test results acquired at emergency department or in one day after admission were collected. The normal range for hemoglobin count was between (115–150) × 10NLR = NC/LYM; PLR = PLT/LYM; MLR = MNC/LYM; and SII = PLT × NC/LYM.The event of DVT in the elderly with intertrochanteric femoral fracture was considered the outcome event in this study. The positive result was characterized as DVT, whereas the negative outcome was defined as No DVT. “Thrombus” was used as a label to record whether patients with intertrochanteric femoral fractures developed a DVT, which was recorded according to preoprerative color Doppler ultrasonography. The following were the diagnostic criteria for DVT in color Doppler ultrasonography: 1. Abnormal echoes. 2. The vein beneath the ultrasound probe at the fracture site should not have been compressed shut. 3. The venous thrombus section should have shown no clear indication of blood flow. 4. A reduction in the should have occurred afflicted limb’s blood flow and vascular width. A skilled sonographer used color doppler ultrasonography to evaluate blood vessels in the lower extremities and provided a diagnostic report to identify DVT. The bilateral common femoral vein, superficial/deep femoral vein, popliteal vein, anterior/posterior tibial vein, as well as peroneal vein were all tested according to the aim of the present study. Because of the limited clinical relevance of superficial or myenteric veins, the present work did not include superficial vein thrombi.Before data analysis, we applied R studio version 4.0.3  to randomly sample the patients into a 7:3 ratio of training group (n = 147) and testing group (n = 62). SPSS 26  was adopted in assessing data for normalcy. Normally-distributed continuous variables were represented by mean and standard deviation and compared by t-test, while abnormally-distributed ones were represented by median and quartile and compared by rank sum test. Numeration variables were represented by percentage n (%) for comparisons among groups by chi-square test or Fisher's test when over 1/5 of cells in contingency table had the predicted frequency of less than 5. To determine the comparability of both groups and to guarantee our prediction model viability, we compared the baseline data of the both groups.P < 0.05) from the univariate analysis were incorporated into multivariate regression, using a backward stepwise strategy to find independent predictors of DVT. P < 0.05 indicated statistical significance for the two-sided tests. A nomogram prediction model was built utilizing age and significant variables found in the multivariate regression and displayed using R studio (version 4.0.3). The predictive model nomogram effectiveness was evaluated by ROC curve and area under the curve (AUC). The calibration curve and mean absolute error were employed with the purpose of assessing the nomogram’s goodness of fit. The clinical effects of the nomogram were evaluated based on decision curve analysis (DCA) using the high-risk threshold.We further classified training group into DVT (n = 28) or No DVT group (n = 119) based on the outcome events. Rank sum test, t-test, Fisher’s test and chi-square test were adopted to compare data between two groups. Two sets of violin plots of deference data were created with R studio (version 4.0.3), which included BMI, WBC, NC, LYM, NLR, PLR, and SII. We drew ROC curves for assessing predictive power of the deference data for DVT. Furthermore, based on these cutoff values, high and low groups within each variable were established. In order to determine the variables connected to the outcome event, univariate logistic regression was initially performed, and odds ratios (ORs) together with associated 95% confidence intervals (CIs) were determined. Significant variables  and 46 women (74.19%) with a mean BMI of 22.67 kg/m2 and age 83.5  years, respectively, made up the testing group. All of the variables including sex, age, BMI, alcoholism, smoking, hypertension, diabetes, fracture site, thrombus, DBP, SBP, Dtime, temperature, BPM, and pulse were not significantly different of both groups (P > 0.05), supporting the model training and verification on both groups  and 109 women (74.15%) comprised the test group with a mean age and BMI of 83  years and 22.43  kg/m2. The DVT group included 7 men (25%) and 21 women (75%), with a mean age of 85  years and a BMI of 21.84  kg/m2. BMI was significantly different of both groups (P < 0.05), but no differences in baseline characteristics (P > 0.05) such as sex, age, alcoholism, smoking, hypertension, diabetes, fracture site, DBP, SBP, Dtime, temperature, BPM, and pulse. Following admission, a series of routine blood tests  and tests for coagulation  were carried out to complete the study data collection. There existed significant differences in WBC, NC, and LYM levels in DVT compared with No DVT groups (P < 0.05), while MNC, PLT, FIB, TT, PT–INR, APTT, D-D dimer, and PT levels did not show significant difference (P > 0.05). We acquired the correlation inflammatory-immune indices including MLR, NLR, PLR, and SII based on routine blood test indexes; typically, PLR was notably different in DVT compared with No DVT groups (P = 0.008). Furthermore, the NLR and SII levels in DVT group obviously increased compared with No DVT group (P < 0.001).  