Pediatric renal transplant recipients (RTx) were studied for longitudinal changes in blood pressure (BP), arterial stiffness by pulse wave velocity (PWV), and graft function.Patients and Methods: 52 RTx patients  were included; office BP (OBP) and 24 h BP monitoring (ABPM) as well as PWV were assessed together with glycemic and lipid parameters and glomerular filtration rate (GFR) at 2.4[1.0–4.7] (T1) and 9.3[6.3–11.8] years (T2) after transplantation (median [range]).Results: Hypertension was present in 67 and 75% of patients at T1 and T2, respectively. Controlled hypertension was documented in 37 and 44% by OBP and 40 and 43% by ABPM. Nocturnal hypertension was present in 35 and 30% at T1 and T2; 24 and 32% of the patients had masked hypertension, while white coat hypertension was present in 16 and 21% at T1 and T2, respectively. Blood pressure by ABPM correlated significantly with GFR and PWV at T2, while PWV also correlated significantly with T2 cholesterol levels. Patients with uncontrolled hypertension by ABPM had a significant decrease in GFR, although not significant with OBP. Anemia and increased HOMAi were present in ~20% of patients at T1 and T2.Conclusion: Pediatric RTx patients harbor risk factors that may affect their cardiovascular health. While we were unable to predict the evolution of renal function based on PWV and ABPM at T1, these risk factors correlated closely with GFR at follow-up suggesting that control of hypertension may have an impact on the evolution of GFR. Pediatric kidney transplant recipients (RTx) have a decreased life expectancy. Although recent studies have shown an improvement in long term survival after RTx, it remains 20–25 years shorter compared to the general population . CardiovHypertension (HT) is a common condition in RTx, with a prevalence reaching up to 80% . While mTwenty-four hour ambulatory blood pressure monitoring (ABPM) is the most suitable method for the diagnosis and follow-up of hypertension, as it can identify masked [elevated blood pressure (BP) occurring outside the clinical setting] and isolated nocturnal hypertension (hypertension during sleep only), as well as blunting of the normal nocturnal dip . Both noPulse wave velocity (PWV) is a validated marker of vascular damage in adult CKD patients, and a predictor of CV events. Such link is yet to be established in children. Elevated arterial stiffness is a common finding in pediatric end-stage renal disease (ESRD) patients , 14, conThe aims of the present study were to (i) assess the prevalence of hypertension as well as the presence of known metabolic CV risk factors and of increased arterial stiffness in a pediatric RTx cohort, (ii) describe longitudinal changes in ABPM and PWV, and (iii) identify associations between blood pressure, arterial stiffness, and graft function.Of the eighty-seven patients controlled at our outpatient clinic, 52 RTx were available for the study. Inclusion criteria were a functioning allograft, with stable kidney function, without rejection episodes for at least 6 months prior to testing, absence of history of overt cardiovascular disease and an evaluable data set for both the first and second follow-up examinations.1) was followed by a second after ~6 years follow-up (T2). At both visits, standard yearly examinations were performed including evaluation of biometric data, laboratory tests, ABPM and PWV measurements (see below for details). Doppler renal ultrasound was part of the annual assessment and no renal artery stenosis was observed.Patients were assessed twice. A first cross-sectional checkup , serum calcium (Ca), and phosphate (P), insulin resistance characterized by the HOMA index, as well as lipid profile at the time of follow-up were retrieved for analysis from the medical records.HOMA index was calculated as fasting insulin multiplied by fasting glucose level divided by 22.5, as described by Matthews et al. . A cut-oThe revised Schwartz formula was used to calculate the glomerular filtration rate (GFR) . ProteinBrachial blood pressure and heart rate were measured by a validated automated oscillometric device  in sitting position using appropriate cuff sizes, with the mean of three measurements being used for analysis. OBP results are presented as absolute values and height-based Z-scores .ABPM was performed by using a validated automated oscillometric device  . BP was Hypertensive children were further classified according to the control of hypertension. Uncontrolled hypertension was defined as SBP and/or DBP values exceeding the 95th percentile for height in patients with or without antihypertensive medication. In patients with controlled hypertension, both SBP and DBP were below the 95th percentile for height and patients taking antihypertensive medication. The normotensive group included patients with SBP or DBP below the 95th percentile without taking antihypertensive medication.Nocturnal dipping was defined as a nocturnal decrease in BP measured by ABPM. Patients with dipping below 10% were considered as non-dippers , 27.Patients with BP exceeding 95th percentile at night, but with normal blood pressure during the day were categorized as having isolated nocturnal hypertension , 29.Masked hypertensives had normotensive OBP values, but had hypertension on ABPM, whereas patients with white coat hypertension had elevated OBP but had normotension on ABPM .Carotid-femoral PWV measurement was performed by applanation tonometry with a PulsePen®™  device, as described previously . All parStatistical analyses were performed using IBM SPSS 26. Age is expressed as median and interquartile ranges. Continuous variables, reported as means and standard deviations, were compared with the Wilcoxon signed-rank test. Categorical variables were compared using McNemar's test. The Mann-Whitney test was used for comparing groups in the cohort.p-value of <0.05 was considered statistically significant.Correlations between variables were assessed by linear regression analysis. A 1 and T2 was 13.6 [11.1–16.2] years and 18.9 [16.8–23.9] years, respectively, with a follow-up of 5.7 [4.6–9.3] years.A total of 52 pediatric and young adult kidney transplant recipients  were included in the study. The median age [IQR] at Tn = 13; 25%); focal segmental glomerulosclerosis (FSGS)  ; cystic kidney disease ; glomerulopathy ; nephronophtisis ; interstitial nephritis ; acute tubular necrosis ; nephrocalcinosis ; Bardet-Biedl syndrome ; Denys-Drash syndrome ; cystinosis ; and unknown .Etiologies of kidney disease were congenital anomalies of the kidney and urinary tract  (tacrolimus or cyclosporine A) and mycophenolate mofetil. The dose of CNI inhibitors was adjusted to be in the target range and all patients were in the range at the time of the examinations. In addition, 60% of the patients were taking steroids at T1 and T2 are detailed in Patient characteristics at Tp < 0.06), with no significant difference in weight and BMI-Z scores between T1 and T2. Of note, while there was an almost −1 SD deficit in height Z score at T1, patient weight was appropriate for age, with a positive BMI Z score at both T1 and T2. Overweight was present in 4 (7.6%) and 6 (11.5%) patients at T1 and T2, respectively.A trend in catch-up growth could be observed during the course of the study , beta-blockers (BB) , ACE-inhibitors (ACEi) or angiotensin receptor blockers (ARB) , diuretics (thiazide or indapamide) and alpha-adrenergic blocking agents . Mean number of antihypertensive medication was 1.3 ± 1.2 at T1 and 1.5 ± 1.2 at T2 (p = NS).Antihypertensive medication consisted of calcium-channel blockers (CCB) . Controlled hypertension based on OBP measurements was 19 (37%) and 23 (44%) at T1 and T2 (p = NS)  and 39 (75%) at T(p = NS) .n = 52) and those who also had ABPM measurements (n = 37) (data not shown).There was no significant difference between the OBP values of the whole cohort . Controlled hypertension based on ABPM was present in 15 (40%) and 18 (49%) patients at T1 and T2, respectively (p = NS).Among those who had ABPM results, 26 (70%) and 31 (84%) had hypertension at T2 (p = NS). The prevalence of non-dippers among uncontrolled hypertensives was 9 (81%) at T1, and 8 (61%) at T2 (p = NS), respectively. Isolated daytime hypertension was present in 5 (14%) and 7 (19%) cases, whereas isolated nocturnal hypertension was present in 9 (24%) and 5 (14%) of cases at T1 and T2, respectively.Of those who had controlled hypertension at the first measurement, 9 (60%) were non-dippers. while this ratio was 7 (39%) at T1 and T2, respectively.Using both ABPM and office results, 9 (24%) and 12 (32%) patients had masked hypertension, while white coat hypertension was present in 6 (16%) and 8 (21%) patients at TDetails relative to blood pressure and PWV results are shown in 1 and T2 in either OBP or ABPM blood pressure Z-scores.There was no significant change between T1 and T2  did not correlate with GFR whether at T1. However, there was a positive correlation between T2 PWV-Z and all systolic and diastolic ABPM-Z scores , while office blood-pressure Z scores showed no correlation with PWV-Z at T2  and PWV-Z at T2 PWV correlated with T2 cholesterol .There was no correlation between GFR and PWV-Z values. Regarding lipid measurements, T2 had a significant decrease in GFR (shown as change in GFR between T1 and T2) compared to controlled hypertensives. This difference was only present if ABPM values were considered, and not for OBP  exhibited a significant decrease in GFR at T2 compared to the controlled group thus suggesting that controlling hypertension may impact the evolution of GFR on the long term . Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.AV and AB organized the database performed the statistical analysis and wrote the first draft of the manuscript. OC, ÉK, KK, and ST wrote sections of the manuscript. AS and GR contributed to conception and design of the study and corrected the manuscript. All authors read and approved the submitted version.This study was supported by the Hungarian National Research, Development and Innovation Office grants NKFI-124549 (GR) and TK2121GYKI (AS), and the Research Group of the Hungarian Academy of Sciences at the First Department of Pediatrics (AS).