In addition to proatherogenic properties, lipoprotein (a) (Lp(a)) has also pro-inflammatory, antifibrinolytic and prothrombogenic features. The aim of the current study was to identify the predictors of functional and morphological properties of the arterial wall in patients after myocardial infarction and increased Lp(a) levels at the beginning and after treatment with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors.Seventy-six post-myocardial infarction patients with high Lp(a) levels were included in the study. Ultrasound measurements of flow-mediated dilation of brachial artery (FMD), carotid intima-media thickness (c-IMT) and pulse wave velocity (PWV) were performed initially and after 6 months of treatment. At the same time points lipids, Lp(a), inflammatory and hemostasis markers were measured in blood samples.p = 0.022), high-sensitivity C-reactive protein , vascular cell adhesion protein 1 (VCAM-1) , overall coagulation potential  and overall hemostasis potential . c-IMT significantly correlated with age at first myocardial infarction  and Lp(a) . PWV significantly correlated with systolic blood pressure , tumor necrosis factor alpha , interleukin-8  and plasminogen activator inhibitor 1 . After treatment FMD reached statistical significance only in univariant analysis with systolic blood pressure  and VCAM-1 . PWV and c-IMT correlated with age  and systolic blood pressure .In linear regression model FMD significantly correlated with age at first myocardial infarction  levels and other biochemical markers associated with Lp(a) are predictors of functional and morphological properties of the arterial vessel wall in post-myocardial patients with high Lp(a) levels initially. However, after 6 months of treatment with PCSK9 inhibitors only age and systolic blood pressure seem to be predictors of these properties.The protocol for this study was registered with clinicaltrials.gov on November, 3 2020 under registration number NCT04613167. LPA gene, and they vary among individuals even by factor of 1000. However, within a single individual, Lp(a) levels are stable throughout life, with no influence of dietary habits or lifestyle [Despite the availability of the evidence based treatment with lipid-lowering drugs, target levels of low-density lipoprotein cholesterol (LDL-C) are achieved in less than 50% of the patients in secondary prevention  and LDL-ifestyle . Elevateifestyle , while hProatherogenic properties of Lp(a) are due to similarity to LDL-C. However, entering of Lp(a) to the intima is not LDL receptor dependent, but it depends on Lp(a) plasma concentration, Lp(a) particle size and permeability of the endothelial cells. Lp(a) affinity for proteoglycans and fibronectin on the endothelial cells is higher than that of LDL-C . Also, tEndothelial dysfunction is a first detectable functional change in the atherosclerotic process . It is dIn the current study we sought to identify the predictors of functional and morphological properties of the arterial wall measured as FMD, c-IMT and PWV. The predictors were searched among Lp(a) levels and biochemical markers directly or indirectly associated with Lp(a) in patients after myocardial infarction and significantly increased Lp(a) levels before and after treatment with PCSK9i.Patient flow diagram is shown in Fig. Patients were treated with PCSK9i; alirocumab 150 mg subcutaneously or evolocumab 140 mg subcutaneously, every two weeks for 6 months. Given that there were no differences between the two treated groups, we combined them for the analysis.Elevated liver transaminases more than three times the normal limit, serum creatinine above 200 mmol/l, or severe renal impairment and a history of acute illness in the past 6 weeks were the main exclusion criteria.All the procedures performed in this study that involved human participants were carried out in accordance with the ethical guidelines of the 1964 Declaration of Helsinki. Approval for this study was obtained from the National Medical Ethics Committee of the Republic of Slovenia (reference number: KME 0120–357/2018/8). The study is registered with CinicalTrials under the number NCT04613167.All patients signed a written informed consent prior to inclusion in the study.The blood pressure was measured in the sitting position after a minimum of 10 min of rest. The average of three measurements was determined. Body mass index was calculated as weight in kilograms divided by square of height in meters, and anthropometric parameters were determined.g. Total cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoproteins A1 and B were determined in the fresh serum by standard colorimetric or immunologic assays on an automated biochemistry analyzer . The same biochemistry analyzer was used to determine Lp(a) with the Denka reagent , which contains apo(a) isoform-insensitive antibodies, and therefore showed minimal apo(a) size-related bias. The Friedewald formula [The blood for laboratory analyzes was taken in the morning after 12 h of fasting. Samples were collected from the antecubital vein into vacuum-sealed 5 ml tubes containing clot activator . Serum was obtained by 15-min centrifugation at 2,000 ×  formula  was usedPlasminogen activator inhibitor-1 (PAI-1) antigen in plasma was measured using a classic sandwich ELISA . Tumor necrosis factor-alpha, high-sensitivity C-reactive protein (hs-CRP), interleukin 6, interleukin 8 and interleukin 10 levels in serum were measured using the Luminex’s xMAP® Technology utilizing magnetic beads coupled with specific antibodies, which allowed multiplexing. All analysis was performed according to manufacturer’s instructions . Overall coagulation potential (OCP), overall hemostasis potential (OHP) and overall fibrinolytic potential as supplementary parameters were determined as described before .Endothelial function was determined by FMD of the brachial artery, according to the guidelines  and as dp values < 0.05 were considered as statistically significant.Kolmogorov–Smirnov test was used to determine the distribution of variables. Variables showing a normal distribution were expressed as means and standard deviation, while non-normally distributed variables were expressed as median and range. In correlation analysis of normally distributed variables Pearson's correlation coefficient was calculated, and Spearman's rank correlation coefficient was calculated for non-normally distributed variables. Multiple regression analysis was used to find the independent determinants for the variations in the properties of the arterial vessel wall. Statistical analysis was performed using IBM SPSS Statistics for Windows, . A total of 76 patients with clinically stable CAD aged 50.9 ± 6.8 years at least 6 months after myocardial infarction, with mean age at the first coronary event of 43 years were included in the study. Their clinical and laboratory parameters before and after treatment are presented in Table r = -0.305; p = 0.002), Lp(a) , hs-CRP , vascular cell adhesion protein 1 (VCAM1) , OCP  and OHP . No correlations were found between FMD and classical risk factor such as systolic or diastolic blood pressure and lipoproteins except Lp(a).Before treatment with PCSK9i significant correlations for FMD were found with age , systolic blood pressure , Lp(a)  and PAI-1 . c-IMT as another measure of functional properties correlated with age , systolic blood pressure , TAFI , PAI-1  and OCP   and VCAM1 , while correlation with age was borderline significant .After six months of treatment with PCSK9i FMD correlated with systolic blood pressure  and systolic blood pressure . PWV also correlated with diastolic blood pressure , while c-IMT correlated with TAFI  .The importance of variables that showed significance in the univariate analysis in predicting FMD before treatment with PCSK9i was tested in several linear regression models. Table p = 0.001) variability of PWV  of variability of c-IMT. After 6 months of treatment with PCSK9i only three parameters at most reached statistical significance in univariant analysis for FMD, PWV and c-IMT, hence linear regression analysis was not possible.Age at the first acute coronary event, Lp(a), interleukin 8, VCAM1, OCP and OHP Table  reached To the best of our knowledge, our study is the first to examine the influence of both, classical risk factors, as well as inflammatory risk factors and factors related to disorders in coagulation fibrinolytic process on the functional and morphological properties of the arterial vessel wall in patients with CAD before and after treatment with PCSK9i. The uniqueness of our research is in the selection of the patients, as we have included the patients in the stable phase of CAD, with well-controlled risk factors other than lipids. Despite treatment with maximum tolerated doses of statins and ezetimibe if needed, their LDL-C levels did not reach the goal values as suggested by the guidelines . In addiNot surprisingly both, functional and morphological properties of the arterial vessel wall before and after treatment with PCSK9i, were statistically significantly associated with age in our study. Considering that elevated concentrations of LDL-C and Lp(a) levels in particular are genetically determined , our patMoreover, the second main part of Lp(a), apo(a), is structurally very similar to plasminogen, which is one of the most important components of the coagulation fibrinolytic system . Since LTo the best of our knowledge, there is no data in the literature on the effects of OHP, OCP or overall fibrinolytic potential on the functional and/or morphological properties of the arterial vessel wall. In our study, OCP and OHP proved to be independent predictive factors for both, functional (FMD) and morphological (c-IMT) properties of the arterial vessel wall. Guven et al. showed that FMD is not associated with TAFI in a group of 35 patients with hypercholesterolemia without obvious atherosclerotic disease. However, they also showed that in those patients treated with simvastatin (40 mg daily) FMD significantly improved, and also the TAFI levels significantly reduced, but without their mutual association . TAFI plIn the current study, we determined which risk factors predict the functional and morphological characteristics of the arterial vessel wall before and after treatment with PCSK9i in post-myocardial infarction patients with moderately increased LDL-C and strongly increased Lp(a) levels and well-controlled other risk factors. In addition to age and arterial blood pressure both, the functional and the morphological properties of the arterial vessel wall of these patients, depend on the values of Lp(a) and related factors of inflammation and hemostasis before PCSK9i treatment. However, after PCSK9i treatment, only well-recognized risk factors such as age and blood pressure seem to predict the arterial wall properties. Given that post-treatment LDL-C levels were ideally controlled, while Lp(a) levels were still significantly elevated, it will be interesting to determine whether the additional distinct lowering of Lp(a) with Lp(a)-specific drugs changes these relationships.