and DVT n = 28). The No DVT group included 31 men (26.05%) and 88 women (73.95%), their average age was 83  years, while their BMI was 22.43  kg/m8. The No19 and DV9/L, 7.43 × 109/L, 7.05 L/L, 212.69 L/L, and 1558.09 × 109/L, respectively) were notably higher than those in the No DVT group . The value of BMI and LYM in the DVT group  obviously decreased compared with No DVT group  , which is contrary to the findings of previous studies, possibly due to the narrow range of BMI values in our study ; training group, 22.67 kg/m2 ). Most patients were roughly within the normal range. This likely led to BMI being a protective factor in the prediction of intertrochanteric fracture thromboses in our model. An increase in BMI within a certain range may represent an increase in muscle strength. The improved blood flow associated with greater muscle strength can reduce the risk of DVT [Currently, BMI’s effect on DVT pathogenesis is unknown. As per one school of thought, cases showing the high BMI probably show relatively more adipose tissues, which may increase inflammatory factor production and enhance tissue factor generation, in turn activating exogenous coagulation pathways as well as promoting thrombus formation . Matsumopatients . This inncidence . In our kg/m2 21.2, 23.92)P < 0.001). As easily available clinical data, NLR can enable faster diagnoses and accurate treatments in clinical medicine.Previously, our understanding of DVT was confined to the Virchow triad, but there is now increasing evidence that the immune-inflammatory system also makes a vital impact on the process of thrombosis . Budnik P < 0.001), which markedly increased compared with BMI . Wang et al. used SII for predicting the survival rate of old cases experiencing hip fractures in their prospective cohort study, and concluded that it had a good predictive value and strong clinical practicability [SII is a popular immunoinflammatory index in recent years. It includes the combination of neutrophils, lymphocytes and PLTs, which allows for better prediction in the field of orthopedics. According to our results, SII represented the strong factor predicting DVT among cases experiencing intertrochanteric femoral fractures. When the SII threshold was 1528.033 in the ROC curve, the AUC was 0.734  This was an unicentric retrospective study which had limited sample size as well as several confounding variables. Clinically significant risk variables, such as time from trauma to admission and age, were not thoroughly examined. A multicenter regression study and thorough examination of data results for risk variables could be conducted in future studies. This will improve the predictive value and accuracy of the model. (2) The preoperative preliminary diagnosis of DVT was caused by a delay in ultrasonography time. When the time to refine the results was extended, the DVT developed in certain individuals differed from the results required for our study. Future studies can incorporate the time of diagnosis, the time of reporting, and the time difference between the two results. (3) This work was not validated by external data and the model's correctness and usefulness were not clarified. When multi-center retrospective studies are conducted in the future, external verification can be carried out with data from other hospitals to confirm the authenticity of the model. (4) A large number of cases were ruled out of this work and the prediction model scope was small. It is suggested to increase the sample size as much as possible on the basis of strictly following the inclusion and exclusion criteria in future multi-center studies. (5) This study only studied the risk of DVT before surgery. The further discussion on the risk of DVT after surgery can be carried out in the future.The BMI, NLR, and SII at admission are independent predictors of DVT in patients with intertrochanteric femoral fractures. These indices can be acquired conveniently and quickly. In addition, the nomogram on the basis of BMI, NLR, and SII can assist clinicians in evaluating the need for DVT. In clinical practice, faster and better treatment decisions can be made visually.Additional file 1. Table S1: Baseline characteristics of all studied patients.Additional file 2. Table S2: Comparison of clinical and laboratory data between the No DVT group and DVT group in the Testing Group.Additional file 3. Table S3: AUC and Cutoff value of ROC curve in the significant variables.Additional file 4. Table S4: Outcomes of the binary logistic regression analysis.


High PWV was associated with advanced age . In the multivariate analysis, reduced muscle mass (p = 0.018), low levels of triiodothyronine (p = 0.002), and triglycerides (p = 0.049) were significant predictors of PWV, but age (p < 0.001) remained an important factor. In conclusion, reduced triiodothyronine together with markers of malnutrition and age were associated with PWV in pre-dialysis CKD patients.Cardiovascular diseases (CVD) are the first cause of chronic kidney disease (CKD) mortality. For personalized improved medicine, detecting correctable markers of CVD can be considered a priority. The aim of this study was the evaluation of the impact of nutritional, hormonal and inflammatory markers on brachial-ankle Pulse Wave Velocity (PWV) in pre-dialysis CKD patients. A cross-sectional observational study was conducted on 68 pre-dialysis CKD patients . Laboratory data were collected, including levels of prolactin, triiodothyronine, TGF α, IL-6, and IL-1β. The high values of brachial-ankle PWV were associated with reduced muscle mass ( High cardiovascular risk in chronic kidney disease (CKD) patients is associated with accelerated atherosclerosis, endothelial dysfunction, and arterial stiffness (AS) and it has major consequences on survival and quality of life. Arterial stiffness is a negative prognostic factor for CKD progression  and for According to experts, the PWV remains a standard parameter for the assessment of AS ,10. TherAS is characterized by chronic structural modifications in the arterial wall expressed by elastin fragmentation and media calcification, but molecular changes in the intimal layer may also occur through the atherosclerotic inflammatory process. ,13.Hyperphosphatemia, the fluctuations of calcium such as hyper and hypocalcemia, hyperparathyroidism, the reduction of alpha Klotho, and the increase in FGF-23 are the main determinants