Elevated blood pressure affects a great part of the elderly population and is the leading risk factor for cardiovascular disease. New approaches have been taken in the fight against this growing problem, in the form of diets  and intermittent fasting). Recent research has shown the promising results regarding diets and their effect on the prevention and improvement of elevated blood pressure. This review attempts to take this a step further, reviewing 26 studies in the search for dietary elements that may be causing this improvement. Although good evidence was found in favor of lycopene, Docosahexaenoic acid (DHA), fiber and anthocyanin, further evidence is needed before any conclusions can be made. In contrast, the evidence shows that licorice increases blood pressure. Elevated blood pressure, also known as, hypertension is a medical condition affecting over 1.13 billion people worldwide and causes approximately 9.4 million deaths due to complications every year .This condition may affect people of all ages but has a predominant prevalence in the adult population, affecting over 50% of adults between 50–59 years of age and approximately 70% of adults over 70 years of age . In the Hypertension is defined in office as blood pressure (BP) of > 140 mmHg systolic and/or with >90 mmHg diastolic, or an average blood pressure of > 130/80 mmHg based on 24 h ambulatory blood pressure monitoring (ABPM) .Hypertension can be classified based on etiology. Primary or essential hypertension is the most common type and is responsible for over 90% of cases, but this type of hypertension has a rather unknown heterogenic origin, although, certain studies have linked genetically, environmental and life factors as possible causes for this disease ,8. SeconCurrent European guidelines for the treatment of hypertension advises all hypertensive patients disregarding of their blood pressure to adopt a change in their life-style, which includes the following: a decrease in sodium consumption < 5 g/days), moderate alcohol consumption, weight reduction, regular physical activity, smoke cessation and other dietary changes, the latest being the object of this review  g/days, . With thDietary changes are important in the fight against hypertension and diets have been a way of implementing these changes. It is well known that the Mediterranean diet has several cardio protective benefits, such as decreasing incidence of cardiovascular disease, decreasing systolic and diastolic blood pressure (DBP), decreasing all causes of death and decreasing risk of stroke . IntermiAll independent authors searched PubMed and MEDLINE for all published results between January 1990 and December 2019 on bioactive compounds and their effect on blood pressure. The following search terms were used: “blood pressure diet” (MeSH Terms) OR “blood pressure” (All Fields) AND “diet” (All Fields) AND “anthocyanian” (All Fields) OR “blood pressure anthocyanian” (All Fields) AND “lycopene” (All Fields) AND “blood pressure lycopene” (All Fields) AND “docosahexaenoic acid” (All Fields) OR “blood pressure DHA” (All Fields) AND “caffeine” (All Fields) OR “blood pressure caffeine”(All fields) AND “dietary fiber”(All fields) OR “blood pressure dietary fiber”(All fields) AND “licorice”(All fields) OR “blood pressure licorice” (All fields). Investigators also searched the bibliographies of relevant articles.Population: individuals with hypertension, normotension;Intervention: individuals with supplementation of described nutrients;Comparison: individuals without supplementation of any nutrients;Outcome: presence/absence of changes in blood pressure;The present review was prepared accordingly to the following criteria:All published studies were only included if they were written in English. Included papers could additionally be studies performed on animals. Investigators independently reviewed each study’s title and abstract according to the prespecified eligibility criteria. Abstracts of interest were included for full-text analysis. Afterwards, authors analyzed all full-text articles and rejected those that did not meet the aforementioned criteria. Any inconsistencies between the reviewers were resolved by discussion with a supervisor (M.W.).All included articles were analyzed independently by the authors. The abstracted information included author names, year of publication, study design, intervention, dose of intervention and main outcomes. The supervisor (M.W.) checked the abstracted information and resolved any disagreements.Anthocyanins are phytochemicals belonging to the polyphenol family. They are naturally occurring water-soluble pigments ranging from red-orange to purple and are found in different fruits and plants, the most common being cyanidin, pelargonidin, peonidin and delphinidin . There iTogether with the above-mentioned qualities, in vitro studies suggest potential vasodilating qualities through the enhancement of endothelial nitric oxide synthase and nitric oxide production ,22. Endop < 0.03 [In a large prospective study from 2011 done by Cassidy et al., a selected population of 157,957 participants from across three cohorts, Nurses Health Study I (NHS I), Nurses Health Study II (NHS II) and from the Health Professionals Follow-up Study (HPFS) were assessed in order to find a relation between flavonoid intake and hypertension incidence. During a 14-year period, the participants answered a follow-up dietary intake questionnaire in order to assess their daily flavonoid intake. The mean flavonoid intake across cohorts was 358–413 mg/day from which 12.5–15.2 mg/day were anthocyanins. The participants were separated based on their total flavonoid intake, which was measured with the US Department of Agriculture (USDA) database. The final observations of this research reported an association between increased consumption of anthocyanins and a reduced risk of hypertension development in the highest quintile of 8% compared to the lower quintile p < 0.03 .In 2012, Jennings et al. conducted a cross-sectional study, using collected data of 1898 women from the TwinsUK registry for the assessment of their flavonoid intake and vascular health. The flavonoid intake was measured through a food frequency questionnaire and the USDA database. The vascular health was measured through peripheral and central blood pressure measurements with a subset population (n = 728), also measuring arterial stiffness thought pulse wave velocity (PWV). The conclusions of this article showed that increased anthocyanin intake was associated with decreased central SBP and MAP by 3.04 ± 1.41 mmHg and 2.31 ± 1.16 mmHg, respectively, as well as decreased arterial stiffness by 0.4 ± 0.22 m/s in the subset population .p < 0.007), this study also showed that no significant changes in sitting BP nor in the 24 h ambulatory BP were found, thus, concluding that anthocyanins could not be recommended as antihypertensive treatment in this particular population [In a study by SS Hassellund et al., 27 male mildly-hypertensive participants were selected in order to carry out a double-blind randomized placebo-controlled crossover study. The participants were subsequently divided into two groups, placebo vs. anthocyanin. During the treatment intervals, the participants took four 80 mg capsules of anthocyanin extract twice a day for four-weeks, followed by a four-week washout. The participants had four visits during each interval, where BP measurements, lab tests, stress tests, and 24-h ambulatory BP were assessed. Although a reduction in resting supine BP was measured  [For the above-mentioned qualities, studies have been conducted in order to test further cardiovascular properties. In 2019, 61 individuals  were recruited for a double-blind, randomized, placebo-controlled study that assessed the blood pressure reduction qualities of lycopene in a dose dependent manner. The individuals were between 35–60 years old and were diagnosed with hypertension stage 1 or 2, without receiving any pharmacological treatment. The individuals were divided into 5 groups, in which different doses were tested: 5 mg, 15 mg and 30 mg of tomato nutrient complex (TNC) and 15 mg of synthetic lycopene and placebo, respectively. The duration of the treatment was 8 weeks with examinations every 2 weeks, which included BP measurements, pulse and physical examination. The 15 mg and 30 mg groups showed significant reduction in SBP at the end of the 8-week period, displaying the following changes: 127.2 ± 6.3 mmHg compared to 137.4 ± 5.6 mmHg at baseline and 130.0 ± 13.0 mmHg compared to 136.4 ± 7.8 mmHg at baseline, respectively. After these findings, 31 subjects agreed to continue for a four-month single-blind treatment with 15mg lycopene. The results were similar with the previous findings, SBP was reduced during the entire treatment period with results showing a decrease of 4.7 ± 6.7 mmHg compared to baseline ( 0.0012) . This stp < 0.0001)) and DBP similarly showing reductions (83.38 ± 6.6 mmHg) compared to baseline (87.44 ± 6.8 mmHg ( p = 0.003)) [p < 0.001) and 140.4 ± 13.3 at baseline changing to 128.7 ± 10.4 (p < 0.001) during the supplementation with tomato extract [In 2005, Engelhard et al. conducted a 16-week single-blind placebo-controlled trial with 31 participants in order to evaluate tomato extract supplementation effects on blood pressure and cardiovascular risk biomarkers. All the participants had grade-1 hypertension with no other comorbidities, nor were they on any hypertensive treatment. The study was divided into a 4-week placebo period, followed by an 8-week treatment period, followed by a 4-week placebo period. During the treatment period, subjects consumed a capsule of 250 mg tomato extract containing 15 mg of lycopene. Follow-up visits were every 2 weeks. Significant blood pressure reduction was noticed during the treatment phase, with the SBP showing considerable reductions (134.02 ± 10.83 mmHg) compared to baseline (144 ± 5.99 mmHg ( 0.003)) . Further extract . Nevertheless, in 2012, Thies et al. observed no significant changes of CVD biomarkers as well as no significant changes in SBP, DBP and PWV. The study enrolled 225 moderately overweight participants (94 men and 131 women), without concomitant diseases between 40 and 65 years of age for a 16-week single-blind, randomized controlled trial. The participants began with a 4-week controlled diet low in tomato and were later divided into three intervention groups; a control group with a low tomato-based diet (<70 mg/week), a lycopene supplemented group (capsule 10 mg/day) and a high tomato-based diet (>70 mg/week). Blood pressure and PWV were measured at baseline and after intervention, whereas blood samples were taken at baseline, after 6 weeks and after 12 weeks . AlthougDocosahexaenoic