Target Organ Protection Research Articles

Assessment of neutrophil/lymphocyte ratio and mean platelet volume values in patients with diabetes mellitus diagnosis: A case-control study.

Diabetes mellitus, fundamentally characterized by hyperglycemia, leads to significant metabolic disturbances. Type 2 diabetes mellitus is a chronic, inflammatory, preventable metabolic disease that is a significant health issue globally. The neutrophil-to-lymphocyte ratio (NLR) is an essential marker of systemic inflammation. We aimed to reveal the relationship between long-term glucose control and NLR, mean platelet volume (MPV), and red blood cell width in patients with type 2 diabetes. This was a retrospective case-control study. A total of 3532 applications in 2 years time were identified. Age, gender, medical history, white blood cell (WBC), hemoglobin, mean corpuscular volume (MCV), MPV, red blood cell width, NLR, hematocrit, platelet, C-reactive protein, Haemoglobin A1C data of the patients were analyzed. 1790 patients were included. A significant positive correlation was found between HbA1c and age, white blood cell, hematocrit, MCV, red blood cell width, NLR, and CRP. A statistically significant negative correlation was found between HbA1c and MCV. The results showed statistically significant differences between NLR, MPV, WBC, MCV, age, and HbA1c levels. Increased HbA1c levels are usually associated with an increase in these parameters. This is important for determining the risk of complications and protecting target organs in diabetic patients. A significant decrease in MCV levels was found as HbA1c levels increased. This suggests that evaluating red blood cells in routine controls of diabetic patients may indicate glycemic control. These findings may be valuable in early diagnosis of complications.

A Real-World Study on the Short-Term Efficacy of Amlodipine in Treating Hypertension Among Inpatients.

Hospitalized hypertensive patients rely on blood pressure medication, yet there is limited research on the sole use of amlodipine, despite its proven efficacy in protecting target organs and reducing mortality. This study aims to identify key indicators influencing the efficacy of amlodipine, thereby enhancing treatment outcomes. In this multicenter retrospective study, 870 hospitalized patients with primary hypertension exclusively received amlodipine for the first 5 days after admission, and their medical records contained comprehensive blood pressure records. They were categorized into success (n=479) and failure (n=391) groups based on average blood pressure control efficacy. Predictive models were constructed using six machine learning algorithms. Evaluation metrics encompassed the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). SHapley Additive exPlanations (SHAP) analysis assessed feature contributions to efficacy. All six machine learning models demonstrated superior predictive performance. Following variable reduction, the model predicting amlodipine efficacy was reconstructed using these algorithms, with the light gradient boosting machine (LightGBM) model achieving the highest overall performance (AUC = 0.803). Notably, amlodipine showed enhanced efficacy in patients with low platelet distribution width (PDW) values, as well as high hematocrit (HCT) and thrombin time (TT) values. This study utilized machine learning to predict amlodipine's effectiveness in hypertension treatment, pinpointing key factors: HCT, PDW, and TT levels. Lower PDW, along with higher HCT and TT, correlated with enhanced treatment outcomes. This facilitates personalized treatment, particularly for hospitalized hypertensive patients undergoing amlodipine monotherapy.

Efficacy of antihypertensive treatment for target organ protection in patients with masked hypertension (ANTI-MASK): a multicentre, double-blind, placebo-controlled trial