of AS in CKD. Classic cardiovascular risk factors also intervene: hypertension, obesity, dyslipidemia, advanced age (through decreased endothelium nitric oxide availability and increased production of vasoconstrictors), diabetes mellitus (DM), and hyperuricemia ,11,12. IIn fact, AS in CKD is based on an enormously increased cardiovascular risk due to, on the one hand, the additional cardiovascular risk factors  and, on the other hand, due to certain particularities of the classic cardiovascular risk factors such as the appearance of the reverse epidemiology phenomenon . It is wThere are also studies that have shown that the hormonal changes occurring in CKD could also influence cardiovascular morbidity and AS. Prolactin is a hormone which is considered as a uremic toxin by some authors. It accumulates with loss of renal function, and it is associated with cardiovascular diseases in the general population and CKD population as well . HyperprThe presence of subclinical hypothyroidism was also recorded in CKD. It was associated with general mortality in advanced CKD . Low triCurrently, it is still not clear how prolactin and triiodothyronine influence cardiovascular diseases in CKD, and if they affect PWV, in fact, what are the most important factors that influence PWV in pre-dialysis CKD patients.That is why the aim of this study was to evaluate the impact of some inflammatory, nutritional, and hormonal markers on PWV in pre-dialysis CKD patients, and as a second aim in the subgroup of the patients with diabetes.We conducted a cross-sectional observational study on a cohort of pre-dialysis CKD patients. The patients were selected from those admitted to the Department of Nephrology, County Clinical Emergency Hospital Cluj, and taken into this study based on the inclusion and exclusion criteria. All patients provided written informed consent. The study methodology was in accordance with institutional and national research ethical standards and with the 1964 Helsinki Declaration and its subsequent amendments.2), and no change in medication during the same 3 months.Inclusion criteria were the following: patients aged ≥ 18 years, diagnosed with CKD for at least 6 months, defined according to Kidney Disease: Improving Global. Outcomes (KDIGO) guidelines, with estimated glomerular filtration rate (eGFR) less than 60 mL/min, , having a stable renal function during 3 months prior to study , and diastolic blood pressure (DBP), comorbidities  and the medication data were registered. The diagnosis of hypertension was established on the basis of BP values, namely SBP/DBP ≥ 140/90 mmHg as well as on the basis of the use of hypotensive drugs. We calculated pulse pressure (PP) as the difference between the SBP and DBP.In addition to body mass index (BMI), nutritional status was assessed by bioimpedance using the Body Composition Monitor, a certified device  which provided body composition as follows: lean tissue mass (LTM) (kg), and adipose tissue mass (ATM) (kg) .Blood samples were collected in the morning after 8 h fasting. Serum electrolytes, albumin, creatinine, lipid profile, inflammatory markers, intact parathormone (iPTH) and the medular response (hemoglobin and white blood cells) were determined. Serum IL-6, IL-1β, TNF-α, prolactin and triiodothyronine were determined by enzyme-linked immunosorbent assay (ELISA) using commercially available kits . The minimum detection limit for TNF-α was 15.6 pg/mL, for IL-6–3.2 pg/mL, for IL-1β–10.2 pg/mL, for prolactin 1.5 ng/mL, and for triiodothyronine < 0.1 ng/mL). Low-density lipoprotein-cholesterol (LDL-cholesterol) was calculated according to the Friedewald formula: LDL cholesterol = total cholesterol-(HDL-cholesterol + triglycerides/5).Brachial-ankle PWV was evaluated to assess arterial stiffness with the Mobil-O-Graph NG device , based on an oscillometric method. The device gave the augmentation pressure, augmentation index, central SBP, central DBP, and PWV. Brachial BP  was initData were presented using different statistical measures depending on the nature of the variables. For normally distributed variables the mean ± standard deviation (SD) was reported. For non-normally distributed variables, median (25th–75th percentile) was used. Nominal variables were expressed as absolute and relative frequencies.To examine the relationships between quantitative variables, either the Spearman or Pearson coefficient of correlation was employed. Spearman coefficient of correlation was used when the relationship was non-linear or when the outliers were present.In the multivariate linear regression analysis, PWV was considered the dependent variable. Independent variables included those that showed significant correlation in the univariate analysis and those previously identified in relevant literature as influencing PWV levels were considered. However, SBP was excluded from the model due to multicollinearity.t-test or Mann–Whitney U test for quantitative variables depending on their distribution , while the Chi-square test or Fisher exact test was used for qualitative variables. A p-value less than 0.05 was considered statistically significant.To compare two groups, different statistical tests were employed based on the nature of the variables. The In this study 80 patients were selected, from which six patients were excluded: four with acute infection, one with acute myocardial infarction, and one with malignancy. Another six patients were excluded due to missing data. Finally, 68 patients remained in the study.The demographical, clinical and laboratory patients’ characteristics are presented in p = 0.001, r = −0.45), low levels of total cholesterol , triglycerides  and, respectively, low levels of the hormonal engage: triiodothyronine   , PP  and advanced age , all of these findings are described in In the analysis of correlations, it was observed