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Polycystic kidney diseases (PKD) are severe forms of genetic kidney disorders. The two main types of PKD are autosomal recessive and autosomal dominant PKD . While ARPKD typically is a disorder of early childhood, patients with ADPKD often remain pauci-symptomatic until adulthood even though formation of cysts in the kidney already begins in children. There is clinical and genetic overlap between both entities with very variable clinical courses. Subgroups of very early onset ADPKD may for example clinically resemble ARPKD. The basis of the clinical variability in both forms of PKD is not well understood and there are also limited prediction markers for disease progression for daily clinical life or surrogate endpoints for clinical trials in ARPKD or early ADPKD.As targeted therapeutic approaches to slow disease progression in PKD are emerging, it is becoming more important to reliably identify patients at risk for rapid progression as they might benefit from early therapy. Over the past years regional, national and international data collections to jointly analyze the clinical courses of PKD patients have been set up. The clinical observations are complemented by genetic studies and biorepositories as well as basic science approaches to elucidate the underlying molecular mechanisms in the PKD field. These approaches may serve as a basis for the development of novel therapeutic interventions in specific subgroups of patients. In this article we summarize some of the recent developments in the field with a focus on kidney involvement in PKD during childhood and adolescence and findings obtained in pediatric cohorts. Polycystic kidney diseases (PKD) are severe systemic disorders that predominantly affect the kidneys and the liver . The twoARPKD is usually diagnosed prenatally or in the first year of life. The disease is characterized by bilateral fibrocystic changes of the kidneys typically presenting with massive organ enlargement due to ubiquitous microcysts mainly developing from the collecting duct. Impairment of kidney function is variable. Antenatal decline of kidney function is associated with oligo-/anhydramnios which subsequently results in pulmonary hypoplasia. Early pulmonary disease in ARPKD is still associated with substantial mortality even in very advanced medical centers. In addition, hepatic involvement due to a developmental defect of bile ducts is an obligatory finding in ARPKD, which may clinically result in hepatic fibrosis with portal hypertension and bile duct dilatations with an increased risk of cholangitis –3.in utero [ADPKD is a more slowly developing disease with clinical symptoms typically becoming prominent in adulthood, even though cyst development starts in childhood or even in utero , 4. The in utero , 5.TablePKHD1 (ARPKD), PKD1 and PKD2 (ADPKD)), but the pronounced and poorly understood clinical variability cannot be fully explained by underlying genotypes. Variants in additional genes and first modifier genes have been identified [PKD1 variants have been identified as a common cause of early-onset PKD [The genes mainly affected in ARPKD and ADPKD are well-known  with ARPKD being an important cause of CKD specially in very young children and ADPKD being the by far most common genetic cause for chronic kidney failure (CKF) in adults. Despite important work by multiple groups –11, therpatients , 13. Yetpatients , 15, butThere is a clear need for evidence-based and targeted treatment in both forms of PKD during childhood and adolescence. ARPKD is a very severe disorder of early childhood. In ADPKD on the other hand cystogenesis starts early in life and kidney function mainly declines once structural changes in the kidney parenchyma are pronounced. It has therefore been suggested that young ADPKD patients could highly profit from early interventions that would retard the development of structural changes in the kidney with subsequent positive long-term effects.Clinical research on ARPKD and pediatric ADPKD has for a long time been hampered by the lack of well-defined primary end points for trials. Most of the current treatment approaches for pediatric PKD therefore remain symptomatic and opinion-based. The current treatment of severely affected children with ADPKD is based on strict antihypertensive therapy , 16.For treatment of adult ADPKD patients multiple clinical trials are ongoing. The vasopressin V2-receptor antagonist Tolvaptan has been shown to retard cyst growth and the loss of kidney function in large cohorts of adult ADPKD patients . A cliniData from preclinical studies show that common molecular and cellular mechanisms in ARPKD and ADPKD contribute to the pathogenesis of the different subtypes of PKD , 17. Thuwww.ARegPKD.org) and ADPedKD (www.ADPedKD.org) [Over the last years we have established the international registry studies ARegPKD (dKD.org) , 19. In PKHD1 variants being associated with severe phenotypes [PKHD1 variants have only recently been described [As ARegPKD has already been running for a few years, the first publications have emerged and can demonstrate the strength and the potential of the chosen international approach. Clinical research in the ARPKD field has been facing the typical problems associated with rare and variable disorders. ARPKD is a very rare disease with an estimated incidence of 1:20.000 –10 it haescribed , 23. AReescribed . To studIn addition to genetics easy-to-obtain clinical data are highly important for stratification of patients into risk groups. A recent study on 385 ARegPKD patients identified prenatal sonographic identification of enlarged kidneys, kidney cysts as well as documentation of oligo-/anhydramnios as candidates for prenatal markers to predict early dialysis dependency in ARPKD patients . Thirty-Thus, clinical and genetic markers have been identified in ARegPKD to categorize kidney disease progression in ARPKD. Such markers could in the future be supported and reinforced by radiological findings or biochemical markers. Most recently, we identified early childhood htTKV as a potential risk marker for kidney survival in ARPKD . Yet, ouPKD1 variant, non-truncating PKD1 variant, PKD2 variant), hypertension before the age of 35 years, first urologic event before the age of 35 years. These variables are weighed differently resulting in a final point score between 0 and 9 points that subsequently allows the classification of patients in three risk categories . A score of ≤3 has a negative predictive value of 81.4% for CKF before 60 years of age, whereas a score >6 shows a positive predictive value of 90.9% for chronic kidney failure before 60 years of age. The Mayo-TKV-Score classifies patients into typical and atypical radiological presentation, with five age-adjusted htTKV subclasses in the typical group (1A-1E in increasing order). Patients in higher classes show more rapid decline of kidney function and thus have a higher risk to develop CKF after 10 years.While ADPKD typically becomes clinically symptomatic in adulthood, cystogenesis starts in childhood or even antenatally. Major clinical variability has been described in ADPKD that can only partially be explained by the underlying genetics. It was for a long time believed that children of patients with ADPKD should not be examined but a “wind of change” has recently been noted in this field . More at2. Patient samples were compared to samples from age-, sex- and BMI-matched healthy controls. While plasma copeptin and urinary EGF did not show major differences, urinary MCP-1 was significantly higher in ADPKD patients compared to controls. This finding was driven by patients with PKD1 variants independent of their underlying genotype. A group of patients with very early onset ADPKD or early symptomatic ADPKD showed higher urinary MCP-1 levels than asymptomatic patients. Human fetal ADPKD kidneys displayed prominent MCP-1 staining and M2 macrophage infiltration and cellular models with PKD1 haploinsufficiency exhibited increased MCP-1 secretion. Thus, urinary MCP-1 may become an easily-obtainable marker of disease severity for subgroups of pediatric ADPKD patients [For progress in pediatric ADPKD research we will need the association of biobanking and deeply phenotyped patients. The samples obtained during a clinical trial on the efficacy of pravastatin in childhood were for example recently used for metabolic profiling of children and young adults with ADPKD . An addipatients . It may patients , 30.Over the past ten years there have been major developments in pediatric PKD research. The field has greatly benefitted from the knowledge and the experiences obtained in the general PKD field and in pediatric nephrology. This includes a better understanding of pathomechanisms as well as the identification of prognostic markers of disease progression in adult ADPKD patients. A concept is emerging in which ARPKD and ADPKD may be seen as two ends of a disease spectrum with overlapping genetic and clinical features Figure . The inf


Multivariate logistic regression analysis revealed that uncontrolled hypertension was significantly associated with BMI (p = .001), pulse pressure (p = .001), total cholesterol (p = .006), and non‐HDL cholesterol (p = .009). In patients with triglycerides levels > 200 mg/dl non‐HDL cholesterol had a significant correlation with uncontrolled hypertension . In conclusion, BMI, pulse pressure, total cholesterol, and non‐HDL cholesterol are significant predictors of uncontrolled hypertension in patients with type 2 diabetes. Also, ineffective monotherapy, medical inertia and patients’ non‐compliance were other contributors to the uncontrolled hypertension.Suboptimal blood pressure (BP) control in patients with type 2 diabetes is associated with adverse micro‐ and macrovascular complications. This study aimed to investigate the predictors of uncontrolled hypertension in an Iranian population with type 2 diabetes. This is a cross‐sectional study of 2612 patients with type 2 diabetes, including 944 patients with hypertension. Controlled and uncontrolled hypertension were assessed. Multivariate logistic regression modeling was used to determined independent predictors of uncontrolled hypertension. Of 2612 patients with type 2 diabetes, 944 (36.1%) patients had hypertension. Of all patients with hypertension, 580 (61.4%) were still on monotherapy. Uncontrolled hypertension was detected in 536 participants (56.8%). Patients with uncontrolled hypertension had significantly higher body mass index (BMI) (29.8±4.8 vs. 28.6±4.6), waist circumference (99.11±10.95 vs. 96.68±10.92), pulse pressure (67.3±17.3 vs. 48.4±10.7), total cholesterol (177.1±45.5 vs. 164.3±40.5), non‐HDL cholesterol (133.0±43.5 vs. 120.1±38.7), triglycerides (175.7±80.3 vs. 157.4±76.7), and Atherogenic Index of Plasma (AIP) (0.57±0.23 vs. 0.52±0.24) ( There were 54.8 million people with diabetes in the middle east and north Africa region in 2019, and this number is expected to rise to 107.6 million in 2045.The prevalence of hypertension among patients with type 2 diabetes is relatively high. This elevated blood pressure (BP) exacerbates both micro‐and macrovascular complications of diabetes mellitus, including retinopathy, nephropathy, coronary artery disease, an impact illustrated particularly in the ADVANCED trial.diabetes need to be further studied. Given the importance of this matter, we aimed to investigate predictors of uncontrolled hypertension among patients with diabetes attending the diabetes clinic of Vali‐Asr Hospital.Various studies had conducted to determine the main predictors of uncontrolled hypertension to help better strategize national health policies.22.1This was a cross‐sectional study using the data extracted from an ongoing prospective cohort study in patients with type 2 diabetes mellitus who were visited in the diabetes clinic of Vali‐Asr Hospital affiliated with Tehran University of Medical Sciences. Patients with type 2 diabetes were included in the study according to the criteria of the American Diabetes Association . The exclusion criteria for this study were type 1 diabetes mellitus, age < 30, and a history of cancer. Patient's medical records were assessed to identify hypertensive patients (Hypertension was defined according to 2019 ADA guideline with a systolic BP of ≥140 mm Hg or diastolic BP of ≥90 mm Hg or use of antihypertensive medication). Measurement of systolic and diastolic BP was performed in the seated position and after 10 min of resting with a standard digital sphygmomanometer. Furthermore, an adapted to the size BP cuff was used in patients with BMI > 30. The measurement of BP was repeated after 15 min, and the average was reported. In the current study, uncontrolled hypertension was defined as having systolic BP > 140 or diastolic BP > 90 in hypertensive patients in the first visit of this study. Briefly, we had three groups in this study: 1‐Normotensive (without hypertension history), 2‐Controlled hypertensive 3‐Uncontrolled