acid (DHA) together with eicosapentaenoic acid (EPA) is a type of polyunsaturated fatty acids (PUFAs) belonging to the omega3 fatty acids, commonly found in oily fish. These PUFAs have been the topic of several studies. Even though guidelines from the American Heart association (AHA) and the European society of cardiology (ESC) recommend the intake of oily fish in their diet to reduce cardiovascular risk, studies have been inconclusive regarding the actual beneficial cardiovascular effects of fish oils. A recent meta-analysis strongly suggests their association with a lower risk of myocardial infarction (MI), total coronary heart disease (CHD), total cardiovascular disease (CVD) and decrease in deaths of those causes . This opp < 0.01) [In 2007, Theobald et al. explored the benefits of fish oil on vascular function in 40 healthy adults between 40 and 65 years. In this crossover study, participants were treated for two periods of 3 months with a wash-out period between them lasting 4 months. The first group took three capsules/day of 500 mg of refined triacylglycerol, providing approximately 0.7 g/DHA, and the other took olive oils capsules (placebo). The results showed a decrease in DBP by 3.3 mmHg  ( < 0.01) . SimilarResults from a research carried out by Sagara et al. found a significant correlation in blood pressure and lipid reduction on subjects treated with DHA. The study analyzed the data from 38 middle-aged males, who were divided into two groups and underwent a 5-week treatment with 2 g of DHA/day or 1 g of olive oil (placebo). None of the subjects had any lipid or hypertensive treatment. Blood pressure and blood samples were taken at baseline and post treatment, at the beginning of the sixth week. The DHA treated group showed a decrease in SBP of 133.0 ± 12.9 compared to 141.4 ± 13.5 at baseline, and a decrease in DBP of 81.9 ± 9.3 compared to 86.7 ± 10.4 at baseline. A high-density lipoprotein cholesterol (HDL-c) increase of 16.7% (8.6 mg/dL) was also reported, and the placebo group also showed an increase in HDL-c of 9.9% (4.5 mg/dL) [Furthermore, in 2019, Cheng et al. used data gathered by the National Health and Nutrition Examination Survey (NHANES) to conduct a cross-sectional study regarding the dietary intake association of omega-3 and omega-6 fatty acids and the incidence of hypertension. The gathered data covered the periods of 2007 and 2014 with a population of 18,434 participants, all being over 18 years of age. The results of this study suggests an association between increased omega-3 and omega-6 fatty acids and a decrease in incidence of hypertension .These studies suggest a positive effect of omega-3 fatty acids in blood pressure reduction . AlthougCoffee is a widely popular warm beverage consumed worldwide. Coffee may be one of the world’s most loved beverages. People all over the world consume almost 9 billion kg every year .In addition to the stimulant effect of caffeine on the central nervous system, it has also been demonstrated to have a pharmacological effect on the cardiovascular system . Howeverp = 0.05) and +2.11 mmHg (p = 0.64), respectively. The study showed no significant rise in systolic and diastolic blood pressure on young normotensive participants after one cup of coffee [A randomized, double-blind, placebo-controlled clinical trial was conducted in 2016 on 104 young normotensive adult participants. Intervention and placebo were single drinks of coffee, caffeinated (80 mg of caffeine) or decaffeinated, respectively. The amount was 250ml per cup. The results showed a mean difference in SBP and DBP of +2.77 mmHg  and were normotensive at the start of the study. The participants were followed up for an average of 5 years. Coffee consumption was categorized according to a standard cup of coffee: 150 mL per cup. They did not take into consideration of the dosage in milligrams of caffeine per cup. The study showed the risk of hypertension was lower for individuals having 3–4 cups per day in both sexes of non-smokers .p > 0.05). The pilot study did not compare effects of a placebo or other sources of caffeine. However, the metabolic changes were compared between baseline/before and after ingestion when evaluating the effects of green coffee [A pilot study in 2018 on 24 women was conducted where green coffee was given which contained 6mg of caffeine. The change in blood pressure values of the women following the consumption of green coffee was not statistically significant  were compared. After a 10-min baseline measurement, the participant would drink either coffee or the placebo. The study showed that mean arterial pressure and systolic blood pressure were higher at times of 30 and 60 min after drinking the coffee when compared to the placebo .Dietary fiber is a type of carbohydrate mostly found in plants and can be classified into soluble/fermentable  and insoluble/non- or partially fermentable  . Dietaryp < 0.001). The analysis also revealed that the effect of psyllium was stronger in participants with a higher baseline blood pressure [In a meta-analysis by Clark CCT et al., significant data was found on the effect of dietary fiber on hypertensive patients in randomized controlled trials. A total of 11 trials with 592 participants were analyzed. It revealed a reduction of 2.04 mmHg in SBP  [In 2018, Machoene D. Sekgala et al. provided a study with 627 young adults in villages in Limpopo, Africa. Dietary fiber intake was measured by a validated 24-h recall method. The majority of participants had reported an extremely low intake of fiber, barely hitting 2 g per day. Log total fiber was inversely proportional with SBP (= 0.051) .A systematic review and meta-analysis of randomized controlled trials by K. Khan et al. found that viscous soluble fiber had a reducing effect on both systolic and diastolic blood pressure. Diets rich in beta-glucans, with median difference of 4 g between the placebo and control group showed a reduction of 2–9 mmHg for SBP and 1–5 mmHg for DBP (95% CI). It was observed that the effects could be stronger in individuals who were originally hypertensive .a non-significant change to SBP (−1.13 mmHg) but a significant reduction in DBP (−1.26 mmHg). The effect was stronger on participants aged above 40 years, but this was only significant for SBP. Changes in blood pressure became less pronounced with increased dose of fiber. Blood pressure reductions tended to be larger in hypertensive populations [In 2005, a meta-analysis of randomized placebo-controlled trials of dietary fiber intake and blood pressure was completed by Streppel et al., where a total of 1404 subjects were included, and sample size ranged from 12 to 201 subjects. In 24 randomized controlled trials, fiber intake was at a mean dose of 11.5 g/dL. It caused ulations .p < 0.001) and no significant changes regarding DBP [Becerril-Alarcon et al. explored the effects of inulin supplementation on 38 middle aged women with breast cancer undergoing neoadjuvant chemotherapy. A total of 19 of the participants had an SBP of > 130 mmHg before the supplementation. The participants were given 15 g of powdered agave inulin or 15 g of maltodextrin as a placebo. The powders were dissolved in 250 mL of water, and were taken during breakfast. The supplementation lasted for 21 days at the same time as they underwent chemotherapy with doxorubicin and cyclophosphamide for the first time. The study found that inulin supplementation had a significant reduction in SBP of 4.21 mmHg  as treatment. The patient’s blood pressure increased from 90/60 mmHg to 130/80 mmHg in an upright position in 7 days of therapy. Therefore, there might be some indications that licorice can be suggested to be used in clinical therapy, but this must be further investigated in a double-blind, randomized, controlled trial to avoid bias .From the abovementioned studies , there sCamellia sinensis) with known antioxidant and anti-inflammatory properties [Epigallocatechin-3-gallate (EGCG), is a major catechin found in green tea ) [In a randomized study conducted by Brown et al., 100 nondiabetic, nonsmoker, obese or overweight male subjects were enrolled to assess the effectiveness of epiallocatechin-3-gallate on insulin resistance as well as associated metabolic risk factors. The subjects were randomly assigned into a placebo group, taking 400 mg lactose capsules or into an EGCG group taking 400 mg EGCG capsules. The capsules were taken twice daily for an 8-week period. The results of this study showed no significant changes in insulin resistance, total cholesterol, HDL-cholesterol and LDL-cholesterol, but they did show a positive DBP reduction ) .Camellia sinensis compounds (CSC) group, with follow-ups at baseline, after 3 weeks and after 3 months. There results were as follows: SBP was 130 ± 6.88 mmHg at baseline, 126 ± 6.3 mmHg at 3 weeks and128 ± 6.3 mmHg at 3-months, while DBP was 80.2 ± 4.15 mmHg at baseline, 76 ± 4.2 mmHg at 3 weeks, and 79 ± 4.2 mmHg at 3 months [Results from a randomized study, carried out by Nantz et al. showed that a standardized twice-a-day dose of decaffeinated green tea products (containing L-theanine and EGCG) effectively reduced SBP and DBP at 3 weeks and only SBP after 3 months. Hundred and eleven healthy men and women between 21–70 years old volunteered for this study and were randomly assigned to either the placebo (PBO) group or the 3 months .In 2012, Bogdanski et al. conducted a 3-month, double-blind, placebo-controlled trial with 56 obese, hypertensive males and females for the purpose of assessing the effect of green tea extract on insulin resistance and associated cardiovascular risk factors. The subjects were randomly assigned to either one capsule/day of green tea extract (GTE) (containing 208 mg EGCG) or placebo (containing cellulose) with results showing a decrease in SBP and DBP  as well as a considerable reduction in LDL-C, TG, insulin resistance and an increase in HDL-C .p < 0.01 and DBP of 77.1 ± 8.5 mmHg at baseline, compared to 82.4 ± 8.2 mmHg after 12 weeks, p < 0.01) at bedtime, as well as improvement of the eye accommodation ability in subjects below the age of 45 [In 2018, 120 healthy subjects between the ages of 20 and 60 were subjects of a 12-week, parallel study conducted by Maeda-Yamamoto et al., whose aim was to determine if visual function and BP could be improved by green tea containing anthocyanin. The subjects were divided into three groups: the first group consumed barley extract (without catechins), the second group consumed “Sunrouge” (containing 323.6 mg EGCG and 11.2 mg anthocyanin) and the third group consumed “Yubukita” (containing 322.2 mg EGCG). The results of this study showed no significant BP or visual improvement in the “Yubukita” group. Moreover, the “Sunrouge” group