that high values of brachial-ankle PWV were associated with reduced values of muscle mass (= −0.25)  and prol= −0.27) . Additiop = 0.019) and triiodothyronine (p = 0.014), PP (p = 0.013), and triglycerides (p = 0.024), respectively, remained with a significant impact on brachial-ankle PWV, but its strongest determinant was age (p < 0.001).In the multivariate analysis it was noted that muscle mass (p = 0.010) and PP (p = 0.009) identified, significantly higher ATM (p = 0.032), and significantly higher IL-1β levels (p = 0.015).Diabetic vs. non-diabetic patients were analyzed . In the p = 0.012, r = 0.46; IL-6 p = 0.034, r = 0.40), age  and serum phosphorus , but not with the eGFR  remained statistically significantly associated with PWV.In the multivariate analysis the parameters which were correlated significantly with brachial-ankle PWV were included in our study, and it was noted that only age  and this could be associated with increased cardiovascular risk. Low values of T3 were associated with AS in our study, consistent with other studies in which FT3, was inversely associated with arterial stiffness in CKD patients . In factProlactine was reported to be correlated with PWV. Carrero et al. observed increased prolactin levels in subjects with endothelial dysfunction/stiffness and which further increased the risk of cardiovascular events and mortality . The incAs evidence in our study, not the high values, but the low values of prolactin, a polypeptide hormone, were associated with the increase in PWA and we consider this type of association as an effect of the protein malnutrition present in the patients enrolled in the study. Moreover, in the study by Haring et al., they noted the association of low prolactin values with increased left ventricular mass, these changes only affecting males , withoutIn diabetic patients, PWV is higher than in the general population and promotes an increase in general and cardiovascular mortality . If a diOther studies also reported that inflammatory markers such as fibrinogen and IL-10 were independently associated with PWV ,51. MoreRegarding the connection between phosphorus and AS as noted in our study, it is probably via vascular calcification. In fact, CKD alters hormonal processes that regulate phosphate levels ; all these processes mentioned favoring hyperphosphatemia . ExcessiAll these processes initiated in pre-dialysis stages of CKD explain the significant cardiovascular changes detected in dialysis CKD patients .In conclusion, in pre-dialysis CKD patients, age is the strongest determinant of PWV even among diabetic patients. Reduced triiodothyronine and prolactin values are associated with arterial stiffness, while also being markers of malnutrition. Inflammatory markers and hyperphosphatemia influenced PWV in diabetic patients. No variations of PWV were recorded with eGFR or determined by the DM presence. Therefore, we speculate that if we detect and treat the inflammatory syndrome, respectively the malnutrition, the triiodothyronine, and prolactin levels, probably the value of PWV can be influenced. We believe that knowing the factors that influence PWV as a marker of AS, can help to administer a personalized treatment.The study has some limitations, the first being the relatively small number of included patients, which makes additional studies necessary in order to validate the correlations and associations between PWV and the level of triiodothyronine, prolactin, and inflammatory markers with nutritional status. Secondly, due to the nature of our cross-sectional data, this study was limited in what we can infer about the causality of the results. Thirdly, by design it was an observational study and the conclusions need to be confirmed in the future, possibly by larger prospective studies.


Both biomarker positivities were significantly higher in the CKD 3-5 group (p = 0.035) compared to the CKD 1-2 group. The central aortic systolic pressure was significantly higher in the diastolic dysfunction group (p = 0.034), while the systolic blood pressure was not. eGFR and hemoglobin levels showed a strong negative correlation, while left ventricular mass index (LVMI), aortic pulse pressure, central aortic systolic pressure, and cfPWV showed a positive correlation with NT-proBNP. cfPWV, aortic pulse pressure, and LVMI showed a strong positive correlation with CITP. Only eGFR was an independent predictor of NT-proBNP by linear regression analysis. NT-proBNP and CITP biomarkers may help to identify IgAN patients at high risk for subclinical heart failure and further atherosclerotic disease.Cardiovascular mortality is a leading cause of death in chronic kidney disease (CKD), as is IgA nephropathy (IgAN). The purpose of this study is to find different biomarkers to estimate the outcome of the disease, which is significantly influenced by the changes in vessels  and the heart. In our cross-sectional study, 90 patients with IgAN were examined. The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was measured as a heart failure biomarker by an automated immonoassay method, while the carboxy-terminal telopeptide of collagen type I (CITP) as a fibrosis marker was determined using ELISA kits. Arterial stiffness was determined by measuring carotid–femoral pulse wave velocity (cfPWV). Renal function and routine echocardiography examinations were performed as well. Based on eGFR, patients were separated into two categories, CKD 1-2 and CKD 3-5. There were significantly higher NT-proBNP ( Chronic kidney disease (CKD) is a global health challenge for health professionals and healthcare providers worldwide ,2. IgA nIn recent years, plasma biomarkers, particularly natriuretic peptides, along with imaging studies, e.g., echocardiographic examinations or coronary CT scans, have been suggested to identify patients at high CV risk in CKD. In chronic kidney disease (CKD), arterial stiffness may be a predictor of cardiovascular (CV) mortality and morbidity . In advaData in the literature about the association between arterial stiffness, subclinical heart failure (NT-pro-BNP), cardiac fibrosis (CITP), and renal function in CKD are limited. We wanted to determine new biomarkers in connection with the influence of renal function on CV complications in IgAN, such as heart failure and atherosclerotic disease prediction, and detection of any association between NT-proBNP as a marker of heart failure, CITP as a marker of atherosclerosis and myocardial fibrosis, and CKD.p = 0.035), cfPWV (p = 0.004), and central aortic systolic pressure (p = 0.037), but not CITP, in the CKD 3-5 group  and CKD 3-5 (GFR: <60 mL/min)). There were significant differences between the two groups in terms of age, eGFR, hypertension, diabetes, LVMI, and hemoglobin level in the baseline characteristics . There w-5 group .p = 0.035) compared to the CKD 1-2 group (p = 0.002) than in the non-hypertrophic group (The number of patients with combined biomarker positivity (NT-proBNP and CITP) was significantly higher in the CKD 3-5 group (-2 group . In the ic group .p = 0.034), while the peripheral systolic blood pressure, NT-proBNP, and CITP did not differ between the two groups (When we divided the patients into two groups based on left ventricular diastolic function (no LVDD (n = 51) vs. LVDD (n = 39)), we found that the diastolic dysfunction group had significantly higher central aortic systolic blood pressure , aortic pulse pressure, central aortic systolic pressure, and cfPWV. CITP showed a strong positive correlation with cfPWV, aortic pulse pressure, and LVMI by Spearman’s correlation .According to univariate and multivariate regression analysis, the independent predictor factors for NT-proBNP were gender, eGFR, and LVMI. There were no independent confounders in the case of CITP, while all of the exemplified parameters had an impact on the univariate analysis . Only eGIn the present study, we demonstrated that NT-proBNP and a combination of NT-proBNP and CITP elevation may predict certain cardiac complications in IgAN. NT-proBNP and CITP biomarkers may help to identify IgAN patients at high risk for subclinical heart failure and further atherosclerotic disease. We found an independent association between eGFR and NT-proBNP, but not with CITP, in IgA nephropathy. There was a strong correlation between NT-proBNP, CITP, and aortic PP and PWVcf. In cases of deteriorated renal function, there was significantly higher central aortic systolic pressure.Our knowledge of the mechanisms underlying the advancement of kidney disease, cardiovascular disease, and all-cause mortality has greatly benefited from measurements of arterial stiffness , which wOhno et al. found that in CKD patients central blood pressure is a stronger predictor of CV and renal disease outcomes compared with brachial blood pressure, and should be used to guide antihypertensive therapy . Our resIn our research, we came to the same conclusion as Uterstellar et al., who identified NT-proBNP as a highly effective indicator of CV prognosis in CKD patients not receiving dialysis ,14. TheyTwo earlier Greek studies showed a connection between altered collagen turnover (collagen type I synthesis) and increased aortic stiffness in treated hypertensive patients without left ventricular (LV) hypertrophy  as well In patients with CKD, particularly those who have HFpEF, Eiros et al. described a link between LVDD and the biomarker combination of high carboxy-terminal propeptide of procollagen type-I (PICP) and low carboxy-terminal telopeptide of collagen type-I to matrix metalloproteinase-1 (CITP:MMP-1) ratio. These results suggest that CKD promotes the development of biomarker-assessed myocardial fibrosis and LVDD in hypertensive patients with HFpEF, and that changes in collagen type I metabolism as measured by the biomarkers PICP and CITP:MMP-1 ratio worsen with the transition to HFpEF in hypertensive patients .We found a positive correlation between CITP and cfPWV, aortic pulse pressure, and LVMI in our cohort, which suggests an association between worsening kidney function and vascular changes, and means that altered collagen turnover (CITP) can be assumed.Because of the high prevalence of myocardial fibrosis in patients with CKD and the direct correlation that exists between the degree of impairment of kidney function and the severity of myocardial fibrosis ,26,27, iAdditional factors favor NT-proBNP as a plasma biomarker for CV outcome prediction in clinical practice over an echocardiography-based method. First, the cut-off values for NT-proBNP were significantly lower (150 pg/mL) than those found in echocardiographic investigations . Second,Liang et al. proved that systolic dysfunction and LVDD demonstrated mutually augmentative effects on CV mortality, and suggested that cardioprotection for patients with CKD should be prioritized at an early stage along with conventional nephroprotection. Therefore, cardioprotective management should be initiated as early as possible after CKD diagnosis .Uremia causes structural alterations in the heart, including thickening of the intramural arteries, cardio-myocyte hypertrophy, and myocardial fibrosis. In response to the compounding effects of traditional risk factors and CKD-related risk factors, these structural changes together predispose patients to LVDD ,36,37. TUnfortunately, we did not examine the effects of RAAS inhibitors in this study. Although we did not examine the role of these factors, these observations may explain the observed differences in the LVDD values of our IgAN patients.We included 90 renal biopsy-proven IgAN patients in our cross-sectional study, and we analyzed their data retrospectively. The University of Pécs Regional Research Ethics Committee approved the