hypertensive individuals. A total of 2612 patients with diabetes were enrolled in the current study. The study protocol was approved by the ethics committee of the Tehran University of Medical Sciences.2.2Patient characteristics such as age, sex, height, weight, waist circumferences, BP, smoking, duration of diabetes and hypertension, medication and laboratory measurements including fasting blood sugar (FBS), hemoglobin A1c(HbA1c), total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), triglyceride (TG), and serum creatinine were extracted from medical records of the first visit. Non‐HDL cholesterol is measured by subtracting HDL‐C from total cholesterol. Body mass index (BMI) (kg/m²) was calculated by weight (kg) divided by square height (m²). The estimated GFR was calculated using the Cockcroft‐Gault formula in each participant. Albuminuria was defined as having 24 h urine albumin of more than 30 mg. In the current study, NCEP ATP III criteria were used to determine metabolic syndrome.2.3p‐value of less than .05. A two‐sample t‐test was used for comparison between two independent groups with a normal distribution. ANOVA with post hoc tests was performed for comparison between three normally distributed independent groups. For non‐normally‐distributed variables, we used Mann‐Whitney U and Kruskal Wallis for comparison between two and three groups, respectively. Also, the chi‐square test was applied for categorical variables. The study analysis for calculating uncontrolled hypertension predictors is limited to the subset of diabetic patients with hypertension. We categorized the data based on good treatment target cut‐offs. We then used univariate binary logistic regression to identify significant determinants of BP control based on these categorized data. We fitted these determinants into a binary logistic model with BP control as a dependent variable to determine significant predictors of BP control, the variables with unadjusted p‐value < .2 for uncontrolled hypertension were recruited in the model. Collinearity between variables was tested by the correlation matrix. Non‐HDL cholesterol and TC, also, TG and AIP had a significant correlation with each other . To test both of their association with the outcome variable, we used them in two separate logistic regression models with other variables included.We used statistical software IBM SPSS version 25 for statistical analysis. Data distribution was explored, and normality tests were performed. For continuous variables, data are presented as mean ± SD or median)Interquartile range) and for categorical variables, it is presented as numbers (percentages). Statistical significance was defined as a two‐tailed 3p < .05). But no significant difference was observed between these two hypertension groups considering age, sex, smoking, duration of diabetes, duration of hypertension, HDL‐C, LDL‐C, HbA1c, e‐GFR, albuminuria, CAD, metabolic syndrome, medications including anti‐diabetic, antihypertensive, and lipid‐lowering agents (p > .05). About 87.2% of individuals with controlled hypertension and 90.8% with uncontrolled hypertension had metabolic syndrome (p = .13).After excluding 353 patients, our study population included 2259 patients with type 2 diabetes. We identified 944 individuals with hypertension history, and from these patients, 536 (56.8%) had uncontrolled hypertension. The demographic and laboratory characteristics of all of our study participants with type 2 diabetes are illustrated in Table 2, p < .001). Obesity was significantly higher in patients with uncontrolled hypertension than patients with controlled hypertension . Additionally, both controlled and uncontrolled hypertension groups had significantly higher BMI than normotensive individuals. BMI was significantly higher in the uncontrolled hypertension group compared to the controlled hypertension group . It should be noted that the age difference between patients with hypertension and patients without hypertension have a potential role in the pulse pressure variation.Pulse pressure was significantly higher in uncontrolled hypertension compared to the controlled hypertension group  and TC . Additionally, we observed significant difference between controlled hypertensive patients and their normotensive peers with regard to TG  and TC .Furthermore, patients with uncontrolled hypertension had significantly higher non‐HDL cholesterol compared to patients with controlled hypertension . Also, AIP was significantly higher among patients with uncontrolled hypertension in comparison with controlled ones .There was a statistically significant difference between controlled and uncontrolled hypertension groups regarding TG . However, it was significantly higher in normotensive patients than uncontrolled hypertensive patients. . Similarly, HbA1C was higher in normotensive patients compared to controlled hypertensive group  .FBS was significantly different between normotensive (190.1±80.1 mg/dl) and controlled (169.0±61.1 mg/dl) or uncontrolled hypertensive patients (174.8 ±63.5 mg/dl) (p = .001).HbA1c was not significantly different between controlled and uncontrolled hypertension groups , while Triglyceride and AIP did not have any significant difference between groups after adjustment for other variables. Furthermore, models with non‐HDL‐C had greater R square than models with total cholesterol (R2 = 0.431 in model 2 and R2 = 0.430 in model 4 Vs. R2 = 0.420 in model 1 and R2 = 0.424), it seems that higher levels of non‐HDL‐C are more suggestive of uncontrolled hypertension compared to total cholesterol. Moreover, based on model 2, the odds ratio of uncontrolled hypertension in patients with non‐HDL‐C more than 160 mg/dl was 2.391 compared to patients with non‐HDL‐C lower than 130 mg/dl (p = .002).Logistic regression models after adjusting for other variables were shown in Table p = .002) .In Table ) Figure . Also, i4This study highlighted four important characteristics associated with uncontrolled hypertension among patients with diabetes, including BMI, pulse pressure, total cholesterol, and non‐HDL cholesterol.4.1p = .004) and by 2.87 times in patients with BMI of more than 30 (p < .001). Likewise, both controlled and uncontrolled hypertensive patients had higher BMI than patients without hypertension. We noted a relatively high frequency of obesity among individuals with controlled and uncontrolled hypertension . Obesity contributes to hypertension by several mechanisms, including sympathetic nervous system activation,This study pointed out that BMI is a significant predictor for uncontrolled BP status in patients with type 2 diabetes, similar to previous studies.4.2Metabolic syndrome is a major cause of cardiovascular mortality.4.3Pulse pressure which is the difference between systolic and diastolic BP is known to be a significant independent risk factor for cardiovascular mortality.4.4We observed that higher triglycerides, total cholesterol, and non‐HD levels were associated with uncontrolled hypertension in univariate analysis. However, after adjusting for other variables in the final regression model, only total cholesterol and non‐HDL cholesterol remained significant predictors for uncontrolled BP. Comparably in a prospective cohort, Ruben O and colleagues showed that the highest quintile of TC and non‐HDL cholesterol increased the likelihood of developing hypertension by 23%, 39%, respectively.p = .002) .The current study showed that higher levels of non‐HDL‐C had a stronger correlation with uncontrolled hypertension among patients with serum triglyceride levels of more than 200 mg/dl  Figure . BesidesNon‐HDL cholesterol is the sum of LDL and VLDL. It includes all Apo B containing lipoproteins and represents a surrogate marker for total Apo B. Apolipoprotein B is a major atherogenic lipoprotein and a strong predictor for the severity of coronary heart disease. When triglyceride levels are lower than < 200 mg/dl, non‐HDL‐C correlates highly with LDL‐C and non‐HDL provides little additional power to predict coronary heart diseases. However, when triglycerides levels are more than 200 mg/dl, VLDL cholesterol levels are elevated, and LDL‐C levels correlate less with non‐HDL‐C. Consequently, in individuals with high triglycerides concentrations, non‐HDL‐C is a better representative of atherogenic lipoproteins than LDL‐C. In very high triglycerides levels , non‐ HDL‐C levels have a less predictive value for coronary heart disease.4.5Existing literature has not reached a consensus on the effect of anti‐diabetic drugs on BP. Our results showed no significant difference between controlled and uncontrolled hypertensive and normotensive groups regarding the type of anti‐diabetic medication, including oral anti‐diabetic agents, insulin, or both, and the type of oral anti‐diabetic agents themselves. Katsi V and colleagues reported that thiazolidinediones, DPP‐4 inhibitors, and SGLT2 inhibitors could have a BP‐lowering effect, and sulfonylureas might increase BP.Like previous studies, no sex disparity was seen considering BP control in patients with diabetes4.6Current evidence supports starting antihypertensive therapy with a two‐drug combination as the first line, based on the latest European society of cardiology and the European society of hypertension(ESC/ESH) 2018.4.7The cross‐sectional nature of our study makes it hard to conclude the causality between the predictors and the outcome variable. Also, the number of patients with OSA was not available.5Although most hypertensive patients were on antihypertensive medication, 56.8% of them had uncontrolled BP. This study suggested that uncontrolled hypertension in patients with type 2 diabetes was positively associated with high BMI, pulse pressure, total cholesterol, and non‐HDL cholesterol. This study showed that non‐HDL cholesterol is a strong correlate of uncontrolled hypertension in patients with both type 2 diabetes and hypertriglyceridemia. Additionally, it was demonstrated that despite suggesting dual antihypertensive therapy as the first line by the latest evidence, more than 50% of patients with hypertension were still on monotherapy. Furthermore, the role of ineffective monotherapy, medical inertia, and patients' non‐compliance in uncontrolled hypertension was illustrated. Identifying these predictors could be of great importance in that, it contributes to better strategic planning for tackling hypertension problems among high‐risk patients.This research is not supported by any particular person or organizationThe authors declare that they have no conflict of interest.Soghra Rabizadeh: conceptualization, methodology, investigation, writing ‐ Original Draft, data curation, writing ‐ Original Draft visualization, critically revising the manuscript. Bahareh Gholami: investigation, writing ‐ Original Draft.: data curation, methodology, writing ‐ Original Draft, visualization, critically revising the manuscript. Shiva Mahmoudzadeh Kani: methodology, investigation, writing ‐ Original Draft, methodology, writing ‐ Original Draft, visualization, review the revised version. Armin Rajab: validation, data curation, methodology, writing ‐ Original Draft, visualization, review the revised version. Hossein Farrokhpour: Investigation, writing ‐ Original Draft, visualization, critically revising the manuscript. .Alireza Esteghamati: validation, investigation, data curation, writing ‐ review & editing, review the revised version. Manouchehr Nakhjavani: conceptualization, methodology, supervision, writing ‐ review & editing, review the revised version. All authors read and approved the final revised manuscript.