In this study we investigated the pressor effects of Cd and β2M in 88 diabetics and 88 non-diabetic controls, matched by age, gender and locality. The overall mean serum β2M was 5.98 mg/L, while mean blood Cd and Cd excretion normalized to creatinine clearance (Ccr) as ECd/Ccr were 0.59 µg/L and 0.0084 µg/L of filtrate (0.95 µg/g creatinine), respectively. The prevalence odds ratio for hypertension rose by 79% per every ten-fold increase in blood Cd concentration. In all subjects, systolic blood pressure (SBP) showed positive associations with age (β = 0.247), serum β2M (β = 0.230), and ECd/Ccr (β = 0.167). In subgroup analysis, SBP showed a strong positive association with ECd/Ccr (β = 0.303) only in the diabetic group. The covariate-adjusted mean SBP in the diabetics of the highest ECd/Ccr tertile was 13.8 mmHg higher, compared to the lowest tertile (p = 0.027). An increase in SBP associated with Cd exposure was insignificant in non-diabetics. Thus, for the first time, we have demonstrated an independent effect of Cd and β2M on blood pressure, thereby implicating both Cd exposure and β2M in the development of hypertension, especially in diabetics.The most common causes of chronic kidney disease, diabetes, and hypertension are significant public health issues worldwide. Exposure to the heavy metal pollutant, cadmium (Cd), which is particularly damaging to the kidney, has been associated with both risk factors. Increased levels of urinary β Hypertension is defined as systolic blood pressure ≥ 140 mmHg, or diastolic blood pressure ≥90 mmHg, and is both a cause and a consequence of chronic kidney disease (CKD) ,3. An inA prospective cohort study of American Indians has provided strong support for a causal link between Cd exposure and hypertension . In this2-microglobulin (β2M) u) was determined using an immunoturbidimetric method. The human beta-2 microglobulin/β2M ELISA pair set  was employed to determine serum and urine concentration of β2M ([β2M]s and [β2M]u) with the low detection limit of 3.13 pg/mL.Fasting plasma glucose concentrations ([Glc]b) was determined with the atomic absorption spectrophotometer . Multielement standards were used to calibrate metal analysis . For the purposes of quality control, analytical accuracy, and precision assurance, reference urine and whole blood metal control levels 1, 2, and 3  were used. All test tubes, bottles, and pipettes used in the metal analysis were acid-washed and rinsed thoroughly with deionized water. When a [Cd]b level was less than its detection limits, the concentration assign was the detection limit divided by the square root of 2 u = urine creatinine concentration (mg/dL). The ratio [x]u/[cr]u was expressed in μg/g of creatinine.Ex was normalized to Ccr as Ex/Ccr = [x]u[cr]p/[cr]u, where x = Cd or β2M; [x]u = urine concentration of x (mass/volume); [cr]p = plasma creatinine concentration (mg/dL); and [cr]u = urine creatinine concentration (mg/dL). Ex/Ccr was expressed as the excretion of x per volume of filtrate p > 0.9 mg/dL.p ≤ 0.7 mg/dL, and Y = −1.209 if [cr]p > 0.7 mg/dL.The GFR is the product of nephron number and mean single nephron GFR, and in theory, the GFR is indicative of nephron function ,29,30. I2. Reduced eGFR was assigned when eGFR ≤ 60 mL/min/1.73 m2.Data were analyzed with IBM SPSS Statistics 21 . The Mann–Whitney U-test was used to assess differences in means between the two groups, and the Pearson chi-squared test was used to assess differences in percentages. Before data were subjected to parametric statistical analysis, the one-sample Kolmogorov–Smirnov test was used to identify a departure from a normal distribution of any continuous variables, and logarithmic transformation was applied when the variables showed rightward skewing. The multivariable logistic regression analysis was used to determine the Prevalence Odds Ratio (POR) for categorical outcomes. Obesity was designated when BMI > 30 kg/m2M excretion, adjusted for covariates and interactions. For all tests, p-values ≤ 0.05 were considered to indicate statistical significance.We employed the univariate analysis of covariance with Bonferroni correction in multiple comparisons to obtain the mean SBP, mean DBP and mean βAmong 176 participants, 88 were diagnosed with diabetes, and 88 were apparently healthy controls who did not have diabetes .2M, mean urine β2M, mean Eβ2M/Ccr, and mean Eβ2M/Ecr all were higher in the diabetics than controls. In contrast, mean eGFR, mean blood Cd, mean urine Cd, mean ECd/Ccr, and mean ECd/Ecr were similar in the two groups.Women constituted 80% of the diabetics and controls. The mean diabetes duration was 9.3 years, and the overall mean age was 60 years. The overall percentages (%) of smokers and the obese were 9.7% and 10.8%. Obesity was 2.78-times more prevalent in diabetics, while % smoking, hypertension, and reduced eGFR did not differ. The mean BMI, mean SBP, mean serum β2M and/or Cd exposure with SBP and DBP were evaluated with the regression analysis, incorporating age, BMI, serum β2M, Cd excretion rate, gender and smoking as the independent variables . Of these six variables, SBP showed a moderate association with age (β = 0.247), serum β2M (β = 0.230), urinary Cd excretion (β = 0.167), and smoking (β = −0.218). In subgroup analysis, SBP was associated with urinary Cd excretion only in the diabetics (β = 0.303), while it showed a strong association with age only in non-diabetics (β = 0.348).In all subjects, age, BMI, serum βIn the equivalent DBP regressions, Cd excretion was associated with DBP only when all subjects were included (β = 0.167), and this DBP-Cd association became insignificant in the subgroup analysis .Additional multiple linear regressions of blood pressure were conducted to evaluate gender differences in the effect of Cd on blood pressure .2M (β = 0.415) and urinary Cd excretion (β = 0.432), while DBP was strongly associated only with urinary Cd excretion (β = 0.454). The association of the DBP in men with serum β2M was not significant . In comparison, there was no significant association between SBP and urinary Cd excretion in women. There was, however, a moderate association of SBP with age (β = 0.310) and serum β2M (β = 0.225).In men, SBP was associated strongly with both serum β2M on kidney outcome in relation to other variables.2M, excretion rates of Cd, smoking, gender, and hypertension together contributed to 19.1% and 15.8% of the variability of eGFR in all subjects (p < 0.001), and women (p = 0.001), respectively. In contrast, the variation in eGFR among men was not significantly associated with any of these independent variables.Age, BMI, eGFR, serum β2M (β = −0.235) when all subjects were included. In subgroup analysis, the inverse association of eGFR with age in women was maintained, but the association of eGFR and serum β2M was weakened and became statistically insignificant. eGFR was inversely associated with age (β = −0.307) and serum βCd/Ccr tertiles . The covariate-adjusted mean SBP tertile was 13.8 mmHg higher in the diabetics of the high than those of the lowest tertile (p = 0.027) (Cd/Ccr) × 100 for tertiles 1, 2 and 3 were ≤0.069, 0.070–0.177 and ≥0.178 µg/L filtrate, respectively.A linear increase in SBP with urinary Cd excretion rate was evident in the diabetic group only a. The co= 0.027) b. The cuCd/Ccr tertile groups . Blood Cd as log10 ([Cd]b) × 103) was associated with a 1.72-fold increase in POR for hypertension (p = 0.013).Age, BMI, serum β2M, urinary excretion rates of β2M and Cd, gender, smoking, diabetes and hypertension.p < 0.001) and women (p < 0.001), respectively.All 10 independent variables contributed to 19.7% and 19.3% of the variability of blood Cd in all subjects . In addition, blood Cd showed a moderate association with hypertension in women only (β = 0.181). In contrast, blood Cd in men was not associated with Cd excretion rate or hypertension, but it did show a strong positive association with smoking (β = 0.496).Blood Cd was not associated with serum β2M excretion, a common sign of Cd-induced nephrotoxicity, has been linked to an increased risk of hypertension in a Japanese population study [2M predicted rapid decline in eGFR, diabetic kidney disease (DKD), cardiovascular disease, and mortality in diabetic patients [2M in the development of hypertension in diabetics who are also exposed to environmental Cd has never been investigated.One of the most widely recognized consequences of chronic kidney damage is hypertension. Hypertension originating from kidney disease is associated predominately with the renin-angiotensin system of blood pressure control ,34. Whilon study . In othepatients ,37,38. H2M seen in diabetics compared with controls  and urinary Cd with SBP was evident from regression analysis (2M (β = 0.230) and Cd excretion rate (β = 0.167), while DBP was associated with excretion of Cd only (β =0.172). In subgroup analysis, SBP was associated with urinary Cd in the diabetic group only (β = 0.303), while an association of DBP with urinary Cd became insignificant due to a reduction in sample size  and Cd excretion (β = 0.432), while DBP was strongly associated only with Cd excretion (β = 0.454). Our finding may help explain the results of a recent Danish cohort study of non-smokers which found an association between environmental Cd exposure and incident heart failure, especially among men [The gender difference was seen in the association of βpressure . Among mmong men .2M particularly in women. This observation is in line with previous studies showing serum β2M as the predictor of rapid decline in eGFR and DKD [Another gender difference was indicated by the regression analysis , where e and DKD ,37,38.F = 3.73, p = 0.031) after adjustment for covariates and interactions. The covariate-adjusted mean SBP in those in the high ECd/Ccr tertile was 13.8 mmHg higher than those in the low tertile (p = 0.027)  b.2 increase in BMI (p = 0.042), and ten-fold increase in blood Cd concentration (p = 0.013), respectively. Of note, blood Cd levels ≥ 0.4 µg/L were found to be associated with 1.5-fold to 2.4-fold increases in risk of hypertension among Caucasian and Mexican-American women enrolled in the U.S. National Health and Nutrition Examination Survey (NHANES) 1999–2006  [In the logistic regression analysis , neitherI p = 0.02, and te 16,222) ,8, Canad 16,222)  have alsCd exposure increased the risk of DKD in a Dutch cross-sectional study, including 231 patients with type 2 diabetes . In a siDiabetes and hypertension are the major causes of CKD and subsequently development of kidney failure ,43. Coll2M on SBP and eGFR has been demonstrated. This implies that both Cd exposure and circulating β2M are involved in the development of hypertension, and eGFR decline, especially in diabetics.This study shows that environmental exposure to low levels of Cd adversely affects blood pressure and GFR in both non-diabetic and diabetic. For the first time, an independent effect of Cd and β