showed an increase in blood pressure  of bioactive peptides . IncreasBioactive peptides can be released during enzymatic proteolysis and fermentation. Many low molecular weight peptides have great ACE inhibition because low molecular weight peptides have a high rate of absorbency in the body. The ACE inhibitory effect is related to the degree of enzymatic hydrolysis and composition of the sequence of the peptide in question. When compared with synthetic ACE inhibitor drugs, ACE inhibitors derived from natural food have minimal side effects like cough, increased blood potassium levels, fatigue and fetal disorder. They have been mainly discovered by hydrolyzing proteins with food-grade proteolytic enzymes to release several peptide fragments into the hydrolysate. Proteins can also be fermented by bacteria through the bacteria’s proteolytic enzymes. The bioactive peptides in the hydrolysate can then be used as a functioning food and purified into nutraceuticals for nonpharmacological therapy. Bioactive peptides can be found in nature in plants, animals, fungi and microbes .p < 0.001) and reduced office DBP by 1.51 mmHg (p < 0.001). The intervention duration varied between 4–21 weeks. Blood pressure reduction was more evident in the Japanese and Finnish studies [A comprehensive meta-analysis was published in 2015 containing 30 studies involving 33 trials with a total of 2200 participants (who were randomized) that were published between 1996 and 2014. They tested the effect of lactotripeptides (LTP) on blood pressure. It showed LTP consumption reduced office SBP by 2.95 mmHg . They had a 4-week wash-out. The results indicated significant reduction in both SBP (–3.9 mmHg) and DBP (–2.5 mmHg). for both .p < 0.001 for both values. The study did not examine whether the reduction in blood pressure was due to the protein or the isoflavones in soybean [A randomized controlled trial was published in 2005 that studied the effect of soybean protein on blood pressure. 302 participants from 35 to 64 years of age were included in the study. Participants were given randomly 40 g of isolated soybean protein supplements per day or complex carbohydrate (control) for 12 weeks. The results showed a significant reduction in SBP (–4.31 mmHg) and DBP (–2.76 mmHg).  soybean .Katsuwonus pelamis). It is a traditional Japanese food which is known to inhibit the angiotensin I-converting enzyme (ACE). From this, they used hydrolyzate “katsuobushi oligopeptide” (KO) and a stronger (S-KO) by ultrafiltration for the consumption for participants. A total of 65 participants with borderline and mildly hypertensive participated in the study. The participants were monitored for 10 weeks. Ingestion of a placebo and SKO tablets (1.5 g/day) were compared. S-type KO significantly lowered blood pressure at a dose that can be used as a daily dietary supplement [In 2001 a study about the effects of “katsuobushi” consumption and blood pressure was published. Katsuboshi is dried, fermented and smoked skipjack tuna (pplement .EGCG, but larger and longer studies are needed before any definitive conclusions should be made. It is also of great importance to assess optimal dosages and populations for the maximization of its effects.In this review, several bioactive compounds and their effects on blood pressure were analyzed. Although not conclusive, there is good evidence suggesting the blood pressure-reducing effect of lycopene, DHA, and fiber, but further studies should be conducted in order to find optimal dosages and populations. There is also some evidence suggesting similar qualities in anthocyanin, but to a lesser degree. More evidence is needed in order to be able to make any definitive conclusions in addition to finding optimal dosages and type of population. There is good evidence regarding Regarding bioactive peptides, the evidence shown in this review suggests a positive effect on blood pressure reduction, but larger quantitative studies need to be performed in order to draw a conclusive correlation. Nevertheless, the evidence to date is promising. There is limited available data regarding caffeine, which shows inconclusive and even conflictive evidence, thus, more studies are needed before any assumption can be made. As for licorice, there is substantial evidence showing its blood pressure-increasing effects and patients should be advised to be cautious and discouraged from its consumption. Apart from licorice, all other substances have been suggested, to a certain degree, to have a positive effect on the cardiovascular system. Thus, their consumption should still be advised in populations at risk.


TM Pulmonary Artery Pressure Sensor  and the usability of the comprehensive CordellaTM Heart Failure System (CHFS).Incorporation of remote monitoring of pulmonary artery pressure and vital signs has been demonstrated to reduce heart failure (HF) hospitalization and all‐cause mortality in selected symptomatic HF patients. The aim of this study is to investigate the safety and accuracy of the new CordellaMulticentre, open‐label, first‐in‐human, feasibility study to evaluate the CHFS and the safety and accuracy of the Cordella™ Pulmonary Artery Pressure Sensor in 15 patients with New York Heart Association class III HF. All patients were successfully implanted with the Cordella Pulmonary Artery Pressure Sensor, without sensor failure. No device system‐related complications, defined as invasive treatment, device explant or death, occurred. The primary efficacy endpoint of a mean pulmonary artery pressure at 90 days was met in all but one patients with a cohort difference of 2.7 mmHg . One patient did not go through the 90‐day right heart catheterization for safety reasons. Patient adherence to daily measurement, transmission of vital signs and pulmonary artery pressure sensor readings were recorded 99% of the time.The initial experience of the CHFS incorporating comprehensive vital signs and pulmonary artery pressure monitoring enables safe and accurate monitoring of HF status. TM Heart Failure System (CHFS) and the investigational CordellaTM Pulmonary Artery Pressure Sensor  provide comprehensive clinical information including PAP, body weight, blood pressure, heart rate and oxygen saturations of HF patients to their physicians, allowing HF patients to be an integral part of the team and provide a proactive HF management platform. SIRONA sought to examine for the first time the safety and accuracy of the Cordella Pulmonary Artery Pressure Sensor and the usability of the CHFS.Incorporation of remotely monitored pulmonary artery pressure (PAP)‐guided treatment algorithm with the aim of maintaining normal PAP range proved to be more effective in reducing heart failure (HF) hospitalizations in selected patients with HF than management based on symptoms and clinical signs.ClinicalTrials.gov Identifier: NCT03375710, CEC Ref. number: 17/061U, date of favourable ethical opinion: 8 November 2017) was a multicentre, open‐label, early feasibility study to evaluate the CHFS and the safety and accuracy of the Cordella™ Pulmonary Artery Pressure Sensor in 15 patients with New York Heart Association (NYHA) class III HF. The study was undertaken in accordance with the Declaration of Helsinki and approved by local ethics committees or institutional review boards. All participants provided written informed consent. Briefly, eligible patients were men or women over 18 years with a diagnosis of NYHA class III HF with reduced or preserved ejection fraction treated for a minimum of 3 months and stable for 1 month prior to enrolment with at least one HF‐related hospitalization or equivalent within the last year. An estimated glomerular filtration rate of ≥30 mL/min/1.73 m2 and appropriate pulmonary artery anatomy, as demonstrated by computed tomography pulmonary angiogram (CTPA), were also required.SIRONA  against the right pectoral region for 20 s and vital signs  were measured using the CHFS. Data were transmitted to the myCordella™ Hub, which guides patients on use of the peripherals, asks the patient health‐related questions, and facilitates patient–clinician communication by re‐transmitting data to the myCordella™ Patient Management Portal Figure1.Post‐procedure follow‐up was scheduled at 1, 3, 6, 9, 12, 18, and 24 months. History and clinical examination were recorded and laboratory assessments undertaken at each visit. Right heart catheterization was performed at baseline and at 3‐ and 12‐month follow‐up in the supine position. The clinicians were blinded to PAP the first 90 days until the accuracy check at 90‐day right heart catheterization.The primary safety endpoint was freedom from device‐related adverse events through 30 days post‐procedure and pressure sensor failure. The primary efficacy endpoint was accuracy of the Cordella Sensor PAP measurements, compared to fluid‐filled catheter 90 days post‐implant. Published data estimate the error of the fluid‐filled catheter as ± 4.0 mmHg. For the Cordella system to be at least as accurate as fluid‐filled, the combined system error has to be less than ± 5.6 mmHg (root square sum of fluid‐filled and Cordella error) with a 95% confidence interval for the total system of ± 11 mmHg. Thus, the pre‐specified primary endpoint was fluid‐filled catheter ± 11 mmHg, with a difference of ± 11 mmHg; in order to meet this endpoint the Cordella Sensor has to be as accurate as a standard‐of‐care fluid‐filled catheter which is ± 4 mmHg.Secondary efficacy endpoints included change in PAP pre‐ and post‐implant, frequency of HF hospitalization or equivalent, change in quality of life (KCCQ and EQ‐5D‐5L) and adherence to myCordella™ Heart Failure System measurements. An independent data safety and monitoring board reviewed all potential procedure‐related serious adverse events and adverse events.The Cordella™ system accuracy was compared to the accuracy of standard‐of‐care commercial products that use fluid‐filled invasive catheters to measure PAP, which have an accuracy of ± 4 mmHg. If ± 4 mmHg is assumed for both Cordella™ and fluid‐filled invasive catheters, then the total system accuracy must be less than ± 5.6 mmHg. This total system accuracy (± 5.6 mmHg) translates into 95% of all Cordella readings must be within ± 11 mmHg of fluid‐filled catheter.Cordella™ readings were compared to reference readings using the Bland–Altman method. A Bland–Altman plot displayed the difference between the measurements from a standard right heart catheterization and the Cordella™ device (y‐axis), vs. the average of these two measurements (x‐axis) for a measurement taken within 24 h of implant and 90 days. This variance corresponds to the documented accuracy of typical standard‐of‐care fluid‐filled invasive catheter pressure measurement systems. Statistical