Masked hypertension is associated with target organ damage (TOD) and adverse health outcomes, but whether antihypertensive treatment improves TOD in patients with masked hypertension is unproven. In this multicentre, randomised, double-blind, placebo-controlled trial at 15 Chinese hospitals, untreated outpatients aged 30-70 years with an office blood pressure (BP) of <140/<90mm Hg and 24-h, daytime or nighttime ambulatory BP of ≥130/≥80, ≥135/≥85, or ≥120/≥70mm Hg were enrolled. Patients had ≥1 sign of TOD: electrocardiographic left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (baPWV) ≥1400cm/s, or urinary albumin-to-creatinine ratio (ACR) ≥3.5mg/mmol in women and ≥2.5mg/mmol in men. Exclusion criteria included secondary hypertension, diabetic nephropathy, serum creatinine ≥176.8μmol/L, and cardiovascular disease within 6 months of screening. After stratification for centre, sex and the presence of nighttime hypertension, eligible patients were randomly assigned (1:1) to receive antihypertensive treatment or placebo. Patients and investigators were masked to group assignment. Active treatment consisted of allisartan starting at 80mg/day, to be increased to 160mg/day at month 2, and to be combined with amlodipine 2.5mg/day at month 4, if the ambulatory BP remained uncontrolled. Matching placebos were used likewise in the control group. The primary endpoint was the improvement of TOD, defined as normalisation of baPWV, ACR or LVH or a ≥20% reduction in baPWV or ACR over the 48-week follow-up. The intention-to-treat analysis included all randomised patients, the per-protocol analysis patients who fully adhered to the protocol, and the safety analysis all patients who received at least one dose of the study medication. This study is registered with ClinicalTrials.gov, NCT02893358. Between February 14, 2017, and October 31, 2020, 320 patients (43.1% women; mean age±SD 53.7±9.7 years) were enrolled. Baseline office and 24-h BP averaged 130±6.0/81±5.9mm Hg and 136±8.6/84±6.1mm Hg, and the prevalence of elevated baPWV, ACR and LVH were 97.5%, 12.5%, and 7.8%, respectively. The 24-h BP decreased on average (±SE) by 10.1±0.9/6.4±0.5mm Hg in 153 patients on active treatment and by 1.3±0.9/1.0±0.5mm Hg in 167 patients on placebo. Improvement of TOD occurred in 79 patients randomised to active treatment and in 49 patients on placebo: 51.6% (95% CI 43.7%, 59.5%) versus 29.3% (22.1, 36.5%; p<0.0001). Per-protocol and subgroup analyses were confirmatory. Adverse events were generally mild and occurred in 38 (25.3%) and 43 (26.4%) patients randomised to active treatment and placebo, respectively (p=0.83). Our results suggest that antihypertensive treatment improves TOD in patients with masked hypertension, highlighting the need of treatment. However, the long-term benefit in preventing cardiovascular complications still needs to be established. Salubris China.

#2940 Expression and modulation of SGLT2 in human podocytes. Not all in tubule

Abstract Background and Aims Inhibitors of the sodium-glucose cotransporter type 2 (iSGLT2) modify important non-glycemic pathways that lead to the protection of target organs. Its renoprotective pleiotropic effects in CKD, associated or not with diabetes, justifies further studies to elucidate the mechanisms of action (MoA) of these drugs. Although the co-transporter SGLT2 is mostly expressed in the proximal tubule, its location and function in other cells, that can be potential therapeutic targets for inhibitor drugs, has not been well studied. We explored the presence of SGLT2 in human podocyte cells and whether it is modified in different situations of cellular stress. Method Differentiated immortalized human podocytes were cultured under different experimental conditions for 24 or 48 h: Normoxia (Control); Normoxia + High concentration of glucose (HG); Hypoxia(1%)+2 h Reoxygenation(H) and the combination H + HG. Cells were also incubated with 0.1 uM Dihydrotestosterone (DHT). SGLT2 gene expression was determined by quantitative PCR and SGLT2 protein was detected by Western Blot (WB) and immunofluorescence (IF). Results Sglt2 gene expression was detected in human podocytes in culture, with an increase of expression after 24 h of exposure to HG. Protein expression by WB showed a trend to increase after 48h of exposure to HG and hypoxia, which was significant with co-incubation with DHT. HG plus DHT also increased the protein expression of SGLT2 under normoxic conditions. The IF measured by intensity of area did not show an increase in the protein expression of the transporter under HG incubation. However, protein expression increased under all hypoxic conditions: Control 50.05 ± 3, Hypoxia 140 ± 16.3 (p &amp;lt; 0.05 vs control) and HG + Hypoxia 253 ± 21.29 (p &amp;lt; 0.001 vs control). Conclusion Our data suggest that podocyte may be one of the therapeutic targets on which the iSGLT2 is acting. The experimental conditions described did not show differences in the expression of the transporter before the single stimulus of glucose, but they did under hypoxia and the combination Hypoxia-high glucose. In addition, co-incubation with testosterone seems to enhance the expression. Studying the MoA of iSGLT2 will open better comprehension of the kidney pathophysiology, particularly in the podocytopathies, regardless of diabetes.

Combined vaccines against angiotensin II receptor type 1 and alpha 1D-adrenergic receptor for hypertension.