Nimodipine is recommended to prevent delayed cerebral ischemia in patients with spontaneous subarachnoid hemorrhage (SAH). Here, we studied hemodynamic side effects of different nimodipine formulations (per os [PO] and intravenous [IV]) in patients with SAH undergoing continuous blood pressure monitoring.This observational cohort study includes consecutive patients with SAH  admitted to a tertiary care center between 2010 and 2021. All patients received prophylactic IV or PO nimodipine. Hemodynamic responses were evaluated based on median values within the first hour after continuous IV nimodipine initiation or PO nimodipine application (601 intakes within 15 days). Significant changes were defined as > 10% drop in systolic blood pressure (SBP) or diastolic blood pressure from baseline . With the use of multivariable logistic regression, risk factors associated with SBP drops were identified.p < 0.001) and were 58 (49–69) years of age. Initiation of IV nimodipine was associated with a > 10% SBP drop in 30% (81/271) of patients, with a maximum effect after 15 min. A start or increase in noradrenaline was necessary in 136/271 (50%) patients, and colloids were administered in 25/271 (9%) patients within 1 h after IV nimodipine initiation. SBP drops > 10% occurred after 53/601 (9%) PO nimodipine intakes, with a maximum effect after 30–45 min in 28/49 (57%) patients. Noradrenaline application was uncommon (3% before and 4% after nimodipine PO intake). Hypotensive episodes to an SBP < 90 mm Hg were not observed after IV or PO nimodipine application. In multivariable analysis, only a higher SBP at baseline was associated with a > 10% drop in SBP after IV (p < 0.001) or PO (p = 0.001) nimodipine application, after adjusting for the Hunt & Hess score on admission, age, sex, mechanical ventilation, days after intensive care unit admission, and delayed cerebral ischemia.Patients were admitted with a median Hunt & Hess score of 3 (2–5; IV 3 [2–5], PO 1 [1–2], Significant drops in SBP occur in one third of patients after the start of IV nimodipine and after every tenth PO intake. Early recognition and counteracting with vasopressors or fluids seems necessary to prevent hypotensive episodes.The online version contains supplementary material available at 10.1007/s12028-023-01760-y. Delayed cerebral ischemia (DCI) occurs in up to 20–30% of patients with spontaneous subarachnoid hemorrhage (SAH) and continues to be one of the most important factors contributing to poor long-term outcome, especially if it leads to cerebral infarction , 2. TradTo date, the only recommended drug for the prevention of DCI is nimodipine, an L-type dihydropyridine calcium channel antagonist , 4. It rSystemic arterial hypotension remains the most important adverse effect of nimodipine treatment , 12. ThiInterestingly, clinical trials testing a formulation of nimodipine do not consistently report adverse events of hypotension, and there is little real-life clinical data describing a temporal relation of per os (PO) and IV nimodipine application and blood pressure changes . MoreoveIn the current study, we report the prevalence of significant blood pressure drops and the development of relevant hypotensive episodes following IV and PO nimodipine in consecutive patients with SAH undergoing continuous blood pressure monitoring through an arterial line. Following our internal protocol, IV nimodipine was applied as continuous infusion in patients with poor-grade SAH, whereas awake patients without swallowing difficulties received PO nimodipine. We hypothesized that blood pressure drops are common after nimodipine application, prompting treatment intensification with vasopressors or fluids.The study design was guided by the STROBE statement on observational studies. This is a retrospective analysis of prospectively collected data of patients with nontraumatic SAH who were admitted to the neurological intensive care unit (ICU) of a tertiary care hospital  between 2010 and 2021. Inclusion criteria were (1) diagnosis of spontaneous SAH confirmed by computed tomography (CT) scan or lumbar puncture irrespective of whether an aneurysm was found; (2) male or female sex and 18 years of age or older; (3) ICU stay for more than 24 h; (4) invasive, continuous blood pressure monitoring to achieve high granularity (5 min) of hemodynamic variables  at the time of nimodipine application (IV or PO). Nineteen patients adhering to the IV nimodipine group were excluded because IV nimodipine was started simultaneously with continuous blood pressure measurement, leading to missing baseline blood pressure values. For calculations of hemodynamics secondary to PO nimodipine administration, only patients in whom PO nimodipine was administered before IV nimodipine were considered . According to our protocol, PO formulations may be given in poor-grade patients before a central venous catheter is installed, followed by a switch to IV nimodipine thereafter. De-escalation from IV to PO nimodipine is usually performed after vasospasm has resolved more than 2 weeks after aneurysmal bleeding. Therefore, none of our analysis with PO formulations occurred after the cessation of IV nimodipine.The conduct of the study was approved by the local ethics committee . Written informed consent was obtained according to local regulations.Patients were treated according to international guidelines , 4. ClinAll patients received prophylactic nimodipine as of admission to the ICU. Nimodipine was applied intravenously in poor-grade patients and orally in good-grade patients based on clinical, laboratory, and radiographic parameters. In some poor-grade patients, oral nimodipine was switched to IV nimodipine as soon as they had a central line. Continuous IV nimodipine  perfusion was started at a testing dosage of 1 mg/h and increased to 2 mg/h if it was hemodynamically tolerated. The targeted daily dose was 48 mg. Dosage reductions were done in the setting of refractory hypotension despite vasopressor escalation. The full dose of 60 mg of oral nimodipine  was given six times a day resulting in a targeted daily dose of 360 mg, as used in the original protocol  h), and most patients (79%) received a reduced testing rate of 1 mg/h initially, corresponding to treatment strategies, followed by the targeted dosage of 2 mg/h. In the remaining patients, the starting dosage was 2 mg/h. The full daily nimodipine dose (48 mg) was administered during 28% of study days, and at least 80% of the targeted daily nimodipine doses (38.4 mg) were reached in 54% of the study days. Ninety-three percent of patients received noradrenaline during the study period (Table 1 h), andInitiation of IV nimodipine was associated with a median SBP decrease of 8 mm Hg from 134 ± 22 mm Hg at baseline to 126 ± 18 mm Hg  were as frequent as decreases > 10% (17%). New onset tachycardia or bradycardia were evident in 1.5% and 4%, respectively within 1 h after nimodipine initiation.btO2) values before and after initiation of IV nimodipine in a limited number of 22 patients.The first increase of the IV nimodipine dosage (1 to 2 mg/h) was performed after 44 (12–97) hours in 180 patients and was associated with a SBP drop from 148 to 143 mm Hg. Fourteen percent of patients (25/180) developed a significant SBP drop > 10% at this time. Supplemental Fig. 2 demonstrates a subanalysis of dynamics of brain tissue oxygen tension (Pn = 18), and in 4% (n = 23) noradrenaline was given within 1 h after nimodipine administration  per patient, resulting in 601 intakes analyzed within the study time. Of the 601 intakes, 577 (96%) corresponded to nimodipine at full 60 mg dose, and 24 (4%) at the reduced dose of 30 mg. The full daily nimodipine dose (360 mg) was delivered in 25% of study days and at least 80% of the targeted nimodipine daily dose (288 mg) was reached in 45% of the study days  intakes corresponding to 32/49 patients (65%) who experienced at least one episode of DBP drop after PO nimodipine within the study period of 15 days. An absolute DBP drop > 10 mm Hg from baseline was observed after 27/601 (5%) intakes.HR increased > 10% in 56 (9%) out of 598 intakes  with a maximum effect observed at about 30 min post intake. New onset tachycardia was observed only in 3/598 (0.5%) episodes.Only weak correlations between SBP drops and HR increases, or DBP drops and HR increases, were observed at rho = 0.117 and rho = 0.119, respectively. The correlation between SBP drops and DBP drops was moderate (rho = 0.493).p < 0.001) or PO (p = 0.001) nimodipine application , DCI (IV p = 0.076) or poor functional 3-month outcome  after adjusting for the H&H score and age. Out of the PO nimodipine group, only 4% and 7% of patients were diagnosed with DCI or poor functional outcome, respectively, thus making statistical analysis unreliable.The median daily nimodipine dose had no independent effect on the occurrence of vasospasm  and 45 (PO) minutes after nimodipine application. These results strongly argue for continuous blood pressure monitoring in patients with SAH.Our data reflect clinical real-life situation comprising a large population of patients with SAH including all severity grades, where continuous blood pressure monitoring was applied. The high granularity of blood pressure readings and the time-locked application of nimodipine allowed a precise analysis of blood pressure changes during the study period. Decreases of > 10% in SBP were evident in every third patient after a starting dosage of 1 mg/h of IV nimodipine. Post oral nimodipine intake, blood pressure drops occurred in 10%, irrespective of the time period after the disease. Importantly, our protocol for PO nimodipine did not diverge from the original protocol published by Pickard et al. . DiffereImportantly, we did not record hypotensive episodes ≤ 90 mm Hg post nimodipine delivery. This is most probably due to our institutional protocol targeting at least 65 mm Hg MAP in all patients with SAH with escalating strategies when DCI is diagnosed. Other reasons include vigilant monitoring and appropriate awareness with counteractive measures being rapidly applied. In this line, escalations of vasopressors were common after IV nimodipine initiation based on patients’ hemodynamic responses. Monitoring cardiac function and blood pressure is one of the important factors after SAH. It is important to notice that changes in blood pressure may have been missed if blood pressure would have been recorded discontinuously. Although we do not have a comparison group to support our hypothesis, continuous monitoring is recommended in poor-grade patients with SAH and should be extended to good-grade patients to detect significant drops in blood pressure that may counteract the neuroprotective effect of nimodipine , 4.In our study, transient dosage reductions have been necessary in some patients. Literature suggests that higher doses of nimodipine may be more efficacious, however their use is limited due the risk of hypotension , 19. It Except for higher baseline blood pressure values, we could not identify any risk factors for blood pressure drops secondary to nimodipine delivery. However, these findings have to be interpreted with caution, because our patients with poor-grade SAH were mostly treated with IV and good-grade patients with PO nimodipine separating them into two distinctive groups. The higher prevalence of blood pressure drops after IV nimodipine compared to PO nimodipine may partly