study protocol, and all participants provided written consent to its completion. The inclusion criterion for the study was confirmed IgAN over the age of 18, while exclusion criteria were previous or current immunosuppressive treatment (due to the modifying effects of the biomarker) and severe comorbidities, such as malignancies that required active treatment or acute infection.2. The CKD-EPI formula was used to estimate renal function . A 24-h blood pressure monitor using Meditech ABPM devices was relied on to determine the patient’s 24 h average systolic and diastolic blood pressure, pulse pressure, and diurnal index. Echocardiography was performed at the start of the study (see below). During these visits, medical events that had occurred since the previous visit were recorded, the patient’s physical status was examined, and detailed laboratory tests were performed. Blood pressure values were determined from the average of three measurements taken after 10 min of rest.At the start of patient enrollment, echocardiography measurements were performed and classic CV risk factors, including hypertension, carbohydrate metabolism disorder, obesity, lipid abnormalities, smoking, and patient medications such as antihypertensive drugs , and statins were recorded. The obesity inclusion criterion was a BMI over 30 kg/m® Gmbh, Mannheim, Germany), while carboxy-terminal telopeptide of collagen type I (CITP) was measured using enzyme-linked immunosorbent assay (ELISA) kits  in the Szentágothai Research Center (University of Pécs) following the manufacturer’s protocol.N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was determined in the accredited Department of Laboratory Medicine , by a fully automated immonoassay method . cfPWV was measured using applanation tonometry . Measurements were performed in the morning in the supine position after at least 10 min of rest in a quiet temperature-controlled room. Pulse wave recording was performed consecutively at two superficial artery sites . The cfPWV was calculated, and central aortic pressure was measured by the device. Augmentation index (Aix) is based on blood pulse-wave reflection, and is an accepted measure of arterial stiffness and risk factor for cardiovascular disease. The Aix is commonly accepted as a measure of the enhancement (augmentation) of central aortic pressure by a reflected pulse wave.2 was calculated using Devereux’s formula, and the cardiac mass was indicated by lean mass. LVMI was determined based on the Cornell criterion and indexed for height (in meters). The left ventricular ejection fraction (LVEF) was calculated by adding the diastolic and systolic volumes of the left ventricle using the unidirectional Simpson method: EF = (Dvol-Svol)/Dvol × 100. Diastolic function was determined by mitral inflow and pulmonary venous flow based on conventional spectral Doppler measurements. We measured the ratio of the E wave to the A wave (E/A ratio), the isovolumetric relaxation time (IVRT), and the deceleration time of the E wave. LVH was defined as abnormal RWT and/or LVMI.Echocardiography was performed with the Aloka SSD 1400; two operators were involved in the study. Left ventricular mass (LVM) was calculated from 2D images of the left ventricular short-axis muscle area and apical left ventricular length (LVM = (5/6 area × length)). The left ventricular mass index (LVMI) of g/mt-test and ANOVA as appropriate. The mean SD was used to express data with a normal distribution. Correlations between continuous variables were evaluated with linear regression using the Pearson test, while the Spearman correlation test was used for categorical variables. Values of p > 0.05 were considered statistically significant.Statistical analyses were performed using SPSS 21.0 software . The Kolmogorov–Smirnov test was used to determine the normality of the data distribution. Non-normally distributed parameters were transformed logarithmically. A comparison of clinical and laboratory parameters was made using Student’s In conclusion, our study confirmed that NT-proBNP both alone and combined with CITP may help identify IgAN patients at high risk for subclinical heart failure and further atherosclerotic disease. In addition, there is an effect of the modification of CKD on the association of these biomarker combinations with LVDD in HFpEF patients. A possible mechanism for the development of heart failure in CKD patients may be an elevation of central aortic systolic pressure. The pathophysiological mechanisms linking the increased prevalence of the biomarker combination with CKD, as well as its association with poor outcomes, must be investigated in larger cohorts.Several limitations need to be acknowledged in our study. First, the present study was a single-center cross-sectional study with a small number of patients, which could have caused selection bias. Second, we cannot say for certain that the association between increased NT-proBNP, CITP, and decreased renal function is causal in our CKD patients. Third, the renal function was estimated, not measured, although the use of eGFR is widely accepted in the literature to describe renal function. Fourth, as a consequence, the low frequency of the biomarker combination as defined in previous studies precluded the performance of subgroup analyses in the current study. In this regard, further studies should be performed to examine the correspondence between histological and biochemical aspects of myocardial fibrosis in different HF stages. Therefore, further analyses in large and independent cohorts of patients are necessary to confirm these findings. Fifth, potential problems related to multiplicity could have influenced the findings. Finally, because they are descriptive in nature, the associations found between renal disease, circulating biomarkers, and LV dysfunction do not establish causality.