Macular VD was significantly correlated with N95 amplitude, irrespective of disease severity . According to regression analyses, N95 amplitude and macular VD were bidirectional significant factors . For patients with mild to moderate glaucoma, N95 amplitude and macular VD were also significantly associated bidirectionally, according to regression analyses . Conclusions: Macular VD was significantly associated with N95 amplitude from PERG. The correlation was prominent in early glaucoma, in contrast to the other structural or functional parameters. When considering that PERG represents the objective function of the retinal ganglion cell (RGC), macular VD was associated with RGC dysfunction before the functional change became apparent on SAP.Purpose: To investigate whether macular vessel density (VD) was associated with the pattern electroretinogram (PERG) in normal tension glaucoma (NTG). Design: Cross-sectional study. Methods: Seventy-six eyes from patients with NTG were included in this study. Macular VD was calculated from the superficial retinal layer, including the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), using the built-in software provided with the optical coherence tomography angiography (OCTA) device. Functional parameters were obtained from standard automated perimetry (SAP) and PERG, using a commercial ERG stimulator. Moreover, structural parameters, such as peripapillary RNFL and macular ganglion cell/inner plexiform layer (GCIPL) thickness, were measured using OCT. Results: Patients with higher VD had higher N95 amplitude ( Glaucoma is a disease characterized by morphological changes in the optic disc and typical visual field (VF) defects of the corresponding topographic area . TherefoPattern electroretinogram (PERG) has been a long-proposed method for evaluating visual function to overcome the limitations of the VF test . RGC funOptical coherence tomography angiography (OCTA) is a method that could visualize the blood flow of the retina. Several studies reported about the vessel density (VD) changes in the peripapillary area and macula in patients with glaucoma, and concurrently found that VD decreased with the increase in the severity of glaucoma ,18,19,20The purpose of this study was to investigate the association between PERG parameters and VD obtained from OCTA in glaucoma patients. If VD from OCTA correlates with PERG, which is an objective electrophysiologic test, we aimed to identify the possibility of clinical application of OCTA, as an additional parameter of visual function.This study was conducted according to the tenets of the Declaration of Helsinki and was approved by the Institutional Review and Ethics Boards of Seoul St. Mary’s Hospital, South Korea. A total of 102 eyes of patients with normal-tension glaucoma (NTG) from the glaucoma clinic of Seoul St. Mary’s Hospital between July 2018 and December 2020 were included in this study. The need for written informed consent was waived by our Review Board.Patients were determined to have glaucomatous VF defects if they satisfied the following conditions: a group of 3 or more spots, 2 of the points had a chance of presence <5% in normal subjects, and 1 spot had a chance of presence <1% in normal subjects for the pattern deviation plot. The VF results were considered reliable if the fixation loss was <20%, false-positive rate was <15%, and false-negative rate was <15%. All subjects exhibited manifestations of glaucomatous optic discs such as increased CDR with localized thinning of the neuroretinal rim, generalized loss of the disc rim, or RNFL defects corresponding to VF defects. Mild glaucoma was defined as mean deviation (MD) of Swedish interactive threshold algorithm (SITA) 24-2 ≥ −6 dB, moderate glaucoma was defined as −6 dB ≥ MD ≥ −12 dB, and severe glaucoma was defined as −12 dB ≥ MD according to Hodapp–Anderson–Parrish criteria . All subThe other inclusion criteria were as follows: (1) best-corrected visual acuity (BCVA) of 20/30 or better, (2) intraocular pressure (IOP) ≤ 21 mmHg without the use of IOP-lowering eyedrops at first visit to the clinic, (3) open angle on gonioscopy, and (4) spherical equivalent within ±5.0 diopters. When both eyes fulfilled the inclusion criteria, one eye per individual was randomly selected.Patients were excluded if they had a history of uveitis; retinal diseases such as retinal vein obstruction, macular degeneration, and diabetic retinopathy; a history of intraocular surgery except for uncomplicated cataract extraction. Patients with any optic-nerve-related disease besides glaucoma, and/or a history of systemic or neurological diseases that might affect the VF or PERG were excluded.All subjects underwent complete ophthalmic examinations including slit-lamp examination, Goldmann applanation tonometry, gonioscopy, and dilated fundus bimicroscopy. SAP 24-2 was performed using SITA program . Circumpapillary RNFL thickness and ganglion cell/inner plexiform layer (GCIPL) thickness were measured using Cirrus spectral-domain optical coherence tomography . Only well-focused OCT images with signal strengths >6 were included.2 was reversed at the rate of 4 reversals per second at a 60-cm distance. The stimulus display covered 48 × 33° of the VF, with each check size of 1.8° visual angle. Subjects focused on the red fixation point at the center of display, and both eyes were examined simultaneously. The reproducibility of the ERG results was identified by previous studies using the intraclass correlation coefficient of the randomly selected measurements [A commercial PERG system  was used to record electroretinogram. One trained examiner performed the examinations. Two Ag/AgCl ground electrodes were placed on both earlobes, and reference electrodes were placed on the ipsilateral lower eyelid. Detailed description of the examination was provided in our previous study ,16. In surements ,16.The macular VD was measured using a swept-source OCTA device . The device used a wavelength of 1050 nm and scanning speed of 100,000 A-scans per second. A 4.5 × 4.5 mm macular scan was obtained in the “angio macula” mode, and the acquired image was automatically centered over the fovea. An active eye tracker system was used to minimize the motion artifacts on the image. The examinations were performed by one trained examiner and only images with quality scores over 70 were selected to ensure that the OCTA images would be of superior quality. The automatically segmented retinal vascular plexus consists of the superficial layer and deep layer. The VD of the superficial layer was used as the macular VD in this study; it was calculated automatically after applying the built-in software projections removal algorithm to the deep retinal and choriocapillary layers. The superficial vascular plexus extends from 2.6 μm below the internal limiting membrane to 15.6 μm below the junction of the inner plexiform layer (IPL) and inner nuclear layer (INL) (IPL/INL) according to the default settings of the device. The VD measurements were composed of five subfields using the Early Treatment Diabetic Retinopathy Study (ETDRS) grid overlay combining the two inner rings . The avep < 0.05 was considered to be statistically significant.All data are presented as the mean ± standard deviation. Student’s t test was used to compare the variables of the higher and lower VD groups. Linear regression analyses were conducted to evaluate the significant factors affecting macular VD or PERG N95 amplitude, and the analyses were applied to the total subjects or only to patients with mild to moderate glaucoma, respectively. All statistical analyses were performed using SPSS version 24.0 . Fially, A total of 102 eyes of patients with NTG, who met the eligibility criteria, underwent VF, OCT, PERG and OCTA examinations. Of the 102 eyes, 17 eyes (16.7%) were excluded from further analysis, owing to the poor quality or presence of motion artifacts on the OCTA images and nine eyes were excluded (8.8%) because the results of SAP or PERG were unreliable. The remaining 76 eyes with NTG were included in the final analysis. p = 0.048). Other parameters, such as RNFL thickness, GCIPL thickness, MD and PSD from SITA 24-2, P50 latency, N95 latency, and P50 amplitude, were not significantly different between the two groups.Participants were classified into the higher and lower VD groups based on the mean value of average macular VD, and their visual functional and structural parameters were compared . N95 ampp = 0.038), SITA 24-2 MD , and N95 amplitude , SITA 24-2, and PERG parameters were analyzed. 2 was the lowest for RNFL thickness (linear R2 = 0.007). Linear R2 of macular VD was higher than that of GCIPL thickness . In short, the association between N95 amplitude and macular VD showed the greatest linearity, compared to that of N95 with GCIPL or RNFL.According to p = 0.035, p = 0.032 for model 2 and 0.033 for model 3, p = 0.030 for RNFL thickness; 0.001 for GCIPL thickness; <0.001 for superior macular VD; 0.017 for temporal macular VD; 0.002 for average macular VD, p = 0.019, p = 0.020 for GCIPL thickness; 0.001 for superior macular VD; 0.046 for temporal macular VD; 0.014 for average macular VD, p = 0.042 and 0.040, respectively, The present study demonstrated the association between PERG amplitude, macular VD and other various structural and functional parameters, including OCT and visual field test, in NTG patients. Macular VD was correlated with the N95 amplitude of PERG, which could reflect RGC function objectively. In subgroup analyses, the association between macular VD and N95 amplitude was remarkable in patients with mild glaucoma, while the other structural parameters did not exhibit any meaningful correlation. Further, N95 amplitude was consistently associated to macular VD, irrespective of disease severity, but was not related to RNFL thickness in mild glaucoma patients. This result could be interpreted as meaning that macular VD may be representative of RGC function as PERG, before the onset of structural (GCIPL or RNFL thickness) or functional (SAP) changes.Studies have reported that several factors hinder the evaluation of visual function in early glaucoma using the VF test ,24,25. TRecently, several studies evaluated the possibility of using OCTA-derived VD as a visual function parameter. Yarmohammadi et al. reported that the association between OCTA and VF was stronger than that of other structural parameters obtained by OCT . A studyTherefore, we deduced that it would be worthwhile to identify whether OCTA was associated with visual function parameters, such as PERG, that represent objective RGC function. From the results of this study, objective RGC function, represented by PERG, was associated with macular VD, and it supported the possibility that macular VD could be a surrogate of visual function in early glaucoma. Dysfunctional neurons may have decreased oxygen demands, and also, inversely, metabolically challenged neurons could have depletion of function ,32. The Recently, two studies were presented evaluating the relationship between PERG and OCTA in glaucoma patients, from the same group. The prior study assessed the correlations between various parameters, including PERG, OCTA, OCT and VF, in an open angle glaucoma (OAG) patient . AccordiThis study has several limitations. First, this study only included NTG patients. NTG has some different clinical characteristics from primary open angle glaucoma, with elevated IOP associated with vascular problems, such as disc hemorrhage or systemic vascular diseases ,36,37. TIn conclusion, macular VD was associated with the N95 amplitude of PERG in NTG patients. Macular VD could reflect the dysfunction of RGC, presented by an electrophysiological test in early glaucoma. Macular VD could be used as a surrogate of visual function in patients with early glaucoma.