be explained by the aforementioned factors. Moreover, nimodipine-associated blood pressure drops were not associated with secondary neurological complications such as DCI or poor functional outcomes. This is most likely due to the overall low prevalence of hypotensive episodes which could have been counteracted by appropriate treatment.Alternative routes of nimodipine administration with drug delivery to the most vulnerable regions minimizing systemic side effects have not yet been proven efficacious. The NEWTON study was conducted to compare the efficacy of intraventricular versus oral nimodipine . It was Reflex tachycardia and reactive HR increases following systemic vasodilation was observed in some patients, although the correlation was only weak. This implies an autonomic control of the cardiovascular system with a preserved baroreflex function. Consequently, the cardiac output remains stable despite blood pressure decreases .Our study was not concepted to compare the efficacy of IV versus PO nimodipine to prevent DCI or poor functional outcome because our patient population significantly differs in terms of disease severity and hospital complications reflecting our standard of care procedures in patients with SAH. There remains some controversy over the formulation in which nimodipine should be given. A recent meta-analysis showed that enteral and intravenous nimodipine may have a similar effectiveness in the prevention of poor outcome and DCI . Some stSome limitations to the study merit consideration. Firstly, we did not correct for other blood pressure lowering medications. However, as already mentioned it is unlikely that they were given concomitantly with nimodipine. Secondly, we did not consider CYP 3A4 inhibitors such as erythromycin, azole antimycotics, and valproic acid that can lead to increased plasma concentrations of nimodipine. Thirdly, we report two distinct groups of patients, which makes any comparisons impossible. Fourthly, we did not include patients with discontinuous blood pressure measurements to achieve a high resolution of blood pressure readings. This approach leads to a selection bias toward poor-grade patients and renders our results speculative for patients with good-grade SAH.Our study depicts time-locked blood pressure evolutions secondary to IV and PO nimodipine applications in patients with SAH. Our results show that although blood pressure drops were common, especially after IV nimodipine delivery in patients with poor-grade SAH, hypotensive episodes could have been prevented. Further randomized controlled studies are needed to test the effect of PO in comparison with IV nimodipine formulations on outcomes in patients with SAH aiming at avoiding blood pressure instability by integration of continuous blood pressure monitoring in the study protocol.Supplementary file 1. Flow chart demonstrating patient selection (PDF 12 kb)Supplementary file 2 (DOCX 49 kb)Supplementary file 3. Median heart rate (HR) over time after oral nimodipine administration in the subgroups of intakes with  and without a significant >10% HR increase (TIF 1471 kb)Supplementary file 4 (DOCX 14 kb)Supplementary file 5 (DOCX 17 kb)Below is the link to the electronic supplementary material.


The Special Issue “Personalized Medicine in Kidney Disease” is focused on the importance of customized medicine in nephrology as it represents one of the main characteristics of successful therapeutic results. This edition included five articles that investigated cutting-edge subjects linked to this topic.Personalized medicine uses the phenotypes and genotypes of individuals to tailor the best therapeutic approach for each patient at the appropriate time, to identify a person’s propensity for disease, and/or to provide timely and targeted prevention. In the context of kidney diseases, it has the potential to completely transform patient care on the basis of individual traits and needs. In particular, personalized medicine approaches in chronic kidney disease (CKD) aim to tailor treatment strategies based on underlying causes, genetic factors, the rate of disease progression, and other personalized factors.CKD can arise through various pathological mechanisms, and it is not an infrequent result of acute renal injury (AKI). The development and progression of CKD can be related to the timing and extent of recovery of renal function after AKI. In this Special Issue, Tain et al.  categoriAn effective approach to limit the CKD-related injuries includes risk assessment and early identification of patients affected. The adoption of screening exams including checking blood pressure, evaluating risk factors, as well as urine and blood tests of kidney function may help to recognize people at a high risk of developing CKD and enables prompt therapy and intervention to halt illness progression. The accurate diagnosis and subtyping of CKD are also necessary for a tailored strategy; nowadays genetic testing accompanies kidney biopsy, as well as other diagnostic procedures, which can all be used to ascertain the underlying etiology of CKD. Treatment choices are likewise influenced by this knowledge, since each CKD cause may call for various management approaches.Personalized medicine also develops treatment plans that are suited to each patient while stressing individualized lifestyle changes. Each patient’s unique demands and risk factors must be considered when selecting elements including nutrition, exercise, quitting smoking, and blood pressure control. Moreover, this method takes into account unique patient characteristics, such as kidney function, comorbidities, and medication tolerance when choosing and administering medications. In this setting, pharmacogenomic techniques may aid in particular in the discovery of genetic variations that affect drug metabolism and response.Additionally, CKD often coexists with other conditions such as diabetes, hypertension, cardiovascular disease (CVD), and pulmonary diseases. A holistic and personalized approach addresses all these comorbidities to tailor a treatment strategy to optimize overall health outcomes. Regular follow-up visits, laboratory checks, and longitudinal monitoring enable prompt intervention and appropriate treatment plan modification. Patients should take an active role in learning about their ailment, available treatments, and associated risks and benefits, to match their therapies with their own preferences, values, and healthcare objectives in shared decision making with the nephrologists. Personalized medicine may also include the proposal of participating in clinical trials or research studies that can provide access to cutting-edge treatment approaches.Personalized treatment for CKD should consider environmental factors that affect kidney health, including lifestyle habits like nutrition, exercise, and stress management. In this setting, a tailored approach takes into account patient preferences, socioeconomic circumstances, and cultural concerns to create customized lifestyle interventions.In fact, prevention is essential to halt the progression of CKD and related comorbidities. Consistent with the goal of reducing the risk of AKI and progression to renal failure, Zisis et al.  found a One aspect that should be emphasized is the role of the kidneys in whole-body homeostasis and their subsequent connection to other organs. This side was highlighted by Gembillo et al. , who desAnother important component of personalized treatment for CKD is represented by genomic medicine, as it is well known that genetic variables are involved in the onset and progression of many renal diseases. More and more gene mutations have been identified and linked to specific kidney illnesses thanks to the advancements in genomic sequencing technologies. Genetic testing can be used even when kidney biopsy may not provide a specific diagnosis or patients are not suitable for it, as late-referrals; it can also help in forecasting how the condition will progress, and guide therapy choices considering particular genetic mutations, for instance in the identification of potential kidney donors for transplantation and risk stratification linked to the procedure.Studies on pharmacogenomics can provide important information on how a genetic asset impacts how each person responds to medications. Genetic variations may affect drug metabolism, its effectiveness, and side effects. Genetic information about a patient can help in drug selection and the adjustment of dosages, thus improving therapy while reducing the risk of side effects. This method is particularly important in kidney disease, since decreased renal function might affect medication clearance and clinical response.The development of tailored therapies can be obtained using molecular profiling tools like gene expression analysis and proteomics, which can shed light on the underlying molecular mechanisms of kidney diseases. Biomarkers, as quantifiable signs that reveal information about the existence, progression, and response to therapy of diseases, are an additional helpful tool. Their role in renal disease may be to evaluate kidney function, spot early warning signals of damage, and forecast treatment outcomes.In this context, Susilo et al.  adopted In addition to traditional methods of obtaining real-life data, large amounts of patient data can be collected using digital health technologies such as wearables, remote monitoring and electronic health records, and finally elaborated with data analytics techniques to identify patterns, predict disease progression and improve treatment plans. Machine learning algorithms can support individualized treatment strategies by helping with risk classification and decision-making.Personalized medicine has a lot of potential, but it has not yet been widely adopted in clinical settings. Some of the challenges include cost, the accessibility of genetic testing, data privacy, and genetic data interpretation. As we better understand the genetic and molecular mechanisms underlying kidney disease, personalized medicine techniques will become increasingly important in optimizing the treatment of patients with kidney disease and improving outcomes.Another important factor that can contribute to the progression of CKD is hypertension. Hypertension represents a major cause of kidney disease progression. According to predictions, high blood pressure will still be the main risk factor in 2040, since it is the main cause of mortality and disability . MaintaiLimiting sodium intake is essential in managing hypertension and reducing fluid retention. Personalized therapy includes dietary counselling to educate patients about the importance of sodium restriction and provide practical guidance on reducing sodium in their diet. Lifestyle changes, such as adopting a healthy diet, regular exercise, weight management and smoking cessation, are integral components of personalized therapy. These modifications can help control blood pressure and reduce the risk of CVD onset.As regards medications, clinical hypertension guidelines are broad suggestions that necessitate clinical judgment to decide how to treat best each patient, on the basis of their unique features. A