Compared with monotherapy, combination therapy with multiple antihypertensive drugs has demonstrated superior efficacy in the management of hypertension. The aim of this study was to explore the efficacy of multitarget combined vaccines in achieving simultaneous antihypertensive and target organ protection effects. Our team has developed ATRQβ-001 and ADRQβ-004 vaccines targeting Ang II type 1 receptor (AT1R) and α1D-adrenergic receptor (α1D-AR), respectively. In NG-nitroarginine methyl ester ( l -NAME) + abilities spontaneously hypertensive rats (SHRs) model, SHRs were simultaneously inoculated with ATRQβ-001 and ADRQβ-004 vaccines. Histological and biochemical analyses were performed to evaluate the antihypertensive effects and target organ protection of the ATRQβ-001 and ADRQβ-004 combined vaccines in comparison with those of the single vaccine. Both ATRQβ-001 and ADRQβ-004 vaccines induced robust antibody production, resulting in persistent high antibody titers in rats. Notably, the combined administration of both vaccines significantly decreased SBP in SHRs compared with treatment with a single vaccine, both before and after l -NAME administration. Furthermore, the combined vaccine regimen demonstrated superior efficacy in protecting against vascular remodeling, myocardial hypertrophy and fibrosis, and kidney injury in SHRs. Mechanistically, the combined vaccines exhibited significantly downregulated the expression of angiotensin II type 1 receptor (AT1R) and α1D-adrenergic receptor (α1D-AR). Importantly, no apparent immune-related adverse effects were observed in animals immunized with the combined vaccines. Preliminary findings from this investigation suggest that co-administration of the novel ATRQβ-001 and ADRQβ-004 vaccines holds potential as a groundbreaking therapeutic strategy for managing hypertension.

Are we ready for an adipocentric approach in people living with type 2 diabetes and chronic kidney disease?

We are entering a new era in the management of adiposity-based chronic disease (ABCD) with type 2 diabetes (T2D) and related chronic kidney disease (CKD). ABCD, T2D and CKD can affect almost every major organ system and have a particularly strong impact on the incidence of cardiovascular disease (CVD) and heart failure. ABCD and the associated insulin resistance are at the root of many cardiovascular, renal and metabolic (CKM) disorders, thus an integrated therapeutic framework using weight loss (WL) as a disease-modifying intervention could simplify the therapeutic approach at different stages across the lifespan. The breakthrough of highly effective WL drugs makes achieving a WL of >10% possible, which is required for a potential T2D disease remission as well as for prevention of microvascular disease, CKD, CVD events and overall mortality. The aim of this review is to discuss the link between adiposity and CKM conditions as well as placing weight management at the centre of the holistic CKM syndrome approach with a focus on CKD. We propose the clinical translation of the available evidence into a transformative Dysfunctional Adipose Tissue Approach (DATA) for people living with ABCD, T2D and CKD. This model is based on the interplay of four essential elements (i.e. adipocentric approach and target organ protection, dysfunctional adiposity, glucose homeostasis, and lifestyle intervention and de-prescription) together with a multidisciplinary person-centred care. DATA could facilitate decision-making for all clinicians involved in the management of these individuals, and if we do this in a multidisciplinary way, we are prepared to meet the adipocentric challenge.

Effects of nitric oxide on microviscosity and polarity of erythrocyte membranes in experiment

Enhancement of methods for protecting target organs during coronary artery bypass surgery determined the development of a technology for delivering nitric oxide (NO) to the systemic blood flow using a cardiopulmonary bypass (CB) apparatus, which makes NO available to all organs and tissues.The aim of the study was to access the effect of perioperative NO conditioning on the coefficients of microviscosity and polarity of sheep etythrocyte membranes during experimental surgical intervention using CB.Material and methods. Study was carried out on 20 sheep weighing 30–34 kg. Two groups were formed. In the CB group, 10 sheep underwent the standard clinical protocol of artificial lung ventilation (ALV) and CB. In the CB + NO group, 10 sheep received NO at a dose of 80 ppm through the circuit of ALV apparatus immediately after tracheal intubation. At the start of CB, NO was delivered to the extracorporeal circulation circuit at a dose of 80 ppm for 90 min. After disconnection from CB, NO supply continued through the ALV apparatus at a dose of 80 ppm for 60 min. The coefficients of microviscosity and polarity of sheep erythrocyte membranes were determined by spectrofluorimetry using pyrene probe.Results and discussion. The implementation of CB was accompanied by a statistically significant decrease in the microviscosity coefficient in the zones of proteinlipid contact of sheep erythrocyte membranes. In the zone of total lipids, the microviscosity coefficient did not change after CB implementation. The membrane polarity coefficient at the final stage of the surgery increased significantly in the zone of annular lipids and did not change in the zone of total lipids. NO supply to the circuit of the extracorporeal circulation neutralizes the revealed increase in the microviscosity and polarity of the annular lipids.Conclusions. The introduction of NO into the extracorporeal circulation circuit at the concentration of 80 ppm prevents a decrease in the coefficients of microviscosity and polarity of annular lipids of erythrocyte membranes that occurs during cardiac surgery.