Multivariable model fitted through logistic regression  had an Area Under the Curve (AUC) of 0.748. Our analysis suggests a significant role played by different preoperative and perioperative variables in influencing the length of hospital stay.The aim of this retrospective investigation is to evaluate the correlation between several preoperative and perioperative factors and the length of hospital stay in patients that underwent elective total hip arthroplasty with overnight admission. Medical records of patients that underwent THA from the beginning of 2016 to the end of 2018 were retrospectively screened. Demographics, comorbidities, whole blood count, intraoperative details, and length of postoperative stay were retrieved. The association between clinical, laboratory and surgical factors and the length of hospital stay was explored by means of negative binomial and logistic regression models. The median length of postoperative hospital stay was four days . After univariate regression a stepwise multivariate regression showed that operative time ( Total hip arthroplasty (THA) represents the gold standard for the elective treatment of symptomatic degenerative and rheumatologic diseases of the hip at later stages . It is cThe main aim of the present study is to investigate the potential correlations of preoperative and perioperative factors with the length of hospital stay in the orthopedic ward, for subjects that underwent elective primary THA. A secondary aim is to develop and evaluate a multivariate model to predict the risk of increased LOS. The null hypothesis is that none of the evaluated factors shows a correlation with the length of hospitalization.A retrospective evaluation of electronic medical records at Campus Bio-Medico University Hospital, in Rome, Italy, was carried out. The STROBE statement was used to check for a correct reporting. Medical records of patients that underwent THA since the 1 January 2016 to the 31 December 2018 were screened. The study was approved by the Ethical Committee of the Institution (Protocol number: 32/19 OSS ComEt CBM). Informed consent for the treatment of personal health information for research purposes was signed by all patients at the first registration at our institution. The study was conducted in respect of the principles of the declaration of Helsinki for research on human subjects.Inclusion criteria were adult subjects that underwent elective primary THA surgery; diagnosis of primary or secondary osteoarthritis; medical record available within electronic database of the institution; complete records including all the clinical data of the patient. Exclusion criteria were the following: revision surgery, hip fracture, oncologic patients, one-stage bilateral procedures, no informed consent given for data collection. All surgeries were carried out at our institution by two experienced surgeons, with a minimum 20 years of experience in adult joint replacement. Selection process is shown in Of the data available in the medical records of the included patients, after accurate review of the literature, consensus was reached within a multidisciplinary team of investigators  upon which data should be included in the analysis. Demographic data included sex and age, and usual residence of the patient. Among comorbidities, patient’s records were screened for presence of diabetes mellitus, arterial hypertension, dyslipidemia, heart failure, coronary disease, Chronic Obstructive Pulmonary Disease (COPD), Chronic Kidney Failure (CKF). The American Society of Anesthesiologists (ASA) score was also extracted. Furthermore, information about smoking habits were retrieved (smokers or smoke in the past). Preoperative whole blood count and inflammatory markers  data were also collected. Surgical details included: surgical approach, operative time, use of cement for cup and/or stem, and intraoperative blood loss. Data on the length of postoperative orthopedic ward stay were retrieved.The LOS was processed as a discrete variable (days of stay after the surgery), obtained by the difference in nights between the date of discharge and the day of surgery. LOS was also transformed into a dichotomous variable, where the median value of the discrete series was used as a cut-off to identify a short  or long (major than the median) stay. Data on usual residence of the patient have been collected to assess whether the patients lived inside or outside the city. Living outside the city (within the region) and living outside the region were processed as two binary (dichotomous) variables. Day of the week of the day of surgery was also found, through the processing of the date of surgery, the series was then transformed from a discrete to a dichotomous one, where “Friday” and “Other weekdays” were the binary values. Estimated Glomerular Filtration Rate (eGFR) was calculated through the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method ,21. The p < 0.10 at univariate analysis. Stepwise selection with backward deletion was carried out, to define a model with all-significant independent predictors. The best-fit negative binomial multivariate model was subsequently fitted in logistic regression, using the dichotomic transformation of LOS as dependent variable. The output was reported as Odds Ratio with 95%CI. A Receiving Operator Characteristics (ROC) curve was plotted and Area Under the Curve (AUC) was calculated. Youden’s index was then calculated to find the cut-off values for continuous predictors. Tabular analysis was carried out to found discriminants in discrete predictors. The significance threshold was conventionally set with p < 0.05. All analyses were conducted with STATA software for statistical computing for Mac .Database consistency and completeness was assessed before proceeding with the planned analysis. Data series had a maximum incompleteness of 8%. Missing data in continuous series were addressed through the imputation of the mean, in discrete or binomial distribution, the median was used for imputation. Continuous variables were shown as mean with standard deviation (SD), while discrete variables through the median and interquartile range (IQR). Categorical Binomial variables were presented as absolute numbers and percentages. Length of hospital stay after surgery was defined as dependent variable, distribution and variance were checked, to choose the best regression model. The association between clinical, laboratory and surgical factors and the length of hospital stay was explored by means of multiple univariate negative binomial regression models and expressed as Incident Risk Ratio (IRR) with 95% confidence intervals (95%CI). A multivariable negative binomial model was also fitted including as independent variables all factors found associated with A total of 743 patients satisfied inclusion and exclusion criteria and their data were collected and analyzed. The mean age was 68.1 years (SD: 10.4) and 333 subjects (44.8%) were male. Patients living outside the city, but within the administrative region were 378 (51.3%), while those living outside the region were 107 (14.5%) .The most commonly observed comorbidity was arterial hypertension (47%), followed by dyslipidemia (20.4%), chronic kidney disease (12.1%) and diabetes mellitus (9%). Details on comorbidities prevalence were reported in The decubitus and surgical approach varied within the cohort, with the lateral decubitus, direct lateral approach being the most common (42.2%), followed by the supine decubitus, anterolateral approach (35.7%). Details are summarized in p = 0.041), an increased value of preoperative white blood cell , increased preoperative creatinine value , increased operative time , increased intraoperative blood loss  and the use of a supine decubitus, anterolateral approach . Conversely, the variables significantly associated to a reduced LOS were limited to the inguinal approach  and lateral decubitus, direct lateral approach . Full coefficients summary is reported in The discrete LOS series approximated Poisson distribution, with large overdispersion. Thus, the negative binomial model was used to fit regression. By fitting multiple univariate models for each independent variable, those significantly associated to the risk of increased LOS were: the presence of Chronic Kidney Failure (CKF)  of 70.2. All independent variables in the model had a significant association with an increased LOS  of 97.5. ROC curve was plotted for the logistic model, showing an AUC of 0.748  [Operative time, intraoperative blood loss and surgical positioning and approach are the intraoperative factors found to be statistically associated to a prolonged LOS. However, although statistically significant, the association of operation time and intraoperative blood loss was definitely slight, with a respective IRR of 1.002 and 1.003 . Given the observed result, these factors could be considered not clinically relevant in defining a real-world risk factor for an increased LOS. However, an increased intraoperative blood loss may lead to an increased likelihood of blood transfusion, thus the need for a prolonged stay. Unfortunately, data on blood transfusion were not available in our database. These results may put the basis for further investigation concerning intraoperative factors influencing THA outcomes and postoperative LOS. Consistently with this observation, in a paper by Abbas et al. , no asso= 0.154) .A recent systematic review  reportedMultivariate models have been rarely investigated in this field. A study by Roger et al. showed that no comorbidity reached a relevant hazard ratio to postpone the discharge after the 5th postoperative day , though The major strength of the present study is the large cohort we reviewed, to achieve clinical relevance and external validity. The results of our investigation are partially in line with those reported in literature, although a few studies reported data of such a wide cohort and no study fitted more than two appropriate models to individuate independent predictors for increased LOS. Furthermore, we investigated all the preoperative and perioperative factors potentially relevant for the duration of stay, according to existing literature, thus preventing selective reporting. However, the study is not free from limitations. Firstly, we limited our analysis considering the orthopaedic ward stay and did not have data on the postoperative rehabilitation time at the rehabilitation facility. Furthermore, no data on functional status of patients before and after surgery and no data on complication were available. Moreover, the retrospective design and the absence of a single surgeon performing the surgeries may be relevant bias for the clinical inference of these results.Future research in this field should be focused on the role of non-steroidal anti-inflammatory drugs (NSAIDs) in influencing the renal homeostasis, with possible drawbacks on progressive kidney failure for those patients that have NSAIDS self-administered in preoperative period, due to the severe ongoing arthritis. Furthermore, there is a lack of data and evidence concerning the role of social and family support for these patients .In conclusion, among the several factors that influence the length of hospital stay after THA, our analysis demonstrated a significant role played by the preoperative creatinine  and of anterolateral approach. Particular attention should be directed to patients with already established CKD at hospital admission, especially concerning increased creatinine and NSAIDs administration in these subjects. The role of surgical approach is still debated in the literature and further investigations should be carried out, with meta-analytic strategies.