treat-to-target strategy stratified by individual characteristics forms the foundation of the clinical recommendations. The causes of apparent treatment-resistant hypertension need to be evaluated in patients in whom the usual first-line medications recommended by the guidelines are ineffective so that treatment can be tailored appropriately ,7.Diabetic individuals have different rates of CKD progression and responses to therapy, underlining the need for individualized care . A fundaDifferent comorbidities can aggravate the kidney involvement in the course of DKD. Hypertension is common in DKD and contributes to further kidney damage. Blood pressure targets and antihypertensive medications are similar to those in hypertensive kidney disease (as mentioned earlier).Adequate proteinuria management also represents an essential element for proper disease control. Medications such as angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) are commonly prescribed to reduce proteinuria and slow the progression of kidney damage. The choice of medication and dosing may be personalized based on kidney function, blood pressure control, and individual tolerability. An important asset in treating DKD is the adoption of sodium-glucose co-transporter-2 inhibitor (SGLT2i). The proximal convoluted kidney tubules express SGLT2 channels that oversee around 90% of the reabsorption of filtered glucose. SGLT2i blocks this activity, resulting in glucosuria and improved glycemic management .Additionally, DKD worsens dyslipidemia and increases the risk of atherosclerotic CVD. Personalized therapy may involve lipid-lowering medications to control cholesterol levels to reduce the risk of CVD. The absolute amount of cardiovascular risk and the initial lipid profile heavily influence the decision to perform lipid-modifying therapy. Most patients who need to lower their levels of low-density lipoprotein cholesterol (LDL-C) are treated with statins first, with the addition of ezetimibe and pro-protein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors to help them attain their LDL-C goals. Based on phenotypic and genetic characteristics, some side effects of statins are somewhat predictable. If triglyceride levels continue to be elevated, fibrates or omega-3 fatty acids can be administered. The RNA-targeted treatments currently under research offer the potential for selective liver targeting for particular lipoproteins like lipoprotein(a), and the long-term lowering of LDL-C with occasional delivery of a small-interfering RNA, which may help to address the issue of adherence to medication .Similar to hypertensive kidney disease, lifestyle modifications play a crucial role in managing DKD. These include following a balanced diet, practicing regular physical activity, weight management, smoking cessation, and stress reduction. Personalized therapy also includes the regular monitoring of kidney function, blood pressure, blood glucose levels, and other relevant parameters. This helps to assess treatment effectiveness, identify any complications, and adjust the treatment plan as needed.For DKD patients, personalized therapy necessitates an individualized strategy that considers each patient’s special traits, preferences, comorbidities, and treatment response . CollaboNutrition therapy plays a crucial role in treating kidney disease and maintaining renal function meeting the specific needs of each patient.An important aspect of appropriate nutrition therapy regards sodium and fluid management. In particular, limiting sodium intake with a correct fluid assumption results in better control of blood pressure and congestion, thus reducing the kidneys’ and heart’s workload. The extent of sodium and fluid restriction must be tailored to the individual’s specific kidney function and the overall health of the patient.The amount and the sources of protein intake should also be adjusted individually depending on the stage of kidney disease and the presence of proteinuria. A low-protein diet in CKD patients appears to slow the natural progression to end-stage renal disease (ESRD) but it is still not appropriate for all patients if the nutrition intervention is not personalized to ensure treatment adherence .Controlling phosphorus and potassium is another crucial aspect of adequate nutrition for CKD patients. High phosphorus levels can contribute to bone and cardiovascular complications , while eAdditionally, dietary modifications may be required to control acid–base levels depending on the patient’s unique situation. This may entail reducing consumption of foods that promote the synthesis of abnormal amounts of hydrogen ions, as this is a major factor in endogenous net acid production acid formation. On the other hand, privileging the consumption of alkaline foods such as fruits and vegetables or the oral intake of alkaline salts  may reprIndividuals with CKD may also have specific nutrient deficiencies due to dietary restrictions or impaired kidney function. Supplementation of certain vitamins and minerals, such as vitamin D, iron, zinc, copper and B-complex vitamins, may be necessary to address these deficiencies ,19,20. HAnother important topic for CKD treatment is Personalized renal replacement therapy (RRT). RRT refers to tailoring the treatment of ESRD to meet the specific needs and characteristics of each patient. In special populations such as in older adults, personalized RRT considers age-related changes, comorbidities, performance status and the goals of care. The treatment plan is adjusted to optimize outcomes while considering the individual’s overall quality of life. In some cases, conservative management or supportive care measures may be considered as fair alternatives to aggressive RRT in older patients.Hemodialysis (HD) represents the most common treatment modality of RRT. Personalizing HD involves optimizing dialysis parameters, such as dialysis frequency, duration, filters, fluid removal and blood flow rates, based on the individual’s clinical condition, residual kidney function, and overall health status. Modifying the HD prescription can help to improve the effectiveness of treatment and minimize complications. Incremental HD may be the preferred approach for ESRD patients who do not need an urgent start and preserve residual kidney function; in these cases, the dialysis dose is increased by degrees to allow a gradual transition that reflects the progressive nature of CKD and reduce the patient’s dialysis burden.Peritoneal dialysis (PD) is another form of RRT that relieves patients with ESRD of the need for frequent hospital dialysis sessions and can enhance quality of life. PD is, by definition, tailored to the patient’s lifestyle, residual kidney function, and the high, average, or low transport rate of each patient’s peritoneum. A PD prescription may be personalized by choosing different dialysis solution types, dwell times, and exchange volumes, which can be adjusted to optimize treatment outcomes and patient comfort.Moreover, personalized RRT can include the option of home-based dialysis therapies, including both HD and PD. Home-based dialysis offers more flexibility and convenience to patients as they have more control over their treatment plan and require less frequent hospital visits. The decision to perform home-based therapy may be shared based on the patient’s preferences, life habits and the presence of care givers where needed.Kidney transplantation is considered the optimal treatment for ESRD because it offers the best long-term outcomes and quality of life. The careful assessment of potential kidney donors, taking into account factors such as blood group compatibility, human leukocyte antigen (HLA) match and the presence of sensitization or pre-existing antibodies is an example of a personalized approach. Adapting the transplant process and the immunosuppressant therapies to the specific needs of the patient can improve the chances of a successful transplant and long-term graft survival.Personalized RRT aims to maximize the benefits of treatment while minimizing the risks and burdens for each patient. The decision-making process should involve a multidisciplinary team of healthcare professionals, including nephrologists, transplant surgeons, nurses, and dietitians, who can assess the patient’s specific needs, preferences, and goals, and collaborate to develop a unique treatment plan.In glomerulonephritis, personalized techniques entail personalizing therapy based on an individual’s particular disease subtype, underlying causes, genetic variables, immune system traits, and patients’ requirements, which may influence therapeutic options. Precision medicine begins with an accurate diagnosis and subtyping of the glomerular diseases, with a combination of clinical assessment, laboratory tests, imaging studies, and kidney biopsy. Determining the precise subtype guides appropriate treatment strategies. Given the genetic background of some forms of glomerulonephritis, personalized medicine may involve genetic testing to identify specific gene mutations or variants associated with the disease, that may also help in predicting disease progression and assessing familial risk. In certain cases, targeted therapies or genetic counselling may be considered based on the identified genetic abnormalities.Another aspect to investigate is represented by the immune profiling, through serological testing, measurement of autoantibodies, complement system evaluation, and other immunological assessments. As glomerular diseases are often expressions of immune system dysregulation, such as immune complex deposition or autoantibody production, a patient’s detailed profile is useful in directing targeted immunosuppressive therapies and monitoring treatment response.Moreover, patient-oriented therapy includes the choice of different strategies based also on comorbidities, severity of disease, preferences, including pregnancy desire ,22. TreaIt is critical to closely monitor disease activity and response to treatment through regular clinical assessments, laboratory tests and imaging studies. In this way, disease flares or progression can be detected early and the treatment plan can be adjusted as needed. Biomarkers such as proteinuria, complement levels or genetic markers can be used to assess disease activity and predict response to treatment. In this Special Issue, Aiello et al. described the prognostic and predictive role of interstitial macrophages in kidney biopsies from patients with IgA nephropathy . The autThe aim of personalized medicine should be to identify a patient’s predisposition for a disease and to carry out timely and targeted prevention, as well as determine the optimal therapeutic approach for each patient affected at the right time. In this context, the Special Issue “Personalized Medicine in Kidney Disease” introduces intriguing new viewpoints and highlights the importance of tailored strategies for each individual, given that treatments may vary largely according to specific kidney diseases and individual characteristics. Applying precision medicine is fundamental to develop therapeutic plans that optimize outcomes and minimize the risk of complications.