Use of metabolites, metabolithotropic agents and nutritional supplements in sports and sports medicine: a modern view on the problem

Aim. The purpose of this study was to conduct an up-to-date semantic analysis of the results of our own research and literature data on the medical and pharmacological characteristics of metabolites, metabolitotropic agents and nutritional supplements, the peculiarities of their use in sports practice and sports medicine.&#x0D; Materials and methods. This study used bibliosemantic, analytical, logical, and generalization methods. The life sciences and biomedical information bibliographic databases MEDLINE, EMBASE, Medline (PubMed), Web of Science, and Cochrane Central were searched to find publications in English that matched the research keywords. The authors carried out an independent search and selection of articles, assessment of the quality of the data, compliance of the presentation and interpretation with the main idea of the study, with the formation of the final list of references.&#x0D; Results. Based on the analysis of modern literature data and the results of our own studies, a generalized medical and pharmacological characteristic of metabolite agents, metabolitotropic drugs and nutritional supplements that can influence the main and compensatory mechanisms of macroergic phosphates production under the influence of physical activity is presented. The mechanisms of action, indications for use and main side effects of drugs and food additives based on ATP, malate, succinate, citrate, pyruvate, carnitine, carnosine, etc. are presented.&#x0D; Conclusions. Semantic analysis data indicate that an urgent problem for sports medicine physicians and pharmacologists is the development and use of metabolites, metabolitotropic agents and nutritional supplements, as well as approaches to their rational combination to improve energy metabolism, replenish ATP reserves in the body that will help ensure the intensity muscular activity and simultaneously protect target organs.

Review and prospect of traditional Chinese medicine in treatment of hypertension

Hypertension, a primary cause of cardiovascular and cerebrovascular events, has become a major global public health problem and caused a heavy burden of health economics on the society. In &quot;the 20 Most Important and Most Preventable Health Problems&quot; released by the Chinese Academy of Engineering, hypertension was ranked the second. Due to the disease complexity, many hypertension patients need to take antihypertensive drugs for life. Although significant progress has been achieved in blood pressure lowering by western medicines, the problems including adverse reactions, poor compliance due to long-term medication, and ineffective mitigation in clinical symptoms related to hypertension remain to be addressed. In the last decade, the research on traditional Chinese medicine(TCM) treatment of hypertension has received much attention and achieved remarkable progress. The TCM treatment of hypertension is the most active area of research with integrated Chinese and western medicine in China. In addition to lowering blood pressure smoothly, TCM can alleviate clinical symptoms, reverse risk factors, improve the quality of life, and protect target organs from the damage caused by hypertension. This article systematically reviews the research progress of TCM in treating hypertension in the last decade from the following four aspects: consensus on guideline, clinical trial, experimental study, and systematic review/Meta-analysis. It summarized the evidence of TCM in reducing blood pressure and clarified the mechanism of TCM in reducing blood pressure, aiming to provide a reference for the TCM diagnosis and treatment of hypertension and the development of new drugs.

Changes in Cardiovascular and Renal Biomarkers Associated with SGLT2 Inhibitors Treatment in Patients with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus is a major health problem worldwide with a steadily increasing prevalence reaching epidemic proportions. The major concern is the increased morbidity and mortality due to diabetic complications. Traditional but also nontraditional risk factors have been proposed to explain the pathogenesis of type 2 diabetes mellitus and its complications. Hyperglycemia has been considered an important risk factor, and the strict glycemic control can have a positive impact on microangiopathy but not macroangiopathy and its related morbidity and mortality. Thus, the therapeutic algorithm has shifted focus from a glucose-centered approach to a strategy that now emphasizes target-organ protection. Sodium-glucose transporter 2 inhibitors is an extremely important class of antidiabetic medications that, in addition to their glucose lowering effect, also exhibit cardio- and renoprotective effects. Various established and novel biomarkers have been described, reflecting kidney and cardiovascular function. In this review, we investigated the changes in established but also novel biomarkers of kidney, heart and vascular function associated with sodium-glucose transporter 2 inhibitors treatment in patients with type 2 diabetes mellitus.

What are the Best Drugs and Combinations in Afro-Descendant Hypertensive Patients?