BackgroundOverseas kidney transplantation is known to be associated with adverse outcomes. In this study, we aim to present a detailed analysis of our three years of experience with overseas kidney transplantation at one of the largest kidney transplant referral sites in the Kingdom of Saudi Arabia.Materials and methodsA retrospective cohort study included patients who underwent kidney transplantation overseas and were subsequently followed up at King Abdulaziz Medical City from January 2016 to July 31, 2019. In addition, we compared the outcomes of the patients who underwent kidney transplantation overseas with a cohort of patients who were transplanted locally within the same period. Patients in both cohorts had to have at least one year of follow-up post-transplantation.ResultsWe included a total of 51 patients who underwent kidney transplantation overseas. The mean age of the cohort was 44.7 years, and 69% were male. Almost 60% of the cohort had one or no comorbidity prior to transplant, with hypertension (84%) and diabetes mellitus (37%) being the leading comorbidities. The cause of end-stage kidney disease was unknown in 55% of our patients. In those who had an identifiable cause, lupus nephropathy and diabetes were the most common causes of kidney failure. In comparison with the locally transplanted cohort, no difference was detected between these groups in their baseline characteristics, type or number of comorbidities, medical or surgical complications postoperatively, and one-year mortality. However, we found that the graft rejection rate was significantly higher in patients transplanted overseas . In addition, the proportion of patients who received anti-thymocyte globulin (ATG) induction was also less in the group with overseas kidney transplantation .ConclusionOverseas transplantation is associated with an increased risk for graft rejection. Our study suggests that overseas kidney transplantation is possibly driven by a lack of donors, especially cadaveric. Counseling patients about risks associated with overseas kidney transplantation and encouraging the public to register for organ donation after death may help curb out this practice. Patients with end-stage kidney disease (ESKD) suffer from a profound effect on their physical, psychological, and financial aspects due to morbidity caused by kidney failure and the requirement of chronic dialysis . For mosThe considerable waiting time has resulted in patients seeking transplantation in countries where barriers to transplant are less, and finding non-related living donors is feasible. Concerns in the medical community have risen due to this trend ,7. Many In this paper, we present our experience with transplant tourism and provide information on trends, outcomes, and challenges associated with this practice. In addition, we hypothesize that the recipients of overseas transplant would have more comorbidities, would show an inferior graft outcome, and have a higher incidence of post-transplant complications. To prove our hypothesis, we compared the overseas kidney transplant cohort with another cohort of patients that underwent kidney transplantation locally within the same period.The study was conducted at King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia. We included patients who underwent kidney transplantation overseas from January 2016 to July 31, 2019, with at least one year of follow-up post-transplantation. The recipients in this cohort underwent the transplant overseas at their own risk and without the consent/endorsement of their treating nephrologists. Consistent with the declaration of Istanbul on organ trafficking and transplant tourism, our center does not support transplant tourism, and such practice is considered exploitation of poor donors by rich individuals and is prohibited . HoweverWe obtained the IRB approval from King Abdullah International Medical Research Center (RC20/386/R) before the initiation of the study. We collected baseline characteristics , transplant-related variables , and post-transplant complications . We compared the baseline characteristics and outcomes of the cohort that underwent kidney transplantation overseas to a cohort of patients that were transplanted locally within the same period and who also had at least one year of follow-up post-transplantation. The details of the locally transplanted cohort were published separately earlier this year . Due to Statistical Package for the Social Sciences  software was used for data analysis. Categorical variables were presented as frequencies and percentages, whereas continuous variables were presented as mean ± standard deviation. We used the chi-squared test or Fisher's exact test to compare dichotomous data. Independent sample t-test analysis was applied to determine whether there was a statistical difference between the two groups' means. Odds ratio (OR) was used to estimate the magnitude of the association between post-transplant clinical outcomes and the location of transplantation.2 (range 16-35). The baseline characteristics of our cohort are presented in Table We identified 51 patients who underwent kidney transplantation overseas and met our inclusion criteria. Their median age was 41 years (range 23-87), and their median pre-transplant BMI was 26 kg/mFocusing on data specific to kidney transplants, as expected, living non-related kidney donation was the commonest source for kidney graft (94%), while 6% of the cohort received kidneys from deceased donors. Due to limited medical records provided by the patients returning after overseas transplants, we were unable to ascertain how the patients got on the waiting list of a different country, nor could we estimate the waiting time to get a deceased donor kidney transplant overseas. The pre-transplant serological testing showed that more than half of patients were positive for cytomegalovirus (CMV), and almost 90% were positive for Epstein-Barr virus (EBV). Anti-thymocyte globulin (ATG) based induction therapy was used in only 22% of patients, while the rest received a basiliximab-based regimen. Nearly all patients (98%) received a maintenance immunosuppressive regimen consisting of tacrolimus, prednisone, and mycophenolate. Regarding clinical course immediately following kidney transplant surgery, only one patient required intensive care unit admission, almost 8% developed surgical compilations , and 31% developed urinary tract infection. The value of serum creatinine at the time of discharge following kidney transplant surgery was missing in almost three-fourths of the cohort, as most of the patients receiving transplantation overseas brought limited records with them. Of those who had a creatinine reading at the time of discharge following the overseas transplant, the median value was 107 umol/l, with a maximum value of 349 umol/l recorded in one patient, and 10% of patients developed delayed graft function. No mortality occurred after one year of follow-up; however, almost 30% of patients developed graft rejection in this period. Long-term post-transplant complications were rare .When comparing the overseas transplanted cohort with their locally transplanted counterparts, we found that patients who had transplantation overseas constituted 21% of the transplant cohort followed up at KAMC during the specified period of the study. The number of patients transplanted overseas decreased by 75% between 2016 and 2018. Half of the overseas transplants occurred in 2016, followed by 11 transplants in 2017, 13 transplants in 2018, and only one in the first half of 2019. On the other hand, the number of kidney transplants performed locally increased by 48% in the same period .The baseline characteristics of the recipients of overseas kidney transplants were similar to our locally transplanted cohort. Although the number of patients with no comorbidities was higher in our local transplant cohort (20% vs. 10%), the difference in the number or types of comorbidities among the two groups did not reach any statistical significance (p=0.23). The type of induction therapy used did differ significantly between the two groups. The use of an ATG-based regimen was more prevalent locally compared to overseas . We did not find any difference in the number or type of surgical/medical complications that developed during initial admission for kidney transplant between the two groups. In addition, the OR for delayed graft function was similar between the two groups . However, the OR for graft rejection in the first year was significantly higher in the overseas group compared to the locally transplanted cohort . When we restricted the analysis to non-related donors, the graft rejection rate remained significantly higher in the overseas transplanted group compared to the locally transplanted cohort  developed graft rejection; all of them were diagnosed upon the patients' first presentation to our hospital within one week of their renal transplant surgery. Thirteen patients (25%) had cellular rejection; 11 of them were treated with pulse steroid followed by a tapering steroid regimen and ATG at a dose of 4-7 mg/kg. The remaining two patients, one had borderline rejection and one had Banff IA, were treated with pulse steroids followed by a tapering dose of prednisone. Only one patient required hemodialysis for two weeks until he recovered his renal function. Two patients had mixed rejection, cellular and antibody-mediated rejection (AMR), and were treated with ATG at a dose of 6-7 mg/kg, pulse steroid followed by a tapering steroid, five sessions of plasma exchange, intravenous immunoglobulins at a dose of 100 mg/kg after each session of plasma exchange and rituximab at a dose of 375 mg/mOver the last three decades, transplant experts have expressed concerns regarding overseas transplantation practice ,14. In tWe also noted that the type of induction therapy varied significantly between the local and overseas groups, where patients who underwent overseas transplants were less likely to receive an ATG-based induction regimen. Our center's approach is to give ATG to the patients with high immunological risk, while patients with low immunological risk can receive basiliximab. This approach is consistent with kidney disease: Improving Global Outcomes (KDIGO) practice guidelines . We hypoThe development of acute rejection of the transplanted kidney reduces long-term graft survival, particularly if not completely reversed ,18. It iSince overseas transplant is commercially driven, patients in overseas transplant centers tend to have the shortest possible postoperative hospital stay and are asked to fly to their home country upon discharge. The mean length of stay of our overseas transplanted group was 3.4 days. This explains why these patients present immediately to our center to establish care for their transplanted kidney and often require hospitalization for re-evaluation for any transplant-related acute complications. We found that patients who transplanted kidney overseas had higher surgical and medical complications in the immediate postoperative period compared to the locally transplanted cohort. Similarly, delayed graft function and long-term post-transplantation complications such as diabetes were also higher in this group; however, these differences did not reach statistical significance. The lack of statistical significance is likely related to the small sample size of the locally transplanted cohort. We hypothesize that patients who underwent transplantation may have had more comorbidities and thus were ineligible to undergo transplantation locally. However, no statistical difference was found between our locally transplanted cohort and those who had transplantation overseas in number or type of comorbidities. This supports our hypothesis that the lack of available donors was the main driver for those patients to seek kidney transplantation overseas. A recent survey showed that the availability of donors is the most common barrier to kidney transplantation . Living-A local survey revealed that only 56% of patients on dialysis were referred for pre-transplant evaluation and 29% were on the active transplant list . It is pIt is reassuring that the number of recipients of commercial transplants has fallen from 2016 to 2019. This may be related to the nationwide initiative that was launched in 2017 to increase public awareness of the importance of organ donation, both living and deceased organ donation. The initiative also increased the awareness of transplant tourism and its associated risks. Our previously reported local data showed that the number of kidney transplants performed at our center had gone up. However, there is still more work to be done to expand the donor pool and limit commercial transplantation. Our study has strengths and limitations. This study is one of the few local studies that provided a comprehensive overview of overseas kidney transplantation in Saudi Arabia. It also offered insight into the outcomes of overseas transplants compared to a reasonably matched locally transplanted cohort who underwent transplantation within the same time frame. Our findings substantiate the previously raised concerns regarding transplant tourism and identify areas of improvement to decrease the commercial transplant. The main limitation of our study is the small sample size, a single-center study, and the short follow-up period. In addition, the observational and the retrospective nature of our study made it susceptible to various types of bias. Further studies are needed to examine the long-term outcomes of transplant tourism and determine the factors that compel patients to seek commercial transplants.Commercial kidney transplantation is associated with a higher rate of rejection episodes than locally performed unrelated kidney transplantation. The use of basiliximab induction without properly assessing the pre-transplant immunological risk may explain the higher rate of rejection. Further studies are highly needed that examine the long-term outcomes of commercial transplantation and identify factors that drive such practice. Also, urgent interventions to increase the donor pool, both living and deceased, and timely referral to transplantation centers are strongly recommended to curb the need for commercial transplantation.