This study provides insight into the applicability of home blood pressure monitoring, which may aid in the development of more effective hypertension management strategies, particularly the use of morning home blood pressure monitoring to aid treatment decisions through telehealth medicine.Hypertension is a significant public health concern in Saudi Arabia, affecting 28.6% of the population. Despite the availability of effective treatments, optimal blood pressure control is not always achieved, highlighting the need for effective management strategies. This study aimed to evaluate the applicability of home, compared to clinic, blood pressure measurements for managing hypertension in the Qassim region of Saudi Arabia. The study included 85 adults undergoing antihypertensive treatment. Home blood pressure measurements were obtained during the day and the evening using automated oscillometric sphygmomanometers, whereas clinic measurements were taken during clinic hours. Home blood pressure readings were significantly lower than clinic blood pressure readings, with mean differences of 20.4 mmHg and 4.1 mmHg for systolic and diastolic blood pressures, respectively. There was a positive correlation between the clinic systolic and diastolic blood pressures (r = 0.549,  Hypertension is a significant public health concern, affecting millions of individuals worldwide, including those from the Saudi Arabian population. Approximately 32% and 28.6% of the global and Saudi Arabian populations, respectively, are hypertensive ,2. HyperDespite the availability of effective treatment options for hypertension, many individuals struggle to achieve optimal blood pressure control. Guideline-directed treatments have been shown to be effective in reducing the incidence of hypertension-related complications, but only 54% of individuals with hypertension achieve their target blood pressure . This hiThe methods available for measuring blood pressure vary in sensitivity and accuracy. They include clinic blood pressure (CBP) measurement, home blood pressure (HBP) measurement, and 24 h ambulatory monitoring ,9. It isStudies exploring the clinical significance of clinic blood pressure measurement accuracy in Saudi Arabia are scarce. However, a study conducted by Mahmud et al. (2020) compared clinic and ambulatory blood pressure monitoring and found that one-third of individuals may have received inappropriate treatment based on the clinic blood pressure measurements . This hiDeveloping effective strategies for managing hypertension in the community requires a thorough understanding of the differences between clinic and HBP measurements. We conducted a comprehensive study in the Qassim region, to identify and examine the variations between these two types of blood pressure measurements among hypertensive individuals. Through this study, we hoped to gain insights into the factors that contribute to the differences between clinic and HBP measurements and to use this information to develop targeted interventions that could improve hypertension management in our community. To summarize, the objective was to improve the health outcomes of individuals with hypertension and to reduce the burden of this condition on the healthcare system.n = 85) and receiving antihypertensive drug treatment at the Prince Sultan Cardiac Center in Qassim, Saudi Arabia  age of 18 years or older, (2) newly diagnosed or known hypertension, with hypertension defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg by the 2018 European Society of Cardiology and the European Society of Hypertension Guidelines, and (3) capable of performing HBP measurements. These included antihypertensive treatment adjustment within three months of enrollment, inconclusive data, or missing data.HBP measurements were performed using automated oscillometric sphygmomanometers. The arm circumference was measured, and the appropriate cuff size was selected. Following a 5 min rest period, a blood pressure reading greater than 140/90 mmHg, and at least two readings taken during a clinic visit, patients were instructed on how to use an HBP monitoring device, such as the BEURER BM 85 (EN 60601-1-2) , GeratheWe checked the blood pressure using the same home device at each patient’s primary health clinic to ensure the accuracy of the HBP readings prior to starting the self-measurement.The first set of measurements were taken within one hour of waking and the second set between 7:00 p.m. and 10:00 p.m. During the follow-up period, patients were contacted after one week to assess their blood pressure control and make any necessary adjustments to the treatments. If the blood pressure was not controlled, further follow-up was scheduled within two weeks for additional management. Once the blood pressure was successfully controlled, follow-up appointments were scheduled at six-month and one-year intervals to ensure blood pressure control in patients using telemedicine.A data sheet with patient demographics and a schedule for blood pressure measurement results, based on dates and times, were given to the patients, and they were trained to complete it.® statistical software package version 18.0  for Windows10®. The findings of the study were summarized in tables, with the representation of continuous variables as the mean and standard deviation. Categorical variables were reported as numbers and percentages, and the chi-square test was used for comparisons. The comparison in this study focused on male and female patients, considering various factors such as age, body mass index (BMI), nationality, smoking status, newly diagnosed hypertension, and whether medication was adjusted in a home or clinic setting. Matrix correlation was used to determine the associations between clinic SBP/DBP and other clinic/home blood pressure variables. The mean difference between the CBP and HBP results was calculated, and Cohen’s d test was used to determine the effect size. Additionally, further analyses were performed to evaluate the difference between the systolic and diastolic blood pressure measurements conducted in the clinic and at home. Statistical significance was set at a p-value of less than 0.05.Statistical analyses were performed using the SPSSn = 59; 69.4%), followed by middle-aged adults , and young adults . The patients had a mean age of 64 years (range: 33–91 years). Majority of the patients in the study were classified as obese , followed by overweight . The patients had a mean BMI of 26.55 kg/m2 (range: 14–39 kg/m2). A significant p-value was observed for BMI and sex across the study population (p = 0.0098). The male-to-female ratio was approximately equal, with 44 (52%) male patients and 41 (48%) female patients  had their antihypertensive medication adjusted following the CBP reading, while 41 (48%) had their medication adjusted after HBP readings. As indicated in Forty-seven patients had a mean BMI of 26.5, with a mean weight of 71.30 kg and a mean height of 162.55 cm. The mean clinic systolic blood pressure (CSBP) was 159.45 mmHg, while the mean clinic diastolic blood pressure (CDBP) was 79.14 mmHg. The mean morning home systolic blood pressure (MHSBP) and morning home diastolic blood pressure (MHDBP) were 140.69 mmHg and 75.76 mmHg, respectively. The mean evening home systolic blood pressure (EHSBP) and evening home diastolic blood pressure (EHDBP) were 138.95 mmHg and 75.20 mmHg, respectively. The mean home systolic (averaged across both daytime and evening readings) and diastolic blood pressures were 138.99 mmHg and 75.03 mmHg, respectively. The mean difference between the clinic and home SBPs was 20.46 mmHg, while the mean difference between the clinic and home DBPs was 4.11 mmHg .p < 0.001) between the CSBP and CDBP, indicating that an increase in CSBP is associated with an increase in CDBP. Additionally, there was a weak positive correlation  between the home systolic blood pressure (HSBP) during the day and the CSBP, suggesting that a higher HSBP during the day might be associated with a higher CSBP.We found a significant positive correlation  between the home diastolic blood pressure (HDBP) during the day and that during the evening, indicating that a higher HDBP during the day may be associated with a higher HDBP during the evening. As shown in p < 0.001; r = 0.885, p < 0.001, respectively), as well as between the mean day–evening DBP and home DBP during the day and evening .Furthermore, we found a significant positive correlation , indicating that HSBP was significantly lower than CSBP. The effect size, measured using Cohen’s d, was large (d = 0.92), indicating a substantial difference between the two results.For SBP, the mean difference between the clinic and home results was 20.4 mmHg . This difference was statistically significant (t (84) = 8.43, p = 0.005), indicating that HDBP was significantly lower than CDBP. The effect size was smaller (d = 0.32), indicating a less substantial difference between the two results compared to the SBP . This difference was also statistically significant (t (84) = 2.91,  the SBP .n = 71; 83.6%), while in the home setting, the majority  had SBP readings of 145 mmHg or above. The data also indicate that most patients in the clinic had a DBP of less than 80 mmHg . However, a higher proportion of patients in the home setting had DBP readings of less than 80 mmHg .Our study findings demonstrated a significant discrepancy between blood pressure readings obtained in clinic and home settings, particularly regarding SBP. While the results for both SBP and DBP were not consistent across both settings, the analysis revealed a noteworthy difference in SBP readings. These results underscore the importance of considering the context in which blood pressure is measured when interpreting blood pressure values, as the measurement methodology can have a substantial effect on the results. These findings suggest that clinic and home monitoring measurements may be independent of each other, and that home monitoring may provide a more accurate representation of a patient’s blood pressure over time. Our study holds great importance for the management of patients, particularly those with elevated HBP values.n = 85, p < 0.001), which has significant implications for the management of hypertension. These results indicate that clinic measurement alone may not provide an accurate representation