analyses were performed in accordance with the pre‐specified statistical analysis plan, and SAS version 9.3  or higher was used to analyse the data.Figure2, 10 (67%) were male and 4 (53%) had an ejection fraction >40% ; transient complete heart block was identified in a single patient as the sensor passed through the right heart; post‐procedure minor haemoptysis was reported in two patients Table2. All TableFigureFigureAt 90 days post‐implantation, PAP values measured by the Cordella Sensor and right heart catheterization were well matched. The primary efficacy endpoint of a mean PAP was met in all patients with a cohort difference of 2.7 mmHg . Systolic and diastolic PAP values were also well matched over a clinically relevant pressure range  as well as PROACTIVE‐HF (NCT04089059).The CHFS incorporating comprehensive vital signs as well as PAP monitoring enables safe and accurate monitoring of HF status.The study was funded by Endotronix Inc. Independent data collection, monitoring and data analysis were undertaken by independent contract research organizations (CROs). AR is supported by a Wellcome Trust Clinical Research Career Development Fellowship (206632/Z/17/Z) . All authors had access to data and were responsible for the decision to submit. None of the Authors received any personal financial compensation of Endotronix Inc.Conflict of interest: A.M.K.R. reports research support from Abbott, Medtronic, Actelion, Novartis, SoniVie, Endotronix. All other authors have nothing to disclose.Figure S1. Single patient‐derived data following informed consent, study enrolment and pulmonary artery pressure sensor implantation. (1) Improved therapeutic adherence to guideline‐directed medical therapy reduced pulmonary artery pressure. (2) Transition from angiotensin‐converting enzyme inhibitor to sacubitril/valsartan reduced pulmonary artery pressure. (3) Increase in pulmonary artery pressure and decreased weight preceded hospital admission with a respiratory infection.Click here for additional data file.Table S1. Pulmonary artery pressure during 90‐day right heart catheterization.Click here for additional data file.


Kidney transplantation is the surgical operation by which one of the two original kidneys is replaced with another healthy one donated by a compatible individual. In most cases, donors are recently deceased. There is the possibility of withdrawing a kidney from a consenting living subject. Usually, living donors are direct family members, but they could be volunteers completely unrelated to the recipient. A much-feared complication in case of kidney transplantation is the appearance of infections. These tend to arise due to immune-suppressor drugs administered as anti-rejection therapy. In this review, we describe the gastrointestinal complications that can occur in subjects undergoing renal transplantation associated with secondary pathogenic microorganisms or due to mechanical injury during surgery or to metabolic or organic toxicity correlated to anti-rejection therapy. Some of these complications may compromise the quality of life or pose a significant risk of mortality; fortunately, many of them can be prevented and treated without the stopping the immunosuppression, thus avoiding the patient being exposed to the risk of rejection episodes.  The fir The condition of suitability for transplantation is subjected to continuous revision and immunological parameters are evaluated to identify the most suitable organ allocation to the patient s profile. Kidney transplantation in most cases is not a lifesaving transplant because dialysis allows survival of patients with renal failure. Compared to dialysis, transplantation is a therapeutic physiological alternative, especially in cases where the renal function returns to normal or close to normal. It allows people not to be dependent on dialysis and overcome the first months of isolation, so that they are able to move in full freedom and also re-enter fully into social and working life .2Kidney transplantation is the surgical procedure by which a kidney taken from a donor is placed in the body of a patient (recipient) with terminal renal insufficiency. There are several types of transplant, which can be classified according to the type of donor from which the organ originates.2.1The organs destined to the donation are taken from patients whose death has been ascertained and with the consent or non-opposition of the family members. In order for an organ to be taken for a transplant, it is necessary that there are no serious diseases or conditions in the donor that could compromise the success of transplant or cause long-term complications for the recipient. Once the suitability of the donor has been ascertained, the organ is removed.(A)Organs come from donors whose brain death has been ascertained. Death is identified with the irreversible cessation of all brain functions due to primary or secondary encephalic damage . This means that all the nerve functions that supervise life have ceased and that only the cardiorespiratory activity is artificially supported to guarantee the blood supply to the organs to be taken.(B)Organs come from donors over 70 years old or over 60 years old with associated risk factors such as impaired renal function or presence of diseases . Once the suitability for the donation has been ascertained , these organs are usually used for a double transplantation in a single recipient .(C)Organs come from donors who died of cardiac death in which any attempt at resuscitation was useless. Death is identified with the irreversible cessation of all vital functions determined by cardiocirculatory arrest with consequent irreversible loss of all functions of the brain. Once the subject (consent or non-opposition of the family) becomes a donor, he or she is subjected to well-defined procedures designed to maintain the fitness of the organs for the purpose of transplantation.The following are the three types of cadaver donors:2.2This procedure requires that the organ to be transplanted comes from a subject still alive. The donor must be of legal age and may be a kinsman (family member), a non-consanguineous associate affective to the recipient or an unknown person. The act of donation is totally free, always revocable and without any kind of constraint/coercion  toward the recipient. The risk of surgery for the donor is the same as any other surgery and it is now widely demonstrated that with a single kidney it is possible to lead a normal life. However, both the donor and the recipient must be aware of the limitations of transplant therapy and aware of all possible clinical complications for both possible personal consequences and psychological implications. For these reasons an explicit and informed consent must be expressed, one must undergo a psychological–psychiatric exam and further evaluation by a special commission is required as well as the clearance of the judicial authority. The living transplantation is beneficial due to the fact the evaluation process of the candidates can be followed so that both the donor and the recipient are in the best conditions of health and it is possible to program the surgery. Furthermore, by reducing the time between organ harvesting and transplantation, better results can be achieved in relation to functional recovery and organ survival. The kidney harvesting surgery is done using laparoscopy procedure, which consists of four holes in the abdomen through which the kidney is extracted. In the absence of complications, the length of hospital stay is 3–4 days. Particular situations may require the need to prepare specific therapeutic and surgical protocols; these may include cases of transplantation (patients with previous transplantation) and the so-called “hyperimmune” patients .2.3NHBD is a type of donation in which the donor suffered a cardiac death, unlike the best known and used donation from deceased donors following brain death, or donors to beating heart (HBD). The spread of this type of transplant has remained for a long time limited to few countries  The term “death due to cardiac arrest” refers to the death that occurs following the cessation of the body circulation for a period of time that determines the irreversible loss of all brain functions, which is ascertained by a doctor by detecting the absence of a heartbeat (asystole) with a 20-min electrocardiogram. The deceased donor for cardiac causes is suitable for the removal of all organs except the heart; the privileged organs are the ones most resistant to ischemic damage, in particular kidneys, liver, and pancreas. Cardiac arrest is the peculiarity but also the main criticality of this mode of donation. During the asystole condition, the kidney does not receive blood supply due to the interruption of the circulation, the refrigeration of the organ and the subsequent reperfusion after the transplant, causing a type of damage defined as ischemia–reperfusion that is potentially higher than that observed in the transplant from a standard donor. To minimize this damage, organ perfusion techniques are used before and after the explant. After the explants, the organs can be kept at 4°C in special storage solutions or positioned inside a dedicated machine that, depending on the model, allows the organ to be perfused in a pulsatile or continuous way with a specific preservation liquid. The latter is the storage method used in the case of NHBD donors (non-beating heart). It has been widely demonstrated that the use of this technique significantly reduces the risk of delay in post-transplant functional recovery (delayed graft function (DGF)), improving the survival of the organ as well as better storage, and it also allows an assessment of suitability before surgery. As in the case of HBDs, organs taken from NHBDs are also assessed on the basis of a series of criteria to establish their suitability before surgery; in order for this type of program to work optimally, the presence of a team is necessary, consisting of various specialized professionals trained to act in a very short time. The data collected so far show a greater number of cases in which there is a delay in functional recovery (DGF) for a prolonged ischemia time. However, the available data show that this event does not affect the long-term survival of the transplanted organ. NHBD is a valid alternative to heartbeat transplantation and an extra chance to receive an organ.2.4Living donor transplantation is the best alternative in case of terminal chronic renal failure . In fact3Complications after a transplant can be related to the surgery itself (infection or abscess) or immunosuppressive therapy that the patient must continue for the life  ,6,7,8. SClostridium difficile (CD) infection represent