Non-invasive ventilation application in neurocritical care with risk of pneumocephalus is controversial. Non-invasive ventilation-related increased intrathoracic pressure increases intracranial pressure via direct transmission of intrathoracic pressure to the intracranial cavity. In addition, increased thoracic pressure decreases venous return to the heart and increases vena jugularis interna pressure, thereby increasing cerebral blood volume. 2 as manifested by a larger increase in PaO2/FiO2 ratio and provide the theoretical basis in pneumocephalus because augmenting the PaO2 more effectively would accelerate nitrogen (N2) washout.Pneumocephalus is one of the major concerns after non-invasive ventilation application in head/brain trauma patients. Non-invasive mechanical ventilation may be performed in limited conditions in head trauma/brain surgery with appropriate and close monitoring. High-flow nasal cannula oxygen therapy can provide higher FiOAs a result, non-invasive mechanical ventilation may be performed in limited manner in head trauma/ brain surgery with appropriate and close monitoring. Non-invasive mechanical ventilation may be used in head trauma/brain surgery with dural injury in limited conditions with appropriate and close monitoring. Patients under treatment with continue positive airway pressure and bi-level positive airway pressure may develop pneumocephalus. High-flow nasal oxygen therapy may be a choice in head trauma/brain surgery patients.1 Non-invasive ventilation (NIV) may provide optimum respiratory support to patients thus avoiding the complications of invasive mechanical ventilation including barotrauma (pneumothorax), volutrauma, biotrauma, ventilator-associated pneumonia and sinusitis, delirium, decreased cardiac output, fluid retention, pulmonary emboli and deep venous thrombosis.3 Recently, NIV has been suggested as a treatment option in patients with trauma, acute respiratory insufficiency and in the early stage of “Acute Respiratory Distress Syndrome” (ARDS).4 However, the NIV application in these conditions is still a matter of discussion in the scientific literature.5Mechanical ventilation is an artificial positive pressure support for respiration to assist breathing in case of respiratory failure (either hypercapnic or hypoxemic). It reduces the patient’s work of breathing by overcoming excessive imposed loads  with subsequent improvements of oxygenation and carbon dioxide elimination.6 Air moves into the cranium via a fistula which acts as a 1-way valve. A decreased cerebrospinal fluid-related decreased intracranial pressure supports air bubbles wiggling through the cranium. Also, increased thoracic pressure decreases venous return to the heart and increases vena jugularis interna pressure, thereby increasing cerebral blood volume.7After an initial cranial defect, air can move into the brain through a paranasal sinüs or the mastoid cells, which can be aggravated by swallowing, coughing or sneezing under a pressure greater than that within the cranium.8 The main goal in managing head trauma/brain surgery patients must be to protect the patient from secondary damage, primarily cerebral ischaemia of the primary injury. Secondary damage occurs due to hypoxia, hypercapnia, hypotension, hypoglycaemia and hyperpyrexia, especially in head/brain trauma patients. Therefore, management of head trauma/brain surgery patients is targeted at optimising cerebral perfusion, oxygenation, and avoiding hypoxia and hypercapnia.9It is important to consider the mechanism and extension of injury when deciding to administer NIV in trauma patients. For example, head, neck and middle face traumas are unsuitable for administration of NIV. Furthermore, high consciousness levels and integrity of the upper airways should be ensured in such cases.The aim of this narrative review is to emphasise the aspects of NIV treatment which may not be reviewed in the literature in this controversial use of NIV in head injury. 2 above 11 kPa) and hypercapnia  and to avoid intubation.11 Before considering NIV on such patients, it is necessary to determine whether the patient’s upper airway is compromised or not. It must be kept in mind that NIV [continue positive airway pressure (CPAP) and bi-level positive airway pressure (BIPAP)] application to prevent respiratory failure may cause pneumocephalus (PNC) which indicates the presence of air in the intracranial cavity.12In patients with head trauma/brain surgery who are conscious in the perioperative period, NIV can be applied to prevent hypoxia  who underwent trans-sphenoidal resection. At the end of 2 weeks, PNC developed in the patient. Chee BNH et al14 performed CPAP in the post-operative period because of OSA in patients with ventriculo-peritoneal shunting after trauma and surgery. Continue positive airway pressure application was discontinued due to developing rhinorrhoea in these patients, and the defect was surgically closed afterwards.Kopelovich et al14If there is a pathology in the area close to the air inlet during NIV application or if the operation is performed in these areas , post-operative NIV applications should be carefully monitored. Non-invasive ventilation applications can be performed more safely after 6 weeks of dural repair.15 reported their findings on the use of CPAP in a morbidly obese patient with OSA who underwent an awake craniotomy. They stated that the patient who was under sedation with dexmedetomidine remained comfortable and cooperative during the operation. Lee et al16 applied CPAP during the perioperative period with a mask under deep sedation to patients with severe chronic obstructive pulmonary disease (COPD) undergoing frontal craniotomy. This procedure is called “awake operation” which does not require a deep sedation. They reported that this application was very effective and that intraoperative NIV administration prevented the development of hypoxemia and hypercarbia. They did not observe any post-operative complications. In another study, patients with OSA under CPAP treatment were divided into 2 groups after trans-sphenoidal pituitary resection.17 One group received CPAP in the post-operative period, while the other group did not, and there were no differences between the 2 groups in terms of post-operative complications.In 2008, Huncke et al18 The Canadian Critical Care Trials Group and the Canadian Critical Care Society Non-invasive Ventilation