of a patient’s blood pressure and that home monitoring may be a more reliable and precise method of monitoring blood pressure over time. Therefore, incorporating home monitoring via telemedicine into the management and treatment of patients with hypertension may be a more effective approach for achieving optimal blood pressure control and reducing the risk of associated complications , as well as for DBP readings, as shown in The higher mean difference observed in our study could be attributed to the larger proportion of patients in our CBP sample with high SBP readings of 160 mmHg or more (n = 76) received blood pressure management either in the clinic or at home after obtaining BP readings, while approximately half of the study population  had their medication adjusted through landline, mobile telephone/modem transmission, or the internet (We observed that 89% of the patients (internet . TeleheaHBP monitoring equipment has been shown to be helpful for the management of hypertension, despite its heterogeneity, but strong and consistent evidence is presented ,27,28. AOne study suggested that the most effective healthcare model for telehealth in hypertension management should incorporate remote monitoring and the transmission of vital signs, particularly blood pressure, medication adherence, and education on lifestyle and risk factors, with video consultation as an optional feature . TeleheaA recent meta-analysis provided significant evidence of the therapeutic benefits of interventions, particularly regarding self-monitoring of blood pressure. The analysis found that when self-monitoring was combined with co-interventions, such as education or lifestyle counseling, it resulted in greater reductions in SBP/DBP compared to usual care controls, with reductions of up to 6.1 mmHg . AdditioAnother systematic review reported that telehealth interventions led by nurses resulted in a significant decrease in blood pressure levels, especially SBP, in the intervention groups. The review also revealed positive effects on reducing cholesterol levels, increasing the consumption of fruits and vegetables, promoting physical activity, and enhancing adherence to medication. Furthermore, the nurse-led interventions were found to have a positive impact on hypertension awareness, self-efficacy, and self-control . Using aIn summary, our study highlights the significance of telehealth and systolic HBP monitoring in the management of hypertension. We found that the clinic blood pressure readings were consistently higher than the home blood pressure readings. Physician- or nurse-led interventions, including the promotion of medication adherence and education on lifestyle factors, are effective in controlling and managing hypertension. Patients should be educated on the importance of HBP monitoring, which is equally significant in hypertension management. Telehealth interventions can enhance access to care and empower patients to take control of their health, making them valuable tools for hypertension management.


Infants who were less than 30 weeks of gestational age were included. After randomization, initial ventilator settings were adjusted for each patient. After the first 2 h of ventilation, the patients were switched to the other ventilator mode for 2 h. The ventilator parameters, vital signs, and blood gas values were evaluated. The study included a total of 28 patients, 14 in the PRVC group and 14 in the bilevel VG group. The mean birth weight was 876 g (range: 530–1170) and the mean gestational age was 26.4 weeks (range: 24–29). The patients’ peak inspiratory pressure (PIP2 and PIP3) was lower after ventilation in bilevel VG mode than in PRVC mode . After 2 h of bilevel VG ventilation, the mean heart rate decreased from 149/min to 140/min (p = 0.001) and the oxygen saturation increased from 91% to 94% (p = 0.01). Both the PRVC and bilevel VG modes of GE ventilators can be used safely in preterm infants, and bilevel VG mode was associated with more favorable early clinical findings. Studies including more patients and comparing with other modes will clarify and provide further evidence on this subject.The present study aimed to compare the bilevel volume guarantee (VG) and pressure-regulated volume control (PRVC) modes of the GE One of the most important steps in reducing neonatal morbidity is to prioritize noninvasive respiratory support and avoid invasive mechanical ventilation. However, the latter is used as rescue therapy in infants with severe respiratory distress. According to US Neonatal Research Network data for 2018, 84.3% of infants at <29 weeks of gestation received conventional mechanical ventilation support during their stay in the NICU [Rapid advances in ventilator technology have resulted in numerous basic and complex respiratory support modes. To understand how a mechanical ventilator works, one must be knowledgeable about the features of these specific modes, how they interact with an alert and spontaneously breathing infant, and mode definitions specific to the ventilator in the unit ,3.At present, tidal volume-targeted synchronized ventilation modes are most recommended for ventilating preterm infants. Tidal volume-targeted synchronized ventilation has been shown to provide shorter ventilatory support duration and lower rates of adverse effects such as pneumothorax, hypocarbia, severe intracranial hemorrhage, mortality, and bronchopulmonary dysplasia (BPD) ,5,6,7.T) [Along with the increase in available ventilator types and modes, ventilator modes have become more complex, and the parameters that were previously entered and adjusted by the clinician are now automatically adjusted by the device. Bilevel volume guarantee (VG) and pressure-regulated volume control (PRVC) modes are examples of this adaptive target scheme . In an aT) ,9.® Carescape R860 model ventilator and test the safety and feasibility of these two modes in preterm neonates.As experience and evidence regarding the use of new tidal volume-targeted devices and modes in neonatal intensive care units (NICUs) are limited, there is a need for safety and efficacy studies and comparative trials of these modes. The present study aimed to compare the bilevel VG and PRVC modes of the GEThis study was conducted in the NICU of Ankara City Hospital between January 2020 and June 2021, serving as a referral for tertiary care. This study was designed as a prospective, randomized crossover study. Infants who were less than 30 weeks of gestational age, required intubation and mechanical ventilation in the first 24 h of life, received surfactant at least once, and were clinically stable at postnatal 24 h were included in the study. Patients whose families did not provide consent, who had major congenital anomalies at admission, or who had congenital heart disease were excluded. Patients who met the selection criteria were randomized after the first surfactant administration to crossover ventilation with bilevel VG and PRVC for 2 h each using the sealed envelope method with grouping by weight. Group 1 (PRVC): Bilevel VG mode first, PRVC mode second, then continued with PRVCGroup 2 (bilevel VG): PRVC mode first, bilevel VG mode second, then continued with bilevel VG.In block randomization, weight stratification categories were determined as 500–750 g, 751–1000 g, and 1001–1250 g. As blinding was not possible due to the nature of the study, the sealed envelope method was used to help ensure balance and reduce bias. 2, positive end-expiratory pressure (PEEP), pressure support (PS), VT, respiratory rate, inspiratory time (Tins), inspiratory pressure minimum (Pmin) and maximum (Pmax). In bilevel VG mode, FiO2, VT, PEEP, respiratory rate, Tins, and Pmax were set. VT was set to 5 mL/kg and the target blood gas values were pH 7.25–7.35, PaCO2 45–55 mmHg, and PaO2 50–70 mmHg.After group assignment, the infants were monitored with the designated ventilation mode. The following ventilator parameters were set in PRVC mode: FiOT. All spontaneous efforts trigger pressure-assisted breaths. In SIMV PRVC mode, the ventilator delivers synchronized pressure-regulated, volume-controlled breaths at the set respiratory rate. For each mechanical breath, the ventilator adjusts the inspiration pressure to the lowest pressure needed to provide the target VThe ventilator provides volume-controlled ventilation for 10 s or two breaths (whichever is longer when the mode is initiated) to determine the patient’s lung compliance. Inspiratory pressure is determined according to lung compliance and used for subsequent breaths. 2O as the upper limit. The difference in inspiratory pressure between breaths does not exceed ±3 cmH2O. If a high airway pressure alarm is activated for the current breath, the target pressure for the next breath is reduced by 0.5 cmH2O.When adjusting inspiratory pressure, the ventilator uses PEEP + Pmin as the lower limit and Pmax—5 cmHT according to the set respiratory rate and Tins values. As in PRVC mode, the ventilator determines lung compliance by providing volume-controlled ventilation over 10 s or two breaths (whichever is longer when the mode is initiated) and this is used to determine inspiratory pressure for subsequent breaths. Inspiratory pressure limits and adjustments are also the same as in PRVC mode. In Bilevel VG mode, if the patient initiates a breath at the PEEP level, a pressure-supported breath is provided at the set PS. The ventilator switches between the PEEP and minimum pressure to maintain the target V®, Chicago, IL, USA, Carescape R860 model ventilator. After randomization, initial ventilator settings were adjusted for each patient and recorded as the starting point. Respiratory rate, heart rate, and pulse oximetry (SpO2 90–94%) values were continuously monitored in all patients. After the first 2 h of ventilation, the patients were switched to the other ventilator mode for 2 h. Ventilator parameters, vital signs, and blood gas values were evaluated at the beginning of the study, after the first ventilation mode, and after the second ventilation mode  data, or estimated postnatally using the New Ballard Score . Respira2 requirement > 40% received early rescue surfactant therapy. All patients in the study received surfactant  within the first 2 h of NICU admission and were monitored using GE®, Carescape R860 model ventilators. In accordance with