the most common pathologies. From 1 to 6 months after transplantation, viral and opportunistic infections occur, mainly from CMV; while after 6 months, 80% of patients are susceptible to infections for pathogens acquired in the community [In particular, gastrointestinal complications can occur in many kidney transplant recipients. Such complications may be secondary to pathogenic microorganisms but may also be induced by mechanical or metabolic causes or by immunosuppressive drugs. Although this type of complication can compromise the quality of life of the transplant or be responsible for mortality, it can generally be prevented or treated without interfering with immunosuppression. Gastrointestinal complications are among the major causes of morbidity and mortality in immunosuppressed subjects ,14,15 T. The digommunity .4Candida [Cryptococcus neoformans and Pneumocystis carinii can also be observed. Predisposing factors for infection are neoplasms, especially lymphomas and leukemia, organ transplants, prolonged therapy with antibiotics or corticosteroids, malnutrition, diabetes, and immunosuppressive therapy. Clinically esophageal candidiasis is diagnosed because of dysphagia, as the lesion of the mucosa is little or not ulcerated and the other symptoms, above all the painful ones  are rare. Nausea and hiccups or even asymptomatic forms are also observed [Candida albicans is the most common species, infections are also caused by C. krusei, C. tropicalis, C. parapsilosis, Torulopsis glabrata, etc.  plays an important role in the pathogenesis of antral gastritis and peptic ulceration in the general population. H. pylori infection can be diagnosed by invasive methods, requiring endoscopy and biopsy sampling  and non-invasive techniques such as urea breath test (breath test), the search for bacterium antigens on fecal samples or the search for specific antibodies in the blood and urine [H. pylori  but not of infection in progress and therefore are defined indirect tests. The prevalence of H. pylori is reported 70% in hemodialysed subjects and 60% in those undergoing kidney transplantation. Gastritis was found in 65% of kidney transplant patients and only in 19% of hemodialysis patients, suggesting that other factors contribute to the onset of gastric lesions [H. pylori was detected in 48% of cases of antrum gastritis; no association was observed between H. pylori infection and plasma levels of cyclosporine or corticosteroids [CMV infection is the most frequent, but other viruses such as HSV and Epstein–Barr virus can be due to serious esophagogastric complications  Table 1Table 1. nd urine ,45,46,47 lesions . Teenan  lesions  performesteroids .6CMV infections are mostly esophagitis. Unlike HSV, CMV can cause systemic symptoms such as fever and weight loss. Being an immunomodulatory virus, other pathogens such as Aspergillus may cause disease  Table 1Table 1. CMV is usually localized in the colon, both segmentally and widespread. Ileal lesions that determine a very serious necrotic enterocolitis have also been described. Diarrhea is associated with abdominal pain, while systemic symptoms such as fever are rare. Gastrointestinal hemorrhages, perforations and toxic megacolon are possible in patients with preexisting gastroenterological diseases. The virus can proliferate in vascular endothelial cells causing vasculitis, thrombotic phenomena and local ulcerations. When the damage is very extensive, an ischemic colitis may occur, which may be an early complication in the first 4 months after kidney transplantation . The mos7Diarrhea is one of the most frequent post-transplant complications and may result in discontinuity of immunosuppressive therapy. Usually supported by bacterial, viral and parasitic causes, the onset can also be determined by drugs used in the post-transplantation period. Caliciviruses can cause a prolonged diarrhea that resolves by reducing the dosage of immunosuppressive drugs. HSV is a rare cause of colitis in transplant recipients . ColonosThe incidence of diarrheal episodes is 12.6%, with 41.5% of cases related to infectious episodes and 34% correlated to drugs . The aveThe CD is responsible for about 50% of diarrheal episodes associated with antibiotic treatment . The modSalmonella infection, which has a clinical syndrome characterized by febrile diarrhea, with or without polymorphonuclear leukocytes in the feces. Bacteremia is common in patients transplanted with salmonella gastroenteritis: approximately 20–30% compared to 3–4% of non-transplant recipients [Campylobacter jejuni is the most commonly reported bacterial cause of foodborne infection which causes gastroenteritis and diarrhea. The epidemiology is similar to that of Salmonella and the clinical syndrome is characterized by febrile diarrhea with nausea and vomiting, and about 70–85% of patients present leukocytes and blood in the stool. CMV causes a febrile syndrome with diarrhea, which can be associated with bleeding, possible perforation, ischemic colitis and/or toxic megacolon [Another infectious cause of post-transplant diarrhea is cipients . Campyloegacolon ,60. In aegacolon . In addiegacolon ,62,63.8Colorectal complications after renal transplantation can occur both early and after transplantation and are a direct consequence of the biological modifications produced by immunosuppressive therapy  Table 1Table 1. 9p < 0.00003), duration of colitis for more than 10 years (p < 0.002) and pancolitis (p < 0.0004). In these settings, a follow-up with a colonoscopy is recommended [Undergoing an organ transplant can save lives, but it can also increase the risk of cancer ,76,77,78ommended .10As stated previously, complications after a transplant can be immunological and non-immunological . The mos11A concept that is emerging strongly in the field of clinical nutrition is the possibility of improving the course of a disease in different and serious conditions, thanks to the modulation of the diet. The state of nutrition can influence the trend, the prevalence of complications and the prognosis of many diseases and is variously compromised during illnesses. Dialysis patients are subject to profound metabolic and nutritional changes that modify the energy balance in a chronic and persistent form. Following the diet is essential for patients, regardless of the method adopted: the food plan makes the dialysis treatment more effective and improves the state of nutrition of the subject. Since the uremic condition is not perfectly correct by the dialysis methods, malnutrition in dialysis is present from 18% to 75% depending on the method used for the assessment of the state of nutrition and is one of the factors responsible for high mortality. On the other hand, also from this point of view, kidney transplantation represents the best substitution therapy for patients with chronic renal failure in terms of survival, quality of life and sensation of subjective well-being. Furthermore, transplantation represents the possibility of liberalizing the diet after the limitations imposed by conservative therapy and dialysis. However, most of the patients who have undergone renal transplantation tend to be overweight because the use of immunosuppressive and corticosteroids, generating among other side effects the increase in appetite, fat mass and retention of sodium and water. This increase will lead to higher calorie needs than the actual energy needs.The outcome of kidney transplantation can be influenced by the patient’s nutritional status. Malnutrition, obesity and other metabolic complications can be prevented or corrected by appropriate food interventions. Weight control therefore plays a fundamental role in therapy and lifestyle. Furthermore, as described above, gastrointestinal complications can occur in many subjects undergoing transplantation. The first tool to be used is proper nutrition, supported by any nutritional approaches, to reduce the symptoms of gastroesophageal pathologies . The die12de novo tumor. Prolonged exposure to immunosuppressive drugs, in fact, seems to negatively influence the ability of antiviral and antitumor immunosurveillance and to enhance the carcinogenic effect of some risk factors, such as ultraviolet rays and some drugs, that seems to promote carcinogenesis through mechanisms independent of the immunosuppressive mechanism. These evidences indicate the need to prepare appropriate screening/surveillance models in these patients to prevent or at least anticipate the diagnosis of post-transplant tumors. In this context, even the correct eating habits can represent an optimal secondary prevention strategy in reducing the risks of transplant rejection due to non-immunological reasons and morbidity and mortality from post-transplant complications.Organ transplantation represents one of the most important clinical achievements of the second millennium due to the positive clinical implications in the treatment of numerous unfavorable and not effectively treatable diseases. In recent years, several therapeutic protocols have been developed and perfected, which more specifically seek to inhibit rejection, trying to safeguard at least in part a residual capacity of the immune system to defend the organism with the reduction in the side effects related to the chronic use of drugs. Currently, the 5-year survival from kidney transplantation is more than 90% in transplant recipients. However, the anti-rejection immunosuppressive drugs necessary for the success of the transplant and for the patient’s survival are directly associated with an increased frequency of infections and tumors associated with viral infections, which are the main causes of morbidity and mortality in people undergoing kidney transplantation; in terms of incidence this risk is quantifiable by about 2- to 3-fold increase in developing any post-transplant