Many dental procedures begin with local anesthesia. Subsequent increase in blood pressure in healthy individuals commonly occurs and may be affected by several factors such as mental and physical stress, painful stimuli, and action of catecholamines present in local anesthetic solutions. The aim of the present study is to compare the effects of 4% articaine with 1 : 100000 epinephrine and 2% lidocaine with 1 : 80000 epinephrine on blood pressure after maxillary infiltration technique. t-test, and paired t-test.  In this randomized clinical trial, 102 patients were randomly assigned into two groups. One group received 4% articaine with 1 : 100000 epinephrine and the other group received 2% lidocaine with 1 : 80000 epinephrine for local maxillary infiltration. Systolic and diastolic blood pressure of both groups was determined twice: once before anesthetic injection and once 10 minutes after injection. The data were statistically analyzed using descriptive statistics, Shapiro–Wilks test, Levene test, chi-square test, independent p=0.127). The mean diastolic blood pressure after injection was 85.02 ± 7.331 in the articaine group and 81.35 ± 12.815 mmHg in the lidocaine group. These values show no statistically significant difference (p=0.080). In both groups, the mean systolic and diastolic blood pressures have increased significantly (p < 0.001).  The mean systolic blood pressure after anesthetic injection in the articaine and lidocaine groups was 125.00 ± 5.67 and 123.16 ± 6.417 mmHg, respectively, showing no statistically significant difference ( Articaine can be regarded as a suitable alternative for lidocaine for maxillary local infiltration, as no significant difference was observed between the effects of the two anesthetic solutions on blood pressure. Many dental procedures are preceded with local anesthesia. Anesthetic drugs are among the most common drugs used in dentistry. It has been estimated that annually more than 300 million cartridges of local anesthetics are used by dentists in the United States .Increased blood pressure is common after injection of local anesthetic drugs . The amoA variety of dental anesthetic drugs are available for dental purposes . Lidocai2 saturation after anesthesia and exodontia showed no significant difference among the groups. However, since the articaine solution with the least concentration of vasoconstrictor had the smallest effect on systolic blood pressure, it was considered safer for anesthesia before dental extraction [Several studies have attempted to compare the hemodynamic effects of different anesthetic solutions. Abu-Mostafa et al. evaluated the hemodynamic effects of articaine and lidocaine solutions with different epinephrine concentrations and concluded that diastolic blood pressure, heart rate, and Otraction . In anottraction .Aside from type of anesthetic drugs, the technique of the injection is important for appropriate anesthesia , 18. TheThis triple-blind randomized clinical trial was approved by the Ethical Committee of Mazandaran University of Medical Sciences (code IR.MAZUMS.REC.1398.544). The protocol for this trial was registered in the Iranian Registry of Clinical Trials (#IRCT20200724048188N1). The trial was performed on candidates for nonsurgical extraction of posterior maxillary teeth attending Department of Oral and Maxillofacial Surgery of Sari Dentistry School, Iran, from October 2018 to July 2019. All patients signed the informed consent form designed in accordance with the principles of the Helsinki Declaration prior to enrollment and were free to withdraw from the study at any stage.Sample size was calculated based on 95% confidence interval, 90% power as 88 . Considering 15% sample loss, the sample size was increased to 102 .Inclusion criteria were class 1 American Society of Anesthesiologists patients aged 18 to 55 years, not taking any medication, no contraindication for administration of epinephrine, containing anesthetics, nonsmoker patients, without dental phobia, without excessive pain or swelling on admission, and not being pregnant. Patients who experienced dental emergencies after injection were excluded from the study.The patients were randomly assigned using computer-generated random numbers into two groups: lidocaine group and articaine group . The patDemographic characteristics of the patients were recorded. All patients were positioned semisupine in the dental chair. Systolic and diastolic blood pressures were measured after a 15-minute rest, while the patient's hand was straight at the heart level using a manual sphygmomanometer . Prior to the injection, the depth of the vestibule at the region was dried with gauze. Then, benzocaine anesthetic gel was applied to the area of injection for 3 minutes. Cartridges of 4% articaine with 1 : 100000 epinephrine and 2% lidocaine with 1 : 80000 epinephrine were used. The anesthetic cartridges were covered with a black tape by a researcher so that the operator does not know the type of the anesthetic drug. The cartridges were placed in an aspirating syringe with a 27-gauge short needle. Two-thirds of the anesthetic solution was infiltrated in the depth of the buccal vestibule of the tooth that was planned for extraction in 40 seconds. An additional 0.3 ml of the anesthetic agent was also injected in the palatal mucosa 1-2 mm below the free gingiva. All the injections were performed by an adequately trained dental student under supervision of an oral and maxillofacial surgeon. 10 minutes after injection, systolic and diastolic blood pressures were measured once again with the same method. The operators tried to control their verbal communication and overall environment of the room for all patients. Following the injection procedure, nonsurgical extraction was performed according to the preexisting treatment plan.t-test was used. To compare the mean systolic and diastolic blood pressures before and after injection in each group, the paired t-test was used. Statistical analysis was performed using Statistical Package for the Social Sciences .The statistician was blind to the experimental groups. Demographic characteristics of the patients were evaluated using descriptive statistics and were represented as means, standard deviations, medians, and frequency percentages. Prior to statistical analysis, normal distribution of the data and equality of variances were assessed using Shapiro–Wilk test and Levene test, respectively. To compare the sex distribution of the two groups, the chi-square test was used. To compare the mean systolic and diastolic blood pressures before and after anesthetic injection between the two groups, the independent p=0.843). Mean age of the study participants in the lidocaine and articaine groups was 38.24 ± 2.080 and 39.63 ± 1.969, respectively. Mean age of the participants was not statistically different between the two experimental groups (p=0.602).102 consecutive patients enrolled in the study; 51 in each experimental group. The lidocaine and articaine groups were consisted of 26 males and 25 females and 27 males and 24 females, respectively. The sex distribution in the two groups was not significantly different . Moreover, mean systolic and diastolic blood pressures after anesthetic injection did not have a statistical significant difference between lidocaine and articaine groups . However, the increase in systolic and diastolic blood pressures of the patients in each experimental group was statistically different (p < 0.001) (Mean systolic and diastolic blood pressures before anesthetic injection were not significantly different between lidocaine and articaine groups (< 0.001) .In the present study, lidocaine and articaine both increased systolic and diastolic blood pressure after maxillary infiltration. However, these drugs were not significantly different in increasing the blood pressure. Similarly, Abu-Mostafa et al. found the same trend of significant increase in their study . This inEpinephrine is used in dental anesthetic solutions as a vasoconstrictor agent for increasing depth and duration of the induced local anesthesia. This agent has various hemodynamic effects. Its alpha-adrenergic effects lead to peripheral vasoconstriction, and its beta-constriction increases heart constrictions and vasodilation is muscles. Therefore, epinephrine increases blood pressure and pulse rate and decreases blood pressure , 22. AkiNo complication related to anesthetic injection, including facial edema, infection, or paresthesia, was observed in the present study. Malamed et al. reported that the most frequent adverse events following the use of articaine were headache, facial edema, infection, gingivitis, and paresthesia. However, due to the low frequency of such events, they concluded that articaine is a safe drug for clinical application .This study had some limitations. Some of the factors affecting the patients' blood pressure, such as emotional status or time of the day, were not controlled. Future studies are needed to clarify the effects of various contributing factors in hemodynamic changes after injection of different anesthetic agents.Articaine can be regarded as a suitable alternative for lidocaine for maxillary local infiltration, as no significant difference was observed between the effects of the two anesthetic solutions on blood pressure.