unit protocols, surfactant therapy for RDS was administered prophylactically at NICU admission or as early rescue therapy in the first two hours according to the following criteria: as per the recommendations of the Turkish Neonatal Society, preterm infants at gestational age < 26 weeks that did not receive antenatal steroid therapy and preterm infants that required intubation in the delivery room received prophylactic surfactant; infants with signs of RDS findings and FiO2 requirement ≥ 60%, respiratory acidosis (pH < 7.2) under PEEP ≥ 7 cm H2O, and recurrent apnea.Noninvasive ventilation techniques and less invasive surfactant administration methods are encouraged in all patients with a good respiratory drive however patients were intubated and mechanically ventilated if they fulfilled the following criteria. Hypoxemia despite FiO2 ≥ 21;Mild BPD, nasal cannula oxygen < 2 L/min, FiO2 ≥ 21;Moderate BPD, nasal cannula oxygen > 2 L/min or nCPAP or NIPPV, FiO2 ≥ 21.Severe BPD, invasive PPV, FiOBPD in a preterm infant < 32 weeks of gestational age is defined as radiographically confirmed persistent parenchymal lung disease and is classified according to oxygen requirement at postmenstrual 36 weeks as follows ,15:Mild PDA refers to the nonclosure of the ductus arteriosus after the first 72 h of life. The diagnosis of hemodynamically significant PDA is made by demonstrating high-volume flow through the PDA on echocardiography. The first choice of medical treatment for PDA in our clinic is ibuprofen in two doses, 10 mg/kg/day followed by 5 mg/kg/day, administered 24 h apart .ROP screening is performed in all infants born at a gestational age of <34 weeks and a birth weight of <1700 g, as well as infants with a gestational age of ≥34 or a birth weight of >1700 g who received cardiopulmonary supportive treatment or is considered by the attending clinician to be at risk of ROP. The first ophthalmological examination is performed at postnatal 4 weeks. In our unit, the criteria specified by the multicenter ETROP (Early Treatment for Retinopathy of Prematurity) study group are used in the application of laser photocoagulation for ROP .Proven sepsis is defined as the presence of clinical and laboratory findings consistent with sepsis and a demonstrated causative pathogen. Clinical sepsis is defined as the presence of clinical and laboratory findings consistent with sepsis for which a causative pathogen could not be demonstrated ,20. IntrData regarding the patients’ survival to discharge, any stage of BPD, PDA requiring medical treatment, any stage of ROP, grade 3–4 IVH, and clinical or proven sepsis was recorded from the patients’ records. Follow-up ventilation management and other supportive treatments were provided by the attending neonatologist in accordance with unit protocols. In our unit, the feeding and care of preterm infants and the diagnosis and management of RDS, BPD, patent ductus arteriosus (PDA), and the retinopathy of prematurity (ROP) were carried out in accordance with Turkish Neonatology Society guidelines ,17,19,22clinicaltrials.gov (accessed on 12 May 2019) (NCT04191239).Written informed consent was obtained from the patients’ families. The study was approved by the Ankara City Hospital Ethics Committee (E1-19-198) in accordance with the Helsinki Declaration and prospectively registered at t-test was used for comparisons of repeated measures within subjects and the Mann–Whitney U test was used for comparisons between the two different groups. Statistical significance was accepted at p < 0.05. The data were analyzed using SPSS for Windows. Descriptive statistics are shown as frequency and percentage, mean and standard deviation, or median and range. A paired samples The study included a total of 28 patients, 14 in the PRVC group and 14 in the bilevel VG group. The mean birth weight was 876 g (range: 530–1170) and the mean gestational age was 26.4 weeks (range: 24–29). The characteristics of the patients are shown in 2 and PIP3) was lower after ventilation in bilevel VG mode than in PRVC mode . After 2 h of bilevel VG ventilation, the mean heart rate decreased from 149/min to 140/min (p = 0.001) and the oxygen saturation increased from 91% to 94% (p = 0.01). There were no significant differences in mean airway pressure, respiratory rate, or blood gas values. The patients’ peak inspiratory pressure (PIPAs shown in 2 retention. CO2 excretion is determined by VT and the respiratory rate. Volume-targeted ventilation (VTV) strategies aim to provide a consistent VT. VTV has been used for many years in pediatric and adult patients, and tidal volume-targeted synchronized ventilation modes are currently the most recommended strategy for ventilating preterm infants.Mechanical ventilation is used when preterm infants have insufficient respiratory effort or in the presence of apnea or CO® Carescape R860 model ventilator are two examples of adaptive target schemes for achieving target VT. This study aimed to compare and evaluate the safety and feasibility of these two modes for use in NICUs equipped with this ventilator model.The bilevel VG mode and PRVC mode of the GEThe literature includes very few studies of these modes and much less information about their use in neonates. 2/FiO2 and PaO2) were significantly better in the PRVC group (p = 0.004). The dead space volume/tidal volume (VD/VT) and inspiratory airway pressures were significantly lower in the PRVC group. In addition, all inflammatory parameters  were significantly lower in the PRVC group. Therefore, it was concluded that the PRVC mode had positive effects during OLV in thoracic surgery [In a study investigating the effects of PRVC and VG ventilation modes on oxygenation parameters, airway pressures, and immunomodulation during one-lung ventilation (OLV) in 70 adult patients undergoing thoracic surgery, oxygenation parameters  more than VCV. A target Vtilation .A study including 39 older intubated patients with chronic obstructive pulmonary disease compared PRVC and SIMV-VC modes and evaluated the efficacy of PRVC mode and its prevention of pulmonary barotrauma. Assessment of respiratory mechanics, arterial blood gas analysis, and vital signs at 2–4 h and at 48 h showed that PRVC resulted in rapid improvement in arterial blood gas parameters while maintaining low peak inspiratory pressure .Kıhtır et al. evaluated 61 children (median age 12) with acute respiratory failure ventilated with PRVC or pressure-control (PC) modes. PC ventilation mode was used on 40 (65.6%) patients and PRVC mode was used on 21 (34.4%) patients. Forty-four patients (72.1%) had hypercapnic respiratory failure and twenty-eight patients (45.9%) had hypoxemic respiratory failure. Although the PC ventilation mode was preferred more frequently in hypoxemic respiratory failure, no difference was found in terms of MV duration, length of stay in the pediatric intensive care unit, and mortality between the two respiratory modes. It was stated that PRVC mode can be used as a safe option for units that do not have sufficient experience in using PC ventilation mode .Another study compared PRVC and SIMV modes in 212 preterm infants under 1250 g who received mechanical ventilation in the first 6 h of life. There was no significant difference between the SIMV and PRVC groups in terms of infants alive and extubated on day 14 (41% vs. 37%), the duration of mechanical ventilation in survivors (median 24 vs. 33 days), or the proportion of infants not needing supplemental oxygen at postmenstrual 36 weeks (57% vs. 63%). Mode change due to unsuccessful ventilation was more frequent in the SIMV group (33%) than in the PRVC group (20%), but the inclusion of this unfavorable outcome did not change the overall result. The authors concluded that PRVC ventilation had no effect on the extubation time compared to SIMV .p < 0.005). In the subgroup analysis of infants under 1000 g, the PRVC group had shorter ventilation duration and a lower incidence of hypotension (p < 0.005). It was reported that PRVC ventilation can be used safely in newborns and may contribute to a lower complication rate [In a study comparing PRVC and IMV modes in 60 neonates under 2500 g who required mechanical ventilation, the duration of ventilation and the incidence of BPD were found to be similar. The incidence of IVH grade 3 or higher was lower in the PRVC group (ion rate .2 values, and air leaks. In our practice, we prefer VG and volume-targeted modes. We planned this study both because GE-brand ventilators have not been evaluated in neonatal and preterm infants in the medical literature and because these devices are available and being used in some hospitals.Volume-targeted, volume-guaranteed ventilation is currently the most valid ventilation mode for preterm infants . Some deIn recent trials, valuable information regarding HFO ventilation in preterm infants has been provided. Although there is information that HFO can reduce BPD when used as the first mode in premature babies, more studies need to be designed on this subject ,30.® Carescape R860 model ventilator in very preterm infants. Moreover, the infants were diagnosed and treated by experienced staff with strictly adapted guidelines. To our knowledge, this is the first study comparing these two modes driven by the GEThe small number of patients is the main limitation of this study. Our results do not indicate that one of these modes is superior or more useful than other modes. However, devices and modes not previously used in neonatal studies were used as treatment options in very small preterm infants and were shown to be safe and applicable in this group. Another limitation may be our selection criteria because the infants included in the study are preterm infants with surfactant-treated RDS. The limited gestational age and the underlying cause may have altered the results. Larger studies including infants with different gestational ages and conditions that lead to intubation and invasive mechanical ventilation are required. In conclusion, both the PRVC and bilevel VG modes of GE ventilators can be used safely in preterm infants, and although the difference may not be very pronounced, bilevel VG mode was associated with more favorable early clinical findings. Studies including more patients and comparing them with other modes will clarify and provide further evidence on this subject.