Subjects with a congenital solitary kidney (CSK) are believed to be at risk of hypertension due to their low number of nephrons. However, as CSK is a congenital abnormality of the kidney or urinary tract (CAKUT), subtle dysplastic changes contributing to hypertension cannot be excluded.We retrospectively compared office blood pressure (OBP) and ambulatory blood pressure monitoring (ABPM) between two groups of children with CAKUT, aged 6–18 years: Group A with a CSK and Group B with two kidneys. All had normal renal parenchyma on scintigraphy and normal renal function. OBP and mean systolic and diastolic 24-h, daytime and nighttime ambulatory BP records were analyzed. The distribution of OBP and APBM as continuous values and the prevalence of hypertension (ambulatory/severe ambulatory or masked hypertension) in the two groups were compared.p = 0.019), mainly because of the greater occurrence of masked hypertension.There were 81 patients in Group A and 45 in Group B. Median OBP standard deviation scores were normal in both groups, without significant differences. Median ABPM standard deviation scores, although normal, were significantly higher in Group A and the prevalence of hypertension was higher (ambulatory/severe ambulatory or masked)  contains supplementary material, which is available to authorized users. Subjects with a congenital solitary kidney (CSK) are believed to be at risk of hypertension, due to their low number of nephrons. During the seventies, studies on animals with extensive renal ablation demonstrated glomerulosclerosis with progressive azotemia, proteinuria, and hypertension . Since tHowever, as CSK is a congenital abnormality of the kidney or urinary tract (CAKUT), subtle dysplastic changes undetected by imaging or standard laboratory assessment may also be present. Thus, hypertension may be secondary to either a low number of nephrons or to subtle dysplastic changes.In order to ascertain whether CSK per se represents a risk factor for higher BP, we compared the BP values of children with CSK with those of children with CAKUT and two kidneys, as they both have, in principle, a similar probability of subtle dysplastic changes.99m dimercaptosuccinic acid or mercaptoacetyltriglycine scintigraphy , normal renal function as assessed by standard laboratory testing at the time of ABPM , and absence of heart or systemic diseases. Twenty-six patients (24%) were excluded from Group A, mainly because of insufficient valid readings at ABPM. From Group B, 114 patients (72%) were excluded due to abnormal scintigraphy or, less frequently, abnormal renal function; some of them also had insufficient readings at ABPM. Ultimately, 126 patients were eligible, 81 in Group A and 45 in Group B , and 159 had different types of CAKUT (Group B). From this population, eligible patients were selected according to the following inclusion criteria: OBP values available at the time of ABPM, a minimum of 80% of valid recordings at ABPM, normal kidney/kidneys morphology at ultrasound and TcMeasurements of OBP were performed by means of the auscultatory method, using an aneroid sphygmomanometer on the non-dominant arm; the 5th Korotkoff sound was recorded for diastolic blood pressure (DBP). Readings were taken three times after at least five minutes rest and the mean of the three measurements was recorded.Values were transformed into Standard Deviation Scores (SDSs) and percentile category for sex and height, according to published normal values .Ambulatory blood pressure monitoring was performed using an oscillometric device , approved by the Association for the advancement of medical instrumentation and the British Hypertension Society , 14, andTwenty-four-hour, daytime and nighttime systolic BP (SBP) and DBP, mean arterial pressure (MAP) data, expressed as mean levels, were converted into SDSs and percentile category for height and sex, using the modified LMS method proposed by Cole and Green , which dNocturnal dipping was expressed as a percentage of day/night difference ([mean awake BP-mean sleep BP]/mean awake BP × 100) for both SBP and DBP. Reduced dipping was defined as a drop ≤ 10% in nocturnal vs. daytime BP values .BP load, which was only available in 79/126 patients, was expressed as the percentage of systolic or diastolic readings above the 95th percentile during the entire 24-h period, and was defined abnormal if ≥ 25% .The distribution of individual values of OBP and APBM was analyzed in the two groups.Normal BP White coat hypertension/Pre-hypertension Masked hypertension Ambulatory hypertension/Severe ambulatory hypertension .Moreover, by comparing mean office SBP and DBP with mean 24-h, daytime and nighttime ABPM data expressed as percentiles , we classified BP into the following four categories:Our categorization differs from that of the American Heart Association (AHA), which includes load, as data on load were only available in a subset of our patients. The main difference is that we combined white coat hypertension and pre-hypertension, which in the AHA scheme are separated according to load values . StagingHypertension as a binary variable was defined as the presence of ambulatory hypertension/severe ambulatory hypertension or masked hypertension.We considered the following outcomes in the two groups: differences in the continuous distribution of OBP and APBM values; differences in the prevalence of the above mentioned four BP classes, differences in the prevalence of hypertension, differences in the prevalence of reduced nocturnal dipping, and abnormal load.The following data, collected at the time of ABPM, were retrieved: demographic and medical history ; clinical data ; laboratory values ; imaging .We analyzed whether the following risk factors were associated with the primary outcome in the CSK group: age, sex, gestational age, prematurity , birth weight, low birth weight (< 2500 g), obesity (body mass index ≥ 95th percentile for age and sex), vesico-ureteric reflux, renal hypertrophy  , eGFR vaStatistical analysis was performed using the open source software R . The ChiNon-parametric tests  were used to analyze the difference in the distribution of a continuous variable in two or more different groups. ABPM values were transformed into SDS scores for height and sex according to published references for the general population, using the procedure described in detail in the section “Blood pressure measurements and evaluation”.A correction for multiple comparisons was applied, where appropriate, according to Holm’s method.p = 0.002) and rate of vesico-ureteric reflux  were significantly different between the two groups, while no significant differences were observed in the other parameters.Of the 126 children included in the study, 81 with CSK  were assigned to Group A; Group B consisted of 45 children with other types of CAKUT . The demographic and clinical data of the two groups are shown in Table Median office SBP and DBP SDS were normal in both groups, and no significant differences between them were observed Table ; the samMedian ABPM SDSs were normal in both cohorts, but significantly higher in Group A for most parameters, even after Holm’s correction Table . FiguresMedian systolic dipping was abnormal in both cohorts, without significant differences between the two groups. Systolic and diastolic load were calculated in 61/81 subjects in Group A and 18/45 in Group B. Median systolic and diastolic load was normal in both groups, but significantly higher in Group A, and the difference was extremely significant for diastolic values, even after Holm’s correction Table .p = 0.027) and nighttime SBP (p = 0.035). However, these differences were not significant after Holm’s correction , with a lower prevalence of normal BP (58.0% vs. 82.2%) and a higher prevalence of the other three classes in Group A; in particular, masked hypertension was much higher in Group A (25.9% vs. 8.9%) (Table p = 0.019). The subset of 79 patients for whom load values were available was divided into the 6 classes recommended by the AHA hypertension guidelines: the trend in the distribution of BP was very similar, especially for the prevalence of ambulatory and masked hypertension , while the prevalence of reduced diastolic dipping was lower .No statistically significant differences in the percentage of patients with reduced dipping were observed between Group A and Group B: in both groups, we observed a similar high prevalence of reduced systolic dipping , while for an abnormal diastolic load it was 18/61 (29.5%) in Group A and 3/18 (16.7%) in Group B (p = 0.278).In the subgroup of 79 patients for whom load values were available, the prevalence of an abnormal systolic load was 47/61 (44.3%) in Group A and 4/18 (22.2%) in Group B  in our cohort. Interestingly, vesico-ureteric reflux was four times more frequent in our cohort in children with CSK showing normal BP than in those with hypertension (24.0% vs. 5.9%), even if the difference was not statistically significant; moreover, although we found no association between the presence of renal hypertrophy and BP, it should be remembered that all kidneys were normal at scintigraphy.None of the risk factors analyzed in our children with CSK were associated with hypertension. In particular, the frequency of hyperfiltration, one of the main mechanisms associated with hypertension and damage progression in animal models with CSK, was comparable in normotensive and hypertensive subjects with CSK . They also observed an inverse correlation between kidney length and ABPM MAP and loads .Westland et al. compared results obtained with office BP and with ABPM in 28 children with CSK, and also found systolic, diastolic, and MAP SDSs within normal limits; however, children with CSK had higher mean ABPM SDSs than patients with acquired solitary kidney, except for nocturnal parameters. Whereas OBP identified 7% of hypertensive children, ABPM revealed 24-h hypertension in 25%, therefore unmasking 18% of subjects with masked hypertension [. Therefore, avoiding excessive salt intake, which is a common characteristic of Western diets and is implicated in cardiovascular disease, appears to be indicated from childhood in children with CSK, as also highlighted in two recent reviews [In sheep, a species in which nephrogenesis is complete before birth, as in humans, CSK is associated with a reduced capacity to maintain an adequate sodium excretion. It is theorized that impaired sodium excretion together with glomerular hyperfiltration exposes subjects with CSK to the risk of a progressive increase in arterial pressure and loss of renal function with aging . The dys reviews , 25.Our study has some limitations. Because of its retrospective nature, there could be some bias in the selection of our patients: firstly, because they were followed in tertiary centers, secondly, because ABPM was not performed systematically in all patients with CAKUT. However, we believe that this potential bias is in some way controlled by the fact that our analysis only included patients with normal renal parenchyma at scintigraphy and normal renal function at standard laboratory assessment. Another limit is that performing a second ABPM in abnormal cases could mitigate the high proportion of masked hypertension, as demonstrated in other follow-up studies . A thirdData from our study confirm that a CSK can be associated with BP increase from childhood. Therefore, children with CSK, even if morphologically and functionally normal at standard laboratory and imaging assessment, deserve long-term follow-up and periodic BP evaluation, also with ABPM, which has proved to be of value in the screening of hypertension in CSK.ESM 1(DOCX 16 kb).