Hypertension in African descendants occurs early, with high rates of cardiovascular events compared to Caucasians. In addition, genetic influence, low levels of plasma renin activity, greater sensitivity to salt, low sodium secretion, and other mechanisms are involved and discussed in this article. For pharmacological treatment, several studies were evaluated, such as CREOLE, ALLHAT, CARDIA, JHS, REGARDS, AASK, ACCOMPLISH, review articles and meta-analyzes and some guidelines, such as European, American, Brazilian to compare treatment indication. Several pharmacological classes, such as calcium channel blockers, Β-blockers, renin angiotensin system inhibitors, aldosterone and diuretics were included in present review in order to compare utilization and indication for Afro-descendant hypertensive patients. We concluded that several relevant points should be considered in the pharmacological treatment of African descendants that include pathophysiological characteristics, early development of lesions in target organs, in addition to higher rates of cardiovascular and renal events. In addition to lifestyle changes, improved nutrition, combined treatment, probably as a first-line treatment, should be considered as an approach, and the drugs used should aim at blood pressure control and inhibition of the inflammatory process, which results in worse outcomes. It is important to highlight that the representativeness of the Afro-descendant population was unsatisfactory for a robust conclusion. in this population, we can infer from the initial pharmacological treatment the use of thiazide-like diuretics, or dihydropyridine calcium channel blocker should be considered, although the institution of fixed combinations with angiotensin enzyme conversion inhibitors or angiotensin receptor blockers are important in the protection of target organs that occurs earlier and more seriously.

Effects of remote ischemic postconditioning on hepatic injury in lipopolysaccharide-induced endotoxemic rats.

Remote ischemic postconditioning (RIPoC) is that several cycles of brief, reversible, mechanical blood flow occlusion and reperfusion of distal organ make protection to target organ. We investigate whether RIPoC ameliorates liver injury in lipopolysaccharide (LPS)-induced sepsis model. Protocol 1) Rats were administered LPS solution and samples were collected at 0, 2, 6, 12, and 18 h after that. Protocol 2) After RIPoC at 2, 6, and 12 h (L+2R+18H, L+6R+18H, L+12R+18H), samples were analyzed at 18 h. Protocol 3) RIPoC performed at 2 h, analysis samples at 6, 12, 18 h (L+2R+6H, L+2R+12H, L+2R+18H), and RIPoC at 6 h, analysis at 12 h (L+6R+12H). Protocol 4) Rats were divided control group, which were injected with only ketamine and RIPoC group, which RIPoC was performed at 2, 6, 10, and 14 h, samples were analyzed at 18 h. In protocol 1, liver enzymes, MDA, TNF-α and NF-kB increased, and SOD decreased over time. In protocol 2, liver enzyme and MDA level were lower and SOD level was higher in L+12R+18H and L+6R+18H groups, compared with L+2R+18H group. In protocol 3, liver enzyme and MDA level were lower and SOD level was higher in L+2R+6H and L+6R+12H groups, compared with L+2R+12H and L+2R+18H groups. In protocol 4, liver enzyme, MDA, TNF-α, and NF-kB levels were lower and SOD level was higher in RIPoC group, compared with control group. RIPoC attenuated liver injury in LPS-induced sepsis model by modifying inflammatory responses and oxidative stress response for a limited period.

TCM understanding and treatment strategy of hypertension complicated with sexual dysfunction

Hypertension and its target organ damage have become a major public health problem. Sexual dysfunction is a new problem in the treatment of modern hypertension. Modern pathophysiological studies have shown that hypertension can lead to sexual dysfunction. In addition, three major hypotensive drugs represented by diuretics can also lead to sexual dysfunction. In traditional Chinese medicine(TCM), hypertension belongs to &quot;vertigo&quot; &quot;headache&quot; &quot;head wind&quot;, etc. In the past, the understanding of the TCM pathogenesis of hypertension was mainly from the perspectives of &quot;liver wind&quot; and &quot;Yang hyperactivity&quot;. However, based on the in-depth research on ancient and modern literature and medical records and many years of clinical practice, it has been identified that kidney deficiency was the key pathogenesis. Hypertension complicated with sexual dysfunction belongs to the category of kidney deficiency syndrome in TCM, especially the deficiency of kidney Yin. Previous studies by other research groups showed that Yin-enriching and kidney-tonifying method could effectively reduce blood pressure, improve sexual dysfunction, reverse risk factors, and protect target organs. This article systematically discussed the TCM understanding, modern pathophysiological mechanism, and the clinical treatment strategy of kidney-tonifying drugs(single drugs and compounds) in the treatment of hypertension complicated with sexual dysfunction in order to provide a scientific basis for kidney-tonifying method in the treatment of hypertension complicated with sexual dysfunction.