Despite a large body of evidence, the implementation of guidelines on hemodynamic optimization and goal-directed therapy remains limited in daily routine practice. To facilitate/accelerate this implementation, a panel of experts in the field proposes an approach based on six relevant questions/answers that are frequently mentioned by clinicians, using a critical appraisal of the literature and a modified Delphi process. The mean arterial pressure is a major determinant of organ perfusion, so that the authors unanimously recommend not to tolerate absolute values below 65 mmHg during surgery to reduce the risk of postoperative organ dysfunction. Despite well-identified limitations, the authors unanimously propose the use of dynamic indices to rationalize fluid therapy in a large number of patients undergoing non-cardiac surgery, pending the implementation of a “validity criteria checklist” before applying volume expansion. The authors recommend with a good agreement mini- or non-invasive stroke volume/cardiac output monitoring in moderate to high-risk surgical patients to optimize fluid therapy on an individual basis and avoid volume overload. The authors propose to use fluids and vasoconstrictors in combination to achieve optimal blood flow and maintain perfusion pressure above the thresholds considered at risk. Although purchase of disposable sensors and stand-alone monitors will result in additional costs, the authors unanimously acknowledge that there are data strongly suggesting this may be counterbalanced by a sustained reduction in postoperative morbidity and hospital lengths of stay. Beside existing guidelines, knowledge and explicit clinical reasoning tools followed by decision algorithms are mandatory to implement individualized hemodynamic optimization strategies and reduce postoperative morbidity and duration of hospital stay in high-risk surgical patients. Postoperative mortality has been reported to vary between 1 and 4% in developed countries . HoweverWhich blood pressure goals should be targeted during anesthesia and the perioperative period?Intraoperative fluids management: restrictive, standard, liberal and beyond?Are dynamic indices and maneuvers useful to predict and manage volume expansion?When should we measure stroke volume (SV) and cardiac output (CO)?Fluids or vasoconstrictors: how to decide?What is the economic impact of hemodynamic monitoring for GDT?To facilitate/accelerate implementation of guidelines on perioperative GDT, a national panel of experts in the field, representative of the whole French territory and who have previously collaborated on guidelines of the French Society of Anesthesiology and Critical Care is proposing an approach based on questions/answers on issues that are frequently mentioned by clinicians. These six relevant questions are:The members of the panel first identified the questions and subsequently organized the answers by summarizing elements of guidelines, knowledge, and explicit clinical reasoning tools followed by decision algorithms when appropriate. The decision algorithms were adopted following a modified Delphi process and the RAND/UCLA Appropriateness Method . We consMonitoring blood pressure is a prerequisite during anesthesia. The main objective is to prevent postoperative complications resulting from either arterial hypo- or hypertension. The arterial pressure can be monitored at different anatomical sites, using various techniques, non-invasively or invasively, and in a continuous or intermittent manner. Although all excessive excursions of arterial pressure may be detrimental, the association between intraoperative arterial hypotension and postoperative complications is the most thoroughly documented.To date, there is no universal definition for arterial hypotension during anesthesia. However, evidence from several large observational studies suggest that intraoperative mean arterial pressure (MAP) below 60–70 mmHg may be associated with postoperative acute kidney injury, myocardial injury, and death –14. Althversus intermittent) measurement of arterial pressure was associated with higher sensitivity to diagnose arterial hypotension during anesthesia, continuous measurement of arterial pressure should be preferred. Non-invasive continuous monitoring of arterial pressure is not yet considered interchangeable with invasive monitoring and there is insufficient evidence to recommend its use in high-risk surgical patients and/or high-risk surgery. Future efforts should concentrate on trying to verify whether treating hypotensive episodes as detected by those new techniques results in improvement in patient outcome rather that repeating validation studies that are bound to provide the same results over and over.Finally, because even short cumulative durations of arterial hypotension are associated with poor outcome and because continuous .Intravenous fluid administration is the most frequent therapeutic intervention to maintain or restore tissue perfusion during surgical procedures. However, it is well established that inadequate volume therapy can result in deleterious effects, especially in frail or high-risk patients. Insufficient fluid administration will lead to reduced flow and potentially inadequate perfusion in some territories where the conductive vessels are more resistive. These territories may differ from one patient to another and can involve every organ. The reduced local blood flow can induce cellular hypoxia and subsequent organ dysfunction or failure. On the other hand, if fluid is administered in excess, venous congestion and edema will ensue. The consequences of fluids in excess are probably as deleterious as the consequences of hypovolemia, and many studies have established a clear relation between positive fluid balance and postoperative complications , 24. ThuTherefore, optimizing tissue perfusion in high-risk patients relies on an individualized approach. The MAP will be maintained above a level close to the usual value of the patient, as suggested above. Minimal value for hemoglobin concentration and transfusion thresholds will vary according to the comorbidities of each patient. And since the ideal values of organ flow for a given patient are unknown, it is recommended to titrate fluids using small iterative boluses  guided by measurements of SV variation  Experts’ opinion:We propose to routinely use a personalized approach of intraoperative fluid infusion/volume expansion based on the individual hemodynamic response to volume titration to reduce the deleterious side effects of fluids and improve patients’ outcome (agreement 100%).Fluid responsiveness is defined as a significant increase in blood flow in response to a fluid bolus . PredictSubsequently, it could be reasonable for routine practice to implement a “validity criteria checklist” before using PPV or similar approaches to estimate fluid responsiveness Table  47]. Wh. Wh47]. Experts’ opinion:We propose to implement a “validity criteria checklist” before using PPV (or similar methods) to estimate fluid responsiveness, then to give iterative small fluid boluses to maintain intraoperative PPV (or similar methods) below the threshold value that defines fluid responsiveness (agreement 100%).While guidelines highly recommend the assessment of CO/SV for perioperative fluid GDT in high-risk surgical patients , less thExperts’ opinion:We propose to use mini- or non-invasive continuous methods to monitor CO/SV rather than invasive reference techniques to implement perioperative GDT in moderate to high-risk patients undergoing non-cardiac surgery (agreement 83%).Two experts pointed out problematic limits regarding accuracy of those mini- or non-invasive methods in patients with hypothermia or peripheral hypoperfusion or receiving continuous infusion of vasopressors.Tissue perfusion means delivering enough oxygen, glucose and other metabolites to every cell, as well as clearing the byproducts of cell metabolism. This is achieved when the flow at the level of the microcirculation of each organ is “adequate”, a condition that is impossible to assess with our current monitoring capabilities. Therefore, we concentrate our attention on the major determinants that will most likely result in adequate microcirculatory blood flow: MAP value that is sufficient to drive blood flow through every organ and a systemic blood flow that is able to cover for the total body oxygen requirements. Thus, ideally, both instantaneous arterial pressure and beat by beat systemic blood flow should be monitored in addition to heart rate to “optimize” tissue perfusion. Diastolic arterial pressure is mainly determined by vascular tone . Low diaDespite the fact that anesthesia induction produces vasodilation and reduces venous return via a reduction in effective volemia or stressed volume (as a consequence of the increased venous capacitance without any reduction in intravascular volume), physicians restore systemic flow by giving intravenous fluids rather than vasoconstrictors. This approach is empirical and does not seem to respond to the primary determinant of reduced venous return, which is increased venous compliance. Rather, it is now established that optimization of both flow and pressure is associated with improved outcomes in high-risk patients Table . Fluids The main vasopressors used in the operating theatre are phenylephrine, ephedrine, and norepinephrine. Their pharmacological effects are somewhat different but there are no data on the superiority of one vasopressor over the others. Phenylephrine could, however, be responsible for a significant decrease in cardiac output and organ perfusion, especially the brain  and in pExperts’ opinion:We propose to use fluids and vasoconstrictors in combination via a GDT algorithm to simultaneously achieve perioperative optimal blood flow and perfusion pressure, avoid volume overload and improve outcome in high-risk surgery patients (agreement 100%).Implementation of GDT and its additional hemodynamic monitoring has a cost. This increased cost could be perceived as an obstacle to hospital adoption. The cost of hemodynamic monitoring is highly variable, not only from one technique to another, but also from one country to the other, depending on reimbursement policies. Whatever such country-dependent pricing policies of monitoring devices, there is a common denominator: postoperative complications dramatically increase hospital costs. Studies have shown that the average cost difference between a patient with one or more complications and a patient without any complication ranges between 10,000€ and 30,000€ , 70. We The « MERCI» equation  enables As an example, if the morbidity rate after colorectal surgery is 25% (M = 25%), the relative reduction in postoperative morbidity is 23% (ER = 23%), and the average cost of complications per patient is 15,000€, the investment to implement hemodynamic monitoring at no net cost is 863€/patient . If the cost of monitoring is less than 863€/patient (which is most often the case), the difference would be savings to the health system. The higher the risk of postoperative complications and the cost of those complications, the more favorable the economic impact of GDT will be. Several studies have used the MERCI equation to predict the economic impact of hemodynamic monitoring in large populations of patients undergoing major non-cardiac surgery , 74, 75.Experts’ opinion:We propose that clinicians explain to national/hospital decision-makers that the extra-cost due to hemodynamic monitoring when implementing a perioperative GDT strategy is counterbalanced by the reduction in postoperative complications and hospital length of stay in high-risk surgery. This could be estimated at each institution level using the MERCI equation (agreement 100%).Because the current guidelines on perioperative hemodynamic optimization are not explicit enough to allow a reproducible decision-making process and also not suited to manage uncertainty, their implementation remains limited in routine practice. Numerous relevant questions are frequently asked by practitioners who need explicit clinical reasoning tools and treatment plans to develop strategies of blood pressure and cardiac output monitoring and optimization on an individual basis and at a reasonable cost.