The aim of our study is to evaluate usability of acid–base balance parameters of in blood taken simultaneously from peripheral artery and the vein. Methods: A total of 49 patients (median age 66 years [interquartile range IQR 45–75]), with CKD stage G4 or G5 were enrolled in this cross-sectional study. All patients were qualified for arteriovenous fistula creation in pre-dialysis period. The samples were taken during surgery, directly after dissection, and evaluated in a point of care testing analyzer. The arteriovenous difference in bicarbonate levels (Δ-HCO3−) was calculated. According to glomerular filtration rate (eGFR) the group was divided into Group A eGFR ≥ 10 mL/min/1.73 m2) and Group B eGFR < 10 mL/min/1.73 m2). Results: In Group A Δ-HCO3− was significantly higher compared to Group B. No such differences were observed in the case of V-HCO3−. Δ-HCO3− positively correlated with eGFR. The discriminative power of Δ-HCO3− for predicting eGFR < 10 mL/min/1.73 m2 was 0.72  which provided 67% sensitivity and 75% specificity. The best cut-off was 0.5 mmol/L. Conclusions: The Δ-HCO3− lower than 0.5 mmol/L may be used as predictor of exhaust buffer capacity. The value of this tool should be tested in larger population.Background: Metabolic acidosis in patients with chronic kidney disease (CKD) is a common complication. A bicarbonate concentration in venous blood (V-HCO Metabolic acidosis (MA) is a common disorder in patients with chronic kidney disease (CKD). The major complications of the metabolic acidosis in CKD include increased muscle protein degradation, with muscle wasting , stimulaVenous blood is usually used to assess acid-base disorders in CKD patients ,7. Much Naturally, simultaneous venous and arterial blood collection is technically difficult, may lead to complications, therefore such diagnostics is not a standard approach. However, in the case of patients qualified for fistula creation, it is possible to collect samples, directly after vessels dissection, during the procedure.+) excretion, as a result of intensive renal aminogenesis, in patients with preserved residual renal function, is responsible for maintaining the equilibrium state. Despite a normal serum bicarbonate concentration, positive acid balance is observed and leads to acidification of muscle and the interstitial compartment of the kidneys  and compared using the independent 2, Group B GFR < 10 mL/min/1.73 m2). The level less than 10 mL/min/1.73 m2 (for the Group B) was selected as the threshold in accordance with the KDIGO guidelines, which point that this level is an indication to start renal replacement therapy  were enrolled in this cross-sectional study.Forty-nine patients , with median eGFR 11 mL/min/1.73 m2+), (V-Ca2+) in arterial and venous blood, lover anion gap (A-AG) and adjusting Arterial Anion Gap for the contribution of serum potassium A-AG (K+), in comparison to Group B was found. Arteriovenous diferences in bicarbonate and base excess  were higher in Group A with lower glomerular filtration rate than in group B (2 [IQR11–15] vs. 8 mL/min/1.73 m2 [IQR 7–9.5]). Bicarbonate level below 22 mmol/L was found in 40 (82%) and 41 (84%) out of 49 patients, in blood samples taken from the artery and vein, respectively. There were no significant diferances in bicarbonate level in both gruops. However, median level of A-HCO3− was not statistically significant higher in Group A of patients  and similarlyV-HCO3− was higher in Group A . Based on the U Mann-Whitney’s test, the following differences were found between both subgroups: In group A significantly higher values of calcium (A-Ca group B . As expe3−), Actual Base Excess (ABE) and Standard Base Excess (SBE), Δ-pH, ArterialAnion Gap (A-AG) and adjusting Arterial Anion Gap for the contribution of serum potassium (A-AG (K+)). 3−. It is a positive correlation, indicating that with lower eGFR values, i.e., more advanced kidney disease, the arteriovenous diferances in bicarbonate concentrations decrease. No significant correlation were found between serum urea, creatinine and calculated eGFR with arterial bicarbonate (A-HCO3−) and venous bicarbonate (V-HCO3−).The indicators of kidney function, i.e., serum urea, creatinine and calculated eGFR, significantly correlated with several acide-base balance parameters . The str2 is Δ-HCO3− with area under curve (AUC) 0.716. The cut point was determined at 0.5 mmol/L , decreases according to the progression of chronic kidney disease. This information was used for further consideration whether this parameter may indicate a very advanced uremic kidney disease, in which the possibilities for acidosis compensation are limited or even impossible. For this reason, patients were divided into 2 subgroups, in terms of glomerular filtration rate (eGFR), where the limit was a value of eGFR < 10 mL/min/1.73 m2. This cut-off point is recommended by KDIGO for initiating renal replacement therapy (RRT) [3−, A-AG , A-AG (K+), adjusting Arterial Anion Gap for the contribution of serum potassium, Δ-pH (arteriovenous pH differences), Δ-ABE , Δ-SBE (arteriovenous differences in Standard Base Excess) we have chosen Δ-HCO3− as the best discriminator for eGFR < 10 mL/min/1.73 m2. Δ-HCO3− of 0.5 mmol/L was proposed as the cut-off point in regard of the highest diagnostic value. In other words, an Δ-HCO3− of less than 0.5 mmol/L is indicative for significant advancement of renal failure, the need for initiation of RRT and significant limitation for acidosis compensation by the body buffers. Other parameters, mentioned above and shown in In the present study, we found that the difference in bicarbonate concentration, between the artery and the vein (Δ-HCOpy (RRT) . Among t2, there was a positive correlation between eGFR and serum bicarbonate concentration, and this relationship was significantly stronger at lower eGFR than at higher eGFR values [In general, the prevalence of metabolic acidosis among CKD patients is higher with more advanced kidney disease. Data from the NHANES III study, including 15.594 subjects, aged 20 years and older, indicate that the prevalence of overt MA, defined as a reduction of bicarbonate in venous blood serum below 22 mmol/L, was observed in 1.3%, 2.3% and 19.1% in CKD stage G3, G4 and G5, respectively . In the R values . CorrespR values .+), Δ-ABE, Δ-SBE, Δ-pH, Δ-HCO3−, Δ-ABE, Δ-SBE—see description of abbreviation in Despite we did not find a significant difference in bicarbonate concentration between Group A and B, probably due to small study group (N = 49), we have identified important markers of acid-base imbalance. Among them, following parameters, significantly correlated with the current kidney function  seems to be independent of all these variables.This pathophysiological complexity of bicarbonate buffer and the fact, that in many patients, even in advanced CKD, the concentration of bicarbonate acidosis is normal, is probably the reason that it is so difficult to reach a positive correlation between eGFR and bicarbonate in small research. To achieve this effect, a much larger group of patients should be recruited for the study than in the current one. However, the authors’ intention was to compare several predictors of parameters that can be used for this purpose and arteriovenous bicarbonate gradient , which may facilitate the decision for beginning of bicarbonate supplementation. We think that further treatment control will be rather based on venous Δ-HCO3−, taking into account changes in venous Δ-HCO3− concentration during therapy and extrapolation with baseline values evaluated during surgery. This, however, will require further research.Our innovative method of assessing acid-base disorders should provide new light on the tissue mechanism of acidosis regulation in chronic kidney disease. We hope that in the future, simultaneous and direct blood sampling in point-of-care testing (POCT) device will precisely diagnose the patient requiring acidosis correction. Naturally, regular puncture of the artery is difficult to perform in CKD patients and is unlikely to be of routine clinical use. On the other hand, we propose a one-time test of both arterial and venous blood bicarbonate  indicators of acidosis should be included in the decision making, regarding acidosis correction. 3−) is the best discriminating factor of advanced kidney disease that identifies exhausting buffer capacity and is suggestive for exhausting buffer capacity. Introduction into clinical practice may change classical thinking and the clinical practice, i.e., guiding the correction of acidosis in a patient with CKD patients in stage G4 and G5. At present, however, the significance of this parameter in clinical practice requires further research, including a prospective evaluation on a larger number of patients with hard endpoints.Arteriovenous bicarbonate gradient (Δ-HCO