S-46-3: ANTIHYPERTENSIVE TREATMENT IN MASKED HYPERTENSION FOR TARGET ORGAN PROTECTION (ANTI-MASK): A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Objective: Masked hypertension is associated with target organ damage and adverse outcomes. However, up to now there is no interventional evidence that antihypertensive therapy will be beneficial to the patients. Design and methods: The ANTIhypertensive treatment in MASKed hypertension for target organ protection (ANTI-MASK) trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial (NCT02893358). Eligible patients were 30 to 70 years old, had untreated masked hypertension and at least one sign of target organ damage (TOD). Masked hypertension was defined as a normal office blood pressure (BP, &lt; 140/90 mmHg) and an elevated 24-hour (&gt; = 130/80 mmHg), daytime (&gt; = 135/85 mmHg) or nighttime BP (&gt; = 120/70 mmHg) at both screening visits. TOD included electrocardiogram diagnosed left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (ba-PWV) &gt; = 1400 cm/s, or a random urinary albumin-to-creatinine ratio (ACR) &gt; = 2.5 mg/mmol in men and &gt; = 3.5 mg/mmol in women. Randomized patients were treated with alisartan 80 mg per day or placebo. If ambulatory BP was uncontrolled, drug dosage was doubled at the 2-month visit, and amlodipine 2.5 mg or matching placebo was added at the 4-month visit. The primary endpoint was the improvement rate of TOD after 12 months treatment, defined as the reverse (yes to no) of TOD or a significant decrease of ba-PWV or ACR by &gt; = 20% of the baseline level. Results: From Feb 2017 to Oct 2020, 317 patients with masked hypertension (43.2% women, mean age 54 years) were randomized in 13 hospitals in China. Overall, baseline office, 24-h, daytime and nighttime BPs averaged 130/81,137/85, 141/87, and 126/77 mmHg, respectively. At baseline, 98% had an elevated ba-PWV, 12% microalbuminuria, and 8% LVH. 252 patients completed the 12-month treatment and 65 (20.5%) withdrew from the trial. In the intention-to-treat analyses, the improvement rate of TOD was significantly higher in the antihypertensive treatment group than the placebo group (47.4% vs 26.1%, P &lt; 0.0001), as well as the decrease of the 24-h systolic/diastolic BPs (-9.1/-5.7 vs -1.5/-1.0 mmHg, P &lt; 0.0001). Conclusions: Antihypertensive treatment was beneficial for patients with masked hypertension in terms of TOD protection.

NEPHROPROTECTIVE THERAPY IN ACUTE PERITONITIS

Increasing the effectiveness of peritonitis treatment remains an urgent issue for abdominal urgent surgery. So far, several effective surgical technologies have been developed. However, conservative therapy in the early postoperative period is an object for development, including the target organ protection influence.&#x0D; The aim of the study is to determine the nephroprotective efficacy of complex treatment with remaxol in acute peritonitis.&#x0D; Materials and Methods. The authors examined 46 patients with acute peritonitis. The patients were divided into two groups: Groups 1 (comparison, n=26) received standardized treatment, Group 2 (main, n=20) was treated with remaxol. Research methods, in addition to routine ones, included the assessment of kidney functional state, endotoxicosis, and oxidative stress.&#x0D; Results. It is revealed that in acute peritonitis, the authors recorded substantial deviations in the functional state of the kidneys, such as endogenous intoxication, and oxidative stress. Maximum imbalance is diagnosed on the 1st day of the early postoperative period. The use of remaxol in the complex therapy of patients with acute peritonitis significantly improves the functional state of the kidneys, thus, optimizing the course of the early postoperative period and reducing the severity of endogenous intoxication. The positive effect of the drug is caused by its ability to manage the oxidative stress, a universal pathogenetic trigger for system and organ damage, including kidneys.&#x0D; Conclusions. Remaxol has a nephroprotective effect and improves the course of the early postoperative period.