guidelines do not recommend NIV application in similar cases due to insufficient findings and controversies.19In the British Thoracic Society guidelines, NIV application in multi-trauma patients with hypoxemic respiratory failure is recommended and rated as C-level and had low-grade evidence.13A pressure of around 15 cmH2O applied to the upper airways by a NIV treatment which is close to the intracranial pressure makes no difference. In the absence of a previous injury, this level of pressure is unlikely to have any effect on air intake into the CNS. However, air can enter the intracranial compartments directly through the fractures of the cranial bones and sinuses as a result of trauma and the defect created by a penetrating body. In such a case, the positive pressure effect of NIV will facilitate air entry through the existing defect. It has been shown that positive pressure applied to the upper airways, even for a short time, can cause pneumocephalus in patients with previous sphenoid sinus bone rupture.Continue positive airway pressure can increase intrathoracic pressure resulting in a decrease in venous return and cardiac output. A decreased venous return may result in an increase in intracranial pressure and together with a decreased cardiac output following an undesirable negative effect on cerebral blood flow that may arise. Non-invasive ventilation treatment in patients with head trauma/brain surgery who require mechanical respiratory support should exclude patients with a reported or suspected fractures of the skull of cranial bones and sinuses, dural defects or fistulas. 20 The administration of nasal high-flow oxygen therapy, another form of non-invasive ventilatory support, may help respiratory mechanics by improving ventilation and increasing oxygenation. It provides nasal respiratory support with optimally heated and humidified oxygen at high-flow rates (up to 60 L per minute).21 In high-flow applications, tidal volume is increased and end-tidal expiratory lung volumes have been shown to improve oxygenation. Moreover, it decreases respiratory rate proportionally to the delivered flow rate.22 High-flow nasal cannula (HFNC) oxygen therapy can provide higher FiO2 as manifested by a larger increase in PaO2/FiO2 ratio and provide the theoretical basis for using HFNC oxygen therapy in PNC because augmenting the PaO2 more effectively would accelerate N2 washout. Based on a previous mathematical model of the rate of PNC absorption, HFNC oxygen therapy can theoretically outperform other conventional oxygen therapy devices such as non-rebreather mask (NRB).26 However, it has also been reported that it does not affect atelectasis compared to standard oxygenation. However, it prevents the closure of airways and prevents dead space ventilation. This delivers high mean airway pressure. Thus, the work of breathing during HFNC therapy is reduced.27 There may be improved intracranial compliance. Pneumocephalus has not been reported in any head trauma/brain surgery patient who has applied for HFNC oxygen therapy.When compensatory mechanisms such as hypoxic pulmonary vasoconstriction become insufficient, pulmonary and extra-pulmonary damage can potentially lead to increased morbidity and mortality.28 applied high-flow intranasal oxygen to a patient with OSA who underwent awake craniotomy. Oxygen and carbon dioxide partial pressure levels remained normal under deep sedation. The patient and the surgeon were highly satisfied. No complications were observed in the post-operative period.Wong et al29 presented 3 cases of post-operative PNC who were symptomatic. All patients improved both clinically and radiographically within a few hours with the administration of HFNC oxygen therapy, faster than in both anecdotal experience and published trials due to its steady FiO2 administration, positive pressure, comfort and low side-effect profile. Additionally, HFNC oxygen therapy may be the ideal mode of oxygen delivery in cases of post-operative PNC. Siegel et al30 there are no reports of oxygen toxicity with the use of HFNC. Otherwise, there are no guidelines regarding contra-indications of HFNC oxygen therapy, but considerations should be taken as with other modes of positive pressure NIV .31Though the concept of pulmonary oxygen toxicity has been well described,35 Nevertheless, it needs to be considered, as early diagnosis and appropriate treatment can modify prognosis. There is no sufficient data about HFNC safety of use in head trauma/brain surgery and further research is needed to evaluate its safety and effectiveness and the frequency of serious adverse events. The resulting knowledge should be used to develop clear guidelines and protocols for the use of HFNC oxygen therapy in such situations.On the other hand, tension PNC with severe neurological sequelae was a rare complication in HFNC in paediatric population receiving respiratory support with HFNC oxygen therapy.As a result, NIV can be applied in conscious and cooperative patients without head and neck trauma, deformed bone and soft tissue damage in the face. In these patients, NIV administration is not recommended in the guidelines as reflected by a “low-grade recommendation” for the use of NIV in trauma patients by the British Thoracic Society guidelines and “no recommendation” by Canadian Critical Care Trials Group/Canadian Critical Care Society NIV Guidelines Group because there is still much disagreement on this issue. Patients undergoing NIV should be monitored strictly because PNC may develop. In recent years, nasal high-flow oxygen application is encouraged in head trauma/brain surgery patients with no complications observed in the post-operative period. Further prospective, randomised, clinical studies are needed on this topic.Non-invasive mechanical ventilation may be performed in limited conditions in head trauma/brain surgery with dural injury with appropriate and close monitoring. During NIV application in patients with head trauma/brain surgery, a close serial neurologic examination based on consciousness and changes in exam should be done in addition to haemodynamic, and respiratory monitoring should be performed. There are many reported cases of PNC developing in patients with CPAP and BIPAP treatment. High-flow nasal oxygen therapy may be a choice in head trauma/brain surgery patients. Further prospective, clinical, randomised controlled trials are needed in this subject.