The TASH score had the highest overall accuracy as reflected by an AUC of 0.782 followed by the mTICCS (0.776). The ETS was the most sensitive (80%), whereas the TASH score had the highest specificity (82%) and the PWH score had the lowest (51.83%). At a cut-off > 5 points, the mTICCS score showed a sensitivity of 77.5% and a specificity of 74.03%. Compared to sophisticated systems, using a higher number of weighted variables, the newly developed mTICCS presents a useful tool to predict the need for an MT in a prehospital situation. This might accelerate the diagnosis of an MT in emergency situations. However, prospective validations are needed to improve the development process and use of scoring systems in the future.The modified Trauma-Induced Coagulopathy Clinical Score (mTICCS) presents a new scoring system for the early detection of the need for a massive transfusion (MT). While validated in a large trauma cohort, the comparison of mTICCS to established scoring systems is missing. This study therefore validated the ability of six scoring systems to stratify patients at risk for an MT at an early stage after trauma. A dataset of severely injured patients (ISS ≥ 16) derived from the database of a level I trauma center (2010–2015) was used. Scoring systems assessed were Trauma-Associated Severe Hemorrhage (TASH) score, Prince of Wales Hospital (PWH) score, Larson score, Assessment of Blood Consumption (ABC) score, Emergency Transfusion Score (ETS), and mTICCS. Demographics, diagnostic data, mechanism of injury, injury pattern (graded by AIS), and outcome  were analyzed. Scores were calculated, and the area under the receiver operating characteristic curves (AUCs) were evaluated. From the AUCs, the cut-off point with the best relationship of sensitivity-to-specificity was used to recalculate sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV). A total of 479 patients were included; of those, blunt trauma occurred in 92.3% of patients. The mean age of patients was 49 ± 22 years with a mean ISS of 25 ± 29. The overall MT rate was 8.4% ( Traumatic hemorrhage still represents a challenging problem in injured patients ,2. In thSeverely injured patients (ISS ≥ 16) that were consecutively admitted to our trauma center (Level 1) between 2010 and 2015 were included in this study. Demographic data, as well as laboratory parameters (hemoglobin (Hb), lactate (Lac), partial thromboplastin time (PTT), International Normalized Ratio (INR)), and imaging data (focused assessment with sonography for trauma (FAST), X-ray, and CT), were collected. Furthermore, the mechanism of injury, injury pattern (graded by AIS), and outcome  were recorded. Due to the retrospective nature of this study, ethical approval was not required.Only scores including parameters that could be reproduced by the data captured in the hospital information system were considered. An MT was defined as the administration of 10 or more units of packed red blood cells (pRBC) in the first 24 h after arrival at the emergency room (ER). Scores were raised by two investigators . In case of discrepancies, results were discussed until consensus was achieved. To identify the risk for needing an MT, the TASH score uses seven independent, weighted variables: systolic blood pressure, sex, hemoglobin, focused assessment for the sonography of trauma (FAST), heart rate, base excess (BE), and extremity or pelvic fractures. Using a logistic function, the TASH score is transformed into the probability of an MT. Consequently, a score ≥ 16 points indicates a > 50% probability of an MT. Furthermore, a score ≥ 27 points is associated with a 100% predicted and obtained risk for an MT ,13.The ABC score uses parameters: penetrating trauma mechanism, systolic blood pressure ≤ 90 mmHg on ER arrival, heart rate ≥ 120 bpm on ER arrival, and positive FAST examination, which are available during the first few minutes after hospital admission of a trauma patient, to assess the risk for an MT .The Larson score is based on the “Joint Theater Trauma Registry” transfusion database, which includes data of US service personnel injured in combat scenarios during overseas deployment. The Larson score includes heart rate, systolic blood pressure, hemoglobin, and base deficit to identify the probability of an MT .The PWH score is based on data from 1891 civilian trauma patients admitted to The Prince of Wales Hospital in Hong Kong. Statistical analyses identified seven parameters: heart rate ≥ 120 bpm, systolic blood pressure ≤ 90 mmHg, Glasgow coma scale ≤ 8, displaced pelvic fracture, computer tomography (CT) scan or FAST-positive for fluid, base deficit > 5 mmol/L, hemoglobin ≤ 7 g/dL, and hemoglobin 7.1–10.0 g/dL, to predict the need for an MT . Based on data from 1103 patients, nine parameters, with different predictive values indicating the need for a blood transfusion, were chosen for the ET score, including systolic blood pressure (SBP) < 90 mmHg or SBP 90–120 mmHg, free fluid on the abdominal ultrasound, clinically unstable pelvic ring fracture, aged 20–60 years or > 60 years, admission from scene of accident, traffic accident, and fall from > 3 m. Score values range from 1 (0.7% probability of an MT) to 9.5 (97% probability of an MT) points .The mTICCS is a modified version of the TICCS . There ap-values. Demographic data as well as injury mechanisms and pattern were described in tables by median and range or frequency and percentage. Comparisons between MT and no MT groups were performed by Wilcoxon rank-sum-test for continuous data or Chi-square-test. Results are presented as mTICCS was compared to TASH, ABC, Larson, PWH, and ETS scores to evaluate its diagnostic accuracy. The different scores were evaluated with the need for an MT within the first 24 h after admission. The area under the receiver operating characteristic curve (AUC) was calculated for each score. The Youden Index was used to determine the cut-off point at which sensitivity and specificity were of equal diagnostic importance. The Youden Index specifies the optimal cut-off point by maximizing the difference between true positive and false positive ratings over all possible cut-off points. Prevalence, sensitivity, specificity, positive predicted values (PPV), and negative predicted values (NPV) with corresponding 95% confidence limits (95% CI) were used for the comparison of scores.p-values. For all comparisons, the significance level was set to 5%, and due to the explorative nature of this study no adjustment was made to the significance level for multiple testing. All analyses were performed by SPSS 25.0  and MedCalc® version 18.9.1 .The AUC of the mTICCS was compared to the AUCs of TASH, ABC, Larson, PWH, and ETS scores to assess and compare the overall diagnostic accuracy. Results were reported as the AUC value with the corresponding 95% confidence limits and n = 40).In total, 479 patients were included in this study. Demographic data, injury mechanisms, as well as mortality rates are displayed in p = 0.0103). However, no significant difference was identified between the AUC of mTICCS and the AUCs of the other scores  and 0.782 (TASH) . mTICCS r scores . Sensitivity was highest for ETS, followed by mTICCS, PWH, TASH, ABC, and Larson, respectively. However, specificity was highest for TASH, followed by Larson, ABC, mTICCS, ETC, and PWH . TASH alConsidering mTICCS as screening tool, 145 were identified at risk of MT (145 test positives among 479 screend patients), and among these 145 patients, 31 went on to need MT (PPV of 21%). In addition, of the 40 patients needing MT in our sample, 31 were correctly identified by mTICCS (sensitivity of 77.50%) while 9 patients were missed . On the other hand, of the 439 patients who do not need MT, 325 were correctly identified (specificity of 74.03%) while 114 were missed .Although early management of acute coagulopathy in trauma victims improves the outcome, timely identification and prediction of a trauma-induced hemorrhage and the associated need for an MT remains challenging ,19. TherIn general, one could assume that more complex scores are superior for prediction of an MT when compared to more compact systems. Accordingly, the TASH score , which iIn addition to ethnicity, other aspects of the study population’s composition need to be considered when comparing the predictive value of different scores. In this context, Brockamp et al. included patients with an ISS > 9 who survived until ICU admission ,15,17. OThe original version of TICCS focused on easy and early application and could be determined before hospital admission ,23. Due The original TICCS was adjusted to the modified version (mTICCS) in regard to the special characteristics of severely injured patients and the need to simplify predictions scores . With thFor the present analysis, a single dataset from a Level 1 trauma center was used, including a significant number of severely injured patients. All containing variables for the scoring systems and algorithms could be assessed. Furthermore, detailed data on transfusion practices and the use of blood products were available. However, data presented in the current study were collected from a retrospective database with information collected after hospital admission. Thus, information about prehospital applications of hemostatic agents with a potential influence on the amount of administered pRBCs was not available and might have caused some bias to the results. Furthermore, the score should be used by paramedics, nursing staff in the emergency room, as well as emergency physicians. Due to the retrospective nature of the study, an interrater liability might occur. Taking these shortcomings into account, prospective validation of the presented scores is urgently needed.Based on its three assessment criteria, including the assessment of general severity, blood pressure, and extent of bodily injury, the mTICCS showed no significant difference in AUC when compared to the AUCs of other established and more sophisticated scores. Yet, due to mTICCS simple applicability, diagnosis can be made very early after hospital admission or even in the prehospital setting. Thus, mTICCS might provide a new useful diagnostic tool to detect patients with ongoing bleeding in need of an MT. Consequently, the time until therapy is initiated can be reduced. Prospective, follow-up studies are needed to determine the effect of this efficiency on outcome parameters.