Application of metabolomics in the diagnosis of non-alcoholic fatty liver disease and the treatment of traditional Chinese medicine.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease around the world, and it often coexists with insulin resistance-related diseases including obesity, diabetes, hyperlipidemia, and hypertension, which seriously threatens human health. Better prevention and treatment strategies are required to improve the impact of NAFLD. Although needle biopsy is an effective tool for diagnosing NAFLD, this method is invasive and difficult to perform. Therefore, it is very important to develop more efficient approaches for the early diagnosis of NAFLD. Traditional Chinese medicine (TCM) can play a certain role in improving symptoms and protecting target organs, and its mechanism of action needs to be further studied. Metabolomics, the study of all metabolites that is thought to be most closely associated with the patients’ characters, can provide useful clinically biomarkers that can be applied to NAFLD and may open up new methods for diagnosis. Metabolomics technology is consistent with the overall concept of TCM, and it can also be used as a potential mechanism to explain the effects of TCM by measuring biomarkers by metabolomics. Based on PubMed/MEDLINE and other databases, this paper retrieved relevant literature NAFLD and TCM intervention in NAFLD using metabolomics technology in the past 5 years were searched, and the specific metabolites associated with the development of NAFLD and the potential mechanism of Chinese medicine on improving symptoms were summarized.

Expert consensus on personalized initiation of glucose-lowering therapy in adults with newly diagnosed type 2 diabetes without clinical cardiovascular disease or chronic kidney disease.

Since it is difficult for clinicians to make a decision among the various types of antidiabetic medications due to their great discrepancy in mechanisms, pharmacological properties, and cardiovascular/renal protection, a relatively "precision" or personalized hypoglycemic treatment suggestion is practical for type 2 diabetes (T2D) management in adults. This expert consensus makes some recommendations based on the characteristics of adult T2D patients without clinical cardiovascular disease (CVD) or chronic kidney disease (CKD) by evidence from large-scale clinical trials. The main consideration for initiating antidiabetic medications is the safety and benefits for prevention of target organ damage, such as CVD and CKD. The choice of personalized glucose-lowering therapy regarding target organ protection is based on the various effects of antidiabetic medications, patients' clinical characteristics and their key risks, as well as the sociological factors. According to the effects on glucose reduction, cardiovascular protection, renal benefit, body weight change, hypoglycemic risk, and liver function impact, the antidiabetic medications are recategorized in this consensus. Combined with the glucose control target and the different effects of hypoglycemic agents, a significant body of recommendations have been developed for optimal T2D management according to the risk factors for atherosclerotic CVD, heart failure, CKD, primary fatty liver, and hypoglycemia. This consensus gives detailed guidance on personalized antidiabetic therapy initiation in newly diagnosed T2D adults, which attaches great importance to both glucose control and target organ protection.

ANTIHYPERTENSIVE TREATMENT IN MASKED HYPERTENSION FOR TARGET ORGAN PROTECTION (ANTI-MASK): A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Objective: Masked hypertension is associated with target organ damage and adverse outcomes. However, up to now there is no interventional evidence that antihypertensive therapy will be beneficial to the patients. Design and method: The ANTIhypertensive treatment in MASKed hypertension for target organ protection (ANTI-MASK) trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial (NCT02893358). Eligible patients were 30 to 70 years old, had untreated masked hypertension and at least one sign of target organ damage (TOD). Masked hypertension was defined as a normal office blood pressure (BP, &lt; 140/90 mmHg) and an elevated 24-hour (&gt; = 130/80 mmHg), daytime (&gt; = 135/85 mmHg) or nighttime BP (&gt; = 120/70 mmHg) at both screening visits. TOD included electrocardiogram diagnosed left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (ba-PWV) &gt; = 1400 cm/s, or a random urinary albumin-to-creatinine ratio (ACR) &gt; = 2.5 mg/mmol in men and &gt; = 3.5 mg/mmol in women. Randomized patients were treated with alisartan 80 mg per day or placebo. If ambulatory BP was uncontrolled, drug dosage was doubled at the 2-month visit, and amlodipine 2.5 mg or matching placebo was added at the 4-month visit. The primary endpoint was the improvement rate of TOD after 12 months treatment, defined as the reverse (yes to no) of TOD or a significant decrease of ba-PWV or ACR by &gt; = 20% of the baseline level. Results: From Feb 2017 to Oct 2020, 317 patients with masked hypertension (43.2% women, mean age 54 years) were randomized in 13 hospitals in China. Overall, baseline office, 24-h, daytime and nighttime BPs averaged 130/81, 137/85, 141/87, and 126/77 mmHg, respectively. At baseline, 98% had an elevated ba-PWV, 12% microalbuminuria, and 8% LVH. 252 patients completed the 12-month treatment and 65 (20.5%) withdrew from the trial. In the intention-to-treat analyses, the improvement rate of TOD was significantly higher in the antihypertensive treatment group than the placebo group (47.4% vs 26.1%, P &lt; 0.0001), as well as the decrease of the 24-h systolic/diastolic BPs (-9.1/-5.7 vs -1.5/-1.0 mmHg, P &lt; 0.0001). Conclusions: Antihypertensive treatment was beneficial for patients with masked hypertension in terms of TOD protection.

Use of Perindopril Arginine/Indapamide/Amlodipine in the Management of Hypertension in Two Sub-Saharan African Island Countries of Madagascar and Mauritius.

IntroductionMost patients with hypertension in sub-Saharan Africa require two or more drugs to control their blood pressure. Triple fixed-dose combination therapy of perindopril arginine/indapamide/amlodipine is more effective in lowering blood pressure, offers better target organ protection and has increased adherence compared to monotherapy and free combination therapy, and is safe to use. This observational study evaluates the effectiveness of perindopril arginine/indapamide/amlodipine in controlling blood pressure at least 1 month after treatment initiation and assesses patient- and physician- reported drug tolerance over a 3-month period in Madagascar and Mauritius.MethodsA total of 198 patients with hypertension in ambulatory care who had been on fixed-dose combination of perindopril arginine, indapamide, and amlodipine for at least 4 weeks were included. The main outcome measures were changes in systolic and diastolic blood pressure, attainment of blood pressure control under 140/90 mmHg and 130/80 mmHg, self-reported drug tolerance by the patient, and perceived drug tolerance by the treating physician. Data was collected at 1 month and 3 months.ResultsMean systolic blood pressure was significantly lower at the 1-month (− 3.4 mmHg, p = 0.002) and 3-month (− 8.5 mmHg, p < 0.0001) visits. Diastolic blood pressure also decreased significantly (− 2.4 mmHg at 1-month, p = 0.017 and − 5.4 mmHg at the 3-month visits, p < 0.0001). At 3 months, 80.4% of the patients attained blood pressure targets less than 140/90 mmHg and 42.7% attained targets less than 130/80 mmHg on the basis of their baseline blood pressure. Excellent drug tolerance was reported by more than 90% of patients and physicians at the 1-month visit and by more than 95% at the 3-month visit.ConclusionTriple fixed-dose therapy of perindopril arginine/indapamide/amlodipine continues to show additional blood pressure-lowering capacity even months after initiating the treatment in patients with hypertension in Madagascar and Mauritius. It is also well tolerated by patients with hypertension and assessed as safe to use by physicians.

Blood pressure control, target organ protection and metabolic disorders control using a fixed combination of azilsartan medoxomil + chlorthalidone in hypertensive patients survived after severe and extremely severe COVID-19

Objective. Evaluation of the possibility of a fixed combination of azilsartan medoxomil + chlorthalidone in additional angioprotection in patients with arterial hypertension (HTN) and high pulse wave velocity (PWV) after confirmed severe or extremely severe COVID-19 (bilateral polysegmental viral pneumonia) treated by genetically engineered biological drugs, who had not previously received combined antihypertensive therapy.Design and methods. An open observational study lasting 12 weeks included 30 patients, 28–31 days after discharge from the hospital after a severe and extremely severe COVID-19, who received or had not previously received antihypertensive therapy. Patients underwent 24-hour blood pressure (BP) monitoring, applanation tonometry (augmentation index and central BP), measurement of PWV, laboratory tests before and after prescription of a fixed combination of azilsartan medoxomil + chlorthalidone.Results. At baseline, patients showed an increase in office blood pressure to 153,06/92,2 mmHg. After treatment with a fixed combination of azilsartan medoxomil + chlorthalidone, a decrease in systolic BP by 18,47% and diastolic BP by 16,24% was observed. According to ambulatory BP monitoring, the decrease in systolic BP was 19,65% and diastolic BP — 24,68%, PWV decreased by 34,4%, augmentation index — by 9,42%, central systolic BP — by 15,48% (p &lt; 0,05). At baseline, vascular age (VA) was increased to 44,96 years compared to the passport age of 35,03 years. After treatment, there was a significant decrease in VA to 38,74 years (p &lt; 0,01). In addition, the levels of C-reactive protein, fibrinogen, D-dimer, glucose, blood urea nitrogen and uric acid significantly decreased.Conclusions. The fixed combination of azilsartan medoxomil + chlorthalidone provides better control of BP. It also helps to improve vascular elasticity (augmentation index, PWV, central systolic BP, decrease in VA) and to reduce post-infectious inflammation in HTN patients after a severe coronavirus infection.